Methods and compositions for enhancing stem cell therapy

Abstract

To provide methods and compositions that can potentiate the function of stem cell therapies.SOLUTION: An aspect of the present disclosure provides a method for potentiating function of a stem cell in a subject, comprising the steps of (a) administering to said subject said stem cell; (b) administering to said subject a pharmaceutical composition comprising an encapsulated cannabinoid compound. Here, the step (b) takes place prior to, concurrent with, or subsequent to the step (a). In some embodiments, the step (b) further comprises at least one terpene compound. In some embodiments, the treatment with the step (b) reduces the side effects usually associated with the step (a). In some embodiments, the steps (a) and (b) exhibit a synergetic effect on a process in the subject.SELECTED DRAWING: None

Description

Technical Field

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[0003] ,

[0001] Cross-reference This application claims the benefit of U.S. Provisional Application No. 62 / 350,708, filed on Jun. 15, 2016, which is hereby incorporated by reference in its entirety for all purposes.

Background Art

[0002] Background Stem cells are involved in both the generation of developing tissues and the regeneration of tissues after injury. Stem cells exhibit two important properties: the ability to self-renew and the ability to produce more specialized cell types.

[0003] Research on stem cells has shown promise for treating many diseases. One of the most established forms of stem cell therapy is bone marrow transplantation, where a patient's hematopoietic stem cells are replaced with donor stem cells. The donor stem cells populate the patient's bone marrow and regenerate the hematopoietic system. Another well-established type of stem cell therapy is the use of epithelial stem cells in the treatment of large skin wounds, such as in burn patients. Cultured cell autograft allows small grafts from uninjured skin to be expanded in culture and enables coverage of extensive wounds. Stem cell therapy has also been successful in treating arthritis, autoimmune diseases, vision and hearing loss, diabetes, and orthopedic conditions. The use of stem cells in neurological diseases is an area of active research, and promising results have been seen in disease models of stroke and multiple sclerosis.

[0004] Many challenges remain in stem cell therapy. The use of autologous adult stem cells is limited by their limited replicative potential. The use of embryonic stem cells can alleviate this concern, but donor stem cells must be carefully matched to minimize immune rejection, and immunosuppressive drugs may still be required. Integration remains an issue because stem cell-derived tissues need to be able to function with existing structures. Control of differentiation and replication is important because stem cells also have the ability to promote unwanted proliferation.

Summary of the Invention

[0005] Abstract There is a great need for methods and compositions that can enhance the function of stem cell therapy. The inventions described herein address this need and also provide other relevant advantages.

[0006] One aspect of the present disclosure provides a method for enhancing the function of stem cells in a subject, comprising the steps of (a) administering the stem cells to the subject; and (b) administering a pharmaceutical composition comprising an encapsulated cannabinoid compound to the subject, wherein (b) is performed before, simultaneously with, or after step (a). In some embodiments, step (b) further comprises at least one terpene compound. In some embodiments, the treatment by step (b) reduces the side effects typically associated with step (a). In some embodiments, steps (a) and (b) exhibit a synergistic effect on the process in the subject.

[0007] In some embodiments, the subject is suffering from or suspected to have one of the following diseases selected from the group: acute leukemia, chronic leukemia, and lymphoma, hereditary platelet abnormalities, plasmacytotoxicity, autoimmune diseases, myeloproliferative disorders, lymphocyte proliferative disorders, phagocytic disorders, myelodysplastic syndromes, histiocytic disorders, congenital immune system disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and multiple sclerosis, stroke, diabetes mellitus, infertility, vision loss or other eye diseases, lysosomal storage disorders, peripheral artery disease, ischemic limb injury, diabetes mellitus, heart disease, liver disease, bone disease, muscular dystrophy, dental disease, and cancer.

[0008] In some embodiments, the subject suffers from an injury selected from the group consisting of spinal and spinal cord injuries, wounds, burns or chemical burns, sports injuries, occupational injuries, or brain injuries.

[0009] In some embodiments, the stem cells are stem cell-derived, such as induced pluripotent stem cells, embryonic stem cells, fetal stem cells, or adult stem cells.

[0010] In some embodiments, the stem cells include AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha-6 integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta-1 integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR(p), END (CD105), PROM1 (CD133), and ALCAM. (CD166), ITGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, Circulating Anticoagulant Protein C (PC), CK19, CLV3, Cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FMS (CD115), FORSE-1, G-A Rufa 16, GDF3, GFPM, Gli2, Gli3, glial fibrillary acidic protein, glycoprotein IB, GSTA1, HAS2 gene expression, Her5, hMYADM, HSA, hsp25, Id2, IL-3R alpha, integrin, interleukin-3 receptor alpha chain, iron oxide nanoparticles, KDR, keratin 15 (also known as CK15, cytokeratin 15), keratin 19 (also known as CK19, cytokeratin 19, K19), Kit, L-selectin (CD 62L), lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, metallothionein (MT) crypt-restricted immunosuppression index (MTCRII), monosomy 7, mouse ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, mutant BCRP, nestin, neurofilament microtubule-associated protein 2, neuron glial antigen 2 (NG2), Notch 1, nrp-1, nucleostemin, OC.3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalixin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, purified LRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, side population (SP), SOX 10. Expresses at least one of the following: SOX2, SOX9, SP phenotype, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5, Stella, Stra8, Stro-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, hemoglobin electrophoresis pattern, thrombomucin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-smoothund, XKrk1, or Zac1.

[0011] In some embodiments, the stem cells are derived from totipotent, pluripotent, dipotent, or unipotent stem cells.

[0012] In some embodiments, the stem cells include fibroblasts, keratinocytes, melanocytes, cold-sensitive primary sensory neurons, auditory hair cells or organelles of Corti, Merkel cells, photoreceptor cells, taste bud cells, cholinergic neurons, adrenergic neurons, peptide-guppy neurons, hepatocytes, adipocytes, hepatic adipocytes, renal glomerulopoda cells, pancreatic duct cells, gallbladder epithelial cells, pericytes, corneal fibroblasts, skeletal muscle cells, cardiomyocytes, Purkinje fibrillates, erythrocytes, megakaryocytes, monocytes, Langerhans cells, osteoclasts, osteoblasts, and dendritic cells. These stem cells are derived from cells that give rise to rhizocytes, microglia, neutrophils, granulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, oocytes, spermatids, follicular cells, Schwann cells, satellite glial cells, intestinal glial cells, astrocytes, neuronal cells, oligodendrocytes, prelentic epithelial cells, crystallin-containing lens fiber cells, growth hormone-producing cells, adrenocorticotropin-producing cells, melanocyte-stimulating hormone-producing cells, thyroid cells, or dental cells.

[0013] In some embodiments, the stem cells are stem cell-derived and delivered via intravenous infusion, intradermal, transplanted microvascular bed of bone marrow, subcutaneous, oral (e.g., ingestion or inhalation), transdermal (topical), transmucosal, rectal administration, manipulated monolayer tissue transplantation, intra-arterial, intramuscular, intratracheal, intraperitoneal, intravitreous, or direct injection into a target site.

[0014] In some embodiments, the pharmaceutical composition comprises nanocapsules, the nanocapsules comprising individual nanocapsules containing the encapsulated cannabinoid compound.

[0015] In some embodiments, the nanocapsules increase stem cell growth. In some embodiments, the nanocapsules are administered after stem cell therapy.

[0016] In some embodiments, the nanocapsules are administered to the target by inhalation. In some embodiments, the nanocapsules are vaporized. In some embodiments, the nanocapsules are sprayed. In some embodiments, the nanocapsules are administered orally. In some embodiments, the nanocapsules are incorporated into food or beverages. In some embodiments, the nanocapsules are administered topically.

[0017] In some embodiments, the nanocapsules are water-soluble.

[0018] In some embodiments, the at least one terpene compound is derived from Quillaja saponaria. In some embodiments, the cannabinoid compound contains cannabidiol (CBD). In some embodiments, the cannabinoid compound contains 0.3% or less of tetrahydrocannabinol (THC). In some embodiments, the nanocapsules are water-soluble.

[0019] In some embodiments, the subject is suffering from or suspected to be suffering from a disease or injury, and after (b), the subject is monitored for the progression of the disease or injury in response to being administered the pharmaceutical composition to the subject.

[0020] In some embodiments, the subject is suffering from or suspected to be suffering from the disease, and after (b), the subject is monitored for progression or regression of the disease in response to administration of the pharmaceutical composition to the subject.

[0021] In another embodiment, the present disclosure provides a composition comprising an effective amount of an encapsulated cannabinoid compound; and a kit comprising instructions for administering a therapeutically effective amount of the food composition to a subject undergoing stem cell therapy.

[0022] In some embodiments, the composition is a food composition. In some embodiments, the composition is a pharmaceutical composition. In some embodiments, the composition comprises nanocapsules, the nanocapsules comprising individual nanocapsules containing the encapsulated cannabinoid compound. In some embodiments, the nanocapsule delivery device is an atomizer. In some embodiments, the nanocapsule delivery device is a vaporizer.

[0023] In some embodiments, the nanocapsules comprise terpene compounds. In some embodiments, the terpene compounds are derived from Quillaja saponaria.

[0024] In certain embodiments, for example, the following items are provided: (Item 1) A method of enhancing the function of stem cells in a subject, comprising: (a) administering the stem cells to the subject; (b) administering to the subject a pharmaceutical composition comprising an encapsulated cannabinoid compound wherein (b) is performed before, simultaneously with, or after step (a). (Item 2) The method according to Item 1, wherein step (b) further comprises at least one terpene compound. (Item 3) The method according to Item 1, wherein the treatment by step (b) reduces the side effects normally associated with step (a). (Item 4) The method according to item 1, wherein the subject is suffering from or suspected of suffering from a disease selected from the group consisting of acute leukemia, chronic leukemia, and lymphoma, hereditary platelet abnormalities, plasma cell disorders, autoimmune diseases, myeloproliferative disorders, lymphoproliferative disorders, phagocyte disorders, myelodysplastic syndromes, histiocytic disorders, congenital immune system disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and multiple sclerosis, stroke, diabetes, infertility, vision loss or other eye diseases, lysosomal storage diseases, peripheral arterial diseases, ischemic limb injuries, diabetes, heart diseases, liver diseases, bone diseases, muscular dystrophy, dental diseases, and cancer. (Item 5) The method according to item 1, wherein the subject is suffering from an injury selected from the group consisting of spinal cord and spinal cord injuries, trauma, burns or chemical burns, sports injuries, occupational injuries, or brain injuries. (Item 6)<​​​​The aforementioned stem cells include AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha-6 integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta-1 integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR (p), END (CD105), PROM1 (CD133), ALCAM (CD166), and I. TGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, Circulating Anticoagulant Protein C (PC), CK19, CLV3, Cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FMS (CD115), FORSE-1, G-Alpha-16, GDF3, GFPM, Gli2, Gli3, glial fibrillary acidic protein, glycoprotein IB, GSTA1, HAS2 gene expression, Her5, hMYADM, HSA, hsp25, Id2, IL-3R alpha, integrin, interleukin-3 receptor alpha chain, iron oxide nanoparticles, KDR, keratin 15 (also known as CK15, cytokeratin 15), keratin 19 (also known as CK19, cytokeratin 19, K19), Kit, L-selectin (CD62L ), lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, metallothionein (MT) crypt-restricted immunopositivity index (MTCRII), monosomy 7, mouse ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, mutant BCRP, nestin, neurofilament microtubule-associated protein 2, neuron glial antigen 2 (NG2), Notch 1, nrp-1, nucleostemin, OC.3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalixin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, purified LRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, side population (SP), SOX10, SO The method according to item 1, expressing at least one of the following: X2, SOX9, SP phenotype, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5, Stella, Stra8, Stro-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, hemoglobin electrophoresis pattern, thrombomucin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-smoothund, XKrk1, or Zac1. (Item 8) The method according to item 1, wherein the stem cells are derived from totipotent, pluripotent, dipotent, or unipotent stem cells. (Item 9) The aforementioned stem cells include fibroblasts, keratinocytes, melanocytes, cold-sensitive primary sensory neurons, auditory hair cells or organ of Corti, Merkel cells, photoreceptor cells, taste bud cells, cholinergic neurons, adrenergic neurons, peptide-guppy neurons, hepatocytes, adipocytes, hepatic adipocytes, renal glomerulopoda cells, pancreatic duct cells, gallbladder epithelial cells, pericytes, corneal fibroblasts, skeletal muscle cells, cardiomyocytes, Purkinje fibrillocytes, erythrocytes, megakaryocytes, monocytes, Langerhans cells, osteoclasts, osteoblasts, dendritic cells, microglia, neutrophil granulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, oocytes, spermatids, follicular cells, Schwann cells, and satellite cells. The method according to item 1, which is derived from stem cells that produce glial cells, enteric glial cells, astrocytes, neuronal cells, oligodendrocytes, prelentic epithelial cells, crystallin-containing lens fiber cells, growth hormone-producing cells, adrenocorticotropic hormone-producing cells, melanocyte-stimulating hormone-producing cells, thyroid cells, or dental cells. (Item 10) The method according to item 1, wherein the stem cells are derived from stem cells delivered via intravenous infusion, intradermal, transplanted microvascular bed of bone marrow, subcutaneous, oral (e.g., ingestion or inhalation), transdermal (topical), transmucosal, rectal administration, manipulated monolayer tissue transplantation, intra-arterial, intramuscular, intratracheal, intraperitoneal, intravitreous, or direct injection into a target site. (Item 11) The method according to item 1, wherein steps (a) and (b) exhibit a synergistic effect on the process in the subject. (Item 12) The method according to item 1, wherein the pharmaceutical composition comprises nanocapsules, and the nanocapsules comprise individual nanocapsules containing the encapsulated cannabinoid compound. (Item 13) The method according to item 12, wherein the nanocapsules increase stem cell growth. (Item 14) The method according to item 12, wherein the nanocapsules are administered after stem cell therapy. (Item 15) The method according to item 12, wherein the nanocapsules are administered to the subject by inhalation. (Item 16) The method according to item 12, wherein the nanocapsules are vaporized. (Item 17) The method according to item 12, wherein the nanocapsules are sprayed. (Item 18) The method according to item 12, wherein the nanocapsules are administered orally. (Item 19) The method according to item 12, wherein the nanocapsules are incorporated into a food or beverage. (Item 20) The method according to item 12, wherein the nanocapsules are administered locally. (Item 21) The method according to item 12, wherein the nanocapsules are water-soluble. (Item 22) The method according to item 2, wherein the at least one terpene compound is derived from Quillaja saponaria. (Item 23) The method according to item 1, wherein the cannabinoid compound comprises cannabidiol (CBD). (Item 24) The method according to item 1, wherein the cannabinoid compound contains 0.3% or less of tetrahydrocannabinol (THC). (Item 25) The method according to item 1, wherein the subject is suffering from or suspected to be suffering from a disease or injury, and after (b), the subject is monitored for the progression of the disease or injury in response to being administered the pharmaceutical composition to the subject. (Item 26) The method of item 25, wherein the subject is suffering from or suspected to be suffering from the disease, and after (b), the subject is monitored for progression or regression of the disease in response to being administered the pharmaceutical composition to the subject. (Item 27) (a) A composition comprising an effective amount of encapsulated cannabinoid compound; and (b) A kit comprising instructions for administering a therapeutically effective dose of a food composition to a subject receiving stem cell therapy. (Item 28) The kit according to item 27, wherein the aforementioned composition is a food composition. (Item 29) The kit according to item 27, wherein the aforementioned composition is a pharmaceutical composition. (Item 30) The kit according to item 27, wherein the composition comprises nanocapsules, and the nanocapsules comprise individual nanocapsules containing the encapsulated cannabinoid compound. (Item 31) The kit described in item 30, in which the nanocapsule delivery device is a sprayer. (Item 32) The kit described in item 30 has a nanocapsule delivery device that is a vaporizer. (Item 33) The kit according to item 30, wherein the nanocapsule contains a terpene compound. (Item 34) The kit described in item 33, wherein the terpene compound is derived from Quillaja saponaria. Other objects and advantages of the present invention will be further recognized and understood in conjunction with the following description and accompanying drawings. The following description may include certain details describing particular embodiments of the present invention, but this should not be construed as limiting the scope of the invention, but rather as illustrating preferred embodiments. With respect to each aspect of the present invention, many modifications known to those skilled in the art are possible, such as those presented herein. A variety of changes and modifications can be made within the scope of the invention without departing from its spirit.

