Therapeutic Combinations for Inflammatory Conditions and Disorders

Abstract

Therapeutic combinations, pharmaceutical compositions, and pharmaceutical kits are provided that include fungi (e.g., Psilocybe species fungi), plants (e.g., Cannabis species, Dipteryx species), and algae (e.g., from the family Bangicaeae, including Pyropia species or Porphyra species), including extracts and bioactive molecules derived therefrom. Methods of producing the disclosed combinations, compositions, and kits are also provided, such as by natural, biosynthetic, or synthetic means. Additionally, methods of using the disclosed combinations, compositions, and kits in the treatment of medical conditions, particularly for treating inflammatory diseases and medical conditions, are further provided, and the disclosed combinations have been demonstrated to offer significant advantages.

Description

[Technical Field]

[0001] cross reference Priority is claimed under PCT Art. 8(1) and Rule 4.10 to U.S. Provisional Patent Application No. 63 / 446,403 (filed February 17, 2023), which is incorporated by reference for all purposes as if fully set forth herein.

[0002] Therapeutic combinations comprising fungi, plants, and algae, including extracts thereof and bioactive molecules derived therefrom, are provided. Pharmaceutical compositions and kits containing these, as well as methods of their use in medicine, particularly for treating inflammatory conditions and disorders, are also provided. [Background technology]

[0003] Globally, approximately 50% of people die from inflammatory diseases (GBD 2017 Causes of Death Collaborators. Lancet. 2018;392(10159):1736-1788). Inflammation can be acute, typically temporary, and can result from injury, for example. Alternatively, inflammation can be chronic and associated with a wide range of diseases, including asthma, autoimmune diseases such as rheumatoid arthritis, cardiovascular disease, metabolic disease, neurodegenerative diseases, gastrointestinal diseases, respiratory diseases, and certain types of cancer.

[0004] Many inflammatory conditions or disorders are incurable, and treatments generally only attempt to alleviate symptoms or slow progression. Thus, there is a desperate need for new treatments that can reduce the severity of symptoms, prevent the development of new symptoms, and reverse disease progression.

[0005] Provided herein are therapeutic combinations, pharmaceutical compositions and kits, and methods of their use, for treating inflammatory conditions and disorders that meet these and other needs and have readily apparent advantages and improvements over prior treatment options.

[0006] Incorporation by Reference Each cited patent, publication, and non-patent literature is incorporated herein by reference in its entirety, as if each were individually incorporated and as if each were fully set forth herein. However, such citation should not be construed as an admission that the cited references are from areas analogous or directly applicable to the present invention, nor should citation be construed as an admission that the documents or underlying information in any jurisdiction are prior art or form part of the common general knowledge in the art. Summary of the Invention

[0007] A simplified summary of some aspects and embodiments is presented in order to provide a basic understanding of the invention. This summary is not an extensive overview and is not intended to identify all key or critical elements of the invention or to delineate the full scope of the invention. Its sole purpose is to present some illustrative embodiments in a simplified form as a prelude to the more detailed description that follows.

[0008] In a first aspect, there is provided a method of preventing or treating an inflammatory condition or disorder, comprising administering to a subject having an inflammatory condition or disorder: a. Fungal part, b. a first plant part; c. a second plant part, and d. A method comprising administering a therapeutic combination comprising an algal portion.

[0009] In another aspect, a method for preventing or treating an inflammatory condition or disorder in a subject, comprising administering to a subject a composition comprising: a. Fungal part, b. a first plant part; c. a second plant part, and d. Algae part, The present invention provides the use of a therapeutic combination comprising:

[0010] A method of preventing or treating an inflammatory condition or disorder, comprising administering to a subject having an inflammatory condition or disorder any of the disclosed embodiments; or a. Fungal part, b. a first plant part; c. optionally, a second plant part, and d. Optionally, an algae portion Also provided are methods comprising administering a therapeutic combination comprising:

[0011] In some embodiments, the fungal portion comprises any of a fungal extract, a primary fungal-derived bioactive molecule, and a secondary fungal-derived bioactive molecule.

[0012] In some embodiments, the first plant part comprises any of a plant extract, a plant-derived primary bioactive molecule, and a plant-derived secondary bioactive molecule.

[0013] In some embodiments, the second plant part comprises any of a plant extract, a plant-derived primary bioactive molecule, and a plant-derived secondary bioactive molecule.

[0014] In some embodiments, the algae portion comprises any of an algae extract, an algae-derived primary bioactive molecule, and an algae-derived secondary bioactive molecule.

[0015] In some embodiments, the fungal portion is derived from a psilocybin-producing species. In some embodiments, the psilocybin-producing species is derived from any of the genera Psilocybe, Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, and Pluteus. In some embodiments, the psilocybin-producing species is derived from the genus Psilocybe. In some embodiments, the psilocybin-producing species from the genus Psilocybe is any of P. cubensis, P. azurescens, P. bohemica, P. semilanceata, P. baeocystis, P. cyanescens, P. tampanensis, P. weilii, P. hoogshagenii, P. stuntzii, P. cyanofibrillosa, and P. liniformans.

[0016] In an embodiment, the first plant part is derived from a Cannabis species, which may be any of Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

[0017] In some embodiments, the second plant part is from a species of the genus Dipteryx. In some embodiments, the species of the genus Dipteryx is Dipteryx odorata.

[0018] In some embodiments, the algae portion is derived from a seaweed species. In some embodiments, the seaweed species is from the family Bangiaceae. In some embodiments, the seaweed species is from the genus Pyropia or Porphyra. In some embodiments, the seaweed species is any of Pyropia yezoensis, Pyropia perforata, and Porphyra umbilicalis.

[0019] In some embodiments, any of the fungal part, the first plant part, the second plant part, and the algal part are administered in separate compositions.

[0020] In some embodiments, the fungal part, the first plant part, the second plant part, and any of the algal part are co-administered, hi some embodiments, the fungal part, the first plant part, the second plant part, and any of the algal part are administered in a single composition.

[0021] In some embodiments, a. The fungal portion contains an extract of Psilocybe cubensis; b. the first plant part comprises a Cannabis sativa extract; c. the second plant part comprises a Dipteryx odorata extract; d. The algae portion contains Pyropia yezoensis extract.

[0022] In some embodiments, the Psilocybe cubensis extract is obtained by ultrasonic extraction or Soxhlet extraction. In some embodiments, the Psilocybe cubensis extract comprises a mixture of an ultrasonically extracted Psilocybe cubensis extract and a Soxhlet extracted Psilocybe cubensis extract in a weight ratio of about 0.5:1 to about 5:1. In some embodiments, the ultrasonically extracted Psilocybe cubensis extract and the Soxhlet extracted Psilocybe cubensis extract are in a weight ratio of 2:1.

[0023] In some embodiments, the Psilocybe cubensis extract contains psilocybin and psilocin. In some embodiments, the Psilocybe cubensis extract contains psilocybin and psilocin in a weight ratio of about 1:5 to about 5:1. In some embodiments, the Psilocybe cubensis extract contains psilocybin and psilocin in a weight ratio of about 5:3. In some embodiments, the Psilocybe cubensis extract contains about 50 μg to about 500 μg of psilocybin and about 20 μg to about 200 μg of psilocin. In some embodiments, the Psilocybe cubensis extract contains about 250 μg of psilocybin and about 150 μg of psilocin. In some embodiments, the Cannabis sativa extract is obtained by Soxhlet extraction. In some embodiments, the Cannabis sativa extract is obtained by Δ 9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In some embodiments, the Cannabis sativa extract contains THC and CBD in a weight ratio of about 1:5 to about 5:1. In some embodiments, the Cannabis sativa extract contains THC and CBD in a weight ratio of about 1:1. In some embodiments, the Cannabis sativa extract contains about 0.1 mg to about 5 mg THC and about 0.1 to 5 mg CBD. In some embodiments, the Cannabis sativa extract contains about 1 mg THC and about 1 mg CBD.

[0024] In some embodiments, the Dipteryx odorata extract is obtained by absolute ethanol percolation. In some embodiments, the Dipteryx odorata extract includes coumarin. In some embodiments, the Dipteryx odorata extract includes about 1 mg to about 10 mg of coumarin. In some embodiments, the Dipteryx odorata extract includes about 1 mg of coumarin.

[0025] In some embodiments, the combination includes about 1 mg to about 20 mg of Pyropia yezoensis extract. In some embodiments, the combination includes about 8 mg of Pyropia yezoensis extract. In some embodiments, the Pyropia yezoensis extract is obtained by ultrasonic extraction. In some embodiments, the Pyropia yezoensis extract includes porphyran.

[0026] In some embodiments, the Psilocybe cubensis extract, the Cannabis sativa extract, the Dipteryx odorata extract, and the Pyropia yezoensis extract are administered in separate compositions.

[0027] In some embodiments, the Psilocybe cubensis extract, Cannabis sativa extract, Dipteryx odorata extract, and Pyropia yezoensis extract are co-administered. In some embodiments, the Psilocybe cubensis extract, Cannabis sativa extract, Dipteryx odorata extract, and Pyropia yezoensis extract are administered in a single composition.

[0028] In some embodiments, the Psilocybe cubensis extract comprises about 20% to about 60% by volume of the single composition, hi some embodiments, the Psilocybe cubensis extract comprises about 45% by volume of the single composition.

[0029] In some embodiments, the Cannabis sativa extract comprises about 5% to about 30% by volume of the single composition, hi some embodiments, the Cannabis sativa extract comprises about 15% by volume of the single composition.

[0030] In some embodiments, the Dipteryx odorata extract comprises about 1% to about 5% by volume of the single composition, hi some embodiments, the Dipteryx odorata extract comprises about 2% by volume of the single composition.

[0031] In some embodiments, the Pyropia yezoensis extract comprises about 5% to about 30% by volume of the single composition, hi some embodiments, the Pyropia yezoensis extract comprises about 15% by volume of the single composition.

[0032] In some embodiments, the single composition further comprises any of a flavoring, a coloring, and a diluent. In embodiments, the flavoring or coloring comprises ginger or bay leaf. In embodiments, the flavoring or coloring is an infusion of ginger and bay leaf with ethanol. In embodiments, the flavoring or coloring comprises about 5% to about 30% by volume of the single composition. In embodiments, the flavoring or coloring comprises about 15% by volume of the single composition. In embodiments, the diluent is water. In embodiments, the water comprises about 5% to about 15% by volume of the single composition. In embodiments, the water comprises about 8% by volume of the single composition.

[0033] In some embodiments, the method or use comprises administering about 10 to 200 mg of the single composition per single dose. In some embodiments, the method or use comprises administering about 50 mg of the single composition per single dose. In some embodiments, the method or use comprises administering 1 to 8 doses of the single composition per day. In some embodiments, the method or use comprises administering 1 to 8 doses of the single composition per day for at least 1 week, 2 weeks, 3 weeks, 1 month, 2 months, or 3 months.

[0034] In some embodiments, the subject experiences a reduction in the severity of symptoms of the inflammatory condition or disorder, hi some embodiments, the reduction in symptom severity is sustained for at least 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, or at least 12 months, as measured from baseline.

[0035] In embodiments, the inflammatory condition or disorder is any of long COVID, rheumatoid arthritis, psoriatic arthritis, reactive arthritis, tendonitis, gout, scleroderma, systemic sclerosis, localized scleroderma, CREST syndrome, sciatica, neuropathy, peripheral neuropathy, hereditary neuropathy, acquired neuropathy, motor neuropathy, sensory neuropathy, autonomic neuropathy, polyneuropathy, sciatica, myalgic encephalomyelitis, chronic fatigue syndrome (CFS), fatty liver, endometriosis, type 1 diabetes, type 2 diabetes, inflammatory bowel disease, asthma, obesity, cancer, Kawasaki disease, vasculitis, uveitis, Crohn's disease, ulcerative colitis, meningitis, allergy, psoriasis, Hashimoto's disease, Guillain-Barré syndrome, hepatitis, celiac disease, multiple sclerosis, fibromyalgia, lupus, and Sjogren's syndrome. In some embodiments, the inflammatory condition or disorder is any of long COVID, CREST syndrome, psoriatic arthritis, Hashimoto's disease, multiple sclerosis, sciatica, peripheral neuritis, post-treatment Lyme disease / chronic Lyme disease (CLD) syndrome, chronic fatigue and immune dysfunction syndrome (CFIDS) / chronic fatigue syndrome (CFS), and inflammatory skin diseases.

[0036] In some embodiments, the inflammatory condition or disorder is long COVID. In some embodiments, the subject experiences a decrease in the severity of long COVID symptoms. In some embodiments, the long COVID symptoms are any of inflammation, fever, chills, cough, shortness of breath, difficulty breathing, fatigue, muscle aches, body aches, headache, loss of taste, loss of smell, sore throat, congestion, runny nose, nausea, vomiting, diarrhea, difficulty thinking or concentrating, sleep disturbances, dizziness, neuropathic pain, irritability, altered taste, altered smell, depression, anxiety, confusion, poor sleep quality, heart palpitations, joint pain, chest pain, and abdominal pain.

[0037] In some embodiments, the inflammatory condition or disorder is CREST syndrome. In some embodiments, the subject experiences a decrease in the severity of CREST syndrome symptoms. In some embodiments, the CREST syndrome symptoms are any of inflammation, stiffness, decreased motor function, calcification, fatigue, depression, Raynaud's phenomenon and poor sleep quality.

[0038] In some embodiments, the inflammatory condition or disorder is psoriatic arthritis. In some embodiments, the subject experiences a decrease in the severity of psoriatic arthritis symptoms. In some embodiments, the psoriatic arthritis symptoms are any of the following: joint swelling or inflammation, plaque, fatigue, itching, nail pits, and red, scaly skin rashes.

[0039] In some embodiments, the inflammatory condition or disorder is Hashimoto's disease. In some embodiments, the subject experiences a decrease in the severity of Hashimoto's disease symptoms. In some embodiments, the Hashimoto's disease symptoms are any of inflammation, swelling, stiffness, decreased motor function, fatigue, decreased endurance, weight gain, muscle weakness, goiter, and pain.

[0040] In some embodiments, the inflammatory condition or disorder is multiple sclerosis. In embodiments, the subject experiences a decrease in the severity of multiple sclerosis symptoms. In embodiments, the multiple sclerosis symptoms are any of inflammation, depression, poor sleep quality, and fatigue.

[0041] In some embodiments, the inflammatory condition or disorder is sciatica. In some embodiments, the subject experiences a decrease in the severity of sciatica symptoms. In some embodiments, the sciatica symptoms are any of inflammation, nerve damage, pain, difficulty walking, muscle weakness, and numbness.

[0042] In some embodiments, the inflammatory condition or disorder is peripheral neuritis. In some embodiments, the subject experiences a decrease in the severity of peripheral neuritis symptoms. In some embodiments, the peripheral neuritis symptoms are any of inflammation, nerve damage, pain, difficulty walking, muscle weakness, or numbness.

[0043] In some embodiments, the inflammatory condition or disorder is post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome. In some embodiments, the subject experiences a decrease in the severity of PTLD / CLD syndrome symptoms. In embodiments, the PTLD / CLD syndrome symptoms are any of the following: difficulty thinking or concentrating, fatigue, pain, irritability, depression, and poor sleep quality.

[0044] In some embodiments, the inflammatory condition or disorder is chronic fatigue and immune deficiency syndrome (CFIDS) / chronic fatigue syndrome (CFS).In some embodiments, the subject experiences a reduction in the severity of chronic fatigue and immune deficiency syndrome (CFIDS) / chronic fatigue syndrome (CFS) symptoms.In some embodiments, the chronic fatigue and immune deficiency syndrome (CFIDS) / chronic fatigue syndrome (CFS) symptoms are any of difficulty thinking or concentrating and reduced energy levels after exertion.

[0045] In some embodiments, the inflammatory condition or disorder is an inflammatory skin disease. In some embodiments, the subject experiences a decrease in the severity of the inflammatory skin disease symptoms. In embodiments, the inflammatory skin disease symptoms are sun sensitivity and allergen intolerance.

[0046] In some embodiments, the therapeutic combination further comprises an additional active agent.

[0047] The foregoing has outlined in broad terms certain pertinent features of the present disclosure so that the detailed description of the present invention that follows may be better understood, and so that the present contribution to the art may be more fully appreciated. This summary should therefore be considered a brief, general overview of only some of the objects and embodiments disclosed herein, and is provided solely for the benefit and convenience of the reader. It is not intended to limit in any way the scope or equivalents of the claims to which the claims are lawfully entitled. Additional features of the present invention are described below. It should be understood by those skilled in the art that all disclosed specific compositions and methods are merely illustrative and may be readily utilized as a basis for modifying or designing other compositions and methods for carrying out the same purposes. Such equivalent compositions and methods also will be understood to be within the scope and spirit of the invention as set forth in the claims.

[0048] The headings within this document are utilized solely to facilitate the reader's review and should not be construed as limiting the invention in any manner.

[0049] To further clarify various aspects of the present invention, a more particular description will be made by reference to certain exemplary embodiments which are illustrated in the drawings. It will be understood that these drawings depict only exemplary embodiments of the invention and should not be considered as limiting its scope. They are provided merely as illustrative illustrations of certain concepts of some embodiments of the invention. Certain aspects of the invention will therefore be described with further specificity and detail, which, again by way of example only, will be described with reference to the accompanying drawings in which: [Brief explanation of the drawings]

[0050] [Figure 1] 1 shows certain synergistic effects of components of an exemplary therapeutic combination on the microglial NF-κB pathway.

[0051] [Figure 2]1 shows certain synergistic effects of components of exemplary therapeutic combinations on ROS / PPARy / Nrf2 crosstalk.

[0052] [Figure 3] FIG. 1 illustrates the production of an exemplary composition by the method of certain described embodiments.

[0053] [Figure 4] FIG. 1 shows an exemplary analysis of a composition by liquid chromatography-mass spectrometry (LC-MS) testing, including chromatograms showing various concentrations of bioactive molecules contained in the composition with parameters disclosed in Table 6.

[0054] [Figure 5] 1 shows an exemplary 1H-NMR spectrum of the disclosed composition having the parameters set forth in Table 6.

[0055] [Figure 6] 1 shows an exemplary analysis of a composition by multiple reaction monitoring (MRM) LC-MS testing, including a chromatogram showing the concentration of bioactive molecules contained in the composition with the parameters disclosed in Table 6.

[0056] [Figure 7] FIG. 1 shows the total antioxidant capacity of Cannabis stocks as measured by the Folin-Ciocalteu assay, where the calculated Gallic Acid Equivalents (GAE) of the Cannabis stocks are plotted in milligrams (mg) per milliliter per liter (mL / L) of a given solution.

[0057] [Figure 8]FIG. 1 shows the total antioxidant capacity of Psilocybe stocks using the Folin-Ciocalteu assay. The calculated GAE of Psilocybe stocks is plotted in mg per mL / L of a given solution.

[0058] [Figure 9] FIG. 1 shows the total antioxidant capacity of Pyropia stocks using the Folin-Ciocalteu assay. The calculated GAE of Pyropia stocks is plotted in mg per mL / L of a given solution.

[0059] [Figure 10] FIG. 1 shows the total antioxidant capacity of Tonka concentrates using the Folin-Ciocalteu assay. The calculated GAE of Tonka concentrates is plotted in mg per mL / L of a given solution.

[0060] [Figure 11] Figure 11 shows the total antioxidant capacity of a cannabis stock (Ca stock), a psilocybe stock (Ps stock), and a cannabis / psilocybe binary blend (Ca / Ps) using the Folin-Ciocalteu assay (i.e., obtained by the Folin-Ciocalteu assay). Figure 11 shows the calculated GAE for the Ca stock, Ps stock, and Ca / Ps in mg per mL / L of solution used. The table below the graph in Figure 11 indicates the statistical significance of the Ca stock vs. Ca / Ps and Ps stock vs. Ca / Ps, indicated by asterisks (P<0.10: *, P<0.05: *, and P<0.01: **). The binary blend of Cannabis and Psilocybe had higher antioxidant capacity than either component alone, and this data suggested an additive effect of the two components contributing to the capacity of the binary blend.

[0061] [Figure 12]Figure 12 shows the total antioxidant capacity of a Cannabis stock (Ca stock), a Pyropia stock (Py stock), and a Cannabis / Pyropia binary blend (Ca / Py) obtained by the Folin-Ciocalteu assay. Figure 12 shows the calculated GAE for the Ca stock, Py stock, and Ca / Py in mg per mL / L of solution utilized. The table below the graph in Figure 12 displays the statistical significance of the Ca stock vs. Ca / Py and Py stock vs. Ca / Py, indicated by an asterisk (as above). The Cannabis and Pyropia binary blend possessed a higher antioxidant capacity than either component alone, and these data suggest a synergistic effect, as the antioxidant capacity of the binary blend was higher than that predicted by adding the values ​​of the two components together.

[0062] [Figure 13] Figure 13 shows the total antioxidant capacity of a cannabis stock (Ca stock), a tonka stock (To stock), and a cannabis / tonka binary blend (Ca / To) as determined by the Folin-Ciocalteu assay. Figure 13 shows the calculated GAE for the Ca stock, To stock, and Ca / To in mg per mL / L of solution utilized. The table below the graph in Figure 13 displays the statistical significance of the Ca stock vs. Ca / To and To stock vs. Ca / To, indicated by an asterisk (as above). The cannabis and tonka binary blend had antioxidant capacity comparable to the cannabis components. Tonka slightly improved antioxidant capacity despite its relatively low percentage in the blend.

[0063] [Figure 14]Figure 14 shows the total antioxidant capacity of Psilocybe stock (Ps stock), Pyropia stock (Py stock), and a Psilocybe / Pyropia binary blend (Ps / Py) obtained by the Folin-Ciocalteu assay. Figure 14 shows the calculated GAE for Ps stock, Py stock, and Ps / Py in mg per mL / L of solution utilized. The table below the graph in Figure 14 represents the statistical significance of Ps stock vs. Ps / Py and Py stock vs. Ps / Py, indicated by an asterisk (as above). The Psilocybe / Pyropia binary blend had slightly lower antioxidant capacity than Psilocybe alone. This suggests that the compounds in the Pyropia stock solution interacted in a way that reduced its antioxidant capacity, i.e., its ability to donate electrons to chemical reactions in the assay.

[0064] [Figure 15] The total antioxidant capacity of Psilocybe stock (Ps stock), Tonka stock (To stock), and a Psilocybe / Tonka binary blend (Ps / To) obtained by the Folin-Ciocalteu assay is shown. Figure 15 shows the calculated GAE for Ps stock, To stock, and Ps / To in mg per mL / L of solution used. The table below the graph in Figure 15 indicates the statistical significance of Ps stock vs. Ps / To and To stock vs. Ps / To, indicated by an asterisk (as above). The Psilocybe / Tonka binary blend had a lower antioxidant capacity than Psilocybe alone. This suggests that compounds in Tonka interacted with compounds in Psilocybe in a way that reduced antioxidant capacity, i.e., its ability to donate electrons to chemical reactions in the assay.

[0065] [Figure 16]Figure 16 shows the total antioxidant capacity of Pyropia stock (Py stock), Tonka stock (To stock), and a Pyropia / Tonka binary blend (Py / To) using the Folin-Ciocalteu assay. Figure 16 shows the calculated GAE for Py stock, To stock, and Py / To in mg per mL / L of solution utilized. The table below the graph in Figure 16 displays the statistical significance of Py stock vs. Py / To and To stock vs. Py / To, indicated by an asterisk (as above). The Pyropia and Tonka binary blend had antioxidant capacity comparable to Pyropia alone. The effect of Tonka alone was undetectable at the dose range tested.

[0066] [Figure 17] The total antioxidant capacity of Cannabis / Psilocybe / Pyropia / Tonka (Ca / Ps / Py / To) blends obtained by the Folin-Ciocalteu assay is shown compared to matched doses of Cannabis stock (Ca stock), Psilocybe stock (Ps stock), Pyropia stock (Py stock), and Tonka stock (To stock). Figure 17 shows the calculated GAE for Ca / Ps / Py / To, Ca stock, Ps stock, Py stock, and To stock in mg per mL / L of solution utilized. The table below the graph shown in Figure 17 presents the statistical significance of Ca / Ps / Py / To vs. Ca stock, Ca / Ps / Py / To vs. Ps stock, Ca / Ps / Py / To vs. Py stock, and Ca / Ps / Py / To vs. To stock, indicated by an asterisk (as above).

[0067] [Figure 18]The total antioxidant capacity of the Cannabis / Psilocybe / Pyropia / Tonka (Ca / Ps / Py / To) blend, as determined by the Folin-Ciocalteu assay, is shown compared to matched doses of each of the binary blends, including Cannabis / Psilocybe (Ca / Ps), Cannabis / Pyropia (Ca / Py), Cannabis / Tonka (Ca / To), Psilocybe / Pyropia (Ps / Py), Psilocybe / Tonka (Ps / To), and Pyropia / Tonka (Py / To). Figure 18 shows the calculated GAE in mg per mL / L of solution utilized for Ca / Ps / Py / To, Ca / Ps, Ca / Py, Ca / To, Ps / Py, Ps / To, and Py / To. The table below the graphs shown in Figure 18 indicates the statistical significance of Ca / Ps / Py / To vs. Ca / Ps, Ca / Ps / Py / To vs. Ca / Py, Ca / Ps / Py / To vs. Ca / To, Ca / Ps / Py / To vs. Ps / Py, Ca / Ps / Py / To vs. Ps / To, and Ca / Ps / Py / To vs. Py / To, indicated by an asterisk (as above).

[0068] [Figure 19]Figure 19 shows the total antioxidant capacity of the Cannabis / Psilocybe / Pyropia / Tonka (Ca / Ps / Py / To) quaternary blend compared to Applicant's "4+" blend (i.e., Applicant's final products disclosed herein as ABS-108 and NIM-01, and as the composition of Example 6) as determined by the Folin-Ciocalteu assay. Figure 19 shows the calculated GAE for Ca / Ps / Py / To and the 4+ blend in mg per mL / L of solution utilized. Figure 19 presents the data as the mean ± standard deviation of duplicate experimental data points for each dose. Figure 19 indicates the statistical significance of Ca / Ps / Py / To versus the 4+ blend, indicated by an asterisk (as above). The 4+ blend exhibited higher antioxidant capacity than the Cannabis / Psilocybe / Pyropia / Tonka 4-component blend, indicating that the additional components in the 4+ blend contribute to the antioxidant properties of the final product. DETAILED DESCRIPTION OF THE INVENTION

[0069] While various aspects and features of particular embodiments have been summarized above, the following detailed description exemplifies several exemplary embodiments in more detail to enable one of ordinary skill in the art to which this invention pertains (equivalently, for brevity, "person of ordinary skill in the art") to implement such embodiments and to make and use the full scope of the invention as claimed.

[0070] Numerous modifications, substitutions, changes, and variations in the described examples, embodiments, applications, and details of the invention exemplified herein may be made by those skilled in the art without departing from the spirit of the invention or the scope of the invention as set forth in the appended claims, and the general principles defined herein can be applied to a wide range of aspects. Thus, the present invention is not intended to be limited to the aspects presented, but is to be accorded the widest scope consistent with the principles and features disclosed. The following description is intended to make such embodiments apparent to those skilled in the art in that they are readily recognizable and easily made without undue experimentation, using only the teachings herein together with general knowledge in the art.

[0071] Among the aspects of the present disclosure are therapeutic combinations comprising fungi, plants, and algae, including extracts thereof and bioactive molecules derived therefrom. Among other aspects of the present disclosure are pharmaceutical compositions, formulations, and kits comprising the therapeutic combinations. Among other aspects of the present disclosure are methods of using the combinations, compositions, and formulations to treat or prevent inflammatory conditions or disorders.

[0072] I. General Definitions and Terminology As used in this specification and claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to an "excipient" includes reference to one or more excipients, and reference to a "biologically active molecule" includes reference to one or more bioactive molecules. Furthermore, a "biologically active molecule" includes reference to a bioactive molecule within another substance, such as an extract, unless expressly or by context indicates that the bioactive molecule has been purified or isolated therefrom, and even in that case, the bioactive molecule can include the other substance as long as it is within the exemplary stated range of purity.

[0073] The terms "comprising," "including," "such as," and "having" are intended to be inclusive and not exclusive (i.e., other elements may be present in addition to the referenced elements). Thus, the term "including" means, and is used interchangeably with, the expression "including but not limited to." The term "or" is used herein to mean, and is used interchangeably with, the term "and / or," unless the context clearly dictates otherwise. The specific use of the term "and / or" does not imply that any use of "or" is solely a conjunction; rather, such use merely highlights the possibility that the term "and / or" may be a conjunction in certain embodiments, but may otherwise be a conjunction like "or." The term "and" is understood to be conjunctive.

[0074] A composition "consisting of" particular bioactive molecules can include only the recited bioactive molecules, and a composition "consisting essentially of" particular bioactive molecules can include the recited bioactive molecules, optionally with additional compounds or other elements that do not materially affect the basic and novel characteristics of the claimed combination, composition, or method. Although the term "one or more" is sometimes used, its absence (or replacement with the singular) does not imply exclusiveness; rather, such use merely highlights the possibility of multiple agents or components in a particular embodiment.

[0075] When ranges are given herein, the disclosure includes embodiments in which the endpoints are included, embodiments in which both endpoints are excluded, and embodiments in which one endpoint is included and the other endpoint is excluded. Both endpoints should be assumed to be inclusive unless otherwise indicated. Also, unless otherwise indicated or otherwise apparent from the context and the understanding of one of ordinary skill in the art, values ​​expressed as ranges are understood to be able to assume, in different embodiments, any specific value or subrange within the stated range, down to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. Furthermore, when a series of numerical values ​​is described herein, it is understood that the disclosure includes embodiments related by analogy to any intervening value or range defined by any two values ​​in the series, with the minimum value taken as a minimum and the maximum value taken as a maximum. Numerical values ​​used herein include values ​​expressed as percentages. For embodiments in which numerical values ​​are preceded by "about" or "approximately," the disclosure includes embodiments in which the exact value is recited. For embodiments where a numerical value is not preceded by "about" or "approximately," the present disclosure includes embodiments where the numerical value is preceded by "about." Unless otherwise stated, all numbers expressing properties such as amounts of ingredients, concentrations, reaction conditions, and the like, used to describe and claim a particular embodiment should therefore be understood to be modified in some instances by the term "about." "Approximately" or "about" is intended to encompass numerical values ​​that fall within a range, in embodiments, within ±10% of the numerical value, in some embodiments, within ±5% of the numerical value, in some embodiments (including some embodiments) within ±2% of the numerical value, in some embodiments, within ±1% of the numerical value, in some embodiments, within ±0.5% of the numerical value, and in some embodiments, within ±0.1% of the numerical value, unless otherwise stated or apparent from the context (except where such numerical value would impermissibly exceed 100% of a possible value).

[0076] In some embodiments, the numerical parameters set forth in the specification and claims are approximations that can vary depending on the desired properties sought to be obtained by a particular embodiment (and as would be understood by one of ordinary skill in the art). The term "substantially," when applied to modifying a feature or limitation herein, should be read to provide an appropriate degree of certainty in light of the context of the disclosure and the knowledge in the art, for example, by using art-recognized standards for measuring the meaning of "substantially" as a term of degree, or by grasping a range as would be understood by one of ordinary skill in the art. In some embodiments, numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments are approximations, the numerical values ​​set forth in the specific examples are reported as precisely as practicable. The numerical values ​​set forth in the embodiments may necessarily contain certain errors resulting from the standard deviation found in their respective testing measurements.

[0077] A comprehensive list of abbreviations utilized by organic chemists of ordinary skill appears in the first issue of each volume of the Journal of Organic Chemistry, typically set forth in a table entitled "Standard List of Abbreviations." The most current list as of the filing date is incorporated herein by reference as if fully set forth herein.

[0078] All technical and scientific terms in this specification have the meanings that are commonly understood by those skilled in the art unless expressly defined otherwise. Further definitions that may assist the reader in understanding the disclosed exemplary embodiments are provided below, but such definitions are not intended to limit the scope of the present disclosure, and it will be understood that they will be properly interpreted and understood (as well as any plain meaning known to those skilled in the art) in light of the language used in the claims and by referring to the entire specification. The terms are intended to describe specific embodiments and are not intended to be limiting.

[0079] Terms that have a specific meaning in the regulatory laws of the jurisdiction in which this application is filed or may be enacted should generally be given that meaning unless the context dictates otherwise. For example, "botanical drug substance" may refer to terms defined through FDA implementing rules and regulations and terms set forth in the U.S. Department of Health and Human Services Food and Drug Administration's Center for Drug Evaluation and Research's "Guidance for Industry Botanical Drug Products, December 2016 (Docket No. FDA-2000-D-0103)" ("FDA. Botanical drug development guidance for industry. 2016. CDER pharmaceutical quality. CMC"). The same applies to other terms, including "botanical drug" and "botanical material."

[0080] For the avoidance of doubt, even though "botanical" is commonly used to mean "pertaining to plants," as used herein, "botanical" in a "botanical" drug substance or drug product shall be understood to include compounds, substances, and products (e.g., extracts) obtained from or derived from fungal material, such as psilocybin-containing or other fungi, as defined by the FDA.

[0081] "Botanical" drug substances or pharmaceuticals are also understood to include compounds, substances, and products (e.g., extracts) obtained or derived from algal material, where "algal material" refers broadly to any material from the polyphyletic group of diverse photosynthetic eukaryotic organisms referred to or understood in the art as "algae," particularly those portions that constitute a biologically active molecule of interest, as known to those skilled in the art.

[0082] Botanical drug substances and drugs, and compositions containing them, may be available by prescription or over the counter ("OTC"), as dietary or nutritional supplements, as "functional foods," or under other regulatory regimes, or may be unregulated (e.g., "natural products").

[0083] As used herein, the term "plant material" includes the entire plant and its parts containing the desired bioactive molecules, such as the above-ground parts of the plant, isolated leaves, stems, flowers, fruits, roots, or any combination of the foregoing. In the case of Cannabis plants, it will be understood that the part primarily used is the flowering female inflorescence ("bud"), which generally contains the highest concentrations of bioactive molecules, such as terpenoids and cannabinoids. However, other plant parts may also be used in the disclosed compositions and methods, as will be understood by those skilled in the art.

[0084] When fungal material is used (e.g., in an extraction process), it may be derived from fungal fruiting bodies ("mushrooms"), fungal sclerotia ("truffles"), as well as any part from mycelium or other fungal material (e.g., bioreactor biomass), unless the context indicates otherwise; any or all such parts, as well as combinations thereof, may be referred to as "fungal material."

[0085] Generally, the names used and procedures performed herein are those well known in the art related to one aspect of this disclosure, such as biology, chemistry, natural product extraction, botany, mycology, phycology, pharmacology, medicine, etc., and are those well known and commonly used in the art. Standard techniques and procedures are those generally performed according to conventional methods in the art.

[0086] II. Components of Therapeutic Combinations, Compositions and Formulations In some embodiments, the therapeutic combination comprises a fungal part, a plant part, and an algal part. In some embodiments, the therapeutic combination comprises a fungal part, a first plant part, optionally a second plant part, and an algal part. In embodiments, the therapeutic combination comprises a fungal part, a first plant part, a second plant part, and an algal part. In some aspects, the provided therapeutic combinations are useful for preventing or treating inflammatory conditions or disorders.

[0087] In some embodiments, the fungal parts, plant parts, or algal parts comprise an extract (i.e., a fungal extract, a plant extract, or an algal extract, respectively). In embodiments, the therapeutic combination comprises a fungal extract, a plant part, and an algal part. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant part, and optionally a second plant part and an algal part. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant part, a second plant part, and an algal part. In some embodiments, the therapeutic combination comprises a fungal part, a first plant extract, and optionally a second plant extract and an algal part. In some embodiments, the therapeutic combination comprises a fungal part, a first plant extract, a second plant extract, and an algal part. In some embodiments, the therapeutic combination comprises a fungal part, a first plant part, and optionally a second plant part and an algal extract. In some embodiments, the therapeutic combination comprises a fungal part, a first plant part, and optionally a second plant part and an algal extract. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant extract, optionally a second plant extract, and an algal part. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant extract, a second plant extract, and an algal part. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant part, optionally a second plant part, and an algal extract. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant part, a second plant part, and an algal extract. In some embodiments, the therapeutic combination comprises a fungal extract, a plant extract, and an algal extract. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant extract, optionally a second plant extract, and an algal extract. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant extract, optionally a second plant extract, and an algal extract. In some embodiments, the therapeutic combination comprises a fungal extract, a first plant extract, optionally a second plant extract, and an algal extract.

