Multipodal serotonergic compounds and prodrugs of serotonin receptor agonists and antagonists

Abstract

Monopodal and multipodal serotonergic agents, including prodrugs of serotonin receptor agonists and antagonists.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 293,730, filed December 24, 2021, U.S. Provisional Patent Application No. 63 / 299,817, filed January 14, 2022, and U.S. Provisional Patent Application No. 63 / 338,994, filed May 6, 2022, the entire contents of each of which are incorporated by reference herein for all purposes.

[0002] The present disclosure relates to novel multipodal compounds and prodrugs of serotonergic compounds, including non-hallucinogenic variants, including psilocin, and therapeutic methods for treating and preventing a variety of human disease states. [Background technology]

[0003] Many people in the world suffer from mental or mood disorders, such as depression, anxiety, compulsive disorder, and post-traumatic stress disorder (PTSD). Altered synaptic connections have been observed in brains affected by these types of diseases and disorders. Certain "psychedelic" drugs, such as psilocybin and LSD, have been found to reduce symptoms of depression and PTSD in clinical trials. This is thought to be due to 5-HT2A receptor signaling, which stimulates something called neuroplasticity. Neuroplasticity helps the brain form new neural connections, which is thought to produce rapid and lasting positive mood effects. Studies have demonstrated that psilocybin-based psychotherapy reduces depressive symptoms in patients almost immediately after a single high dose.

[0004] However, hallucinogen-based pharmacotherapies have several limitations that inhibit their widespread adoption. Most notably, tryptamine drugs such as psilocybin and LSD are hallucinogenic and must be administered in a clinical setting in the presence of a medical professional. Second, well-known 5-HT2A receptor agonists such as psilocin (the active compound of the prodrug psilocybin) are known to be cardiotoxic due to their potent agonistic effects at the 5-HT2B receptor.

[0005] To date, little (if any) research has been conducted to develop tryptamine-like analogs or tryptamine mimetics that are non-hallucinogenic and non-cardiotoxic. Thus, there remains a need to develop novel active compounds that exhibit these properties to provide patients with a therapeutic option that can be administered daily / weekly alone in their own homes without oversight from a medical professional. Summary of the Invention

[0006] Provided herein are compounds of formula I: [ka] (In the formula, Group A is a residue of a first active compound that comprises a serotonergic agent; Group B is a residue of a second active compound; L is a covalent bond between group A and group B. and salts, solvates, hydrates and prodrugs thereof are disclosed.

[0007] Provided herein is a compound of formula V: [ka] (In the formula, Group A is the residue of an active compound that includes a serotonergic agent; L1 and L5 are independently a covalent bond, O, or NR 10 , and S; L2 and L4 in each occurrence are independently O, C(R 10 )2, NR 10 , and S; L3 in each occurrence is independently O, NR 10 , S, C(R 10 )2, C(R 10 )=C(R 10 ), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl; R at each occurrence 10 are independently hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, NO2, -N(R9)2, -SR9, halo, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, OP(O)(OR9)2, -OSO2R8, and the structure of formula IVB: [ka] is selected from Group B is a residue of a second active compound; R8 is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; R9 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; n, p, and q in each occurrence are integers independently selected from 0 to 10; Z' is selected from hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, or when L5 is O, Z' is X + You can also choose from, where X + is a pharma- ceutically acceptable cation.

[0008] In some embodiments, Group A and / or Group B are independently selected from compounds of Formula II and III: [ka] (In the formula, X and Y are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl, or Y together with X and the nitrogen atom therebetween forms a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; W1 is selected from NR1, O, S, S(O), SO2, Se, Se(O), and SeO2; W2 is selected from -CD2-, -CHD-, -(CD2)2-, -CH2-, and -(CH2)2-; Z4 is selected from N and CR4; Z5 is selected from N and CR5; Z6 is selected from N and CR6; Z7 is selected from N and CR7; R1 is selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, -C(O)R8, -C(O)OR8, -P(O)(OR9), -C(O)N(R9), -SOR8, and -SOR8; R2, R3, R 3’ , R6 and R7 are each independently selected from hydrogen, deuterium, -N(R9)2, -SR9, halo, optionally substituted C1-C8 alkyl, -C1-C8 alkoxy, and optionally substituted C2-C8 alkenyl; or Y is absent, and R3, taken together with the carbon to which it is attached and the nitrogen atom to which X is attached, form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; or X is absent and R2, taken together with the carbon to which it is attached and the nitrogen atom to which Y is attached, form a 5-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; R4 and R5 are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -N(R9)2, -SR9, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8; each R8 is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; Each R9 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl. and residues of salts, solvates, hydrates, and prodrugs thereof.

[0009] In some embodiments, the compound of formula I is selected from the compound of formula IA: [ka] (Wherein, Group B, Linker L, X, Y, W1, W2, R2, R3, R 3’ , Z4, Z5, Z6, and Z7 are as defined herein; L can replace a hydrogen in an R4 group when Z4 is CR4, a hydrogen in an R5 group when Z5 is CR5, a hydrogen in an R6 group when Z6 is CR6, or a hydrogen in an R7 group when Z7 is CR7; L can replace a hydrogen atom in X or R2 group).

[0010] In some embodiments, the compound of formula I is selected from the compound of formula IB: [ka] (Wherein, linkers L, X, Y, W1, W2, R2, R3, R 3’ , Z4, Z5, Z6, and Z7 are as defined herein.

[0011] In some embodiments, the linker "L" in formula I is selected from formula IV: [ka] (In the formula, L1 and L5 in each occurrence are independently a covalent bond, O, NR 10 , and S; L2 and L4 in each occurrence are independently O, C(R 10 )2, NR 10 , and S; L3 in each occurrence is independently O, NR 10 , S, C(R 10 )2, C(R 10 )=C(R 10 ), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl; R at each occurrence 10 are independently hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, NO2, -N(R9)2, -SR9, halo, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, OP(O)(OR9)2, -OSO2R8, and the structure of formula IVA: [ka] is selected from n, p, and q in each occurrence are integers independently selected from 0 to 10.

[0012] The present disclosure also relates to compositions comprising, consisting of, or consisting essentially of a compound of formula I and / or formula V and an excipient. The present disclosure further relates to pharmaceutical compositions comprising a therapeutically effective amount of a compound of formula I and / or formula V, wherein the excipient is a pharma- ceutically acceptable carrier. Unless otherwise indicated, reference to formula I is intended to generally include embodiments relating to all sub-formulas (e.g., formula IA, formula IB, formula IC, formula ID, formula IDd, formula IDe, formula IE, formula IEa, formula IF, formula IG).

[0013] The present disclosure also relates to compositions comprising, consisting of, or consisting essentially of a compound of Formula I and / or Formula V and an excipient. The present disclosure further relates to pharmaceutical compositions comprising a therapeutically effective amount of a compound of Formula I and / or Formula V, wherein the excipient is a pharma- ceutically acceptable carrier.

[0014] The present disclosure further relates to a method for preventing or treating a psychiatric disorder, comprising administering a therapeutically effective amount of a compound of Formula I and / or Formula V or a pharmaceutical composition containing same to a subject in need thereof.

[0015] Embodiments of the present disclosure also relate to compositions comprising, consisting of, or consisting essentially of a first compound selected from compounds of Formula I and / or Formula V; and a second active compound. In certain embodiments, the second active compound comprises a serotonergic compound.

[0016] Also described herein are methods for preventing or treating inflammation and / or pain, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I and / or Formula V, or a composition (e.g., a pharma- ceutically acceptable composition) containing the compound of Formula I and / or Formula V. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] compound Provided herein are compounds of formula I: [ka] (In the formula, Group A is a residue of a first active compound that comprises a serotonergic agent; Group B is a residue of a second active compound; L is a covalent bond between group A and group B. and salts, solvates, hydrates and prodrugs thereof are disclosed.