[0025] Reference All publications, patents, and patent applications listed herein are incorporated herein by reference to the same extent that each individual publication, patent, or patent application is specifically and individually indicated as being incorporated by reference. [Modes for carrying out the invention]

[0026] (Detailed explanation) Various embodiments of the present invention are illustrated and described herein, but it will be apparent to those skilled in the art that such embodiments are presented merely as examples. Numerous variations, modifications, and substitutions are now conceivable to those skilled in the art without departing from the present invention. It should be understood that various alternative forms to the embodiments of the present invention described herein may be adopted in the practice of the present invention. The following claims define the scope of the present invention and thereby encompass the methods and structures within the scope of these claims and their equivalents.

[0027] As used herein, the terms “about” or “near” refer to within + / - 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the specified amount.

[0028] As used herein, “treat,” “cure,” “alleviate,” and “relieve” are interchangeable. These terms refer to approaches to achieve beneficial or desired outcomes, including but not limited to therapeutic and / or preventive benefits. A therapeutic benefit means the eradication or remission of the underlying disorder being treated. A therapeutic benefit may also be achieved by the eradication or remission of one or more physiological symptoms associated with the underlying disorder, such that improvement is observed in the patient, even though the patient may still suffer from the underlying disorder.

[0029] As used herein, the term "migration ability" may refer to the ability of therapeutic cells to migrate to a lesion site. The term "migration ability" may also refer to the ability of stem cells to migrate under culture conditions.

[0030] This disclosure provides a method for enhancing the function of stem cells in a subject, comprising the steps of (a) administering the stem cells to the subject; and (b) administering a pharmaceutical composition comprising an encapsulated cannabinoid compound to the subject, wherein (b) is performed before, simultaneously with, or after step (a).

[0031] stem cells The stem cells used in this disclosure may be induced pluripotent stem cells, embryonic stem cells, fetal stem cells, or adult stem cells. Fetal stem cells may be either fetal-specific stem cells derived from the fetus itself or extraembryonic fetal stem cells.

[0032] The stem cells used in this disclosure may be induced pluripotent stem cells (iPSCs), which are non-pluripotent cells, typically stem cells artificially induced from adult somatic cells, produced by inducing the expression of one or more stem cell-specific genes. Such stem cell-specific genes include, but are not limited to, the family of octameric transcription factors, i.e., Oct-3, Oct-4; the family of Sox genes, i.e., Sox1, Sox2, Sox3, Sox15, and Sox18; the family of Klf genes, i.e., Klf1, Klf2, Klf4, and Klf5; the family of Myc genes, i.e., c-myc and L-myc; the family of Nanog genes, i.e., OCT4, NANOG, and REX1; or LIN28. An example of iPSC is Takahashi K. et al. (20 (2007) Cell Vol. 131: pp. 861-862; Takahashi K. and Yamanaka S. (200 (6th year) Cell Vol. 126: pp. 663-666; Okita K. et al. (2007) Nature Vol. 448: pp. 260-262; Yu, J. et al. (2007) Science Vol. 318: pp. 1917-1920; and Nakagawa, M. et al. (2008) Nat. Biotechnol. Vol. 26: pp. 101-106.

[0033] The stem cells used in the compositions and methods disclosed herein can be induced in a variety of ways. For example, stem cells can be isolated from the tissues in which they are used in the treatment or from other tissues. In some examples, stem cells are isolated from blood, brain, bone marrow, blood vessels, skeletal muscle, skin, teeth, heart, intestines, or liver tissue. Stem cells can be isolated from the subject, from the subject's relatives, from a donor, from a tissue bank, or from a stem cell bank.

[0034] The stem cells used in this disclosure can be isolated from blood (i.e., hematopoietic tissue). Possible sources of human hematopoietic tissue include, but are not limited to, embryonic hematopoietic tissue, fetal hematopoietic tissue, and postnatal hematopoietic tissue. Embryonic hematopoietic tissue may be the yolk sac or embryonic liver. Fetal hematopoietic systems may be selected from fetal liver, fetal bone marrow, and fetal peripheral blood. Postnatal hematopoietic systems may be umbilical cord blood, bone marrow, normal peripheral blood, recruited peripheral blood, hepatic hematopoietic tissue, or splenic hematopoietic tissue.

[0035] The stem cells used may express any stem cell marker. Many stem cell markers are known in the art, and some examples of stem cell markers that can be expressed include AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha-6 integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta-1 integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR(p), E ND (CD105), PROM1 (CD133), ALCAM (CD166), ITGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, Circulating Anticoagulant Protein C (PC), CK19, CLV3, Cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FMS (CD115), FORSE-1, G-alpha-16, GDF3, GFPM, Gli2, Gli3, glial fibrillary acidic protein, glycoprotein IB, GSTA1, HAS2 gene expression, Her5, hMYADM, HSA, hsp25, Id2, IL-3R-alpha, integrin, interleukin-3 receptor alpha chain, iron oxide nanoparticles, KDR, keratin 15 (also known as CK15, cytokeratin 15), keratin 19 (also known as CK19, cytokeratin 19, K19), Kit, L - Selectin (CD62L), Lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, Metallothionein (MT) Crypt-Restricted Immunopositivity Index (MTCRII), Monosomy 7, Mouse Ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, Mutant BCRP, Nestin, Neurofilament Microtubule-Associated Protein 2, Neuron Glial Antigen 2 (NG2), Notch 1, NRP-1, Nucleostemin, OC.3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalixin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, purified LRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, side population (SP), SOX This includes, but is not limited to, 10, SOX2, SOX9, SP phenotype, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5, Stella, Stra8, Stro-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, hemoglobin electrophoresis patterns, thrombomucin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-Smoothund, XKrk1, and Zac1.

[0036] Stem cells may express any single stem cell marker, or they may express several stem cell markers. In some cases, stem cells may express at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or more stem cell markers.

[0037] In some cases, stem cells may express cannabinoid receptors or putative cannabinoid receptors. Stem cells may express cannabinoid receptor type 1, cannabinoid receptor type 2, or another cannabinoid receptor. Examples of other cannabinoid receptors include GPR18, GPR55, and GPR119.

[0038] The stem cells used in this disclosure can be maintained in a culture before administration to a subject by any method known in the art. The stem cells can be maintained in serum-containing or serum-free medium with or without a feeder layer. The stem cells can be maintained in conditioned medium.

[0039] Stem cells can be partially differentiated before administration to a target. Many methods for differentiating stem cells into either mixed cell populations or specific cell lineages are known in the art. For example, embryonic stem cells or iPSCs can be cultured under conditions that allow for the formation of embryoid bodies, and thus differentiation can be induced. In another example, embryonic stem cells or iPSCs can be differentiated on a layer of stromal cells. In yet another example, embryonic stem cells or iPSCs can be differentiated on extracellular matrix proteins.

[0040] The presence of growth factors, serum, or small molecules in the culture medium can affect the differentiation of embryonic stem cells or iPSCs. These growth factors include, but are not limited to, osteomorphogenetic proteins, colony-stimulating factors, epidermal growth factor, ephrin, fibroblast growth factor, fetal bovine growth hormone, GDNF ligand family, hepatocyte growth factor, insulin-like growth factor, interleukins, keratinocyte growth factor, migration-stimulating factors, macrophage-stimulating proteins, myostatin, neuregulin, neurotrophin, placental growth factor, platelet-derived growth factor, transforming growth factor, tumor necrosis factor alpha, vascular endothelial growth factor, and Wnt signaling pathway proteins.

[0041] For example, differentiation into cardiomyocytes can be induced by culturing mouse embryonic stem cells in the presence of VEGF, activin, BMP4, StemPro34, glutamine, ascorbic acid, bFGF, and FGF10 (Kokkinopoulos, Ioannis et al., "Cardiomyocyte differentiation from mouse embryonic stem cells using a simple and defined protocol." Developmental Dynamics Vol. 245, No. 2 (2016): pp. 157-165). In another example, human iPSCs can be proliferated with SCF, TPO, FLT3L, VEGF, IL-3, IL-6, and EPO to induce differentiation into erythrocytes (Dorn, Isabel et al., "Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin." Haematologica Vol. 100, No. 1 (2015): pp. 32-41).

[0042] The stem cells used in the disclosures described herein may be capable of differentiating into any number of cell types. For example, the stem cells used may be totipotent, pluripotent, dipotent, or unipotent. In some preferred applications, the stem cells used are pluripotent or dipotent.

[0043] The stem cells used in this disclosure may be capable of differentiating into one or more cells from the ectoderm, mesoderm, or endoderm lineages. Examples of cells that differentiate from the ectoderm lineage include, but are not limited to, epidermal cells, neurogenic cells, and neurogliogenic cells. Examples of cells that differentiate from the mesoderm lineage or give rise to specific mesodermal cells include, but are not limited to, adipogenic, smooth muscle-forming, chondrogenic, cardiac-forming, dermatogenic, hematopoietic, angiogenic, myogenic, nephrogenic, urogenogenic, osteogenic, pericardiogenic, or stromal cells. Examples of cells that differentiate from the endoderm lineage include, but are not limited to, pleurigenic cells, and hepatogenic cells, cells that give rise to the lining of the intestine, as well as cells that give rise to pancreatic and visceral-forming cells.

[0044] The stem cells used in this disclosure may be capable of differentiating into any type of mature cell or precursor. Selected examples of cell types include autonomic nerve cells, blood and immune system cells, central nervous system neurons and glial cells, contractile cells, exocrine epithelial cells, extracellular matrix cells, germ cells, cardiomyocytes, hormone-secreting cells, endothelial cells, stromal cells, keratinizing epithelial cells, lens cells, metabolic and storage cells, nervous system cells, nurse cells, sensory organ and peripheral neuron-supporting cells, sensory transducer cells, skeletal muscle cells, and wet stratified barrier epithelial cells.