[0088] In some embodiments, the therapeutic combination comprises a bioactive molecule derived from a fungus, a bioactive molecule derived from a plant, and / or a bioactive molecule derived from an algae. In some embodiments, the therapeutic combination comprises a bioactive molecule derived from a fungus and a bioactive molecule derived from a plant. In some embodiments, the therapeutic combination comprises a bioactive molecule derived from a plant and a bioactive molecule derived from an algae. In some embodiments, the therapeutic combination comprises a bioactive molecule derived from a fungus, a bioactive molecule derived from a plant, and a bioactive molecule derived from an algae. In some embodiments, the therapeutic combination comprises a bioactive molecule derived from a fungus, a bioactive molecule derived from a plant, a bioactive molecule derived from an algae, and a bioactive molecule derived from a fungus, a plant, and / or an algae. In some embodiments, the therapeutic combination comprises a bioactive molecule derived from a fungus, a first bioactive molecule derived from a plant, a second bioactive molecule derived from a plant, and a bioactive molecule derived from an algae.

[0089] In some embodiments, the therapeutic combination comprises a bioactive molecule from Psilocybe cubensis, a bioactive molecule from Cannabis sativa, a bioactive molecule from Pyropia yezoensis, and a bioactive molecule from Dipteryx odorata. In some embodiments, the therapeutic combination comprises two or more of a bioactive molecule from Psilocybe cubensis, a bioactive molecule from Cannabis sativa, a bioactive molecule from Pyropia yezoensis, and a bioactive molecule from Dipteryx odorata. In some embodiments, the therapeutic combination includes three or more of a bioactive molecule from Psilocybe cubensis, a bioactive molecule from Cannabis sativa, a bioactive molecule from Pyropia yezoensis, and a bioactive molecule from Dipteryx odorata. In some embodiments, the therapeutic combination includes all four of a bioactive molecule from Psilocybe cubensis, a bioactive molecule from Cannabis sativa, a bioactive molecule from Pyropia yezoensis, and a bioactive molecule from Dipteryx odorata.

[0090] In some embodiments, the disclosed therapeutic combinations are botanical formulations as prepared in embodiments herein, comprising whole extracts of Psilocybe cubensis fungus, Cannabis sativa plant, Pyropia yezoensis algae, and Dipteryx odorata bean. In some embodiments, the disclosed therapeutic combinations are botanical formulations comprising whole extracts of two or more of Psilocybe cubensis fungus, Cannabis sativa plant, Pyropia yezoensis algae, and Dipteryx odorata bean. In some embodiments, the disclosed therapeutic combination is a botanical formulation comprising whole extracts of three or more of the following: Psilocybe cubensis fungus, Cannabis sativa plant, Pyropia yezoensis algae, and Dipteryx odorata bean. In some embodiments, the disclosed therapeutic combination is a botanical formulation comprising whole extracts of all four of the following: Psilocybe cubensis fungus, Cannabis sativa plant, Pyropia yezoensis algae, and Dipteryx odorata bean.

[0091] As will be further understood in light of the present disclosure, bioactive molecules may be provided in an extract, such as a whole extract, a fraction or subfraction thereof, or may be provided as isolated compounds, substantially purified compounds, or purified compounds (including those produced by biosynthetic or synthetic means), and combinations thereof.

[0092] In some embodiments, the fungal-derived bioactive molecule is neither a plant-derived bioactive molecule nor an algae-derived bioactive molecule (i.e., the fungal-derived bioactive molecule is found only in fungi). In some embodiments, the plant-derived bioactive molecule is neither a fungal-derived bioactive molecule nor an algae-derived bioactive molecule (i.e., the plant-derived bioactive molecule is found only in plants). In embodiments, the algae-derived bioactive molecule is neither any fungal-derived bioactive molecule nor any plant-derived bioactive molecule (i.e., the algae-derived bioactive molecule is found only in algae).

[0093] In some embodiments, the fungal-derived bioactive molecule is also either a plant-derived bioactive molecule or an algae-derived bioactive molecule (i.e., it is found in plants or algae, but not both). In some embodiments, the plant-derived bioactive molecule is also either any fungal-derived bioactive molecule or an algae-derived bioactive molecule (i.e., it is also found in fungi or algae, but not both). In some embodiments, the algae-derived bioactive molecule is also either any fungal-derived bioactive molecule or a plant-derived bioactive molecule (i.e., it is also found in fungi or plants, but not both).

[0094] In some embodiments, the fungal-derived bioactive molecule is also a plant-derived bioactive molecule or an algae-derived bioactive molecule (i.e., it is also found in plants or algae). In some embodiments, the plant-derived bioactive molecule is also a fungal-derived bioactive molecule or an algae-derived bioactive molecule (i.e., it is also found in fungi or algae). In embodiments, the algae-derived bioactive molecule is also a fungal-derived bioactive molecule or a plant-derived bioactive molecule (i.e., it is also found in fungi or plants).

[0095] The term "secondary," as in "secondary biological activity," is used herein to mean, and may be used interchangeably with, the terms "secondary" or "additional," and is not intended to necessarily imply a particular degree of priority compared to a term "primary," as in "primary biological activity," and therefore should not necessarily imply a lesser degree of importance or significance in terms of providing or contributing to any particular advantage, benefit, or synergy, or for any particular disclosed use, such as importance or significance in any particular combination, composition, kit, or method, or for any particular disclosed use.

[0096] A. Fungi Fungi, unlike plants, do not contain chlorophyll and are saprophytic (feeding on dead plants and animals), parasitic (feeding on living hosts), or symbiotic (sharing mutually beneficial relationships with other organisms) organisms. Fungi reproduce both sexually and asexually by spores produced in a variety of ways. Exemplary fungi include Phycomycetes, Ascomycetes, and Basidiomycetes. Fungi may include those commonly referred to as yeasts, rusts, smuts, mildews, molds, and mushrooms. As used herein, "fungi" should be understood to include both filamentous and non-filamentous species, and the term will be understood to include all forms of the word, including "fungi" and "fungi."

[0097] In some exemplary embodiments, the fungus is a psilocybin-producing fungus. A "psilocybin-producing" fungus (or psilocybin-producing fungus) is any fungus that produces or is capable of producing psilocybin. More than 100 species of fungi in the genus Psilocybe produce psilocybin. Psilocybin-producing species can also be found in numerous other genera, including Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, and Pluteus. In some embodiments, the psilocybin-producing species is from any of these genera. In embodiments, the psilocybin-producing species is from any of the genera Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, and Psilocybe. In embodiments, the psilocybin-producing species is from Psilocybe. Different species of psilocybin mushrooms, and different strains thereof, will be well known or easily identifiable to those skilled in the art.

[0098] In some embodiments, the psilocybin-producing fungus is a Psilocybe species fungus. In some embodiments, the Psilocybe species fungus is P. acutipilea, P. allenii, P. alutacea, P. angulospora, P. antioquiensis, P. araucariicola, P. atlantis, P. aquamarina, P. armandii, or the like. dii (mexicana), P. aucklandiae, P. aztecorum, P. azurescens, P. baeocystis, P. banderillensis, P. bispora, P. brasiliensis, P. brunneocystidiata, P. caeruleoannulata leoannulata, P. caerulescens, P. caerulipes, P. callosa, P. carbonaria, P. caribaea, P. chuxiongensis, P. collybioides, P. columbiana, P. congolensis, P. cordyspora ordispora, P. cubensis, P. cyanescens, P. cyanofibrillosa, P. dumontii, P. egonii, P. eximia, P. fagicola, P. farinacea, P. fimetaria, P. fuliginosa, P. fultadoana, P.furtadoana, P. galindoi, P. gallaeciae, P. graveolens, P. guatapensis, P. heimii, P. herrerae, P. hispanica, P. hoogshagenii, P. inconspicua, P. indica, P. isabelae ), P. jacobsii, P. jaliscana, P. kumaenorum, P. laurae, P. lazoi, P. liniformans, P. mexicana, P. mairei, P. makarorae, P. mammillata, P. medullosa, P. meridensis , P. meridionalis, P. mescaleroensis, P. moseri, P. muliercula, P. naematoliformis, P. natalensis, P. natarajanii, P. neorhombispora, P. neoxalapensis, P. ovoideocystidiata P. ovoideocystidiata, P. papuana, P. paulensis, P. pelliculosa, P. pintonii, P. pleurocystidiosa, P. plutonia, P. portoricensis, P. pseudoaztecorum, P. puberula, P. cubensis, P.quebecensis, P. rickii, P. rostrate, P. rzedowskii, P. samuiensis, P. schultesii, P. semilanceata, P. septentrionalis, P. serbica, P. sierrae, P. sylvatica , P. singinger, P. strictipes, P. stuntzii, P. subacutipilea, P. subaeruginascens, P. subaeruginosa, P. subcaerulipes, P. subcubensis, P. subpsilocybioides, P P. subtropicalis, P. tampanensis, P. thaicordispora, P. thaiaerugineomaculans, P. thaiduplicatocystidiata, P. uruguayensis, P. uxpanapensis, P. venenata , P. villarrealiae, P. weilii, P. weldenii, P. weraroa, P. wrightii, P. yungensis, P. zapotecoantillarum, P. zapotecocaribaea, or P. zapotecorum species, including strains thereof.

[0099] In some embodiments, the psilocybin-producing fungus is not a Psilocybe species fungus. Other psilocybin-producing fungi that are not of the Psilocybe species will be readily apparent to those of skill in the art. Non-limiting examples include Conocybe siligineoides, Conocybe velutipes, Copelandia tropica, Inocybe aeruginascens, Inocybe caerulata, Inocybe coelestium, Inocybe corydalina, Inocybe haemacta, Inocybe tricolor, Galerina steglichii, Gymnopilus aeruginosus, and the like. aeruginosus, Gymnopilus braendlei, Gymnopilus cyanopalmicola, Gymnopilus dilepis, Gymnopilus dunensis, Gymnopilus intermedius, Gymnopilus lateritius, Gymnopilus luteofolius, Gymnopilus luteoviridis, Gymnopilus luteus, Gymnopilus palmicola palmicola), Gymnopilus purpuratus, Gymnopilus subpurpuratus, Gymnopilus subspectabilis, Gymnopilus validipesvalidipes, Gymnopilus viridans, Panaeolus venezolanus, Panaeolus tropicalis, Panaeolus tirunelveliensis, Panaeolus rubricaulis, Panaeolus olivaceus, Panaeolus moellerianus, Panaeolus microsporus, Panaeolus lentisporus, Panaeolus fimicola, Panaeolus cyanescense cyanescens, Panaeolus cinctulus, Panaeolus chlorocystis, Panaeolus cambodginiensis, Panaeolus bisporus, Panaeolus axfordii, Panaeolus africanus, Panaeolus affinis, Pholiotina cyanopus, Pholiotina smithii, Pluteus albostipitatus, Pluteus americanus americanus, Pluteus cyanopus, Pluteus glaucus, Pluteus glaucotinctus, Pluteus nigroviridis, Pluteus phaeocyanopusThese include Pluteus phaeocyanopus, Pluteus salicinus, Pluteus saupei, Pluteus velutinornatus, and Pluteus villosus.

[0100] In embodiments, the fungal-derived bioactive molecule is any of those described in Venturella et al. Int J Mol Sci. 2021;22(2):634; Anusiya et al. Bioengineered. 2021;12(2):11239-11268; Thu et al. Molecules. 2020;25(8):1972; Muszynska et al. Food Chem. 2018;243:373-381; and Mishraki-Berkowitz et al. J Forensic Sci. 2020;65(5):1450-1457.

[0101] 1. Primary and secondary bioactive molecules derived from fungi In some embodiments, the therapeutic combination comprises a fungal portion. In some embodiments, the fungal portion comprises a fungal extract. In some embodiments, the fungal portion comprises a bioactive molecule derived from a fungus. In some embodiments, the fungal extract comprises a bioactive molecule derived from a fungus. In embodiments, the fungal portion comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a fungus. In embodiments, the fungal extract comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a fungus. In embodiments, the disclosed therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a fungus.

[0102] In some embodiments (equivalently, and simply as a shorthand to save space, referred to as "in embodiments"), the fungal portion is derived from a psilocybin-producing fungus. The fungus can be any psilocybin-producing fungus known or ascertainable by those skilled in the art, including, by way of non-limiting example, certain species from the genera Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, Pluteus, and Psilocybe. The different species of psilocybin-producing fungi, and different strains thereof, are described herein and are well known or readily identifiable to those skilled in the art.

[0103] In embodiments where a fungal portion is described as being "derived from" a fungus, it will be understood that the fungal portion includes, by way of non-limiting example, fungal material such as raw (i.e., unprocessed) fungal biomass, fungal extracts (e.g., extracts described herein such as aqueous and / or ethanolic extracts), or fungal-derived material that includes a molecule that is naturally present in a fungus (e.g., a primary or secondary bioactive molecule described in an embodiment herein), whether or not said molecule is actually obtained by isolating the molecule from the fungus or whether or not it is obtained by another means (e.g., chemical synthesis).

[0104] In some embodiments, the fungal portion of the therapeutic combination is derived from a psilocybin-producing species. In some embodiments, the fungal portion of the therapeutic combination is derived from a species of the genus Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, Pluteus, or Psilocybe. In some embodiments, the fungal portion comprises a fungal extract from a psilocybin-producing species. In some embodiments, the fungal portion comprises a fungal extract from a species of the genus Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, Pluteus, or Psilocybe. In embodiments, the fungal portion comprises a bioactive molecule from a psilocybin-producing species. In embodiments, the fungal portion comprises a biologically active molecule from a species of the genus Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, Pluteus, or Psilocybe.In some embodiments, the fungal portion is from a species of the genus Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, or Psilocybe. In some embodiments, the fungal portion comprises a fungal extract from a species of the genus Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, or Psilocybe. In embodiments, the fungal portion comprises a bioactive molecule from a species of the genus Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, or Psilocybe.

[0105] In some embodiments, the fungus is a Psilocybe species fungus. In some embodiments, the fungal portion is derived from a Psilocybe species fungus. In some embodiments, the fungal portion is from the species P. azurescens, P. bohemica, P. semilanceata, P. baeocystis, P. cyanescens, P. tampanensis, P. cubensis, P. weilii, P. hoogshagenii, P. stuntzii, P. cyanofibrillosa, and / or P. liniformans. In some embodiments, the fungal portion comprises a fungal extract from a Psilocybe species fungus. In some embodiments, the fungal portion comprises a fungal extract derived from any of the species P. azurescens, P. bohemica, P. semilanceata, P. baeocystis, P. cyanescens, P. tampanensis, P. cubensis, P. weilii, P. hoogshagenii, P. stuntzii, P. cyanofibrillosa, and / or P. liniformans. In some embodiments, the fungal portion comprises a fungal extract derived from a Psilocybe species fungus.In embodiments, the fungal portion comprises a bioactive molecule derived from any of the species P. azurescens, P. bohemica, P. semilanceata, P. baeocystis, P. cyanescens, P. tampanensis, P. cubensis, P. weilii, P. hoogshagenii, P. stuntzii, P. cyanofibrillosa, and / or P. liniformans.

[0106] In embodiments, the fungal portion comprises any of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, and aerginascin. In embodiments, the fungal portion comprises a fungal extract comprising any of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, and aerginascin. In embodiments, the fungal portion comprises a primary bioactive molecule from a fungus selected from the group consisting of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, and aerginascin. In embodiments, the fungal portion comprises psilocybin. In embodiments, the fungal portion comprises psilocin. In embodiments, the fungal portion comprises baeocystin. In embodiments, the fungal portion comprises norbaeocystin. In embodiments, the fungal portion comprises norpsilocin. In embodiments, the fungal portion comprises aerginascin. In embodiments, the fungal portion comprises a fungal extract comprising psilocybin. In embodiments, the fungal portion comprises a fungal extract comprising psilocin. In embodiments, the fungal portion comprises a fungal extract comprising baeocystin. In embodiments, the fungal portion comprises a fungal extract comprising norbaeocystin. In embodiments, the fungal portion comprises a fungal extract comprising norpsirosin. In embodiments, the fungal portion comprises a fungal extract comprising aeruginascin. In embodiments, the fungal portion comprises a primary bioactive molecule derived from a fungus, wherein the molecule is psilocybin. In embodiments, the fungal portion comprises a primary bioactive molecule derived from a fungus, wherein the molecule is psirosin. In embodiments, the fungal portion comprises a primary bioactive molecule derived from a fungus, wherein the molecule is baeocystin. In embodiments, the fungal portion comprises a primary bioactive molecule derived from a fungus, wherein the molecule is norbaeocystin. In embodiments, the fungal portion comprises a primary bioactive molecule derived from a fungus, wherein the molecule is norpsirosin. In embodiments, the fungal portion comprises a primary bioactive molecule derived from a fungus, wherein the molecule is aeruginascin.

[0107] In some embodiments, the fungal portion comprises both psilocybin and psilocin. In some embodiments, the fungal portion comprises a fungal extract containing both psilocybin and psilocin. In some embodiments, the fungal portion comprises both psilocybin and psilocin as primary bioactive molecules from the fungus. In some embodiments, the fungal portion comprises both psilocybin and psilocin in a weight ratio of about 100:1 to 1:100, 50:1 to 1:50, 10:1 to 1:10, 5:1 to 1:5, 2:1 to 1:2, 5:3 to 3:5, or 3:2 to 2:3 (inclusive). In some embodiments, the fungal portion comprises psilocybin and psilocin in a molar ratio of 100:1 to 1:100, 50:1 to 1:50, 10:1 to 1:10, 5:1 to 1:5, 2:1 to 1:2, 5:3 to 3:5, or 3:2 to 2:3 (inclusive).

[0108] In some embodiments, the fungal portion comprises both psilocybin and psilocin in a weight ratio of about 100:1, 50:1, 10:1, 5:1, 2:1, 5:3, 3:2, or 1:1. In some embodiments, the fungal portion comprises both psilocybin and psilocin in a molar ratio of about 100:1, 50:1, 10:1, 5:1, 2:1, 5:3, 3:2, or 1:1. In some embodiments, the fungal portion comprises both psilocybin and psilocin in a weight ratio of about 1:100, 1:50, 1:10, 1:5, 1:2, 3:5, 2:3, or 1:1. In some embodiments, the fungal portion comprises both psilocybin and psilocin in a molar ratio of about 1:100, 1:50, 1:10, 1:5, 1:2, 3:5, 2:3, or 1:1.

[0109] In some embodiments, the fungal portion comprises both psilocybin and psilocin in a weight ratio of about 5:3, 3:2, 1:1, 2:3, or 3:5. In some embodiments, the fungal portion comprises both psilocybin and psilocin in a molar ratio of about 5:3, 3:2, 1:1, 2:3, or 3:5.

[0110] In some embodiments, the fungal parts, fungal extracts, or mixtures of fungal-derived bioactive molecules comprise psilocybin and psilocin in a weight ratio of about 5:3, 3:2, or 1:1. In embodiments, the fungal parts, fungal extracts, or mixtures of fungal-derived bioactive molecules comprise psilocybin and psilocin in a molar ratio of about 5:3, 3:2, or 1:1. In some embodiments, the fungal parts, fungal extracts, or mixtures of fungal-derived bioactive molecules comprise psilocybin and psilocin in a weight ratio of about 5:3. In embodiments, the fungal parts, fungal extracts, or mixtures of fungal-derived bioactive molecules comprise psilocybin and psilocin in a molar ratio of about 5:3.

[0111] In some embodiments, the fungal portion comprises a β-carboline (beta-carboline). In some embodiments, the fungal portion comprises a fungal extract comprising a β-carboline. In some embodiments, the fungal portion comprises a primary bioactive molecule derived from a fungus, wherein the primary bioactive molecule is a β-carboline. In embodiments, the β-carboline is harmane, harmine, harmol, harmalol, harmaline, tetrahydroharmine, pinoline, cordysinin C, cordysinin D, norharmane, perloline, β-carboline (9H-pyrido[3,4-b]indole), or another L-tryptophan-derived β-carboline. While "β-carboline" can refer to both individual compounds and a class of related compounds, use of the term herein shall be understood to refer to the class of compounds (including when described as "β-carboline") unless the context requires otherwise.

[0112] In embodiments, the fungal-derived secondary bioactive molecules are polysaccharides (including α- and β-glucans and polysaccharide-protein complexes), peptides (including proteins such as lectins), terpenes or terpenoids (including mono- and sesquiterpene oils, diterpenes, triterpenoids, sterols, carotenoid pigments), phenolic compounds (including phenolic acids, hydroxycinnamic acids, hydroxybenzoic acids, ligands, tannins, flavonoids, stilbenes, oxidized polyphenols), minerals (potassium, phosphorus, sodium), and the like. Vitamins (including ascorbic acid, vitamin D, riboflavin, folate, thiamine, pantothenic acid, and niacin), amino acids (including essential amino acids and histidine, isoleucine, leucine, lysine, methionine, phenylalanine, taurine, threonine, tryptophan, and valine), lipids (including saturated, monounsaturated, and polyunsaturated fatty acids such as oleic acid, linoleic acid, and linolenic acid), choline, or lactones.

[0113] B. Plant In some embodiments, the therapeutic combination comprises a plant part. In some embodiments, the plant part comprises a plant extract. In some embodiments, the plant part comprises a plant-derived bioactive molecule. In some embodiments, the plant extract comprises a plant-derived bioactive molecule. For example, in embodiments, the plant part comprises a primary bioactive molecule and / or a secondary bioactive molecule from a plant. In embodiments, the plant extract comprises a primary bioactive molecule and / or a secondary bioactive molecule from a plant. In some embodiments, the disclosed therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule from a plant.

[0114] In embodiments where a plant part is described as being "derived from" a plant, it will be understood that the plant part includes, by way of non-limiting example, plant material such as raw (i.e., unprocessed) plant biomass, plant extracts (e.g., extracts described herein, such as aqueous and / or ethanolic extracts), or plant-derived material that includes a molecule that is naturally present in the plant (e.g., a primary or secondary bioactive molecule described in an embodiment herein), whether or not the molecule is actually obtained by isolating the molecule from the plant or whether or not it is obtained by another means (e.g., chemical synthesis).

[0115] Plants are photosynthetic eukaryotes of the kingdom Plantae. In some embodiments, the therapeutic combination comprises a plant extract. In some embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a plant. In some embodiments, the therapeutic combination comprises a Cannabis extract and / or a Dipteryx extract. In some embodiments, the therapeutic combination comprises a Cannabis extract. In some embodiments, the therapeutic combination comprises a Dipteryx extract. In some embodiments, the therapeutic combination comprises both a Cannabis extract and a Dipteryx extract. In some embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a plant of the Cannabis and / or Dipteryx genus. In some embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a plant of the Cannabis genus.

[0116] 1. Cannabis The genus Cannabis is a genus of flowering plants in the family Cannabaceae. The number of species in the genus is disputed; some recognize Cannabis sativa, Cannabis indica, and Cannabis ruderalis as separate species, others include C. ruderalis within C. sativa, others include C. sativa, C. indica, and C. ruderalis as subspecies of the single species C. sativa, and still others treat C. sativa L. as a single, unclassified species. As used herein, "Cannabis" refers to all such encompassing species, subspecies, cultivars, varieties, strains, chemovarietals, etc., including the genus Cannabis, regardless of such terminology. As used herein, merely for shorthand purposes, and without taking a position on the above controversy, the term "Cannabis" refers to C. sativa, C. indica, and C. ruderalis, and further includes genetic crosses, self-crosses, and hybrids thereof.

[0117] In some embodiments, the plant parts of the therapeutic combination are derived from Cannabis. In embodiments where a plant part is described as being "derived" from Cannabis, it will be understood that the plant part includes, by way of non-limiting example, Cannabis material such as raw (i.e., unprocessed) Cannabis biomass, Cannabis extracts (e.g., aqueous and / or ethanolic extracts described herein, such as water), or Cannabis-derived material that includes a molecule that is naturally present in Cannabis (e.g., a primary or secondary bioactive molecule described in an embodiment herein), whether said molecule is actually obtained by isolating the molecule from Cannabis, or whether it is obtained by another means (e.g., chemical synthesis).

[0118] In some embodiments, the therapeutic combination comprises a Cannabis extract. In some embodiments, the therapeutic combination comprises a first bioactive molecule derived from Cannabis. In some embodiments, the combination comprises a second bioactive molecule derived from Cannabis.

[0119] a. Cannabis-derived primary and secondary bioactive molecules In some embodiments, the therapeutic combination comprises a first bioactive molecule and / or a second bioactive molecule derived from Cannabis.

[0120] In some embodiments, the primary bioactive molecule derived from Cannabis is a cannabinoid. Cannabinoids are a diverse class of small molecules grouped together due to their ability to act on cannabinoid receptors. Cannabinoid receptors are present throughout the brain and central and peripheral nervous systems of humans and other mammals. There are two main types of cannabinoid receptors, known as cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). CB1 receptors are primarily present in the central nervous system (i.e., brain and spinal cord) as well as in the lungs, liver, and kidneys. CB1 receptor-mediated signaling plays an important role in neural circuits mediating mood, motivation, and emotional behavior. CB2 receptors are primarily present in the immune system and hematopoietic stem and progenitor cells, and may also be present in neurons.

[0121] Cannabinoids are known to those skilled in the art and are also described and elucidated in part by Radwan et al. Molecules. (May 8, 2021); 26(9):2774 ("Radwan"), which is incorporated by reference as if fully set forth herein. Without being bound by these, cannabinoids according to Radwan's classification include 11 cannabinoid subclasses: cannabichromene (CBC), cannabidiol (CBD), cannabielsoin (CBE), cannabigerol (CBG), cannabicyclol (CBL), cannabinol (CBN), cannabinodiol (CBND), cannabiditriol (CBT), (-)-Δ 8 -trans-tetrahydrocannabinol (Δ 8 -THC) type, (-)Δ 9 -trans-tetrahydrocannabinol (Δ 9-THC)-type, and miscellaneous types of cannabinoids. Non-limiting examples of cannabinoids that are understood to be useful in the practice of this disclosure are known from the disclosure of Radwan and see below. In embodiments, the primary bioactive molecule from Cannabis is any such cannabinoid.

[0122] In some embodiments, the primary bioactive molecule derived from Cannabis is Δ 9 -THC-type cannabinoids, Δ 8 - Any of THC-type cannabinoids, CBG-type cannabinoids, CBD-type cannabinoids, CBND-type cannabinoids, CBE-type cannabinoids, CBL-type cannabinoids, CBN-type cannabinoids, CBC-type cannabinoids, CBT-type cannabinoids, and various types of cannabinoids. Δ 9 Examples of -THC-type cannabinoids include Δ 9 -THC-C5, Δ 9 -THCAA-C5, Δ 9 -THCAB-C5, Δ 9 -THC-C4, Δ 9 -THCAA-C4, Δ 9 -THCV, Δ 9 -THCVAA, Δ 9 -THCO, Δ 9 -THCOAA, Δ 9 -THC-aldehyde, β-fenchyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, α-fenchyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, epi-bornyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, Bornyl (-)-Δ 9 -trans-Tetrahydrocannabinolate, α-terpenyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, 4-terpenyl(-)-Δ 9-trans-Tetrahydrocannabinolate, α-cadinyl(-)-Δ 9 -Tetrahydrocannabinolate, γ-eudesmyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, 8α-hydroxy-(-)-Δ 9 -trans-tetrahydro-cannabinol, 8β-hydroxy-(-)-Δ 9 -trans-Tetrahydrocannabinol, 11-acetoxy-(-)-Δ 9 -trans-Tetrahydrocannabinolic acid A, 8-oxo-(-)-Δ 9 -trans-tetrahydrocannabinol, cannabidiol, (-)-Δ 9 -trans-tetrahydrocannabiphorol, (-)-Δ 9 -trans-tetrahydrocannabihexol.

[0123] Δ 8 Examples of -THC-type cannabinoids include Δ 8 -THC, Δ 8 -THCA, 10α-OH-Δ 8 -THC, 10β-OH-Δ 8 -THC, 10a-α-hydroxy-10-oxo-Δ 8 -THC, etc.

[0124] Examples of CBG-type cannabinoids include (£)CBG, (£)CBGA, (£)CBGG, (£)CBGAM, (£)CBGV, (£)CBGVA, (Z)CBGA, 5-acetyl-4-hydroxycannabigerol, (±)-6,7-trans-epoxycannabigerolic acid, (±)-6,7-cis-epoxycannabigerolic acid, (±)-6,7-cis-epoxycannabigerol, (±)-6,7-trans-epoxycannabigerol, camagerol, and sesquicannabigerol.

[0125] Examples of CBD-type cannabinoids include CBD-C5, CBDA-C5, CBDM-C5, CBD-C4, CBDV, CBDVA, CBD-C1, CBDH, CBDP, and CBDD. Examples of CBND-type cannabinoids include CBND-C3 and CBND-C5. Examples of CBE-type cannabinoids include CBE-C5, CBEAA-C5, CBEAB-C5, CBE-C3, and CBEAB-C3. Examples of CBL-type cannabinoids include CBL, CBLA, and CBLV. Examples of CBC-type cannabinoids include CBC, CBCA, ±CBCV, +CBCV, CBCVA, 4-acetoxy-CBC, (±)-3"-hydroxy-Δ4"-cannabichromene, (-)-7-hydroxy-canna-bichromene, and CBC-C3. Examples of CBN-type cannabinoids include CBN-C5, CBNA-C5, CBN-C4, CBN-C3, CBN-C2, CBN-C1, CBNM-C5, 8-OH-CBN, 8-OH-CBNA, 1'S-OH-CBN, and 4-terpenyl-cannabinolate. Examples of CBT-type cannabinoids include (-)-trans-CBT-C5, (+)-trans-CBT-C5, (±)-cis-CBT-C5, (±)-trans-CBT-C3, CBT-C3-homolog, (-)-trans-CBT-OEt-C5, (-)-trans-CBT-OEt-C3, 8,9-Di-OH-CBT-C5, CBDA-C5, and 9-OH-CBT-C5 ester.

[0126] Examples of various types of cannabinoids include DCBF-C5, CBF-C5, OH-iso-HHCV-C3OTHC, cannabiditran, cis-Δ 9 -THC, CBCON-C5, CBR, CBTT, CBCN-C5, CBCN-C3, cis-iso-Δ 7 -THCV, trans-iso-Δ 7 -THCV, trans-iso-Δ 7-THC, CBCNB, CBCNC, CBCND, (-)-(7R)-Cannabicoumarononic acid, 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol, 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone, 5-acetoxy-6-geranyl-3-n-pentyl-1,4-benzoquinone, CBM, CBX, 10α-hydroxy-Δ 9,11 -Hexahydrocannabinol, 9β,10β-epoxy-hexahydrocannabinol, 9α-hydroxyhexahydrocannabinol, 7-oxo-9α-hydroxyhexahydrocannabinol, 10α-hydroxyhexahydrocannabinol, 10αR-hydroxyhexahydrocannabinol, and 9α-hydroxy-10-oxo-Δ 6a,10a -THC is one example.

[0127] In embodiments, the Cannabis-derived primary bioactive molecule is Δ 9 -THC-C5, Δ 9 -THCAA-C5, Δ 9 -THCAB-C5, Δ 9 -THC-C4, Δ 9 -THCAA-C4, Δ 9 -THCV, Δ 9 -THCVAA, Δ 9 -THCO, Δ 9 -THCOAA, Δ 9 -THC-aldehyde, β-fenchyl(-)-Δ 9 -trans-tetrahydrocannabinolate, α-fenchyl(-)-Δ 9 -trans-tetrahydro-cannabinolate, epi-bornyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, Bornyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, α-terpenyl(-)-Δ 9 -trans-Tetrahydrocannabinolate, 4-terpenyl(-)-Δ 9 -trans-tetrahydrocannabinolate, α-cadinyl(-)-Δ 9-trans-tetrahydrocannabinolate, γ-eudesmyl(-)-Δ 9 -trans-tetrahydrocannabinolate, 8α-hydroxy-(-)-Δ 9 -trans-Tetrahydrocannabinol, 8β-hydroxy-(-)-Δ 9 -trans-Tetrahydrocannabinol, 11-acetoxy-(-)-Δ 9 -trans-tetra-hydrocannabinolic acid A, 8-oxo-(-)-Δ 9 -trans-tetrahydrocannabinol, cannabidiol, (-)-Δ 9 -trans-tetrahydro-cannabiphorol, (-)-Δ 9 -trans-tetrahydrocannabihexol, Δ 8 -THC, Δ 8 -THCA, 10α-OH-Δ 8 -THC, 10β-OH-Δ 8 -THC, 10a-α-hydroxy-10-oxo-Δ 8-THC, (E)CBG, (E)CBGA, (E)CBGG, (E)CBGAM, (E)CBGV, (E)CBGVA, (Z)CBGA, 5-acetyl-4-hydroxy-cannabigerol, (±)-6,7-trans-epoxycannabigerolic acid, (±)-6,7-cis-epoxycannabigerolic acid, (±)-6,7-cis-epoxycannabigerol, (±)-6,7-trans-epoxycannabigerolic acid Gerol, Camageol, Sesquicannabigerol, CBD-C5, CBDA-C5, CBDM-C5, CBD-C4, CBDV, CBDVA, CBD-C1, CBDH, CBDP, CBDD, CBND -C3, CBND-C5, CBE-C5, CBEAA-C5, CBEAB-C5, CBE-C3, CBEAB-C3, CBL, CBLA, CBLV, CBC, CBCA, ±CBCV, +CBCV, CBCV A, 4-acetoxy-CBC, (±)-3"-hydroxy-Δ4"-cannabichromene, (-)-7-hydroxy-cannabichroman, CBC-C3, CBN-C5, CBNA-C5, CBN-C4, CBN-C3, CBN-C2, CBN-C1, CBNM-C5, 8-OH-CBN, 8-OH-CBNA, 1'S-OH-CBN, 4-terpenyl-cannabinolate, (-)-trans-CBT-C5, ( +)-trans-CBT-C5, (±)-cis-CBT-C5, (±)-trans-CBT-C3, CBT-C3-homolog, (-)-trans-CBT-OEt-C5, (-)-trans-CBT-OEt-C3, 8,9-di-OH-CBT-C5, CBDA-C5, 9-OH-CBT-C5 ester, DCBF-C5, CBF-C5, OH-iso-HHCV-C3OTHC, cannabiditran, cis-Δ 9 -THC, CBCON-C5, CBR, CBTT, CBCN-C5, CBCN-C3, cis-iso-Δ 7 -THCV, trans-iso-Δ 7 -THCV, trans-iso-Δ 7-THC, CBCNB, CBCNC, CBCND, (-)-(7R)-Cannabicoumarononic acid, 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol, 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone, 5-acetoxy-6-geranyl-3-n-pentyl-1,4-benzoquinone, CBM, CBX, 10α-hydroxy-Δ 9,11 -Hexahydrocannabinol, 9β,10β-epoxyhexahydrocannabinol, 9α-hydroxyhexahydrocannabinol, 7-oxo-9α-hydroxyhexahydrocannabinol, 10α-hydroxyhexahydrocannabinol, 10αR-hydroxyhexahydrocannabinol and 9α-hydroxy-10-oxo-Δ 6a,10a -THC. In embodiments, "cannabinoid" also includes cannabinoid carboxylic acids and their carboxylate salts (see U.S. Pat. No. 9,376,367).