[0018] In some embodiments, Group A and / or Group B are independently selected from compounds of Formula II and III: [ka] (In the formula, X and Y are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl, or Y together with X and the nitrogen atom therebetween forms a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; W1 is selected from NR1, O, S, S(O), SO2, Se, Se(O), and SeO2; W2 is selected from -CD2-, -CHD-, -(CD2)2-, -CH2-, and -(CH2)2-; Z4 is selected from N and CR4; Z5 is selected from N and CR5; Z6 is selected from N and CR6; Z7 is selected from N and CR7; R1 is selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, -C(O)R8, -C(O)OR8, -P(O)(OR9), -C(O)N(R9), -SOR8, and -SOR8; R2, R3, R 3’ , R6 and R7 are each independently selected from hydrogen, deuterium, -N(R9)2, -SR9, halo, optionally substituted C1-C8 alkyl, -C1-C8 alkoxy, and optionally substituted C2-C8 alkenyl; or Y is absent, and R3, taken together with the carbon to which it is attached and the nitrogen atom to which X is attached, form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; or Y is absent, and R2, taken together with the carbon to which it is attached and the nitrogen atom to which X is attached, form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; R4 and R5 are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -N(R9)2, -SR9, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8; each R8 is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; Each R9 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl. and residues of salts, solvates, hydrates, and prodrugs thereof.

[0019] As used herein, the "residue" of an active compound, such as the compounds of formulas II and III, refers to the remaining portion of the compound after taking into account the attachment of a covalent linker "L" to the compound. For example, if Group A is a residue of a compound of formula II, Z5 is CR5, R5 is -OH, and the linker "L" is attached to the compound of formula II by replacing the hydrogen on the -OH group of R5, then the "residue" of formula II is as follows: [ka] As used herein, the term "alkyl" refers to a linear, branched or cyclic saturated hydrocarbon group. When the alkyl group is a cyclic alkyl group, it may be referred to as a "cycloalkyl". As used herein, an alkyl group has 1 to 20 carbon atoms, 1 to 10 carbon atoms, 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 3 carbon atoms. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butylpentyl, isopentyl, hexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, and cyclodecyl. When an alkyl group having a specific number of carbons is named by a chemical name or specified by a molecular formula, all positional isomers having that number of carbons may be included; thus, for example, "butyl" includes n-butyl, isobutyl, sec-butyl, and tert-butyl; "propyl" includes n-propyl and isopropyl. In some embodiments, a deuterium atom may be substituted for a hydrogen atom. When alkyls as described herein are referred to as "substituted," they can be substituted with any substituent(s) such as those found in the exemplary compounds and embodiments disclosed herein, as well as deuterium, aryl, heteroaryl, hydroxy, alkoxy, alkylsulfonamido, arylsulfonamido, and halo.

[0020] As used herein, the term "alkenyl" refers to an alkyl group containing one or more carbon-carbon double bonds. An "alkynyl" group is an alkyl group containing one or more carbon-carbon triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, allyl, CH=CH(CH3), -CH=C(CH3)2, -C(CH3)=CH2, -C(CH3)=CH(CH3), -C(CH2CH3)=CH2, -C≡CH, -C≡C(CH3), -C≡C(CH2CH3), -CH2C≡CH, CH2C≡C(CH3) and CH2C≡C(CH2CH3), among others. When the alkenyl and alkynyl groups described herein are referred to as "substituted," they can be substituted with any substituent(s) such as those found in the exemplary compounds and embodiments disclosed herein, as well as deuterium, aryl, heteroaryl, hydroxy, alkoxy, alkylsulfonamido, arylsulfonamido, and halo.

[0021] As used herein, the term "cycloalkenyl" refers to a partially saturated cyclic alkyl group.

[0022] As used herein, the term "alkoxy" refers to --O-(alkyl), where alkyl is as defined above.

[0023] As used herein, the term "aryl" refers to an aromatic carbocyclic group of 6 to 14 carbon atoms having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl). In some embodiments, the heteroaryl group contains 6 to 14 carbons, and in other cases 6 to 12 or even 6 to 10 carbon atoms in the ring portion of the group. Particular aryls include phenyl, biphenyl, naphthyl, and the like. The phrase "aryl group" also includes groups containing condensed rings, such as fused aromatic-aliphatic ring systems (e.g., indanyl, tetrahydronaphthyl, and the like). When aryls described herein are referred to as "substituted," they can be substituted with any substituent(s) such as those found in the exemplary compounds and embodiments disclosed herein, as well as deuterium, aryl, alkyl, heteroaryl, hydroxyl, and halo.

[0024] As used herein, the term "heteroaryl" refers to an aromatic ring system having 1-4 heteroatoms as ring atoms in the heteroaromatic ring system, with the remainder of the atoms being carbon atoms. In some embodiments, heteroaryl groups contain 3-6 ring atoms, and in other cases 6-9 or even 6-10 atoms in the ring portion of the group. Suitable heteroatoms include oxygen, sulfur and nitrogen. In certain embodiments, the heteroaryl ring system is monocyclic or bicyclic.

[0025] As used herein, the term "heterocyclic ring" or "heterocyclyl" or "heterocycloalkyl" refers to a non-aromatic cycloalkyl in which one to four of the ring carbon atoms are replaced with a heteroatom independently selected from O, S, and N. In some embodiments, a heterocyclyl group contains 3 to 10 ring members, while other such groups have 3 to 5, 3 to 6, or 3 to 8 ring members. A heterocyclyl can also be attached to other groups at any ring atom (i.e., at any carbon atom or heteroatom of the heterocyclic ring). Heterocycloalkyl groups can be substituted or unsubstituted. Heterocyclyl groups include saturated and partially saturated ring systems. Additionally, the term heterocyclyl is intended to encompass any non-aromatic ring containing at least one heteroatom, which ring can be fused to an aryl or heteroaryl ring, regardless of the attachment to the remainder of the molecule. The phrase also includes bridged polycyclic ring systems containing heteroatoms. When heterocyclyls described herein are referred to as "substituted," they can be substituted with any substituent(s) such as those found in the exemplary compounds and embodiments disclosed herein, as well as deuterium, aryl, alkyl, heteroaryl, hydroxyl, and halo.

[0026] As used herein, the term "hetero moiety" refers to any group containing a heteroatom, such as amino, O, Se, Se(O), SeO2, S, S(O), and SO2.

[0027] As used herein, the terms "halo" or "halogen" refer to a fluorine, chlorine, bromine or iodine atom.

[0028] As used herein, the term "hydroxyl" refers to an --OH group.

[0029] As used herein, the term "alkylsulfonamide" refers to a moiety containing -S(=O)2-NR2, where each R group is selected from alkyl and H.

[0030] As used herein, the term "arylsulfonamide" refers to a moiety containing -S(=O)2-NR2, where each R group is selected from aryl and H.

[0031] In some embodiments, the compounds of formula I, II, III, and V contain one or more chiral centers. In some circumstances, the compounds of formula I, II, III, and V comprise racemic mixtures. In some embodiments, the compounds of formula I, II, III, and V comprise (S) enantiomers. In some embodiments, the compounds of formula I, II, III, and V comprise (R) enantiomers. In some embodiments, the designations (S) and (R) refer to the absolute stereochemistry of compounds with multiple stereocenters. In such cases, the conformation of one of those chiral centers may be referred to in terms of its relative (D) or (L) configuration.

[0032] In some embodiments, X and Y are independently selected from hydrogen, deuterium, and optionally substituted C1-C8 alkyl, where the alkyl group contains a cycloalkyl moiety (e.g., cyclopropyl, cyclobutyl, etc.).

[0033] In some embodiments, R, R, R 3’ , R6, and R7 are each independently selected from hydrogen, deuterium, -N(R9)2, -SR9, halo, optionally substituted C1-C8 alkyl, -C1-C8 alkoxy, and optionally substituted C2-C8 alkenyl, or Y is absent, and R3, taken together with the carbon to which it is attached and the nitrogen atom to which X is attached, forms a 5-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9. 3’ , R6 and R7 are each independently selected from hydrogen, deuterium, halo, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl.

[0034] In some embodiments, R4 and R5 are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -N(R9)2, -SR9, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8. In some embodiments, R4 and R5 are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8.