[0045] The stem cells used in this disclosure may be capable of differentiating into any mature cell or precursor. Selected examples of cells include salivary gland mucinous cells (polysaccharide-rich secretion), salivary gland No. 1 cells (glycoprotein enzyme-rich secretion), von Ebner gland cells of the tongue (taste bud cleansing), mammary gland cells (milk secretion), lacrimal gland cells (tear secretion), ear canal gland cells (earwax secretion), eccrine sweat gland dark cells (glycoprotein secretion), eccrine sweat gland clear cells (small molecule secretion), apocrine sweat gland cells (odor secretion, sex hormone sensitive), Moll cell glands in the eyelids (special sweat glands), sebaceous gland cells (lipid-rich sebum secretion), and Bowman gland cells of the nose (olfactory secretion). (cleansing the skin), Brunner's gland cells of the duodenum (enzymes and alkaline mucus), seminal vesicle cells (secreting seminal components including fructose from swimming sperm), prostate cells (secreting seminal components), bulbourethral gland cells (mucus secretion), Bartholin's gland cells (vaginal lubricant secretion), Little cell glands (mucus secretion), endometrial cells (carbohydrate secretion), goblet cells of the respiratory and digestive tract (mucus secretion), gastric wall mucinous cells (mucus secretion), gastric gland enzymatic cells (pepsinogen secretion), gastric gland acid-secreting cells (hydrochloric acid secretion), pancreatic acinar cells (bicarbonate and digestive enzyme secretion), small intestine Pituitary cells (lysozyme secretion), type II lung cells (surfactant secretion), Clara cells of the lung, growth hormone-producing cells, prolactin-producing cells, thyroid-stimulating hormone-producing cells, gonadotropin-producing cells, adrenocorticotropin-producing cells, mesopituitary cells, macrocellular neurosecretory cells, intestinal and respiratory tracheal cells, thyroid cells, thyroid epithelial cells, parafollicular cells, parathyroid cells, parathyroid chief cells, eosinophilic cells, adrenal cells, chromaffin cells, testosterone-secreting Leydig cells of the testis, estrogen-secreting follicular membrane cells, progesterone-secreting cells Streptococcal luteal cells of ruptured follicles that secrete sterone, granulosa luteal cells, follicular membrane luteal cells, juxtaglomerular cells (renin secreting), macula densa cells of the kidney, circumpolar cells of the kidney, mesangial cells of the kidney, epidermal keratinocytes (differentiated epidermal cells), epidermal basal cells (stem cells), keratinocytes of fingernails and toenails, nail bed basal cells (stem cells), melanocytes, medullary hair stem cells, cortical hair stem cells, cuticle hair stem cells, cuticle root sheath cells, root sheath cells of the Huxley layer, root sheath cells of the Henle layer, outer root sheath cells, hair matrix cells (stem cells), cornea, tongue, oral cavity, esophagus, anal canal,Surface epithelial cells of stratified squamous epithelium of the distal urethra and vagina, basal cells (stem cells) of the epithelium of the cornea, tongue, oral cavity, esophagus, anal canal, distal urethra and vagina, urothelial cells (lining the inner walls of the bladder and ureters), auditory hair cells of the organ of Corti, auditory hair cells of the organ of Corti, basal cells of the olfactory epithelium (stem cells of olfactory neurons), cold-sensitive primary sensory neurons, thermal primary sensory neurons, Merkel cells of the epidermis (tactile sensors), olfactory receptor neurons, pain-sensitive primary sensory neurons (various types), photoreceptor cells of the retina of the eye, photoreceptor rod cells, and blue-sensitive cone cells of the eye. Cells, green-sensitive cone cells of the eye, red-sensitive cone cells of the eye, proprioceptive primary sensory neurons (various types), tactile primary sensory neurons (various types), type I carotid somatic cells (blood pH sensors), type II carotid somatic cells (blood pH sensors), type I hair cells of the vestibular system of the ear (acceleration and gravity), type II hair cells of the vestibular system of the ear (acceleration and gravity), type I taste bud cells, cholinergic neurons (various types), adrenergic neurons (various types), peptide-glucan neurons (various types), endocosal cells of the organ of Corti, organ of Corti External column cells, internal phalangeal cells of the organ of Corti, external phalangeal cells of the organ of Corti, boundary cells of the organ of Corti, Hensen's cells of the organ of Corti, vestibular supporting cells, taste bud supporting cells, olfactory epithelial supporting cells, Schwann cells, satellite glial cells (encapsulated peripheral nerve cell bodies), enteric glial cells, astrocytes (various types), neuronal cells (many different types, classification still incomplete), oligodendrocytes, spindle neurons, prelentic epithelial cells, crystallin-containing lens fiber cells, hepatocytes (liver cells), adipocytes (white adipocytes and brown adipocytes), hepatic adipocytes, renal parietal cells, renal glomeruli Podocytes, renal proximal tubular brush margin cells, thin segment cells of the loop of Henle, renal distal tubular cells, renal collecting duct cells, chief cells, interstitial cells, type I lung cells (lining the inner surface of the air spaces of lung cells), pancreatic duct cells (acinate central cells), non-striatal duct cells (sweat glands, salivary glands, mammary glands, etc.), chief cells, interstitial cells, duct cells (seminal vesicles, prostate, etc.), intestinal brush margin cells (including microvilli), exocrine gland striatal duct cells, gallbladder epithelial cells, testicular efferent duct non-ciliary cells, epididymal chief cells, epididymal basal cells, ameloblast epithelial cells (tooth enamel secretion), lunar epithelial cells of the vestibular system of the ear (proteoglycan secretion),Interdental epithelial cells of the organ of Corti (secreting the tectorial membrane covering hair cells), loose connective tissue fibroblasts, corneal fibroblasts (corneal stromal cells), tendon fibroblasts, bone marrow reticular tissue fibroblasts, other non-epithelial fibroblasts, pericytes, nucleus pulposus cells of the intervertebral disc, cementoblasts / cementocytes (secreting periapical Ivan cells), odontoblasts / dentinocytes (secreting dentin), hyaline chondrocytes, fibrochondrocytes, elastic Chondrocytes, osteoblasts / osteocytes, bone progenitor cells (osteoblast stem cells), vitreous cells of the vitreous humor of the eye, stellate cells of the perilymphatic space of the ear, hepatic stellate cells (Ito cells), pancreatic stellate cells, red skeletal muscle cells (slow-twitch muscle), white skeletal muscle cells (fast-twitch muscle), intermediate skeletal muscle cells, nuclear bag cells of muscle spindles, nuclear chain cells of muscle spindles, satellite cells (stem cells), normal cardiomyocytes, nodular cardiomyocytes, Purkinje fibers, smooth muscle cells (various types), iris Myoepithelial cells, exocrine myoepithelial cells, erythrocytes (red blood cells), megakaryocytes (platelet precursors), monocytes (leukocytes), connective tissue macrophages (various types), epidermal Langerhans cells, osteoclasts (in bone), dendritic cells (in lymphoid tissue), microglia (in the central nervous system), neutrophil granulocytes, eosinophil granulocytes, basophil granulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, natural killer cells, reticulocytes, stem cells and related precursors for the hematopoietic and immune systems (various types), oogonia / oocytes, spermatocytes, spermatocytes, spermatogonia (stem cells for spermatocytes), sperm, follicular cells, Sertoli cells (in the testes), thymic epithelial cells, and interstitial kidney cells.

[0046] The stem cells used may be a single type of stem cell, a mixed population of stem cells, or two or more separate populations of stem cells. The stem cells used may originate from a single source or multiple sources. The stem cells may differentiate into a single cell type or into several different cell types.

[0047] The stem cells used in this disclosure may be genetically modified. For example, iPSCs generated from autologous cells may be modified to correct defects or mutations. Modification methods may include CRISPR, zinc finger nucleases, Talen, homologous recombination, transfection, or transduction. This modification can be used to stop a gene, replace a defective gene, or increase the expression of a gene product.

[0048] The stem cells of this disclosure can be delivered by any method in the art. Methods known in the art include parenteral delivery, e.g., intravenous infusion, intradermal delivery, delivery to the microvascular bed of transplanted bone marrow, subcutaneous delivery, oral delivery (e.g., ingestion or inhalation), transdermal (topical delivery), transmucosal delivery, rectal delivery, or transplantation of engineered monolayer tissue. In certain embodiments, a population of modified cells is administered via a route selected from the group consisting of intra-arterial, intramuscular, subcutaneous, transdermal, intratracheal, intraperitoneal, intravitreous, and intranasal delivery, and delivered to a target site, e.g., in a bone compartment, to the heart, or by direct injection into the cerebrospinal fluid. In certain embodiments, a population of modified cells is administered to or near a site of injury. In some embodiments, cells can be administered simultaneously or sequentially by multiple routes and sites.

[0049] The delivery route of stem cells depends on the application. For example, stem cells can be delivered topically for skin treatment. Stem cells can be delivered intravenously for the treatment of blood disorders. Stem cells can be delivered intramuscularly for the treatment of muscle disorders. Stem cells can be delivered intracerebrally via intranasal delivery for the treatment of brain disorders. Stem cells can be delivered intracardiacally via intramyocardial injection for the treatment of heart disorders. Stem cells can also be delivered intravenously for the treatment of several non-blood-related diseases and disorders.

[0050] In some embodiments, stem cells can be administered together with a scaffold support. Suitable scaffold supports include bioactive glass, hydrogels, photopolymerizable poly(ethene) glycol hydrogels, collagen gels, Matrigel (Corning), or decellularized tissues such as cartilage or connective tissue. Stem cells can be added to the scaffold after it has formed, or the scaffold can be formed around the stem cells.

[0051] The stem cells disclosed herein can be used to treat diseases. Examples of the types of diseases that can be treated include hematological disorders, cancer, immunological disorders, cardiovascular diseases, muscular disorders, metabolic disorders, neurological disorders, connective tissue disorders, and ocular disorders. Stem cells can be used to replace cells lost and / or damaged by disease. Stem cells can be used to replace cells that have harmful mutations.

[0052] Some examples of hematological disorders that can be treated with stem cell therapy include, but are not limited to, acute leukemia, chronic leukemia, lymphoma, hereditary platelet disorders, plasmacytotoxicity, autoimmune diseases such as lupus, myeloproliferative disorders, lymphoproliferative disorders, phagocytic disorders, myelodysplastic syndromes, histiocytic disorders, or congenital immune system disorders. For example, leukemia can be treated by using cytotoxic drugs and / or radiotherapy to kill cancerous and non-cancerous hematopoietic stem cells, and then replacing the stem cells with donor bone marrow. The stem cells from the donor bone marrow then regrow the hematopoietic system. Stem cell treatment for autoimmune diseases may involve killing mature autoreactive immune cells with cytotoxic drugs and / or radiation, and then regrowing the hematopoietic system with previously isolated autologous hematopoietic stem cells.

[0053] Examples of neurological disorders that can be treated by the methods of this disclosure include, but are not limited to, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, and stroke. These disorders are associated with the loss of neurons and / or glial cells, and stem cell therapy may be able to replace these cells.

[0054] Treatment of cardiovascular and muscular diseases involves the use of stem cells to replace lost or damaged muscle fibers. Human embryonic stem cell-derived cardiomyocytes have been shown to integrate well into guinea pig hearts (Shiba, Yuji et al., "Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts." Nature, Vol. 489, No. 7415 (2012): pp. 322-325).

[0055] Other examples of diseases that can be treated by the methods of this disclosure include, but are not limited to, diabetes mellitus, infertility, lysosomal storage disorders, peripheral artery disease, heart disease, liver disease, bone disease, muscular dystrophy, dental disease, or cancer.

[0056] Stem cell therapy has been successfully used to regenerate teeth in mice (Ohazama, A. et al., "Stem-cell-based tissue engineering of murine teeth." Journal of Dental Research, Vol. 83, No. 7 (2004): pp. 518-522. Stem cell therapy combined with gene editing is being used to restore hearing in chickens with hearing impairments (Izumikawa, Masahiko et al., "Auditory hair cell replacement and hearing"). improvement by Atoh1 gene therapy in deaf mammals.”Nature medicine Volume 11, Issue 3 (2005): pp. 271-276. Delivering retinal stem cells to the eye can treat blindness caused by macular degeneration. Embryonic stem cells can differentiate into insulin-producing beta cells that can be delivered to the pancreas to treat diabetes.

[0057] The methods disclosed herein can also be used to treat injuries. Injuries that can potentially be treated with stem cells include spinal cord injuries and spinal cord injuries, wounds, burns or chemical burns, sports injuries, occupational injuries, or brain injuries. In adults, wounds often heal through the formation of scar tissue, and by placing stem cells in the wound, tissue regeneration can be enabled, and healing may be promoted without the formation of scar tissue. Stem cells can be used in spinal cord injuries to promote healing and motor recovery (Cummings, Brian J. et al., "Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice." Proceedings of the National Academy). (of Sciences of the United States of America, Vol. 102, No. 39 (2005): pp. 14069-14074).

[0058] The function of stem cell therapy can be measured by any method known in the art. Stem cell function can be measured in vitro by any method known in the art, including, but not limited to, gene expression analysis, stem cell marker expression, cell morphology, cell migration, cell growth, rate and stability of stem cell proliferation, spontaneous differentiation, induced differentiation, response to growth factors, or expression of lineage markers. Cell surface antigens and biochemical markers can be evaluated by immunocytochemistry, immunofluorescence, fluorescence-activated cell sorting, ELISA, Western blotting, qPCR, RNA-seq, or microarrays.

[0059] The function of stem cells can be measured in vivo. For example, stem cell function can be measured by biopsy of target tissue and analysis of transplanted stem cell-derived tissue. PCR amplification of variable number tandem repeat (VNTR) loci can be used to identify donor and recipient cells. Furthermore, these cells can be characterized with respect to morphology, cell surface antigens, biochemical markers, gene expression, karyotype analysis, and biological activity. Cell surface antigens and biochemical markers can be evaluated by immunocytochemistry, immunofluorescence, fluorescence-activated cell sorting, ELISA, Western blotting, qPCR, RNA-seq, or microarrays. The efficacy of treatment can be assayed by measuring the expression of markers for desired cell types and for undesired cell types. The efficacy of treatment can be assayed by measuring the function of target tissue or cell type. For example, the efficacy of cardiac stem cell treatment can be examined by measuring the increase in ejection fraction (EF); the percentage of blood ejected from the left ventricle with each heartbeat, electrocardiogram, echocardiogram, exercise / nuclear stress test, Holter monitoring, or by measuring the expression of cardiac markers or non-cardiac markers, such as neurological markers. In another example, the effectiveness of treatment with neural-derived stem cells can be measured by testing for changes in neurological function such as spatial memory, working memory, motor coordination, MRI, PET scans, and quality of life outcomes. In yet another example, the effectiveness of treatment with hepatocyte stem cells can be measured by liver enzyme tests, which are commonly used clinically and measure the presence of liver enzymes such as ALT and AST in the blood. In one aspect of the present invention, it may improve the migratory ability of stem cells. In some examples, enhancing the function of stem cells in a subject may refer to improving any aspect of stem cell therapy.Some non-limiting examples include increased stem cell survival in the subject, increased stem cell self-regeneration in the subject, increased replication of transient amplified cells derived from stem cells, increased engraftment of stem cells into desired niches in the subject, increased stem cell migration ability, increased stem cell homing to desired tissues or organs, increased differentiation of stem cells into desired cell types or multiple cell types, decreased engraftment of stem cells into undesired niches in the subject, decreased differentiation of stem cells into undesired cell types or multiple cell types, reduced side effects associated with the treatment, improved functional recovery obtained from stem cell treatment, reduced doses of immunosuppressants required, or extension of stem cell lifespan in the subject.

[0060] Subjects receiving a pharmaceutical composition containing encapsulated cannabinoid compounds before, concurrently with, or after stem cell therapy may show improved outcomes compared to subjects who do not receive the pharmaceutical composition. For example, subjects receiving the pharmaceutical composition may experience fewer side effects, milder side effects, or shorter durations of side effects. Subjects may show more rapid recovery, stronger recovery, longer-lasting recovery, or improved function of the treated organ or organ system compared to subjects who do not receive the pharmaceutical composition. Examples of side effects that may be reduced include nausea, vomiting, fatigue, temporary hair loss, infection, bleeding, anemia, graft-versus-host disease, veno-occlusive disease, gastrointestinal problems, skin problems, pain, parotid gland inflammation, grafting syndrome, lung problems, kidney problems, neurological and muscular problems, transplant failure, graft rejection, heart problems, eye problems, thyroid problems, developmental problems, bladder problems, central nervous system problems, fertilization problems, and cancer.

