Compositions and uses of psilocybin and psilocin

Description

1 / 71 COMPOSITIONS AND USES OF PSILOCYBIN AND PSILOCIN Divided from BR112024026292-8, filed on 05.06.2023. FIELD OF THE INVENTION

[0001] This invention is directed to crystalline forms of a psilocybin and psilocin compound and to the uses of the compounds in the treatment of mental health disorders and / or other conditions and disorders of the central nervous system. BACKGROUND INFORMATION

[0002] Several natural plants and fungi contain psychedelic compounds that cause alterations in brain function or activity (neuroactive compounds) and can also cause individuals to experience hallucinogenic or similar experiences (psychedelic compounds). Among the most common types of naturally occurring psychedelics is psilocybin, which has been found in over 180 species of mushrooms globally. Mushrooms containing psilocybin also have other neuroactive and psychedelic compounds, the most abundant of which is its primary metabolite, psilocin. In humans, psilocybin is metabolized in the gastrointestinal system, primarily to psilocin, which is then absorbed and causes the psychedelic effects.

[0003] These psychedelic effects are dose-dependent and typically include alterations in visual, auditory, and cognitive experiences. These psilocybin experiences can occur because both psilocybin and psilocin are similar in structure to the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), and both bind to a variety of 5-HT receptors.

[0004] In contrast to psilocybin, psilocin is chemically unstable and oxidizes rapidly when exposed to air. For this reason, there have been very few clinical or research studies on the impact of psilocin administered alone or in comparison to Petition 870260077978, dated 05 / 08 / 2026, p. 82 / 164 2 / 71 psilocybin. Preclinical studies that have been conducted suggest that the

[0005] Psilocin has a faster absorption rate and a faster onset of action than psilocybin. Psilocin binds to a different range of 5-HT receptors and at different concentrations than psilocybin and, as such, has a different range of actions.

[0006] Due to the different properties of psilocybin and psilocin, a compound combining psilocybin and psilocin can be expected to have unique and beneficial properties compared to either compound alone.

[0007] It has been suggested that psychedelics, such as psilocybin and psilocin, could be useful in treating certain mental health disorders and central nervous system disorders. This is believed to be especially true for disorders that are resistant to currently available treatments, such as post-traumatic stress disorder (PTSD) and treatment-resistant major depressive disorder, also called treatment-resistant depression (TRD).

[0008] There is a need for new treatments for a wide variety of mental health disorders and central nervous system disorders. One such treatment may be a crystalline form of psilocybin and psilocin, especially for use in disorders resistant to current treatments.

[0009] SUMMARY

[00010] This disclosure provides several new compositions and their uses, including the crystalline forms of psilocin and psilocybin: Petition 870260077978, dated 05 / 08 / 2026, p. 83 / 164 3 / 71 psilocin psilocybin

[00011] Described and identified in this document as Crystal Forms A, B, and C. Crystal Form A can be distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 10.1°. An XRPD pattern of Crystal Form A may further comprise a significant peak at a 2Θ angle of about 19.16°. An XRPD pattern of Crystal Form A may further comprise significant peaks at 2Θ angles of about 10.74°, about 25.3°, and about 24.07°. In addition, an XRPD pattern of Crystal Form A may further comprise significant peaks at 2Θ angles of about 14.54°, about 16.5°, about 13.44°, about 23.42°, and about 8.62°. Crystalline Form B can be distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of approximately 18.54°. An XRPD pattern of Crystalline Form B may additionally comprise a significant peak at a 2Θ angle of approximately 8.54°.An XRPD pattern of Crystal Form B may additionally comprise significant peaks at 2Θ angles of approximately 22.78°, approximately 14.27°, and approximately 21.12°. Furthermore, an XRPD pattern of Crystal Form B may additionally comprise significant peaks at 2Θ angles of approximately 14.12°, approximately 10.05°, approximately 9.94°, approximately 24.94°, and approximately 25.02°. Crystal Form C may be distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of approximately 9.18°. An XRPD pattern of Crystal Form C may additionally comprise a significant peak at a 2Θ angle of approximately 17.95°. An XRPD pattern of the C crystal form may additionally comprise significant peaks at 2Θ angles of approximately 10.42°. Petition 870260077978, dated 05 / 08 / 2026, page 84 / 164 4 / 71 24.22° and approximately 18.38°. In addition, an XRPD pattern of the C crystal form may further comprise significant peaks at 2Θ angles of approximately 19.82°, approximately 17.46°, approximately 14.82°, approximately 22.38°, and approximately 14.06°.

[00012] In one embodiment, the present application provides a pharmaceutical composition comprising a crystalline form of psilocin and psilocybin and a pharmaceutically acceptable excipient. In one embodiment, the crystalline form is Crystalline Form A, Crystalline Form B, or Crystalline Form C. In one embodiment, Crystalline Form A is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 10.1°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 19.16°; at 2Θ angles of about 10.74°, about 25.3°, and about 24.07°; and / or the XRPD pattern further comprises a significant peak at 2Θ angles of about 14.54°, about 16.5°, about 13.44°, about 23.42°, and about 8.62°. In one embodiment, Crystalline Form A has a psilocybin to psilocin ratio of about 1:1. In one embodiment, Crystalline Form A has a chemical purity of about 95% or more.In some embodiments, Crystalline Form A contains no more than about 5 mol% of other solid forms. In some embodiments, the composition of Crystalline Form A of psilocin and psilocybin comprises about 95 mol% of Crystalline Form A, about 2.5 mol% of psilocin, and about 2.5 mol% of psilocybin. In one embodiment, Crystalline Form A is a cocrystal formed between psilocin and psilocybin. In one embodiment, Crystalline Form A is a salt formed between psilocin and psilocybin.

[00013] In one embodiment, the B crystal form is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 18.54°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 8.54°; the XRPD pattern Petition 870260077978, dated 05 / 08 / 2026, p. 85 / 164 5 / 71 still comprises a significant peak at 2Θ angles of about 22.78°, about 14.27°, and about 21.12°, and / or the XRPD pattern still comprises a significant peak at 2Θ angles of about 14.12°, about 10.05°, about 9.94°, about 24.94°, and about 25.02°. In one embodiment, Crystalline Form B has a psilocybin to psilocin ratio of about 1.3:1. In one embodiment, Crystalline Form B has a psilocybin to psilocin ratio of about 1:1. In one embodiment, Crystalline Form B has a chemical purity of about 95% or more. In some embodiments, Crystalline Form B contains no more than about 5 mol% of other solid forms. In some embodiments, the composition of Psilocin and Psilocybin Crystalline Form B comprises approximately 95 mol% of Crystalline Form B, approximately 2.5 mol% of psilocin, and approximately 2.5 mol% of psilocybin.In one embodiment, Crystalline Form B is a cocrystal formed between psilocin and psilocybin. In another embodiment, Crystalline Form B is a salt formed between psilocin and psilocybin.

[00014] In one embodiment, the Crystalline Form C is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 9.18°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 17.95°; the XRPD pattern further comprises a significant peak at 2θ angles of about 10.42°, about 24.22° and about 18.38°; and / or the XRPD pattern further comprises a significant peak at 2θ angles of about 19.82°, about 17.46°, about 14.82°, about 22.38° and about 14.06°. In one embodiment, the Crystalline Form C has a psilocybin to psilocin ratio of about 1:1. In one embodiment, the Crystalline Form C has a chemical purity of about 95% or more. In some embodiments, the Crystalline Form C contains no more than about 5 mol% of other solid forms. In some embodiments, the Crystalline Form C is composed of psilocin and psilocybin. Petition 870260077978, dated 05 / 08 / 2026, p. 86 / 164 6 / 71 comprises about 95 mol% of Crystalline Form C, about 2.5 mol% of psilocin and about 2.5 mol% of psilocybin. In one embodiment, Crystalline Form C is a cocrystal formed between psilocin and psilocybin. In another embodiment, Crystalline Form C is a salt formed between psilocin and psilocybin.

[00015] In one embodiment, the present invention provides a method of treating or improving a disease or disorder by administering to an individual a composition comprising a crystalline form of psilocin and psilocybin, thereby treating the disease or disorder.

[00016] In one modality, the disease or disorder is either a mental health disorder or a central nervous system (CNS) disorder. In one modality, the mental health disorder is selected from depressive disorders, anxiety disorders, post-traumatic stress disorder, and addiction disorders. In one modality, the CNS disorder is selected from chronic pain disorders and cognitive disorders.

[00017] In one embodiment, the present invention provides a method of stimulating neurogenesis or neurite growth comprising administering to an individual a composition comprising a crystalline form of psilocin and psilocybin, thereby stimulating neurogenesis or neurite growth. In some embodiments, stimulation of neurogenesis or neurite growth results in an increase in neuronal length. DESCRIPTION OF THE DRAWINGS

[00018] Figure 1 shows an X-ray diffractogram (XRPD) graph of the powder of Crystalline Form A.

[00019] Figure 2 shows an XRPD plot of Crystalline Form B.

[00020] Figure 3 shows an XRPD plot of the crystalline form. Petition 870260077978, dated 05 / 08 / 2026, page 87 / 164 7 / 71 W.

[00021] Figure 4 shows the thermogram graph of thermogravimetry coupled with mass spectrometry (TGMS) of crystalline Form A.

[00022] Figure 5 shows the differential scanning calorimetry (DSC) thermogram graph of Crystalline Form A.

[00023] Figure 6 shows the TGMS thermogram graph of Crystalline Form B.

[00024] Figure 7 shows the DSC thermogram graph of Crystalline Form B.

[00025] Figure 8 shows the TGMS thermogram graph of the crystalline form C.

[00026] Figure 9 shows the DSC thermogram graph of the crystalline form C.

[00027] Figure 10 shows the 1H-NMR of the crystalline form A and psilocybin.

[00028] Figure 11 shows the Ή-NMR of crystalline form A and psilocybin between 6 ppm and 7.5 ppm.

[00029] Figure 12 shows the Ή-NMR of crystalline Form A, of Crystalline form B of psilocybin.

[00030] Figure 13 shows the Ή-NMR of crystalline Form A, of Crystalline form B of psilocybin between 6 ppm and 7.5 ppm.

[00031] Figure 14 shows the dynamic vapor sorption (DVS) isotherm of Crystalline Form A.

[00032] Figure 15 shows the DVS isotherm of crystalline Form B.

[00033] Figure 16 shows the DVS isotherm of crystalline Form C.

[00034] Figure 17 shows the HPLC chromatogram of Crystalline Form A. Petition 870260077978, dated 05 / 08 / 2026, page 88 / 164 8 / 71

[00035] Figure 18 shows the HPLC chromatogram of crystalline form B.

[00036] Figure 19 shows the HPLC chromatogram of the crystalline form C.

[00037] Figure 20 shows the molecular structure and atom numbering scheme for the Psilocin-Psilocybin pair, obtained from simulated annealing based on diffraction data from the Crystalline Form A powder.

[00038] Figure 21 shows the crystal clustering scheme and H-bonds in the crystal of Crystalline Form A along the [1 0 0] direction.

[00039] Figure 22 shows the graphical representation of the final Rietveld refinement cycles for crystal form A.

[00040] Figure 23 shows h5HT2a-dependent Ca2+ release. Compound activity was quantified as Ca2+ release from CHO-K1 cells that stably express h5HT2a and treated with isolated compounds at 0.1 nM - 10 μM (left); or (right) an equimolar 1:1 combination of psilocin and psilocybin.

[00041] Figure 24 shows the h5HT2a-dependent recruitment of parrestin 2. The activity of the compound was quantified as parrestin 2 recruitment from h5HT2a-expressing CHO-K1 cells treated with compounds at 0.1 nM - 10 μM.

[00042] Figure 25 shows the binding to [3H]cetanserin, the affinity of the compound was estimated using membranes of CHO-K1 cells that stably express h5HT2a and incubated with compounds at 0.1 nM - 10 μM, for 2 h.

[00043] Figure 26 shows the physiological changes in C57BL / 6 mice. The activity of the compound was quantified in C57BL / 6 mice for catalepsy (10 min) (top), nociception in the tail flick test for latency (15 min) (middle) and Petition 870260077978, dated 05 / 08 / 2026, p. 89 / 164 9 / 71 Body temperature relative to baseline (20 min) (bottom).

[00044] Figure 27 shows the head twitch response in C57BL / 6 mice, the rodent-modeled hallucination was quantified in C57BL / 6 mice, from 0 to 10 minutes after compound administration (ip), with the observed head twitch time courses per minute being presented for LSD (top), psilocin (middle) and psilocybin (bottom).

[00045] Figure 28 shows the Open Field Test in C57BL / 6 mice, the activity of the compound was quantified in C57BL / 6 mice for the OFT, 30 minutes after treatment, regarding the total distance traveled (top left), speed (middle left) and time in the central quadrant (bottom left), with movement traces representative of Ethovision in male C57BL / 6 mice (right).

[00046] Figure 29 shows the EPM in C57BL / 6 mice. The activity of the compound was quantified in C57BL / 6 mice for the EPM, 30 min after treatment, regarding the total distance traveled and speed (top left), time in each arm of the EPM (bottom left), number of entries in the arm (bottom right). Representative movement traces of Ethovision in male C57BL / 6 mice (top right).

[00047] Figure 30 shows the pharmacokinetic quantification of psilocin in C57BL / 6 mouse plasma. Validation of the HPLC-MS / MS method to date has included internal standard selection (top left), voltage optimization (top right), solvent optimization to organize the mobile phase (middle, top), fragmentation and standard curve creation (middle, bottom), with an example chromatogram from mouse plasma shown in the bottom panel.

[00048] Figure 31 shows the EdU+ / NeuN+ / EdU+ data after Petition 870260077978, dated 05 / 08 / 2026, page 90 / 164 10 / 71 treatment with psilocybin and / or psilocin.

[00049] Figure 32 shows Ki67+ data after treatment with psilocybin and / or psilocin.