[0035] In certain embodiments, at least one of R4 and R5 is selected from a C1-C5 alkoxy group, or in some embodiments, a C2-C4 alkoxy group, which may be a linear or branched C1-C5 alkoxy group or a C2-C4 alkoxy group, e.g., linear, and may be methoxy or ethoxy. In some embodiments, R5 is a C1-C5 alkoxy. In some embodiments, R4 is selected from hydrogen and fluorine, and R5 is a C1-C5 alkoxy. In some embodiments, at least one of R4 and R5 is selected from a C1-C5 alkyl or a C1-C4 alkyl, e.g., a linear C1-C4 alkyl. In some embodiments, R5 is selected from methyl, ethyl, n-propyl, or n-butyl, and e.g., methyl or ethyl. In some embodiments, at least one of R4 and R5 is halo. In some embodiments, R4 is fluoro. In some embodiments, R4 is fluoro, and R5 is selected from hydrogen and a C1-C5 alkoxy. In some embodiments, at least one of R4 or R5 is -OC(O)R8. In some embodiments, R4 is selected from -OC(O)R8, and R5 is hydrogen or fluoro.

[0036] In some embodiments, R8 is selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl. In some embodiments, R9 is selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl. In some embodiments, R8 is selected from methyl, ethyl, propyl, and isopropyl. In some embodiments, R9 is selected from methyl, ethyl, propyl, and isopropyl.

[0037] Exemplary halo atoms for compounds of formula II and III include chloro, bromo, fluoro, and iodo. In certain embodiments, compounds of formula I and / or formula V include at least one fluoro.

[0038] In some embodiments, W1 is selected from NR1, O, S, S(O), SO2, Se, Se(O), and SeO2. In some embodiments, W1 is NR1. In some embodiments, W1 is O. In some embodiments, W1 is S. In some embodiments, W1 is Se. In some embodiments, Z6 is selected from N and CR6; Z7 is selected from N and CR7. In some embodiments, Z6 is N. In some embodiments, Z7 is N.

[0039] In some embodiments, R1 is selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, -C(O)R8, -C(O)OR8, -P(O)(OR9)2, -C(O)N(R9)2, -SOR8, and -S02R8. In some embodiments, R1 is hydrogen. In some embodiments, R1 is optionally substituted C1-C8 alkyl. In some embodiments, R1 is optionally substituted C2-C4 alkyl. In some embodiments, R1 is methyl. In some embodiments, R1 is ethyl. In some embodiments, R1 is isopropyl.

[0040] In some embodiments, W2 is selected from -CD2-, -CDH-, -(CD2)2-, -CH2-, and -(CH2)2-. In some embodiments, W2 is selected from -CH2-. In some embodiments, W2 is selected from -(CH2)2-. In some embodiments, W2 is selected from -CD2-. In some embodiments, W2 is selected from -(CD2)2-. In some embodiments, W2 is -CDH-. In some embodiments, when W2 is -CDH-, W2 represents a stereocenter in the (R) or (S) conformation.

[0041] In certain embodiments, the alkyl groups of formulas II and III are selected from C1-C8 alkyl, C2-C8 alkyl, C3-C8 alkyl, and C4-C8 alkyl, or methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, etc. In certain embodiments, the alkenyl groups of formulas II and III are selected from C2-C8 alkenyl, C3-C8 alkenyl, and C4-C8 alkenyl, or ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, etc.

[0042] In certain embodiments, the alkyl and alkenyl groups of formulas II and III can be unsubstituted or substituted with one or more groups selected from aryl, heteroaryl, hydroxy, alkoxy, alkylsulfonamido, arylsulfonamido, and halo.

[0043] In certain embodiments, the cycloalkenyl and heterocyclyl groups of formulas II and III can be unsubstituted or substituted with one or more groups selected from deuterium, alkyl, alkenyl, aryl, heteroaryl, hydroxy, alkoxy, alkylsulfonamido, arylsulfonamido, and halo.

[0044] In certain embodiments, the aryl and heteroaryl groups of formulas II and III can be unsubstituted or substituted with one or more groups selected from aryl, alkyl, heteroaryl, hydroxyl, and halo. In certain embodiments, the alkoxy groups of formulas II and III can be unsubstituted or substituted with one or more groups selected from aryl, alkyl, heteroaryl, hydroxyl, and halo.

[0045] In some embodiments, X and / or Y can be a straight chain C1-C4 alkyl or C2-C4 alkenyl. In some embodiments, X and Y are each methyl, X and Y are each ethyl, or X is methyl and Y is ethyl. In certain embodiments, X and / or Y are C1-C8 alkyl or C2-C8 alkenyl, optionally substituted with at least one halo group, e.g., fluorine. In certain embodiments, at least one of X or Y comprises a group selected from -CF3, -CHF2, -CH2F, -CH2CF3, -CH2CHF2, and -CH2CH2F. In certain embodiments, at least one of X or Y comprises a group selected from -CD3, -CH2CD3, -CD2CH3, and -CD2CD3.

[0046] In some embodiments, X is an unsubstituted C1-C8 alkyl. In some embodiments, X is methyl. In some embodiments, X is ethyl. In some embodiments, X is n-propyl. In some embodiments, X is isopropyl. In some embodiments, X is cyclopropyl. In some embodiments, Y is hydrogen. In some embodiments, Y is an unsubstituted C1-C8 alkyl. In some embodiments, Y is methyl. In some embodiments, Y is ethyl. In some embodiments, Y is n-propyl. In some embodiments, Y is isopropyl. In some embodiments, Y is cyclopropyl.

[0047] In some embodiments, R, R, R3’ , R and R are each independently selected from hydrogen, deuterium, halo, or C-C alkyl, e.g., linear C-C alkyl. In some embodiments, R, R, R 3’ , R6, and R7 are each independently selected from hydrogen, deuterium, halo, methyl, ethyl, n-propyl, isopropyl, n-butyl, and isobutyl. 3’ , R6 and R7 are each independently selected from hydrogen, deuterium, methyl, and ethyl.

[0048] In some embodiments, R2 is hydrogen. In some embodiments, R3 and R 3’ are each independently selected from hydrogen, methyl, and ethyl. In some embodiments, R is hydrogen. In some embodiments, R is methyl and R 3’ is hydrogen. In some embodiments, R and R 3’ In some embodiments, R and R 3’ In some embodiments, R is hydrogen and R 3’ is deuterium. In some embodiments, R and R 3’ When R and R are not the same, they represent a stereocenter, in which case the compound of formula II or III includes a racemic mixture. 3’ When R is not the same, a stereocenter is represented, in which case the compound of formula II or III comprises an (S) enantiomer. In some embodiments, when R is not hydrogen, a stereocenter is represented, in which case the compound of formula II or III comprises an (R) enantiomer. In some embodiments, the racemic mixture can be resolved to provide a pure enantiomer or a mixture enriched in either the (R) or the (S) enantiomer.

[0049] In some embodiments, R6 and R7 are each independently selected from hydrogen, halo, methyl, ethyl, n-propyl, isopropyl, n-butyl, and isobutyl. In some embodiments, R6 is selected from hydrogen and halo. In some embodiments, R6 is selected from hydrogen and fluorine. In some embodiments, R6 is fluorine. In some embodiments, R6 is selected from alkoxy and halo. In some embodiments, R6 is selected from methoxy, chloro, and fluoro. In some embodiments, R6 is fluorine. In some embodiments, R6 is methoxy. In some embodiments, R7 is selected from hydrogen and optionally substituted C1-C4 alkyl. In some embodiments, R7 is selected from hydrogen, methyl, and ethyl. In some embodiments, R7 is optionally substituted C1-C4 alkyl. In some embodiments, when R6 is fluoro, R7 is selected from hydrogen and optionally substituted C1-C4 alkyl.

[0050] In some embodiments, R4 is hydrogen and R5 is selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8. In some embodiments, R5 is selected from C1-C8 alkyl, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8. In some embodiments, R5 is selected from C2-C8 alkyl, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8. In some embodiments, R5 is hydroxy. In some embodiments, R5 is -OC(O)R8. In some embodiments, R8 is C1-C4 alkyl. In some embodiments, R8 is methyl.