[0061] Stem cell treatments and cannabinoid compositions can be administered concurrently. The terms “concurrent administration,” “administered in combination with,” and their grammatical equivalents encompass the administration of two or more drugs to an animal, thereby ensuring that both drugs and / or their metabolites are present in the animal simultaneously. Concurrent administration includes concurrent administration in separate compositions, administration in separate compositions at different time points, or administration in a composition in which both drugs are present. Concurrently administered drugs may be in the same formulation. Concurrently administered drugs may also be in different formulations.

[0062] The subject matter of this disclosure may include humans and other animals, such as pets (e.g., dogs, cats, birds, small animals, snakes) and livestock or farm animals (e.g., cattle, pigs, horses, sheep, chickens). The compositions of this disclosure can be used in veterinary applications. In some embodiments, the subject matter of the disclosure described herein is humans.

[0063] The subjects may be adults. In some embodiments, the subjects are not adults. In some embodiments, the subjects are fetuses.

[0064] The subjects may be humans or animals with diseases suitable for treatment with stem cells. Examples of diseases that can be treated with stem cells are discussed above. The subjects may also be humans or animals with injuries suitable for treatment with stem cells. Examples of injuries that can be treated with stem cells are discussed above.

[0065] Cannabinoid composition The compositions administered to subjects to enhance stem cell function contain encapsulated cannabinoid compounds. Cannabinoids used in the compositions disclosed herein include cannabigerol type (CBG), cannabigerol acid (CBGA), cannabigerol acid monomethyl ether (CBGAM), cannabigerol monomethyl ether (CBGM), cannabichromene type (CBC), cannabichromanone (CBCN), cannabichromene acid (CBCA), cannabiclomevalin type (CBCV), cannabiclomevalic acid (CBCVA), cannabidiol type (CBD), tetrahydrocannabinol type (THC), isotetrahydrocannabinol type (iso-THC), cannabinol type (CBN), cannabinol acid (CBNA), cannabinol methyl ether (CBNM), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiolcol (CBN-C1), and Cannabinodiol (CBND), cannabiersoin type (CBE), cannabiersonate A (CBEA-A), cannabiersonate B (CBEA-B), cannabicyclool type (CBL), cannabicycloalic acid (CBLA), cannabicyclovaline (CBLV), cannabicitran type (CBT), cannabitriol, cannabitriol valine (CBTV), ethoxycannabithiol valine (CBTVE), cannabivarin type (CBV), cannabinodivaline (CBVD), tetrahydrocannabivarin type (THCV), cannabidivaline type (CBDV), cannabigerovaline type (CBGV), cannabigerovaline acid (CBGVA), cannabifuran (CBF), dehydrocannabifuran (DCBF), and cannabilipsol (CBR) cannabinoids may include, but are not limited to, these.

[0066] The cannabinoids used in the compositions and methods of this disclosure may be derived from a variety of sources, including, but are not limited to, hemp (e.g., hemp stalks, hemp stems, hemp seeds), cannabis (e.g., cannabis flowers, cannabis leaves, cannabis stalks, cannabis stems, cannabis seeds), Echinacea purpurea, Echinacea angustifolia, Echinacea pallida, Acmella oleracea, Helichrysum umbraculigerum, Radula marginata, kava, black truffle, Syzygium aromaticum (clove), Rosmarinus oficinalis, basil, oregano, black pepper, lavender, true cinnamon, marabatrum, cananga odorata, copaifera spp., and hops.

[0067] Encapsulated cannabinoids may contain at least approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. Encapsulated cannabinoids may contain up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. Encapsulated cannabinoids may be contained in amounts of approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. Encapsulated cannabinoids may be contained in amounts of approximately 1 to approximately 10 micrograms per capsule. The encapsulated cannabinoids may be present in amounts of at least about 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule. Encapsulated cannabinoids may be present in amounts of up to approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight per capsule.The encapsulated cannabinoids may be present in amounts of approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule.

[0068] Cannabinoids may be incorporated into products, such as food, in amounts of at least approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Cannabinoids can be incorporated into products, such as food, in amounts of up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Cannabinoids can be incorporated into products, such as food, in amounts of approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Cannabinoids can also be incorporated into products, such as food, in amounts of approximately 50 to 150 milligrams. Cannabinoids make up at least approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and 2% by weight of the product. It can be incorporated into products, such as food, in amounts of %, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.Cannabinoids are present in the product at a maximum of approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and 2% by weight. It can be incorporated into products, such as food, in amounts of 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight. Cannabinoids are present in the following amounts in the product: approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, and 3% by weight. It can be incorporated into products, such as food, in amounts of 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.

[0069] The cannabinoid compounds used in the encapsulated cannabinoid compounds disclosed herein may include, but are not limited to, compounds of the class of cannabidiol, including, cannabidiolic acid (CBDA), cannabidiol monomethyl ether (CBDM), cannabidiol-C4 (CBD-C4), cannabidivaline (CBDV), cannabidivaric acid (CBDVA), cannabidiolcol (CBD-C1), and combinations thereof. CBD may include delta-1-cannabidiol, delta-2-cannabidiol, delta-3-cannabidiol, delta-3,7-cannabidiol, delta-4-cannabidiol, delta-5-cannabidiol, delta-6-cannabidiol, and combinations thereof.

[0070] The encapsulated cannabidiol compound may be contained in amounts of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabidiol compound may be contained in amounts of up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabidiol compound may be contained in amounts of approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated cannabidiol compound may be contained in amounts of approximately 1 to approximately 10 micrograms per capsule. The encapsulated cannabidiol compound may be contained in an amount of at least about 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule.The encapsulated cannabidiol compound may be contained in a maximum of approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight in the capsule. The encapsulated cannabidiol compound may be contained in amounts of approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule.

[0071] Compositions containing encapsulated cannabinoid compounds may be water-soluble. Compositions containing encapsulated cannabinoid compounds may be water-soluble even when atmospheric gravity is lower than sea level. Encapsulated cannabinoid compounds may be soluble at temperatures ranging from about 6°C to about 55°C. Encapsulated cannabinoid compounds may be soluble at pressures ranging from about 1 atmosphere to about 5 atmospheres. Encapsulated cannabinoid compounds may be soluble under ambient conditions, which can be about 15°C to about 30°C and about 1 atmosphere to about 3 atmospheres. For example, about 2.5 milligrams of a composition may be soluble in 25 milliliters of water.

[0072] Cannabidiol compounds may be present in products, such as food, in amounts of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Cannabidiol compounds may be present in products, such as food, in amounts of up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Cannabidiol compounds may be present in products, such as food, in amounts of approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Cannabidiol compounds may be present in products, such as food, in amounts of approximately 50 to approximately 150 milligrams. Cannabidiol compounds are present in the product at least about 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and 2% by weight. It may be contained in a product, for example, food, in amounts of 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.Cannabidiol compounds are present in the product at a maximum of approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and double. It may be contained in a product, for example, food, in amounts of 10%, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight. Cannabidiol compounds are present in the following amounts in the product: approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and 2% by weight. It may be contained in a product, for example, food, in amounts of %, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.

[0073] The compositions and methods of this disclosure may include tetrahydrocannabinol (THC) as a certain type of cannabinoid. THC may include delta-9-THC, delta-8-THC, and combinations thereof. THC may include delta-6a,7-tetrahydrocannabinol, delta-7-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, delta-9,11-tetrahydrocannabinol, delta-9-tetrahydrocannabinol, delta-10-tetrahydrocannabinol, delta-6a,10a-tetrahydrocannabinol, and combinations thereof. Delta-9-tetrahydrocannabinol may include stereoisomers such as (6aR,10aR)-delta-9-tetrahydrocannabinol, (6aS,10aR)-delta-9-tetrahydrocannabinol, (6aS,10aS)-delta-9-tetrahydrocannabinol, (6aR,10aS)-delta-9-tetrahydrocannabinol, and combinations thereof.

[0074] In some embodiments, the capsules may contain THC. The THC compound may be present in amounts of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated THC compound may be present in amounts of up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated THC compound may be present in amounts of approximately 1 to approximately 10 micrograms per capsule. The encapsulated THC compound may be present in amounts of approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated THC compound may be present in amounts of at least about 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule.The encapsulated THC compound may be present in amounts of up to approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight per capsule. The encapsulated THC compound may be present in amounts of approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule.

[0075] THC compounds may be present in products, such as food, in amounts of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). THC compounds may be present in products, such as food, in amounts of up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). THC compounds may be present in products, such as food, in amounts of approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). THC compounds may be present in products, such as food, in amounts of approximately 50 to approximately 150 milligrams. THC compounds, at least about 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight It may be contained in a product, for example, food, in amounts of %, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.THC compounds are present in the product at a maximum of approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and 2% by weight. It may be contained in a product, for example, food, in amounts of 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight. THC compounds are present in approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, and 3% by weight. It may be contained in a product, for example, food, in amounts of 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.

[0076] In some cases, the compositions of the Disclosure do not contain psychoactive amounts of THC. For example, the cannabinoids in the compositions of the Disclosure may contain THC at a concentration of 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 5%, 1%, 0.7%, 0.5%, 0.3%, or less than 0.1% of the total amount of cannabinoid compounds. In some cases, the ratio of non-THC cannabinoids (e.g., cannabidiol) to THC in the compositions of the Disclosure is greater than or equal to about 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, or 100:1. In some cases, the compositions of the Disclosure contain less than 0.3% THC.

[0077] In some embodiments, the compositions of this disclosure may include antioxidants. Antioxidants may inhibit oxidation by reactive species. Antioxidants may refer to compounds that inhibit or delay the oxidation of other molecules by inhibiting the initiation or propagation of an oxidative chain reaction. Antioxidants may be compounds that neutralize reactive oxygen species that can cause oxidative stress. Antioxidants may be compounds that act as oxygen scavengers or chelators. Antioxidants may neutralize free radicals by donating one of their own electrons. Antioxidants may be enzymatic or non-enzymatic molecules. Enzymatic antioxidants include enzymes that metabolize oxidative toxic intermediates such as reactive oxygen species. Enzymatic molecules include enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and ascorbate oxidase. Non-enzymatic molecules may include glutathione, vitamin C, uric acid, albumin, bilirubin, vitamin E (alpha-tocopherol), carotenoids (e.g., beta-carotene), and flavonoids.

[0078] The compositions of this disclosure may include, but are not limited to, one or more terpene compounds, including terpenoids such as monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. Terpenes may be acyclic, monocyclic, or polycyclic. Examples of terpenes include myrcene, limonene, linalool, trans-ocimene, cis-ocimene, alpha-pinene, beta-pinene, alpha-humulene (alpha-caryophyllene), beta-caryophyllene, delta-3-carene, trans-gamma-bisabolene, cis-gamma-bisabolene, trans-alpha-farnesene, cis-beta-farnesene, beta-fencol, beta-phellandrene, guayole, alpha-guaene, alpha-eoidesmol, beta-eoidesmol, gamma-eoidesmol, This may include, but is not limited to, terpinolene, alpha-selinene, beta-selinene, alpha-terpineol, fencone, camphene, cis-sabinene hydrate, alpha-trans-bergamotene, alpha-cis-bergamotene, borneol, gamma-curcumene, alpha-thugen, epi-alpha-bisabolol, ipsdienol, alpha-ylangene, beta-elemene, gamma-mulorene, alpha-cadinene, alpha-longipinene, caryophyllene oxide, and combinations thereof.

[0079] The encapsulated terpenes may be present in amounts of at least approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per microcapsule. Encapsulated terpenes may be present in amounts of up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 micrograms per capsule. The encapsulated terpene compound may be present in an amount of about 1 to about 10 micrograms per capsule. The encapsulated terpene may be present in an amount of at least about 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule. Encapsulated terpenes may be present in amounts of up to approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight per capsule.Encapsulated terpenes may be present in amounts of approximately 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight of the capsule.

[0080] Terpene compounds may be present in products, such as food, in amounts of at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Terpene compounds may be present in products, such as food, in amounts of up to approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Terpene compounds may be present in products, such as food, in amounts of approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, or 500 milligrams (mg). Terpene compounds may also be present in products, such as food, in amounts of approximately 50 to approximately 150 milligrams. The terpene compounds make up at least about 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and 2% by weight of the product. It may be contained in a product, for example, food, in amounts of %, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.Terpene compounds are present in the product at a maximum of approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, and 2% by weight. It may be contained in a product, for example, food, in amounts of 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight. Terpene compounds make up approximately 0.01% by weight, 0.02% by weight, 0.03% by weight, 0.04% by weight, 0.05% by weight, 0.06% by weight, 0.07% by weight, 0.08% by weight, 0.09% by weight, 0.1% by weight, 0.2% by weight, 0.3% by weight, 0.4% by weight, 0.5% by weight, 0.6% by weight, 0.7% by weight, 0.8% by weight, 0.9% by weight, 1% by weight, 2% by weight, It may be included in a product, for example, food, in amounts of 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight, 18% by weight, 19% by weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, or 50% by weight.

[0081] The compositions of this disclosure may be enriched with cannabinoids compared to hemp oil. For example, a composition may include hemp oil and cannabinoids from plant sources such as extracts (e.g., hemp extract) and essential oils. A composition may contain cannabinoids at concentrations about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% higher than hemp oil.

[0082] The compositions of this disclosure may be enriched with cannabidiol compounds compared to hemp oil. For example, a composition may include hemp oil and cannabidiol compounds from plant sources such as extracts (e.g., hemp extract) and essential oils. A composition may contain cannabidiol compounds at concentrations about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% higher compared to hemp oil.