[00050] Figure 33 shows data from Sox2-positive cells after treatment with psilocybin and / or psilocin.

[00051] Figure 34 shows the results of neurite growth after treatment with psilocybin and / or psilocin. DETAILED DESCRIPTION

[00052] The present invention is based on the important discovery that psilocybin and psilocin form crystalline forms and, specifically, that crystalline forms of a composition comprising psilocybin and psilocin may be useful for treating certain mental health disorders and central nervous system disorders, as well as for stimulating neurogenesis.

[00053] Before the present compositions and methods are described, it should be understood that this invention is not limited to the particular processes, formulations, compositions, or methodologies described, as these may vary. It should also be understood that the terminology used in the description is only to describe particular versions or embodiments and is not intended to limit the scope of the embodiments contained herein, which will be limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used in this document have the same meanings as commonly understood by one of ordinary skill in the art. Although any methods and materials similar or equivalent to those described in this document may be used in the practice or testing of the embodiments contained herein, preferred methods, devices, and materials are now described.All posts mentioned in this document are incorporated by reference in their entirety. Nothing contained herein should be... Petition 870260077978, dated 05 / 08 / 2026, p. 91 / 164 11 / 71 interpreted as an admission that the embodiments contained herein do not have the right to precede such disclosure by virtue of prior invention.

[00054] It should also be noted that, as used in this document and the accompanying claims, the singular forms a, an, oea include the plural reference, unless the context clearly dictates otherwise.

[00055] The transition term comprising, which is synonymous with including, containing, or characterized by, is inclusive or unlimited and does not exclude additional elements or steps of the method not described.

[00056] As used in this document, the term consists of or consisting of means that the composition, formulation or method includes only the elements, steps or ingredients specifically described in the particular embodiment or claim.

[00057] As used in this document, the term essentially consisting of or essentially consists of means that the composition, formulation or method includes only the elements, steps or ingredients specifically described in the particular embodiment or claim and may optionally include additional elements, steps or ingredients that do not materially affect the basic and novel characteristics of the particular embodiment or claim. For example, the only active ingredient(s) in the formulation or method that treats the specified condition (e.g., nutrient depletion) is / are the therapeutic(s) specifically described in the particular embodiment or claim.

[00058] As used in this document, two modalities are mutually exclusive when one is defined as being something that is different from the other. Petition 870260077978, dated 05 / 08 / 2026, p. 92 / 164 12 / 71

[00059] When ranges of values ​​are disclosed, and the notation n1...to n2 or between n1...to n2 is used, where n1 and n2 are the numbers, then, unless otherwise specified, this notation is intended to include the numbers themselves and the range between them. This range may be integral or continuous between, and including, the final values. As an example, the range 1 °C to 3 °C, which is intended to include 1 °C, 3 °C and everything in between for any number of significant digits (e.g., 1.255 °C, 2.1 °C, 2.9999 °C etc.).

[00060] As used in this document, the term about means more or less 10% of the numerical value of the number with which it is being used. Therefore, about 50% means in the range of 45% to 55%. For example, about 100°C means a temperature in the range of 90°C to 110°C. For example, an angle 2Θ of about 10° means an angle 2Θ in the range of 9° to 11°.

[00061] The term substantially free, or as used in this document, alone or in combination, and is used interchangeably with the term substantially pure, refers to a compound that is free from all other compounds within the detection limits, as measured by any means, including nuclear magnetic resonance (NMR), gas chromatography / mass spectrometry (GC / MS), or liquid chromatography / mass spectrometry (LC / MS). In the embodiments, substantially free may be less than about 1.0%, less than about 0.5%, less than about 0.4%, less than about 0.3%, less than about 0.2%, less than about 0.1%, less than about 0.05%, or less than about 0.01%. Crystalline Forms

[00062] This disclosure includes the modalities directed to a composition comprising a crystalline form of psilocin and psilocybin: Petition 870260077978, dated 05 / 08 / 2026, p. 93 / 164 13 / 71 psilocin psilocybin

[00063] In some embodiments, the crystalline form of the composition comprising psilocin and psilocybin is Crystalline Form A.

[00064] In some embodiments, Crystal Form A is distinguished by an XRPD pattern comprising a significant peak at a 2θ angle of about 10.1°. In some embodiments, the XRPD pattern of Crystal Form A may additionally comprise a significant peak at a 2θ angle of about 19.16°. In some embodiments, the XRPD pattern of Crystal Form A may additionally comprise significant peaks at 2Θ angles of about 10.74°, about 25.3°, and about 24.07°. In some embodiments, the XRPD pattern of Crystal Form A may additionally comprise significant peaks at 2Θ angles of about 14.54°, about 16.5°, about 13.44°, about 23.42°, and about 8.62°. In some embodiments, the A crystal form is distinguished by an XRPD pattern as shown in Figure 1.

[00065] In one embodiment, Crystalline Form A has a TGMS thermograph that corresponds substantially to the representative TGMS thermogram, as shown in Figure 4. In some embodiments, an insignificant weight loss is observed. Weight loss (1.3%) is observed between 40-200 °C by TGMS for Crystalline Form A.

[00066] In one embodiment, Crystalline Form A has a DSC thermogram that corresponds substantially to that shown in Figure 5. In certain embodiments, Crystalline Form A is distinguished by a DSC graph comprising a pronounced endothermic event at a temperature of about 255°C.

[00067] In some embodiments, the Crystalline Form A has a Petition 870260077978, dated 05 / 08 / 2026, p. 94 / 164 14 / 71 psilocybin to psilocin ratio of approximately 1:1, approximately 1.1:1, approximately 1.2:1, approximately 1.3:1, approximately 1.4:1, approximately 1.5:1, approximately 1.6:1, approximately 1.7:1, approximately 1.8:1, approximately 1.9:1, approximately 2:1, approximately 1:1.1, approximately 1:1.2, approximately 1:1.3, approximately 1:1.4, approximately 1:1.5, approximately 1:1.6, approximately 1:1.7, approximately 1:1.8, approximately 1:1.9, or approximately 1:2. In some embodiments, Crystalline Form A has a psilocybin to psilocin ratio of approximately 1:1.

[00068] In some embodiments, Crystalline Form A has a chemical purity of about 95% or more, is about 96% or more, is about 97% or more, is about 98% or more, is about 98.5% or more, is about 99% or more, is about 99.5% or more, or is about 99.8% or more. In some embodiments, Crystalline Form A is substantially pure.

[00069] In some embodiments, Crystalline Form A contains no more than about 0.01 mol%, about 0.02 mol%.about 0.03% by mol, about 0.04% by mol, about 0.05% by mol, about 0.06% by mol, about 0.07% by mol, about 0.08% by mol, about 0.09% by mol, about 0.1% by mol, about 0.15% by mol, about 0.2% by mol, about 0.25% by mol, about 0.3% by mol, about 0.35% by mol, about 0.4% by mol, about 0.45% by mol, about 0.5% by mol, about 0.55% by mol, about 0.6% by mol, about 0.65% by mol, about 0.7% by mol, about 0.75% by mol, about 0.8% by mol, about 0.85% by mol, search for 0.9 % em mol, search for 0.95 % em mol, search for 1 % em mol, search for 2 % em mol, search for 3 % em mol, search for 4 % em mol, search for 5 % em mol, search for 6 % em mol, search for 7 % em mol, search for 8 % em mol, search for 9 % em mol, search for 10 % em mol, search for % em mol, search for 12 % em mol, search for 13% in mol, search for % in mol, search for 15% in mol, search for 16% in mol, search in % in mol, search for 18% in mol, search for 19% in mol, search. Petition 870260077978, dated 05 / 08 / 2026, p. 95 / 164 15 / 71 mol% of other solid forms, for example, amorphous form. In some embodiments, Crystalline Form A is substantially free of other solid forms.

[00070] In some embodiments, the composition of Psilocin and Psilocybin Crystalline Form A comprises about 99 mol% of Crystalline Form A, about 0.5 mol% of psilocin and about 0.5 mol% of psilocybin; about 98 mol% of Crystalline Form A, about 1.0 mol% of psilocin and about 1.0 mol% of psilocybin; about 97 mol% of Crystalline Form A, about 1.5 mol% of psilocin and about 1.5 mol% of psilocybin; about 96 mol% of Crystalline Form A, about 2.0 mol% of psilocin and about 2.0 mol% of psilocybin; approximately 95 mol% of crystalline form A, approximately 2.5 mol% of psilocin and approximately 2.5 mol% of psilocybin; approximately 94 mol% of crystalline form A, approximately 3.0 mol% of psilocin and approximately 3.0 mol% of psilocybin; approximately 93 mol% of crystalline form A, approximately 3.5 mol% of psilocin and approximately 3.5 mol% of psilocybin;approximately 92 mol% of crystalline form A, approximately 4.0 mol% of psilocin and approximately 4.0 mol% of psilocybin; approximately 91 mol% of crystalline form A, approximately 4.5 mol% of psilocin and approximately 4.5 mol% of psilocybin; or approximately 90 mol% of crystalline form A, approximately 5.0 mol% of psilocin and approximately 5.0 mol% of psilocybin.

[00071] In some embodiments, the crystalline form A is anhydrous.

[00072] In some embodiments, Crystalline Form A is a salt formed between psilocin and psilocybin.

[00073] In some embodiments, Crystalline Form A is a cocrystal formed between psilocin and psilocybin.

[00074] Some modalities are directed to a composition comprising a crystalline form of psilocin and psilocybin: Petition 870260077978, dated 05 / 08 / 2026, p. 96 / 164 16 / 71 psilocin psilocybin in which the crystalline form A is distinguished by unit cell parameters that are substantially the same as follows: Unit cell dimensions: a = 9.3674(3) A b = 11.2660(6) A c = 24.2741(9) A α = 90 degrees β = 90 degrees γ = 90 degrees Space group = P212121 Molecules / asymmetric unit = 1

[00075] In some embodiments, the unit cell parameters were measured around 296 K.

[00076] In some embodiments, Crystalline Form A has a hydrogen bonding geometry substantially as listed in Table A. Table A DH,,,A DH [A] H,,,A [A] D,,,A [A] DH...A [°] O1-H1.N23i 0.88(2) 1.60(2) 2.46(2) 162(2) N11-H11...O3 0.96(5) 2.17(4) 2.97(4) 140(6) N17-H17...O2 0.85(7) 1.83(7) 2.59(6) 147(8) N28-H28...O1iv 0.87(7) 2.32(6) 3.13(5) 153(10) O34-H34...O3v 0.88(10) 1.69(8) 2.49(7) 151(5)

[00077] In some embodiments, the Crystalline Form A has atomic coordinates of atoms other than hydrogen that are substantially Petition 870260077978, dated 05 / 08 / 2026, page 97 / 164 17 / 71 as listed in Table B. Table B xyz U(eq) O1 0.1251(14) 0.0326(16) 0.4198(4) 0.0253 O2 0.077(3) 0.0094(13) 0.3153(5) 0.0253 O3 0.190(3) 0.190(2) 0.3483(6) 0.0253 P4 0.0916(7) 0.0915(7) 0.3636(3) 0.0253 O5 -0.054(2) 0.157(3) 0.3724(5) 0.0253 C6 -0.1818(8) 0.102(5) 0.3771(8) 0.0253 C7 -0.221(2) 0.009(6) 0.4089(13) 0.0253 C8 -0.357(3) -0.030(9) 0.4084(19) 0.0253 C9 -0.466(2) 0.022(11) 0.375(2) 0.0253 C10 -0.4261(9) 0.116(10) 0.3436(15) 0.0253 N11 -0.512(3) 0.188(12) 0.3068(16) 0.0253 C12 -0.386(5) 0.277(10) 0.2836(13) 0.0253 C13 -0.265(4) 0.250(7) 0.3069(10) 0.0253 C14 -0.2791(18) 0.156(7) 0.3445(10) 0.0253 C15 -0.139(6) 0.313(5) 0.2890(13) 0.0253 C16 -0.082(4) 0.261(6) 0.2343(10) 0.0253 N17 0.054(6) 0.324(5) 0.2219(15) 0.0253 C18 0.140(5) 0.246(6) 0.1809(13) 0.0253 C19 0.146(7) 0.370(3) 0.269(2) 0.0253 C21 0.8842(18) 0.5884(19) 0.9383(6) 0.0253 C22 0.7490(17) 0.7295(10) 0.9827(10) 0.0253 N23 0.8087(12) 0.6116(8) 0.9893(5) 0.0253 C24 0.7012(15) 0.5244(13) 1.0037(8) 0.0253 C25 0.591(2) 0.533(3) 0.9591(11) 0.0253 C26 0.508(4) 0.422(3) 0.9490(17) 0.0253 C27 0.543(5) 0.306(3) 0.963(2) 0.0253, Petition 870260077978, dated 05 / 08 / 2026, page 98 / 164 18 / 71 N28 0.435(7) 0.236(4) 0.942(3) 0.0253 C29 0.337(7) 0.302(6) 0.917(3) 0.0253 C30 0.212(8) 0.268(7) 0.891(3) 0.0253 C31 0.124(7) 0.356(9) 0.868(3) 0.0253 C32 0.161(6) 0.474(8) 0.872(3) 0.0253 C33 0.292(5) 0.508(6) 0.899(3) 0.0253 O34 0.330(4) 0.628(6) 0.906(3) 0.0253 C35 0.379(5) 0.422(5) 0.920(2) 0.0253