[0051] In some embodiments, R5 is hydrogen and R4 is selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8. In some embodiments, R4 is selected from C1-C8 alkyl, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8. In some embodiments, R5 is selected from C1-C8 alkyl, -C2-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8. In some embodiments, R5 is -OC(O)R8. In some embodiments, R8 is C1-C4 alkyl. In some embodiments, R8 is methyl.

[0052] In certain embodiments, one or more hydrogen atoms on the compound of formula II or III can be replaced with one or more deuterium atoms. For example, in certain embodiments, R6 can include a deuterium atom as a hydrogen replacement, or when R7 is -CH3, each hydrogen atom can be replaced to form -CD3. Similarly, another non-limiting example includes when X and / or Y are -CH3, each hydrogen atom can be replaced to form -CD3.

[0053] In some embodiments, the compound of formula I is selected from the compound of formula IA: [ka] (Wherein, Group B, Linker L, X, Y, W1, W2, R2, R3, R 3’ , Z4, Z5, Z6, and Z7 are as defined herein; L can replace a hydrogen in an R4 group when Z4 is CR4, a hydrogen in an R5 group when Z5 is CR5, a hydrogen in an R6 group when Z6 is CR6, or a hydrogen in an R7 group when Z7 is CR7; L can replace a hydrogen atom in X or R2 group).

[0054] For the avoidance of doubt, the linker L does not bind to Z4, Z5, Z6, or Z7 when these are N.

[0055] In some embodiments, the compound of formula I is selected from the compound of formula IB: [ka] where L is a covalent linker; X, X1, Y and Y1 in each occurrence are independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl, or Y or Y1 together with X or X1, respectively, and the nitrogen atom therebetween form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; W1 and W 1a is independently selected from NR1, O, S, S(O), SO2, Se, Se(O), and SeO2; W2 and W 2a is independently selected from -CD2-, -CHD-, -(CD2)2-, -CH2-, and -(CH2)2-; Z4 and Z 4a is independently selected from N and CR4; Z5 and Z 5a is independently selected from N and CR5; Z6 and Z 6a is independently selected from N and CR6; Z7 and Z 7a is independently selected from N and CR7; R1 in each occurrence is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, -C(O)R8, -C(O)OR8, -OP(O)(OR9), -C(O)N(R9), -SOR8, and -SOR8; R2, R3, R6, R7, R 2a , R 3a , R 3’ and R 3a’ is independently selected from hydrogen, deuterium, -N(R9)2, -SR9, halo, optionally substituted C1-C8 alkyl, -C1-C8 alkoxy, and optionally substituted C2-C8 alkenyl; Or Y or Y1 is absent, and R3 or R 3a taken together with the carbon to which it is attached and the nitrogen atom to which X or X1 is attached, respectively, form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; Or X or X1 is absent and R2 or R 2a each taken together with the carbon to which it is attached and the nitrogen atom to which Y or Y1 is attached forms a 5-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; R4 and R5 in each occurrence are independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -N(R9)2, -SR9, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8; R8 at each occurrence is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; R9 at each occurrence is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; L is Z4 and / or Z 4a When R4 is CR4, hydrogen in R4 is replaced by Z5 and / or Z 5a When R5 is CR5, hydrogen in R5 is replaced by Z6 and / or Z 6a is CR6, hydrogen in R6 group, or Z7 and / or Z 7aWhen is CR7, hydrogen in the R7 group can be replaced; L can replace a hydrogen atom in X or R2 group).

[0056] For the avoidance of doubt, the linker L is Z4, Z 4a , Z5, Z 5a , Z6, Z 6a , Z 7a or when Z7 is N, it is not bound to these.

[0057] In some embodiments, the linker "L" is selected from Formula IV: [ka] (wherein L1, L2, L3, L4, L5, n, p, and q are as defined herein).

[0058] In some embodiments, L and L at each occurrence are independently a covalent bond, O, NR 10 In some embodiments, L1 and L5 are selected from, and S. In some embodiments, L1 and L5 are the same. In some embodiments, L1 and L5 are different. In some embodiments, L1 and L5 are both O. In some embodiments, L1 and L5 are both a covalent bond.

[0059] In some embodiments, L and L are independently O, C(R 10 )2, NR 10 In some embodiments, L2 and L4 are selected from O and C(R 10 In some embodiments, at least one of L2 or L4 is selected from C(R 10 )2.

[0060] In some embodiments, L3 at each occurrence is independently O, NR10 , S, C(R 10 )2, C(R 10 )=C(R 10 ), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl. In some embodiments, L3 at each occurrence is selected from S and C(R 10 In some embodiments, L3 at each occurrence is selected from S. In some embodiments, L3 at each occurrence is selected from C(R 10 )2 is selected.

[0061] In some embodiments, R in each occurrence 10 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, NO2, -N(R9)2, -SR9, halo, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8, where R8 and R9 are as defined herein. In some embodiments, R 10 For each occurrence, R is hydrogen. 10 is, for each occurrence, independently selected from hydrogen and methyl.

[0062] In other embodiments, R 10 is independently selected from any of the variables listed in the preceding paragraph and structures of formula IVA: [ka] (wherein L3, L4, L5, p, q, and Group B are as defined herein).

[0063] In some embodiments, one R 10 When R comprises the structure of formula IVA, the compound of formula I may be referred to as a "tripod" derivative (see, for example, compound [IIq] below). In some embodiments, R 10When two of the above groups contain the structure of formula IVA, the compound may be referred to as a "tetrapod" derivative (see, for example, compound [IIr] below).

[0064] In some embodiments, n is selected from 0 to 10, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 3.

[0065] In some embodiments, p is selected from 0 to 10, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, p is 0. In some embodiments, p is 2.

[0066] In some embodiments, q is selected from 0 to 10, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, q is 0. In some embodiments, q is 3. In some embodiments, q is 1.

[0067] In some embodiments, the compounds described herein are selected from formula IC: [ka] (Wherein, Group B, X, Y, W1, W2, R2, R3, R 3’ , Z4, Z5, Z6, Z7, L1, L2, L3, L4, L5, n, p, q are as defined herein; L5 can replace a hydrogen in an R4 group when Z4 is CR4, a hydrogen in an R5 group when Z5 is CR5, a hydrogen in an R6 group when Z6 is CR6, or a hydrogen in an R7 group when Z7 is CR7; L can replace a hydrogen atom in X or R2 group).

[0068] In some embodiments, the compounds described herein are selected from formula ID: [ka] (In the formula, X, Y, W1, W 1a , W2, W 2a , R2, R 2a , R3, R 3a , R 3’ , R 3a’ , Z4, Z 4a , Z5, Z 5a , Z6, Z 6a , Z7, Z 7a , L1, L2, L3, L4, L5, n, p, and q are as defined herein; L1 can replace a hydrogen in an R4 group when Z4 is CR4, a hydrogen in an R5 group when Z5 is CR5, a hydrogen in an R6 group when Z6 is CR6, or a hydrogen in an R7 group when Z7 is CR7; L1 can replace a hydrogen atom in X or R2 group; L5 can replace hydrogen, Z 4a When is CR4, hydrogen in the R4 group is replaced by Z 5a When R5 is CR5, hydrogen in the R5 group is replaced by Z 6a When is CR6, hydrogen in the R6 group is replaced by Z 7a When is CR7, hydrogen in the R7 group can be replaced; L5 can replace a hydrogen atom in X or R2 group).

[0069] In some embodiments, the compounds described herein are selected from formula IE: [ka] (In the formula, X, Y, R1, R2, R3, R 3’ , L1, L2, L3, L4, L5, n, p, and q are as defined herein; L1 is attached to carbon 4, 5, 6, or 7 where L1 replaces a hydrogen on that carbon; or L1 is connected to one or two nitrogens when R1 or X, respectively, are absent; L5 is attached to carbon 4a, 5a, 6a, or 7a where L5 replaces a hydrogen on the carbon; Or L5 is attached to the nitrogen of 1a or 2a when R1 or X is absent).