[0083] The compositions of this disclosure may be enriched with THC compounds compared to hemp oil. For example, a composition may include hemp oil and THC compounds from plant sources such as extracts (e.g., hemp extract) and essential oils. A composition may contain THC compounds at concentrations about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% higher compared to hemp oil.

[0084] The compositions of this disclosure may be enriched with terpenes compared to hemp oil. For example, a composition may include hemp oil and terpenes from plant sources such as extracts (e.g., hemp extract) and essential oils. The compositions may contain terpenes at concentrations about 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% higher compared to hemp oil.

[0085] The encapsulated cannabinoid compounds contained in the compositions of this disclosure may be derived from a variety of sources. The compound sources may be natural products, such as plant extracts or essential oils. The compounds in the compositions of this disclosure may be derived from hemp oil containing cannabinoid compounds, THC compounds, and terpene compounds. The compounds in the compositions of this disclosure may be derived from essential oils, including but not limited to those discussed further in this disclosure. These compounds may contain cannabinoid compounds and terpene compounds. In some cases, all compounds or components in the compositions are natural or of natural origin. In some cases, all compounds or components in the compositions are vegetarian. In some cases, all compounds or components in the compositions are vegan.

[0086] The terpenes and / or essential oils in the compositions of this disclosure may be selected to provide benefits for specific conditions or subjects. Terpenes and / or essential oils may be used in combination with each other and in combination with cannabinoids to, for example, reduce cellular oxidative stress and, in some cases, alleviate one or more health conditions. For example, terpinolenes, terpineols and linalools or lavender, valerian and jasmine essential oils may be combined with cannabinoids or cannabis extracts to act as sleep aids or to treat sleep disorders.

[0087] Alpha-pinene can be used as an anti-inflammatory agent, anti-angiogenic agent, anti-ulcer agent, and bronchodilator.

[0088] Linalool can be used as a sedative, analgesic, antimicrobial, antibacterial, and anticonvulsant to improve Alzheimer's disease or its symptoms by reducing anxiety and inflammation (e.g., lung inflammation).

[0089] Myrcene can be used as an antibacterial agent, neuroprotective agent, antinociceptive agent, and analgesic, as well as to alleviate neuropathic pain, peptic ulcers, and inflammation. Depending on the concentration, myrcene can be used as a sedative (e.g., myrcene above 0.5%) or to provide an energy-boosting effect (e.g., myrcene below 0.5%).

[0090] Limonene can be used to reduce anxiety and depression, dissolve cholesterol-containing gallstones, neutralize stomach acid, support normal peristalsis, relieve heartburn and gastroesophageal reflux, improve immune function, and as a chemopreventive agent against cancer.

[0091] Ocimen can be used as an antifungal, antitumor, and cytotoxic agent.

[0092] Terpinolene can be used for its antioxidant, mood-regulating, central nervous system (CNS) modulating, anti-inflammatory, antidiarrheal, antifilariatic, antifungal, antimalarial, anti-amebic, antibacterial, cytotoxic, and anticancer effects.

[0093] Terpineol can be used to relax the subject, aid digestion, improve gastrointestinal disorders, and relieve influenza, bronchitis, cough, nasal congestion, and sinusitis.

[0094] Beta-caryophyllene can be used as an anti-inflammatory, antitumor, and analgesic agent.

[0095] Geraniol can be used as an antidepressant to reduce or prevent neuropathy, as an anti-angiogenic agent, as an anticancer agent to improve the efficacy of anticancer drugs, as an antioxidant to inhibit the growth of cancer cells (e.g., lung cancer), as a chemopreventive agent against cancer, as an anti-inflammatory and apoptotic agent to reduce inflammation and apoptosis (e.g., in hepatocytes), as an antioxidant to reduce oxidative stress, and as an antimicrobial agent.

[0096] Alpha-humulene can be used as an appetite suppressant, anti-inflammatory agent, insecticide, antibacterial agent, antioxidant, and allelopathic substance.

[0097] Phellandrene can be used as an antidepressant and analgesic.

[0098] Karen can be used as an antioxidant, antiproliferative agent, and antimicrobial agent, and to reduce the production of excess bodily fluids such as tears, mucus, or sweat.

[0099] Terpinene can be used as an antioxidant, anti-inflammatory, antimicrobial, and antiproliferative agent to reduce oxidative stress and to manage diabetes.

[0100] Fencol can be used as an antibacterial agent, anti-mycobacterial agent, antimicrobial agent, and antioxidant.

[0101] Borneol can be used as a TRPA1 inhibitor, anti-inflammatory agent, and antinociceptor to reduce hyperalgesia.

[0102] Bisabolol can be used as an anticancer agent (for example, to induce apoptosis in leukemia), an antitumor agent (for example, pancreatic cancer), and an antigenotoxic agent.

[0103] Phytol can be used to relax subjects by inhibiting the breakdown of GABA, as an anxiety reliever, to suppress menadione-induced oxidative stress, and as an antimicrobial agent.

[0104] Camphene can be used as an antioxidant for pain relief, as an antitumor agent to induce apoptosis in cancer cells (e.g., melanoma), and as an antibacterial agent.

[0105] Sabinene can be used as an antioxidant, antimicrobial agent, and anticancer agent (e.g., for oral, liver, lung, colon, melanoma, and leukemia), to support liver function, aid digestion, relieve arthritis, and alleviate skin conditions.

[0106] Camphor can be used as a local anesthetic, muscle relaxant, antipathogenic agent, and antimicrobial agent to improve skin healing (e.g., reconstructed human epithelium).

[0107] Isoborneol can be used as an antioxidant, cytotoxic agent, and DNA protectant to inhibit herpes simplex virus type 1 and HIV.

[0108] Menthol can be used as an analgesic, to desensitize α3β4 nicotinic acetylcholine receptors, as an antinociceptor, and as an anti-inflammatory agent.

[0109] Nerolidol can be used as an antifungal, antimicrobial, antioxidant, and antimalarial agent.

[0110] Guaiol can be used as an antimicrobial, antifungal, and antibiotic agent.

[0111] Isopuregol can be used as a gastric protective agent and anti-inflammatory agent to enhance the permeability of compounds to transdermal administration and to reduce the severity of attacks.

[0112] Geranyl acetate can be used as an antimicrobial agent, antibacterial agent, and antioxidant.

[0113] Cymene can be used as an anti-inflammatory, anti-analgesic, antioxidant, and antidiabetic agent to aid in weight loss, aid in immune disorders, and prevent acute lung injury.

[0114] Eucalyptol can be used as an antifungal agent, an antioxidant to reduce inflammation (e.g., lung inflammation), and an anticancer agent.

[0115] Pulegone can be used as an insecticide and antioxidant to enhance skin penetration.

[0116] The compositions of this disclosure appear to include one or more essential oils or essential oil compounds. As essential oils, these are not limited to, but include: linalool; β-caryophyllene; β-myrcene; D-limonene; humulene; α-pinene; ylang-ylang (Cananga odorata); yarrow (Achillea millefolium); violet (Viola odorata); vetiver (Vetiveria zizanoides); vanilla (Vanilla plantifolia); tuberose (Polianthes tuberosa); thyme (Thymus vulgaris L.); tea tree (Melaleuca alternifolia); tangerine (Citrus reticulata); black spruce (Picea mariana); spruce (Tsuga Canadensis); citronella (Nardostachys jatamansi); spruce (Mentha spicata); sandalwood (Santalum spicatum); rosewood (Aniba rosaeodora); rosemary verbenone (Rosmarinus Rosemary (Rosmarinus officinalis); Rose (Rosa damascena); Baby ginger (Pelargonium roseum); Ravensara (Ravensara aromatica); Ply (Zingiber cassumunar); Pine grass (Pinus sylvestris L.); Petitgrain (Citrus aurantium); Peppermint (Mentha piperita); Black pepper (Piper nigrum L.)); Patchouli (Pogostemon cablin); Palo Santo (Bursera graveolens); Palmarosa (Cymbopogon martini); Osmanthus fragrans; Oregano (Origanum vulgare); Sweet Orange (Citrus sinensis); Oakmoss (Evernia prunastri); Nutmeg (Myristica fragrans); Niaouli (Melaleuca viridifloria); Neroli (also known as Orange Blossom) (Citrus aurantium); Myrtle (Myrtus communis); Myrrh (Commiphora. myrrha); mimosa (Acacia decurrens); melissa (Melissa officinalis L.); sweet marjoram (Origanum majorana); manuka (Leptospermum scoparium); red mandarin (Citrus deliciosa); mandarin (Citrus deliciosa); white lotus (Nelumbo nucifera); pink lotus (Nelumbo nucifera); blue lotus (Nelumbo nucifera); lime (Citrus aurantifolia); lily (Lilum) aurantum); lemongrass (Cymbopogon citratus); lemon (Citrus limonum); lavender (Lavandula angustifolium); lavandin (Lavandula hybrida grosso); kanuka (Kunzea ericoides); juniper berry (Juniperus cummunis); jasmine (Jasminum officinale); jasmine abs (Jasminum sambac); strawflower (Helichrysum italicum); white grapefruit (Citrus x paradisi); pink grapefruit (Citrus paradisi); ginger (Zingiber officinalis); geranium (Pelargonium) graveolens); Bourbon geranium (Pelargonium graveolens, 'Herit'); Gardenia jasminoides; Galbanum (Ferula galbaniflua); Frankincense (Boswellia carterii); Frangipani (Plumeria alba); White fir needle (Abies alba); Siberian fir needle (Abies siberica); Canadian fir needle (Abies balsamea); Sweet fennel (Foeniculum vulgare); Eucalyptus Smithii, Eucalyptus Radiata, Eucalyptus Globulus, Eucalyptus Citriodora, Eucalyptus Blue Mallee (Eucalyptus polybractea); Elemi (Canarium luzonicum); Dill (Anethum graveolens); Cypress (Cupressus sempervirens); Cumin (Cuminum cyminum); Coriander (Coriandum) sativum; cocoa (Theobroma cacao); clove (Eugenia caryophylatta); clary sage (Salvia sclarea); cistus (also known as Labdanum) (Cistus ladaniferus L.); cinnamon (Cinnamomum zeylanicum); Roman chamomile (Anthemis nobilis); blue chamomile (Matricaria chamomilla); celery seeds (Apium graveolins); Western red cedar (Thuja plicata); cedarwood, blood (Juniperus virginiana); cedarwood atlas (Cedrus atlantica); carrot seeds (Daucus Examples include carota; cardamom (Elettaria cardamomum); caraway seeds (Carum carvi); cajaputi (Melaleuca cajuputi); caddisfly (Juniperus oxycedrus); American white birch (Betula alba); American birch (Betula lenta); bergamot (Citrus bergamia); bay laurel (Laurus nobilis); basil (Ocimum basilicum); oak sanctum (Ocimum sanctum); basil (Ocimum basilicum); balsam poplar (Populus balsamifera); balsam Peru (Myroxylon balsamum); angelica (Angelica archangelica L.); and combinations thereof.

[0117] The compositions of this disclosure may include, but are not limited to, one or more additional ingredients including mushrooms or mushroom derivatives (e.g., Reishi, Chaga, Maitake, Oyster mushroom, Oriental tomentosa), maca (Lepidium meyenii), Polygonum multiflorum (also known as he show wu or shou wu chih), superfoods or superfood derivatives (e.g., blueberries, acai berries, Inca berries, goji berries, camu camu, coconut, lucuma, kale, cacao (e.g., cacao powder, cacao butter), sacha inchi, chia, flax, hemp, amaranth, quinoa, moringa oleifera), and combinations thereof.

[0118] The compounds used in the compositions of this disclosure can be extracted by a variety of methods. For example, extraction can be carried out by maceration, injection, decoction, leaching, Soxhlet extraction, pressurized solvent extraction, countercurrent extraction, sonication, or supercritical fluid (e.g., carbon dioxide) extraction.

[0119] In some cases, the compounds used in the compositions of this disclosure are extracted via supercritical fluid (e.g., carbon dioxide) extraction. For example, cannabinoid compounds can be extracted from hemp (e.g., hemp stalks and stems) using supercritical carbon dioxide extraction.

[0120] The compositions of this disclosure may include pregnenolone, including its derivatives. Pregnenolone can help protect subjects from cannabis poisoning, such as THC. Pregnenolone or its derivatives may be formulated to be water-soluble. The compositions of this disclosure may contain pregnenolone or its derivatives in amounts between about 1 and 50 milligrams (mg). For example, the unit dose of this disclosure may contain pregnenolone in amounts between about 1 and 50 milligrams (mg). The compositions of this disclosure (e.g., unit doses) may contain about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg of pregnenolone. A composition of the present disclosure (e.g., a unit dose) may contain at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg of pregnenolone. A composition of the present disclosure (e.g., a unit dose) may contain up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mg of pregnenolone. A composition containing pregnenolone may be used in combination with any other compounds, components, or formulations described herein, including esters, cyclodextrin complexes, capsules (e.g., sodium alginate capsules), immediate-release formulations, delayed or extended-release formulations, transchoucho formulations, and sublingual formulations.

[0121] The compositions of this disclosure comprise encapsulated cannabinoid compounds. The capsules may contain components discussed in this disclosure, such as cannabinoid compounds. In some embodiments, compositions comprising terpene compounds, cannabidiols, THC, and / or others may also be encapsulated. In some cases, compositions may be encapsulated without the use of liposomes. In some cases, compositions may be encapsulated without the use of micelles. In some cases, compositions may be encapsulated without the use of liposomes or micelles. The compounds of the compositions may exist in forms including, but not limited to, liquids, gels, semi-solids, and solids, and may be encapsulated. The encapsulated compositions disclosed herein may be further processed into forms including, but not limited to, solids, powders, liquids, suspensions, gels, tablets, foods, lotions, cosmetics, and other forms discussed in this disclosure.

[0122] Encapsulation can be performed using encapsulation devices, including microfluidic droplet generators or encapsulation devices. An exemplary microencapsulation device is described, for example, in U.S. Patent No. 7,482,152, which is incorporated herein by reference in its entirety. Microfluidic droplets or emulsions can be generated by a flow of fluid to be encapsulated using an immiscible carrier fluid. For example, an oil fluid to be encapsulated can be flowed together with an aqueous carrier fluid, or an aqueous fluid to be encapsulated can be flowed together with an oil carrier fluid. Air can also be used as the fluid. Microfluidic droplet generators useful for microencapsulation include those using parallel flow, cross flow (e.g., flow at a T-junction), flow focusing, flow through a perforated plate, and flow through a nozzle. Droplet size can be controlled by parameters including the device geometry, relative flow rate of the fluid flow, and operating pressure.