[0128] Each cannabinoid will also be understood to include its isomers, such as structural and stereoisomers (including enantiomers), -A and -B isomers of each cannabinoid, double bond isomers, and other such isomers known to those skilled in the art. Thus, "THC" will, in embodiments, be understood to include THC-A and THC-B. Reference to a cannabinoid includes various alkyl chain lengths attached thereto, as exemplified by Cn, where "n" refers to the number of carbon atoms in each alkyl chain. Thus, "THC" also includes THC-C1, THC-C2, THC-C3, THC-C4, THC-C5, THC-C6, and THC-C7. Reference to a given cannabinoid also includes all possible isomers, such as its -A and -B isomers, along with all possible combinations of alkyl chain lengths, including chains consisting of 1, 2, 3, 4, 5, 6, or 7 carbon atoms, but is not limited to these. Thus, as used herein, reference to "THC" includes THC-C1 A, THC-C1 B, THC-C2 A, THC-C2 B, THC-C3 A, THC-C3 B, THC-C4 A, THC-C4 B, THC-C5 A, THC-C5 B, THC-C6 A, THC-C6 B, THC-C7 A, and THC-C7 B. As will be apparent to those skilled in the art, such logic applies to all cannabinoids disclosed herein. THC is used merely to illustrate such logic and should not be construed as limiting.

[0129] In embodiments, cannabinoids may further comprise additional chemical moieties substituted thereon, including methyl, alkyl, alkenyl, methoxy, alkoxy, acetyl, carboxyl, carbonyl, oxo, ester, hydroxyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, cycloalkylalkenyl, cycloalkenylalkyl, cycloalkenylalkenyl, heterocyclylalkenyl, heteroarylalkenyl, arylalkenyl, heterocyclyl, aralkyl, cycloalkylalkyl, heterocyclylalkyl, heteroarylalkyl, etc. In embodiments, cannabinoids include "synthetic cannabinoids."

[0130] In some embodiments, the plant parts include both THC and CBD. In some embodiments, the plant parts include a plant extract containing both THC and CBD. In some embodiments, the plant parts include both THC and CBD as primary bioactive molecules from a plant (e.g., Cannabis). In some embodiments, the plant parts include both THC and CBD in a weight ratio of about 100:1 to 1:100, 50:1 to 1:50, 10:1 to 1:10, 5:1 to 1:5, 2:1 to 1:2, 5:3 to 3:5, or 3:2 to 2:3 (inclusive). In some embodiments, the plant parts include both THC and CBD in a molar ratio of about 100:1 to 1:100, 50:1 to 1:50, 10:1 to 1:10, 5:1 to 1:5, 2:1 to 1:2, 5:3 to 3:5, or 3:2 to 2:3 (inclusive).

[0131] In some embodiments, the plant parts contain both THC and CBD in a weight ratio of about 100:1, 50:1, 10:1, 5:1, 2:1, 5:3, 3:2, or 1:1. In some embodiments, the plant parts contain both THC and CBD in a molar ratio of about 100:1, 50:1, 10:1, 5:1, 2:1, 5:3, 3:2, or 1:1. In some embodiments, the plant parts contain THC and CBD in a weight ratio of about 1:100, 1:50, 1:10, 1:5, 1:2, 3:5, 2:3, or 1:1. In some embodiments, the plant parts contain both THC and CBD in a molar ratio of about 1:100, 1:50, 1:10, 1:5, 1:2, 3:5, 2:3, or 1:1. In embodiments, the plant parts include both THC and CBD in a weight ratio of about 1:5 to 5:1, including about 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, and 5:1. In some embodiments, the plant parts include both THC and CBD in a molar ratio of about 1:5 to 5:1, including about 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, and 5:1. In embodiments, the plant parts include both THC and CBD in a weight ratio of about 1:1. In embodiments, the plant parts include both THC and CBD in a molar ratio of about 1:1. In embodiments, the plant parts include a plant extract (e.g., a Cannabis extract) that includes both THC and CBD, such as in any of the weight ratios above. In embodiments, the Cannabis extract includes both THC and CBD in any of the molar ratios above. In embodiments, the Cannabis extract contains both THC and CBD in any of the molar ratios above.

[0132] In some embodiments, the therapeutic combination includes a second bioactive molecule derived from Cannabis, hi some embodiments, the second bioactive molecule derived from Cannabis is a flavone and / or flavonoid, a terpene and / or terpenoid, a carbohydrate, a fatty acid or fatty acid ester (FAE), an amide, an amine, a phytosterol, or a phenolic compound.

[0133] Flavonoids are a broad class of water-soluble polyphenolic molecules (i.e., containing a phenyl group (-CH) linked to a hydroxyl group (-OH)), of which approximately 20 species are widely present in cannabis. Their primary function is to provide color to plants, particularly flowers. In cannabis, the deep purple color is due to the flavonoids anthocyanins and anthoxanthins. In addition to coloring, flavonoids have been shown to confer health benefits through regulating cell signaling pathways and through various anti-inflammatory, antioxidant, antifungal, and anticancer activities. For example, the cannabis flavonoid apigenin has potent anxiolytic, anti-inflammatory, and anticancer properties, and butin has been shown to reduce oxidative stress-related cellular dysfunction. Other bioactive flavonoids found in Cannabis include cannaflavin, kaempferol, orientin, luteolin, quercetin, silymarin, and vitexin.

[0134] In embodiments, flavonoids include those broadly described in Radwan 2021, including orientin, vitexin, isovitexin, apigenin, luteolin, kaempferol, and quercetin flavonoids, which, in embodiments, may be methylated, glycosylated, prenylated, or geranylated.

[0135] In embodiments, the flavonoid is orientin, orientin-O-glucoside, orientin-7-O-glucoside, orientin-7-O-rhamnoglucoside, vitexin, vitexin-O-glucoside, vitexin-7-O-glucoside, vitexin-7-O-rhamnoglucoside, citisoside, citisoside glucoside, isovitexin, isovitexin-O-glucoside, isovitexin-7-O-glucocarbinoside, isovitexin-7-O-rhamnoglucoside, apigenin-7-O-glucoside, apigenin-7-O-glucuronide , apigenin-7-O'P-coumaroylglucoside, 6-prenylapigenin, apigenin-6,8-di-gluco-pyranoside, luteolin-C-glucuronide, luteolin-7-O-glucuronide, crabflavin A, crabflavin B, crabflavin C, chrysoeriol, kaempferol-3-O-diglucoside, quercetin-3-O-glucoside, quercetin-3-O-diglucoside, kaempferol-3-O-sophoroside, quercetin-3-O-sophoroside, rutin, quercetin, naringenin, or naringin.

[0136] Terpenes are a large class of organic hydrocarbon compounds containing one or more repeating units of a five-carbon building block known as the isoprene unit (i.e., 2-methyl-1,3-butadiene, which has the molecular formula CH). As a group, terpenes, which are isoprene polymers, are often referred to as the "isoprenoid group." The isoprene units may be linked end-to-end to form linear chains or may be arranged to form rings (hence the molecular formula CH). n where n is the number of linked isoprene units. Terpenes are classified according to the number of isoprene units they contain: hemiterpenes (1 unit), monoterpenes (2 units), sesquiterpenes (3 units), diterpenes (4 units), sesterterpenes (5 units), triterpenes (6 units), sesquaterpenes (7 units), tetraterpenes (8 units), and polyterpenes (9 or more units).

[0137] Terpenes are sometimes referred to as "terpenoids" when they undergo oxidation and acquire additional oxygen-containing functional groups (e.g., after cannabis is cured and dried) or when modified by the addition or removal of functional groups (e.g., methyl groups (-CH3)). The presence and specific combinations of terpenes impart distinctive odors and flavors to different plants (and different cannabis strains). In cannabis, terpenes are the largest group of phytochemicals, with at least 120 molecules identified. Terpenes typically account for 10-20% of the total oil secreted by the resin glands of cannabis. Terpenes comprise the majority of the chemicals in smoke from heated or vaporized cannabis flowers, often accounting for more than 50%, while cannabinoids typically account for 10-20%.

[0138] While cannabinoids are more commonly understood to be responsible for the psychosomatic effects of cannabis, terpenes also exhibit a wide range of such effects (see, e.g., Russo. Br J Pharmacol. 2011;163(7):1344-1364). For example, the terpene β-myrcene has been shown to have sedative effects and is thought to be responsible for the heavy "body high." β-Myrcene has also been demonstrated to reduce inflammation, block liver carcinogenesis, and act as an analgesic and muscle relaxant. The terpenes linalool, nerolidol, and pulegone also exhibit sedative effects. Others, such as limonene and terpinolene, in contrast, exhibit stimulating effects. Other terpenes exhibit more distinct effects. For example, α-humulene has appetite suppressant properties. Limonene has anticancer, anxiolytic, and immunostimulatory properties, and nerolidol also possesses anticancer properties. β-Caryophyllene has anti-inflammatory and gastric cytoprotective effects. Pentacyclic triterpenes such as β-amyrin and cycloartenol exhibit antibacterial, antifungal, anti-inflammatory, and anticancer properties.

[0139] Terpenes readily cross the blood-brain barrier (BBB) ​​and, when ingested, may exert their effects by modulating neurotransmitters in the brain. For example, linalool has been shown to modulate glutamatergic and gabaminergic neurotransmitters, which may explain its analgesic, anxiolytic, anti-inflammatory, and anticonvulsant properties. α-Pinene is an acetylcholinesterase inhibitor and may therefore aid memory. Phytol, a diterpene, increases gabaminergic expression. Other terpenes have been shown to affect serotonergic and dopaminergic neurotransmitters.

[0140] Some terpenes interact directly with the ECS. For example, β-caryophyllene selectively binds to CB2 receptors as a functional CB2 agonist, supporting its anxiolytic and antidepressant properties. Terpenes have also been shown to alter cell membrane permeability and modulate the effects of THC and other cannabinoids. Because terpenes are lipophilic, they interact with lipid membranes, ion channels, a variety of different receptors (including both G protein-coupled odorant receptors and neurotransmitter receptors), and enzymes. Through these and other mechanisms, terpenes in cannabis may not only elicit effects alone or in combination with other terpenes, but may also modulate (including synergistically) the effects of the various cannabinoids present.

[0141] In embodiments, the Cannabis-derived secondary bioactive molecule may be any of a hemiterpene, monoterpene, sesquiterpene, diterpene, sesterterpene, triterpene, sesquiterpene, tetraterpene, polyterpene, carbohydrate, fatty acid and its ester, amide, amine, phytosterol, or phenolic compound.

[0142] Examples of monoterpenes include myrcene, cis-β-ocimene, trans-β-ocimene, p-cymene, α-terpinene, β-phellandrene, γ-terpinene, α-terpinolene, α-phellandrene, 3-phenyl-2-methyl-prop-1-ene, α-pinene, β-pinene, camphene, Δ 3 -Karen, Δ 4 -carene, sabinene, α-thujene, linalool, citral B, nerol, geraniol, epsilon, citronellol, 2-methyl-2-hepten-6-one, geranylacetone, m-mentha-1,8-(9)-dien-5-ol, carvacrol, carvone, α-terpineol, terpinen-4-ol, purugone, dihydrocarvone, β-terpineol, dihydrocarbyl acetate, p-cymen-8-ol, β-cyclositol These include ral, safranal, cis-linalool oxide, perylene, sabinol, thujyl alcohol, linalool oxide, cis-carveol, cis-sabinene hydrate, sabinene hydrate, 8-cineole, 1,4-cineole, piperitone oxide, piperitenone oxide, fenchyl alcohol, fenchone, borneol, bornyl acetate, camphor, camphene hydrate, α-pinene oxide, pinocarveol, and pinocarvone.

[0143] Examples of sesquiterpenes include α-caryophyllene, β-caryophyllene, caryophyllene oxide, curcumene, α-trans-bergamotene, α-selinene, β-farnesene, longifolene, humulene epoxide I, humulene epoxide II, caryophyllene alcohol (caryophyllenol), β-bisabolene, alloaromadendrene, calamenene, α-copaene, nerolidol, α-gujunene, iso-caryophyllene, β-selinene, selina-3,7(11)-diene, selina-4(14),7(11)-diene, α-bisabolol, α-cedrene, α-cubebene, δ-bisabolol, α-cedrene, α-cubebene, δ-bisabolol, δ-bisabolene ... Examples of diterpenes include phytol and neophytadiene. Examples of triterpenes include freidolin and epifreedelanol. Examples of diterpenes include phytol and neophytadiene. Examples of triterpenes include freidolin and epifreedelanol. Examples of different types of terpenes include vomifoliol, dihydrovomifoliol, β-ionone, and dihydroactinidiolide.

[0144] Examples of phenolic compounds include, for example, lignans, spiroindanes, dihydrostilbenes, dihydrophenanthrene derivatives, stilbenoids, cannabispirans, denbinobin, catechin, chlorogenic acid, caffeic acid, epicatechin, luteolin-7-O-glucoside, p-coumaric acid, caffeoyl, tyramine, ferulic acid, quercetin-3-glucoside, kaempferol, apigenin-7-glucoside, luteolin, cannabidiol, and apigenin, in addition to those disclosed as being part of the terpenes and flavonoids.

[0145] In embodiments, the Cannabis-derived secondary bioactive molecule may be any of the following: orientin, orientin-O-glucoside, orientin-7-O-glucoside, orientin-7-O-rhamnoglucoside, vitexin, vitexin-O-glucoside, vitexin-7-O-glucoside, vitexin-7-O-rhamnoglucoside, citisoside, citisoside-glucoside, isovitexin, isovitexin-O-glucoside, isovitexin-7-O-glucocarbinoside, isovitexin-7-O-rhamnoglucoside, apigenin-7-O-glucoside, apigenin-7-O-glucuronide, apigenin-7-O'P-coumaroylglucoside, 6-prenylapigenin, apigenin Flavonoids including β-6,8-di-glucopyranoside, luteolin-C-glucuronide, luteolin-7-O-glucuronide, crabflavin A, crabflavin B, crabflavin C, chrysoeriol, kaempferol-3-O-diglucoside, quercetin-3-O-glucoside, quercetin-3-O-diglucoside, kaempferol-3-O-sophoroside, quercetin-3-O-sophoroside, rutin, quercetin, naringenin, and naringin; myrcene, cis-β-ocimene, trans-β-ocimene, p-cymene, α-terpinene, β-phellandrene, γ-terpinene, α-terpinolene, α-phellandrene, 3-phenyl-2-methyl-prop-1-ene, α-pinene, β-pinene, camphene, Δ 3 -Karen, Δ 4-Carene, sabinene, α-thujene, linalool, citral B, nerol, geraniol, epsilon, citronellol, 2-methyl-2-hepten-6-one, geranylacetone, m-mentha-1,8-(9)-dien-5-ol, carvacrol, carvone, α-terpineol, terpinen-4-ol, purugone, dihydrocarvone, β-terpineol, dihydrocarbyl acetate, p-cymen-8-ol, β-cyclocitral, safranal, cis-linalool oxide, perylene, sabinol, thujyl alcohol, linalool oxide, cis-carveol, cis-sabinene hydrate, sabinene hydrate, 8-cineole, 1,4-cineole, piperitol phenone oxide, piperitenone oxide, fenchyl alcohol, fenthion, borneol, bornyl acetate, camphor, camphene hydrate, α-pinene oxide, pinocarveol, pinocarvone, α-caryophyllene, β-caryophyllene, caryophyllene oxide, curcumene, α-trans-bergamotene, α-selinene, β-farnesene, longifolene, humulene epoxide I, humulene epoxide II, caryophyllene alcohol (caryophyllenol), β-bisabolene, allo-aromadendrene, calamenene, α-copaene, nerolidol, α-gurjunene, iso-caryophyllene, β-selinene, selina-3,7(11)-diene, selina-4(14),7(11)-diene, α-bisabolol, α-cedrene, α-cubebene, δ-cadinene, epi-β-santalene, farnesol, γ-cadinene, γ-elemene, γ-eudesmol, guaol, ledol, trans-trans-α-farnesene, (Z)-β-farnesene, farnesylacetone, α-cadinene, α-cis-bergamotene, α-eudesmol, α-guaene, α-longipinene, α-ylangene, β-elemene, β-eudesmol, epi-α-bisabolol, γ-cis-bisabolene, γ-curcumene, γ-muolene, γ-trans-bisabolene, viridiflorene, germacrene-B, clobandiol, phytol, neophytadiene, phytolene, Lydrin, epifreedelanol, vomifoliol, dihydrovomifoliol, β-ionone and dihydroactinidiolide, carbohydrates, fatty acids and their esters, amides, amines, phytosterols, and lignans, phenolic compounds including spiroindanes, dihydrostilbenes, and dihydrophenanthrene derivatives, stilbenoids, cannabispirans, denbinobin, catechin, chlorogenic acid, caffeic acid, epicatechin, luteolin-7-O-glucoside, p-coumaric acid, caffeoyl, tyramine, ferulic acid, quercetin-3-glucoside, kaempferol, apigenin-7-glucoside, luteolin, cannabidiol, and apigenin.

[0146] In embodiments, the cannabis-derived bioactive molecule is selected from the group consisting of those disclosed in Russo. Br J Pharmacol. 2011; 163(7):1344-1364; Gertsch et al. Br J Pharmacol. 2010; 160(3):523-529; Tahir et al. J Cannabis Res. 2021 Mar 15; 3(1):7; Thomas & ElSohly. Biosynthesis and pharmacology of phytocannabinoids and related chemical constituents. The Analytical Chemistry of Cannabis; Elsevier: Amsterdam, The Netherlands, 27-41; De Backer et al. J Chromatogr B Analyt Technol Biomed Life Sci. 2009; 877(32):4115-4124; and Hazekamp et al. J Liq Chromatogr Relat Technol. 2004;27(15):2421-2439).

[0147] 2. Dipteryx In some embodiments, the plant parts of the therapeutic combination are derived from Dipteryx. In embodiments where a plant part is described as being "derived" from Dipteryx, it will be understood that the plant part includes, by way of non-limiting example, Dipteryx material such as raw (i.e., unprocessed) Dipteryx biomass, a Dipteryx extract (e.g., an extract described herein, e.g., an aqueous extract, such as an aqueous solution, and / or an ethanolic extract), or material derived from Dipteryx, including a molecule naturally occurring in Dipteryx (e.g., a primary or secondary bioactive molecule described in an embodiment herein), whether the molecule is actually obtained by isolating the molecule from Dipteryx or whether it is obtained by another means (e.g., chemical synthesis).

[0148] In some embodiments, the therapeutic combination comprises a Dipteryx extract. In some embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule from a species of the genus Dipteryx.

[0149] In some embodiments, the primary bioactive molecule and / or the secondary bioactive molecule is from Dipteryx, while in other embodiments, the primary bioactive molecule and / or the secondary bioactive molecule is from another genus in the tribe Dipterygeae, which further includes the genera Monopteryx, Pterodon, and Taralea.

[0150] In embodiments, the primary and / or secondary bioactive molecules are derived from Dipteryx, including D. odorata, also referred to herein as "kumaru tree" or "kumaru." Dipteryx is a genus of large trees in the family Fabaceae, native to South and Central America and the Caribbean, and formerly known as the genus Coumarouna. In some embodiments, the bioactive molecule, such as coumarin, is derived from a plant in the Dipteryx genus, such as Dipteryx odorata (i.e., coumarin), while in other embodiments, the bioactive molecule, such as coumarin, is derived from a plant in another genus, including any genera in the Amburaneae tribe, such as Amburana, Mildbraediodendron, Myrocarpus, Myrospermum, Myroxylon, and Petaladenium. Thus, in some embodiments, species from such other genera, and extracts and bioactive molecules therefrom, are considered equivalents of similar extracts and bioactive molecules from Dipteryx.

[0151] In some embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from the species Dipteryx odorata.

[0152] Dipteryx odorata is known by many names, including Coumarouna odorata, cumar tree (Brazil), tonka bean tree, Brazilian teak, Tonkin bean, rumara, cumar (Guyana), cumarzeiro (Portugal), Charapira (Peru), Charapira del Murcielago (Peru), Zihuahuaco (Peru), and Sarapia (Venezuela, Colombia), all of which may be used interchangeably or considered equivalent in accordance with the disclosure herein. Dipteryx odorata is a large tropical rainforest canopy tree that grows up to 30 meters in height in the Amazon. It can be found in Brazil, Venezuela, Guyana, French Guiana, Suriname, Nigeria, Peru, and Colombia. Historically, the seeds and bark of Dipteryx odorata have been used by local Amazonian people: the seeds were fermented with rum and used as a shampoo for snakebites, cuts, bruises, coughs, and rheumatism; the seed oil was used to prevent earaches and ear infections; and the bark was used as a bath additive for fever sufferers.

[0153] The seeds (also called "tonka beans") from the cumar tree (Tonka bean) contain the bioactive molecule coumarin, which has a pleasant vanilla-like scent and has been used as a flavoring agent in perfumes, soaps, foods, and tobacco products. These preparations typically involve fermenting the beans (e.g., with local rum) and drying (typically air-drying), resulting in a dusting of coumarin crystals on the outside of the seeds, giving them a matte appearance.

[0154] In embodiments, the disclosed combinations (e.g., "therapeutic combinations," a term that also includes the disclosed compositions by implication) that include bioactive molecules from Dipteryx, such as coumarin, can exhibit antispasmodic, emmenagogue, cardiotonic, antiasthmatic, and anti-inflammatory effects.

[0155] a. Primary and secondary bioactive molecules from Dipteryx In some embodiments, the therapeutic combination comprises a first bioactive molecule and / or a second bioactive molecule derived from Dipteryx.

[0156] In embodiments, the primary bioactive molecule from Dipteryx is coumarin (2H-chromen-2-one, 2H-1-benzopyran-2-one), a colorless crystalline solid that gives tonka beans their characteristic vanilla-like odor and flavor and may also act as a chemical defense against predators.

[0157] Coumarins are obtained from Dipteryx and countless other plant species, including vanilla grass (Anthoxanthum odoratum), sweet woodruff (Galium odoratum), sweetgrass (Hierochloe odorata), sweet clover (Melilotus spp.), cinnamon, including Ceylon cinnamon or "true cinnamon" (Cinnamomum verum), Chinese cinnamon or Chinese cassia (C. cassia), Indonesian cinnamon or Padang cassia (C. burmannii), Saigon cinnamon or Vietnamese cassia (C. loureiroi), Deatong (Carphephorus odoratissimus), Tilo (Justicia pectoralis), mullein (Verbascum spp.), many cherry trees in the Prunus genus, and in trace amounts from strawberries, blackcurrants, apricots, and cherries (Ananthakrishnan et al. Int J Food Sci Pollut Res (2018) 14:199–204). Prop. 2018;21:50-57; Wang et al. J Agric Food Chem. 2013;61(18):4470-476; Khan & Ehab. Deertongue. In: Leung's Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. John Wiley & Sons. 2010.240-242; Ieri et al. Food Chem. 2012;135(4):2157-2162; and National Center for Biotechnology Information. PubChem Compound Summary for CID 323, Coumarin). In some alternative embodiments, the coumarin is extracted, isolated, or otherwise obtained from any of these or other such species other than from Dipteryx.

[0158] In some embodiments, the biologically active molecule is a compound derived from coumarin (e.g., a phenylpropanoid, a coumarin, or a coumarinoid) and may be used in the disclosed combinations, compositions, and methods; such compounds include, for example, the biologically active molecules umbelliferone, aesculetin, herniarin, psoralen, dicoumarol, imperatorin, brodifacoum, bromadiolone, difenacoum, auraptene, ansacrine, phenprocoumon, PSB-SB-487, PSB-SB-1202, scopoletin, and warfarin (see, e.g., Laposata et al. N Engl J Med. 2007;356(2):174-182; Syah et al. Nat Prod Res. 2009;23(7):591-594).

[0159] In embodiments, the secondary bioactive molecule from Dipteryx is coumaric acid, a coumarin derivative, an isoflavone, a lupeol derivative, a fatty acid ester, (±)-balanofonin, (-)-lariciresinol, 3'-hydroxyretsin-8-methyl ether, 5-methoxyxanthocercin A, 6,4'-dihydroxy-3'-methoxyaurone, 7-hydroxychromone, 7,3'-dihydroxy-8,4'-dimethoxy-isoflavone, betulin, butin, coumaric acid-β-glucoside, dipteryxin, dip The compounds are tellixic acid, eriodictyol, ferulic acid, isoliquiritigenin, lupeol, melilotoside, melilotoside-1-p-coumaryl-β-d-glucose, methyl-linolenic acid, methyl-oleic acid, O-coumaric acid, O-hydroxycoumaric acid, odoratin, P-hydroxybenzoic acid, lettucin, lettucin-8-methyl ether, sulfuretin, salicylic acid, afrormicin, castinin, linoleic acid, oleic acid, 3',4',7'-trihydroxyflavone, luteolin, and umbelliferone.

[0160] In embodiments, bioactive molecules derived from Dipteryx further include those found in Trincone, A. (Ed.). (2019). Enzymatic Technologies for Marine Polysaccharides (1st ed.). CRC Press; Jofre et al. Mar Drugs. 2020; 18(2): 75; or Gomez-Zavaglia et al. Antioxidants (Basel). 2019; 8(9): 406.

[0161] C. Algae In some embodiments, the therapeutic combination comprises an algae part. In some embodiments, the algae part comprises an algae extract. In some embodiments, the algae part comprises an algae-derived bioactive molecule. In some embodiments, the algae extract comprises an algae-derived bioactive molecule. For example, in some embodiments, the algae part comprises a primary bioactive molecule and / or a secondary bioactive molecule from algae. In embodiments, the algae extract comprises a primary bioactive molecule and / or a secondary bioactive molecule from algae. In embodiments, the disclosed therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule from algae.

[0162] In embodiments where the algae parts are described as being "derived" from algae, it will be understood that the algae parts include algae-derived materials, including, by way of non-limiting example, algal matter such as raw (i.e., unprocessed) algal biomass, algal extracts (e.g., extracts described herein such as aqueous extracts and / or ethanolic extracts), or molecules naturally present in algae (e.g., primary or secondary bioactive molecules described in embodiments herein), whether said molecules are actually obtained by isolating the molecule from the algae or whether they are obtained by another means (e.g., chemical synthesis).

[0163] Algae, broadly defined, refers to a large, polyphyletic group of photosynthetic eukaryotic organisms. In general, there is no universally accepted definition of algae, but one way of describing the multiple groups that encompass "algae" is that they have chlorophyll as their primary photosynthetic pigment and lack a sterile cell envelope around their reproductive cells (Lee. Phycology. Cambridge University Press. 2008).

[0164] Algae include species that can live in freshwater and / or saltwater and generally include Euglenophyta (euglenoids), Chrysophyta (golden brown algae and diatoms), Pyrrophyta (fire algae), Chlorophyta (green algae), Rhodophyta (red algae), Phaeophyta (brown algae), and Xanthophyta (yellow-green algae) (Baweja & Sahoo. (2015). Classification of algae. The algae world, 31-55).

[0165] In embodiments, the disclosed combinations include marine algae. In embodiments, the marine algae is any of brown algae (Phaeophyta), green algae (Chlorophyta), and red algae (Rhodophyta). In embodiments, the marine algae is marine red algae. In embodiments, the marine red algae is from the family Bangiaceae. In embodiments, the marine red algae is from the genus Pyropia or Porphyra.

[0166] Culturally, Porphyra has been cultivated in East Asia and used to produce "nori" and other forms of edible seaweed, such as that used in sushi, and to bind and fix rice to other proteins, such as fish. Some species of Porphyra are also harvested in Western Europe to produce seaweed bread, eaten primarily in Wales as part of traditional local cuisine (Harford. Laver. https: / / www.eatweeds.co.uk / laver-porphyra.ndAccessed June 6, 2022).

[0167] In one embodiment, the red algae is Porphyra umbilicalis. Broadly speaking, umbilicalis is a membranous, monolamellar alga with irregularly lobed olive- to brown-colored leaves (up to 200 mm long) that split from a central holdfast, generally giving it a lettuce-like appearance. Like other Porphyra species, umbilicalis grows on rocks and occasionally mussels in mid-tide and splash zones, and is abundant from spring through summer. In one embodiment, the red algae is Pyropia perforata. Perforata is generally purple / green in color, has lobed blades, and can reach 30 cm in width and length. Perforata grows epiphytically on rocks or other algae. In one embodiment, the red alga is Pyropia yezoensis, which has a disc-shaped holdfast and a short stalk, membranous, single-layered folded blades, and is colored red, brown, or dark green.

[0168] 1. Primary and secondary bioactive molecules derived from algae In some embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from algae.

[0169] In embodiments, the algae-derived primary bioactive molecule is a primary bioactive molecule from a genus of the family Bangiaceae, hi embodiments, the algae-derived primary bioactive molecule is a primary bioactive molecule from a species of the genus Pyropia or Porphyra.

[0170] In embodiments, the primary bioactive molecule derived from algae is a primary bioactive molecule derived from Porphyra umbilicalis. In embodiments, the primary bioactive molecule derived from algae is a primary bioactive molecule derived from Pyropia perforata. In embodiments, the primary bioactive molecule derived from algae is a primary bioactive molecule derived from Pyropia yezoensis.

[0171] In embodiments, the primary bioactive molecule from Pyropia or Porphyra is a porphyran or oligoporphyran, a polysaccharide, a peptide (e.g., monopeptide, dipeptide, tripeptide, protein), a phycobiliprotein (e.g., phycoerythrin, phycoerythrobilin, phycocyanin, allophycocyanin), a mycosporine amino acid (e.g., Porphyra-334, shinorine), an essential amino acid (e.g., isoleucine, leucine, threonine, methionine, phospholipid ... essential amino acids (e.g., phenylalanine, lysine, histidine, valine, arginine, cysteine), non-essential amino acids (e.g., aspartic acid, glutamic acid, glycine, tyrosine, serine, alanine, proline), carotenes (e.g., lutein, zeoxanthin, α-carotene, β-carotene, astaxanthin), intermediate carotenoids (e.g., α-cryptoxanthin, zeinoxanthin, β-cryptoxanthin), glycoproteins, and aminosulfonic acids (e.g., taurine).

[0172] In embodiments, the primary bioactive molecule from Pyropia or Porphyra is a porphyran or oligoporphyran. In embodiments, the primary bioactive molecule from Pyropia or Porphyra is a polysaccharide. In embodiments, the polysaccharide is any of glucose, fructose, galactose, and mannose. In embodiments, the primary bioactive molecule from Pyropia or Porphyra is a peptide. In embodiments, the peptide is any of monopeptides, dipeptides, tripeptides, and proteins. In embodiments, the primary bioactive molecule from Pyropia or Porphyra is a phycobiliprotein. In embodiments, the phycobiliprotein is any of phycoerythrin, phycoerythrobilin, phycocyanin, and allophycocyanin. In embodiments, the primary biologically active molecule from Pyropia or Porphyra is a mycosporine amino acid. In embodiments, the mycosporine amino acid is any of Porphyra-334 and shinorine. In embodiments, the primary biologically active molecule from Pyropia or Porphyra is an essential amino acid. In embodiments, the essential amino acid is any of isoleucine, leucine, threonine, methionine, phenylalanine, lysine, histidine, valine, arginine, and cysteine. In embodiments, the primary biologically active molecule from Pyropia or Porphyra is a non-essential amino acid. In embodiments, the non-essential amino acid is any of aspartic acid, glutamic acid, glycine, tyrosine, serine, alanine, and proline. In embodiments, the primary bioactive molecule from Pyropia or Porphyra is a carotene, hi embodiments, the carotene is any of lutein, zeoxanthin, α-carotene, β-carotene, and astaxanthin.In embodiments, the primary bioactive molecule from Pyropia or Porphyra is an intermediate carotenoid. In embodiments, the intermediate carotenoid is any of α-cryptoxanthin, zeinoxanthin, and β-cryptoxanthin. In embodiments, the primary bioactive molecule from Pyropia or Porphyra is a glycoprotein. In embodiments, the primary bioactive molecule from Pyropia or Porphyra is an aminosulfonic acid. In embodiments, the aminosulfonic acid is taurine.

[0173] In embodiments, the therapeutic combination comprises a bioactive molecule derived from algae, and in embodiments, the bioactive molecule is a secondary bioactive molecule derived from algae. In embodiments, the secondary bioactive molecule derived from algae is a secondary bioactive molecule derived from a genus of the family Bangiaceae. In embodiments, the secondary bioactive molecule derived from algae is a secondary bioactive molecule derived from a species of the genus Pyropia or Porphyra. In embodiments, the secondary bioactive molecule derived from algae is a secondary bioactive molecule derived from Porphyra umbilicalis. In embodiments, the secondary bioactive molecule derived from algae is a secondary bioactive molecule derived from Pyropia yezoensis.

[0174] In embodiments, the secondary bioactive molecule derived from Pyropia or Porphyra is any of a mineral, a vitamin, a lipid, a phenolic compound, and a phlorotannin.

[0175] In embodiments, the secondary bioactive molecule derived from Pyropia or Porphyra is a mineral. In embodiments, the mineral is any of potassium, phosphorus, magnesium, sodium, calcium, manganese, iron, copper, and zinc. In embodiments, the secondary bioactive molecule derived from Pyropia or Porphyra is a vitamin. In embodiments, the vitamin is any of vitamin K, ascorbic acid, folic acid, and cobalamin. In embodiments, the secondary bioactive molecule derived from Pyropia or Porphyra is a lipid. In embodiments, the lipid is a fatty acid such as eicosapentaenoic acid and palmitic acid. In embodiments, the secondary bioactive molecule derived from Pyropia or Porphyra is a phenolic compound. In embodiments, the phenolic compound is any of flavonoids, phenolic acids, polyphenolamides, and other phenolic compounds as would be understood by one of ordinary skill in the art. In embodiments, the secondary bioactive molecule from Pyropia or Porphyra is a phlorotannin, hi embodiments, the phlorotannin is any of fucol, phloroethol, fucophloroethol, equol, fuhalol, and kalmarol.

[0176] III. Obtaining bioactive molecules In some embodiments, the biologically active molecules of the therapeutic combination are commercially available and commercially sourced (e.g., Cayman Chemical Co., Ann Arbor, MI; Sigma-Aldrich, Burlington, MA).

[0177] In embodiments, the disclosed primary and secondary bioactive molecules may be obtained via, by way of non-limiting examples: extraction, synthesis, biosynthesis, whole plants, Cannabis flowers or Cannabis biomass, fruiting mycelia, fungal mycelium, fungal biomass produced in bioreactors, truffles (hardened fungal bodies), cumar seeds (tonka beans), or Porphyra or Pyropia algae, whether whole, isolated, and / or collected as fractions. Exemplary means of obtaining the bioactive molecules are disclosed.

[0178] A. Extraction In some embodiments, the extracts (e.g., fungal extracts, plant extracts, or algal extracts) used in the disclosed therapeutic combinations are obtained by use of extraction techniques known to those of skill in the art, hi some embodiments, the disclosed primary and secondary bioactive molecules are provided in the form of extracts produced according to extraction techniques known to those of skill in the art.

[0179] Without being bound by theory, broadly, extraction systems function by introducing a substance, such as a fungal, plant, and / or algal substance (e.g., containing desired primary and / or secondary bioactive molecules), into a solvent capable of separating the desired primary and / or secondary bioactive molecules from the substance to form a solution (extract) containing the solvent and the primary and / or secondary bioactive molecules.

[0180] The extracts can be used directly in the disclosed combinations, compositions, or methods, or can first be further processed, such as by further extraction, filtration, distillation, fractionation, sub-fractionation, isolation, and / or purification, and other such methods known in the art, including combinations thereof.

[0181] Various types of extraction systems exist, utilizing different methods and having different parameters (e.g., temperature, pressure, solvents), which can be tailored to a desired end product, e.g., a desired primary and / or secondary bioactive molecule. Many such characteristics will be known to those skilled in the art. Without being bound by theory, for example, extraction systems generally follow the rule that "like dissolves like." Thus, polar solvents are used to extract polar bioactive molecules, and nonpolar solvents are used to extract nonpolar bioactive molecules (Lowery & Richardson, Mechanism and Theory in Organic Chemistry, 3rd ed. Harper Collins Publishers; 1987).

[0182] General methods for extracting primary and / or secondary bioactive molecules, creating plant, algal, and fungal extracts thereof, and producing purified products containing the desired compounds free of undesirable plant, algal, or fungal material, chemicals, and other impurities are known in the art, and are described, for example, in U.S. Pat. Nos. 6,403,126, 8,846,409, and 8,895,078. See U.S. Patent Nos. 10,059,684, 10,239,808, 10,246,431, 10,300,494, 10,307,447, 10,406,453, 10,413,845, and 10,414,709, as well as U.S. Patent Application Publication Nos. 2003 / 0017216A1 and 2016 / 0038437A1, and the references cited therein, all of which are incorporated herein as if fully set forth herein.