[00078] In some embodiments, Crystalline Form A has atomic coordinates of hydrogen atoms substantially as listed in Table C. Table C xyz U(eq) H1 0.1396(11) 0.074(2) 0.4502(3) 0.0253 H7 -0.151(3) -0.029(5) 0.4319(14) 0.0253 H8 -0.379(5) -0.097(9) 0.431(2) 0.0253 H9 -0.563(3) -0.005(13) 0.374(2) 0.0253 H11 -0.612(2) 0.172(14) 0.3030(19) 0.0253 H12 -0.389(6) 0.337(10) 0.2556(15) 0.0253 H15A -0.075(5) 0.294(4) 0.3185(12) 0.0253 H15B -0.147(8) 0.398(5) 0.2858(18) 0.0253 H16A -0.146(5) 0.280(7) 0.2048(11) 0.0253 H16B -0.074(3) 0.176(5) 0.2375(8) 0.0253 H17 0.041(8) 0.386(5) 0.2026(19) 0.0253 H18A 0.205(4) 0.181(6) 0.1844(12) 0.0253 H18B 0.203(6) 0.295(7) 0.1601(17) 0.0253 H18C 0.075(4) 0.206(7) 0.1563(10) 0.0253 H19A 0.213(7) 0.336(3) 0.2941(19) 0.0253 H19B 0.086(8) 0.405(2) 0.296(2) 0.0253 Petition 870260077978, dated 05 / 08 / 2026, p. 99 / 164 19 / 71 H19C 0.211(9) 0.429(4) 0.255(2) 0.0253 H21A 0.951(2) 0.627(3) 0.9141(7) 0.0253 H21B 0.817(3) 0.575(3) 0.9093(5) 0.0253 H21C 0.944(2) 0.520(2) 0.9427(10) 0.0253 H22A 0.778(2) 0.8072(10) 0.9708(14) 0.0253 H22B 0.715(2) 0.7579(14) 1.0176(12) 0.0253 H22C 0.6710(17) 0.7266(16) 0.9571(11) 0.0253 H24A 0.6599(17) 0.542(2) 1.0390(8) 0.0253 H24B 0.742(2) 0.4463(11) 1.0054(11) 0.0253 H25A 0.635(3) 0.565(3) 0.9267(9) 0.0253 H25B 0.5179(14) 0.587(3) 0.9706(16) 0.0253 H27 0.629(5) 0.2905(18) 0.984(3) 0.0253 H28 0.436(8) 0.159(4) 0.946(4) 0.0253 H30 0.186(9) 0.185(8) 0.890(4) 0.0253 H31 0.037(8) 0.334(10) 0.851(4) 0.0253 H32 0.100(6) 0.533(9) 0.856(4) 0.0253 H34 0.294(4) 0.682(7) 0.884(3) 0.0253

[00079] In some embodiments, the crystalline form of the composition comprising psilocin and psilocybin is Crystalline Form B.

[00080] In some embodiments, Crystal Form B is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 18.54°. In some embodiments, Crystal Form B is distinguished by an XRPD pattern of Crystal Form B that may additionally comprise a significant peak at a 2Θ angle of about 8.54°. In some embodiments, Crystal Form B is distinguished by an XRPD pattern of Crystal Form B that may additionally comprise significant peaks at 2Θ angles of about 22.78°, about 14.27°, and about 21.12°. In some embodiments, Crystal Form B is distinguished by an XRPD pattern of Crystal Form B that may additionally comprise significant peaks at Petition 870260077978, dated 05 / 08 / 2026, pp. 100 / 164 20 / 71 angles 2θ of approximately 14.12°, approximately 10.05°, approximately 9.94°, approximately 24.94°, and approximately 25.02°. In some embodiments, the B crystal form is distinguished by an XRPD pattern of Figure 2.

[00081] In one embodiment, Crystalline Form B has a TGMS thermograph that corresponds substantially to the representative TGMS thermogram, as shown in Figure 6. In some embodiments, an insignificant weight loss is observed. Weight loss (15.8%) is observed between 40-200 °C by TGMS for Crystalline Form B.

[00082] In one embodiment, Crystalline Form B has a DSC thermogram that corresponds substantially to that shown in Figure 7. In certain embodiments, Crystalline Form B is distinguished by a DSC graph comprising a large endothermic event at a temperature of about 168.2°C.

[00083] In some embodiments, Crystalline Form B has a psilocybin to psilocin ratio of about 1:1, about 1.1:1, about 1.2:1, about 1.3:1, about 1.4:1, about 1.5:1, about 1.6:1, about 1.7:1, about 1.8:1, about 1.9:1, about 2:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9 or about 1:2. In some embodiments, Crystalline Form B has a psilocybin to psilocin ratio of about 1.3:1. In some forms, the crystalline form B has a psilocybin to psilocin ratio of approximately 1:1.

[00084] In some embodiments, Crystalline Form B has a chemical purity of about 95% or greater, is about 96% or greater, is about 97% or greater, is about 98% or greater, is about 98.5% or greater, is about 99% or greater, is about 99.5% or greater, or is about 99.8% or greater. In some embodiments, Crystalline Form B is substantially pure. Petition 870260077978, dated 05 / 08 / 2026, pp. 101 / 164 21 / 71

[00085] In some embodiments, the crystalline form B contains no more than about 0.01 mol%, about 0.02 mol%. about 0.03 mol%, about 0.04 mol%, about 0.05 mol%, about 0.06 mol%, about 0.07 mol%, about 0.08 mol%, about 0.09 mol%, about 0.1 mol%, about 0.15 mol%, about from 0.2 mol%, about 0.25 mol%, about 0.3 mol%, about 0.35 mol%, about 0.4 mol%, about 0.45 mol%, about 0.5 mol%, about 0.55 mol%, about 0.6 mol%, about 0.65 mol%, approx. 0.7 mol%, about 0.75 mol%, about 0.8 mol%, about 0.85 mol%, about 0.9 mol%, about 0.95 mol%, about 1 mol%, about 2 mol%, about 3 mol%, about 4 mol%, about 5 mol%, about 6 mol%, about 7 mol%, about 8 mol%, about 9 mol%, about 10 mol%, about mol%, about 12 mol%, about 13 mol%,approximately % by mol, approximately 15% by mol, approximately 16% by mol, approximately % by mol, approximately 18% by mol, approximately 19% by mol, approximately % by mol, of other solid forms, for example, amorphous form. In some embodiments, Crystalline Form B is substantially free of other solid forms.

[00086] In some embodiments, the B crystalline form is anhydrous.

[00087] In some embodiments, the crystalline form B is a salt formed between psilocin and psilocybin.

[00088] In some embodiments, Crystalline Form B is a cocrystal formed between psilocin and psilocybin.

[00089] In some embodiments, the crystalline form of the composition comprising psilocin and psilocybin is Crystalline Form C.

[00090] In some embodiments, the C crystal form is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of approximately 9.18°. In some embodiments, the Form Petition 870260077978, dated 05 / 08 / 2026, pp. 102 / 164 Crystalline form C is distinguished by an XRPD pattern of Crystalline form C that may additionally comprise a significant peak at a 2Θ angle of about 17.95°. In some embodiments, Crystalline form C is distinguished by an XRPD pattern of Crystalline form C that may additionally comprise significant peaks at 2Θ angles of about 10.42°, about 24.22°, and about 18.38°. In some embodiments, Crystalline form C is distinguished by an XRPD pattern of Crystalline form C that may additionally comprise significant peaks at 2Θ angles of about 19.82°, about 17.46°, about 14.82°, about 22.38°, and about 14.06°. In some embodiments, Crystalline form C is distinguished by an XRPD pattern as shown in Figure 3.

[00091] In one embodiment, Crystalline Form C has a TGMS thermograph that corresponds substantially to the representative TGMS thermogram, as shown in Figure 8. In some embodiments, an insignificant weight loss is observed. Weight loss (13.5%) is observed between 40-160 °C by TGMS for Crystalline Form C.

[00092] In one embodiment, the C crystal form has a DSC thermogram that corresponds substantially to that shown in Figure 9. In certain embodiments, the C crystal form is distinguished by a DSC graph comprising a large endothermic event at a temperature of about 25-140°C, with a peak at 98.7°C.

[00093] In some embodiments, Crystalline Form C has a psilocybin to psilocin ratio of about 1:1, about 1.1:1, about 1.2:1, about 1.3:1, about 1.4:1, about 1.5:1, about 1.6:1, about 1.7:1, about 1.8:1, about 1.9:1, about 2:1, about 1:1.1, about 1:1.2, about 1:1.3, about 1:1.4, about 1:1.5, about 1:1.6, about 1:1.7, about 1:1.8, about 1:1.9 or about 1:2. In some embodiments, Crystalline Form C has a psilocybin to psilocin ratio of about 1:1. Petition 870260077978, dated 05 / 08 / 2026, pp. 103 / 164 23 / 71

[00094] In some embodiments, the C crystalline form has a chemical purity of about 95% or more, is about 96% or more, is about 97% or more, is about 98% or more, is about 98.5% or more, is about 99% or more, is about 99.5% or more, or is about 99.8% or more. In some embodiments, the C crystalline form is substantially pure.

[00095] In some embodiments, the crystalline form C contains no more than about 0.01 mol%, about 0.02 mol%. about 0.03 mol%, about 0.04 mol%, about 0.05 mol%, about 0.06 mol%, about 0.07 mol%, about 0.08 mol%, about 0.09 mol%, about 0.1 mol%, about 0.15 mol%, about from 0.2 mol%, about 0.25 mol%, about 0.3 mol%, about 0.35 mol%, about 0.4 mol%, about 0.45 mol%, about 0.5 mol%, about 0.55 mol%, about 0.6 mol%, about 0.65 mol%, approx. 0.7 mol%, about 0.75 mol%, about 0.8 mol%, about 0.85 mol%, about 0.9 mol%, about 0.95 mol%, about 1 mol%, about 2 mol%, about 3 mol%, about 4 mol%, about 5 mol%, about 6 mol%, about 7 mol%, about 8 mol%, about 9 mol%, about 10 mol%, about mol%, about 12 mol%, about 13 mol%,approximately % by mole, approximately 15% by mole, approximately 16% by mole, approximately % by mole, approximately 18% by mole, approximately 19% by mole, approximately % by mole, of other solid forms, for example, amorphous form. In some embodiments, the crystalline form C is substantially free of other solid forms.

[00096] In some embodiments, the C crystalline form is anhydrous.

[00097] In some embodiments, the crystalline form C is a salt formed between psilocin and psilocybin.

[00098] In some embodiments, the C crystal form is a Petition 870260077978, dated 05 / 08 / 2026, pp. 104 / 164 24 / 71 cocrystal formed between psilocin and psilocybin. Pharmaceutical Compositions