[0123] Examples of encapsulated compositions, including encapsulated cannabinoid compositions, are provided in WO2016 / 094810, which is fully incorporated herein by reference.

[0124] Encapsulation can be performed with a predetermined range of operating parameters, such as different flow rates or pressures. Encapsulation can be performed at pressures of at least approximately 10 pounds / square inch (psi), 20 psi, 30 psi, 40 psi, 50 psi, 60 psi, 70 psi, 80 psi, 90 psi, 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psi, 700 psi, 800 psi, 900 psi, 10000 psi, 2000 psi, 3000 psi, 4000 psi, 50000 psi, 6000 psi, 7000 psi, 8000 psi, 9000 psi, 10000 psi, 15000 psi, 20000 psi, 25000 psi, 30000 psi, 35000 psi, 40000 psi, 45000 psi, 50000 psi, or higher. Encapsulation can be performed at pressures of up to approximately 10 pounds / square inch (psi), 20 psi, 30 psi, 40 psi, 50 psi, 60 psi, 70 psi, 80 psi, 90 psi, 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psi, 700 psi, 800 psi, 900 psi, 1000 psi, 2000 psi, 30000 psi, 4000 psi, 5000 psi, 6000 psi, 7000 psi, 8000 psi, 9000 psi, 10000 psi, 15000 psi, 20000 psi, 25000 psi, 30000 psi, 35000 psi, 40000 psi, 45000 psi, or 50000 psi. Microencapsulation can be performed at pressures of approximately 10 pounds / square inch (psi), 20 psi, 30 psi, 40 psi, 50 psi, 60 psi, 70 psi, 80 psi, 90 psi, 100 psi, 200 psi, 300 psi, 400 psi, 500 psi, 600 psi, 700 psi, 800 psi, 900 psi, 1000 psi, 2000 psi, 3000 psi, 4000 psi, 5000 psi, 6000 psi, 7000 psi, 8000 psi, 9000 psi, 10000 psi, 15000 psi, 20000 psi, 25000 psi, 30000 psi, 35000 psi, 40000 psi, 45000 psi, 50000 psi or higher.Encapsulation is performed at a rate of at least approximately 1 mL / min, 2 mL / min, 3 mL / min, 4 mL / min, 5 mL / min, 6 mL / min, 7 mL / min, 8 mL / min, 9 mL / min, 10 mL / min, 20 mL / min, 30 mL / min, 40 mL / min, 50 mL / min, 60 mL / min, 70 mL / min, 80 mL / min, 90 mL / min, 100 mL / min, 110 mL / min, 120 mL / min, 130 mL / min, 140 mL / min, 150 mL / min, 160 mL / min, 170 mL / min, 180 mL / min, 190 mL / min, 200 mL / min, 210 mL / min, 220 mL / min It can be performed at flow rates of min, 230 mL / min, 240 mL / min, 250 mL / min, 260 mL / min, 270 mL / min, 280 mL / min, 290 mL / min, 300 mL / min, 310 mL / min, 320 mL / min, 330 mL / min, 340 mL / min, 350 mL / min, 360 mL / min, 370 mL / min, 380 mL / min, 390 mL / min, 400 mL / min, 410 mL / min, 420 mL / min, 430 mL / min, 440 mL / min, 450 mL / min, 460 mL / min, 470 mL / min, 480 mL / min, 490 mL / min, 500 mL / min or more.Encapsulation is possible up to approximately 1 milliliter per minute (mL / min), 2mL / min, 3mL / min, 4mL / min, 5mL / min, 6mL / min, 7mL / min, 8mL / min, 9mL / min, 10mL / min, 20mL / min, 30mL / min, 40mL / min, 50mL / min, 60mL / min, 70 mL / min, 80mL / min, 90mL / min, 100mL / min, 110mL / min, 120mL / min, 130mL / min, 140mL / min, 150mL / min, 160mL / min, 170mL / min, 180mL / min, 190mL / min, 200mL / min, 210mL / min, 220mL The process can be carried out at flow rates of 1 / min, 230 mL / min, 240 mL / min, 250 mL / min, 260 mL / min, 270 mL / min, 280 mL / min, 290 mL / min, 300 mL / min, 310 mL / min, 320 mL / min, 330 mL / min, 340 mL / min, 350 mL / min, 360 mL / min, 370 mL / min, 380 mL / min, 390 mL / min, 400 mL / min, 410 mL / min, 420 mL / min, 430 mL / min, 440 mL / min, 450 mL / min, 460 mL / min, 470 mL / min, 480 mL / min, 490 mL / min, or 500 mL / min.Encapsulation is approximately 1 milliliter per minute (mL / min), 2mL / min, 3mL / min, 4mL / min, 5mL / min, 6mL / min, 7mL / min, 8mL / min, 9mL / min, 10mL / min, 20mL / min, 30mL / min, 40mL / min, 50mL / min, 60mL / min, 70mL / m in, 80mL / min, 90mL / min, 100mL / min, 110mL / min, 120mL / min, 130mL / min, 140mL / min, 150mL / min, 160mL / min, 170mL / min, 180mL / min, 190mL / min, 200mL / min, 210mL / min, 220mL / min This can be done at flow rates of 230 mL / min, 240 mL / min, 250 mL / min, 260 mL / min, 270 mL / min, 280 mL / min, 290 mL / min, 300 mL / min, 310 mL / min, 320 mL / min, 330 mL / min, 340 mL / min, 350 mL / min, 360 mL / min, 370 mL / min, 380 mL / min, 390 mL / min, 400 mL / min, 410 mL / min, 420 mL / min, 430 mL / min, 440 mL / min, 450 mL / min, 460 mL / min, 470 mL / min, 480 mL / min, 490 mL / min, 500 mL / min, or higher.

[0125] A droplet generator can use multiple parallel droplet generation operations in parallel. For example, a droplet generator (e.g., a device with plates and channels) can use at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or more droplet generation features (e.g., holes, channels, nozzles). A droplet generator can use up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 droplet generation features. The droplet generator can use approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more droplet generation features.

[0126] Encapsulation can be carried out through an emulsification process. For example, a composition can be emulsified in a mixer such as a stirrer, impeller, centrifugal mixer, or high-shear mixer. High-shear mixers can include batch high-shear mixers and in-line high-shear mixers (e.g., rotor-stator mixers). Emulsification can also be carried out without a mixer by combining a thermodynamically preferred fluid to form an emulsion with the help of one or more emulsifiers or surfactants, of which optional.

[0127] The encapsulation process can be carried out with the help of one or more emulsifiers or surfactants. Emulsifiers and surfactants may include, but are not limited to, saponins (e.g., Quillaja tree extract such as Q-NATURALE®, yucca extract), lecithin, soy lecithin, mustard seed husk extract, sodium stearoyl lactylate, polysorbate 20, and combinations thereof.

[0128] The encapsulated cannabinoid compound may contain one or more stabilizers or gelling agents that can be used to stabilize the capsule or emulsion. These stabilizers or gelling agents may include, but are not limited to, alginates (also known as algin or alginic acid) and agar. Alginates may be used in a variety of forms, including, but not limited to, inorganic salts such as sodium alginate, potassium alginate, calcium alginate, and combinations thereof. Alginates may be derived from sources such as seaweed (e.g., Macrocystis pyrifera, Ascophyllum nodosum, Laminaria spp.) or bacteria (e.g., Pseudomonas spp., Azotobacter spp.). Crosslinking agents or solutions, such as calcium chloride, may be used to stabilize or gel the capsule.

[0129] Encapsulated cannabinoid compounds can be characterized by their size (e.g., diameter). The size of the capsule (e.g., droplet) can be approximately 0.154 micrometers. The size of the capsule can be less than or equal to approximately 0.154 micrometers. The size of the capsule can be greater than or equal to approximately 0.154 micrometers. The capsule sizes are approximately 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0. Possible values ​​are 8, 0.85, 0.9, 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500 micrometers. The capsule sizes are approximately 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0 It may be less than or equal to 0.9, 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500 micrometers.The capsule sizes are approximately 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9 , 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, or 500 micrometers may be greater than or equal to these. Capsule size may be approximately 0.1 to 0.2 micrometers. Capsule size may be approximately 0.05 to 0.25 micrometers. Capsule size may be approximately 0.05 to 0.55 micrometers. Capsule size may be approximately 0.05 to 1 micrometer. The size distribution in a population of capsules can be homogeneous or substantially homogeneous. For example, a population of capsules could be approximately 20, 19, 18, 17, 16, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2. It may be characterized by a variance or multivariance index (PDI) of 1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.45, 1.40, 1.35, 1.30, 1.25, 1.20, 1.15, 1.14, 1.13, 1.12, 1.11, 1.10, 1.09, 1.08, 1.07, 1.06, 1.05, 1.04, 1.03, 1.02, 1.01, or less than or equal to 1.00.

[0130] The composition containing an effective amount of encapsulated cannabinoid compound is administered to the subject. The terms “effective amount” or “therapeutic effective amount” refer to the amount of encapsulated cannabinoid compound described herein sufficient to achieve the intended application, including but not limited to enhancing stem cell function and / or treating disease in the subject. The therapeutic effective amount may vary depending on the subject and condition being treated, e.g., the subject’s weight and age, the severity of the disease condition, the method of administration, etc., which can be readily determined by those skilled in the art. The term also applies to the dose that induces a specific response in target cells, e.g., a change in the expression of stem cell markers. The specific dose will vary depending on the particular formulation of the encapsulated cannabinoid compound, the administration regimen to be followed, whether it is administered in combination with other compounds, the timing of administration, the tissue to which it is administered, the route of administration, and the body’s delivery system through which it is carried.

[0131] Any of the compositions in question can be provided as a unit dosage form. A unit dosage is the amount of a compound, such as a cannabinoid compound, delivered alone or in combination with other components, administered to the subject at one or approximately one point in time. Other components that may be included with the unit dosage include, but are not limited to, cosmetics, food carriers, food bars, baked goods, dairy products, oils, beverages, solid medications (e.g., tablets), or liquid medications. The unit dose of cannabinoid compounds may be approximately 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000 or more milligrams (mg). The unit dose of a cannabinoid compound may be at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000 or more milligrams (mg). The unit dose of cannabinoid compounds can be up to approximately 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000 or more milligrams (mg). The unit dose can be the dose per hour. The unit dose can be the dose per day. A unit dose may provide approximately 1 / 24, 1 / 12, 1 / 8, 1 / 6, 1 / 4, 1 / 3, 1 / 2, or all of the daily dose of one or more cannabinoids relating to the subject. A unit dose may be in the form of a tablet, gel, liquid, food, food bar, container of liquid of a specified volume, or other form described herein, packaged for single consumption or administration.

[0132] The amount of the composition of the present invention administered may depend on the subject being treated, the severity of the disorder or condition, the administration rate, and the properties of the composition and the encapsulated cannabinoid compound. The amount of the composition administered may also depend on the type and amount of stem cells administered. The effective dosage ranges from about 0.1 mg to about 2000 mg per kg of body weight per day. For example, for a 70 kg person, this can reach about 7 mg / day to about 1.75 g / day. In some cases, dosage levels below the lower limit of the above range may be overly sufficient, while in other cases, even larger doses may be used without causing any adverse side effects, for example, by dividing such larger doses into several smaller doses for administration throughout the day. Doses may be administered over periods of several hours, several days, several weeks, or several months. The composition containing the encapsulated cannabinoid compound can be administered to the subject in any of several ways to bring about enhancement of stem cell function. The composition can be administered, for example, orally or transdermally. Other delivery routes include, but are not limited to, intranasal, sublingual, transmucosal, or intradermal. The effective amount of the composition may be in a dosing unit formulation containing, as needed, a conventional non-toxic, physiologically acceptable carrier, adjuvant, and vehicle.

[0133] Oral administration can be achieved using oral dosage forms. Oral dosage forms may be solid (e.g., tablets or bulk powder) or liquid (e.g., suspensions or slurries). Tablets can include tablets, caplets, capsules including soft gelatin capsules, and lozenges. Tablets may further contain suitable binders, lubricants, diluents, disintegrants, colorants, flavorings, flow inducers, and melting agents.

[0134] Compositions containing encapsulated cannabinoid compounds formulated for oral administration can be incorporated into food compositions. Food compositions may be beverages, solid foods, or semi-solid foods. Food compositions may contain encapsulated cannabinoid compounds and food carriers. Food carriers can be virtually any food. Examples of food carriers include, but are not limited to, food bars (granola bars, protein bars, candy bars, etc.), cereal products (oatmeal, breakfast cereals, granola, etc.), bakery products (bread, donuts, crackers, bagels, pastries, cakes, etc.), beverages (milk-based beverages, sports drinks, fruit juices, alcoholic beverages, mineral water), pasta, grains (rice, corn, oats, rye, wheat, flour, etc.), egg products, snacks (candy, chips, gum, chocolate, etc.), meat, fruits, and vegetables.

[0135] Compositions containing encapsulated cannabinoid compounds can be administered transdermally, for example, via a patch. Compositions of the Disclosure can be administered intravenously. Compositions of the Disclosure can be administered topically. Compositions of the Disclosure can be administered by topical exposure to an aqueous solution, such as by immersing a subject in a float tank. Compositions of the Disclosure can be formulated as bath salts or liquid bath products that can be dissolved or dispersed in water (e.g., a bathtub) for skin exposure, for example, by immersion of a subject. Compositions containing encapsulated cannabinoid compounds for topical or transdermal application may be provided as cosmetic or personal care products, such as soaps (e.g., solid, bar, liquid, or foam), hand sanitizers, lotions, massage oil masks, makeup, moisturizers, sunscreens, toothpastes, mouthwashes, or throat sprays.

[0136] To enhance stem cell function, compositions containing encapsulated cannabinoid compounds can be administered using a variety of different mechanisms. The compositions may be delivered as aerosol spray preparations, either sprayed from a pressurized pack or aerosolized from a dry powder inhaler. Suitable propellants that can be used in sprayers include, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, and carbon dioxide. Dosage can be determined, in the case of pressurized aerosols, by providing a valve for delivering a controlled amount of the compound.