[0183] The exemplary extraction methods and systems disclosed in such references and elsewhere herein should not be construed as limiting, and many variations will be appreciated by those skilled in the art. While exemplary extraction methods, including those described herein, are disclosed as a series of steps, other extraction methods useful in practicing the present disclosure and obtaining bioactive molecules may deviate from such steps, including altering, removing, adding, or rearranging such steps, as would be understood by one of ordinary skill in the art in light of this disclosure and general knowledge in the art.

[0184] As used herein, "extract" may refer to, for example, a botanical extract (e.g., a fungus, Psilocybe, plant, Cannabis, Dipteryx, algae, or other extract containing the primary and / or secondary bioactive molecules disclosed herein) prepared from a botanical source ("botanical" is defined herein). In some embodiments, the extract undergoes further extraction, filtration, fractionation, sub-fractionation, partial, substantial, or complete purification, or other processing to obtain a particular bioactive molecule separated from other components, and such bioactive molecule is found in a filtrate, fraction, sub-fraction, partially purified product, substantially purified product, fully purified product, isolate, or the like, and may, in some cases, be obtained as a single component or multiple single components separated from all other components. In some embodiments, the extract is obtained as a whole plant extract, whole fungal extract, or whole algae extract without being fractionated, subfractionated, partially purified, substantially purified, or completely purified, or other processed to obtain a specific bioactive molecule separated from other components, which may be referred to herein as a "whole extract." In alternative embodiments of any exemplary embodiment disclosed herein, the whole extract is replaced with a fraction, subfractionated, partially purified, substantially purified, completely purified, isolated, etc., as well as a single bioactive molecule or molecules from the extract (including in the extract), or a molecule produced synthetically, such as by partial or complete chemical synthesis, or biosynthesis.

[0185] Therefore, extracts may include purified extracts. As will be understood by those skilled in the art, "purified extract" may refer to a plant extract that has undergone further processing after preparation. In some exemplary embodiments, the purified extract may be, for example, a product obtained by soaking or heating the preparation in water and / or alcohol (e.g., depending on whether and to what extent the desired bioactive molecule is water-soluble), stirring, cooling the resulting liquid, filtering, removing unwanted products (repeated as necessary), and then evaporating enough liquid solvent to obtain the desired concentration (or completely, for example, to obtain an amorphous or crystalline precipitate), or using a spray dryer to produce a purified dry powder. Other purification techniques are known to those skilled in the art, and generally, extraction and purification techniques for obtaining highly pure bioactive compounds will be known to those skilled in the art.

[0186] To maintain the purified dry powder as a flowable powder that is easy to work with during formulation, for example when adding the dry powder to a capsule, starch or other carriers may be added to the purified extract, but when referring to the weight of the "purified extract," such carriers, diluents, or excipients are excluded from the total amount.

[0187] In embodiments, the extract may be "standardized," which refers to an extract that contains a primary and / or secondary bioactive molecule at a particular concentration. Methods for producing a standardized extract will be known to those skilled in the art, such as quantifying the concentration of the extract and diluting the extract to a standardized concentration by adding a carrier, diluent, or excipient, or further concentrating the extract to increase the concentration.

[0188] "Natural" may refer to a substance that is isolated, extracted, or otherwise obtained from a natural source, such as a fungus, plant, or algae. Thus, naturally occurring primary or secondary bioactive molecules, such as natural cannabinoids, may be isolated or extracted from a Cannabis plant. Accordingly, in various disclosed embodiments, compositions are derived from plant sources, including fungi, plants, and algae, as extracts or by other means, and comprise a botanical drug substance or a Cannabis-derived drug substance. In embodiments, such compositions comprise a botanical or Cannabis-derived drug. In other embodiments, such compositions comprise a botanical or Cannabis-derived drug that is substantially free of impurities.

[0189] In some embodiments, when the disclosed combinations or compositions include multiple extracts (e.g., fungal extracts, plant extracts, algae extracts), the concentrations of bioactive molecules contained therein are quantified (e.g., according to the methods disclosed herein and other methods known to those skilled in the art). The concentrations of bioactive molecules in the extracts may vary based on the concentrations of the bioactive molecules in the corresponding source material (e.g., raw fungal, plant, or algae biomass). Thus, the concentrations of bioactive molecules in the disclosed compositions may vary from batch to batch based on the variability of the extracts between batches. In accordance with FDA regulations (FDA. Botanical Drug Development Guidance for Industry. 2016. CDER Drug Quality. CMC), bioactive molecules (e.g., primary and / or secondary bioactive molecules disclosed herein) can be added to the extracts disclosed herein (e.g., fungal, plant, or algae extracts) or to the disclosed combinations or compositions containing such extracts. This may be done, for example, to standardize the disclosed combinations or compositions and ensure a consistent concentration of bioactive molecules from batch to batch, even though raw materials or extracts thereof may vary in their concentration of bioactive molecules.

[0190] 1. Exemplary Extraction of Molecules from Fungi In embodiments, the therapeutic combination comprises a first bioactive molecule and / or a second bioactive molecule from a fungus, hi embodiments, the first bioactive molecule and / or the second bioactive molecule are obtained by extraction of fungal material.

[0191] Without wishing to be bound by theory, fungal extraction methods can generally be described as follows: first, fungal material containing the desired primary and / or secondary bioactive molecules is obtained, optionally dried (e.g., using means such as a low temperature oven, a food dehydrator, and / or a commercial dryer), optionally ground, crushed, soaked, and / or milled to form a substantially fine powder, which is optionally sieved, for example, for consistency.

[0192] The fungal material is then combined with a solvent (e.g., methanol, ethanol, water, or a mixture thereof) capable of extracting the desired primary and / or secondary bioactive molecules to form a slurry, which is then stirred for a predetermined period of time, e.g., about 24 hours, to promote extraction. The solvent is then filtered and collected. In embodiments, the filter may include cheesecloth, filter paper, and / or a filtration system. If desired, the extract may be evaporated using any of several evaporation methods that involve the application of heat, such as ambient temperature evaporation, rotary evaporation, vacuum evaporation, and those that utilize ovens to create more concentrated extracts, as well as combinations thereof. In embodiments, the fungal material may be resaturated with the same or a different solvent after the initial filtration to complete secondary, tertiary, or further extractions. Extraction methods and variations thereof may be selected as appropriate by those skilled in the art.

[0193] In embodiments, heated extraction is utilized. In embodiments, heated extraction generally follows the process described above, except, for example, that the solvent is heated, stirring is completed in a heated environment, or the extraction is otherwise performed at an elevated temperature relative to ambient temperature. In embodiments, the extraction is completed at a temperature at which psilocybin is substantially dephosphorylated to psilocin. In embodiments, heated extraction is completed at a temperature greater than about 70°C. In embodiments, the extraction is performed below a temperature at which substantial dephosphorylation of psilocybin occurs. In embodiments, the extraction occurs at a temperature or temperature range selected to produce a desired ratio of psilocybin to psilocin, for example, based on the ratios in the starting materials.

[0194] In some embodiments, ultrasonic extraction is utilized. In some embodiments, mushrooms or other fungal material are dried, cut, and / or crushed prior to ultrasonic extraction. In some embodiments, an ultrasonic extractor is utilized to expose the fungal material to ultrasonic vibrations via an ultrasonic probe. In some embodiments, the ultrasonic probe vibrates at 20 kHz or greater. Without being bound by theory, as ultrasonic waves travel through a liquid, they generate high-pressure (compression) and low-pressure (rarefaction or expansion) cycles (Hielscher Ultrasonics. Fast and Simple Ultrasonic Cannabis Extraction. https: / / www.hielscher.com / fast-simple-ultrasonic-cannabis-extraction.htm. Accessed February 19, 2024). During the low-pressure vacuum cycle, tiny vacuum bubbles or cavities are generated in the liquid, which grow through several pressure cycles. The compression phase of the liquid and bubbles creates a positive pressure, while the rarefaction phase creates a vacuum (negative pressure). During the compression-expansion cycle, cavities in the liquid grow until they are too large to absorb any more energy, at which point they implode. The implosion of these cavities produces a variety of high-energy sonomechanical effects known as acoustic / ultrasonic cavitation (id.), during which gas bubbles are generated in the sonicated liquid, rupturing the cell walls of plant tissue and releasing intracellular compounds, including primary and / or secondary bioactive molecules (Suslick. Sonoluminescence and Sonochemistry. In: Meyers, Ed. Encyclopedia of Physical Science and Technology. 3rd ed. Academic Press. 2001).

[0195] In some embodiments, extraction is performed using a Soxhlet extractor. In some embodiments, the Soxhlet extraction is performed using an ethanol and water solvent (e.g., 80% ethanol and 20% water). In some embodiments, the solvent is heated to reflux, and the solvent vapor rises up a distillation arm and flows into a chamber containing a thimble of fungal material. A condenser on top of the apparatus cools the solvent vapor and drips it into the chamber containing the fungal material. As a result, the chamber containing the fungal material slowly fills with warm solvent. When the Soxhlet chamber is nearly full, the chamber is emptied by a siphon, and the solvent is returned to the distillation flask. In some embodiments, the Soxhlet extraction is performed for about 6 to about 10 hours, including about 6 hours, about 7 hours, about 8 hours, about 9 hours, or about 10 hours, using standard equipment known to those skilled in the art. In some embodiments, the Soxhlet extraction is performed for about 7 hours. In other embodiments, the Soxhlet extraction is performed for less than 6 hours or more than 10 hours.

[0196] Extracts of fungal material (including primary and / or secondary bioactive molecules) produced according to different methods described herein or other methods known to those of skill in the art can be combined to provide various benefits. For example, fungal extracts produced according to different techniques may contain different concentrations of primary and / or secondary bioactive molecules, and combining such extracts in the disclosed therapeutic combinations can impart advantageous or synergistic properties.

[0197] In some embodiments, the fungal portion of the disclosed therapeutic combination comprises a mixture of fungal extracts. In some embodiments, the fungal portion of the disclosed therapeutic combination comprises a mixture of ultrasonic and Soxhlet extracts. In some embodiments, the mixture comprises an ultrasonic:Soxhlet ratio (e.g., volume ratio (v / v) or weight ratio (w / w) of extraction solutions, or a molar ratio, such as the molar ratio of one or more constituent bioactive molecules in the extract) of about 0.5:1 to 10:1, including ranges between these values, including 0.5:1, 1:1, 1.25:1, 1.5:1, 1.75:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.

[0198] In some embodiments, the mixture of fungal extracts comprises ultrasonic extract and Soxhlet extract in an ultrasonic:Soxhlet volume ratio of about 0.5:1 to 10:1 (including ranges between these values), including 0.5:1, 1:1, 1.25:1, 1.5:1, 1.75:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, and 10:1. In some embodiments, the mixture comprises ultrasonic extract and Soxhlet extract in a weight ratio of about 0.5:1 to about 5:1, including 5:1, 1:1, 1.25:1, 1.5:1, 1.75:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, and 5:1. In some embodiments, the mixture comprises an ultrasonic:Soxhlet molar ratio (e.g., a molar ratio such as the molar ratio of one or more constituent bioactive molecules in the extract) of about 0.5:1 to 10:1 (including ranges between these values), including 0.5:1, 1:1, 1.25:1, 1.5:1, 1.75:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.

[0199] In some embodiments, the mixture comprises an ultrasonic extract and a Soxhlet extract in an ultrasonic:Soxhlet weight ratio of about 2:1.

[0200] Advantages of combining different fungal extracts in the disclosed combinations may include, for example, improved solution stability during extraction of the fungal-derived bioactive molecules described herein. For example, certain compositions disclosed herein include psilocin and / or psilocybin as components of the fungal portion. The instability of psilocybin, particularly psilocin, has long been recognized. However, the mechanism of degradation and the precise chemistry of the products remain a topic of ongoing research. Studies of Psilocybe mushrooms injured to expose the alkaloids to environmental oxygen have revealed that psilocybin is dephosphorylated to psilocin, and its hydroxyl group is oxidized to produce a 4-oxo decomposition product (Lenz et al. Angew Chem Int Ed Engl. 2020;59(4):1450-1454) (Lenz et al., 2020). Studies into possible solution degradation mechanisms have revealed that oxidative dimerization may also contribute to psilocin's solution instability (Lenz et al. Chemistry. 2021;27(47):12166-12171) ("Lenz et al., 2021"). In some embodiments, combining fungal extracts (e.g., as in the disclosed combinations where the fungal portion includes both an ultrasonic extract and a Soxhlet extract) protects the resulting combination from oxidative degradation. Without being bound by theory, different levels of primary and / or secondary bioactive molecules in different fungal extracts, which may include naturally occurring stabilizers and antioxidants, may, in combination, produce additive or synergistic effects that stabilize the resulting formulation against degradation pathways such as oxidative dimerization. In embodiments, oxidative degradation of the compositions may be monitored quantitatively (e.g., by chemical analytical methods such as those disclosed in Lenz et al., 2020 and Lenz et al., 2021; or otherwise known to those of skill in the art) or qualitatively (e.g., by visual monitoring of the characteristic "bluing" reaction of psilocybin- and / or psilocin-containing extracts and substances).

[0201] In some embodiments, the disclosed combinations, in which the fungal portion comprises multiple fungal extracts, may also have other advantageous properties, such as increased miscibility with other portions of the combination (e.g., plant and / or algae portions) during extraction of the fungal-derived bioactive molecules disclosed herein. As an example, some disclosed compositions contain components with high water solubility (e.g., fungal extracts containing psilocybin and / or psilocin, or fungal extracts containing these compounds) and components with low water solubility (e.g., plant parts containing cannabinoids or cannabis extracts). During preparation and storage of such compositions, precipitation may occur due to mutual incompatibility between the primary and / or secondary bioactive molecules and the solvent system. Without being bound by theory, different levels of the primary and / or secondary bioactive molecules in different fungal extracts may result in additive or synergistic effects that stabilize the resulting formulation against precipitation.

[0202] In some embodiments, the disclosed combinations, in which the fungal portion comprises multiple different fungal extracts, have improved stability (e.g., against oxidation and / or precipitation) such that additional stabilizing excipients (e.g., antioxidants, stabilizers) are not required for the combination to be sufficiently stable under ambient conditions. Reducing or eliminating the need for such additional stabilizing excipients may provide additional benefits, such as improved bioavailability, as these components may inhibit absorption of the primary and / or secondary bioactive molecules.

[0203] 2. Exemplary Extraction of Molecules from Cannabis In embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a Cannabis species, hi embodiments, the primary bioactive molecule and / or the secondary bioactive molecule can be obtained via extraction of Cannabis plant material.

[0204] In embodiments, an exemplary extraction system is as follows: First, in embodiments, substantially dried Cannabis plant material is obtained. In embodiments, the dried Cannabis plant material may then be ground and optionally milled to obtain a fine powder, and optionally sieved. As discussed above, milling and micronization increases the surface area available for the solvent to interact with the material, and therefore may increase the yield of desired primary and / or secondary bioactive molecules within the material. In embodiments, the dried, optionally ground, and / or milled plant material is then placed into an extraction system that generally includes a loop through which chilled ethanol (maintained between -30°C and -40°C) is circulated. Evaporation is used to remove the solvent, followed by distillation and filtration to further concentrate the extract and remove impurities.

[0205] In such an exemplary extraction system, decarboxylation occurs at high temperature and pressure (which occurs at about 110°C at standard pressure). For example, if a product without the intoxicating effects of THC is desired, an extraction process using temperatures and pressures below threshold values ​​can be selected. Column chromatography, for example, can also be used to remove THC after extraction.

[0206] Although the exemplary extraction processes or systems are disclosed as a series of steps being performed or being performed in the system, it will be understood that deviations from these steps, such as altering, removing, and adding various steps at any time during the extraction, are within the scope of the present disclosure.

[0207] In some exemplary embodiments, ethanol extraction is used, but it is understood that this is only one extraction process that can produce an extract useful in a therapeutic combination. In other embodiments, other extraction methods and solvents can be used, non-limiting examples of which include subcritical and supercritical CO2 extraction, hydrocarbon extraction with butane, propane, other hydrocarbon liquids and gases, and mixtures thereof in any proportion, alcohol extraction with methanol or isopropyl alcohol, and other such extraction methods known to those skilled in the art, including variations thereof, for example, in temperature, pressure, and equipment. While any such extraction method can be used, it should be understood that certain extraction methods may offer certain advantages depending on the desired composition of the extract, as described in this disclosure and known to those skilled in the art.

[0208] As a non-limiting example, supercritical extraction, such as supercritical CO2 extraction, is useful for extracting cannabinoids and preserving terpenoids. Hot alcohol extraction is useful for extracting and decarboxylating cannabinoids, but also extracts various pigments and impurities. Cold alcohol extraction is more successful but less effective at isolating terpenes and cannabinoids from impurities than hot alcohol extraction. Hydrocarbon extraction, including butane and propane extraction, is effective at reducing impurities and pigments in extracts and is more efficient than cold alcohol extraction, for example.

[0209] Cannabis-derived primary and / or secondary bioactive molecules may be obtained by extraction of the Cannabis plant and used to prepare Cannabis-derived drug substances and Cannabis-derived pharmaceutical products.

[0210] "Cannabis-derived drug substance" may refer to a botanical drug substance derived from the Cannabis plant (including plant parts, plant part biomass, and plant exudates), and may include, by way of non-limiting and purely illustrative example, primary extracts prepared by processes including maceration, percolation, extraction with solvents such as C1-C5 alcohols (e.g., ethanol), hydrocarbons (e.g., propane, butane), and sub- or supercritical carbon dioxide.

[0211] "Cannabis-derived medicinal products" may refer to primary cannabis extracts that have been further purified, for example, by distillation or chromatography. Those skilled in the art will recognize that when certain solvents are used to prepare the primary extract, the resulting extract may contain non-specific lipid-soluble materials. Those skilled in the art will recognize that such impurities can be removed by a variety of processes, including winterization (e.g., cooling to -20°C followed by filtration to remove waxy ballast), further extraction or filtration, and distillation.

[0212] 3. Exemplary Extraction of Molecules from Dipteryx In embodiments, the therapeutic combination comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from Dipteryx, hi embodiments, the primary bioactive molecule and / or the secondary bioactive molecule are obtained via extraction of kumaru seed (tonka bean).

[0213] As previously mentioned, the primary bioactive molecule in Dipteryx is coumarin, which can be extracted from coumarin seeds via extraction with polar solvents, such as, in embodiments, water, alcohols including, but not limited to, ethanol and methanol; and various ethers. An exemplary extraction system utilizing ethanol is described below.

[0214] In embodiments, ethanol extraction may be utilized to extract coumarin from coumarine seeds. In embodiments, the ethanol extraction may be ethanol percolation, in embodiments, using absolute ethanol. In embodiments, the ethanol percolation extraction system functions by first crushing the coumarine seeds to allow the ethanol solvent to enter and exit the beans. Preferably, the seeds are sufficiently crushed to increase the surface area for extraction and form a plant mass. The seeds are then placed in a filter placed over a collection device. Ethanol is then poured over the seed material, passed through the filter, and collected in the collection device. In embodiments, this is complete only when the color of the ethanol indicates that substantially no additional bioactive molecules have been collected.

[0215] Next, if necessary, excess ethanol is evaporated. This can be accomplished by applying heat to the resulting solution or by utilizing ambient evaporation. Other extraction methods may also be used, as known to those skilled in the art. Furthermore, although coumarin is directly mentioned, it should be readily understood that, for example, secondary bioactive molecules derived from coumarin may also be extracted using the same or similar methods and may be present in the extract if the exemplary ethanol extraction method is utilized. Furthermore, the concentrations of the primary and / or secondary bioactive molecules can be determined as disclosed herein.

[0216] 4. Determining the Concentration of the Primary and / or Secondary Bioactive Molecules It will be appreciated that determining the concentration of primary and / or secondary bioactive molecules within an extract or within fungal, plant and / or algal material is within the capabilities of one of ordinary skill in the art. Several such means are disclosed below and may be used in embodiments.

[0217] As a non-limiting example of such a means, the concentrations of primary bioactive molecules from various Psilocybe species are shown below in Table 1 (taken from Mahmood. Bioactive Alkaloids from Fungi: Psilocybin. In: Ramawat, K., Merillon, JM. (eds) Natural Products. Springer, 2013 and organized by psilocybin content; see also Stamets. Psilocybin Mushrooms of the World: An Identification Guide. Ten Speed ​​Press. 1996), which shows the w / w% of psilocybin, psilocin, and baeocystin in dried mushrooms (containing negligible moisture weight, or sometimes referred to as "cracker dried"), as further described herein. [Table 1]

[0218] Thus, 100 mg of P. cubensis extract may, in some embodiments, contain about 0.63 mg of psilocybin, and 275 mg of P. azurescens extract may, in embodiments, contain about 4.895 mg.

[0219] It will be understood that the growth conditions of organisms such as fungi (as well as plants and algae) can affect the concentration of bioactive molecules found therein. The concentration of bioactive molecules can vary depending on the part of the organism from which they are obtained (e.g., cap vs. stem or mycelium, flower vs. leaf or stem, etc.), and other variables known in the art. One will understand how to select such growth conditions, part of the organism, etc., and how to determine the concentration of bioactive molecules using the disclosed methods or methods commonly known in the art.

[0220] In embodiments, the concentrations of primary and / or secondary bioactive molecules in fungi, plants, and / or algae are determined using liquid chromatography, such as high performance liquid chromatography (HPLC). Broadly, HPLC works by using a pump to pass a pressurized liquid solvent containing a sample mixture (in this case, a fungal extract) through a column filled with a solid adsorbent. Individual components in the sample interact differently with the adsorbent, resulting in different flow rates for each component, and the components are separated as they exit the column.

[0221] In embodiments, the concentrations of primary and / or secondary bioactive molecules in fungi, plants, and / or algae are determined using reverse-phase HPLC and single-wavelength detection, as disclosed in Samuelsson et al. Physiol Plant. 1977;40:315-319, incorporated herein by reference. Broadly speaking, reverse-phase HPLC generally proceeds in the same manner as the exemplary HPLC methods disclosed above, but with a hydrophobic stationary phase rather than a hydrophilic one. That is, hydrophobic molecules adsorb to the column packing, and hydrophilic molecules are eluted and detected first.

[0222] In embodiments, the concentration of primary and / or secondary bioactive molecules in fungi, plants, and / or algae is determined using liquid chromatography and mass spectrometry (LC / MS), as exemplified by Goff et al. Anal Chim Acta. 2024;1288:342161, incorporated herein by reference.

[0223] In embodiments, the concentration of primary and / or secondary bioactive molecules in fungi, plants, and / or algae is determined using hydrophilic interaction liquid chromatography (HILIC), as described in Veress et al. The Applications Book. 2019;32(7):387-388, incorporated herein by reference. Broadly speaking, HILIC is a normal-phase HPLC technique that utilizes a reversed-phase type eluent. The column has a hydrophilic stationary phase, and the eluent includes water, a buffer, and a high concentration of a water-miscible organic solvent.

[0224] In embodiments, the concentrations of primary and / or secondary bioactive molecules in fungi, plants, and / or algae are determined using rapid personal quantification tools that can be used to determine concentrations, such as the PSILO-QTest (Miraculix; Jena, Germany), which is useful for determining the concentration of psilocybin in fungi. The PSILO-QTest detects concentration using a chemical color reaction, with color intensity being proportional to the concentration of the bioactive molecule. In some embodiments, characterization of the fungal, plant, and / or algal parts of the disclosed combinations (e.g., characterization of the primary and / or secondary bioactive molecules) includes characterizing free and / or bound amino acids using known chromatographic techniques (e.g., LC-MS, HPLC). In embodiments, characterization includes determining the concentration of taurine in the fungal, plant, and / or algal parts.

[0225] B.Synthesis In embodiments, the primary and secondary bioactive molecules disclosed herein may be synthetic, where "synthetic," as used herein, can refer to substances produced in a laboratory by chemical synthesis (e.g., by a series of chemical processes or reactions using chemical substrates, reagents, and optionally catalysts), or by biosynthesis as discussed herein (e.g., including compounds from bioengineered organisms, and thus also referred to as including "biosynthesis" or "synthetic biology" or "synbio").

[0226] In general, methods for chemical synthesis, including the biologically active molecules disclosed herein, are well known in the art. Thus, methods for the synthesis of biologically active molecules and / or starting materials can be found in general references known in the art (e.g., Greene & Wuts. Protective Groups in Organic Chemistry. 2nd ed. Wiley. 1991; Harrison et al. Compendium of Synthetic Organic Methods. Vol. 1-8. John Wiley and Sons, 1971-1996; Beilstein. Beilstein Handbook of Organic Chemistry. 1990; Feiser et al. Reagents for Organic Synthesis. Vol. 1-17. Wiley Interscience. 1967-1994; Trost & Fleming. Comprehensive Organic Synthesis. Pergamon Press. 1991; Theilheimer's Synthetic Methods of Organic Chemistry. Volumes 1-45. Karger. 1991; March. Advanced Organic Chemistry. Wiley Interscience. 1991; Larock. Comprehensive Organic Synthesis. These methods are readily understood by those skilled in the art by consulting the following publications: "Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. 1995; Paquette, Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. 1995"; and can be used to synthesize biologically active molecules when they cannot be obtained by extraction or the like.Generally, these approaches are used for similar compounds (Shulgin & Shulgin, PiHKAL, A chemical love story, Transform Press, Berkeley CA, 1992; Glennon et al., J Med Chem. 1986; 29(2):194-199; Nichols et al. J Med Chem. 1991; 34(1):276-281; ​​Kedrowski et al., Organic Letters. 2007; 9(17):3205-3207; Heravi & Zadsirjan. Current Organic Synthesis. 2016; 13(6):780-833; Keri et al. Eur J Med Chem. 2017; 138:1002-1033; Perez Silanes et al. J Heterocycl. Chem. 2001;38(5):1025-1030; and references therein), and such applications are known and understood by those skilled in the art.

[0227] In embodiments, the disclosed primary and secondary bioactive molecules are obtained by biosynthesis. Biosynthesis refers to the production of molecules, such as the primary and / or secondary bioactive molecules utilized in the therapeutic combination, within a cell or a cell-free system. In embodiments, the primary and / or secondary bioactive molecules useful in the therapeutic combination can be produced via biosynthesis. Methods for biosynthesis of bioactive molecules will be readily apparent to those skilled in the art in light of the general literature known in the art (see, e.g., WO 2021 / 052989, WO 2019 / 173797, WO 2021 / 086513, and WO 2019 / 180309, all of which are incorporated herein by reference). Non-limiting examples of biosynthetic pathways known in the art include pathways for cannabinoids, flavonoids, carotenoids, psilocybin, psilocin, and other indole alkaloids (such as the primary and secondary bioactive molecules found in fungi), amino acids, and peptides (including monopeptides, dipeptides, tripeptides, and proteins).

[0228] In embodiments, the fungal-derived primary and / or secondary bioactive molecules are produced by biosynthesis. In embodiments, the plant-derived primary and / or secondary bioactive molecules are produced by biosynthesis. In embodiments, the algae-derived primary and / or secondary bioactive molecules are produced by biosynthesis.

[0229] C. Separation, Fractionation, and Purification In embodiments, the primary and / or secondary bioactive molecules are obtained through isolation, fractionation, and / or purification. Fractionation refers to a separation process in which a volume of a mixture is divided into several smaller portions, called fractions, during a phase transition, the composition of which varies along a gradient.

[0230] In embodiments, fractions containing target primary and / or secondary bioactive molecules may be obtained via fractional distillation, column chromatography, fractional crystallization, fractional freezing, and bioassay-guided fractionation.

[0231] In embodiments, the isolation of primary and / or secondary bioactive molecules can be completed from the extract containing the primary and / or secondary bioactive molecules.Many methods for separating compounds from extracts are known to those skilled in the art.However, exemplary methods include thin layer chromatography, column chromatography, flash chromatography, Sephadex chromatography, and high performance liquid chromatography (Sasidharan et al. AJTCAM. 2011;8(1):1-10).

[0232] In embodiments, the extract may be further purified to isolate specific primary and / or secondary bioactive molecules. In embodiments, such purification techniques are known to those skilled in the art and may include HPLC and centrifugal partition chromatography (CPC).

[0233] D. Compound In embodiments, the disclosed primary and / or secondary bioactive molecules are pure or substantially pure. As used herein, the terms "pure" or "substantially pure" refer to a substance that is substantially or essentially free from components that normally accompany the substance when it is synthesized, manufactured, or otherwise produced. A "pure" or "substantially pure" preparation of a primary and / or secondary bioactive molecule is therefore defined as a preparation having a chromatographic purity (of the desired bioactive molecule) of greater than 90%, more preferably greater than 95%, more preferably greater than 96%, more preferably greater than 97%, more preferably greater than 98%, more preferably greater than 99%, more preferably greater than 99.5%, and most preferably greater than 99.9%, as determined by area normalization of an HPLC profile or other similar detection method. Preferably, a pure or substantially pure primary and / or secondary bioactive molecule is substantially free of other active compounds not intended for administration to a subject. In this context, "substantially free" means that active compounds other than the primary and / or secondary bioactive molecules intended for administration to a subject are not detectable by HPLC or other similar detection methods or are below the desired detection threshold as defined above.

[0234] The disclosed primary and / or secondary bioactive molecules may contain one or more asymmetric centers, giving rise to enantiomers, diastereomers, and other stereoisomers. The present disclosure includes all such possible isomers, including racemates and optically pure forms, as well as mixtures thereof. Optically active isomers can be prepared using chiral synthons or chiral reagents or separated using conventional techniques. Various methods for preparing optically active forms and determining activity are known in the art.

[0235] The present disclosure also includes primary and / or secondary bioactive molecules that have at least one desired isotopic substitution of an atom at or above the natural abundance of that isotope, i.e., are isotopically enriched. Isotopes are atoms with the same atomic number but different mass numbers, i.e., the same number of protons but different numbers of neutrons. An example is deuterium ( 2 H) and tritium ( 3 Any isotope of hydrogen, including H, may be used anywhere within the depicted structures to achieve the desired result. Alternatively, or in addition, any isotope of carbon, e.g. 13 C and 14 C may also be used. Isotopic substitution, e.g., deuterium substitution, may be partial or complete. Partial deuterium substitution means that at least one hydrogen is replaced with deuterium. In embodiments, the isotope is enriched to at least 60%, 70%, 80%, 90%, 95%, or 99% or more at any desired position. In one embodiment, deuterium is enriched to 90%, 95%, or 99% at the desired position.

[0236] It will be understood that the primary and / or secondary biologically active molecules used in the disclosed methods also include pharmaceutically acceptable salts of such molecules. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases, which can be synthesized by conventional chemical methods. Generally, such salts are prepared by reacting the free acid or base form of these agents with a stoichiometric amount of an appropriate base or acid in water, an organic solvent, or a mixture of the two; generally, non-aqueous media (e.g., ether, ethyl acetate, ethanol, isopropanol, or acetonitrile) are preferred. For therapeutic use, salts of compounds are those in which the counterion is pharmaceutically acceptable. Exemplary salts include 2-hydroxyethanesulfonate, 2-naphthalenesulfonate, 2-napsylate, 3-hydroxy-2-naphthoate, 3-phenylpropionate, 4-acetamidobenzoate, acefirate, acetate, aceturate, adipate, alginate, aminosalicylate, ammonium salt, anthonate, ascorbate, aspartate, benzenesulfonate, benzoate, besylate, bicarbonate, bisulfate, tartrate, borate, butyrate, calcium edetate, calcium, camphor carbonate, camphorate, camphorsulfonate, camsylate, carbonate, cholate, citrate, clavulate, cyclopentanepropionate, cypionate, d-aspartate, d-camsylate, d- Lactate, decanoate, dichloroacetate, digluconate, dodecyl sulfate, edetate, edisylate, estolate, esylate, ethanesulfonate, ethyl sulfate, fumarate, furate, fusidate, galactarate (mucoate), galacturonate, gallate, gentate, gluceptate, glucoheptanoate, gluconate, glucuronate, glutamate, glutarate, glycerophosphate, glycolate, glycolylsanilate, hemisulfinate, heptanoate (enanthate), heptanoate, hexafluorophosphate, hexanoate, hexylresorcinate, hippurate, hibenzoate, hydrabamate, hydrobromide, hydrobromide / hydrobromide, hydrochloride, hydroiodide, hydroxide,Hydroxybenzoate, hydroxynaphthoate, hydroiodide, isethionate, isothionate, l-aspartate, l-camsylate, l-lactate, lactate, lactobionate, laurate, laurylsulfonate, lithium, magnesium, malate, maleate, malonate, mandelate, mesotartarate, mesylate, methanesulfonate, methyl bromide, methyl nitrate, methyl sulfate, mucate, myristate, N-methylglucamine ammonium salt, napadisilate, naphthylate, napsylate, nicotinate, nitrate, octanoate, oleate, orotate, oxalate, p-toluenesulfonate, palmitate Examples of suitable salts include salts of hydroxybenzoates, ...

[0237] It will be understood that prodrugs of the primary and / or secondary biologically active molecules are also within the scope of this disclosure. The term "prodrug" refers to a precursor of a biologically active agent. A prodrug undergoes chemical or metabolic transformation to become a biologically active agent, such as the conversion of the prodrug psilocybin to the active metabolite psilocin.

[0238] In the case of solid compositions, it is understood that the disclosed primary and / or secondary bioactive molecules may exist in different forms. For example, the primary and / or secondary bioactive molecules may exist in stable and metastable crystalline forms, isotropic and amorphous forms, milled forms, and nanoparticulate forms, all of which are intended to be within the scope of this disclosure. Furthermore, the primary and / or secondary bioactive molecules may include crystalline forms, also known as polymorphs. Polymorphs include different crystal packing arrangements of the same elemental composition of a bioactive molecule. Polymorphs typically differ in X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, solubility, etc. Various factors, such as recrystallization solvent, crystallization rate, and storage temperature, may result in the predominance of a single crystal.

[0239] It should be understood that the substitution of any of the disclosed primary and / or secondary bioactive molecules with their ions, free bases, salt forms, polymorphs, hydrate or solvate forms, co-crystals, or isomerically or enantiomerically enriched mixtures provides merely alternative embodiments within the scope of the present disclosure (including formulation and dosage modifications, as necessary or desired, made in accordance with the teachings herein and ordinary skill in the art). Furthermore, compositions within the scope of the present disclosure should be understood to be open-ended and may include additional primary and / or secondary bioactive molecules, active or inactive agents, and ingredients.

[0240] In some embodiments, the disclosed primary and / or secondary bioactive molecules, or pharmaceutically acceptable salts, hydrates, solvates, or prodrugs thereof, are manufactured and tested in accordance with Good Laboratory Practice (GLP) or Good Manufacturing Practice (GMP) requirements, and / or their equivalents, and any related practices, e.g., in Canada, when referring to the Cannabis plant, the Good Manufacturing Practices (GPP) of the Cannabis Regulations.

[0241] IV. Therapeutic Combinations and Compositions In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains algal parts.

[0242] In some embodiments, the therapeutic combination comprises: a. Fungal extract, b. a first plant part; c. a second plant part, and d. Contains algal parts.

[0243] In some embodiments, the therapeutic combination comprises: a. a fungal extract derived from a psilocybin-producing fungus; b. a first plant part; c. a second plant part, and d. Contains algal parts.

[0244] In some embodiments, the therapeutic combination comprises: a. a fungal extract from a species of the genus Psilocybe; b. a first plant part; c. a second plant part, and d. Contains algal parts.

[0245] In some embodiments, the therapeutic combination comprises: a. Psilocybe cubensis extract, b. a first plant part; c. a second plant part, and d. Contains algal parts.

[0246] In some embodiments, the therapeutic combination comprises: a. fungal-derived bioactive molecules, b. a first plant part; c. a second plant part, and d. Contains algal parts.

[0247] In some embodiments, the therapeutic combination comprises: Psilocybin, b. a first plant part; c. a second plant part, and d. Contains algal parts.

[0248] In some embodiments, the therapeutic combination comprises: Psilocybin, b. Psilocin, c. a first plant part; d. a second plant part, and e. Contains algal parts.