[00099] In one embodiment, the present application provides a pharmaceutical composition comprising a crystalline form of psilocin and psilocybin and a pharmaceutically acceptable excipient. [000100] In one embodiment, the crystalline form is Crystalline Form A, Crystalline Form B, or Form C. In one embodiment, Crystalline Form A is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 10.1°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 19.16°; at 2Θ angles of about 10.74°, about 25.3°, and about 24.07°; and / or the XRPD pattern further comprises a significant peak at 2Θ angles of about 14.54°, about 16.5°, about 13.44°, about 23.42°, and about 8.62°. In one embodiment, Crystalline Form A has a psilocybin to psilocin ratio of about 1:1. In one embodiment, Crystalline Form A has a chemical purity of about 95% or more. In some embodiments, the pharmaceutical composition of Crystalline Form A contains no more than about 5 mol% of other solid forms.In some embodiments, the pharmaceutical composition of Psilocin and Psilocybin Crystalline Form A comprises about 95 mol% of Crystalline Form A, about 2.5 mol% of psilocin, and about 2.5 mol% of psilocybin. In one embodiment, Crystalline Form A is a cocrystal formed between psilocin and psilocybin. In another embodiment, Crystalline Form A is a salt formed between psilocin and psilocybin. [000101] In one embodiment, Crystalline Form A is distinguished by unit cell parameters that are substantially the same as the following: Unit cell dimensions: a = 9.3674(3) A Petition 870260077978, dated 05 / 08 / 2026, pp. 105 / 164 25 / 71 b = 11.2660(6) À c = 24.2741(9) À α = 90 degrees β = 90 degrees γ = 90 degrees Space group = P2i2i2i Molecules / asymmetric unit = 1 [000102] In one embodiment, the unit cell parameters were measured around 296K. In one embodiment, Crystalline Form A has a hydrogen bond geometry substantially as listed in Table A. In one embodiment, Crystalline Form A has atomic coordinates of non-hydrogen atoms substantially as listed in Table B. In one embodiment, Crystalline Form A has atomic coordinates of hydrogen atoms substantially as listed in Table C. In one embodiment, Crystalline Form A is a cocrystal formed between psilocin and psilocybin. In one embodiment, Crystalline Form A is a salt formed between psilocin and psilocybin. [000103] In one embodiment, Crystalline Form B is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 18.54°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 8.54°; the XRPD pattern further comprises a significant peak at 2θ angles of about 22.78°, about 14.27° and about 21.12° and / or the XRPD pattern further comprises a significant peak at 2Θ angles of about 14.12°, about 10.05°, about 9.94°, about 24.94° and about 25.02°. In one embodiment, Crystalline Form B has a psilocybin to psilocin ratio of about 1.3:1. In one embodiment, Crystalline Form B has a psilocybin to psilocin ratio of approximately 1:1. In another embodiment, Crystalline Form B has a chemical purity of Petition 870260077978, dated 05 / 08 / 2026, pp. 106 / 164 26 / 71 approximately 95% or more. In some embodiments, the pharmaceutical composition of Crystalline Form B contains no more than about 5 mol% of other solid forms. In some embodiments, the pharmaceutical composition of Crystalline Form B of psilocin and psilocybin comprises about 95 mol% of Crystalline Form B, about 2.5 mol% of psilocin, and about 2.5 mol% of psilocybin. In one embodiment, Crystalline Form B is a cocrystal formed between psilocin and psilocybin. In one embodiment, Crystalline Form B is a salt formed between psilocin and psilocybin. [000104] In one embodiment, Crystalline Form C is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 9.18°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 17.95°; the XRPD pattern further comprises a significant peak at 2θ angles of about 10.42°, about 24.22° and about 18.38°; and / or the XRPD pattern further comprises a significant peak at 2θ angles of about 19.82°, about 17.46°, about 14.82°, about 22.38° and about 14.06°. In one embodiment, Crystalline Form C has a psilocybin to psilocin ratio of about 1:1. In one embodiment, the Crystalline Form C has a chemical purity of about 95% or more. In some embodiments, the pharmaceutical composition of the Crystalline Form C contains no more than about 5 mol% of other solid forms.In some embodiments, the pharmaceutical composition of the C-shaped crystalline form of psilocin and psilocybin comprises about 95 mol% of C-shaped crystalline form, about 2.5 mol% of psilocin, and about 2.5 mol% of psilocybin. In one embodiment, the C-shaped crystalline form is a cocrystal formed between psilocin and psilocybin. In another embodiment, the C-shaped crystalline form is a salt formed between psilocin and psilocybin. [000105] As used in this document, composition Petition 870260077978, dated 05 / 08 / 2026, pp. 107 / 164 27 / 71 pharmaceutical refers to a formulation comprising an active ingredient and, optionally, a pharmaceutically acceptable vehicle, diluent, or excipient. The term active ingredient may refer interchangeably to an effective ingredient and is intended to refer to any agent capable of inducing a desired effect after administration. Examples of active ingredients include, but are not limited to, chemical compounds, drugs, therapeutic agents, small molecules, etc. In one embodiment, the active ingredient is a crystalline form of psilocybin and psilocin, such as Crystalline Form A, Crystalline Form B, or Form C described in this document. [000106] The terms excipient and pharmaceutically acceptable excipient, as used in this document, are intended to be generally synonymous and are used interchangeably with the terms vehicle, pharmaceutically acceptable vehicle, diluent, pharmaceutically acceptable diluent. By pharmaceutically acceptable it is understood that the vehicle, diluent or excipient must be compatible with the other ingredients of the formulation and not harmful to its recipient, nor to the activity of the active ingredient of the formulation. Pharmaceutically acceptable vehicles, excipients or stabilizers are well known in the art, for example, Remington's Pharmaceutical Sciences, 16th edition, Osol, A. Ed. (1980).Pharmaceutically acceptable vehicles, excipients, or stabilizers are not toxic to receptors at the dosages and concentrations used, and may include buffers such as phosphate, citrate, and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol; butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight polypeptides (less than about 10 residues); proteins. Petition 870260077978, dated 05 / 08 / 2026, pp. 108 / 164 Examples of carriers include, but are not limited to, liposomes, nanoparticles, ointments, micelles, microspheres, microparticles, creams, emulsions, and gels. Examples of carriers include: 28 / 71 such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates, including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or nonionic surfactants such as TWEEN®, PLURONICS®, or polyethylene glycol (PEG).Examples of excipients include, but are not limited to, anti-caking agents such as magnesium stearate; binders such as saccharides and their derivatives (sucrose, lactose, starches, cellulose, sugar alcohols and the like); proteins such as gelatin and synthetic polymers; lubricants such as talc and silica; and preservatives such as antioxidants, vitamin A, vitamin E, vitamin C, retinyl palmitate, selenium, cysteine, methionine, citric acid, sodium sulfate, and parabens. Examples of diluents include, but are not limited to, water, alcohol, saline solution, glycol, mineral oil, and dimethyl sulfoxide (DMSO). [000107] In one embodiment, the pharmaceutically acceptable excipient is selected from phosphate buffer; citrate buffer; ascorbic acid; methionine; octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenolic alcohol; butyl alcohol; benzyl alcohol; methylparaben; propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; m-cresol; low molecular weight polypeptides (less than about 10 residues); serum albumin; gelatin; immunoglobulins; polyvinylpyrrolidone glycine; glutamine; asparagine; histidine; arginine; lysine; monosaccharides; disaccharides; Petition 870260077978, dated 05 / 08 / 2026, pp. 109 / 164 29 / 71 glucose; mannose; dextrins; EDTA; trehalose, lactose, dextrose, sucrose, sorbitol, mannitol, starches, acacia gum, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methylcellulose, including eutectic solvents, eutectic-based ionic liquids, ionic liquids, sorbitol; sodium; saline solution; metallic surfactants; non-ionic surfactants; polyethylene glycol (PEG); magnesium stearate; water; alcohol; saline solution; glycol; mineral oil and dimethyl sulfoxide (DMSO). [000108] The active compound may be effective over a wide range of dosages and can generally be administered in a therapeutically effective amount. It will be understood, however, that the amount of the compound actually administered will normally be determined by a physician according to the relevant circumstances, including the condition being treated, the chosen route of administration, the actual compound administered, the age, weight and response of the individual patient, the severity of the patient's symptoms and the like. Treatment Method [000109] In one embodiment, the present invention provides a method of treating or improving a disease or disorder by administering to an individual a composition comprising a crystalline form of psilocin and psilocybin, thereby treating the disease or disorder. [000110] In one modality, the disease or disorder is selected from either a mental health disorder or a central nervous system (CNS) disorder. In one modality, the mental health disorder is selected from depressive disorders, anxiety disorders, post-traumatic stress disorder, and addiction disorders. In one modality, the CNS disorder is selected from chronic pain disorders and cognitive disorders. Petition 870260077978, dated 05 / 08 / 2026, pp. 110 / 164 30 / 71 [000111] In one embodiment, the present invention provides a method of stimulating neurogenesis or neurite growth, comprising administering to an individual a composition comprising a crystalline form of psilocin and psilocybin, thereby stimulating neurogenesis or neurite growth. In some embodiments, stimulation of neurogenesis or neurite growth results in an increase in neuronal length. [000112] In some modalities, stimulation of neurogenesis or neurite growth results in an improvement in impaired cognitive performance or other neurological performance associated with a central nervous system condition. In some modalities, the central nervous system condition is selected from Alzheimer's disease, Parkinson's disease, Huntington's chorea, senile dementia, Pick's disease, parkinsonian dementia syndrome, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonic epilepsy, sleep deprivation, depression, stroke, ischemia, brain trauma, psychological and physical trauma, chronic pain of any cause, cognitive disorders, and cognitive deterioration. [000113] In one embodiment, the crystalline form is Crystalline Form A, Crystalline Form B, or Crystalline Form C. In one embodiment, Crystalline Form A is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 10.1°; the XRPD pattern further comprises a significant peak at a 2θ angle of about 19.16°; at 2Θ angles of about 10.74°, about 25.3°, and about 24.07°; and / or the XRPD pattern further comprises a significant peak at 2Θ angles of about 14.54°, about 16.5°, about 13.44°, about 23.42°, and about 8.62°. In one embodiment, Crystalline Form A has a psilocybin to psilocin ratio of about 1:1. In one embodiment, the crystalline form A has a purity Petition 870260077978, dated 05 / 08 / 2026, pp. 111 / 164 31 / 71 chemical composition of about 95% or more. In some embodiments, Crystalline Form A contains no more than about 5 mol% of other solid forms. In some embodiments, the composition of Crystalline Form A of psilocin and psilocybin comprises about 95 mol% of Crystalline Form A, about 2.5 mol% of psilocin, and about 2.5 mol% of psilocybin. In one embodiment, Crystalline Form A is a cocrystal formed between psilocin and psilocybin. In one embodiment, Crystalline Form A is a salt formed between psilocin and psilocybin. [000114] In one embodiment, Crystalline Form A is distinguished by unit cell parameters that are substantially the same as the following: Unit cell dimensions: a = 9.3674(3) A b = 11.2660(6) A c = 24.2741(9) A α = 90 degrees β = 90 degrees γ = 90 degrees Space group = P212121 Molecules / asymmetric unit = 1 [000115] In one embodiment, the unit cell parameters were measured around 296K. In one embodiment, Crystal Form A has a hydrogen bond geometry substantially as listed in Table A. In one embodiment, Crystal Form A has atomic coordinates of non-hydrogen atoms substantially as listed in Table B. In one embodiment, Crystal Form A has atomic coordinates of hydrogen atoms substantially as listed in Table C. In one embodiment, Crystal Form A is a cocrystal formed between psilocin and Petition 870260077978, dated 05 / 08 / 2026, pp. 112 / 164 32 / 71 psilocybin. In one embodiment, the crystalline form A is a salt formed between psilocin and psilocybin. [000116] In one embodiment, Crystalline Form B is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 18.54°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 8.54°; the XRPD pattern further comprises a significant peak at 2θ angles of about 22.78°, about 14.27° and about 21.12° and / or the XRPD pattern further comprises a significant peak at 2Θ angles of about 14.12°, about 10.05°, about 9.94°, about 24.94° and about 25.02°. In one embodiment, Crystalline Form B has a psilocybin to psilocin ratio of about 1.3:1. In one embodiment, Crystalline Form B has a psilocybin to psilocin ratio of about 1:1. In another embodiment, Crystalline Form B has a chemical purity of about 95% or more. In some embodiments, Crystalline Form B contains no more than about 5 mol% of other solid forms.In some embodiments, the composition of the crystalline form B of psilocin and psilocybin comprises about 92 mol% of crystalline form B, about 2.5 mol% of psilocin, and about 2.5 mol% of psilocybin. In one embodiment, crystalline form B is a cocrystal formed between psilocin and psilocybin. In another embodiment, crystalline form B is a salt formed between psilocin and psilocybin. [000117] In one embodiment, the C crystal form is distinguished by an XRPD pattern comprising a significant peak at a 2Θ angle of about 9.18°; the XRPD pattern further comprises a significant peak at a 2Θ angle of about 17.95°; the XRPD pattern further comprises a significant peak at 2θ angles of about 10.42°, about 24.22° and about 18.38°; and / or the XRPD pattern further comprises a significant peak at 2θ angles of about 19.82°, about 17.46°, about 14.82°, about 22.38° and about Petition 870260077978, dated 05 / 08 / 2026, pp. 113 / 164 33 / 71 14.06°. In one embodiment, Crystalline Form C has a psilocybin to psilocin ratio of about 1:1. In one embodiment, Crystalline Form C has a chemical purity of about 95% or more. In some embodiments, Crystalline Form C contains no more than about 5 mol% of other solid forms. In some embodiments, the composition of the psilocin and psilocybin Crystalline Form C comprises about 95 mol% of Crystalline Form C, about 2.5 mol% of psilocin, and about 2.5 mol% of psilocybin. In one embodiment, Crystalline Form C is a cocrystal formed between psilocin and psilocybin. In one embodiment, Crystalline Form C is a salt formed between psilocin and psilocybin. [000118] The terms treat, treated, treating, or treatment, as used in this document, refer to both therapeutic treatment and prophylactic or preventive measures, where the objective is to prevent or delay (reduce) an undesirable physiological condition, disorder, or disease, or to obtain beneficial or desired clinical outcomes. For the purposes of this invention, beneficial or desired clinical outcomes include, but are not limited to, symptom relief; reduction in the extent of the condition, disorder, or disease; stabilization (i.e., non-worsening) of the state of the condition, disorder, or disease; delay in the onset or reduction in the progression of the condition, disorder, or disease; improvement in the state of the condition, disorder, or disease; and remission (whether partial or total, whether induction of or maintenance of, whether detectable or undetectable), or increase or improvement of the condition, disorder, or disease.Treatment aims to elicit a clinically significant response without excessive side effects. It also aims to prolong survival compared to the expected survival without treatment. Treatment can also be preemptive, meaning it can include disease prevention. (The prevention of a disease.) Petition 870260077978, dated 05 / 08 / 2026, pp. 114 / 164 34 / 71 may involve complete protection against the disease, for example, as in the case of preventing infection by a pathogen, or it may involve preventing the progression of the disease. For example, disease prevention may not mean the complete exclusion of any disease-related effects at any level, but instead may mean preventing the symptoms of a disease at a clinically significant or detectable level. Disease prevention may also mean preventing the progression of a disease to a later stage of the disease and prolonging disease-free survival compared to disease-free survival if treatment were not received. [000119] The term treatment is used in this document interchangeably with the term therapeutic method and refers both to 1) treatments or therapeutic measures that cure, slow down, reduce the symptoms of, and / or halt the progression of, a