[0070] In some embodiments of compounds of formula IE, the linker at one end is connected to the first indole skeleton by a covalent bond between L1 and the 4th, 5th, 6th, or 7th carbon of the indole skeleton. In some embodiments, L1 is a covalent bond and the carbonyl of the linker is connected to the 4th, 5th, 6th, or 7th carbon of the indole skeleton. Alternatively, in some embodiments, L1 is a covalent bond and the carbonyl of the linker is connected to the 1st or 2nd nitrogen when R1 or X is absent.

[0071] In some embodiments, the opposite end of the linker is connected to group B by a covalent bond between L5 and carbon 4a, 5a, 6a, or 7a of the indole backbone. In some embodiments, the opposite end of the linker is connected to group B by a covalent bond between C(=O) of the linker and carbon 4a, 5a, 6a, or 7a of the indole backbone. Alternatively, in some embodiments where L5 is a covalent bond, the other end of the linker is connected to the indole by a covalent bond between C(=O) of the linker and nitrogen 1a or 2a when R1 or X is absent.

[0072] In certain embodiments, one or more hydrogen atoms on the compounds of formula I, II, III, and / or V can be replaced with one or more deuterium atoms. For example, in certain embodiments, R7 can include a deuterium atom as a replacement for hydrogen, or when R7 is -CH3, each hydrogen atom can be replaced to form -CD3. Similarly, another non-limiting example includes when X and / or Y are -CH3, each hydrogen atom can be replaced to form -CD3.

[0073] In some embodiments, compounds of formula V are described: [ka] (wherein groups A, L1, L2, L3, L4, L5, n, p, q, and Z' are as defined herein).

[0074] In some embodiments, Z' is selected from hydrogen, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl; and when L5 is O, Z' is selected from X + You can also choose from, where X + is a pharma- ceutically acceptable cation. Exemplary X+ cations include, but are not limited to, NH4+, K+, Na+, Ca+, and the like. In some embodiments, group A is a residue of a cannabinoid, such as Delta-8-THC, Delta-9-THC, THCA, THCV, THCVA, CBC, CBCA, CBCV, CBCVA, CBD, CBDA, CBDV, CBDVA, CBG, CBGA, CBGV, or CBGVA. In certain embodiments, when A is a cannabinoid, L1 is an oxygen derived from the phenolic oxygen of the cannabinoid. In some embodiments, L5 is an oxygen. In some embodiments, the sum of n, p, and q is greater than 2. In some embodiments, the sum of n, p, and q is an integer selected from 3 to about 16, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 14, or 16. In some embodiments, L2 and L4 are both -CH2-, and L3 is selected from -CH=CH- and -CH2-.

[0075] In certain embodiments, it has been surprisingly discovered that compounds of formula V in which the sum of n, p, and q is greater than 2 can rapidly "self-cleave" in vivo to provide an active compound (e.g., Delta-9-THC, derived from prodrug compound Vd, described below). Without being bound to any particular theory, it is believed that compounds in which the sum of n, p, and q is less than 3 do not undergo such rapid self-cleavage in vivo because this requires intramolecular formation of a constrained ring of 5 atoms or less, which is not optimal for the flexible ring of 6 atoms or more that is formed when the sum of n, p, and q is 3 or greater.

[0076] In certain embodiments, Group A in the compounds of formula I and / or V is selected from the group consisting of buspirone (8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione) or its enolate (enol alcohol) equivalent, 5-OH-buspirone, 6-OH-buspirone, tandospirone ((1R,2R,6S,7S)-4-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}-4-azatricyclo[5.2.1.02,6]decane-3,5-dione), gepirone (4,4-dimethyl-1-[4-(4-pyrimidin-2-yl)piperazin-1-yl]butyl}-4-azatricyclo[5.2.1.02,6]decane-3,5-dione), zymidine-2-ylpiperazin-1-yl)butyl]piperidine-2,6-dione), alnespirone ((+)-4-dihydro-2H-chromen-3-yl]-propylamino]butyl]-8-azaspiro[4.5]decane-7,9-dione), binospirone (8-[2-(2,3-dihydro-1,4-benzodioxin-2-ylmethylamino)ethyl]-8-azaspiro[4.5]decane-7,9-dione), ipsapirone (9,9-dioxo-8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-9.6-thia-8-azabicyclo[4.3]lambda-6.0]nona-1,3,5-trien-7-one), perospirone (3aR,7aS)-2-{4-[4-(1,2-benzisothiazol-3-yl)piperazin-1-yl]butyl}hexahydro-1H-isoindole-1,3(2H)-dione, befiladol (F-13,640) (3-chloro-4-fluorophenyl-[4-fluoro-4-([(5-methylpyridin-2-yl)methylamino]methyl)piperidin-1-yl]methanone, repinotan ((R -(-)-2-[4-[(chroman-2-ylmethyl)-amino]-butyl]-1,1-dioxo-benzo[d]isothiazolone), piclozotan (3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one), osemozotan (5-(3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3-benzodioxole), Resinoxan (4-fluoro-N-[2-[4-[(3S)-3-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-8-yl]piperazin-1-yl]ethyl]benzamide), flibanserin (1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1,3-dihydro-2H-benzimidazol-2-one), 8-OH-DPAT (7-(dipropylamino)-5,6,7,8-tetrahydronaphthalene) In certain embodiments, Group B in the compound of formula I is a residue of a 5-HT1A agonist selected from the 5-HT1A agonists listed above.

[0077] In certain embodiments, Group A in the compounds of formula I and / or V is a residue of a serotonin 5-HT2B receptor antagonist selected from agomelatine, amisulpride, ariprazole, carprazine, clozapine, cyproheptadine, mCCP, sarpogrelate, lisuride, tegasulod, metadoxine, and promethazine. In certain embodiments, Group B in the compounds of formula I is a residue of a serotonin 5-HT2B receptor antagonist selected from the 5-HT2B receptor antagonists above.

[0078] In certain embodiments, Group A in the compound of Formula I and / or V is a residue of a 5-HT2C receptor agonist selected from lorcaserin, babicaserin, aripiprazole, YM-348, PRX-00933, and meta-chlorophenylpiperazine. In certain embodiments, Group B in the compound of Formula I is a residue of a 5-HT2C receptor agonist selected from the 5-HT2C receptor agonists above.

[0079] In some embodiments, group A in the compounds of formula I and / or V is a residue of a serotonergic agent selected from any of the serotonergic agents listed herein. In some embodiments, group B in the compounds of formula I is a residue of a serotonergic agent selected from any of the serotonergic agents listed herein. In some embodiments, group A in the compounds of formula I and / or V is a residue of an antidepressant selected from any of the antidepressants listed herein. In some embodiments, group B in the compounds of formula I is a residue of an antidepressant selected from any of the antidepressants listed herein.

[0080] In certain embodiments, Group B in the compounds of Formula I and / or V is a residue of an adrenergic agonist selected from any of the adrenergic agonists listed herein. In certain embodiments, Group B in the compounds of Formula I and / or V is a residue of a dopaminergic agonist selected from any of the dopaminergic agonists listed herein. In certain embodiments, Group B in the compounds of Formula I and / or V is a residue of an anxiolytic selected from any of the anxiolytics listed herein.

[0081] Exemplary compounds of Formula I include variants of Dipsilocin™ shown below: [ka] [ka] [ka] As well as any salt, solvate, hydrate, and prodrug of compounds [Ia] to [In], but are not limited to these.

[0082] Other exemplary compounds of formula I include: [ka] [ka] [ka] [ka] [ka] [ka] [ka] As well as any salt, solvate, hydrate, and prodrug of compounds [IIa] to [IIz] are included.

[0083] Other exemplary compounds of formula I include: [ka] [ka] [ka] [ka] [ka] As well as any salt, solvate, hydrate, and prodrug of compounds [IIIa] to [IIIw] are included.

[0084] In some embodiments, compounds of formula V, including but not limited to: [ka] As well as salts, solvates, hydrates, and prodrugs of any of compounds [Va] to [Vd] are described.