[0137] The composition can be administered to a subject in various forms to enhance the function of stem cells. The composition can be administered as a dry powder. For example, an oil-based composition (e.g., hemp oil) can be combined with a drying or powdering agent such as cyclodextrin. In some cases, the powder composition can be provided on its own. In other cases, the powder composition can be provided in other products or compositions such as food or composition, cosmetics or other products, and in compositions such as those disclosed herein.

[0138] Compositions containing encapsulated cannabinoid compounds can be administered in any suitable form, including but not limited to liquid, gel, semi-liquid (e.g., a viscous liquid containing some solid), semi-solid (a solid containing some liquid), or solid form. Compositions can be provided, for example, in tablet, capsule, food, chewable, non-chewable, transchucral, sublingual, slow-release, non-slow-release, sustained-release, or non-sustained-release form.

[0139] Compositions containing encapsulated cannabinoid compounds for inhalation or inhalation include solutions and suspensions in pharmaceutically acceptable aqueous solvents or organic solvents, or mixtures thereof, as well as powders. Liquid or solid compositions may contain appropriate excipients as described above. Preferably, the compositions of the present invention are administered orally, intranasally, or via respiratory routes for topical or systemic effects. Compositions in acceptable solvents may be sprayed using an inert gas. Sprayed solutions may be inhaled directly from a spraying device, or the spraying device may be attached to a face mask, tent, or intermittent positive pressure respirator. Solutions, suspensions, or powder compositions may be administered orally or intranasally from a device that delivers the formulation in an appropriate manner.

[0140] The compositions of this disclosure may contain one or more additional agents, whether active or passive. Examples of such agents include sweeteners, flavorings, colorants, fillers, binders, lubricants, excipients, preservatives, or processing agents. Additional pharmaceutically acceptable excipients (in the case of pharmaceuticals) or other additives (in the case of non-pharmaceutical applications) may be added to the compositions. For example, any generally acceptable soluble or insoluble inactive pharmaceutical filler (diluent) material may be included in the final product (e.g., solid dosage form) if desired. Such inactive pharmaceutical fillers may include monosaccharides, disaccharides, polyhydric alcohols, inorganic phosphates, sulfates, or carbonates, and combinations thereof. Examples of suitable inactive pharmaceutical fillers include sucrose, dextrose, lactose, xylitol, fructose, sorbitol, calcium phosphate, calcium sulfate, calcium carbonate, microcrystalline cellulose, and combinations thereof. Effective amounts of any generally acceptable pharmaceutical lubricant, such as calcium or magnesium soap, may be added.

[0141] In related but separate embodiments, the Disclosure provides food compositions comprising an effective amount of encapsulated cannabinoids and a food carrier for enhancing the function of stem cells. Any type, amount, or form of composition comprising the encapsulated cannabinoids disclosed herein is applicable to preparing the food compositions disclosed herein.

[0142] Food compositions or foods may include food bars, including but not limited to granola bars, protein bars, candy bars, and energy bars. Food compositions or foods may include cereal products, including but not limited to oatmeal, grain flours (e.g., wheat flour, rice flour, corn flour, barley flour), breakfast cereals, granola, bread, pasta, mochi, and popcorn. Food compositions or foods may include bakery products, including but not limited to bread, pastries, brownies, cakes, pies, donuts, crackers, and muffins. Food compositions or foods may include dairy products, including but not limited to milk, fermented milk, curd, whey, yogurt, cream, cheese, butter, clear butter, ghee, and ice cream. Food compositions or foods may include nut butter or seed butter, including but not limited to peanut butter, almond butter, cashew butter, hazelnut butter, macadamia nut butter, pecan butter, pistachio butter, walnut butter, pumpkin seed butter, sesame seed butter, soybean butter, and sunflower seed butter. Food compositions or foods may include, but are not limited to, oils such as olive oil, coconut oil, vegetable oil, canola oil, corn oil, peanut oil, sunflower seed oil, almond oil, avocado oil, rice bran oil, cottonseed oil, flaxseed oil, linseed oil, grape seed oil, hemp oil, mustard oil, macadamia oil, palm oil, tea oil, walnut oil, margarine, lard, butter, clear butter, ghee, or taro (e.g., cooking oil). Food compositions or foods may also include sports foods such as energy gels, sports drinks, energy powders, energy bars, energy shots, protein powders, and protein drinks (e.g., protein shakes).Food compositions or foods may include, but are not limited to, beverages such as water, electrolyte drinks, soda, coconut water, tea (e.g., jun tea, black tea, green tea, white tea, herbal tea), coffee, soft drinks, alcoholic beverages (e.g., cocktails, liquor, spirits, beer, wine, malt drinks), water, juices (e.g., apple juice, orange juice, tomato juice, vegetable juice, cranberry juice), sports drinks, electrolyte-rich water, vitamin-rich water, hangover remedies, milk (e.g., dairy-based milk, coconut milk, almond milk, soy milk, hemp milk, rice milk, oat milk, cashew milk, hazelnut milk), and yogurt. Food compositions or foods may include, but are not limited to, fungal or fermented foods or beverages such as kefir, jun, amasi, amazake, appa, ayran, dougu, bagoong, brum, cheonggukjang, chicha, kombucha, fermented tofu, kimchi, lassi, miso, poi, yakult, and yogurt.

[0143] The compositions of this disclosure may include pet or other animal products, such as animal foods (e.g., dog food, cat food), treats, and nutritional supplements (e.g., liquids, sprays, or powders to be applied to food or water). These compositions may be formulated or administered for household or pet animals (e.g., dogs, cats, small animals, birds), livestock and other farm animals (e.g., cattle, pigs, horses, sheep, goats), zoo animals, or any other vertebrate animals. Compositions for administration to animals may be formulated with encapsulated or unencapsulated cannabinoid-rich oils alone or in combination with essential oils, terpenes, and other components described herein. Compositions for administration to animals may be mixed with feed or water, prepared for spray application (e.g., mixed with glycerin), for intravenous administration (e.g., in syringes or IV bags), in the form of ointments, vitamins, liquid vitamin pumps, treats, or other forms.

[0144] Packaging for food compositions containing encapsulated cannabinoids can take the form of several three-dimensional structures. Packaging may be configured for a single service. Packaging may be disposable. In non-limiting examples, packaging may be a pouch, can, flexible container, or sealed tube. Food packaging may be made from any of a variety of materials, including Mylar®, Aclar®, polyethylene, foil, and aluminum. Food compositions may be packaged in retort pouches or flexible bowls with lids, food condiment pouches, or full-panel drawer cans. Food composition packaging may incorporate utensils such as forks, spoons, knives, or scissors. Packaging may be configured so that parts are removed to facilitate consumption. For example, packaging may remain sealed during rehydration or reheating; for consumption, parts of the packaging may be removed. Packaging may be configured for rehydration of dehydrated food composition powder. For example, food and beverage packaging may further include a septum adapter to allow rehydration of dehydrated food. Sealed containers containing food compositions may be configured to be fixed to a tray. Dry, powdery, or easily crumbled foods may be coated with gelatin to reduce crumbling. Oxygen may be removed from the package and replaced with nitrogen gas and an oxygen scavenger. Nitrogen gas may be introduced into the package before sealing. The package may be sealed with a vacuum seal. The package may be sealed with a Hg vacuum of approximately 15 to 35 inches.

[0145] The kit may include a food composition containing an effective amount of encapsulated cannabinoid compound. The kit may be configured to be consumed by the subject under various conditions.

[0146] In addition to enhancing stem cell function, administration of the compositions of this disclosure to a subject may result in one or more additional beneficial effects. These beneficial effects may include, but are not limited to, pain relief, reduced bacterial growth, reduced blood glucose levels, improved blood lipid and cholesterol profiles, increased fat burning, reduced appetite, stimulated appetite, reduced vomiting or nausea, reduced seizures or convulsions, antifungal effects, reduced inflammation, reduced arthritis (e.g., rheumatoid arthritis), reduced insomnia or assisted sleep, reduced arterial occlusion, inhibited cancer cell growth, improved psoriasis, calming effects, anticonvulsant effects, reduced anxiety, promoted bone growth, reduced bowel contractions, and neurological protection.

[0147] The compositions described herein can offer several advantages, including but not limited to increased storage stability, increased bioavailability, increased biological activity, and delayed release. When administered to a subject, the compositions described herein may have a variety of release profiles, half-lives, and metabolic properties. The composition in question may comprise a plurality of capsules, each of which is characterized by exhibiting at least one of the following: (a) an S-shaped release profile of at least one cannabinoid compound; (b) a plasma half-life of at least one cannabinoid compound that is more than twice as long as that of at least one cannabinoid compound not in encapsulated form; (c) a first-pass metabolism of at least one cannabinoid compound that is reduced by at least 50% compared to at least one cannabinoid compound not in encapsulated form; (d) an elimination rate of at least one cannabinoid compound from the subject's body that is reduced by at least 20% compared to at least one cannabinoid compound not in encapsulated form; or (e) a degradation rate of at least one cannabinoid compound at an ambient temperature of at least 20°C that is less than about 50% of the degradation rate of at least one cannabinoid compound not in encapsulated form.

[0148] The compositions described herein may have a storage half-life of at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 240, 270, 300, 330, or 360 days. In some cases, the compositions described herein may have a storage half-life of at least about 1, 2, 3, 4, or 5 years. The encapsulated composition may be characterized by a cannabinoid degradation rate at an ambient temperature of at least 20°C that is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% lower than the degradation rate of the unencapsulated cannabinoid composition.

[0149] Cannabinoid compositions in encapsulated form may be characterized by their plasma half-lives in subjects at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.5, 4.0, 4.5, or 5.0 times that of unencapsulated cannabinoid compositions. The plasma half-life of a composition can be determined experimentally by administering the composition to a subject, taking plasma samples from the subject at multiple time points, and measuring the concentration of one or more compounds of interest in those plasma samples. The concentration of one or more compounds of interest will reach a peak value in plasma and then decrease as one or more compounds are metabolized, broken down, or removed from the bloodstream. The plasma half-life is the time it takes for the plasma concentration value to be halved.

[0150] The cannabinoid release profile can be S-shaped (e.g., having an "S"-shaped curve such as a logistic function). The cannabinoid release profile can be non-S-shaped. The cannabinoid release profile can be linear. The cannabinoid release profile can be non-linear. The cannabinoid release profile can be instantaneous. The cannabinoid release profile can be non-instantaneous. The cannabinoid release profile can be delayed. The cannabinoid release profile can be constant or sustained. The cannabinoid release profile can be variable or non-sustained.

[0151] Tablets can be formulated in a sustained-release format. Methods for preparing sustained-release tablets are known in the art; see, for example, U.S. Patent Application Publication 2006 / 0051416 and U.S. Patent Application Publication 2007 / 0065512. Gradual-release tablets are also known in the art; an example of such a tablet is described, for example, in U.S. Patent No. 3,456,049. Slow-release or sustained-release forms may delay the disintegration or absorption of the composition or one or more of its components.

[0152] In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within one hour of administration to the subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within two hours of administration to the subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 3 hours of administration to the subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 4 hours of administration to the subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 5 hours of administration to the subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 6 hours of administration to the subject.In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 7 hours of administration to the subject. In some cases, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or less of the cannabinoid compound is released from the capsule within 8 hours of administration to the subject.

[0153] The release profile is the relationship between time and the amount of compound released into a target or the concentration of the compound within the target (e.g., in plasma). The release profile can be measured using a method similar to that of plasma half-life. The composition can be administered to a target, and samples (e.g., plasma or blood samples) can be taken from the target at multiple time points. The concentration of one or more compounds of interest can be measured in such samples, and the release profile can be plotted.

[0154] Compounds ingested by a subject via the gastrointestinal system are transported to the liver and can then enter the systemic circulation. Compounds that are readily metabolized and broken down in the liver may have substantially reduced activity due to first-pass metabolism through the liver. Encapsulation of compounds (e.g., microencapsulation) can reduce the first-pass metabolism of compounds in the liver. Compositions in encapsulated form may be characterized by first-pass metabolism in subjects at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% less than that of unencapsulated cannabinoid compositions. The encapsulated composition may be characterized by a cannabinoid elimination rate from the subject that is at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% less than that of the unencapsulated cannabinoid composition.

[0155] The compositions described herein may have improved bioavailability, bioactivity, or both when administered to a subject. Bioavailability is the proportion of the administered dose of the unchanged compound that reaches systemic circulation. Cannabinoid compositions in encapsulated form may be characterized by bioavailability in a subject at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10.0 times greater than that of unencapsulated cannabinoid compositions. Cannabinoid compositions in encapsulated form may be characterized by their bioavailability in at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% of the target. Bioactivity, or biological activity, is the activity induced by one or more active components in the composition. Microencapsulated cannabinoid compositions may be characterized by their bioavailability in subjects at least 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10.0 times that of unencapsulated cannabinoid compositions.

[0156] The compositions described herein can be used to treat subjects having diseases including, but not limited to, the conditions described in paragraph

[0064] . The compositions described herein can be used to treat subjects having injuries including, but not limited to, the conditions described in paragraph

[0064] .

[0157] Treating the diseases used herein includes therapeutic and / or preventive benefits. Preventive effects include delaying or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, delaying, halting, or reversing the progression of a disease or condition, or any combination thereof.

[0158] The methods disclosed herein can produce synergistic effects. Using cannabinoid compositions in conjunction with stem cells can synergistically enhance the function of stem cells. In some examples, stem cell treatments and cannabinoid compositions may be administered in sub-therapeutic doses. In some embodiments, sub-therapeutic doses of stem cells and / or cannabinoid compositions may be used. A sub-therapeutic dose of a drug or treatment is less than the effective dose of that drug or treatment, but when combined with another drug or treatment in an effective or sub-therapeutic dose, it can produce desirable results for the physician, for example, due to synergistic effects in the resulting effective effect or reduction of side effects.