diagnosed pathological condition or disorder, and to 2) prophylactic / preventive measures. Those who need treatment may include individuals who already have a specific medical disorder, as well as those who may ultimately acquire the disorder (i.e., those who need preventive measures). [000120] The terms therapeutically effective amount, effective dose, therapeutically effective dose, effective quantity, or similar terms refer to the amount of the compound in question that will elicit the biological or medical response in a tissue, system, animal, or human being that is being sought by the researcher, veterinarian, physician, or other clinician. Generally, the response is an improvement in a patient's symptoms or a desired biological outcome (e.g., improvement in PTSD symptoms). The effective amount can be determined Petition 870260077978, dated 05 / 08 / 2026, pp. 115 / 164 35 / 71 as described in this document. [000121] The terms administration of and / or administering should be understood to mean providing a pharmaceutical composition in a therapeutically effective quantity to the individual requiring treatment. Routes of administration may be enteral, topical, or parenteral. As such, routes of administration include, but are not limited to, intracutaneous, subcutaneous, intravenous, intra-arterial, intraorbital, intracardiac, intradermal, transdermal, subarachnoid, intraspinal, oral, sublingual, buccal, rectal, nasal, and infusion administrations. Suitable unit dosage forms include, but are not limited to, powders, tablets, pills, capsules, lozenges, suppositories, patches, nasal sprays, injectables, implantable continuous-release formulations, lipid complexes, etc. [000122] The term patient is generally synonymous with the term guinea pig and includes all mammals, including humans. Examples of patients include humans, livestock such as cows, goats, sheep, pigs and rabbits, and companion animals such as dogs, cats, rabbits and horses. Preferably, the patient is a human being. [000123] Mental health disorders, or mental illnesses, refer to a wide range of disorders that include, but are not limited to, mood disorders, depressive disorders, mood instability disorders, mixed anxiety and depression disorder, bipolar disorders, anxiety disorders, generalized anxiety disorders, social anxiety disorders, phobic disorders, panic attack disorders, schizophrenia, psychosis, schizoaffective disorders, eating disorders, anorexia nervosa, bulimia nervosa, substance abuse disorders, addiction disorders, alcohol abuse or dependence, and substance abuse or dependence. Petition 870260077978, dated 05 / 08 / 2026, pages 116 / 164 36 / 71 narcotics, cocaine abuse or dependence, mixed drug abuse or dependence, behavioral addictions, gambling disorder, trauma-related disorders, post-traumatic stress disorder, bereavement-related disorders, loss-related disorders, end-of-life disorders, cancer disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), personality disorders, and obsessive-compulsive disorders, and any combinations thereof. The complete list of currently accepted mental health disorders is given in the Diagnostic and Statistical Manual, 5th Edition (DSM-5), which is incorporated by reference in this document in its entirety.Central nervous system (CNS) disorders include, but are not limited to, psychological and physical trauma following burns, injury or any other physical cause, post-amputation, post-brain injury, post-stroke, post-heart attack, post-diabetes, chronic pain disorders, migraines, chronic headaches, chronic back pain, chronic arthritic pain, chronic pain of any cause, cognitive disorders, cognitive decline, Alzheimer's disease, dementia at any stage, dementia of any cause, age-related memory decline, neuropsychiatric disorders, fetal alcohol spectrum disorders (FAS), autism spectrum disorders, multiple sclerosis, Parkinson's disease, Fragile X syndrome, Down syndrome, fatigue, chronic fatigue, insomnia of any cause, and all post-COVID syndromes.The severity of symptoms varies such that some individuals suffer from debilitating illness that prevents normal social functioning, while others suffer from intermittent, recurring episodes throughout their lives. Although the presentation and diagnostic criteria between mental illnesses and CNS conditions are distinct in part, there are important common endophenotypes between the diseases, and comorbidities are frequently present. Petition 870260077978, dated 05 / 08 / 2026, pp. 117 / 164 37 / 71 [000124] Specifically, there are phenotypic endophenotypes associated with alterations in mood, cognition, and behavior. Interestingly, many of these endophenotypes also extend to neurological conditions. For example, attention deficits are reported in patients with attention deficit disorder, attention deficit hyperactivity disorder, eating disorders, substance use disorders, schizophrenia, depression, obsessive-compulsive disorder, traumatic brain injury, Fragile X, Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. [000125] Depressive disorders are characterized by low mood, feelings of sadness or hopelessness, increased irritability, sleep disturbance, decreased energy and fatigue, poor concentration, decreased self-esteem or feelings of worthlessness, lack of interest or pleasure in things, slowed movement, thoughts that it would be better to be dead and self-harm, and actively considering and attempting suicide, and include major depressive disorder, bipolar depression, treatment-resistant depression, and dysthymic disorder. [000126] Anxiety disorders are characterized by feeling nervous, anxious, having difficulty breathing, avoiding people or activities, worrying excessively, physical symptoms including chest pain, heart palpitations, sweating, nausea, stomach pain, headache, neck pain, poor sleep, poor concentration, sweating and dizziness, and include generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, phobias and separation anxiety disorder. [000127] Post-traumatic stress disorder (PTSD) is characterized by flashbacks, nightmares, involuntary memories, emotional distress, or physical reactions after being reminded of the trauma, avoidance of anything that might trigger such memories, avoidance of Petition 870260077978, dated 05 / 08 / 2026, pp. 118 / 164 38 / 71 activities, social isolation, increased anger or aggression, increased irritability, participation in risky behavior, poor concentration, trouble sleeping, and an increased fear response, which can also be described as those with dissociated experiences. [000128] Substance abuse and dependence disorders are identified when an individual makes recurrent use of alcohol or drugs that cause significant deterioration in areas that negatively impact health, work, school, and home, with the severity depending on the type and frequency of substance use, social and interpersonal problems related to this use, impact on family, friends, work, school, and relationships, withdrawal symptoms, tolerance, unsuccessful attempts to stop, physical and mental health problems resulting from this use, and intense cravings, and include alcohol use disorder, marijuana use disorder, hallucinogen use disorder, inhalant use disorder, opioid use disorder, sedative-hypnotic or anxiolytic use disorder, stimulant use disorder, tobacco use disorder, and substance use disorder.with these disorders occurring alone or in combination. [000129] Chronic pain disorders are characterized by pain in one or more regions of the body, including headache, lower back pain, neck pain, arthritis pain, pain in the context of cancer, neurogenic pain, psychogenic pain, and include conditions such as chronic arthritis, osteoarthritis, chronic fatigue syndrome, endometriosis, fibromyalgia, inflammatory bowel disease, interstitial cystitis, temporomandibular joint dysfunction, vulvodynia, cluster headaches, migraine, herpes zoster, frozen shoulder, complex regional pain syndrome, gout, post-surgical pain syndrome, intervertebral disc prolapse, sciatica, and neuralgia. Petition 870260077978, dated 05 / 08 / 2026, pp. 119 / 164 39 / 71 triplet. [000130] Cognitive disorders are characterized by brain malfunction, such that memory and other functions deteriorate, including movement, speech, concentration and focus, problem-solving, sleep analysis, tremors, fatigue, dizziness, headaches, hallucinations, and confabulation, and include age-related memory deterioration, Alzheimer's disease, Picks' disease, vascular dementia, post-stroke dementia, multi-infarct dementia, Parkinson's disease, frontal lobe dementia, alcohol-induced dementia, and amnesia disorders, including Korsakoff's syndrome. [000131] Neurogenesis is a vital process in the brains of animals and humans, whereby new nerve cells are continuously generated throughout the organism's lifespan. These newly formed cells are able to differentiate into functional cells of the central nervous system and integrate into existing neural circuits in the brain. Stimulating neurogenesis, or neurite growth, can improve cognitive performance associated with various central nervous system conditions, such as depression and anxiety. [000132] In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided for use in the treatment of post-traumatic stress disorder (PTSD). In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided for use in the treatment of treatment-resistant PTSD. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant PTSD. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form B, is provided for use in the treatment of Petition 870260077978, dated 05 / 08 / 2026, pp. 120 / 164 40 / 71 Treatment-resistant PTSD. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant PTSD. In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant PTSD. In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form B, is provided for use in the treatment of treatment-resistant PTSD. In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant PTSD. [000133] In one embodiment, a method of treating PTSD is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In one embodiment, a method of treating treatment-resistant PTSD is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In one embodiment, a method of treating treatment-resistant PTSD is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A.In one embodiment, a treatment method for treatment-resistant PTSD is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form B. In another embodiment, a treatment method for treatment-resistant PTSD is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and... Petition 870260077978, dated 05 / 08 / 2026, pp. 121 / 164 41 / 71 psilocin, Crystalline form C. [000134] In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided for use in the treatment of depression. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided for use in the treatment of treatment-resistant depression. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant depression. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form B, is provided for use in the treatment of treatment-resistant depression. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant depression.In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant depression. In another embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form B, is provided for use in the treatment of treatment-resistant depression. In another embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant depression. [000135] In one embodiment, a method of treating depression is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In another embodiment, a method of treating treatment-resistant depression is provided comprising administering to an individual in need of it an effective dose of a Petition 870260077978, dated 05 / 08 / 2026, pp. 122 / 164 42 / 71 crystalline forms of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In one embodiment, a method of treating treatment-resistant depression is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A. In another embodiment, a method of treating treatment-resistant depression is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form B. In another embodiment, a method of treating treatment-resistant depression is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form C. [000136] In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided for use in the treatment of anxiety. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided for use in the treatment of treatment-resistant anxiety. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant anxiety. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form B, is provided for use in the treatment of treatment-resistant anxiety. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant anxiety.In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant anxiety. In another embodiment, a form is provided. Petition 870260077978, dated 05 / 08 / 2026, pp. 123 / 164 43 / 71 High-purity crystalline psilocybin and psilocin, Crystalline Form B, for use in the treatment of treatment-resistant anxiety. In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant anxiety. [000137] In one embodiment, a method of treating anxiety is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In one embodiment, a method of treating treatment-resistant anxiety is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In one embodiment, a method of treating treatment-resistant anxiety is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A.In one embodiment, a treatment method for treatment-resistant anxiety is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form B. In another embodiment, a treatment method for treatment-resistant anxiety is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form C. [000138] In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided for use in the treatment of pain. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof, is provided. Petition 870260077978, dated 05 / 08 / 2026, pp. 124 / 164 44 / 71 combinations thereof, for use in the treatment of treatment-resistant pain. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant pain. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form B, is provided for use in the treatment of treatment-resistant pain. In one embodiment, a crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant pain. In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form A, is provided for use in the treatment of treatment-resistant pain. In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form B, is provided for use in the treatment of treatment-resistant pain.In one embodiment, a high-purity crystalline form of psilocybin and psilocin, Crystalline Form C, is provided for use in the treatment of treatment-resistant pain. [000139] In one embodiment, a method of treating pain is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In one embodiment, a method of treating treatment-resistant pain is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A, Crystalline Form B, Crystalline Form C, or combinations thereof. In one embodiment, a method of treating treatment-resistant pain is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A. In one embodiment, a method of treating treatment-resistant pain is provided comprising administering to an individual in need of it an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form A. Petition 870260077978, dated 05 / 08 / 2026, pages 125 / 164 45 / 71 an individual who needs it receives an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form B. In one embodiment, a treatment method for treatment-resistant pain is provided comprising administering to an individual who needs it receives an effective dose of a crystalline form of psilocybin and psilocin, Crystalline Form C. [000140] In some embodiments, the composition is administered by intracutaneous, subcutaneous, intravenous, intra-arterial, intradermal, transdermal, oral, sublingual, buccal or nasal routes. [000141] In some embodiments, the method also includes the administration of a second pharmaceutically active compound. [000142] In some embodiments, the second pharmaceutically active compound is one or more of an anxiolytic drug, an antidepressant drug, or an analgesic drug. [000143] In some embodiments, the second pharmaceutically active compound is a psychoactive alkaloid. In some embodiments, the psychoactive compound or alkaloid is psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenine, bufotenidine, 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), 4-hydroxytryptamine, N,N,N-trimethyl-4-hydroxytryptamine ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elimoclavine, ergometrine or chanoclavine, or any combination thereof. [000144] In some embodiments, the second pharmaceutically active compound is administered simultaneously with the composition. [000145] In some embodiments, the second pharmaceutically active compound is administered sequentially with the composition. [000146] In some modalities, the method also includes the administration of guided therapy. Petition 870260077978, dated 05 / 08 / 2026, pp. 126 / 164 46 / 71 [000147] In some modalities, guided therapy is administered simultaneously with the compounding. [000148] In some modalities, guided therapy is administered sequentially with the compound. [000149] In some modalities, guided therapy is administered simultaneously with the second pharmaceutically active compound. [000150] In some modalities, guided therapy is administered sequentially with the second pharmaceutically active compound. [000151] The following examples are provided to further illustrate embodiments of the present invention, but are not intended to limit the scope of the invention. Although they are typical