[0085] In some embodiments, the compounds of formula I and / or formula V include salts. In some embodiments, the compounds of formula I and / or formula V include pharma- ceutically acceptable salts. Exemplary salts include, but are not limited to, HCl, HI, HBr, HF, ascorbate, hydrofumarate, fumarate, oxalate, maleate, and the like. In certain embodiments, the compounds of formula I and / or formula V are in their free base form. In some embodiments, the compounds of formula I and / or formula V include salts, such as [1:1] salts (e.g., HCl, hydrofumarate) or [2:1] salts (e.g., oxalate, fumarate). In some embodiments, for a [1:1] salt, one ammonium cation of one compound of formula II or III is in equilibrium with one anion (Cl-, I-, etc.). For a [2:1] salt, two ammonium cations of two molecules of formula II or III are in equilibrium with a dianionic species, such as a dianion derived from a diacid, e.g., oxalic acid and fumaric acid. Other exemplary salts include zwitterionic forms of compounds of formula II or III, e.g., when R1 is -P(O)(OH)2, -OH on R1 is deprotonated to give -O - and quaternary ethylammonium (e.g., -(CH2)2N + H(CH3)2) are also included.

[0086] Other exemplary compounds of formula ID include the subgenus of formula IDd described below and in Table 1: [ka] (In the formula, W2 and W 2a is -CH2-; Z4 and Z 4a are each CR4, where L1 and L5 replace R4 groups; Z5 and Z 5a is CR5; Z6 and Z 6a is CR6; Z7 and Z 7a is CR7; L1 and L5 are O; L2 and L4 at each occurrence are independently selected from O, CH2, NH, and S; L3 at each occurrence is independently selected from S and CH2; p is an integer selected from 0, 1, 2, and 3; n and q are each an integer independently selected from 0, 1, 2, 3, 4, 5, and 6. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10] [Table 1-11] [Table 1-12] [Table 1-13]

[0087] Compositions and methods As used herein, the term "5-HT1A" refers to the 5-HT1A receptor. As used herein, the term "5-HT2A" refers to the 5-HT2A receptor.

[0088] As used herein, the term "effective amount" in reference to a compound disclosed herein means an amount capable of treating or preventing a disorder, disease or condition disclosed herein, or a symptom thereof.

[0089] As used herein, the term "hallucination" (and related terms, e.g., "hallucinogenic" and "hallucinogen") refers to perceptions in the absence of external stimuli that have the properties of real perception. In some embodiments, the hallucinations can be vivid, substantial, and are perceived to be located in an external, objective space. As used herein, hallucinations can occur in any sensory modality, including, but not limited to, visual, auditory, olfactory, gustatory, tactile, proprioceptive, equilibrium, nociceptive, thermoceptive, and chronoceptive. In some embodiments, the hallucination is selected from visual hallucinations, auditory hallucinations, olfactory hallucinations, gustatory hallucinations, tactile hallucinations, proprioceptive hallucinations, equilibrium hallucinations, nociceptive hallucinations, thermoceptive hallucinations, chronoceptive hallucinations, and any combination thereof. In some embodiments, the hallucination is a visual hallucination.

[0090] As used herein, the terms "prevent" or "preventing" refer to a method of delaying and / or eliminating, in whole or in part, the onset, recurrence or spread of a disorder, disease or condition; inhibiting a subject from acquiring a disorder, disease or condition; or reducing a subject's risk of acquiring a disorder, disease or condition.

[0091] As used herein, the term "treat" or "treating" refers to the total or partial alleviation of a disorder, disease or condition, or one or more symptoms associated with a disorder, disease or condition, or the slowing or halting of further progression or worsening of those symptoms, or alleviating or eradicating the cause(s) of the disorder, disease or condition itself.

[0092] Further embodiments of the present disclosure describe novel compounds and compositions, as well as methods of administering them.In some embodiments, the compounds provided herein are for use in the methods provided herein.In some embodiments, the present disclosure provides the use of the compounds provided herein in the preparation of medicaments for treating one or more of the diseases or disorders provided herein.

[0093] In certain embodiments, the method comprises administering a serotonin 5-HT1A agonist and a serotonin 5-HT2A agonist. Without being bound to any particular theory, in certain embodiments, it has been surprisingly discovered that administering a serotonin 5-HT1A agonist and a serotonin 5-HT2A agonist can be effective in preventing or treating one or more of the conditions described herein. In certain embodiments, it has also been surprisingly discovered that administering a serotonin 5-HT1A agonist and a hallucinogenic 5-HT2A agonist can effectively treat a patient without the patient experiencing the hallucinogenic effects of the 5-HT2A agonist. Without intending to be bound by any particular theory, it is believed that a patient may experience therapeutic effects without experiencing hallucinogenic symptoms typically attributed to administration of a 5-HT2A agonist because the 5-HT1A agonist can "turn off" the hallucinogenic effects of the 5-HT2A agonist without significantly altering its agonism at the 5-HT2A receptor. In some embodiments, the 5-HT1A agonist is a partial agonist. In some embodiments, the 5-HT1A agonist is a full agonist. In some embodiments, the 5-HT2A agonist is a partial agonist. In some embodiments, the 5-HT2A agonist is a full agonist. In some embodiments, the 5-HT1A and / or 5-HT2A agonist may be selected from compounds of formula I and formula V herein. In some embodiments, the 5-HT1A and 5-HT2A agonists are the same compound (e.g., compounds of formula II or III).

[0094] In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered simultaneously. In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered at different times. In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered simultaneously in the same composition. In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered together as part of a compound of formula I, where group A is a 5-HT1A agonist residue (e.g., 8-OH-DPAT or 6-OH-buspirone linked to the linker "L" via a free hydroxyl group) and group B is a 5-HT2A agonist residue (e.g., psilocin or linked to the linker "L" via a free hydroxyl group).

[0095] In some embodiments, it has been surprisingly discovered that by utilizing multipodal (e.g., dimeric) compounds of formula I, two or more active compounds can be effectively delivered across the blood-brain barrier (BBB). For example, in some embodiments, it has been surprisingly discovered that linking a first compound (e.g., serotonergic drug A) to a second compound (e.g., active drug B) can enhance the overall efficacy of BBB penetration, half-life, and / or target activity when administered to a patient in need thereof. This is because co-administration of a particular compound (e.g., a serotonergic drug) with another drug (e.g., a cannabinoid) can have a synergistic effect on the resulting therapeutic properties of the compound.

[0096] As defined herein, a "full agonist" shall mean an agonist having an Emax% of at least 90% for a relevant serotonin receptor agonist assay (e.g., BRET2, calcium mobilization, beta-arrestin) when compared to an industry-accepted control compound for that particular receptor assay (e.g., serotonin (5-OH-tryptamine)). In some embodiments, a "full agonist" will exhibit an Emax% of at least 90, at least 91, at least 92, at least 93, at least 94, at least 95, at least 96, at least 97, at least 98, or at least 99%. Also, as defined herein, a "partial agonist" shall mean an agonist having an Emax% of less than 90% for a relevant serotonin receptor when compared to an industry-accepted control compound for that particular receptor assay (e.g., serotonin (5-OH-tryptamine)). In some embodiments, a "partial agonist" will exhibit an Emax% of less than 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10%, or even less than 5%. In some embodiments, a partial agonist will exhibit an Emax% of about 0.1 to about 89.9%, such as about 1 to about 89, about 5 to about 85, about 50 to about 88, about 40 to about 85, about 35 to about 75, about 25 to about 65, or about 20 to about 55%.