[0249] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Plant extracts, c. a second plant part, and d. Contains algal parts.

[0250] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. plant extracts from the genus Cannabis; c. a second plant part, and d. Contains algal parts.

[0251] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Plant-derived bioactive molecules, c. a second plant part, and d. Contains algal parts.

[0252] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Cannabis sativa extract, c. a second plant part, and d. Contains algal parts.

[0253] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Cannabis-derived bioactive molecules; c. a second plant part, and d. Contains algal parts.

[0254] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. cannabinoids, c. a second plant part, and d. Contains algal parts.

[0255] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. THC, c. a second plant part, and d. Contains algal parts.

[0256] In some embodiments, the therapeutic combination comprises: a. Fungal part, b.CBD, c. a second plant part, and d. Contains algal parts.

[0257] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Dipteryx extract, c. a second plant part, and d. Contains algal parts.

[0258] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Dipteryx odorata extract, c. a second plant part, and d. Contains algal parts.

[0259] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Bioactive molecules derived from Dipteryx; c. a second plant part, and d. Contains algal parts.

[0260] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Bioactive molecules from Dipteryx odorata, c. a second plant part, and d. Contains algal parts.

[0261] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Bioactive molecules derived from tonka beans, c. a second plant part, and d. Contains algal parts.

[0262] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. Coumarin, c. a second plant part, and d. Contains algal parts.

[0263] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains algae extract.

[0264] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules derived from algae.

[0265] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules derived from red algae (Rhodophyta).

[0266] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules from genera in the family Bangiaceae.

[0267] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains Pyropia extract.

[0268] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains Pyropia yezoensis extract.

[0269] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules derived from the genus Pyropia.

[0270] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules derived from Pyropia yezoensis.

[0271] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules derived from Pyropia perforata.

[0272] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules derived from the genus Porphyra.

[0273] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains bioactive molecules derived from Porphyra umbilicalis.

[0274] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains porphyran.

[0275] In some embodiments, the therapeutic combination comprises: a. Fungal part, b. a first plant part; c. a second plant part, and d. Contains taurine.

[0276] In some embodiments, the therapeutic combination comprises: a. Fungal extract, b. a first plant extract; c. a second plant extract, and d. Contains algae extract.

[0277] In some embodiments, the therapeutic combination comprises: a. Psilocybe extract, b. Cannabis extract; c. Dipteryx extract, and d. Contains Pyropia extract.

[0278] In some embodiments, the therapeutic combination comprises: a. Psilocybe extract, b. Cannabis extract; c. Dipteryx extract, and d. Contains Porphyra extract.

[0279] In some embodiments, the therapeutic combination comprises: a. Psilocybe cubensis extract, b. Cannabis sativa extract, c. Dipteryx odorata extract and d. Contains Pyropia yezoensis extract.

[0280] In some embodiments, the therapeutic combination comprises: a. fungal-derived bioactive molecules, b. a first plant-derived bioactive molecule; c. a second plant-derived bioactive molecule, and d. Contains bioactive molecules derived from algae.

[0281] In some embodiments, the therapeutic combination comprises: a. Bioactive molecules derived from Psilocybe cubensis, b. Bioactive molecules derived from Cannabis sativa, c. Bioactive molecules from Dipteryx odorata, and d. Contains bioactive molecules derived from Pyropia yezoensis.

[0282] In some embodiments, the therapeutic combination comprises: a. Psilocybe extract, b. THC, CBD, d. Coumarin, and e. Contains Pyropia extract.

[0283] In some embodiments, the therapeutic combination comprises: Psilocybin, b. THC, c. Coumarin, and d. Contains Pyropia extract.

[0284] In some embodiments, the therapeutic combination comprises: a. Psilocin, b. THC, c. Coumarin, and d. Contains taurine.

[0285] In some embodiments, the therapeutic combination comprises: Psilocybin, b.CBD, c. Coumarin, and d. Contains Pyropia extract.

[0286] In some embodiments, the therapeutic combination comprises: a. Psilocin, b.CBD, c. Coumarin, and d. Contains Pyropia extract.

[0287] In some embodiments, the therapeutic combination comprises: Psilocybin, b. THC, c. Coumarin, and d. Contains taurine.

[0288] In some embodiments, the therapeutic combination comprises: Psilocybin, b. THC, c. Coumarin, and d. Contains porphyran.

[0289] In embodiments, the therapeutic combination includes a fungal portion, a fungal extract (e.g., a Psilocybe cubensis extract), or a fungal-derived bioactive molecule (e.g., from Psilocybe cubensis). In embodiments, the fungal portion, fungal extract, or fungal-derived bioactive molecule comprises at least 99%, 99%, 98%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, or less than 1% by volume (including ranges between these values) of the therapeutic combination. In embodiments, the fungal portion, fungal extract, or fungal-derived bioactive molecule comprises about 10% to about 70%, about 20% to about 60%, about 30% to about 50%, or about 40% to about 50% by volume of the therapeutic combination. In embodiments, the fungal portion, fungal extract, or fungal-derived bioactive molecule comprises about 45% by volume of the therapeutic combination.

[0290] In embodiments, the therapeutic combination includes a first plant part, a first plant extract (e.g., Cannabis sativa), or a bioactive molecule derived from a first plant (e.g., Cannabis sativa). In embodiments, the first plant part, first plant extract, or bioactive molecule derived from the first plant comprises at least 99%, 99%, 98%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, or less than 1% by volume (including ranges between these values) of the therapeutic combination. In embodiments, the first plant part, first plant extract, or first plant-derived bioactive molecule comprises about 1% to about 50%, about 5% to about 30%, or about 10% to about 20% by volume of the therapeutic combination. In embodiments, the first plant part, first plant extract, or first plant-derived bioactive molecule comprises about 15% by volume of the therapeutic combination.

[0291] In embodiments, the therapeutic combination includes a second plant part, a second plant extract (e.g., a Dipteryx odorata extract), or a bioactive molecule from a second plant (e.g., from Dipteryx odorata). In embodiments, the second plant part, second plant extract, or bioactive molecule from a second plant comprises at least 99%, 98%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, or less than 1% (inclusive of ranges between these values) of the therapeutic combination. In embodiments, the second plant part, second plant extract, or second plant-derived bioactive molecule comprises about 1% to about 20%, about 1% to about 10%, or about 1% to about 3% by volume of the therapeutic combination. In embodiments, the second plant part, second plant extract, or second plant-derived bioactive molecule comprises about 2% by volume of the therapeutic combination.

[0292] In embodiments, the therapeutic combination includes an algae part, an algae extract (e.g., a Pyropia yezoensis extract), or an algae-derived (e.g., from Pyropia yezoensis) bioactive molecule. In embodiments, the algae part, algae extract, or algae-derived bioactive molecule comprises at least 99%, 98%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1%, or less than 1% (inclusive of ranges between these values) of the therapeutic combination. In embodiments, the algae parts, algae extracts, or algae-derived bioactive molecules comprise about 1% to about 50%, about 5% to about 30%, or about 10% to about 20% by volume of the therapeutic combination. In embodiments, the algae parts, algae extracts, or algae-derived bioactive molecules comprise about 15% by volume of the therapeutic combination.

[0293] In an embodiment, the first plant part and the second plant part are from different plant genera. In an embodiment, the first plant part and the second plant part are from different plant species. In an embodiment, the first plant part and the second plant part are from different plant extracts. In an embodiment, the first plant part and the second plant part comprise different primary bioactive molecules. In an embodiment, the first plant part and the second plant part comprise different secondary bioactive molecules. In an embodiment, the first plant part and the second plant part are from the same plant genus. In an embodiment, the first plant part and the second plant part are from the same plant species. In an embodiment, the first plant part and the second plant part are from the same plant extract. In an embodiment, the first plant part and the second plant part comprise the same primary bioactive molecule. In an embodiment, the first plant part and the second plant part comprise the same secondary bioactive molecule.

[0294] In some embodiments, the single composition further comprises any of a flavoring agent, a coloring agent, and a diluent. For example, in embodiments, the flavoring agent or coloring agent comprises ginger or bay leaf. In embodiments, the flavoring agent or coloring agent is a decoction of ginger and bay leaf with ethanol. In embodiments, the flavoring agent or coloring agent comprises about 1% to about 50%, about 5% to about 50%, about 5% to about 40%, about 5% to about 30%, about 5% to about 20%, about 10% to about 30%, or about 10% to about 20% by volume of the single composition. In embodiments, the flavoring agent or coloring agent comprises about 15% by volume of the single composition.

[0295] In embodiments, the diluent is water. In embodiments, the diluent (e.g., water) comprises about 1% to about 30%, about 5% to about 30%, about 5% to about 20%, or about 5% to about 15% by volume of the single composition. In embodiments, water comprises about 8% by volume of the single composition.

[0296] In embodiments, therapeutic combinations comprising a primary and / or secondary bioactive molecule derived from a fungus and a primary and / or secondary bioactive molecule derived from a plant will be synergistic or have a synergistic effect. In embodiments, therapeutic combinations comprising a primary and / or secondary bioactive molecule derived from a fungus and a primary and / or secondary bioactive molecule derived from a plant will be synergistic or have a synergistic effect. In embodiments, therapeutic combinations comprising a primary and / or secondary bioactive molecule derived from a fungus and a primary and / or secondary bioactive molecule derived from an algae will be synergistic or have a synergistic effect. In embodiments, therapeutic combinations comprising a primary and / or secondary bioactive molecule derived from a plant and a primary and / or secondary bioactive molecule derived from an algae will be synergistic or have a synergistic effect. In embodiments, a therapeutic combination comprising a primary and / or secondary bioactive molecule derived from a fungus, a primary and / or secondary bioactive molecule derived from a plant, and a primary and / or secondary bioactive molecule derived from an algae will be synergistic or have a synergistic effect.

[0297] A. Synergy In embodiments, "synergy" may refer to a combination that is more effective than the additive effect of any two or more single primary and / or secondary bioactive molecules. For example, synergy allows for the effective treatment of a disease using lower amounts (doses) of the individual therapies. This may include lower doses of the first primary and / or secondary bioactive molecule or the second primary and / or secondary bioactive molecule ("apparent one-way synergy"), or lower doses of both the first and / or secondary bioactive molecules ("two-way synergy") than would normally be required when using either the primary and / or secondary bioactive molecule alone. For example, lower doses may result in increased safety and / or reduced toxicity without reducing efficacy. Synergy may also result in improved efficacy, including improved disease avoidance or mitigation, compared to single therapies.

[0298] "Synergistic effect" will also be understood to include an increase in potency, bioactivity, bioaccessibility, bioavailability, or therapeutic effect (including one or more additional therapeutic effects) that is greater than the additive contribution of the components acting alone and / or greater than the contribution of the isolated primary and / or secondary bioactive molecules alone.

[0299] There are many methods known to those skilled in the art for determining whether there is synergy with respect to a particular effect, i.e., whether the effect of two or more components when mixed together is greater than the sum of the effects of the individual components applied alone, thereby resulting in "1 + 1 > 2." Suitable methods include isobologram (or contour) analysis (Huang et al. Front Pharmacol. 2019; 10: 1222) or the Loewe additivity equation (Loewe & Muischnek. Archiv f experiment Pathol u Pharmakol. 1926; 114: 313-326). Synergistic effects can also be calculated using methods such as the sigmoid-Emax equation (Holford & Scheiner. Clin Pharmacokinet. 1981; 6(6): 429-453) and the median effect equation (Chou & Talalay. Adv Enzyme Regul. 1984; 22: 27-55). The graphs corresponding to the above equations are the concentration-effect curve and the combination index curve, respectively. The above equations can be applied to experimental data to generate corresponding graphs that can help evaluate the effect of the combination.

[0300] In embodiments, the combination comprises a first and / or second bioactive molecule derived from a psilocybin-producing fungus and a first and / or second bioactive molecule derived from Cannabis. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0301] In embodiments, the combination comprises a primary and / or secondary bioactive molecule from a psilocybin-producing fungus and a primary and / or secondary bioactive molecule from Dipteryx. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0302] In embodiments, the combination includes a primary and / or secondary bioactive molecule from a psilocybin-producing fungus and a primary and / or secondary bioactive molecule from a Pyropia or Porphyra fungus. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0303] In embodiments, the combination comprises a first and / or second bioactive molecule derived from Cannabis and a first and / or second bioactive molecule derived from Dipteryx. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0304] In embodiments, the combination comprises a primary and / or secondary bioactive molecule derived from Cannabis and a primary and / or secondary bioactive molecule derived from Pyropia or Porphyra, hi embodiments, the combination will be synergistic or have a synergistic effect.

[0305] In embodiments, a combination includes a primary and / or secondary bioactive molecule from Dipteryx with a primary and / or secondary bioactive molecule from Pyropia or Porphyra, hi some embodiments, the combination will be synergistic or have a synergistic effect.

[0306] In embodiments, the combination includes a first and / or second bioactive molecule from a psilocybin-producing fungus, a first and / or second bioactive molecule from Cannabis, and a first and / or second bioactive molecule from Dipteryx. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0307] In embodiments, the combination includes a primary and / or secondary bioactive molecule from a psilocybin-producing fungus, a primary and / or secondary bioactive molecule from Cannabis, and a primary and / or secondary bioactive molecule from Pyropia or Porphyra. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0308] In embodiments, the combination includes a primary and / or secondary bioactive molecule from a psilocybin-producing fungus, a primary and / or secondary bioactive molecule from a Dipteryx, and a primary and / or secondary bioactive molecule from a Pyropia or Porphyra. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0309] In embodiments, the combination includes a primary and / or secondary bioactive molecule from Cannabis, a primary and / or secondary bioactive molecule from Pyropia or Porphyra, and a primary and / or secondary bioactive molecule from Dipteryx. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0310] In embodiments, the combination includes a primary and / or secondary bioactive molecule from a psilocybin-producing fungus, a primary and / or secondary bioactive molecule from Cannabis, a primary and / or secondary bioactive molecule from Dipteryx, and a primary and / or secondary bioactive molecule from Pyropia or Porphyra. In some embodiments, the combination will be synergistic or have a synergistic effect.

[0311] In embodiments, the therapeutic combination comprises a first and / or second bioactive molecule from one or more of Copelandia, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, and Psilocybe, and a first and / or second bioactive molecule from one or more of Cannabis. In some embodiments, the therapeutic combination will be synergistic or have a synergistic effect.

[0312] In embodiments, the therapeutic combination comprises a first and / or second bioactive molecule from one or more of Copelandia, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, and Psilocybe, and a first and / or second bioactive molecule from one or more of Cumarus. In some embodiments, the combination is synergistic or will have a synergistic effect.

[0313] In embodiments, the therapeutic combination comprises a first and / or second bioactive molecule from one or more of Copelandia, Gymnopilus, Inocybe, Panaeolus, Pholiotina, Pluteus, and Psilocybe, and a first and / or second bioactive molecule from one or more of Pyropia or Porphyra. In some embodiments, the therapeutic combination is synergistic or will have a synergistic effect.

[0314] In some embodiments, the disclosed therapeutic combinations are botanical preparations containing minimal or low doses of whole extracts of C. sativa plants, P. cubensis fungi, P. yesoensis algae, and D. odorata beans compared to doses that would otherwise be understood or predicted in the art, and the synergistic effect is the ability of these given dosages to provide an effect. Because the disclosed combinations, compositions, and methods synergistically enable the effective use of surprisingly low doses of one or more bioactive molecules, in some embodiments, these low doses avoid receptor depletion, avoid activation of autoregulatory compensatory measures, or avoid induced compensatory physiological effects.

[0315] B. Additional activators The disclosed therapeutic combinations can also be used with additional active agents that, for example, contribute to or provide an additive therapeutic effect or contribute to or provide a synergistic effect. "Agent" can refer to an agent that affects or modulates the activity of a target, such as a receptor. In embodiments, the agent is a ligand for a receptor and modulates the activity of the receptor. In embodiments, the agent binds to, blocks, activates, inhibits, or affects activity at a given receptor system (e.g., via an allosteric reaction).

[0316] In embodiments, the additional active agent is an anti-inflammatory agent. "Anti-inflammatory agent" refers to an agent that can reduce inflammation or swelling. In embodiments, the anti-inflammatory agent is selected from the group consisting of salicylates, steroids, phosphodiesterase inhibitors, interleukin inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and other agents useful in the treatment of inflammatory diseases.

[0317] In embodiments, the anti-inflammatory agent is a salicylate. In embodiments, the salicylate is selected from the group consisting of magnesium salicylate, aspirin, diflunisal, aspirin / citric acid / sodium bicarbonate, salsalate, and choline salicylate. In embodiments, the salicylate is magnesium salicylate. In embodiments, the salicylate is aspirin. In embodiments, the salicylate is diflunisal. In embodiments, the salicylate is aspirin / citric acid / sodium bicarbonate. In embodiments, the salicylate is salsalate. In embodiments, the salicylate is choline salicylate.

[0318] In embodiments, the anti-inflammatory agent is a steroid. In embodiments, the steroid is a corticosteroid or a glucocorticoid. In embodiments, the steroid is a corticosteroid. In embodiments, the corticosteroid is selected from the group consisting of betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone. In embodiments, the corticosteroid is betamethasone. In embodiments, the corticosteroid is budesonide. In embodiments, the corticosteroid is cortisone. In embodiments, the corticosteroid is dexamethasone. In embodiments, the corticosteroid is hydrocortisone. In embodiments, the corticosteroid is methylprednisolone. In embodiments, the corticosteroid is prednisolone. In embodiments, the corticosteroid is prednisone. In embodiments, the corticosteroid is triamcinolone.

[0319] In embodiments, the steroid is a glucocorticoid. In embodiments, the glucocorticoid is selected from the group consisting of triamcinolone, methylprednisolone, budesonide, dexamethasone, prednisone, hydrocortisone, betamethasone, prednisolone, and deflazacort. In embodiments, the glucocorticoid is triamcinolone. In embodiments, the glucocorticoid is methylprednisolone. In embodiments, the glucocorticoid is budesonide. In embodiments, the glucocorticoid is dexamethasone. In embodiments, the glucocorticoid is prednisone. In embodiments, the glucocorticoid is hydrocortisone. In embodiments, the glucocorticoid is betamethasone. In embodiments, the glucocorticoid is prednisolone. In embodiments, the glucocorticoid is deflazacort.

[0320] In embodiments, the anti-inflammatory agent is a phosphodiesterase inhibitor. In embodiments, the phosphodiesterase inhibitor is selected from the group consisting of a phosphodiesterase type 1 inhibitor, a phosphodiesterase type 2 inhibitor, a phosphodiesterase type 3 inhibitor, a phosphodiesterase type 4 inhibitor, or a phosphodiesterase type 5 inhibitor. In embodiments, the phosphodiesterase inhibitor is a phosphodiesterase type 4 inhibitor. In embodiments, the phosphodiesterase type 4 inhibitor is selected from the group consisting of apremilast, crisaborole, and roflumilast. In embodiments, the phosphodiesterase type 4 inhibitor is apremilast. In embodiments, the phosphodiesterase type 4 inhibitor is crisaborole. In embodiments, the phosphodiesterase type 4 inhibitor is roflumilast.

[0321] In embodiments, the anti-inflammatory agent is an interleukin inhibitor. In embodiments, the interleukin inhibitor is selected from the group consisting of dupilumab, ustekinumab, secukinumab, ixekizumab, mepolizumab, guselkumab, benralizumab, tocilizumab, risankizumab, sarilumab, brodalumab, anakinra, reslizumab, tildrakizumab, canakinumab, rilonacept, tralokinumab, daclizumab, siltuximab, spesolimab, basiliximab, and satralizumab. In embodiments, the interleukin inhibitor is dupilumbab. In embodiments, the interleukin inhibitor is ustekinumab. In embodiments, the interleukin inhibitor is secukinumab. In embodiments, the interleukin inhibitor is ixekizumab. In embodiments, the interleukin inhibitor is mepolizumab. In embodiments, the interleukin inhibitor is guselkumab. In embodiments, the interleukin inhibitor is benralizumab. In embodiments, the interleukin inhibitor is tocilizumab. In embodiments, the interleukin inhibitor is risankizumab. In embodiments, the interleukin inhibitor is sarilumab. In embodiments, the interleukin inhibitor is brodalumab. In embodiments, the interleukin inhibitor is anakinra. In embodiments, the interleukin inhibitor is reslizumab. In embodiments, the interleukin inhibitor is tildrakizumab. In embodiments, the interleukin inhibitor is canakinumab. In embodiments, the interleukin inhibitor is rilonacept. In embodiments, the interleukin inhibitor is tralokinumab. In embodiments, the interleukin inhibitor is daclizumab. In embodiments, the interleukin inhibitor is siltuximab. In embodiments, the interleukin inhibitor is spesolimab. In embodiments, the interleukin inhibitor is basiliximab. In embodiments, the interleukin inhibitor is satralizumab.

[0322] In embodiments, the anti-inflammatory agent is a nonsteroidal anti-inflammatory drug (NSAID) selected from the group consisting of diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, meclofenamate, mefenamic acid, nabumetone, naproxen, tolmetin, piroxicam, meloxicam, ketorolac, ketoprofen, sulindac, esomeprazole / naproxen, diclofenac / misoprostol, famotidine / ibuprofen, diflunisal, oxaprozin, lansoprazole / naproxen, and a selective COX-2 inhibitor.

[0323] In an embodiment, the NSAID is diclofenac. In an embodiment, the NSAID is etodolac. In an embodiment, the NSAID is fenoprofen. In an embodiment, the NSAID is flurbiprofen. In an embodiment, the NSAID is ibuprofen. In an embodiment, the NSAID is indomethacin. In an embodiment, the NSAID is meclofenamate. In an embodiment, the NSAID is mefenamic acid. In an embodiment, the NSAID is nabumetone. In an embodiment, the NSAID is naproxen. In an embodiment, the NSAID is tolmetin. In an embodiment, the NSAID is piroxicam. In an embodiment, the NSAID is meloxicam. In an embodiment, the NSAID is ketorolac. In an embodiment, the NSAID is ketoprofen. In an embodiment, the NSAID is sulindac. In an embodiment, the NSAID is esomeprazole / naproxen. In an embodiment, the NSAID is diclofenac / misoprostol. In an embodiment, the NSAID is famotidine / ibuprofen. In an embodiment, the NSAID is diflunisal. In an embodiment, the NSAID is oxaprozin. In an embodiment, the NSAID is lansoprazole / naproxen.

[0324] In embodiments, the NSAID is a selective COX-2 inhibitor. In embodiments, the selective COX-2 inhibitor is selected from the group consisting of celecoxib, etoricoxib, lumiracoxib, rofecoxib, valdecoxib, and amlodipine / celecoxib. In embodiments, the selective COX-2 inhibitor is celecoxib. In embodiments, the selective COX-2 inhibitor is etoricoxib. In embodiments, the selective COX-2 inhibitor is lumiracoxib. In embodiments, the selective COX-2 inhibitor is rofecoxib. In embodiments, the selective COX-2 inhibitor is valdecoxib. In embodiments, the selective COX-2 inhibitor is amlodipine / celecoxib.

[0325] In embodiments, the anti-inflammatory agent is a disease-modifying antirheumatic drug (DMARD). In embodiments, the DMARD is a synthetic DMARD. In embodiments, the synthetic DMARD is selected from the group consisting of methotrexate, leflunomide, hydroxychloroquine, azathioprine, and sulfasalazine. In embodiments, the synthetic DMARD is methotrexate. In embodiments, the synthetic DMARD is leflunomide. In embodiments, the synthetic DMARD is hydroxychloroquine. In embodiments, the synthetic DMARD is azathioprine. In embodiments, the synthetic DMARD is sulfasalazine.

[0326] In embodiments, the DMARD is a biologic DMARD. In embodiments, the biologic DMARD is selected from the group consisting of a TNF inhibitor, an interleukin-1 inhibitor, an interleukin-6 inhibitor, a T cell inhibitor, a B cell inhibitor, and a Janus kinase inhibitor. In embodiments, the biologic DMARD is a TNF inhibitor. In embodiments, the biologic DMARD is an interleukin-1 inhibitor. In embodiments, the biologic DMARD is an interleukin-6 inhibitor. In embodiments, the biologic DMARD is a T cell inhibitor. In embodiments, the biologic DMARD is a B cell inhibitor. In embodiments, the biologic DMARD is a Janus kinase inhibitor.

[0327] In embodiments, the TNF inhibitor is selected from the group consisting of adalimumab, etanercept, infliximab, golimumab, and certolizumab. In embodiments, the TNF inhibitor is adalimumab. In embodiments, the TNF inhibitor is etanercept. In embodiments, the TNF inhibitor is infliximab. In embodiments, the TNF inhibitor is golimumab. In embodiments, the TNF inhibitor is certolizumab. In embodiments, the interleukin-1 inhibitor is anakinra.

[0328] In embodiments, the interleukin-6 inhibitor is tocilizumab or sarulimab. In embodiments, the interleukin-6 inhibitor is tocilizumab. In embodiments, the interleukin-6 inhibitor is sarulimab. In embodiments, the T cell inhibitor is abatacept. In embodiments, the B cell inhibitor is rituximab. In embodiments, the Janus kinase inhibitor is selected from the group consisting of tofacitinib, baricitinib, and upadacitinib. In embodiments, the Janus kinase inhibitor is tofacitinib. In embodiments, the Janus kinase inhibitor is baricitinib. In embodiments, the Janus kinase inhibitor is upadacitinib.

[0329] In embodiments, the anti-inflammatory agent is another agent useful in treating inflammatory diseases. The term "other agent useful in treating inflammatory diseases" may be used interchangeably herein with the term "other agent," unless the context dictates otherwise. In embodiments, the other agent may be an analgesic, an anesthetic, a peptide, an enzyme, a coenzyme, a calcium channel blocker, an immunomodulator, an immunosuppressant, a proton pump inhibitor, an antidepressant (e.g., citalopram, escitalopram, fluocetine, fluvoxamine, paroxetine, lithium, bupropion, sertraline, amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, or venlafaxine), an opioid (e.g., fentanyl, methadone, morphine, or buprenorphine), biguanides (e.g., metformin), central nervous system agents (e.g., sodium phenylbutyrate / taurursodiol), antivirals (e.g., uncoating inhibitors, entry inhibitors, M pro-inhibitors, ritonavir, nilmatrervir, amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, saquinavir, tipranavir, asunaprevir, boceprevir, grazoprevir, glecaprevir, paritaprevir, simeprevir, Protease inhibitors such as telaprevir, GC376, nelfinavir, ensitrevir (Xocova) or simnotrervir, immunostimulants, latency breakers, reverse transcriptase, reverse transcriptase inhibitors such as azuvudine, integrase inhibitors (integrate), nucleoside analogues such as remedesivir, ganciclovir, ribavarin, valganciclovir, cidofovir, dulemidevir (VV116), odeldesivir (GS-5245) or acyclovir, ACE2 decoy receptor drugs, replication inhibitors, RdRp inhibitors, polymerase inhibitors such as molnupiravir, favipiravir, bemnifosbuvir (AT-527) or sofosbuvir, drugs acting on viral decapping, chemokine receptor antagonists such as maraviroc, neuraminidase inhibitors such as zanamivir or oseltamivir, fusion inhibitors, interferons such as interferon alpha, interferon beta or interferon gamma, integrase strand transfer inhibitors such as dolutegravir,nucleoside reverse transcriptase inhibitors (NRTIs) such as abacavir, stavudine, entecavir, lamivudine or zidovudine or non-nucleoside reverse transcriptase inhibitors and anticonvulsants (e.g., carbamazepine, oxcarbazepine, lamotrigine, valproic acid, topiramate, levetiracetam, brivaracetam or seletracetam),

[0330] In embodiments, the other agent is an analgesic. In embodiments, the other agent is an anesthetic. In embodiments, the other agent is a peptide. In embodiments, the other agent is an enzyme. In embodiments, the other agent is a coenzyme. In embodiments, the other agent is a calcium channel blocker. In embodiments, the other agent is an immunomodulatory agent. In embodiments, the other agent is an immunosuppressant, such as a macrolide, including rapamycin. In embodiments, the other agent is a proton pump inhibitor. In embodiments, the other agent is an antidepressant. In embodiments, the other agent is an opioid. In embodiments, the other agent is a biguanide. In embodiments, the other agent is a central nervous system agent. In embodiments, the other agent is an antiviral agent. In embodiments, the other agent is an anticonvulsant.

[0331] In some embodiments, the additional active agent is a serotonergic agent. In embodiments, "serotonergic agent" refers to any compound that binds to, blocks, or otherwise affects the activity of a serotonin receptor, including any serotonin receptor subtype (e.g., via an allosteric response). In embodiments, the serotonergic agent binds to a serotonin receptor. In embodiments, the serotonergic agent indirectly affects the serotonin receptor, e.g., through interactions that affect the responsiveness of other molecules at the serotonin receptor. In embodiments, the serotonergic agent is an agonist, e.g., a compound that activates the serotonin receptor. In embodiments, the serotonergic agent is an antagonist, e.g., a compound that binds to but does not activate the serotonin receptor, e.g., blocks the receptor. In embodiments, the serotonergic agent is an effector molecule, e.g., a compound that binds to an enzyme for allosteric modulation. In embodiments, serotonergic agents act (directly or indirectly) on multiple types of receptors, including receptors other than serotonergic receptors or other monoaminergic receptors. In embodiments, serotonergic agents block the serotonin transporter (SERT), resulting in increased synaptic concentrations of serotonin and increased neurotransmission. In embodiments, serotonergic agents are serotonin uptake or reuptake inhibitors. In embodiments, serotonergic agents act as reuptake modulators, inhibiting plasma membrane transporter-mediated reuptake of serotonin from synapses to presynaptic neurons, resulting in increased extracellular concentrations of serotonin and increased neurotransmission. In embodiments, serotonergic agents inhibit the activity of one or both monoamine oxidases, resulting in increased concentrations of serotonin and increased neurotransmission. In embodiments, the serotonergic agent is an antidepressant or anxiolytic, such as an SSRI, a serotonin-norepinephrine reuptake inhibitor (SNRI), a tricyclic antidepressant (TCA), a monoamine oxidase inhibitor (MAOI), or an atypical antidepressant.In other embodiments, the serotonergic agent is selected from the group consisting of: (1) serotonin transport inhibitors; (2) serotonin receptor modulators; (3) serotonin reuptake inhibitors; (4) serotonin and norepinephrine reuptake inhibitors; (5) serotonin dopamine antagonists; (6) monoamine reuptake inhibitors; (7) pyridazinone aldose reductase inhibitors; (8) serotonin receptor stimulants; (9) serotonin synthesis stimulants; (10) serotonin receptor agonists; (11) serotonin receptor antagonists; and (12) serotonin metabolites.

[0332] In embodiments, the additional active agent is any of phenolic compounds, terpenes, polysaccharides, polyphenols, lipids, organic acids, polyunsaturated fatty acids (PUFAs), imminosugars, and tocopherols extracted from fungi, algae, and / or plants. In embodiments, the additional active agent is extracted from a genera including any of Cheirolophus, Rhaponticoides, Volutaria, Zingiber, Rosmarinus, Salvia, Thymus, Origanum, Ocimum, Melissa, Mentha, Origanum, Satureja, Hyssopus, Laurus, Bacopa, Bupleurum, Camellia, Berberis, and Lathyrus. In embodiments, the additional active agent is extracted from the Zingiber genus, e.g., from Zingiber officinale. In embodiments, the additional active agent is extracted from Zingiber officinale rhizome. In embodiments, the additional active agent is extracted from the Laurus genus, e.g., from Laurus nobilis. In embodiments, the additional active agent is extracted from Laurus nobilis leaves. In embodiments, the disclosed compositions include an additional active agent derived from Zingiber, such as from Zingiber officinale rhizome, and an additional active agent derived from Laurus, such as from L. nobilis leaves.

[0333] In embodiments, the additional active agent may be any of an amino acid, an antioxidant, an anti-inflammatory agent, an analgesic, an antineuropathic agent, an antinociceptive agent, an antimigraine agent, an anxiolytic agent, an antidepressant, an antipsychotic agent, an anti-PTSD agent, a cannabinoid, an NMDA antagonist, a dissociative agent, an immunostimulant, an anticancer agent, an antiemetic agent, an appetite stimulant, an antiulcer agent, an antihistamine, an antihypertensive agent, an anticonvulsant, an antiepileptic agent, a bronchodilator, a neuroprotective agent, a nootropic, an entheogen, an entactogen, an empathogen, a hallucinogen, a monoamine oxidase inhibitor (e.g., a RIMA), a tryptamine, a terpene, a phenethylamine, a sedative, a stimulant, a metabolic or glucose regulator (e.g., metformin), a serotonergic agent, and a vitamin. These agents may be in ionic, free base, or salt form, and may be isomers, prodrugs, derivatives (preferably physiologically functional derivatives), or analogs.

[0334] In embodiments, the one or more additional active agents may be administered in separate dosage forms or as a single dosage form comprising one or more primary and / or secondary bioactive molecules according to the present disclosure in combination with one or more additional active agents.

[0335] V. Pharmaceutical Compositions In some aspects, pharmaceutical compositions comprising the therapeutic combination are disclosed. A "pharmaceutical composition" (also shortened to "composition" unless the context indicates otherwise) comprises a quantity of the therapeutic combination (e.g., in unit dosage form) together with a pharmaceutically acceptable carrier, diluent, or excipient. It will be understood that some embodiments do not comprise a single carrier, diluent, or excipient alone, but rather a plurality of carriers, diluents, and / or excipients. It will also be understood that the term "formulation," as used in embodiments herein, is equivalent to the terms "composition" and "pharmaceutical composition," unless the context clearly indicates otherwise.

[0336] In some embodiments, the disclosed combinations or compositions include non-naturally occurring carriers, diluents, or excipients, examples of which would be known to one of ordinary skill in the art. In some embodiments, "non-naturally occurring" refers to a carrier, diluent, or excipient used in the disclosed combinations or compositions that does not naturally occur in the fungi, plants, and / or algae, or in the same fungi, plants, and / or algae from which the extracts and / or bioactive molecules of the combination or composition are or may be derived.

[0337] The compositions can be prepared by standard pharmaceutical formulation techniques such as those disclosed in Remington: The Science and Practice of Pharmacy (2005) 21st ed., Mack Publishing Co., Easton, Pa.; The Merck Index (1996) 12th ed., Merck Publishing Group, Whitehouse, NJ; Pharm. Principles of Solid Dosage Forms (1993), Technomic Publishing Co., Inc., Lancaster, Pa.; and Ansel and Stoklosa, Pharm. Calculations (2001) 11th ed., Lippincott Williams & Wilkins, Baltimore, Md.; and Poznansky et al. Drug Delivery Systems (1980), R.L. Juliano, ed., Oxford, NY, pp. 253-315. "Pharmaceutically acceptable" as used in reference to an agent means that the agent is generally safe and, within the scope of sound medical judgment, suitable for use in contact with the cells of humans and other animals without undue toxicity, irritation, allergic response, or complications, and is commensurate with a reasonable risk / benefit ratio.

[0338] The compositions comprising the therapeutic combination can be formulated into any suitable dosage form, for example, aqueous oral dispersions, aqueous oral suspensions, solid dosage forms including oral solid dosage forms, aerosols, controlled release dosage forms, fast melt dosage forms, effervescent formulations, self-emulsifying dispersions, solid solutions, liposomal dispersions, lyophilized formulations, tablets, capsules, pills, powders, patches, inhalants, nebulizers, pulsatile release formulations, multiparticulate formulations, immediate release formulations, controlled release formulations, sustained release formulations, extended release formulations, modified release formulations, and mixed immediate and controlled release formulations.

[0339] In embodiments, the composition is formulated in a unit dosage form. A "unit dosage form" refers to a physically discrete unit suitable as a unitary dosage for a subject to be treated, containing a predetermined amount of a biologically active molecule calculated to produce a desired therapeutic effect, together with a suitable pharmaceutical carrier, diluent, or excipient. Unit dosage forms can be used for ease of administration and uniformity of dosage. A unit dosage form can contain a single dose or individual dose or unit, sub-dose, or an appropriate fraction thereof (e.g., one-half of a "total amount") of the composition to be administered. Unit dosage forms include capsules, troches, cachets, lozenges, tablets, ampoules, and vials, which may contain a freeze-dried or lyophilized composition; for example, a sterile liquid carrier may be added prior to administration or in vivo delivery. Unit dosage forms include ampoules and vials containing a liquid composition. Unit dosage forms include compounds for transdermal administration, such as "patches" that contact the epidermis for long or short periods of time.