of those that may be used, other procedures, methodologies or techniques known to those skilled in the art may be used alternatively. Examples Example 1 Salt Sorting [000152] Lyophilization / Recrystallization: Physical mixtures of psilocin and psilocybin, in a 1:1 ratio, were prepared in Water:Acetonitrile (60:40 v / v) + 0.1% formic acid. The solution was divided into 11 small vials to obtain 30 mg of psilocin content in each vial. The solvent was removed by lyophilization. The amorphous material obtained was then resuspended in 10 solvents, and the samples were heated to 50°C and cooled to 5°C, with a constant heating rate of 10°C / h and variable cooling rates of -20°C / h, 10°C / h, and -5°C / h from the first to the third cycle. After the temperature profile, the solids were collected, dried at room temperature and under vacuum, and analyzed by XRPD. All solids were then exposed to 40°C / 75% RH (AAC) for 2 days and measured again by XRPD. The results are shown in Table 1. Petition 870260077978, dated 05 / 08 / 2026, pp. 127 / 164 47 / 71 Table 1 ID of the Experiment Solvent Concentration (mg / mL) HT-XRPD Room-dried Vacuum-dried AAC Room-dried AAC - Vacuum-dried TCS1 1,4-dioxane 157.5 Amorphous Crystalline form A pc Crystalline form C pc Crystalline form C pc TCS2 Ethanol 163.7 Crystalline form A Crystalline form A Crystalline form A Crystalline form A TCS3 Acetone 92.1 Crystalline form A pc Crystalline form A pc Crystalline form C pc Crystalline form C pc TCS4 Acetonitrile 90.0 Amorphous Amorphous Crystalline form C Crystalline form C pc TCS5 MEK 214.1 Crystalline form A pc Crystalline form A pc Crystalline form C Crystalline form C pc TCS6 EtOAc 204.7 Amorphous Amorphous Crystalline form C pc Crystalline form C pc TCS7 TBME 123.8 Amorphous Crystalline form C Crystalline form C pc TCS8 2-propanol 117.4 Amorphous Crystalline form C pc Crystalline form C Petition 870260077978, dated 05 / 08 / 2026, pages 128 / 164 48 / 71 TCS9 THF 133.7 Amorphous Crystalline form A pc Crystalline form C Crystalline form C TCS10 n-heptane 79.3 Amorphous Crystalline form A pc Crystalline form C pc Crystalline form C pc pc = slightly crystalline [000153] Paste Conversion: Physical mixtures of psilocin and psilocybin in a molar ratio were prepared in mixtures of organic solvents to form suspensions. Samples were heated to 50°C and cooled to 5°C, with a constant heating rate of 10°C / h and variable cooling rates of -20°C / h, 10°C / h and -5°C / h from the first to the third cycle. Then, the samples were aged at room temperature for 72 hours. After the aging time was complete, the solids were separated from the liquid phases by centrifugation and dried under ambient conditions and under vacuum before being analyzed by HT-XRPD. All solids were exposed to 40°C / 75% RH (AAC) for 2 days and re-measured by XRPD. The results are shown in Table 2. Table 2 Psilocin (mg) Psilocybin (mg) Solvent Volume (mL) Solids after Temperature Profile? HT-XRPD Room Dried Vacuum Dried AAC Room Dried AAC Vacuum Dried TCS22 14.59 24.33 TFE / IPA 10 / 90 250 Yes Crystalline Form A Crystalline Form A Crystalline Form A Crystalline Form A Petition 870260077978, dated 05 / 08 / 2026, pp. 129 / 164 49 / 71 TCS23 14.63 23.74 TFE / Isopropyl Acetate 10 / 90 250 Yes Crystalline Form A Crystalline Form A Crystalline Form A Crystalline Form A TCS24 14.09 23.82 TFE / Toluene 10 / 90 200 Yes Crystalline Form B Crystalline Form B Crystalline Form B Crystalline Form B TCS25 14.13 23.68 Acetonitrile / Water 80 / 20 250 Yes Crystalline Form C pc pc Crystalline Form C pc Crystalline Form C TCS26 14.78 24.22 THF / Water 80 / 20 300 Yes Crystalline Form C pc Crystalline Form C Crystalline Form C pc = slightly crystalline Example 2 XRPD analysis [000154] XRPD patterns were obtained using a high-throughput Ardena T2 XRPD configuration. The plates were mounted on a Bruker General Area Detector Diffraction System (GADDS) equipped with a VANTEC-500 gas area detector corrected for intensity and geometric variations. Measurement accuracy calibration (peak positions) was performed using the NIST SRM1976 (Corundum) standard. [000155] Data collection was performed at room temperature using monochromatic Cu Ka radiation in the 2Θ region between 1.5° and 41.5°, which is the most distinct part of the XRPD pattern. The diffraction pattern of each well was collected in two 2θ bands (1.5° < 2Θ < 21.5° for the first frame and 19.5° < 2Θ < 41.5° for the second), with an exposure time of 90 s for each frame. No background subtraction or curve smoothing was applied to the XRPD patterns. Petition 870260077978, dated 05 / 08 / 2026, pages 130 / 164 50 / 71 [000156] The cell parameters, as well as the crystal system, were obtained using the LSI-Index indexing program (Coelho, 2003; Coelho & Kern, 2005). The space group was selected based on reflections and crystal specific mass. The cell parameters, purity, and instrument parameters were refined using the Whole Powder Pattern Decomposition method. [000157] For the Rietveld calculation, the cell parameters, the crystal system, as well as the positions of the atoms were taken from the single crystal file (cif). During refinement, the following parameters were refined: cell constants, background, instrument geometry, zero displacement, and absorption. [000158] Neither the positions of the atoms nor the parameters of thermal motion were refined throughout the process. The following adjustment criteria were used: Yo,me Yc,m are the observed and calculated data, respectively, at data point m. M is the number of data points, P is the number of parameters, wm is the weighting given to the data point m which, for the count statistic, is given by wm = 1 / σ (Yo,m)2, where σ(Yo,ιη) is the error in Yo,m, [000159] The XRPD of the crystal form A of the Exp TCS2 ID is shown in Figure 1, with the peak table shown in Table 3. Table 3 ID of the PEAK ANGLE (20) SPACING D INTENSITY Petition 870260077978, dated 05 / 08 / 2026, pp. 131 / 164 51 / 71 1 8.62 10.24 26.92 2 10.1 8.75 74.3 3 10.67 8.28 41 4 10.74 8.23 ​​41.53 5 11.91 7.42 24.79 6 12.78 6.92 25.41 7 12.86 6.88 24.14 8 13.44 6.58 29.73 9 14.47 6.12 32.64 10 14.54 6.08 34.64 11 16.5 5.37 32.75 12 16.57 5.34 31.21 13 17.38 5.1 22.03 14 19.16 4.63 53.76 15 19.78 4.48 23.48 16 19.86 4.47 24.04 17 23.42 3.79 28.95 18 23.58 3.77 22.25 19 24.07 3.69 39.17 20 24.18 3.68 38.57 21 25.22 3.53 39.39 22 25.3 3.52 40.24 23 26.46 3.36 11.13 24 26.58 3.35 11.27 25 27.51 3.24 11.77 26 27.62 3.23 15.04 [000160] The XRPD of the B crystal form of the Exp TCS24 ID is mos- as shown in Figure 2, with the peak table shown in Table 4. Petition 870260077978, dated 05 / 08 / 2026, pp. 132 / 164 52 / 71 Table 4 Peak ID Angle (2θ) Spacing D Intensity 1 8.54 10.34 51.89 2 9.3 9.5 17.17 3 9.94 8.89 22.07 4 10.05 8.79 23.38 5 10.39 8.51 16.39 6 14.12 6.27 23.75 7 14.27 6.2 28.34 8 18.54 4.78 78.66 9 19.34 4.58 14.35 10 20.3 4.37 17.49 11 20.46 4.33 13.31 12 21.12 4.2 24.94 13 22.78 3.9 29.16 14 24.94 3.57 21.53 15 25.02 3.55 18.84 16 25.68 3.47 16.68 17 26.42 3.37 18.3 [000161] The XRPD of the C crystal form of the Exp TCS26 is shown in Figure 3, with the peak table shown in Table 5. Table 5 Peak ID Angle (2θ) Spacing D Intensity 1 5.26 16.78 32.39 2 9.18 9.62 78.06 3 10.42 8.48 56.63 4 14.06 6.29 33.31 5 14.82 5.97 34.45 Petition 870260077978, dated 05 / 08 / 2026, pp. 133 / 164 53 / 71 6 15.38 5.75 31.18 7 17.46 5.07 35.33 8 17.95 4.94 58.28 9 18.38 4.82 42.18 10 19.82 4.47 36.34 11 22.38 3.97 34.22 12 24.22 3.67 52.57 13 25.3 3.52 24.13 14 27.58 3.23 32.32 Example 3 Analysis by TGMS and DSC [000162] The mass loss due to solvent or water loss from the crystals was determined by TGA / DSC. Monitoring the sample weight during heating in a TGA / DSC 3+ STARe system (Mettler-Toledo GmbH, Switzerland) resulted in a weight vs. temperature curve and a heat flux signal. The TGA / DSC 3+ was calibrated for temperature with indium and aluminum samples. The samples (approximately 2 mg) were weighed into 100 pL aluminum crucibles and sealed. The seals were punctured and the crucibles heated in the TGA from 25 to 300°C at a heating rate of 10°C min-1. Dry N2 gas was used for purging. [000163] The gases from the TGA samples were analyzed using an Omnistar GSD 350 mass spectrometer (Pfeiffer Vacuum GmbH, Germany). This is a quadrupole mass spectrometer, which analyzes masses in the temperature range of 0-200°C. [000164] Thermal events were obtained from DSC thermograms recorded with a DSC3+ STARe heat flow system (Mettler-Toledo GmbH, Switzerland). The DSC3+ was calibrated for temperature and enthalpy with a small piece of indium (mf = 156.6°C; δH = 28.45 J / g) and zinc (mf = 419.6°C; δHf = 107.5 J / g). The samples Petition 870260077978, dated 05 / 08 / 2026, pages 134 / 164 54 / 71 (approximately 2 mg) samples were sealed in standard 40 μL aluminum pans, perforated, and heated in a DSC from 25°C to 300°C at a heating rate of 10°C / min. Dry N2 gas, at a flow rate of 50 mL / min, was used to purge the DSC equipment during the measurement. [000165] TGMS analysis of Crystalline Form A showed a mass loss of 1.3% between 40 and 200°C, due to residual ethanol / water. Thermal decomposition began above 200°C. The DSC trace showed a single endothermic event at Tpico of 255.0°C (Tinitial 252.5°C), which corresponds to the melting of Crystalline Form A. The TGMS thermogram of Crystalline Form A is shown in Figure 4 and the DSC thermogram of Crystalline Form A is shown in Figure 5. [000166] TGMS analysis of Crystalline Form B showed a mass loss of 15.8% between 40 and 200°C, due to TFE and toluene, based on the MS signal. Thermal decomposition began above 200°C. The DSC trace showed a large endothermic event at Tpeak of 168.2°C (Tinitial 156.1°C), which corresponds to the desolvation of Crystalline Form B. The TGMS thermogram of Crystalline Form B is shown in Figure 6 and the DSC thermogram of Crystalline Form B is shown in Figure 7. [000167] TGMS analysis of Crystalline Form C showed a mass loss of 13.5% between 40 and 160°C, due to water, based on the MS signal. Thermal decomposition began above 160°C. The DSC trace showed a broad endothermic event between 25-140°C (Tpeak 98.7°C, Initial T 84.7°C), which corresponds to the dehydration of Crystalline Form C. The TGMS thermogram of Crystalline Form B is shown in Figure 8 and the DSC thermogram of Crystalline Form B is shown in Figure 9. Example 4 NMR Spectroscopy Petition 870260077978, dated 05 / 08 / 2026, pages 135 / 164 55 / 71 [000168] 1H-D2O NMR spectroscopy was used to characterize the integrity of the psilocybin compound and psilocybin-psilocin polymorphs (crystalline form A and crystalline form B). Spectra were recorded at room temperature on a 500 MHz instrument (Bruker BioSpin GmbH) using standard pulse sequences. Data were processed using Spectrus Processor 2016.2.2 software from ACD Labs (Advanced Chemistry Development Inc., Canada). [000169] Figure 10 superimposes the Ή-NMR of Crystalline Form A and psilocybin, while Figure 11 shows the Ή-NMR of Crystalline Form A and psilocybin between 6 ppm and 7.5 ppm. Figure 12 superimposes the 1H-NMR of Crystalline Form A, Crystalline Form B, and psilocybin, while Figure 13 superimposes the Ή-NMR of Crystalline Form A, Crystalline Form B, and psilocybin between 6 ppm and 7.5 ppm. Example 5 Analysis by DVS [000170] Moisture sorption isotherms were collected on a Surface Measurement Systems DVS Adventure system (London, UK). The sample size was approximately 10 mg of solid material. A complete sorption and desorption isotherm was recorded by varying the relative humidity from 40 - 95 - 0 - 40%, in 10% steps, at a constant temperature of 25°C. The weight balance per step was set at dm / dt of 0.002% / min. The sample was then measured by HTXRPD. [000171] Crystalline Form A: The total mass difference between 0-95% RH was 3.6%, and the mass absorption at 80% RH was 2.4%, indicating that the material is moderately hygroscopic according to the EP hygroscopicity classification. The solid recovered after DVS was analyzed by XRPD, which confirmed that PSY1 is physically stable after the sorption-desorption cycle. The DVS isotherm of Form Petition 870260077978, dated 05 / 08 / 2026, pages 136 / 164 Crystalline 56 / 71 A is represented in Figure 14. [000172] Crystalline Form B: The total mass difference between 0-95% RH was 8.0%, and the mass absorption at 80% RH was 4.3%, indicating that the material is moderately hygroscopic, according to the EP hygroscopicity classification. The solid recovered after DVS was analyzed by XRPD, which confirmed that PSY5 is physically stable after the sorption-desorption cycle. The DVS isotherm of Crystalline Form B is shown in Figure 15. [000173] Crystalline Form C: The total mass difference between 0-95% RH was 16.4%, and the mass absorption at 80% RH was 1.8%, indicating that the material is slightly hygroscopic, according to the EP hygroscopicity classification. The solid recovered after DVS was analyzed by XRPD, which confirmed that Crystalline Form C is physically stable after the sorption-desorption cycle. The gradual absorption of water between 20-95% RH was 5.2%, which corresponds to 1.5 water molecules. The DVS isotherm of Crystalline Form B is shown in Figure 16. Example 6 Analysis by UPLC Analytical method by UPLC UPLC System: • UPLC: Agilent 1290 • Detector 1: UV detector set to 267 nm • Detector 2: MSD XT in Positive Scan Mode UPLC conditions: • Autosampler temp.: TA • Column: ACE Avanor C18-PVP (100 x 2.1 mm; 1.7 pm) • Column temperature: 40°C Gradient: • Mobile phase A: 0.7 grams of Petition 870260077978, dated 05 / 08 / 2026, pp. 137 / 164 57 / 71 Ammonium formate 0.1% formic acid in water • Mobile phase B: 0.1% formic acid in methanol • Flow rate: 0.27 mL / min • Running time: 25 minutes • Gradient: Time [min]: Eluent A: Eluent B: 0 95% 5% 4 95% 5% 16.5 30% 70% 20 30% 70% 20.1 95% 5% 25 95% 5% Sample preparation: • Concentration: approximately 1.0 mg / mL • Solvent: Water:Acetonitrile (60:40 v / v) + 0.1% of formic acid • Injection volume: 1 μL [000174] Crystalline Form A: Reference solutions of psilocin were made at concentrations of approximately 1 mg / mL. A solution of approximately 2 mg / mL of Crystalline Form A was made in ACN / water 40 / 60 %v / %v + 0.01% formic acid. The stoichiometry (psilocybin:psilocin) of Crystalline Form A was determined to be 1:1. The HPLC chromatogram is shown in Figure 17. [000175] Crystalline Form B: Reference solutions of psilocin were made at concentrations of approximately 1 mg / mL. A solution of approximately 2 mg / mL of Crystalline Form B was made in ACN water 40 / 60 %v / %v + 0.01% formic acid. Applying the equation presented below (1), the stoichiometry (psilocybin:psilocin) of Crystalline Form B was determined to be 1.3:1. The HPLC chromatogram is shown in Figure 18. [000176] Crystalline Form C: Reference solutions of psilocin Petition 870260077978, dated 05 / 08 / 2026, pages 138 / 164 58 / 71 were made at concentrations of approximately 1 mg / mL. A solution of approximately 2 mg / mL of crystalline form C was made in ACN / water 40 / 60 %v / %v + 0.01% formic acid. The stoichiometry (psilocybin:psilocin) of crystalline form C was determined to be 1:1. The HPLC chromatogram is shown in Figure 19. Example 7 Crystal Structure [000177] High-Resolution X-ray Powder Diffraction (HR-XRPD): HR-XRPD data for Crystalline Form A were collected on a D8 Advance diffractometer using Cu αί (1.54056 A) radiation with a germanium monochromator in TA. Diffraction data were collected in the 2Θ 2.15 - 41.5° range. Detector scanning, on a solid-state LynxEye detector, was performed using 0.0157° per step, with a scan rate of 5 seconds / step. Samples were measured in an 8 mm long glass capillary with an outer diameter of 0.3 mm. Before transferring to the capillary, the analyzed solids (from Example 1, ID of Exp TCS2) were ground in an agate mortar until all visible crystals disappeared and the material became a fine powder. [000178] The cell parameters, as well as the crystal system, were obtained using the LSI-Index indexing program. The space group was selected based on reflections and crystal specific mass. The cell parameters, purity, and instrument parameters were refined using the Whole Powder Pattern Decomposition method. [000179] The structure was solved using simulated annealing techniques, as implemented in TOPAS6. For both Psilocin and Psilocybin components, the Z_Matrix model was created using cif files from the Cambridge Structural Data Base, CCDC1238288 for Psilocin and CCDC2128419 for Psilocybin. Petition 870260077978, dated 05 / 08 / 2026, pp. 139 / 164 59 / 71 [000180] Rietveld refinement was performed using TOPAS6 (Bruker, 2017). All bond distances and angles were fixed and, except for the following torsion angles (C6-O5-P4-O2; C16-C15-C13-C14; C25-C24-N23-C22; C26-C25-C24-N23), only rotation and translation of the molecules were allowed. [000181] The following adjustment criteria were used: • Yo,m and Yc,m are the observed and calculated data, respectively, at data point m. • M is the number of data points. • P is the number of parameters. • wm is the weighting given to data point m, which, for the count statistic, is given by wm = 1 / a(Yo,m)², where σ(Yo,ιη) is the error at Yo,m. [000182] The structure was determined using the simulated annealing method, with the rigid body allowing both molecules to rotate and translate freely within a unit cell. In addition, the torsion angles of the phosphate, as well as both amine groups, were treated as variables. After obtaining a chemically reasonable solution, the model was refined using the Rietveld algorithm. [000183] Crystalline Form A crystallizes in the orthorhombic primitive space group based on reflection conditions and simulated annealing results from the P212121 space group. Table 6 presents the final crystal and refinement data for the chosen model. Petition 870260077978, dated 05 / 08 / 2026, pages 140 / 164 60 / 71 Table 6: Crystal data and final Rietveld parameters for the Psilocin-Psilocybin polymorph Crystalline form A. T [K] 296(2) λ[A] 1.54056 Crystal system Orthorhombic Space group P2i2i2i Unit cell dimensions a[A] 9.3674(3) b[A] 11.2660(6) c[A] 24.2741(9) V[A3] 2561.7(2) Z (Z') 4(1) Dc [g / cm3] 1.267 Cap size [mm2] 0.5 x 8 2Θ Size per step [°] 0.016 No. of steps 2503 Time per step [s] 17 2Θ Range [°] 2.15^ 41.5 Rexp 3.31 Rwp 4.11 Rp 2.85 GOF 1.24 RBrag 1.95 Impurities, other forms [%] Below the detection limit [000184] The solution revealed that there is a Psilocin-Psilocybin pair in the asymmetric unit without additional solvent or API molecules. All x, y, z positions of the atoms can be found. Figure 20 shows the molecular structure of Psilocin-Psilocybin in crystalline form A. As can be seen, the phosphate group of Psilocybin interacts directly with the N atom of the Psilocin amine. The crystal is Petition 870260077978, dated 05 / 08 / 2026, pp. 141 / 164 61 / 71 is maintained by an extensive network of intermolecular hydrogen bonds, in which each non-protonated O or N atom serves as an acceptor, while each NH and OH acts as a donor. Table 7 presents the geometry of all hydrogen bonds found in the analyzed crystal. Table 7: Hydrogen bonds found in the Psilocybin crystal. Psilocybin in crystalline form A. DH...A DH [A] H...A [A] D...A [A] DH...A [°] O1-H1...N23' 0.88(2) 1.60(2) 2.46(2) 162(2) N11-H11...O3 0.96(5) 2.17(4) 2.97(4) 140(6) N17-H17...O2 0.85(7) 1.83(7) 2.59(6) 147(8) N28-H28...O1iv 0.87(7) 2.32(6) 3.13(5) 153(10) O34-H34...O3v 0.88(10) 1.69(8) 2.49(7) 151(5) Symmetry transformations: (i) 1-x, y-0.5, 1.5-z; (ii) x-1, y, z; (iii) -x, 0.5+y, 0.5-z; (iv) 0.5-x, -y, 0.5+z; (v) 0.5-x, 1-y, 0.5+z [000185] The hydrogen bonding network of the crystalline form A forms a layered structure, with alternating layers built from Psilocin and Psilocybin molecules. These layers are parallel to the ab plane, as shown in Figure 21. [000186] The atomic coordinates and equivalent isotropic shift parameters (A2x103) for non-hydrogen atoms of Form A are shown in Table 8. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. Table 8 xyz U(eq) O1 0.1251(14) 0.0326(16) 0.4198(4) 0.0253 O2 0.077(3) 0.0094(13) 0.3153(5) 0.0253 O3 0.190(3) 0.190(2) 0.3483(6) 0.0253 P4 0.0916(7) 0.0915(7) 0.3636(3) 0.0253 O5 -0.054(2) 0.157(3) 0.3724(5) 0.0253 Petition 870260077978, dated 05 / 08 / 2026, pages 142 / 164 62 / 71 C6 -0.1818(8) 0.102(5) 0.3771(8) 0.0253 C7 -0.221(2) 0.009(6) 0.4089(13) 0.0253 C8 -0.357(3) -0.030(9) 0.4084(19) 0.0253 C9 -0.466(2) 0.022(11) 0.375(2) 0.0253 C10 -0.4261(9) 0.116(10) 0.3436(15) 0.0253 N11 -0.512(3) 0.188(12) 0.3068(16) 0.0253 C12 -0.386(5) 0.277(10) 0.2836(13) 0.0253 C13 -0.265(4) 0.250(7) 0.3069(10) 0.0253 C14 -0.2791(18) 0.156(7) 0.3445(10) 0.0253 C15 -0.139(6) 0.313(5) 0.2890(13) 0.0253 C16 -0.082(4) 0.261(6) 0.2343(10) 0.0253 N17 0.054(6) 0.324(5) 0.2219(15) 0.0253 C18 0.140(5) 0.246(6) 0.1809(13) 0.0253 C19 0.146(7) 0.370(3) 0.269(2) 0.0253 C21 0.8842(18) 0.5884(19) 0.9383(6) 0.0253 C22 0.7490(17) 0.7295(10) 0.9827(10) 0.0253 N23 0.8087(12) 0.6116(8) 0.9893(5) 0.0253 C24 0.7012(15) 0.5244(13) 1.0037(8) 0.0253 C25 0.591(2) 0.533(3) 0.9591(11) 0.0253 C26 0.508(4) 0.422(3) 0.9490(17) 0.0253 C27 0.543(5) 0.306(3) 0.963(2) 0.0253 N28 0.435(7) 0.236(4) 0.942(3) 0.0253 C29 0.337(7) 0.302(6) 0.917(3) 0.0253 C30 0.212(8) 0.268(7) 0.891(3) 0.0253 C31 0.124(7) 0.356(9) 0.868(3) 0.0253 C32 0.161(6) 0.474(8) 0.872(3) 0.0253 C33 0.292(5) 0.508(6) 0.899(3) 0.0253 O34 0.330(4) 0.628(6) 0.906(3) 0.0253 C35 0.379(5) 0.422(5) 0.920(2) 0.0253, [000187] The hydrogen coordinates and parameters of Petition 870260077978, dated 05 / 08 / 2026, pages 143 / 164 63 / 71 isotropic displacements (A2x103) of Form A are shown in Table 9. U(eq) is defined as one-third of the trace of the orthogonalized Uij tensor. Table 9 x y z U(eq) H1 0,1396(11) 0,074(2) 0,4502(3) 0,0253 H7 -0,151(3) -0,029(5) 0,4319(14) 0,0253 H8 -0,379(5) -0,097(9) 0,431(2) 0,0253 H9 -0,563(3) -0,005(13) 0,374(2) 0,0253 H11 -0,612(2) 0,172(14) 0,3030(19) 0,0253 H12 -0,389(6) 0,337(10) 0,2556(15) 0,0253 H15A -0,075(5) 0,294(4) 0,3185(12) 0,0253 H15B -0,147(8) 0,398(5) 0,2858(18) 0,0253 H16A -0,146(5) 0,280(7) 0,2048(11) 0,0253 H16B -0,074(3) 0,176(5) 0,2375(8) 0,0253 H17 0,041(8) 0,386(5) 0,2026(19) 0,0253 H18A 0,205(4) 0,181(6) 0,1844(12) 0,0253 H18B 0,203(6) 0,295(7) 0,1601(17) 0,0253 H18C 0,075(4) 0,206(7) 0,1563(10) 0,0253 H19A 0,213(7) 0,336(3) 0,2941(19) 0,0253 H19B 0,086(8) 0,405(2) 0,296(2) 0,0253 H19C 0,211(9) 0,429(4) 0,255(2) 0,0253 H21A 0,951(2) 0,627(3) 0,9141(7) 0,0253 H21B 0,817(3) 0,575(3) 0,9093(5) 0,0253 H21C 0,944(2) 0,520(2) 0,9427(10) 0,0253 H22A 0,778(2) 0,8072(10) 0,9708(14) 0,0253 H22B 0,715(2) 0,7579(14) 1,0176(12) 0,0253 H22C 0,6710(17) 0,7266(16) 0,9571(11) 0,0253 H24Aa 0,6599(17) 0,542(2) 1,0390(8) 0,0253 H24B 0.742(2) 0.4463(11) 1.0054(11) 0.0253, Petition 870260077978, dated 05 / 08 / 2026, pages 144 / 164 64 / 71 H25A 0.635(3) 0.565(3) 0.9267(9) 0.0253 H25B 0.5179(14) 0.587(3) 0.9706(16) 0.0253 H27 0.629(5) 0.2905(18) 0.984(3) 0.0253 H28 0.436(8) 0.159(4) 0.946(4) 0.0253 H30 0.186(9) 0.185(8) 0.890(4) 0.0253 H31 0.037(8) 0.334(10) 0.851(4) 0.0253 H32 0.100(6) 0.533(9) 0.856(4) 0.0253 H34 0.294(4) 0.682(7) 0.884(3) 0.0253 [000188] Figure 22 shows the graphical representation of the final Rietveld refinement cycles, which confirms that the model fits the diffractogram collected for Crystalline Form A very well. Example 8 Calcium release assay [000189] CHO-K1 AequoScreen cells, which stably express h5HT2a, contain an aequorin protein that, when bound to Ca2+, is capable of catalyzing the breakdown of the coelenterazine molecule to produce light. The levels of light emitted are proportional to the release of Ca2+ from the endoplasmic reticulum. CHO-K1 cells were treated with between 0.1 nM - 10 μM of each compound for 1 min before chemiluminescence was recorded. The resulting data are then fitted to a three-parameter nonlinear regression to determine potency (EC50) and efficacy (Emax). The results are shown in Figure 23. Data were fitted to a three-parameter nonlinear regression in GraphPad (v. 9). n = 3-29 independent experiments performed in duplicate or triplicate. Data are expressed as mean ± SEM. EC50 and Emax are described in Table 10. Table 10 Compound pEC50 ± SEM (EC50 nM) Emax (%) ± SEM n LSD 7.5 ± 0.31 (28) 100 ± 9.9 29 Petition 870260077978, dated 05 / 08 / 2026, pages 145 / 164 65 / 71 5HT 6.5 ± 0.31 (320) 140 ± 19 7 Psilocin 9.3 ± 0.55 (0.53) 89 ± 11 4 Psilocybin 5.8 ± 0.38 (1,500) 69 ± 15 6 Norpsilocin 7.1 ± 0.80 (72) 45 ± 14 3 Ergotaminea 5.6 ± 0.75 (2,300) 39 ± 13 5 Psilocin:Psilocybin 1:1 8.3 ± 0.70 (4.5) 75 ± 14 5 [000190] Psilocin is a potent activator of Ca2+ release. Psilocybin is demonstrably less potent and effective. An equimolar 1:1 mixture of psilocin and psilocybin produces a Ca2+ release response intermediate between that of each compound alone. Example 9 Barrestina 2 recruitment essay [000191] CHO-K1 cells express the fusion proteins h5HT2a-smBiT and parrestin 2-lgBiT. When h5HT2a and parrestin 2 come into contact with each other, the smBiT and lgBiT peptides complement each other to produce a complete NanoBit luciferase enzyme. When complete, the enzyme is able to catalyze the breakdown of the coelenterazine molecule to produce light. The levels of light emitted are proportional to the interactions between h5HT2a and parrestin 2. CHOK1 cells were treated with between 0.1 nM - 10 μM of each compound for 2 h, during which time chemiluminescence was recorded. The area under the curve data for cumulative chemiluminescence were then fitted to a three-parameter nonlinear regression to determine potency (EC50) and efficacy (Emax). The results are shown in Figure 24. The data were fitted to a three-parameter nonlinear regression in GraphPad (v. 9). n = 3-13 independent experiments performed in duplicate or triplicate.The data are expressed as mean ± SEM. EC50 and Emax are described in Table 11. Table 11 Petition 870260077978, dated 05 / 08 / 2026, pp. 146 / 164 66 / 71 Compound pEC50 ± SEM (EC50 nM) Emax (%) ± SEM n LSD 7.8 ± 0.50 (16) 100 ± 16 13 5HT 7.6 ± 1.1 (28) 81 ± 35 3 Psilocin 7.7 ± 0.67 (22) 89 ± 22 4 Psilocybin Did Not Converge -34 ± 5.9 3 Norpsilocin 8.6 ± 1.7 (2.4) 2.9 ± 27 3 Ergotamine 8.1 ± 1.0 (7.3) 106 ± 25 3 LSD 7.8 ± 0.50 (16) 100 ± 16 13 [000192] Psilocin is an activator of parrestin 2 recruitment. Psilocybin is not potent or effective. The potency of psilocin and psilocybin is greater in the Ca2+ release assay than in the parrestin 2 recruitment assay. Example 10 Barrestina 2 Recruitment Essay [000193] CHO-K1 cells, which stably express h5HT2a, are cultured, collected, and frozen at -80°C. Cells are thawed as needed and subjected to pressure cavitation using a Dounce homogenizer to disrupt cell membranes. Cell membranes are then collected by subjecting cell lysates to high-speed centrifugation at 20,000 x g for 30 min at 4°C. Homogenization and centrifugation are repeated to enrich the sample for receptor-containing cell membranes. CHO-K1 cell membranes are co-incubated with 1 nM [3H]ketanserin and between 0.1 nM - 10 μM of each compound for 2 h. Samples are then pipetted onto filter paper before being rinsed and washed by vacuum filtration three times, dried, and incubated overnight in scintillation fluid. The remaining bound radioactivity is then read on a liquid scintillation counter and normalized to the maximum LSD response (i.e., 0%).The resulting data are then fitted to a three-parameter nonlinear regression, for... Petition 870260077978, dated 05 / 08 / 2026, pages 147 / 164 67 / 71 determine the affinity (Ki). The results are shown in Figure 25. The data were fitted to a three-parameter nonlinear regression in GraphPad (v. 9). n = 3-6 independent experiments. Data are expressed as mean ± SEM. EC50 and Emax are described in Table 12. Table 12 Compound pKi ± SEM (Ki nM) n LSD 7.4 ± 0.16 (36) 6 5HT 7.5 ± 0.17 (34) 3 Psilocin 8.5 ± 0.26 (3.4) 6 Psilocybin 6.4 ± 0.34 (390) 3 Ergotamine 6.9 ± 0.55 (110) 5 Example 11 Physiology: Catalepsy, Body Temperature, and Nociception [000194] C57BL / 6 mice were treated with increasing doses of compounds, as indicated, by ip injection. The tests were as follows: Body temperature is measured before administration of the first dose of the compound, for baseline. Catalepsy - bar gripping assay, 10 min after compound administration. Mice are positioned so that their forepaws grasp a 0.7 cm ring clamp, positioned 4.5 cm above the surface of the test space. The time the ring is gripped is recorded (sec). The assay is terminated if the mouse turns its head or body, or makes 3 consecutive escape attempts, up to a maximum of 60 s. Nociception - 15 min after compound administration, the mouse's tail is placed in water at 52°C. The latency to remove the tail from the water is recorded up to a maximum of 20 s. Body temperature - rectal thermometer 20 min after compound administration. The results are shown in Figure 26.The data were plotted in GraphPad (v. 9). n > 6 animals per dose. The data are... Petition 870260077978, dated 05 / 08 / 2026, pages 148 / 164 68 / 71 expressed as mean ± SEM. [000195] Psilocin and psilocybin do not produce catalepsy. Neither drug nor combination would be expected to produce freezing or spastic behavior. Psilocin and psilocybin produce dose-dependent hypothermia. Finally, psilocin significantly reduces pain perception, peaking at 1 mg / kg. Example 12 Modeling hallucinations in rodents: Head twitch response (HTR) [000196] C57BL / 6 mice were treated with increasing doses of compounds, as indicated by ip injection. Mice were placed inside a transparent cylinder and video-recorded for 10 minutes immediately after compound administration. Head twitching was recorded by an individual blinded to the treatment as a rhythmic lateral head shake, distinct from grooming or vertical head nodding. Results are shown in Figure 27. Data were plotted on GraphPad (v. 9). n > 3 animals per dose. Data are expressed as mean ± SEM. [000197] Psilocin and psilocybin produce a time-dependent head twitch response as a model of hallucination or dissociation in rodents. At various doses tested, the peak effect appeared to occur 3-4 min after administration of the compound. In contrast, the peak effect of LSD appeared to occur around 7 min after administration. Example 13 Locomotor effects: open field test (OFT) [000198] C57BL / 6 mice were treated with increasing doses of compounds, as indicated by ip injection. Mice are placed in an open field 30 min after compound administration. The open field measures 1 m x 1 m; the test lasts 5 Petition 870260077978, dated 05 / 08 / 2026, pages 149 / 164 69 / 71 min. The total distance traveled, speed, and time spent in the central quadrant of the field are recorded and analyzed using EthoVision XT (Noldus, v. 17). The results are shown in Figure 28. The data were plotted in GraphPad (v. 9). n > 4 animals per dose. Data are expressed as mean ± SEM. [000199] Psilocin and psilocybin produce a dose-dependent decrease in movement, speed, and time in the center of the open field, with significant effects occurring for movement and speed—but not for time in the center—at the highest doses tested (i.e., 7 or 10 mg / kg). Example 14 Cognitive performance and anxiety: Elevated plus maze (EPM) [000200] C57BL / 6 mice were treated with 3 mg / kg of compounds by ip injection. Mice are placed in the EPM 30 min after compound administration. The EPM measures 1 m x 1 m; the test lasts 5 min. Total distance traveled, speed, arm entries, and time in each arm are recorded and analyzed using EthoVision XT (Noldus, v. 17). Results are shown in Figure 29. Data were plotted on GraphPad (v. 9). n = 3-5 animals per treatment. Data are expressed as mean ± SEM. [000201] Based on preliminary evidence requiring additional animals, 3 mg / kg ip of psilocin significantly reduces time in the closed arm (p=0.029, unpaired t-test), but not time in the open arm (p=0.12, unpaired t-test); and no significant difference in arm entries. The data show a trend toward a reduction in overall movement and speed, consistent with OFT data. Example 15 Pharmacokinetics (PK) Petition 870260077978, dated 05 / 08 / 2026, pages 150 / 164 70 / 71 [000202] Psilocin D-10 is prepared as an internal standard for the quantification of psilocin in mouse plasma samples (Figure 30, left, top). The quantification of the compound is optimized using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS / MS) (AB SciEx 4000 QTRAP®) for the voltage (Figure 30, right, top), the organic solvent (80% methanol + 0.1% formic acid, 90% methanol + 0.1% formic acid, 100% methanol + 0.1% formic acid, 90% acetonitrile + 0.1% formic acid, or 100% methanol + 0.1% formic acid) (Figure 30, left, middle, top), the injection volume, and the flow rate. and the creation of a standard curve (Figure 30, right, middle, at the top).The chosen organic solvent is 100% acetonitrile + 0.1% formic acid (Figure 30, red line on the right, middle, top) because it exhibits the highest signal-to-noise ratio and the narrowest peak; and the injection volume and flow rate for best performance are 5 μL at 0.2 mL / min. Fragmentation patterns and mass-to-charge ratios (m / z) were determined for psilocin D-10 (Figure 30, left, middle, bottom). A standard curve was constructed for the detection of psilocin in mouse plasma, with the upper and lower quality controls set at 2.5 ng / mL and 400 ng / mL, respectively (Figure 30, right, middle, bottom). Example 16 Neurogenesis and plasticity in healthy brain organoids [000203] The effects of 16, 50, 160, 500, and 1600 nM psilocybin, psilocin, or psilocybin + psilocin, in a 1:1 molar ratio, were measured after exposure (6 hours, then total clearance) in three experiments. Control brain organoids were used to start, with the results validated in patient-derived organoids. Petition 870260077978, dated 05 / 08 / 2026, pages 151 / 164 71 / 71 [000204] Three-month-old human brain organoids were exposed to a 6-hour pulse of EdU after final drug treatment. Newborn neurons were quantified (e.g., EdU+ / NeuN+ / EdU+) to determine the extent of neurogenesis. The Ki67+ / Sox2+ co-label was used to study changes in the progenitor pool. EdU+ / NeuN+ / EdU+ data are shown in Figure 31, Ki67+ data are shown in Figure 32, and data from Sox2-positive cells are shown in Figure 33. [000205] Three-month-old organoids were exposed to psilocybin or psilocin or psilocybin + psilocin, in a 1:1 molar ratio, for 6 hours, and then spliced ​​into small pieces and placed on Matrigel® plates for 2 days. TUJ1 was used to mark neurite growth, which was quantified in terms of length (m) and number of branches. The results of neurite growth are shown in Figure 34. [000206] Treatment with psilocybin + psilocin, in a 1:1 molar ratio combination, was found to result in an approximate 20% increase in neurogenesis from a single dose over six hours, with a corresponding decrease in proliferation. Neuronal length, two days after administration, was observed to be the greatest with psilocybin + psilocin in a 1:1 molar ratio combination, approximately doubling at the highest dose and greater than psilocybin alone. [000207] Although the invention has been described with reference to the examples above, it will be understood that modifications and variations are included within the spirit and scope of the invention. Consequently, the invention is limited only by the claims. Petition 870260077978, dated 05 / 08 / 2026, pp. 152 / 164