[0159] A “synergistically effective therapeutic dose” or “synergistically effective amount” of a drug or treatment is an amount that, when combined with another drug or treatment in an effective or therapeutic dose or less, produces a greater effect than either of the two drugs used alone. In some embodiments, a synergistically effective therapeutic dose of a drug or treatment, when used in combination, produces a greater effect than the additive effect of each of the two drugs or treatments used individually. In certain preferred embodiments of this disclosure, stem cell therapies and cannabinoid compositions exhibit a synergistic effect.

[0160] In some cases, efficacy can be assessed by determining changes in overall survival, improvement in disease-related symptoms, disease-free survival, progression-free survival, and / or time to treatment failure. Efficacy can be determined by a variety of non-limiting methods, including monitoring changes in gene expression levels and biomarker expression levels. [Examples]

[0161] (Example 1) Microencapsulated cannabinoids improve stem cell engraftment. A hemp oil composition containing cannabinoids, including cannabidiol, is prepared. The composition is microencapsulated via a microfluidic nozzle device. The microcapsules are administered to subjects before they undergo stem cell treatment. After the subjects receive stem cell treatment, they show increased stem cell engraftment compared to control subjects who did not receive the cannabinoid-containing microcapsules.

[0162] (Example 2) Microencapsulated cannabinoids improve stem cell survival during transplantation. A hemp oil composition containing cannabinoids, including cannabidiol, is prepared. The composition is microencapsulated via a microfluidic nozzle device. The microcapsules are administered to subjects before they receive stem cell treatment. After the subjects receive stem cell treatment, the subjects have more viable stem cells compared to control subjects who did not receive the cannabinoid-containing microcapsules.

[0163] (Example 3) Microencapsulated cannabinoids reduce immune activation against transplanted stem cells. A hemp oil composition containing cannabinoids, including cannabidiol, is prepared. The composition is microencapsulated via a microfluidic nozzle device. The microcapsules are administered to subjects simultaneously with bone marrow transplantation. Subsequently, a reduction in graft rejection is observed compared to control subjects who did not receive the cannabinoid-containing microcapsules. Graft rejection is determined by using PCR amplification of variable number tandem repeat (VNTR) loci to identify donor and recipient cells in the bone marrow.

[0164] (Example 4) Cannabinoids affect gene expression in mouse embryonic stem cells. Mouse embryonic stem cells are cultured in media treated with either cannabidiol (1 μM, 5 μM, 10 μM, or 50 μM) or a vehicle control. Samples are harvested on days 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, and RNA is extracted for next-generation sequencing. Expression analysis is performed on the sequencing data to determine genes differentially expressed in cannabidiol-treated cells. Differential expression of stem cell markers, differentiation markers, DNA replication, cell cycle, proliferation, apoptosis, and cannabinoid pathway genes may be of particular interest.

[0165] (Example 5) Cannabinoids influence globulation in mouse embryonic stem cells. Mouse embryonic stem cells are cultured in medium treated with either cannabidiol (1 μM, 5 μM, 10 μM, or 50 μM) or a vehicle control for 10 days. After 10 days of culture, the cells are transferred to a sphere formation assay. Each treatment group is scored for the number of spheres formed, the size and shape of the spheres formed, the cell types found in each sphere, and the number of times the spheres can be passaged. Stem cells treated with cannabidiol may form spheres with higher efficacy, may form spheres with more neural cells than spheres formed by vehicle-treated cells, or may form spheres with more or less different cell types compared to vehicle-treated cells.

[0166] (Example 6) Cannabinoids increase the engraftment of mouse hematopoietic stem cells delivered by tail vein injection. Mouse hematopoietic stem cells are isolated from the bone marrow of mice expressing GFP under the control of a constitutive promoter. Recipient mice are prepared by exposing congenic mice to radiation sufficient to deplete the population of hematopoietic stem cells. The isolated hematopoietic stem cells are delivered to recipient mice by tail vein injection. After injection, the mice are fed either a control diet or a diet supplemented with a microencapsulated hemp oil composition containing cannabinoids, including cannabidiol. Blood samples are collected from both groups of mice at weeks 4, 8, 12, 16, 20, 24, 28, and 32, and the number of donor-derived cells is determined by screening the cells for GFP expression.

[0167] Additional experiments will be conducted using the protocol described above to determine the efficacy of transplanting hematopoietic stem cells derived from genetically engineered mice lacking cannabinoid receptors (CB nulls) into CB null recipient mice.

[0168] (Example 7) Cannabinoids enhance stem cell treatment after spinal cord injury. Mouse neural stem cells expressing green fluorescent protein (GFP) under the control of a constitutive promoter are treated for 10 days with either cannabidiol (1 μM, 5 μM, 10 μM, or 50 μM) or a vehicle control. The cells are then directly transplanted into the spinal cords of mice with spinal cord injury. Mice are maintained on a control diet or a diet supplemented with a microencapsulated hemp oil composition containing cannabinoids, including cannabidiol, at concentrations similar to those used in cell culture media. Mice are monitored daily for signs of spinal cord recovery of motor function based on the Basso Mouse Scale (BMS) score, an exercise assessment scale based on frequency analysis of seven exercise categories, and a ro-rod treadmill test. Two months after stem cell treatment, the mice are sacrificed and their spinal cords are histologically examined. Mice receiving cannabinoid-treated stem cells and cannabinoid-supplemented diets show more rapid and stronger recovery.

[0169] Preferred embodiments of the present invention have been shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided merely as examples. The present invention is not intended to be limited by any particular example provided herein. The present invention has been described with reference to the foregoing specification, but the descriptions and examples of embodiments herein are not intended to be construed as limiting. Hereinafter, those skilled in the art will come up with many variations, modifications, and substitutions without departing from the present invention. Furthermore, it will be understood that all aspects of the present invention are not limited to any particular figures, configurations, or relative proportions described herein, depending on a wide variety of conditions and variables. It should be understood that in carrying out the present invention, various substitutes may be used for the embodiments of the present invention described herein. Accordingly, the present invention is intended to encompass any such substitutes, modifications, variations, or equivalents. The following claims define the scope of the present invention, and the methods and structures within these claims, as well as their equivalents, are intended to be encompassed thereby.

Claims

1. i) a combination for improving stem cell engraftment, ii) for improving stem cell survival during transplantation, or iii) for reducing immune activation against transplanted stem cells, The aforementioned stem cells; and Pharmaceutical composition containing encapsulated cannabinoid compounds The encapsulated cannabinoid compound is characterized by at least one of the following: a) an S-shaped release profile; b) a plasma half-life more than twice that of the cannabinoid compound not in encapsulated form; c) a first-pass metabolism reduced by at least 50% compared to the cannabinoid compound not in encapsulated form; d) an elimination rate from the subject's body reduced by at least 20% compared to the cannabinoid compound not in encapsulated form; or e) a degradation rate at an ambient temperature of at least 20°C which is less than 50% of the degradation rate of the cannabinoid compound not in encapsulated form. The aforementioned pharmaceutical composition is a combination administered before, simultaneously with, or after the administration of the stem cells.

2. The combination according to claim 1, wherein the pharmaceutical composition further comprises at least one terpene compound.

3. The combination according to claim 1, wherein the pharmaceutical composition reduces the side effects typically associated with the administration of the stem cells.

4. The combination according to claim 1, wherein the subject is suffering from or suspected of suffering from a disease selected from the group consisting of chronic leukemia, lymphoma, hereditary platelet abnormalities, plasmacytotoxicity, autoimmune diseases, myeloproliferative disorders, lymphocyte proliferative disorders, phagocyte disorders, myelodysplastic syndromes, histiocytic disorders, congenital immune system disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and multiple sclerosis, stroke, diabetes mellitus, infertility, vision loss or other eye diseases, lysosomal storage disorders, peripheral artery disease, ischemic limb injury, diabetes mellitus, heart disease, liver disease, bone disease, muscular dystrophy, dental disease, and cancer.

5. The combination according to claim 1, wherein the subject is suffering from an injury selected from the group consisting of spinal and spinal cord injury, wound, burn or chemical burn, sports injury, occupational injury, or brain injury.

6. The combination according to claim 1, wherein the stem cells are derived from stem cells, which are induced pluripotent stem cells, embryonic stem cells, fetal stem cells, or adult stem cells.

7. The aforementioned stem cells include AA4, AA4.1, P-gp (CD243), ABCB5, ABCG2 (CDw338), ALDH, alkaline phosphatase, alpha-6 integrin, WNT2B, antithrombin III (AT), asialoGM1, Bcl-2, beta-1 integrin, bromodeoxyuridine, c-kit (CD117), c-Met, C1qR (p), END (CD105), PROM1 (CD133), A LCAM (CD166), ITGB1 (CD29), TNFRSF8 (CD30), PECAM-1 (CD31), Siglec-3 (CD33), CD34, CD44, NCAM (CD56), CD73, CD9, CD90, CDCP1, Circulating Anticoagulant Protein C (PC), CK19, CLV3, Cyclic CMP, ECMA-7, EDR1, EEC, FGF-4, Flk-2, Flk1(+), Flt3 / Flk2, FM S (CD115), FORSE-1, G-alpha-16, GDF3, GFPM, Gli2, Gli3, Glial fibrillary acidic protein, Glycoprotein IB, GSTA1, Her5, hMYADM, HSA, hsp25, Id2, IL-3R-alpha, Integrin, Interleukin-3 receptor alpha chain, KDR, Keratin 15 (also known as CK15, cytokeratin 15), Keratin 19 (also known as CK19, cytokeratin 19, K19) ), Kit, L-selectin (CD62L), lamin A / C, Lewis X antigen (Le(X)), LeX, Lgr5, Lrp4, MCM2, MCSP, monosomy 7, mouse ortholog of ARX, MRP4, Msi-1, Musashi, Musashi-1, mutant BCRP, nestin, neurofilament microtubule-associated protein 2, neuron glial antigen 2 (NG2), Notch 1, nrp-1, nucleostemin, OC. 3, Oct-4, OST-PTP, P-gp / MDR1, p21, p63, p75, PCLP, PCNA, PECAM, PgP-1, phosphorylated-p38, podocalixin, procalcitonin (PCT), PSC, pSV2gpt, PTPRC, rat liver fatty acid binding protein / human growth hormone transgene (Fabpl / hGH), RC1 antigen, Rex-1, Sca-1, SCF, sialyl-lactotetra, SOX10, SOX2, SOX9, SSEA-1, SSEA-3, SSEA-4, Stat3, Stat5,The combination according to claim 1, expressing at least one of Stella, Stra8, Str-1, tartrate-resistant acid phosphatase (TRAcP), TdT, telomerase reverse transcriptase, thrombomutin, Thy-1, Tra-1-60, TWIST1, VEGFR-2, vimentin, X-smoothund, XKrk1, or Zac1.

8. The combination according to claim 1, wherein the stem cells are derived from stem cells exhibiting totipotency, pluripotency, dipotency, or unipotency.

9. The aforementioned stem cells include fibroblasts, keratinocytes, melanocytes, cold-sensitive primary sensory neurons, auditory hair cells or organ of Corti, Merkel cells, photoreceptor cells, taste bud cells, cholinergic neurons, adrenergic neurons, peptide-guppy neurons, hepatocytes, adipocytes, hepatic adipocytes, renal glomerulopoda cells, pancreatic duct cells, gallbladder epithelial cells, pericytes, corneal fibroblasts, skeletal muscle cells, cardiomyocytes, Purkinje fibrillates, erythrocytes, megakaryocytes, monocytes, Langerhans cells, osteoclasts, osteoblasts, dendritic cells, microglia, and neutrophils. The combination according to claim 1, which is derived from stem cells that produce globulogranulocytes, hybridoma cells, mast cells, helper T cells, suppressor T cells, cytotoxic T cells, natural killer T cells, B cells, oocytes, spermatids, follicular cells, Schwann cells, satellite glial cells, intestinal glial cells, astrocytes, neuronal cells, oligodendrocytes, prelentic epithelial cells, crystallin-containing lens fiber cells, growth hormone-producing cells, adrenocorticotropin-producing cells, melanocyte-stimulating hormone-producing cells, thyroid cells, or dental cells.

10. The combination according to claim 1, wherein the stem cells are delivered by intravenous injection, intradermal, transplanted microvascular bed of bone marrow, subcutaneous, oral (e.g., ingestion or inhalation), transdermal (topical), transmucosal, rectal administration, transplanted monolayer tissue, intra-arterial, intramuscular, intratracheal, intraperitoneal, intravitreous, or direct injection into a target site.

11. The combination according to claim 1, wherein the stem cells and the pharmaceutical composition exhibit a synergistic effect on the process in the subject.

12. The combination according to claim 1, wherein the pharmaceutical composition comprises nanocapsules, and the nanocapsules comprise individual nanocapsules containing the encapsulated cannabinoid compound.

13. The combination according to claim 12, wherein the nanocapsules increase stem cell growth.

14. The combination according to claim 12, wherein the nanocapsules are administered after stem cell therapy.

15. The combination according to claim 12, wherein the nanocapsules are administered to the target by inhalation.

16. The combination according to claim 12, wherein the nanocapsules are vaporized.

17. The combination according to claim 12, wherein the nanocapsules are sprayed.

18. The combination according to claim 12, wherein the nanocapsules are administered orally.

19. The combination according to claim 12, wherein the nanocapsules are incorporated into a food or beverage.

20. The combination according to claim 12, wherein the nanocapsules are administered locally.

21. The combination according to claim 12, wherein the nanocapsules are water-soluble.

22. The combination according to claim 2, wherein at least one terpene compound is derived from Quillaja saponaria.

23. The combination according to claim 1, wherein the cannabinoid compound comprises cannabidiol (CBD).

24. The combination according to claim 1, wherein the cannabinoid compound comprises 0.3% or less of tetrahydrocannabinol (THC).

25. The combination according to claim 1, wherein the subject is suffering from or suspected to be suffering from a disease or injury, and the subject is monitored for the progression of the disease or injury in response to the administration of the pharmaceutical composition to the subject after the administration of the pharmaceutical composition to the subject.

26. The combination according to claim 25, wherein the subject is suffering from or suspected to be suffering from the disease, and after the administration of the pharmaceutical composition, the subject is monitored for progression or regression of the disease in response to the administration of the pharmaceutical composition to the subject.