[0097] In some embodiments, a 5-HT1A agonist, as used herein, is any of buspirone (8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione) or its enolate (enol alcohol) equivalent, 5-OH-buspirone, 6-OH-buspirone, tandospirone ((1R,2R,6S,7S)-4-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}-4-azatricyclo[5.2.1.02,6]decane-3,5-dione), gepirone (4,4-dimethyl-1-[4-(4- pyrimidin-2-ylpiperazin-1-yl)butyl]piperidine-2,6-dione), alnespirone ((+)-4-dihydro-2H-chromen-3-yl]-propylamino]butyl]-8-azaspiro[4.5]decane-7,9-dione), binospirone (8-[2-(2,3-dihydro-1,4-benzodioxin-2-ylmethylamino)ethyl]-8-azaspiro[4.5]decane-7,9-dione), ipsapirone (9,9-dioxo-8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-9.6-thia-8-azabicyclo[4.3]lambda-6.0]nona-1,3,5-trien-7-one), perospirone (3aR,7aS)-2-{4-[4-(1,2-benzisothiazol-3-yl)piperazin-1-yl]butyl}hexahydro-1H-isoindole-1,3(2H)-dione, befiladol (F-13,640) (3-chloro-4-fluorophenyl-[4-fluoro-4-([(5-methylpyridin-2-yl)methylamino]methyl)piperidine-1-yl 1,2-Dioxo-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one), osemozotan (5-(3-[((2S)-1,4-benzodioxan-2-yl)methyl]methanone), repinotan ((R)-(-)-2-[4-[(chroman-2-ylmethyl)-amino]-butyl]-1,1-dioxo-benzo[d]isothiazolone), piclozotan (3-chloro ... (1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1,3-dihydro-2H-benzodioxol), flesinoxan (4-fluoro-N-[2-[4-[(3S)-3-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-8-yl]piperazin-1-yl]ethyl]benzamide), flibanserin (1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1,3-dihydro-2H-benzoimidazo[4-fluoro-N-[2-[4-[(3S)-3-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-8-yl]piperazin-1-yl]ethyl)benzamide), The compound is selected from the group consisting of 1-[(2R)-3,4-dihydro-2H-chromen-2-yl]-N-([5-(4-fluorophenyl)pyridin-3-yl]methyl)methanamine, 8-OH-DPAT (7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol), and sarizotan (EMD-128,130) (1-[(2R)-3,4-dihydro-2H-chromen-2-yl]-N-([5-(4-fluorophenyl)pyridin-3-yl]methyl)methanamine), a compound of formula II or III, or a prodrug, salt, or derivative thereof.

[0098] In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered simultaneously. In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered at different times. In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered sequentially. In some embodiments, the serotonin 5-HT1A agonist is administered first and the 5-HT2A agonist is administered second. In some embodiments, the serotonin 5-HT2A agonist is administered about 30 minutes to about 12 hours, for example, about 1 hour to about 6 hours, after administration of the 5-HT1A agonist. In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2A agonist are administered simultaneously in the same composition. In some embodiments, the 5-HT1A agonist is selected from buspirone, 5-OH-buspirone, 6-OH-buspirone, and 8-OH-DPAT. In some embodiments, the 5-HT1A agonist is buspirone. In some embodiments, the 5-HT1A agonist is selected from a compound of formula I, such as, for example, a compound of formula IE and a compound of formula V. In some embodiments, the 5-HT2A agonist is hallucinogenic. In some embodiments, the 5-HT2A agonist is non-hallucinogenic. In some embodiments, the 5-HT2A agonist is selected from a compound of formula I, such as, for example, a compound of formula IE and a compound of formula V.

[0099] In some embodiments, the 5-HT2A agonist and the 5-HT1A agonist may comprise the same compound. In some embodiments, the compounds of formula II and III described herein may act as both 5-HT1A receptor and 5-HT2A receptor agonist. In some embodiments, the compounds described herein are full agonists for both 5-HT1A and 5-HT2A.

[0100] In some embodiments, the 5-HT1A agonist and the 5-HT2A agonist are full agonists at the 5-HT1A and 5-HT2A receptors, respectively. In some embodiments, the 5-HT1A agonist exhibits a higher level of molar potency (i.e., a lower EC50) for activating the 5-HT1A receptor than the 5-HT2A agonist exhibits when activating the 5-HT2A receptor. 50 ) without being bound by any particular scientific theory, in certain embodiments, it has been surprisingly discovered that compounds that are agonists for 5-HT1A and 5-HT2A (but exhibit a higher molar potency for 5-HT1A) may be useful for patients needing / desiring non-hallucinogenic 5-HT2A modulation. In other embodiments, the 5-HT1A agonist is a partial agonist (e.g., buspirone) and the 5-HT2A agonist is a full agonist for the 5-HT1A and 5-HT2A receptors, respectively. In other embodiments, the 5-HT1A agonist is a partial agonist (e.g., buspirone) and the 5-HT2A agonist is a partial agonist for the 5-HT1A and 5-HT2A receptors, respectively.

[0101] In certain embodiments, a method is described for treating, preventing, ameliorating, or curing a disease or disorder through a non-hallucinogenic therapeutic treatment regimen that includes modulation of the 5-HT1A receptor. In certain embodiments, the method includes identifying a subject in need of treatment for a disease or condition associated with modulation of the 5-HT1A receptor; selecting a compound of formula I (e.g., formula IE) and / or formula V; and administering the compound to the subject in need of treatment, wherein the compound modulates activity at both the 5-HT1A receptor and the 5-HT2A receptor. In certain embodiments, the compound of formula I and / or formula V is a full agonist at the 5-HT1A receptor. In certain embodiments, the compound of formula I and / or formula V is a full agonist at both the 5-HT1A receptor and the 5-HT2A receptor. In certain embodiments, the compound of formula I and / or formula V is a partial agonist at the 5-HT1A receptor and a full agonist at the 5-HT2A receptor. In certain embodiments, the compounds of Formula I and / or Formula V are partial agonists at the 5-HT1A receptor and partial agonists at the 5-HT2A receptor. In certain embodiments, the compounds of Formula I and / or Formula V have a higher molar potency (lower EC 50 ) is shown.

[0102] In certain embodiments, the 5-HT1A agonist has an EC for activating the 5-HT1A receptor of less than about 100 nM, e.g., less than about 75 nM, less than about 50 nM, less than about 25 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. 50 In certain embodiments, the 5-HT2A agonist has an EC for activating the 5-HT2A receptor of less than about 100 nM, e.g., less than about 75 nM, less than about 50 nM, less than about 25 nM, less than about 15 nM, less than about 10 nM, or less than about 5 nM. 50 In certain embodiments, the 5-HT1A agonist has an EC for activating the 5-HT1A receptor of about 0.01 nM to about 100 nM, e.g., about 0.05 to about 50 nM, about 0.1 to about 25 nM, or about 0.5 to about 10 nM. 50In certain embodiments, the 5-HT2A agonist has an EC for activating the 5-HT2A receptor of about 0.01 nM to about 100 nM, e.g., about 0.05 to about 50 nM, about 0.1 to about 25 nM, or about 0.5 to about 10 nM. 50 In certain embodiments, the 5-HT2A agonist has an EC for activating the 5-HT2A receptor of about 5 nM to about 75 nM, e.g., about 10 to about 60 nM, about 15 to about 50 nM, or about 20 to about 40 nM. 50 In some embodiments, the 5-HT1A agonist / 5-HT2A agonist has an EC ratio of 5-HT1A receptor:5-HT2A receptor in the range of about 1:2 to about 1:100, e.g., about 1:5 to about 1:50 or about 1:10 to about 1:40. 50 In some embodiments, the active drugs of the compounds of Formula I (e.g., a first active compound of Group A and a second active compound of Group B, respectively) independently have an EC50 of the 5-HT1A receptor:5-HT2A receptor in the range of about 1:2 to about 1:100, e.g., about 1:5 to about 1:50, or about 1:10 to about 1:40, when the compounds are released (e.g., in vivo). 50 Ratios are shown. Full vs. partial agonism (Emax%) and molar potency (EC 50 Relevant test parameters for determining 5-HT function include those known to one of skill in the art, such as the 5-HT functionality assay further described in the Biological Examples below.