Claims

1 / 5 CLAIMS 1. Composition, characterized in that it comprises a crystalline form of psilocin and psilocybin: psilocin psilocybin wherein the crystalline form is Crystalline Form A; wherein Crystalline Form A is distinguished by an XRPD pattern comprising a peak at a 2Θ angle of 10.1° and 19.16°; and wherein Crystalline Form A is a cocrystal formed between psilocin and psilocybin.

2. Composition according to claim 1, characterized in that the XRPD pattern further comprises a peak at 2Θ angles of 10.74°, 25.3° and 24.07°.

3. Composition according to claim 2, characterized in that the XRPD pattern further comprises a peak at 2Θ angles of 14.54°, 16.5°, 13.44°, 23.42° and 8.62°.

4. Composition according to claim 1, characterized in that crystalline form A is distinguished by a DSC plot comprising a pronounced endothermic event at a temperature of about 255 °C.

5. Composition according to claim 1, characterized in that crystalline form A has a psilocybin to psilocin ratio of about 1:

1.

6. Composition according to claim 1, characterized in that crystalline form A has a chemical purity of about 95% or more.

7. Composition according to claim 1, characterized in that the crystalline form A contains no more than Petition 870260077978, dated 05 / 08 / 2026, page 76 / 164 2 / 5 about 5 mol% of other solid forms.

8. Composition according to claim 1, characterized in that the crystalline form A of psilocin and psilocybin comprises about 95 mol% of crystalline form A, about 2.5 mol% of psilocin and about 2.5 mol% of psilocybin.

9. Pharmaceutical composition, characterized in that it comprises a crystalline form of psilocin and psilocybin and a pharmaceutically acceptable excipient psilocin psilocybin wherein the crystalline form is Crystalline Form A; wherein Crystalline Form A is distinguished by an XRPD pattern comprising a peak at a 2Θ angle of 10.1° and 19.16°; and wherein Crystalline Form A is a cocrystal formed between psilocin and psilocybin.

10. Pharmaceutical composition according to claim 9, characterized in that the XRPD standard further comprises a peak at 2Θ angles of 10.74°, 25.3° and 24.07°.

11. Pharmaceutical composition according to claim 10, characterized in that the XRPD standard further comprises a peak at 2Θ angles of 14.54°, 16.5°, 13.44°, 23.42° and 8.62°.

12. Pharmaceutical composition, according to claim 9, characterized in that the crystalline form A is distinguished by a DSC plot comprising a pronounced endothermic event at a temperature of about 255 °C.

13. Pharmaceutical composition according to claim 9, characterized in that the crystalline form A has a psilocybin to psilocin ratio of about 1:

1. Petition 870260077978, dated 05 / 08 / 2026, page 77 / 164 3 / 5 14. Pharmaceutical composition, according to claim 9, characterized in that the crystalline form A has a chemical purity of about 95% or more.

15. Pharmaceutical composition, according to claim 9, characterized in that the crystalline form A of psilocin and psilocybin comprises about 95 mol% of crystalline form A, about 2.5 mol% of psilocin and about 2.5 mol% of psilocybin.

16. Use of a crystalline form of psilocin and psilocybin: ho PH OHó' HH psilocin psilocybin, characterized by being for preparing a composition, medicine or product for the treatment or improvement of a disease or disorder or for the stimulation of neurogenesis or neurite growth.

17. Invention, characterized by any form of its embodiment or in any applicable category of claim, for example, product or process or use, or any other type of claim encompassed by the matter initially described, disclosed or illustrated in the patent application; Crystalline form of psilocin or psilocybin: \l— ΗΠ PH \,— N HO. / N OHÓ' ΗH psilocin psilocybin; and / or Petition 870260077978, dated 05 / 08 / 2026, p.78 / 164 4 / 5 Pharmaceutical composition or product comprising a crystalline form of psilocin and psilocybin and a pharmaceutically acceptable excipient psilocin psilocybin and / or Single or separate composition comprising a crystalline form of psilocin and psilocybin: psilocin psilocybin in combination with a second pharmaceutically active compound; and / or Use of a crystalline form of psilocin and / or psilocybin: psilocin psilocybin to prepare a composition, medicament or product for the treatment or prevention of a disease, disorder or health condition; and / or Use of a crystalline form of psilocin and / or psilocybin: Petition 870260077978, dated 05 / 08 / 2026, p.79 / 164 5 / 5 Psilocin psilocybin in combination with a second pharmaceutically active compound to prepare a single or separate composition, single or separate medicine or single or separate product for the treatment or prevention of a disease, disorder or health condition; and / or Use of a crystalline form of psilocin and / or psilocybin: psilocin psilocybin to prepare a composition, medicine or product in combination with a second pharmaceutically active compound for the treatment or prevention of a disease, disorder or health condition; and / or Single or separate product comprising a crystalline form of psilocin and psilocybin: psilocin psilocybin in combination with a second pharmaceutically active compound. Petition 870260077978, dated 05 / 08 / 2026, p. 80 / 164.

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