[0340] In embodiments, the pharmaceutical compositions are formulated into pharmaceutically acceptable oral dosage forms, including oral solid dosage forms and oral liquid dosage forms.

[0341] In embodiments, the composition is formulated as a pharmaceutically acceptable oral solid dosage form, including lozenges, troches, tablets, capsules, caplets, powders, pellets, multiparticulates, beads, spheres, capsules, pills, and / or any combination thereof. The oral solid dosage form may be formulated as an immediate release, controlled release, extended release, sustained release, or modified release. In embodiments, the solid dosage form may include pharmaceutically acceptable excipients such as fillers, diluents, lubricants, surfactants, glidants, binders, dispersants, suspending agents, disintegrants, thickeners, film-forming agents, granulation aids, flavoring agents, sweeteners, coating agents, solubilizers, and combinations thereof. In embodiments, the solid dosage form may contain pharmaceutically acceptable additives, such as compatible carriers, complexing agents, ionic dispersion modifiers, disintegrants, surfactants, lubricants, colorants, wetting agents, plasticizers, stabilizers, humectants, and antifoaming agents, alone or in combination, and may further contain auxiliary active agents, including preservatives, antioxidants, and probiotics, such as antibacterial agents, including biocides, antiviral agents, and antifungal agents. Preservatives can be used to inhibit microbial growth or enhance the stability of active ingredients to extend the shelf life of pharmaceutical compositions, and include EDTA, EGTA, benzalkonium chloride, and benzoates, such as benzoic acid or sodium benzoate. Antioxidants include compounds such as vitamin A, vitamin C (ascorbic acid), vitamin E, tocopherols, other vitamins or provitamins, and alpha-lipoic acid (ALA).

[0342] In embodiments, the composition is formulated as a pharmaceutically acceptable oral liquid dosage form. Non-limiting examples of oral liquid dosage forms include tinctures, drops, emulsions, syrups, elixirs, suspensions, and solutions. In embodiments, oral liquid dosage forms can be formulated using any pharmaceutically acceptable excipient known to those skilled in the art for preparing liquid dosage forms, as well as solvents, diluents, carriers, excipients, and the like, selected appropriately depending on the solubility and other properties of the primary and / or secondary biologically active molecules and other components disclosed herein. Non-limiting examples of solvents include, for example, water, glycerin, simple syrup, alcohol, medium-chain triglycerides (MCTs), and combinations thereof.

[0343] In embodiments, oral liquid dosage forms may be monophasic or biphasic, the former being a substantially homogeneous solution dissolved in water or a non-aqueous solvent, and the latter referring to an oral liquid dosage form in which the bioactive molecules are not completely dissolved in the common solvent. In embodiments, solid particles (i.e., bioactive molecules) within an oral liquid dosage form may form a sediment at the bottom of the container over time, requiring vigorous shaking to redisperse the bioactive molecules. Non-limiting examples of monophasic liquid dosage forms include syrups, lycates, spirits / essences, elixirs, and fluid extracts. Non-limiting examples of biphasic liquid dosage forms include oral suspensions, oral emulsions, and mixtures.

[0344] Liquid dosage forms for oral administration can be prepared as liquid suspensions or solutions using sterile liquids, such as, but not limited to, oils, water, alcohol, pharmaceutically suitable surfactants, suspending agents, and emulsifying agents. In embodiments, liquid formulations can also be prepared as single-dose or multi-dose beverages. In embodiments, suspensions can contain oils, including, but not limited to, peanut oil, sesame oil, cottonseed oil, corn oil, and olive oil. Suitable oils also include carrier oils, such as MCT and long-chain triglyceride (LCT) oils. In embodiments, suspension formulations can contain esters of fatty acids, such as ethyl oleate, isopropyl myristate, fatty acid glycerides, and acetylated fatty acid glycerides. In embodiments, suspension formulations can contain alcohols, such as ethanol, isopropyl alcohol, and hexadecyl alcohol; glycerol, and propylene glycol. In embodiments, ethers, such as polyethylene glycol; petroleum hydrocarbons, such as mineral oil and petrolatum; and water can also be used in suspension formulations. In embodiments, suspensions may comprise an aqueous liquid or a non-aqueous liquid, an oil-in-water liquid emulsion, or a water-in-oil emulsion.

[0345] In addition to the primary and / or secondary bioactive molecules, the liquid dosage form may contain additives such as (a) disintegrants, (b) dispersants, (c) wetting agents, (d) preservatives, (e) thickeners, (f) sweeteners, and / or (g) flavoring agents. In addition to the above additives, in embodiments, the liquid formulations of the present disclosure may contain inert diluents commonly used in the art, such as water or other solvents, solubilizers, emulsifiers, flavoring agents, and / or sweeteners. In embodiments, cosolvents and adjuvants may be added to the formulation.

[0346] In embodiments of modified release formulations, the plasma half-life compared to the plasma half-life of an immediate release formulation is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 50%, at least 75%, at least 100%, or any value therebetween. In embodiments of modified release formulations, the formulations are designed to provide equivalent area under the curve (AUC) and similar safety and efficacy profiles, but with a lag time to peak concentration (t) of at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 50%, at least 75%, at least 100%, or any value therebetween. In embodiments, the formulations are designed to result in a product having a specific time course based on an optimal therapeutic window, for example, less than about 30 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 90 minutes, about 2 hours, about 3 hours, about 4 hours, and more than 4 hours (inclusive).

[0347] In embodiments, a formulation is selected based on its absorption surface area. In embodiments, a tincture, such as those described in the formulation examples below, may be selected based on its pre-digestive absorption by epithelial tissue.

[0348] In some embodiments, multiple formulations are combined, and a therapeutic combination includes two or more pharmaceutical compositions together, which can be provided as a single pharmaceutical kit. In some embodiments, one or more portions of the therapeutic combination are provided as an inhalable formulation, such as for a soft mist inhaler, and the remaining portion of the combination is provided as a tincture. In some embodiments, one or more portions of the therapeutic combination are provided as an inhalable formulation, and the remaining portion of the combination is provided as an orally dissolving strip. In some embodiments, one or more portions of the therapeutic combination are provided as a tincture, and the remaining portion of the combination is provided as an orally dissolving strip. In some embodiments, one or more portions of the therapeutic combination are provided as an inhalable formulation, and the remaining portion of the combination is provided as an oral spray, such as an oromucosal spray. In some embodiments, one or more portions of the therapeutic combination are provided as a tincture, and the remaining portion of the combination is provided as an oral spray.

[0349] In embodiments, three or more separate formulations are combined, and thus the therapeutic combination comprises three or more pharmaceutical compositions together, which may be provided as a single pharmaceutical kit. In embodiments, four or more, five or more, six or more, or seven or more separate formulations are combined, and thus the therapeutic combination comprises three or more, four or more, five or more, six or more, or seven or more pharmaceutical compositions together, which may be provided as a single pharmaceutical kit.

[0350] In embodiments, the pharmaceutical composition is formulated as an inhalation formulation. Non-limiting examples of inhalation formulations include soft mist inhalation formulations, dry powder aerosol formulations, and vaporization formulations. In embodiments, the inhalation formulation is a soft mist inhalation formulation ("soft mist" formulation). Soft mist formulations can be produced by combining a liquid containing a biologically active molecule in a cartridge or syringe. The cartridge or syringe is then placed in a soft mist inhalation device, such as those described in International Publication No. 2020 / 167893 and U.S. Patent No. 9,108,011, both of which are incorporated herein by reference. One may also choose to include a solubilizer (e.g., polysorbate 80, also known as TWEEN®-80) to aid in homogenization of the formulation. In embodiments, the liquid containing the biologically active molecule may be a liquid extract obtained via the methods disclosed herein, with or without a solubilizer. In embodiments, the inhalation formulation may be a dry powder aerosol formulation, in which the bioactive molecule is provided as a powder and aerosolized by an inhaler device, such as a metered dose inhaler (MDI).

[0351] In embodiments, the inhalation formulation is a vaporizable formulation. The vaporizable formulation may be any of vape juice, e-liquid, e-juice, etc. In embodiments, the vaporizable formulation may be liquid (e.g., including oil) and / or solid (e.g., including wax or dry powder). In embodiments, the vaporizable formulation may be produced by mixing bioactive molecules in a suitable liquid ("base liquid"), and the resulting formulation can be vaporized by a heating element (such as those found in vape pens, e-cigarettes, e-pipes, and other such electronic smoking devices). Examples of suitable liquids include propylene glycol (PG), vegetable glycerin (VG), polyethylene glycol (PEG), and mixtures thereof, in any proportion. In embodiments, the base liquid may include a low-viscosity liquid that acts as a diluent, such as water and / or ethanol (including when ethanol is a distilled spirit, e.g., vodka). In embodiments, the vaporizable formulation contains a flavoring, which may be any flavor or flavor concentrate.

[0352] In embodiments, the pharmaceutical composition is formulated as an effervescent powder.

[0353] In embodiments, the pharmaceutical composition is formulated into a pharmaceutically acceptable transdermal application that can be administered transdermally. Non-limiting examples of transdermal formulations include ointments, creams, suspensions, lotions, pastes, gels, sprays, foams, oils, and the like, and any combination thereof.

[0354] In embodiments, the pharmaceutical composition is formulated for subcutaneous, intravenous, intraarterial, intraperitoneal, intraosseous, intramuscular, intrathecal, or intracerebroventricular injection (an "injectable formulation"). In embodiments, the injectable formulation may be prepared by dissolving, suspending, or emulsifying the first bioactive molecule and / or the second bioactive molecule in an aqueous or non-aqueous solvent, non-limiting examples of which include oils such as vegetable oils, synthetic aliphatic acid glycerides, and esters of higher aliphatic acids or propylene glycol; and may also include additives such as solubilizers, stabilizers, and suspending agents, preservatives, wetting agents, emulsifiers, dispersing agents, and isotonic agents.

[0355] In some embodiments, compositions are formulated for particular tissues or for particular routes of administration other than oral gastrointestinal administration, e.g., mucosal (e.g., sublingual, buccal, rectal, vaginal, nasal), IV, intramuscular (IM), subcutaneous (SC), dermal, intranasal, inhalation, etc. Such administration may, in some embodiments, result in fewer side effects, less toxicity, increased efficacy, improved selectivity, increased bioavailability, and minimized drug-drug interactions.

[0356] Injectable formulations may contain additives such as preservatives, wetting agents, emulsifiers, and dispersing agents. Prevention of microbial growth can be ensured by various antibacterial and antifungal agents, such as parabens, benzoic acid, benzyl alcohol, chlorobutanol, phenol, and sorbic acid, and isotonicity agents, such as sugars and sodium chloride, may also be included. Prolonged drug absorption from injectable dosage forms can be achieved by the use of absorption delaying agents, such as aluminum monostearate and gelatin. Injectable formulations designed for sustained release via SC or IM injection can avoid first-pass metabolism and require lower doses of the primary and / or secondary bioactive molecules to maintain desired plasma levels. In such formulations, the particle size and particle size range of the primary and / or secondary bioactive molecules can be used to control the release of the primary and / or secondary bioactive molecules by controlling their dissolution rate in fat or muscle.

[0357] In embodiments, the composition is formulated into a pharmaceutically acceptable nanostructured formulation, such as a nanoemulsion, nanocapsule, nanoparticle conjugate, or nanoencapsulated oral, sublingual, buccal, or nasal spray. In embodiments, the nanostructured formulation is prepared with reference to the general knowledge in the art (see, for example, Jaiswal et al. 3 Biotech. 2015;5(2):123-127).

[0358] In some embodiments, when a therapeutic combination, pharmaceutical composition, or other formulation includes a natural or naturally occurring compound, at least one of the carriers, diluents, and / or excipients used in the combination, composition, or formulation is non-natural or of non-natural origin, or other agents, such as additional active agents, in the disclosed combinations, compositions, or formulations are non-natural or of non-natural origin, i.e., a natural compound is combined with a non-natural component, such that the combination, composition, or formulation includes at least one non-natural component and, in embodiments, provides a surprising synergistic effect. When each of the compounds in the combination, composition, or formulation is natural or found in nature, the combination, composition, or formulation and / or the compounds therein, in embodiments, demonstrate characteristics significantly different from the natural product itself.

[0359] By way of non-limiting, merely suggestive example, the following formulations can be prepared and used in the methods of the present disclosure.

[0360] In all exemplary formulation embodiments disclosed below, the formulation may comprise solely fungal-derived bioactive molecules and solely plant-derived bioactive molecules ("may comprise solely" means not comprising additional disclosed bioactive molecules, but the formulation may further comprise one or more carriers, diluents, or excipients, other inactive ingredients, and / or, in some embodiments, additional active agents disclosed herein). In embodiments, the formulation may comprise solely fungal-derived bioactive molecules and solely plant-derived bioactive molecules (i.e., when the molecules are extracted, isolated, derived, or otherwise obtained from a single genus, and not necessarily only found in one genus). In embodiments, the formulation may comprise solely fungal-derived bioactive molecules and solely plant-derived bioactive molecules (i.e., when the molecules are extracted, isolated, derived, or otherwise obtained from a single species, and not necessarily only found in a single species). In embodiments, the formulation may comprise solely one fungal-derived bioactive molecule and one plant-derived bioactive molecule.

[0361] In some embodiments, the formulation may comprise a bioactive molecule derived from a psilocybin-producing species and a bioactive molecule derived from a Cannabis plant alone. In embodiments, the formulation is selected from the group consisting of Psilocybe azurescens, Psilocybe bohemica, Psilocybe semilanceata, Psilocybe baeocystis, Psilocybe cyanescens, Psilocybe tampanensis, Psilocybe cubensis, Psilocybe weilii, Psilocybe hoogshagenii, Psilocybe stuntzii, Psilocybe cyanofibrillosa, and Psilocybe tampanensis. In embodiments, the formulation may comprise a bioactive molecule derived from a psilocybin-producing species and a bioactive molecule derived from a Cannabis plant, independently.In embodiments, the formulation is selected from the group consisting of Psilocybe azurescens, Psilocybe bohemica, Psilocybe semilanceata, Psilocybe baeocystis, Psilocybe cyanescens, Psilocybe tampanensis, Psilocybe cubensis, Psilocybe weilii, Psilocybe hoogshagenii, Psilocybe stuntzii, Psilocybe cyanofibrillosa, and Psilocybe tampanensis. In an embodiment, the formulation may contain one bioactive molecule derived from the Psilocybe fungus and one bioactive molecule derived from the Cannabis plant, respectively. In an embodiment, the formulation may contain one bioactive molecule derived from the Psilocybe fungus and one bioactive molecule derived from the Cannabis plant, respectively. "Psilocybe fungus" refers to the Psilocybe fungus. In an embodiment, the formulation may contain one bioactive molecule derived from the Psilocybe fungus and one bioactive molecule derived from the Cannabis plant, respectively.

[0362] For example, the following embodiments may optionally use psilocybin (or psilocin) alone or both; CBD (or THC) alone or both; and coumarin, whole Pyropia extract, ethanol, and ginger (and any other disclosed active or inactive ingredients), i.e., some embodiments may not include any one or more of coumarin, whole Pyropia extract, and ethanol, and flavorings and / or colorings such as ginger (and any other disclosed active or inactive ingredients). Thus, in some embodiments, exemplary formulations include psilocybin and CBD alone. In embodiments, exemplary formulations include psilocin and CBD alone. In embodiments, exemplary formulations include psilocybin, psilocin, and CBD alone. In embodiments, exemplary formulations include psilocybin, THC, and CBD alone. In embodiments, exemplary formulations include psilocin, THC, and CBD alone. In embodiments, exemplary formulations comprise psilocybin, psilocin, and THC alone. In embodiments, exemplary formulations comprise psilocybin and THC alone. In embodiments, exemplary formulations comprise psilocin and THC alone. As noted above, "comprising solely" means not comprising additional disclosed bioactive molecules, although the formulation may further comprise one or more carriers, diluents, or excipients disclosed herein, other inactive ingredients, and / or, in some embodiments, additional active agents, or active agents suitable for the formulation, such as those known in the art.

[0363] In some embodiments, any one or more of psilocybin, psilocin, THC, and CBD can be substituted with another bioactive molecule, for example, another bioactive molecule from the same fungus or plant. In some embodiments, flavorings and / or colors (equivalent but abbreviated as "flavorings / colorings") are optional. Thus, any of the following examples that do not include flavorings / colorings are additional embodiments. In some embodiments, the exemplary "flavorings / colorings" are ethanol and ginger. In some embodiments, the formulations include additional active agents. In the absence of active and / or inactive ingredients from the disclosed exemplary formulations, the formulations are prepared as described, with modifications understood by those of ordinary skill in the art, using common skill and knowledge in the art. Where ingredients can be provided as solids or liquids, those skilled in the art will understand how to convert between mass amounts and volume amounts, including alternative or variable concentrations of ingredients, whether solid or liquid.

[0364] Example 1: Tincture Prepare a tincture in the following proportions: [Table 2]

[0365] The solution is prepared by mixing bioactive molecules derived from fungi, plants, and algae, and / or extracts containing the same ("bioactive molecules and / or extracts containing the same") with flavoring agents and a solvent. In embodiments, amounts or proportions of ingredients, such as when expressed by weight or percentage, include the term "about." In some embodiments, "about" by weight or "about" by percentage refers to a range of ±2%, including when the term "about" is implied by context. Thus, for example, in an embodiment in which psilocybin (or a psilocybin-containing fungal extract) is 45% of the formulation, the amount in the embodiment refers to "about" 45% psilocybin or psilocybin-containing extract; in some such embodiments, the amount "about" 45% refers to an amount of 45% ±2%, i.e., an amount of 43% to 47%, inclusive, of psilocybin or psilocybin-containing extract. In some other embodiments, an amount expressed as a mass or percentage also refers to "about" that amount, where "about" has the meaning set forth elsewhere.

[0366] In embodiments, the fungal extract comprises about 45% of each dose and contains about 400 μg of combined psilocybin and psilocin per dose; the Cannabis extract comprises about 15% of each dose and contains about 1 mg of CBD and about 1 mg of THC per dose; the coumarin extract comprises about 2% of each dose and contains about 1 mg of coumarin per dose; the algae extract (in embodiments, a Pyropia extract) comprises about 15% of each dose; the flavoring and / or coloring (in some preferred embodiments, an ethanol decoction of ginger and bay leaves, and in some embodiments, another flavoring and / or coloring that may be in ethanol, water, or another diluent) comprises about 15% of each dose; and the added water comprises about 8% of each dose. In some embodiments, the tinctures or other liquid formulations herein further comprise a solubilizing agent such as cyclodextrin, lecithin, propylene glycol, xanthan gum, or a combination thereof.

[0367] Tinctures can be prepared by exposing fungi, plants and / or algae to a solvent capable of extracting the desired primary and / or secondary bioactive molecules, combining the extracts, and then optionally adding flavors and / or colors.

[0368] In some embodiments, the solvent is alcohol. In embodiments, the alcohol may be, for example, 40% to 60% alcohol, or 80% to 90% alcohol, and then diluted to 40% to 60% alcohol. In some embodiments, the solvent is water. In some embodiments, the solvent may be an acid, such as acetic acid.

[0369] As an example, food colorings may be added to tinctures to give the solution a certain appearance, and may contain additional compounds sufficient to improve the taste of the tincture. In embodiments, the food colorings may include compounds that improve the biological activity of the primary bioactive molecule and / or the secondary bioactive molecule. Examples of food colorings suitable for use with the disclosed extracts, compositions, and tinctures include turmeric extract, cinnamon extract, beetroot extract, carrot extract, caramel, blueberry extract, blackberry extract, and ginger extract.

[0370] In some embodiments, the subject is administered one dose of a tincture having the amounts of ingredients as prescribed above, two doses of a tincture in the amounts as prescribed above, three such doses, four such doses, five such doses, or more than five such doses daily. In some preferred embodiments, the daily dose is four doses.

[0371] Example 2: Oral spray and oral mucosal spray formulations An oral spray can be prepared containing the same ingredients, amounts (units) of ingredients, and overall proportions as in Example 1. When the oral spray is formulated for oral mucosal (e.g., sublingual or buccal) administration, it may further contain a penetration enhancer and / or a mucoadhesive polymer.

[0372] Example 3: Soft mist inhalation formulation A soft mist inhalation formulation is prepared as follows: The soft mist inhalation formulation contains the same ingredients, amounts (units) of ingredients, and overall proportions as in Example 1 above: A solution is prepared by combining bioactive molecules derived from fungi, plants, and algae, and / or extracts containing same, with flavors / colors and a solvent.

[0373] Bioactive molecules and / or the extracts containing them are mixed and combined.Then, the combined bioactive molecules and / or the extracts containing them can be combined with ethanol and / or water, and optionally added preservatives, such as benzalkonium chloride, to make a volume of, for example, 15mL.Can refer to Anderson.Int J Chron Obstruct Pulmon Dis.2006;1(3):251-259 and Dalby et al.Med Devices (Auckl).2011;4:145-155, both of which are incorporated herein by reference in their entirety.

[0374] Example 4: Vaporized formulation A vaporization formulation containing 500 μg of psilocybin, 300 μg of psilocin, 2 mg of CBD, 2 mg of THC, 2 mg of coumarin, 16 mg of whole Pyropia extract, 16 mg of flavors / colors, and 10 mL of a 50:50 base liquid (50% PG, 50% VG) is prepared as follows: the bioactive molecules and / or extracts containing them are mixed and combined (in solid form and / or as part of one or more liquid extracts) with a 50:50 base liquid prepared for use in any liquid vaporization device or apparatus, such as an e-liquid vaporizer, e-cigarette, mod, or vape pen. Flavors / colors (including, for example, ginger and / or bay leaf) may optionally be added. This formulation can also be prepared for any oil, thin oil, e-juice, or e-liquid vaporizer, according to those skilled in the art.

[0375] Example 5: Tablet and divisible multi-acting tablet formulations Tablets containing 500 μg of psilocybin, 300 μg of psilocin, 1 mg of CBD, 1 mg of THC, 1 mg of coumarin, 16 mg of whole Pyropia extract, 170 mg of microcrystalline cellulose, 10 mg of colloidal silicon dioxide, and 7.5 mg of stearic acid are prepared by combining the bioactive molecules and / or extracts containing them with other ingredients and compressing them to form tablets.

[0376] Divisible, multi-action tablets containing 1000 μg of psilocybin, 600 μg of psilocin, 2 mg of CBD, 2 mg of THC, 2 mg of coumarin, 32 mg of whole Pyropia extract, 35 mg of microcrystalline cellulose, 45 mg of starch, 4.5 mg of sodium carboxymethyl starch, 0.5 mg of magnesium stearate, 1 mg of talc, and 4 mg of polyvinylpyrrolidone (PVP) (as a 10% solution in water) are prepared as follows: The bioactive molecules and / or extracts containing them, starch, and cellulose are passed through a No. 20 mesh US sieve and thoroughly mixed. The PVP solution is mixed with the resulting powder, which is then passed through a 16 mesh US sieve. The resulting granules are dried at 50-60°C and passed through a 16 mesh US sieve. Sodium carboxymethyl starch, magnesium stearate, and talc are passed through a 30-mesh US sieve and added to the granules. After mixing, the granules are compressed on a tablet machine to give tablets. The tablets are scored to allow equal dosing of half the dose.

[0377] Example 6: Capsule formulation Capsules containing 500 μg of psilocybin, 300 μg of psilocin, 2 mg of CBD, 2 mg of THC, 2 mg of coumarin, 16 mg of whole Pyropia extract, 119 mg of cellulose and / or starch, and 1 mg of magnesium stearate are prepared by blending these and other bioactive molecules and / or extracts with the cellulose and / or starch and magnesium stearate, passing the mixture through a No. 20 mesh U.S. sieve, and filling it into hard or soft gelatin capsules.

[0378] Example 7: Alternative capsule formulations that may contain additional active agents Capsules each containing 1000 μg of psilocybin, 600 μg of psilocin, 2 mg of CBD, 2 mg of THC, 2 mg of coumarin, 16 mg of whole Pyropia extract, 50 mg of a serotonergic agent, 100 mg of cellulose and / or starch, and 1 mg of magnesium stearate are prepared as follows: the bioactive molecules and / or extracts containing them, the cellulose and / or starch, and the magnesium stearate are blended, passed through a No. 20 mesh US sieve, and filled into hard or soft gelatin capsules. Optionally, additional active agents may be added during blending. In some embodiments, the additional active agent is a serotonergic agent, such as an antidepressant or an anxiolytic. In some embodiments, the additional active agent is an anti-inflammatory agent, as described herein or generally known in the art.

[0379] Example 8: Suspension formulation A suspension formulation containing 250 μg of psilocybin, 150 μg of psilocin, 1 mg of CBD, 1 mg of THC, 1 mg of coumarin, and 8 mg of whole Pyropia extract is prepared as follows: The bioactive molecules and / or their constituent extracts are mixed with 1.75 g of sucrose and 4 mg of xanthan gum, passed through a 10-mesh US sieve, and mixed with a solution of 50 mg of sodium carboxymethylcellulose (11%) and 50 mg of microcrystalline cellulose (89%) in water. 10 mg of sodium benzoate and optional flavors / colors (see section) are diluted with a portion of the water and added with stirring. Sufficient water is then added to 5 mL.

[0380] Example 9: Intravenous solution formulation An intravenous formulation containing 250 μg of psilocybin, 150 μg of psilocin, 1 mg of CBD, 1 mg of THC, 1 mg of coumarin, 8 mg of whole Pyropia extract, and 1000 mL of isotonic saline can be prepared as follows: the bioactive molecules and / or extracts containing them are dissolved in a suitable solvent, such as isotonic saline or other suitable solvent; additional active or inactive ingredients, such as solubilizers and preservatives, can be added as described above and within the general knowledge in the art. It will be understood that the amount of each bioactive molecule and / or extract can be adjusted accordingly to achieve the desired mg / mL.

[0381] Example 10: Injectable liquid formulation An injectable formulation containing 250 μg of psilocybin, 150 μg of psilocin, 1 mg of CBD, 1 mg of THC, 1 mg of coumarin, 8 mg of whole Pyropia extract, and 5 mL of isotonic saline can be prepared as follows: the bioactive molecules and / or extracts containing them are dissolved in an appropriate solvent, such as isotonic saline or other suitable solvent; additional active or inactive ingredients, such as preservatives, can be added as described above and within the knowledge of the art. It will be understood that the amount of each bioactive molecule and / or extract can be adjusted accordingly to achieve the desired mg / mL.

[0382] Example 11: Topical formulation for transdermal administration A topical formulation containing 400 μg of psilocybin, 250 μg of psilocin, 2 mg of CBD, 2 mg of THC, 2 mg of coumarin, 8 mg of whole Pyropia extract, 30 mg of emulsifying wax, and 20 mg of liquid paraffin in a total amount equal to 100 g of white soft paraffin can be prepared as follows: Heat the white soft paraffin until melted. Add the liquid paraffin and emulsifying wax and stir until dissolved. Add the bioactive molecules and / or extracts containing them and continue stirring until dispersed. Then, cool the mixture until solid.

[0383] Example 12: Cut matrix sublingual or buccal tablet formulation Sublingual or buccal tablets containing 500 μg of psilocybin, 300 μg of psilocin, 2 mg of CBD, 2 mg of THC, 2 mg of coumarin, 8 mg of whole Pyropia extract, 210.5 mg of glycerol, 143 mg of water, 4.5 mg of sodium citrate, 26.5 mg of polyvinyl alcohol, and 15.5 mg of polyvinylpyrrolidone (PVP) are prepared as follows: glycerol, water, sodium citrate, polyvinyl alcohol, and PVP are mixed by continuous stirring while maintaining a temperature of approximately 90°C. Once the polymers are in solution, the solution is cooled to approximately 50-55°C, and the bioactive molecules and / or extracts containing them are slowly mixed in. The homogeneous mixture is poured into an inert mold to create a drug-containing diffusion matrix approximately 2-4 mm thick. The diffusion matrix is ​​then cut to form individual tablets of appropriate size.

[0384] Example 13: Individually formed sublingual or buccal lozenge formulations Sublingual or buccal lozenges containing 500 μg of psilocybin, 300 μg of psilocin, 2 mg of CBD, 2 mg of THC, 2 mg of coumarin, 8 mg of whole Pyropia extract, 350 mg of silica gel powder, 400 mg of citric acid powder, 600 mg of acacia powder, 1 g of polyethylene glycol (PEG), and optionally 100 mg of flavoring / coloring are prepared as follows: The silica gel powder, citric acid powder, acacia powder, optional flavoring / coloring, and PEG are mixed with continuous stirring at a temperature of approximately 90°C. Once the PEG has melted and the other ingredients have gone into solution, the solution is cooled to approximately 50-55°C and the bioactive molecules and / or extracts containing them are slowly mixed in. The homogeneous mixture is poured into separate molds and allowed to cool. See also incorporated U.S. Patent No. 10,034,832 and its examples.

[0385] Example 14: Intranasal Delivery Formulation A nasal spray formulation for intranasal delivery containing 250 μg of psilocybin, 150 μg of psilocin, 1 mg of CBD, 1 mg of THC, 1 mg of coumarin, 8 mg of whole Pyropia extract, 50 μL of DMSO, and 5 mL of MCT in saline (1% Cremophor) to a total volume of 10 mL can be prepared as follows: a solution of approximately 1 mg / mL of the bioactive molecule(s) and / or extract(s) containing the same is / are dissolved in 49.5% MCT, 49.5% saline, 0.5% DMSO, and 0.5% Cremophor is prepared for use in the nasal spray device. In other embodiments, the nasal formulation can be prepared as a dry powder for inhalation, for example, by combining the bioactive molecule(s) and / or extract(s) containing the same with lactose and blending for use in a dry powder inhaler, or as described in U.S. Patent Application Publication No. 2015 / 0367091 A1 and the references cited therein.

[0386] In some exemplary embodiments, the disclosed therapeutic combinations or compositions include the primary biologically active molecules in the table below from each listed component of the combination or composition, and such combinations or compositions can be formulated according to the disclosed examples or as another exemplary formulation according to this disclosure and general knowledge in the art: [Table 3] [Table 4] [Table 5]

[0387] It should be noted that while certain primary and / or secondary bioactive molecules, and certain extracts containing them, are disclosed above, this should not be construed as limiting the disclosure or limiting the formulation of Example 1 to the primary and / or secondary bioactive molecules disclosed above. Thus, in embodiments, the formulation of Example 1 (or other examples herein) contains additional or fewer primary and / or secondary bioactive molecules than those disclosed; including any of the primary and / or secondary bioactive molecules disclosed herein for each of the fungal extract, Cannabis extract, Cumar extract, and algae extract.

[0388] In some alternative embodiments of this example, the formulation comprises at least one bioactive molecule derived from a fungus and at least one bioactive molecule derived from a plant, wherein the fungal bioactive molecule comprises one derived from a psilocybin-producing species, such as the genera Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina, and Pluteus, and the plant bioactive molecule comprises one derived from a cannabinoid-producing species, such as the Cannabis species. In some such alternative embodiments, the formulation further does not comprise any fungal bioactive molecules or plant bioactive molecules, other than those derived from psilocybin-containing species and cannabinoid-producing species. In some such alternative embodiments, the formulation further does not contain bioactive molecules derived from fungi or plants, except for those derived from the genera Copelandia, Galerina, Gymnopilus, Inocybe, Panaeolus, Pholiotina, and Pluteus, and those derived from the genus Cannabis. In some such alternative embodiments, the formulation does not contain bioactive molecules derived from the genus Dipteryx. In some such alternative embodiments, the formulation does not contain bioactive molecules derived from algae, seaweed, the Bangiaceae family, or the genera Pyropia and Porphyra. In some such alternative embodiments, the only bioactive molecules are psilocybin, psilocin, CBD, and THC. In some such alternative embodiments, the only biologically active molecules are psilocybin, CBD, and THC. In some such alternative embodiments, the only biologically active molecules are psilocybin and CBD. In some such alternative embodiments, the only biologically active molecules are psilocybin and THC.In some such alternative embodiments, the only bioactive molecules are psilocin, CBD, and THC. In some such alternative embodiments, the only bioactive molecules are psilocin and CBD. In some such alternative embodiments, the only bioactive molecules are psilocin and THC.

[0389] It will be understood that the above formulation examples are illustrative only. Any of the disclosed primary and / or secondary bioactive molecules may be utilized in the formulation examples and in the dosage ranges applicable to that primary and / or secondary bioactive molecule. Reference to specific primary and / or secondary bioactive molecules is merely exemplary, and it will be understood that any example bioactive molecule may be substituted with other primary and / or secondary bioactive molecules disclosed herein.

[0390] Furthermore, it will be readily understood that the disclosed compositions are not limited to combinations of a single primary and / or secondary bioactive molecule, or (when formulated as a pharmaceutical composition) limited to only a single carrier, diluent, and / or excipient, but may also include combinations of multiple primary and / or secondary bioactive molecules (including additional bioactive molecules), and / or multiple carriers, diluents, and excipients. Thus, the pharmaceutical compositions of the present disclosure may include any of the primary and / or secondary bioactive molecules disclosed above. That is, in embodiments, the disclosed compositions include primary and / or secondary bioactive molecules derived from fungi, plants, and algae, optionally in combination with one or more other bioactive molecules (or derivatives and analogs thereof), along with one or more pharmaceutically acceptable carriers, diluents, and / or excipients, and further along with one or more other active agents.

[0391] In embodiments, the disclosed compositions are formulated to augment an existing therapeutic effect, to provide an additional therapeutic effect, to increase adherence or ease of use, to increase a desired property such as stability or shelf life, to reduce an undesirable effect or property, to alter a property in a desired manner (such as pharmacokinetics or pharmacodynamics), to modulate a desired system or pathway (e.g., a neurotransmitter system), or to provide a synergistic effect.

[0392] "Therapeutic effects" that may be increased or added in embodiments of the present disclosure include, but are not limited to, known antioxidant, anti-inflammatory, analgesic, anti-neuropathic, anti-nociceptive, anti-migraine, anti-anxiety, anti-depressant, anti-psychotic, anti-PTSD, dissociative, immunostimulatory, anti-cancer, anti-emetic, appetite stimulant, anti-ulcer, antihistamine, anti-hypertensive, anti-convulsant, anti-epileptic, bronchodilator, neuroprotective, brain function improving, empathogenic, psychedelic, sedative, or stimulant effects, as well as effects that improve symptoms caused by inflammatory conditions or disorders.

[0393] The goals of augmenting an existing therapeutic effect, providing an additional therapeutic effect, increasing adherence or ease of use, increasing a desired property such as stability or shelf life, decreasing an undesirable effect or property, altering a property in a desired manner (such as pharmacokinetics or pharmacodynamics), modulating a desired system or pathway (e.g., a neurotransmitter system), or inducing a synergistic effect are, in embodiments, achieved by including an additional active agent.

[0394] The type of formulation employed for administration of the primary and / or secondary bioactive molecules employed in the disclosed methods will generally be determined by the primary and / or secondary bioactive molecules employed, the route of administration and the type of pharmacokinetic profile desired from the primary and / or secondary bioactive molecules, and the condition of the subject. It will be understood that any of the above embodiments can also be combined to form additional embodiments.

[0395] A. Route of Administration The disclosed pharmaceutical compositions are suitable for administration by various routes, including, but not limited to, enteral administration, such as oral, sublingual, buccal, and rectal administration, bolus injection or continuous infusion, parenteral administration, including intravenous, intraarterial, intraperitoneal, intraosseous, intramuscular, intrathecal, intracerebroventricular, intravaginal, intraocular, intranasal, intradermal, topical, auricular, intraocular, transdermal, and subcutaneous administration.

[0396] In embodiments, the pharmaceutical compositions are administered as oral solid and liquid dosage forms; as sublingual or buccal administration; as injections, including intravenous, intraarterial, intraperitoneal, intraosseous, intramuscular, intrathecal, and intracerebroventricular administration; rectally, vaginally, intraocularly, nasally, intradermally, topically, auricularly, transdermally, and subcutaneously.

[0397] In embodiments where administration is enteral, parenteral, or both, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered systemically to the subject. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered orally to the subject. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered intravenously to the subject. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered to the subject by inhalation. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered nasally to the subject. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered to the subject by injection. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered topically (transdermally) to the subject. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered ophthalmically to the subject. In embodiments, an effective amount of the first bioactive molecule and / or the second bioactive molecule is administered rectally to the subject. In embodiments, the primary and / or secondary biologically active molecules employed in the methods disclosed and described herein are effectively administered to a subject by other means and are prepared in any acceptable composition known to those skilled in the art. In embodiments, such compositions can be prepared in any manner known in the pharmaceutical arts, including at least one biologically active molecule (Sheth et al., Compressed tablets. In: Pharmaceutical Dosage Forms: Tablets Eds. HALieberman and L. Lachman. Vol. 1. 1980. 109. Marcel Dekker).

[0398] In embodiments, the primary and / or secondary bioactive molecules disclosed herein are administered by multiple routes, which may vary between subjects, such as patients, according to subject preferences, comorbidities, side effect profiles, pharmacokinetic and pharmacodynamic considerations, and other factors. Embodiments include the presence of other substances along with the primary and / or secondary bioactive molecules, such as those known to those skilled in the art, to enhance absorption via various routes (e.g., gastrointestinal, transdermal, etc.), prolong the effect of the drug, and / or achieve higher or stable serum levels, or modifications in the preparation to enhance the therapeutic effect of the primary and / or secondary bioactive molecules disclosed herein.

[0399] In embodiments, the pharmaceutical compositions are suitable as oral solid or liquid dosage forms administered sublingually, bucally, rectally, vaginally, ocularly, auricularly, nasally, intradermally, topically, and transdermally; or as intravenous, intraarterial, intraperitoneal, intramedullary, intramuscular, intrathecal, intracerebroventricular, and subcutaneous injections, including physiologically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, liposomes, and sterile powders for reconstitution into sterile injectable solutions or dispersions.

[0400] In embodiments, the compositions may be administered via enteral or parenteral means, where enteral means include, but are not limited to, oral solid and liquid dosage forms, sublingual and buccal administration, and rectal administration; and parenteral means of administration include, but are not limited to, bolus injection or continuous infusion, intravenous, intraarterial, intraperitoneal, intraosseous, intramuscular, intrathecal, intraventricular, intravaginal, intraocular, intranasal, intradermal, topical, auricular, transdermal, and subcutaneous administration; as well as other equivalent means known to those skilled in the art.

[0401] Enteral administration includes administration through any part of the digestive tract. Non-limiting examples include oral (oral), including oral solid and liquid dosage forms, and rectal, which may, in some embodiments, be preferably formulated as a tincture. Parenteral administration refers to administration by any means that does not involve the digestive tract, including intravenous (into a vein), intraarterial (into an artery), intraosseous injection (into the bone marrow), intramuscular (into a muscle), intracerebral (into the brain parenchyma), intraventricular (into the ventricular system), intrathecal (injection into the spinal canal), auricular (through the ear), ocular (through the eye), vaginal (intravaginal), and subcutaneous (subcutaneous). In embodiments, parenteral administration may include sublingual and / or buccal administration. In embodiments, the pharmaceutical composition may be administered to a subject via injection. In embodiments, the pharmaceutical composition may be administered to a subject via the nasal system or the mouth, for example, in the form of an oral solid dosage form and / or an oral liquid dosage form; inhalation via a nasal spray or oral inhaler; spray from a nebulizer, such as a machine that atomizes liquid medicine; or buccal / sublingual administration. In embodiments, the pharmaceutical composition may be administered to a subject via a combination of administration means. In embodiments, the pharmaceutical composition may be administered to a subject via enteral administration means. In embodiments, the pharmaceutical composition may be administered to a subject via parenteral administration means. In embodiments, the composition may be administered to a subject via at least one enteral administration means and at least one parenteral administration means. In embodiments, equivalent routes of administration known to those skilled in the art are utilized.

[0402] In some embodiments, the therapeutic combination may be administered via multiple routes of administration. For example, in embodiments, the fungal portion of the disclosed combination is administered via one route of administration, and the plant and algal portions are administered via different routes of administration. In embodiments, the plant portion of the disclosed combination is administered via one route of administration, and the fungal and algal portions are administered via different routes of administration. In embodiments, the algal portion of the disclosed combination is administered via one route of administration, and the plant and fungal portions are administered via different routes of administration.

[0403] Administering different (fungal, plant, or algal) parts of the disclosed combinations to different tissues may maximize the therapeutic effect of the combination, reduce side effects, reduce patient discomfort, and / or increase bioavailability. In one illustrative example, the disclosed combinations consist of plant parts containing cannabinoids (e.g., THC) or cannabis extract, which are administered to the oral mucosa via a spray; while the remaining components (e.g., fungal, plant, and / or algal parts) are delivered to pulmonary epithelial cells via a soft-mist inhaler. In some embodiments, administration according to this illustrative procedure results in reduced pharyngeal irritation (e.g., in individuals sensitive to inhaled cannabis or cannabinoids), maximizes the bioavailability of the remaining components (e.g., fungal, plant, and / or algal parts), and improves the pharmacokinetic profile of the components of the therapeutic combination, for example, by promoting the uptake of longer-lasting plant parts (e.g., THC or cannabis extract) while mitigating the uptake of shorter-lasting parts.

[0404] In another example, the disclosed combination includes an algae portion containing Pyropia or Pyropia extract, which is administered to the oral mucosa via an oral spray, while the remaining components (e.g., fungal, plant, and / or algal portions) are delivered to the pulmonary epithelial cells via a soft mist inhaler. In some embodiments, administration according to this exemplary procedure results in reduced pharyngeal irritation, maximizes the bioavailability of the components (e.g., fungal, plant, and / or algal portions), and improves the pharmacokinetic profile of the therapeutic combination components; for example, by moderating the uptake of shorter-lasting algae portions (e.g., Pyropia or Pyropia extract) while promoting the uptake of longer-lasting portions.

[0405] B. Administration Method In some embodiments, methods for administering the primary and / or secondary bioactive molecules disclosed herein are provided. As used herein, the terms "subject," "user," "patient," and "individual" are used interchangeably and refer to any mammal, preferably a human. Such terms will be understood to include anyone with an indication for which the combinations, compositions, or methods described herein may be effective, or who may otherwise benefit from the invention. In general, it will be understood that all of the disclosed combinations, compositions, and methods will work for all individuals, although individual differences are to be expected.

[0406] Methods are provided for using a therapeutically effective amount of a pharmaceutical composition of the present disclosure comprising a primary bioactive molecule and / or a secondary bioactive molecule disclosed herein in a mammal, preferably a human, including for treating an inflammatory condition or disorder, including in a healthy individual.

[0407] Administration of a pharmaceutical composition in an "effective amount," "therapeutically effective amount," "therapeutically effective dose," or "pharmacologically effective amount" refers to an amount of the primary and / or secondary bioactive molecule sufficient to produce the desired therapeutic effect, e.g., relief to some extent of one or more symptoms of the disease or condition being treated. That result can be reduction and / or alleviation of the signs, symptoms, or causes of a disease or disorder, or other desired alteration of a biological system. A "therapeutically effective amount" includes, for example, a prophylactically effective amount.

[0408] An "effective amount" of a primary bioactive molecule and / or a secondary bioactive molecule disclosed herein is an amount effective to achieve a desired pharmacological effect or meaningful therapeutic improvement. It is understood that an "effective amount" or "therapeutically effective amount" may vary from subject to subject due to variations in metabolism of compounds such as a primary bioactive molecule and / or a secondary bioactive molecule disclosed herein, variations in age, weight, and the general condition of the subject, the condition being treated, the severity of the condition being treated, and the judgment of the prescribing physician. An effective amount will vary depending on the subject and the disease state or health benefit being treated, the subject's weight and age, the severity of the disease state or the extent of the health benefit being sought, the method of administration, and the like, all of which can be readily determined by one of ordinary skill in the art. Additionally, pharmacogenomic information about a particular patient (e.g., the influence of genotype on the pharmacokinetic, pharmacodynamic, or efficacy profile of a therapeutic agent) may influence the dosage used.

[0409] As used herein, "therapeutic effect" or "therapeutic efficacy" refers to a response after treatment in a mammal, preferably a human, that is deemed to be a desirable and beneficial treatment. Thus, depending on the disorder being treated or the improvement in physiological or psychological function desired, and on the specific components in the disclosed compositions being considered, these responses will vary, as would be readily understood by one skilled in the art. For example, in embodiments, "therapeutic effect" may refer to the effect caused by the disclosed compositions or the use of the disclosed compositions in the disclosed methods, such as treating inflammatory conditions and disorders, as disclosed herein.

[0410] A "therapeutically effective dose" refers to the dose required to elicit a desired result in the patient receiving treatment. Thus, a therapeutically effective dose may, in embodiments, refer to the dose of a pharmaceutical composition or therapeutic combination required to deliver a measurable, patient-specific biological effect in the treatment or prevention of a condition or disorder. A "therapeutically effective dose" may be used interchangeably with a "therapeutically effective amount" or an "effective amount."

[0411] 1. Medication It will be readily understood that dosages may vary depending on whether the treatment is therapeutic or prophylactic, the onset, progression, severity, frequency, duration, probability or susceptibility of the condition being treated, the desired clinical endpoint, previous, concurrent or subsequent treatments, the general health, age, sex, and race of the subject, bioavailability, potential adverse systemic, regional or local side effects, the presence of other disorders or diseases in the subject, and other factors that will be appreciated by one of ordinary skill in the art (e.g., medical history or family history).

[0412] In all embodiments herein that include a dosage of less than about 1 mg, it will be understood that such dosage includes the additional specific dosages of about 0.5 mg or less, about 0.25 mg or less, about 0.1 mg or less, about 0.05 mg or less, about 0.005 mg or less, about 0.001 mg or less, and about 0.0005 mg or less.

[0413] In all embodiments herein, including doses of at least about 1 mg or greater, up to and including about 75 mg, such doses may be further expressed as the specified doses (all such milligram doses being understood to be accompanied by the modifier "about"): 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, 54 mg, 55 mg, 56 mg, 57 mg, 58 mg, 59 mg, 60 mg, 61 mg, 62 mg, 63 mg, 64 mg, 65 mg, 66 mg, 67 mg, 68 mg, 69 mg, 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, 76 mg, 77 mg, 78 mg, 79 mg, 80 mg, 81 mg, 82 mg, 83 mg, 84 mg, 85 mg, 86 mg, 87 mg, 88 mg, 89 mg, 90 mg, 91 mg, 92 mg, The term "amount" is understood to include 0 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, 54 mg, 55 mg, 56 mg, 57 mg, 58 mg, 59 mg, 60 mg, 61 mg, 62 mg, 63 mg, 64 mg, 65 mg, 66 mg, 67 mg, 68 mg, 69 mg, 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, and amounts within these ranges.

[0414] In all embodiments herein including a 75 mg dose, as well as doses greater than 75 mg, including 100 mg, 150 mg, 200 mg, or greater than 200 mg, such doses may be 75 mg, 76 mg, 77 mg, 78 mg, 79 mg, 80 mg, 81 mg, 82 mg, 83 mg, 84 mg, 85 mg, 86 mg, 87 mg, 88 mg, 89 mg, 90 mg, 91 mg, 92 mg, 93 mg, 94 mg, 95 mg, 96 mg, 97 mg, 98 mg, 99 mg, 100 mg, 150 mg, 200 mg, or greater than 200 mg. mg, 101mg, 102mg, 103mg, 104mg, 105mg, 106mg, 107mg, 108mg, 109mg, 110mg, 111mg, 112mg, 113mg, 114mg, 115mg, 116mg, 117mg, 118mg, 119mg, 120mg, 121mg, 122mg, 123mg, 124mg, 125mg, 126mg, 127mg, 128mg, 129mg, 130mg, 131mg, 132mg, 133mg, 134mg, 135 mg, 136mg, 137mg, 138mg, 139mg, 140mg, 141mg, 142mg, 143mg, 144mg, 145mg, 146mg, 147mg, 148mg, 149mg, 150mg, 151mg, 152mg, 153mg, 154mg, 155mg, 156mg, 157mg, 158mg, 159mg, 160mg, 161mg, 162mg, 163mg, 164mg, 165mg, 166mg, 167mg, 168mg, 169mg, 170 It will be understood that the above ranges include the additional specific dosage amounts of 171 mg, 172 mg, 173 mg, 174 mg, 175 mg, 176 mg, 177 mg, 178 mg, 179 mg, 180 mg, 181 mg, 182 mg, 183 mg, 184 mg, 185 mg, 186 mg, 187 mg, 188 mg, 189 mg, 190 mg, 191 mg, 192 mg, 193 mg, 194 mg, 195 mg, 196 mg, 197 mg, 198 mg, 199 mg, and 200 mg. Such dosage amounts will be further understood to include amounts within these ranges, and in all such embodiments, a single dose may further exceed 200 mg, including 225 mg, 250 mg, or amounts greater than 250 mg.

[0415] In embodiments where the combination and / or composition comprises a primary bioactive molecule and / or a secondary bioactive molecule derived from a fungus, the primary bioactive molecule and / or the secondary bioactive molecule may be present in a single dose (whether or not such dose is present in a unit dosage form) in an amount less than about 1 mg, about 1 mg, or more than about 1 mg, including up to about 75 mg. In embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or more than 75 mg, including more than 200 mg.

[0416] In embodiments, when a combination and / or composition includes a primary bioactive molecule and / or a secondary bioactive molecule derived from a fungus, the primary bioactive molecule and / or the secondary bioactive molecule may be present in an amount such that a single dose (whether or not such dose is present in a unit dosage form) is about 100 μg or less (including 95 μg, 90 μg, 85 μg, 80 μg, 75 μg, 70 μg, 65 μg, 60 μg, 55 μg, 50 μg, 45 μg, 40 μg, 35 μg, 30 μg, 25 μg, 20 μg, 15 μg, 10 μg, 5 μg or less), or is at least about 100 μg, or more, and greater than 1,000 μg, including up to and including 1,500 μg, 2,000 μg, about 5,000 μg, and in some embodiments, greater than 5,000 μg.

[0417] In some embodiments, the fungal-derived primary bioactive molecule is any of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, and β-carboline, and the primary bioactive molecule may be present in an amount such that a single dose (whether or not such dose is present in a unit dosage form) is about 100 μg or less, at least about 100 μg or more, and 1,000 μg or more, including up to and including 1,500 μg, 2,000 μg, and about 5,000 μg.

[0418] In embodiments, the fungal-derived primary bioactive molecule is psilocybin. In embodiments, psilocybin is present in an amount such that a single dose is between about 10 and 1000 μg. In embodiments, psilocybin is present in an amount such that a single dose is between about 50 and 500 μg. In embodiments, psilocybin is present in an amount such that a single dose is between about 100 and 400 μg. In embodiments, psilocybin is present in an amount such that a single dose is between about 200 and 300 μg. In embodiments, psilocybin is present in an amount such that a single dose is about 250 μg.

[0419] In embodiments, the fungal-derived primary bioactive molecule is psilocin. In embodiments, psilocin is present in an amount such that a single dose is between about 10 and 500 μg. In embodiments, psilocin is present in an amount such that a single dose is between about 20 and 300 μg. In embodiments, psilocin is present in an amount such that a single dose is between about 20 and 200 μg. In embodiments, psilocin is present in an amount such that a single dose is between about 100 and 200 μg. In embodiments, psilocin is present in an amount such that a single dose is about 150 μg.

[0420] In embodiments, when the fungal-derived secondary bioactive molecule is a polysaccharide, peptide, terpene or terpenoid, phenolic compound, mineral, vitamin, amino acid, lipid, choline, or lactone, the secondary bioactive molecule may be present in an amount such that a single dose (whether or not such dose is present in a unit dosage form) is about 1 mg or more, including less than about 1 mg, about 1 mg, up to and including about 75 mg. In embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or more than 75 mg, including more than 200 mg.

[0421] For all embodiments herein that include a dosage of about 100 μg or less, it will be understood that such embodiments include further specific dosage amounts, including about 95 μg, about 90 μg, about 85 μg, about 80 μg, about 75 μg, about 70 μg, about 65 μg, about 60 μg, about 55 μg, about 50 μg, about 45 μg, about 40 μg, about 35 μg, about 30 μg, about 25 μg, about 20 μg, about 15 μg, about 10 μg, about 5 μg, and about 5 μg or less.

[0422] In all embodiments herein, including dosages of at least about 100 μg or more, and greater than 1,000 μg up to and including 1,500 μg, 2,000 μg, 5,000 μg, the following dosages are also available: 110 μg, 120 μg, 130 μg, 140 μg, 150 μg, 160 μg, 170 μg, 180 μg, 190 μg, 200 μg, 210 μg, 220 μg, 230 μg, 240 μg, 250 μg, 260 μg, 270 μg, 280 μg, 290 μg, 300 μg, 310 μg, 320 μg, 330 μg, 340 μg, 350 μg, 360 μg, 370 μg, 380 μg, 390 μg, 400 μg, 410 μg, 420 μg, 430 μg, 440 μg, 450 μg, 460 μg, 470 μg, 480 μg, 490 μg, 500 μg, 510 μg, 520 μg, 530 μg, 540 μg, 550 μg, 560 μg, 570 μg, 580 μg, 590 μg, 600 μg, 610 μg, 620 μg, 630 μg, 640 μg, 650 μg, 660 μg, 670 μg, 680 μg, 690 μg, 700 μg, 710 μg, 720 μg, 730 μg 40μg, 250μg, 260μg, 270μg, 280μg, 290μg, 300μg, 310μg, 320μg, 330μg, 340μg, 350μg, 360μg, 370μg, 380 μg, 390μg, 400μg, 410μg, 420μg, 430μg, 440μg, 450μg, 460μg, 470μg, 480μg, 490μg, 500μg, 510μg, 520μg , 530μg, 540μg, 550μg, 560μg, 570μg, 580μg, 590μg, 600μg, 610μg, 620μg, 630μg, 640μg, 650μg, 660μg, 6 70μg, 680μg, 680μg, 700μg, 710μg, 720μg, 730μg, 740μg, 750μg, 760μg, 770μg, 780μg, 790μg, 800μg, 810 μg, 820 μg, 830 μg, 840 μg, 850 μg, 860 μg, 870 μg, 880 μg, 890 μg, 900 μg, 910 μg, 920 μg, 930 μg, 940 μg, 950 μg, 960 μg, 970 μg, 980 μg, 990 μg, and 1000 μg, and in some embodiments will further be understood to include certain dosage amounts greater than 5,000 μg.

[0423] In embodiments where the combination and / or composition includes a plant-derived primary and / or secondary bioactive molecule, the primary and / or secondary bioactive molecule may be present in an amount such that a single dose (whether or not such dose is present in a unit dosage form) is less than about 1 mg, about 1 mg, or more than about 1 mg, including up to and including about 75 mg. In embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or more than 75 mg, including more than 200 mg.

[0424] In embodiments, where the plant-derived primary bioactive molecule is any of cannabinoids (e.g., THC, CBD), coumarin, coumarin-derived compounds, i.e., coumarin derivatives (e.g., phenylpropanoids, coumarins, or coumarinoids), the primary bioactive molecule may be present in an amount such that a single dose (whether or not such dose is present in a unit dosage form) is less than about 1 mg, about 1 mg, or more than about 1 mg, including up to and including about 75 mg. In embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or more than 75 mg, including more than 200 mg.

[0425] In embodiments, the plant-derived primary bioactive molecule is a cannabinoid. In embodiments, the cannabinoid is THC. In embodiments, THC may be present in an amount such that a single dose is about 0.1 to 5 mg (whether or not such a dose is present in a unit dosage form). In embodiments, THC is present in an amount such that a single dose is between about 0.5 to 2 mg. In embodiments, THC is present in an amount such that a single dose is between about 0.5 to 1.5 mg. In embodiments, THC is present in an amount such that a single dose is about 1 mg. In embodiments, the cannabinoid is CBD. In embodiments, CBD may be present in an amount such that a single dose is about 0.1 to 5 mg (whether or not such a dose is present in a unit dosage form). In embodiments, CBD is present in an amount such that a single dose is between about 0.5 to 2 mg. In embodiments, CBD is present in an amount such that a single dose is between about 0.5 to 1.5 mg. In an embodiment, the CBD is present in an amount such that a single dose is about 1 mg.

[0426] In embodiments, the plant-derived primary bioactive molecule is coumarin. In embodiments, the coumarin is present in an amount such that a single dose is about 1-10 mg (whether or not such a dose is present in a unit dosage form). In embodiments, the coumarin is present in an amount such that a single dose is between about 0.1-10 mg. In embodiments, the coumarin is present in an amount such that a single dose is between about 0.1-5 mg. In embodiments, the coumarin is present in an amount such that a single dose is between about 0.5-2 mg. In embodiments, the coumarin is present in an amount such that a single dose is between about 0.5-1.5 mg. In embodiments, the coumarin is present in an amount such that a single dose is about 1 mg.

[0427] In embodiments, the plant-derived secondary bioactive molecule is a flavone or flavonoid, a terpene or terpenoid, a carbohydrate, a fatty acid or fatty acid ester (FAE), an amide, an amine, a phytosterol, a phenolic compound, coumaric acid, an isoflavone, a lupeol derivative, (±)-balanofonin, (-)-lariciresinol, 3'-hydroxyretsin-8-methyl-ether, 5-methoxyxanthocercin A, 6,4'-dihydroxy-3'-methoxyaurone, 7-hydroxychromone, 7,3'-dihydroxy-8,4'-dimethoxyisoflavone, betulin, butin, coumaric acid-β-glucoside, dipteryxin, dipterixic acid, eriodictyol, ferulic acid, isoli In some embodiments, the secondary bioactive molecule may be quilitigenin, lupeol, melilotoside, melilotoside-1-p-coumaryl-β-d-glucose, methyllinolenic acid, methyloleic acid, O-coumaric acid, O-hydroxycoumaric acid, odoratin, P-hydroxybenzoic acid, retsucin, retsucin-8-methyl-ether, sulfuretin, salicylic acid, afrormicin, castinin, linoleic acid, oleic acid, 3',4',7'-trihydroxyflavone, luteolin, or umbelliferone, and may be present in an amount such that a single dose (whether or not such a dose is present in a unit dosage form) is less than about 1 mg, about 1 mg, or more than about 1 mg, including up to about 75 mg. In embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or more than 75 mg, including more than 200 mg.

[0428] In embodiments where the combination and / or composition includes a primary bioactive molecule and / or a secondary bioactive molecule derived from algae, the primary bioactive molecule and / or the secondary bioactive molecule may be present in an amount such that a single dose (whether or not such dose is present in a unit dosage form) is less than about 1 mg, about 1 mg, or more than about 1 mg, up to and including about 75 mg. In embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or more than 75 mg, including more than 200 mg.

[0429] In embodiments, the algae-derived primary bioactive molecule is a primary bioactive molecule from a species of the genus Pyropia or Porphyra. In some embodiments, where the primary bioactive molecule from a species of the genus Pyropia or Porphyra is a porphyran or oligoporphyran, a polysaccharide, an oligopolysaccharide, a monosaccharide, a peptide, a phycobiliprotein, a mycosporine-like amino acid, an essential amino acid, a non-essential amino acid, a carotene or intermediate carotenoid, a glycoprotein, or an aminosulfonic acid (such as taurine), a single dose (whether or not such dose is present in a unit dosage form) may be present in an amount such that it is less than about 1 mg, about 1 mg, or more than about 1 mg, up to and including about 75 mg. In embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or more than 75 mg, including more than 200 mg.

[0430] In embodiments, the primary bioactive molecule derived from Pyropia or Porphyra may be present in an amount such that a single dose is about 1 to 20 mg (whether or not such dose is present in a unit dosage form). In embodiments, the primary bioactive molecule derived from Pyropia or Porphyra may be present in an amount such that a single dose is about 8 mg (whether or not such dose is present in a unit dosage form).

[0431] In embodiments where the combination or composition includes Pyropia yezoensis extract, the extract may be present in an amount such that a single dose is about 1-20 mg (whether or not such a dose is present in a unit dosage form). In embodiments, the Pyropia yezoensis extract is present in an amount such that a single dose is between about 1-10 mg. In embodiments, the Pyropia yezoensis extract is present in an amount such that a single dose is between about 5-10 mg. In embodiments, the Pyropia yezoensis extract is present in an amount such that a single dose is between about 8 mg.

[0432] In embodiments where the algae-derived secondary bioactive molecule is any of a mineral, vitamin, lipid, phenolic compound, or phlorotannin, it may be present in an amount such that a single dose is less than about 1 mg, about 1 mg, greater than about 1 mg, including up to and including about 75 mg (whether or not such a dose is present in a unit dosage form), in embodiments, a single dose may be 100 mg, 150 mg, 200 mg, or greater than 75 mg, including greater than 200 mg.

[0433] In some embodiments, the disclosed therapeutic combinations (i.e., particularly the disclosed therapeutic combinations comprising a fungal-derived bioactive molecule and a plant-derived bioactive molecule) are administered in a total daily dose of between about 50 mg and 1 g. In embodiments, the total daily dose is between about 50 mg and 1 g, between 100 mg and 500 mg, and preferably between 100 mg and 400 mg. In embodiments, each individual dose of the disclosed therapeutic combination is between 5 mg and 500 mg, or between 10 mg and 400 mg, or between 10 mg and 100 mg.

[0434] In embodiments, for example, when the disclosed combinations are administered in a single composition, a single dose is about 10 mg to 1000 mg, about 10 mg to 200 mg, about 20 mg to 200 mg, about 10 mg to 100 mg, about 20 mg to 100 mg, about 20 mg to 80 mg, or about 30 mg to 60 mg. In embodiments, a single dose is about 50 mg.

[0435] In embodiments, the single composition is administered 1 to 8 doses per day. In embodiments, the single composition is administered once per day. In embodiments, the single composition is administered twice per day. In embodiments, the single composition is administered three times per day. In embodiments, the single composition is administered four times per day. In embodiments, the single composition is administered five times per day. In embodiments, the single composition is administered six times per day. In embodiments, the single composition is administered seven times per day. In embodiments, the single composition is administered eight times per day. In embodiments, the single dose is administered 1 to 8 doses per day for at least 1 week, 2 weeks, 3 weeks, 1 month, 2 months, or 3 months.

[0436] In embodiments, the patient is administered a therapeutically effective dose of the primary and / or secondary bioactive molecules on a regular or chronic basis, where the patient receives the primary and / or secondary bioactive molecules daily, several times per day (at least once, at least twice, at least three times, at least four times, or more than four times per day); on a set repeating schedule, where the patient receives a therapeutically effective amount of the primary and / or secondary bioactive molecules every day, every three, every four, every five, every six, every seven, or more frequently than every seven days; or, in some embodiments, on a varying schedule consisting of multiple days "on" (when a therapeutically effective dose of the primary and / or secondary bioactive molecules is administered) and multiple days "off" (when no administration occurs), e.g., 1 day administered and 2 days off, 2 days administered and 3 days off, 3 days administered and 4 days off, etc., or other such schedules that would be apparent to one of skill in the art (see, e.g., what are known as microdosing protocols of Paul Stamets or James Fadiman).

[0437] It is understood that in some embodiments, the actual dose administered may be determined or adjusted by a physician in light of any patient-specific aspects that may affect the way the primary and / or secondary bioactive molecules interact with the patient, such as the relevant circumstances, the method of delivery, the patient's age, the patient's weight, whether the patient has any comorbidities, other medications the patient is taking (routinely or currently), and metabolic variability, variability in patient response, and the like, all taken into account in conjunction with the teachings of the present disclosure, and therefore, any disclosed dosage ranges are not intended to limit the scope of the invention. In some cases, dosage levels below the lower end of the disclosed ranges may be more than adequate, while in other embodiments, doses above the ranges may be employed without causing adverse side effects, although, for example, such larger doses may also be divided into several smaller doses for administration, either together or separately.

[0438] In some embodiments, the primary and / or secondary bioactive molecules may be administered and dosed in accordance with good medical practice, taking into account the method and schedule of administration, pre-existing and concomitant medications and supplements, the individual patient's clinical condition and the severity of the underlying disease, the patient's age, sex, weight, tolerance, and other such factors relevant to the healthcare professional, as well as knowledge of the specific compounds used, all of which are considered in conjunction with the teachings of the present disclosure. Dosages may vary from patient to patient, for individual patients over time, and for different combinations and formulations, but can be determined by one of ordinary skill in the art. Determining the appropriate dosage includes not only determining the single dose, but also determining the route of administration, the number and timing of administrations, and the preferred time of day or time during a psychotherapy session for administration.

[0439] In embodiments, the patient may self-administer the dose, which may be on a dosing schedule as described above. In embodiments, the combination and / or disclosed compositions may be prescribed to the patient, who obtains a therapeutically effective dose from a pharmacy or healthcare provider.

[0440] The dosage, frequency, or duration of administration may be increased or decreased as indicated by the desired clinical results, the state of the disease or condition, the side effects of the treatment or therapy, or the concomitant medication. The concentration or concentration ratio of the components of the disclosed combinations and compositions may also be varied as indicated by the desired clinical results, the state of the disease or condition, the side effects of the treatment or therapy, or the concomitant medication. For example, in some embodiments, the disclosed combinations include tryptamine (e.g., psilocin and / or psilocybin, e.g., as a component of a fungal part, such as a fungal extract from a psilocin- and / or psilocybin-containing fungus). In some such embodiments, patients receiving monoamine oxidase inhibitor (MAOI) medication may be administered a composition with a reduced concentration of tryptamine (e.g., psilocin and / or psilocybin), because MAOIs are expected to reduce the metabolic excretion of tryptamine, thereby affecting the ratio and synergistic effect of the bioactive molecules upon administration of the disclosed compositions. In another example, the proportions of components of the disclosed compositions may be increased or decreased depending on an individual's tolerance. For example, individuals who frequently consume cannabis products often develop tolerance to the effects of cannabinoids. In some embodiments, individuals with significant tolerance to cannabis or cannabinoids (e.g., THC) may be administered compositions with increased concentrations of THC to account for such tolerance. In yet another example, individuals with certain medical conditions may be particularly sensitive or resistant to the effects of the disclosed compositions. By way of example only, in some embodiments, an individual with Lewy Body Dementia (LBD) may be administered a disclosed composition with a reduced concentration of cannabinoids (e.g., THC) or cannabis extract, for example, if there is a reasonable suspicion (e.g., at the discretion of a physician or other healthcare professional) that the cannabinoid or cannabis extract may worsen the cognitive or psychiatric symptoms of LBD and / or increase the patient's sensitivity to the composition or any of its components.In another merely illustrative example, an individual with clinical depression may be administered the disclosed compositions having increased concentrations of tryptamine (e.g., psilocin and / or psilocybin, e.g., as a component of a fungal portion such as a fungal extract from a psilocin- and / or psilocybin-containing fungus), which may provide clinical benefits such as promoting serotonin regulation, neuroplasticity, and connectivity.

[0441] One of ordinary skill in the art having the benefit of this disclosure will understand the factors that can affect the dosage, frequency, and timing necessary to provide a sufficient or effective amount to provide a therapeutic effect or benefit, and to do so depending on the type of therapeutic effect desired, as well as to avoid or minimize side effects.

[0442] In other embodiments, appropriate doses for achieving a therapeutic effect, including the upper and lower limits of any dose range, can be determined by individuals, including non-clinicians, by reference to available public information and knowledge and by reference to subjective considerations regarding desired outcomes and effects.

[0443] In embodiments, the biologically active molecules of the therapeutic combination may be administered to a patient as a single composition. In embodiments, the biologically active molecules of the therapeutic combination may be administered to a patient separately, sequentially, or simultaneously. In embodiments, the biologically active molecules in the therapeutic combination may be formulated individually as pharmaceutical compositions and then administered to a patient separately, sequentially, or simultaneously.

[0444] In embodiments, sequential administration refers to administration of one combination agent shortly after administration of another combination agent (e.g., within about 5 minutes of administration of the first combination agent), simultaneous administration refers to administration of each combination agent substantially simultaneously, and separate administration refers to administration with a time lapse between administrations. In embodiments in which the combination agents are administered separately, such administration can include an lapse of time between each administration of about 5 to about 30 minutes, about 10 to about 60 minutes, about 30 to about 180 minutes, about 180 to about 360 minutes, or more than 360 minutes, such as 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, 36 hours, 48 ​​hours, 72 hours, 5 days, 7 days, 10 days, 14 days, 21 days, 30 days, and any such time period therebetween that would be readily apparent to one of skill in the art.

[0445] The time lapse between doses should not be confused with the frequency with which the doses are administered. As will be understood by one of skill in the art, the frequency of administration can depend on the disease and condition being treated and the administration of the first and / or second bioactive molecules disclosed herein. By way of non-limiting example, it may be desirable to administer the combination agent between about 1 and about 8 times per day, including once daily, twice daily, three times daily, four times daily, five times daily, six times daily, seven times daily, and eight times daily. In some embodiments, for example, one of the combination agents (i.e., one of the bioactive compounds in the combination) may be administered twice daily or three times daily, while another combination agent is administered once daily or twice daily, and any additional combination agents are administered according to other appropriate dosing schedules applicable thereto.

[0446] Additionally, dosing schedules include days 1-7, or 14, 21, 28, 29, 30, 31, 35, 42, 49, 60, 75, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, and 700. , may continue in the same pattern or in an altered pattern for a particular period of time greater than 7 days, and the manner in which administration is completed (i.e., by separate, sequential, or simultaneous administration) may be adjusted as necessary so that the overall administration schedule may include only sequential, simultaneous, or separate administration, or may include a combination of two of sequential, simultaneous, or separate administration, or may include all of sequential, simultaneous, or separate administration. That is, in embodiments, the frequency of administration and the period of time that lapses between administrations will depend on the particular primary and / or secondary bioactive molecules utilized and the condition being treated.

[0447] In embodiments, depending on the desired therapeutic effect, administration may include separate, sequential, or simultaneous oral, sublingual, buccal, intravenous, intraarterial, intraperitoneal, intramedullary, intramuscular, intrathecal, intracerebroventricular, rectal, vaginal, ocular, nasal, dermal, topical, otic, transdermal, or combinations thereof, as will be apparent to one of skill in the art. Furthermore, as noted above, in embodiments, a patient may receive the combination agent via multiple administrations, where each administration is not by the same means of administration. As disclosed herein, this may be advantageous in situations where the first and / or second bioactive molecules have varying durations of action and maximum plasma concentrations.

[0448] In embodiments, the disclosed first and / or second bioactive molecules are administered in a single composition. In embodiments, the disclosed first and / or second bioactive molecules are administered separately. In embodiments, the disclosed first and / or second bioactive molecules are administered sequentially. In embodiments, the disclosed first and / or second bioactive molecules are administered simultaneously. In embodiments, the timing of administration of the disclosed first and / or second bioactive molecules (including whether multiple administrations of the first and / or second bioactive molecules are required) depends on the particular first and / or second bioactive molecules administered to an individual and the indication being treated.

[0449] VI. Medical Kits In embodiments, particularly when the formulation is prepared in a single unit dosage form, the suggested dosage should be known by reference to the format of the formulation itself. In other embodiments, the suggested dosage can be known by reference to the administration means or by reference to the packaging and label, package insert, marketing materials, training materials, or other information and knowledge available to those skilled in the art or the general public. Accordingly, another aspect of the present disclosure provides a pharmaceutical kit comprising a pharmaceutical composition or formulation of the present disclosure, recommended administration guidelines or prescribing information, and a suitable container. Individual unit dosage forms can be contained in a multi-dose kit or container. The pharmaceutical composition can also be packaged in single or multiple unit dosage forms for uniformity of dosage and ease of administration. Accordingly, another aspect of the present disclosure provides a pharmaceutical kit comprising a pharmaceutical composition or formulation of the present disclosure, recommended administration guidelines or prescribing information, and a suitable container. Individual unit dosage forms can be contained in a multi-dose kit or container. The pharmaceutical composition can also be packaged in single or multiple unit dosage forms for uniformity of dosage and ease of administration.

[0450] In an exemplary pharmaceutical kit, the capsules, tablets, caplets, or other unit dosage forms are packaged in a blister pack. A "blister pack" refers to any of several types of preformed containers, particularly plastic packaging, containing individual single-dose containers (e.g., cavities or pockets), which are individually sealed and individually openable.

[0451] Blister packs include pharmaceutical packs known to those skilled in the art, such as Aclar® Rx160, Rx20e, SupRx, and UltRx 2000, 3000, 4000, and 6000 (Honeywell). Within the definition of multi-dose container, what are often referred to as blister packs, include blister trays, blister cards, strip packs, push-through packs, and the like. Preferably, information related to dosing and proper administration (if necessary) is printed directly on the multi-dose kit (e.g., on the blister pack or other internal packaging holding the disclosed combination or composition); however, the kits of the present disclosure can further include package inserts and other printed instructions (e.g., on the external packaging) for administering the disclosed combinations or compositions and for their proper therapeutic use.

[0452] In embodiments, patients have the option of using online software, such as websites, or downloadable software, such as mobile applications, to support compliance or provide data related to treatment. Such software can be used, for example, to track the last dose taken and the total dose taken, provide reminders and alerts for upcoming doses, provide feedback to prevent taking doses outside of a set schedule, allow recording of specific subjective effects, or provide a means for unstructured journaling. Such data collection can be used to support individual patient compliance, improve or adjust individual patient care plans, and can be anonymized, aggregated, and analyzed (including by AI or natural language processing means) to enable research into the effectiveness of various treatment methods.

[0453] VII. Treatment method In some aspects, methods of treating a subject having an inflammatory condition or disorder are provided. In some aspects, the disclosed methods of treatment comprise administering a therapeutic combination or pharmaceutical composition described herein.

[0454] "Treatment" covers any treatment of a disorder in a mammal, particularly a human, and in embodiments includes one or more of the following: (a) preventing the disorder from occurring in a subject who may be predisposed to the disorder but has not yet been diagnosed with it; (b) inhibiting the disorder, i.e., arresting its onset (e.g., including prevention); (c) alleviating the disorder, i.e., causing regression of the disorder or its clinical symptoms; (d) protecting against or alleviating symptoms or conditions caused by or associated with the disorder; (e) reducing, reducing, suppressing, ameliorating, or preventing the onset, severity, duration, progression, frequency, or probability of one or more symptoms or conditions associated with the disorder; and (f) preventing or suppressing the worsening or progression of symptoms or conditions associated with the disorder. For purposes of this disclosure, the therapeutic amount required to effectively treat will be understood to be the amount that provides objective evidence of improvement, for example, in a patient with clinically diagnosable symptoms. The effect may be preventative, in that it completely or partially prevents the disorder or its symptoms, and / or therapeutic, in that it partially or completely cures the disorder and / or adverse effects caused by the disorder.

[0455] The terms "inflammation," "inflammatory condition," and "inflammatory disorder" may be used interchangeably herein, such as when generally discussing methods, and unless the context suggests otherwise, although it is understood that the terms may have distinct meanings in certain contexts.

[0456] The term "pro-inflammatory" is used in some embodiments to describe factors that increase, up-regulate, or cause inflammation. The term "anti-inflammatory" is used in some embodiments to describe factors that down-regulate or reduce inflammation.

[0457] Inflammation is an immune response to tissue insults such as microbial infection, acute injury, oxidative stress, chemical irritants, or other such dysregulation of normal tissue function. Inflammatory responses are orchestrated by the innate immune system, which can sense molecular patterns of pathogens and tissue damage, initiate various inflammatory pathways that act to eliminate harmful stimuli, and restore damaged tissues to a homeostatic state. These responses are self-terminating, but termination can fail for multiple reasons, leading to a chronic stage of the inflammatory response (Ahmed. Front Biol. 2011:6(4):274-281).

[0458] Inflammation is often associated with or underlying various pathological conditions, including major cardiovascular and neuropsychiatric disorders (Nichols. Cardiovascular Psychiatry Neurol. 2009:475-108). In the brain, for example, microglia sense pathogens and cellular damage and initiate appropriate immune responses (Nayak et al. Annu Rev Immunol. 2014;32:367-402). Consequently, microglia induce neuroinflammation through phagocytosis and cytokine release, "calling for" the correct type of backup cellular response, orchestrated via the NF-κB inflammatory amplification and TNF pathways (Kettenmann et al. Physiol Rev. 2011;91(2):461-553). This microglial inflammatory response and its reduction by the bioactive molecules of the disclosed compositions is shown in FIG. 1, where 102 indicates an exemplary bioactive molecule from a first plant part (e.g., THC), 104 indicates an additional exemplary biomolecule from the first plant part (e.g., CBD), 106 indicates an exemplary biomolecule from a fungal part (e.g., psilocybin, psilocin), 108 indicates an exemplary biomolecule from a second plant part (e.g., coumarin), and 110 indicates an exemplary biomolecule from an algal part (e.g., taurine).

[0459] Inflammation can be classified as either acute or chronic. Acute inflammation refers to the inflammatory response initiated by the innate immune system in response to initial detection of harmful effects such as pathogen invasion, tissue damage, and other harmful conditions. The innate immune system encompasses a variety of cell types, proteins, receptors, and signaling pathways. Immune cells, including macrophages, dendritic cells, mast cells, neutrophils, and lymphocytes, as well as non-immune cells, including epithelial cells, endothelial cells, and fibroblasts, host a set of pattern recognition receptors (PRRs). PRRs recognize conserved structures in microorganisms, called pathogen-associated molecular patterns (PAMPs), and endogenous molecules associated with cellular damage, called damage-associated molecular patterns (DAMPs) (Tang e...

Claims

1. 1. A method for preventing or treating an inflammatory condition or disorder, comprising administering to a subject having an inflammatory condition or disorder: a. fungal part, b. a first plant part; c. a second plant part, and d. algae part 20. A method comprising administering a therapeutic combination comprising:

2. 10. The method of claim 1, wherein the fungal portion is from a psilocybin-producing species.

3. 3. The method of claim 2, wherein the psilocybin-producing species is from any of the genera Psilocybe, Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, and Pluteus.

4. 4. The method of claim 3, wherein the psilocybin-producing species is from the genus Psilocybe.

5. The psilocybin-producing species from the genus Psilocybe include P. cubensis, P. azurescens, P. bohemica, P. semilanceata, P. baeocystis, P. cyanescens, P. tampanensis, P. weilii, P. hoogshagenii, P. stuntzii, P. cyanofibrillosa, and P. The method according to claim 4, wherein the species is any one of P. liniformans.

6. 2. The method of claim 1, wherein the first plant part is from a species of the genus Cannabis.

7. 7. The method of claim 6, wherein the species of the genus Cannabis is any of Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

8. 10. The method of claim 1, wherein the second plant part is from a species of the genus Dipteryx.

9. 9. The method of claim 8, wherein the species of the genus Dipteryx is Dipteryx odorata.

10. 10. The method of claim 1, wherein the algae part is from a species of marine algae.

11. 11. The method of claim 10, wherein said species of seaweed is from the family Bangiaceae.

12. 12. The method of claim 11, wherein said species of seaweed is from the genus Pyropia or Porphyra.

13. 13. The method of claim 12, wherein the species of seaweed is any of Pyropia yezoensis, Pyropia perforata, and Porphyra umbilicalis.

14. 10. The method of claim 1, wherein any of the fungal part, the first plant part, the second plant part, and the algal part are administered in separate compositions.

15. 10. The method of claim 1, wherein any of the fungal part, the first plant part, the second plant part, and the algal part are administered simultaneously.

16. 16. The method of claim 15, wherein any of the fungal part, the first plant part, the second plant part, and the algal part are administered in a single composition.

17. a. the fungal portion comprises a Psilocybe cubensis extract; b. the first plant part comprises a Cannabis sativa extract; c. the second plant part comprises a Dipteryx odorata extract; d. the algae portion comprises Pyropia yezoensis; The method of claim 1.

18. 18. The method of claim 17, wherein the Psilocybe cubensis extract is obtained by ultrasonic extraction or Soxhlet extraction.

19. 18. The method of claim 17, wherein the Psilocybe cubensis extract comprises a mixture of an extract of Psilocybe cubensis obtained by ultrasonic extraction and an extract of Psilocybe cubensis obtained by Soxhlet extraction in a weight ratio of about 0.5:1 to about 5:

1.

20. 20. The method of claim 19, wherein the weight ratio of the Psilocybe cubensis extract obtained by ultrasonic extraction to the Psilocybe cubensis extract obtained by Soxhlet extraction is 2:

1.

21. 18. The method of claim 17, wherein the Psilocybe cubensis extract comprises psilocybin and psilocin.

22. 22. The method of claim 21, wherein the Psilocybe cubensis extract comprises psilocybin and psilocin in a weight ratio of about 1:5 to about 5:

1.

23. 23. The method of claim 22, wherein the Psilocybe cubensis extract comprises psilocybin and psilocin in a weight ratio of about 5:

3.

24. 22. The method of claim 21, wherein the Psilocybe cubensis extract comprises from about 50 μg to about 500 μg of psilocybin and from about 20 μg to about 200 μg of psilocin.

25. 25. The method of claim 24, wherein the Psilocybe cubensis extract comprises about 250 μg of psilocybin and about 150 μg of psilocin.

26. 18. The method of claim 17, wherein the Cannabis sativa extract is obtained by Soxhlet extraction.

27. The Cannabis sativa extract is ９ - tetrahydrocannabinol (THC) and cannabidiol (CBD).

28. 28. The method of claim 27, wherein the Cannabis sativa extract comprises THC and CBD in a weight ratio of about 1:5 to about 5:

1.

29. 29. The method of claim 28, wherein the Cannabis sativa extract comprises THC and CBD in a weight ratio of about 1:

1.

30. 28. The method of claim 27, wherein the Cannabis sativa extract comprises about 0.1 mg to about 5 mg of THC and about 0.1-5 mg of CBD.

31. 31. The method of claim 30, wherein the Cannabis sativa extract comprises about 1 mg of THC and about 1 mg of CBD.

32. 18. The method of claim 17, wherein the Dipteryx odorata extract is obtained by absolute ethanol percolation.

33. 18. The method of claim 17, wherein the Dipteryx odorata extract comprises coumarin.

34. 18. The method of claim 17, wherein the Dipteryx odorata extract comprises from about 1 mg to about 10 mg of coumarin.

35. 35. The method of claim 34, wherein the Dipteryx odorata extract comprises about 1 mg of coumarin.

36. 18. The method of claim 17, wherein the combination comprises about 1 mg to about 20 mg of Pyropia yezoensis extract.

37. 37. The method of claim 36, wherein the combination comprises about 8 mg of Pyropia yezoensis extract.

38. 18. The method of claim 17, wherein the Pyropia yezoensis extract is obtained by ultrasonic extraction.

39. 18. The method of claim 17, wherein the Pyropia yezoensis extract comprises porphyran.

40. 18. The method of claim 17, wherein any of the Psilocybe cubensis extract, the Cannabis sativa extract, the Dipteryx odorata extract, and the Pyropia yezoensis extract are administered in separate compositions.

41. 18. The method of claim 17, wherein any of the Psilocybe cubensis extract, the Cannabis sativa extract, the Dipteryx odorata extract, and the Pyropia yezoensis extract are administered simultaneously.

42. 42. The method of claim 41, wherein any of the Psilocybe cubensis extract, the Cannabis sativa extract, the Dipteryx odorata extract, and the Pyropia yezoensis extract are administered in a single composition.

43. 43. The method of claim 42, wherein the Psilocybe cubensis extract comprises from about 20% to about 60% by volume of the single composition.

44. 44. The method of claim 43, wherein the Psilocybe cubensis extract comprises about 45% by volume of the single composition.

45. 43. The method of claim 42, wherein the Cannabis sativa extract comprises from about 5% to about 30% by volume of the single composition.

46. 46. ​​The method of claim 45, wherein the Cannabis sativa extract comprises about 15% by volume of the single composition.

47. 43. The method of claim 42, wherein the Dipteryx odorata extract comprises about 1% to about 5% by volume of the single composition.

48. 48. The method of claim 47, wherein the Dipteryx odorata extract comprises about 2% by volume of the single composition.

49. 43. The method of claim 42, wherein the Pyropia yezoensis extract comprises from about 5% to about 30% by volume of the single composition.

50. 50. The method of claim 49, wherein the Pyropia yezoensis extract comprises about 15% by volume of the single composition.

51. 43. The method of claim 42, wherein the single composition further comprises any of a flavoring agent, a coloring agent, and a diluent.

52. 52. The method of claim 51, wherein the flavoring or coloring agent comprises ginger or bay leaf.

53. 53. The method of claim 52, wherein the flavoring or coloring agent is an ethanol decoction of ginger and bay leaves.

54. 53. The method of claim 52, wherein the flavoring agent or the coloring agent comprises from about 5% to about 30% by volume of the single composition.

55. 55. The method of claim 54, wherein the flavoring agent or the coloring agent comprises about 15% by volume of the single composition.

56. 52. The method of claim 51, wherein the diluent is water.

57. 52. The method of claim 51, wherein the water comprises from about 5% to about 15% by volume of the single composition.

58. 58. The method of claim 57, wherein the water comprises about 8% by volume of the single composition.

59. 43. The method of claim 42, comprising administering about 10 to 200 mg of the single composition per single dose.

60. 60. The method of claim 59, comprising administering about 50 mg of the single composition per single dose.

61. 61. The method of claim 60, comprising administering from 1 to 8 doses of said single composition per day.

62. 62. The method of claim 61, comprising administering 1 to 8 doses of the single composition per day for at least 1 week, 2 weeks, 3 weeks, 1 month, 2 months, or 3 months.

63. 10. The method of claim 1, wherein the subject experiences a decrease in the severity of symptoms of the inflammatory condition or disorder.

64. 64. The method of claim 63, wherein the reduction in symptom severity is sustained for at least 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, or at least 12 months as measured from baseline.

65. 2. The method of claim 1, wherein the inflammatory condition or disorder is any of long-term COVID-19, rheumatoid arthritis, psoriatic arthritis, reactive arthritis, tendonitis, gout, scleroderma, systemic sclerosis, localized scleroderma, CREST syndrome, sciatica, neuropathy, peripheral neuropathy, hereditary neuropathy, acquired neuropathy, motor neuropathy, sensory neuropathy, autonomic neuropathy, polyneuropathy, sciatica, myalgic encephalomyelitis, chronic fatigue syndrome (CFS), fatty liver, endometriosis, type 1 diabetes, type 2 diabetes, inflammatory bowel disease, asthma, obesity, cancer, Kawasaki disease, vasculitis, uveitis, Crohn's disease, ulcerative colitis, meningitis, allergy, psoriasis, Hashimoto's disease, Guillain-Barré syndrome, hepatitis, celiac disease, multiple sclerosis, fibromyalgia, lupus, and Sjogren's syndrome.

66. 66. The method of claim 65, wherein the inflammatory condition or disorder is any of long-COVID, CREST syndrome, psoriatic arthritis, Hashimoto's disease, multiple sclerosis, sciatica, peripheral neuritis, post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome, chronic fatigue and immune deficiency syndrome (CFIDS) / chronic fatigue syndrome (CFS), and inflammatory skin diseases.

67. 66. The method of claim 65, wherein the inflammatory condition or disorder is long COVID.

68. 68. The method of claim 67, wherein the subject experiences a reduction in the severity of long COVID symptoms.

69. 69. The method of claim 68, wherein the symptom of long COVID is any of inflammation, fever, chills, cough, shortness of breath, difficulty breathing, fatigue, muscle aches, body aches, headache, loss of taste, loss of smell, sore throat, congestion, runny nose, nausea, vomiting, diarrhea, difficulty thinking or concentrating, sleep disturbances, dizziness, neuropathic pain, irritability, changes in taste, changes in smell, depression, anxiety, confusion, poor quality of sleep, heart palpitations, joint pain, chest pain, and abdominal pain.

70. 66. The method of claim 65, wherein the inflammatory condition or disorder is CREST syndrome.

71. 71. The method of claim 70, wherein the subject experiences a decrease in the severity of CREST syndrome symptoms.

72. 72. The method of claim 71, wherein the CREST syndrome symptom is any of inflammation, rigidity, decreased motor function, calcification, fatigue, depression, Raynaud's phenomenon, and poor sleep quality.

73. 66. The method of claim 65, wherein the inflammatory condition or disorder is psoriatic arthritis.

74. 74. The method of claim 73, wherein the subject experiences a decrease in the severity of psoriatic arthritis symptoms.

75. 75. The method of claim 74, wherein the psoriatic arthritis symptom is any of the following: swollen or inflamed joints, plaque, fatigue, itching, nail pits, and red, scaly rashes on the skin.

76. 66. The method of claim 65, wherein the inflammatory condition or disorder is Hashimoto's disease.

77. 77. The method of claim 76, wherein the subject experiences a decrease in the severity of Hashimoto's disease symptoms.

78. 80. The method of claim 79, wherein the Hashimoto's disease symptom is any of inflammation, swelling, stiffness, decreased motor function, fatigue, decreased endurance, weight gain, muscle weakness, goiter, and pain.

79. 66. The method of claim 65, wherein the inflammatory condition or disorder is multiple sclerosis.

80. 80. The method of claim 79, wherein the subject experiences a decrease in the severity of multiple sclerosis symptoms.

81. 81. The method of claim 80, wherein the multiple sclerosis symptom is any of inflammation, depression, poor sleep quality, and fatigue.

82. 66. The method of claim 65, wherein the inflammatory condition or disorder is sciatica.

83. 82. The method of claim 81, wherein the subject experiences a decrease in the severity of sciatica symptoms.

84. 83. The method of claim 82, wherein the sciatica symptoms are any of inflammation, nerve damage, pain, difficulty walking, muscle weakness and numbness.

85. 66. The method of claim 65, wherein the inflammatory condition or disorder is peripheral neuritis.

86. 86. The method of claim 85, wherein the subject experiences a decrease in the severity of peripheral neuritis symptoms.

87. 87. The method of claim 86, wherein the peripheral neuritis symptom is any of inflammation, nerve damage, pain, difficulty walking, muscle weakness or numbness.

88. 66. The method of claim 65, wherein the inflammatory condition or disorder is post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome.

89. 89. The method of claim 88, wherein the subject experiences a reduction in the severity of Post-Treatment Lyme Disease (PTLD) / Chronic Lyme Disease (CLD) syndrome symptoms.

90. 90. The method of claim 89, wherein the post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome symptoms are any of difficulty thinking or concentrating, fatigue, pain, irritability, depression, and poor sleep quality.

91. 66. The method of claim 65, wherein the inflammatory condition or disorder is chronic fatigue and immune deficiency syndrome (CFIDS) / chronic fatigue syndrome (CFS).

92. 92. The method of claim 91, wherein the subject experiences a decrease in the severity of Chronic Fatigue and Immune Deficiency Syndrome (CFIDS) / Chronic Fatigue Syndrome (CFS) symptoms.

93. 93. The method of claim 92, wherein the Chronic Fatigue and Immune Deficiency Syndrome (CFIDS) / Chronic Fatigue Syndrome (CFS) symptom is any of difficulty thinking or concentrating and decreased energy levels after exertion.

94. 66. The method of claim 65, wherein the inflammatory condition or disorder is an inflammatory skin disease.

95. 95. The method of claim 94, wherein the subject experiences a decrease in the severity of inflammatory skin disease symptoms.

96. 96. The method of claim 95, wherein the inflammatory skin disease symptom is sun sensitivity and allergen intolerance.

97. For preventing or treating an inflammatory condition or disorder in a subject, a. fungal part, b. a first plant part; c. a second plant part, and d. algae part, 20. The use of a therapeutic combination comprising:

98. 98. The use of claim 97, wherein the fungal portion is from a psilocybin-producing species.

99. 99. The use of claim 98, wherein the psilocybin-producing species is from any of the genera Psilocybe, Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, and Pluteus.

100. 100. The use of claim 99, wherein the psilocybin-producing species is from the genus Psilocybe.

101. The psilocybin-producing species from the genus Psilocybe include P. cubensis, P. azurescens, P. bohemica, P. semilanceata, P. baeocystis, P. cyanescens, P. tampanensis, P. weilii, P. hoogshagenii, P. stuntzii, P. cyanofibrillosa, and P. The use according to claim 100, wherein the species is any of P. liniformans.

102. 98. The use of claim 97, wherein the first plant part is from a species of the genus Cannabis.

103. 103. The use of claim 102, wherein the species of the genus Cannabis is any of Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

104. 98. The use of claim 97, wherein the second plant part is from a species of the genus Dipteryx.

105. 105. The use of claim 104, wherein the species of the genus Dipteryx is Dipteryx odorata.

106. 98. The use of claim 97, wherein the algae part is from a species of seaweed.

107. 107. The use of claim 106, wherein said species of seaweed is from the family Bangiaceae.

108. 98. The use of claim 97, wherein said species of seaweed is from the genus Pyropia or Porphyra.

109. 109. The use according to claim 108, wherein said species of seaweed is any of Pyropia yezoensis, Pyropia perforata and Porphyra umbilicalis.

110. 98. The use of claim 97, wherein any of the fungal part, the first plant part, the second plant part and the algal part are administered in separate compositions.

111. 98. The use of claim 97, wherein any of the fungal part, the first plant part, the second plant part, and the algal part are administered simultaneously.

112. 112. The use of claim 111, wherein any of the fungal part, the first plant part, the second plant part, and the algal part are administered in a single composition.

113. a. the fungal portion comprises a Psilocybe cubensis extract; b. the first plant part comprises a Cannabis sativa extract; c. the second plant part comprises a Dipteryx odorata extract; d. the algae portion comprises Pyropia yezoensis; 98. The use according to claim 97.

114. 114. The use according to claim 113, wherein the Psilocybe cubensis extract is obtained by ultrasonic extraction or Soxhlet extraction.

115. 114. The use of claim 113, wherein the Psilocybe cubensis extract comprises a mixture of an extract of Psilocybe cubensis obtained by ultrasonic extraction and an extract of Psilocybe cubensis obtained by Soxhlet extraction in a weight ratio of about 0.5:1 to about 5:

1.

116. 116. The use according to claim 115, wherein the weight ratio of the Psilocybe cubensis extract obtained by ultrasonic extraction to the Psilocybe cubensis extract obtained by Soxhlet extraction is 2:

1.

117. 114. The use of claim 113, wherein the Psilocybe cubensis extract comprises psilocybin and psilocin.

118. 118. The use of claim 117, wherein the Psilocybe cubensis extract comprises psilocybin and psilocin in a weight ratio of about 1:5 to about 5:

1.

119. 119. The use of claim 118, wherein the Psilocybe cubensis extract comprises psilocybin and psilocin in a weight ratio of about 5:

3.

120. 118. The use of claim 117, wherein the Psilocybe cubensis extract comprises from about 50 μg to about 500 μg of psilocybin and from about 20 μg to about 200 μg of psilocin.

121. 121. The use of claim 120, wherein the Psilocybe cubensis extract comprises about 250 μg of psilocybin and about 150 μg of psilocin.

122. 114. The use of claim 113, wherein the Cannabis sativa extract is obtained by Soxhlet extraction.

123. The Cannabis sativa extract is ９ - The use according to claim 113, comprising THC (THC) and cannabidiol (CBD).

124. 124. The use of claim 123, wherein the Cannabis sativa extract comprises THC and CBD in a weight ratio of about 1:5 to about 5:

1.

125. 125. The use of claim 124, wherein the Cannabis sativa extract comprises THC and CBD in a weight ratio of about 1:

1.

126. 124. The use of claim 123, wherein the Cannabis sativa extract comprises about 0.1 mg to about 5 mg THC and about 0.1-5 mg CBD.

127. 127. The use of claim 126, wherein the Cannabis sativa extract comprises about 1 mg of THC and about 1 mg of CBD.

128. 114. The use according to claim 113, wherein the Dipteryx odorata extract is obtained by absolute ethanol percolation.

129. 114. The use of claim 113, wherein the Dipteryx odorata extract comprises coumarin.

130. 114. The use of claim 113, wherein the Dipteryx odorata extract comprises from about 1 mg to about 10 mg of coumarin.

131. 131. The use of claim 130, wherein the Dipteryx odorata extract comprises about 1 mg of coumarin.

132. 114. The use of claim 113, wherein the combination comprises from about 1 mg to about 20 mg of Pyropia yezoensis extract.

133. 133. The method of claim 132, wherein the combination comprises about 8 mg of Pyropia yezoensis extract.

134. 114. The use according to claim 113, wherein the Pyropia yezoensis extract is obtained by ultrasonic extraction.

135. 114. The use of claim 113, wherein the Pyropia yezoensis extract comprises porphyran.

136. 114. The use of claim 113, wherein the Psilocybe cubensis extract, the Cannabis sativa extract, the Dipteryx odorata extract, and the Pyropia yezoensis extract are administered in separate compositions.

137. 114. The use of claim 113, wherein the Psilocybe cubensis extract, the Cannabis sativa extract, the Dipteryx odorata extract, and the Pyropia yezoensis extract are administered simultaneously.

138. 138. The use of claim 137, wherein the Psilocybe cubensis extract, the Cannabis sativa extract, the Dipteryx odorata extract, and the Pyropia yezoensis extract are administered in a single composition.

139. 139. The use of claim 138, wherein the Psilocybe cubensis extract comprises from about 20% to about 60% by volume of the single composition.

140. 140. The use of claim 139, wherein the Psilocybe cubensis extract comprises about 45% by volume of the single composition.

141. 139. The use of claim 138, wherein the Cannabis sativa extract comprises from about 5% to about 30% by volume of the single composition.

142. 142. The use of claim 141, wherein the Cannabis sativa extract comprises about 15% by volume of the single composition.

143. 139. The use of claim 138, wherein the Dipteryx odorata extract comprises from about 1% to about 5% by volume of the single composition.

144. 144. The use of claim 143, wherein the Dipteryx odorata extract comprises about 2% by volume of the single composition.

145. 139. The use of claim 138, wherein the Pyropia yezoensis extract comprises from about 5% to about 30% by volume of the single composition.

146. 146. The use of claim 145, wherein the Pyropia yezoensis extract comprises about 15% by volume of the single composition.

147. 139. The use of claim 138, wherein the single composition further comprises any of a flavoring agent, a coloring agent, and a diluent.

148. 148. The use of claim 147, wherein the flavoring or coloring agent comprises ginger or bay leaf.

149. 149. The use of claim 148, wherein the flavoring or coloring agent is a decoction of ginger or bay leaves with ethanol.

150. 149. The use of claim 148, wherein the flavoring agent or the coloring agent comprises from about 5% to about 30% by volume of the single composition.

151. 151. The use of claim 150, wherein the flavoring agent or the coloring agent comprises about 15% by volume of the single composition.

152. 148. The use of claim 147, wherein the diluent is water.

153. 148. The use of claim 147, wherein the water comprises from about 5% to about 15% by volume of the single composition.

154. 154. The use of claim 153, wherein the water comprises about 8% by volume of the single composition.

155. 139. The use of claim 138, comprising administering about 10 to 200 mg of the single composition per single dose.

156. 156. The use of claim 155, comprising administering about 50 mg of the single composition per single dose.

157. 157. The use of claim 156, comprising administering from 1 to 8 doses of the single composition per day.

158. 158. The use of claim 157, comprising administering 1 to 8 doses of the single composition per day for at least 1 week, 2 weeks, 3 weeks, 1 month, 2 months or 3 months.

159. 98. The use of claim 97, wherein the subject experiences a decrease in the severity of the symptoms of the inflammatory condition or disorder.

160. 160. The use of claim 159, wherein the reduction in symptom severity is sustained for at least 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, or at least 12 months as measured from baseline.

161. 98. The use of claim 97, wherein the inflammatory condition or disorder is any of long-COVID, rheumatoid arthritis, psoriatic arthritis, reactive arthritis, tendonitis, gout, scleroderma, systemic sclerosis, localized scleroderma, CREST syndrome, sciatica, neuropathy, peripheral neuropathy, hereditary neuropathy, acquired neuropathy, motor neuropathy, sensory neuropathy, autonomic neuropathy, polyneuropathy, sciatica, myalgic encephalomyelitis, chronic fatigue syndrome (CFS), fatty liver, endometriosis, type 1 diabetes, type 2 diabetes, inflammatory bowel disease, asthma, obesity, cancer, Kawasaki disease, vasculitis, uveitis, Crohn's disease, ulcerative colitis, meningitis, allergy, psoriasis, Hashimoto's disease, Guillain-Barré syndrome, hepatitis, celiac disease, multiple sclerosis, fibromyalgia, lupus, and Sjogren's syndrome.

162. The use of claim 161, wherein the inflammatory condition or disorder is any of long-COVID, CREST syndrome, psoriatic arthritis, Hashimoto's disease, multiple sclerosis, sciatica, peripheral neuritis, post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome, chronic fatigue and immune deficiency syndrome (CFIDS) / chronic fatigue syndrome (CFS), and inflammatory skin diseases.

163. 162. The use of claim 161, wherein the inflammatory condition or disorder is long COVID.

164. The use of claim 163, wherein the subject experiences a reduction in the severity of long COVID symptoms.

165. 165. The use of claim 164, wherein the symptoms of long COVID are any of inflammation, fever, chills, cough, shortness of breath, difficulty breathing, fatigue, muscle aches, body aches, headache, loss of taste, loss of smell, sore throat, congestion, runny nose, nausea, vomiting, diarrhea, difficulty thinking or concentrating, sleep disturbances, dizziness, neuropathic pain, irritability, changes in taste, changes in smell, depression, anxiety, confusion, poor sleep quality, heart palpitations, joint pain, chest pain, and abdominal pain.

166. 162. The use of claim 161, wherein the inflammatory condition or disorder is CREST syndrome.

167. 167. The use of claim 166, wherein the subject experiences a decrease in the severity of CREST syndrome symptoms.

168. 168. The use of claim 167, wherein the CREST syndrome symptom is any of inflammation, rigidity, decreased motor function, calcification, fatigue, depression, Raynaud's phenomenon, and poor sleep quality.

169. 162. The use of claim 161, wherein the inflammatory condition or disorder is psoriatic arthritis.

170. 170. The use of claim 169, wherein the subject experiences a decrease in the severity of psoriatic arthritis symptoms.

171. 171. The use of claim 170, wherein the psoriatic arthritis symptoms are any of swollen or inflamed joints, plaque, fatigue, itching, nail pits, and red, scaly rashes on the skin.

172. 162. The use of claim 161, wherein the inflammatory condition or disorder is Hashimoto's disease.

173. 173. The use of claim 172, wherein the subject experiences a reduction in the severity of Hashimoto's disease symptoms.

174. 174. The use of claim 173, wherein the Hashimoto's disease symptoms are any of inflammation, swelling, stiffness, decreased motor function, fatigue, decreased endurance, weight gain, muscle weakness, goiter, and pain.

175. 162. The use of claim 161, wherein the inflammatory condition or disorder is multiple sclerosis.

176. 176. The use of claim 175, wherein the subject experiences a reduction in the severity of multiple sclerosis symptoms.

177. 177. The use of claim 176, wherein the multiple sclerosis symptom is any of inflammation, depression, poor sleep quality, and fatigue.

178. 162. The use of claim 161, wherein the inflammatory condition or disorder is sciatica.

179. 179. The use of claim 178, wherein the subject experiences a reduction in the severity of sciatica symptoms.

180. 180. The use of claim 179, wherein the sciatica symptoms are any of inflammation, nerve damage, pain, difficulty walking, muscle weakness and numbness.

181. 162. The use of claim 161, wherein the inflammatory condition or disorder is peripheral neuritis.

182. 182. The use of claim 181, wherein the subject experiences a reduction in the severity of peripheral neuritis symptoms.

183. 183. The use of claim 182, wherein the peripheral neuritis symptoms are any of inflammation, nerve damage, pain, difficulty walking, muscle weakness or numbness.

184. 162. The use of claim 161, wherein the inflammatory condition or disorder is post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome.

185. 185. The use of claim 184, wherein the subject experiences a reduction in the severity of post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome symptoms.

186. The use of claim 185, wherein the post-treatment Lyme disease (PTLD) / chronic Lyme disease (CLD) syndrome symptoms are any of difficulty thinking or concentrating, fatigue, pain, irritability, depression, and poor sleep quality.

187. 162. The use of claim 161, wherein the inflammatory condition or disorder is chronic fatigue and immune deficiency syndrome (CFIDS) / chronic fatigue syndrome (CFS).

188. The use of claim 187, wherein the subject experiences a reduction in the severity of Chronic Fatigue and Immune Deficiency Syndrome (CFIDS) / Chronic Fatigue Syndrome (CFS) symptoms.

189. 189. The use of claim 188, wherein the Chronic Fatigue and Immune Deficiency Syndrome (CFIDS) / Chronic Fatigue Syndrome (CFS) symptoms are any of difficulty thinking or concentrating and reduced energy levels after exertion.

190. 162. The use of claim 161, wherein the inflammatory condition or disorder is an inflammatory skin disease.

191. 191. The use of claim 190, wherein the subject experiences a reduction in the severity of inflammatory skin disease symptoms.

192. 193. The use of claim 192, wherein the inflammatory skin disease symptoms are sun sensitivity and allergen intolerance.

193. 193. The use of any one of claims 97 to 192, wherein the therapeutic combination further comprises an additional active agent.

194. A method for preventing or treating an inflammatory condition or disorder, comprising administering to a subject having an inflammatory condition or disorder a therapeutic combination for use according to any one of claims 97 to 193, or a. fungal part, b. a first plant part; c. optionally, a second plant part, and d. Optionally, an algae portion 20. A method comprising administering a therapeutic combination comprising:

195. 195. The method of claim 194, wherein the fungal portion is from a psilocybin-producing species.

196. 196. The method of claim 195, wherein the psilocybin-producing species is from any of the genera Psilocybe, Athelia, Conocybe, Copelandia, Fibularhizoctonia, Galerina, Gymnopilus, Inocybe, Mycena, Panaeolus, Pholiotina, and Pluteus.

197. 197. The method of claim 196, wherein the psilocybin-producing species is from the genus Psilocybe.

198. The psilocybin-producing species from the genus Psilocybe include P. cubensis, P. azurescens, P. bohemica, P. semilanceata, P. baeocystis, P. cyanescens, P. tampanensis, P. weilii, P. hoogshagenii, P. stuntzii, P. cyanofibrillosa, and P.

198. The method of claim 197, wherein the species is any of P. liniformans.

199. 195. The method of claim 194, wherein the first plant part is derived from a species of the genus Cannabis.

200. 200. The method of claim 199, wherein the species of the genus Cannabis is any of Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

201. 195. The method of claim 194, wherein the second plant part is from a species of the genus Dipteryx.

202. 202. The method of claim 201, wherein the species of the genus Dipteryx is Dipteryx odorata.

203. 195. The method of claim 194, wherein the algae portion is from a species of marine algae.

204. 204. The method of claim 203, wherein said species of seaweed is from the family Bangiaceae.

205. 205. The method of claim 204, wherein said species of seaweed is from the genus Pyropia or Porphyra.

206. 206. The method of claim 205, wherein said species of seaweed is any of Pyropia yezoensis, Pyropia perforata, and Porphyra umbilicalis.

207. 207. The method of any one of claims 195-206, wherein the fungal part comprises any of a fungal extract, a fungal-derived primary bioactive molecule and a fungal-derived secondary bioactive molecule.

208. 208. The method of any one of claims 195 to 207, wherein the first plant part comprises any of a plant extract, a plant-derived primary bioactive molecule, and a plant-derived secondary bioactive molecule.

209. 209. The method of any one of claims 195 to 208, wherein the second plant part comprises any of a plant extract, a plant-derived primary bioactive molecule, and a plant-derived secondary bioactive molecule.

210. 210. The method of any one of claims 195-209, wherein the algae parts comprise any of an algae extract, an algae-derived primary bioactive molecule, and an algae-derived secondary bioactive molecule.

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