[0103] In some embodiments, novel compounds and compositions are also described, as well as methods of administering them. In certain embodiments, the methods include administering a serotonin 5-HT2A agonist and a serotonin 5-HT2B antagonist. Without being bound to any particular theory, in certain embodiments, it has been surprisingly discovered that administering a serotonin 5-HT2A agonist and a serotonin 5-HT2B antagonist can be effective in preventing or treating one or more of the conditions described herein. In some embodiments, it has been surprisingly discovered that administering a serotonin 5-HT2A agonist and a serotonin 5-HT2B antagonist can effectively treat patients while also reducing serotonin 5-HT2B-induced cardiac toxicity (e.g., cardiac valve fibrosis and hypertrophy). In some embodiments, it has also been surprisingly discovered that administering a serotonin 5-HT2B antagonist and a 5-HT2A agonist can be safely and effectively used to treat patients described herein without the patient experiencing hallucinogenicity that may be associated with hallucinogenic 5-HT2A agonists. In some embodiments, the 5-HT2A agonist is a full agonist. In some embodiments, the 5-HT2A agonist is a partial agonist. In some embodiments, the 5-HT2B antagonist is a full antagonist. In some embodiments, the 5-HT2B antagonist is a partial antagonist.

[0104] Exemplary serotonin 5-HT2B receptor antagonists include, but are not limited to, agomelatine, amisulpride, ariprazole, carprazine, clozapine, cyproheptadine, mCCP, sarpogrelate, lisuride, tegasulod, metadoxine, and promethazine. In some embodiments, the 5-HT2B antagonist is not an antagonist at any of the other serotonin 5-HT type receptor subtypes, such as 5-HT1A and 5-HT2A. In some embodiments, the 5-HT2B receptor antagonist is also a full or partial agonist at the 5-HT1A and / or 5-HT2A receptors.

[0105] In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2B antagonist are administered simultaneously. In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2B antagonist are administered at different times. In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2B antagonist are administered simultaneously in the same composition. In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2B antagonist are administered together as part of a compound of formula I, where group A is a 5-HT2B antagonist residue and group B is a 5-HT2A agonist residue (e.g., psilocin linked to a linker "L" via a free hydroxyl group). In some embodiments, the serotonin 5-HT1A agonist and the 5-HT2B antagonist are administered sequentially. In some embodiments, the serotonin 5-HT2B antagonist is administered first and the 5-HT2A agonist is administered second. In some embodiments, the serotonin 5-HT2A agonist is administered about 30 minutes to about 12 hours, for example, about 1 hour to about 6 hours, after administration of the 5-HT2B antagonist. In some embodiments, the 5-HT2A agonist is hallucinogenic. In some embodiments, the 5-HT2A agonist is non-hallucinogenic. In some embodiments, the 5-HT2A agonist is selected from a compound of formula I, for example, compounds of formula IE and formula V.

[0106] In some embodiments, novel compounds and compositions, as well as methods of administering the same, are also described. In certain embodiments, the methods include administering a serotonin 5-HT2A agonist and a serotonin 5-HT2C agonist. Without being bound to any particular theory, in certain embodiments, it has been surprisingly discovered that administering a serotonin 5-HT2A agonist and a serotonin 5-HT2C agonist can be effective in preventing or treating one or more of the conditions described herein. In some embodiments, it has been surprisingly discovered that administering a serotonin 5-HT2A agonist and a serotonin 5-HT2C agonist can effectively treat a patient while also reducing or eliminating the hallucinogenic "trip" typically associated with 5-HT2A agonists. In some embodiments, the 5-HT2A agonist is a full agonist. In some embodiments, the 5-HT2A agonist is a partial agonist. In some embodiments, the 5-HT2C agonist is a full agonist. In some embodiments, the 5-HT2C agonist is a partial agonist.

[0107] Exemplary serotonin 5-HT2C receptor agonists include, but are not limited to, lorcaserin, babicaserin, aripiprazole, YM-348, PRX-00933, and meta-chlorophenylpiperazine.In some embodiments, the 5-HT2C agonist is not an agonist at any of the other serotonin 5-HT type receptor subtypes, such as 5-HT1A and 5-HT2B.In some embodiments, the 5-HT2C receptor agonist is inactive or only a partial agonist at 5-HT1A and / or 5-HT2B receptors.

[0108] In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2C agonist are administered simultaneously. In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2C agonist are administered at different times. In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2C agonist are administered simultaneously in the same composition. In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2C agonist are administered together as part of a compound of formula I, where group A is a 5-HT2C agonist residue and group B is a 5-HT2A agonist residue (e.g., psilocin linked to a linker "L" via a free hydroxyl group). In some embodiments, the serotonin 5-HT2A agonist and the 5-HT2C agonist are administered sequentially. In some embodiments, the serotonin 5-HT2C agonist is administered first and the 5-HT2A agonist is administered second. In some embodiments, the serotonin 5-HT2A agonist is administered about 30 minutes to about 12 hours, for example, about 1 hour to about 6 hours, after administration of the 5-HT2C agonist. In some embodiments, the 5-HT2A agonist is hallucinogenic. In some embodiments, the 5-HT2A agonist is non-hallucinogenic. In some embodiments, the 5-HT2A agonist is selected from a compound of formula I, for example, compounds of formula IE and formula V.

[0109] In some embodiments, the 5-HT2A agonist and the 5-HT2C agonist may comprise the same compound. In some embodiments, the compounds of formula I (e.g., compounds of formula IE) and formula V may act as both 5-HT2C and 5-HT2A receptor agonists. In some embodiments, the compounds described herein are full agonists for both 5-HT2A and 5-HT2C. In some embodiments, the compounds described herein act as partial agonists at 5-HT2A and full agonists at 5-HT2C. In some embodiments, the compounds described herein are partial agonists for both 5-HT2A and 5-HT2C. In some embodiments, the compounds described herein act as agonists at 5-HT2A and 5-HT2C, but are only partial agonists (or inactive) at the 5-HT2B receptor.

[0110] In certain embodiments of the compounds described herein, applicants have discovered that the size and nature of the alkyl groups for X and / or Y can dramatically affect the metabolism of such compounds. For example, compounds such as 5-MeO-dimethyltryptamine (5-MeO-DMT) and dimethyltryptamine (DMT) are theorized to be inactive upon oral administration due to rapid metabolism of the methylamino group by monoamine oxidase (MAO) enzymes. On the other hand, the oral stability of psilocin (4-OH-dimethyltryptamine) is largely due to the intramolecular coordination (hydrogen bonding) between the 4-OH group and the dimethylamino group, which is also theorized to effectively block / inhibit rapid MAO degradation.

[0111] Without being bound to any particular scientific theory, applicants have surprisingly found that substituting the alkyl groups X and / or Y with substituents such as deuterium and fluorine can aid in inhibiting MAO degradation of those groups even in the absence of a hydrogen bond donor (e.g., -OH) at the 4-position. Also, or alternatively, applicants have found that using non-methyl alkyl groups, such as ethyl or n-propyl, for X and / or Y can also slow down or inhibit rapid MAO metabolism upon oral administration. This in turn allows for the preparation of orally available compounds of formula I and / or formula V that are highly active serotonergic agents that do not require special formulation procedures (e.g., dosages containing MAO inhibitors) or the presence of a hydrogen bond donor at the 4-position, which in some cases can negatively affect the properties of the base compound (e.g., reduced 5-HT1A and / or 5-HT2A agonism).

[0112] In some embodiments, Applicants also provide for the alpha-deuteration (R and / or R 3’ Applicants have surprisingly discovered that heavier deuterium isotopes (where R3 or R4) can dramatically improve the pharmacokinetics of those compounds. Without being bound to any particular scientific theory, it is believed that the heavier deuterium isotopes interfere with the enzymatic metabolism of those compounds. However, in some embodiments, it may not be desirable to "over-deuterate" the compounds, for example by including deuterium species for groups X and Y or deuterium at the beta position (i.e., W2), which may further alter the pharmacokinetic profile of the compound in an undesirable manner (e.g., greatly extended half-life). Thus, in some embodiments, Applicants have discovered that minimal deuteration can be used to achieve the desired pharmacokinetic outcome. For example, in some embodiments, ... 3’A single deuterium atom at the alpha position can significantly enhance the desired pharmacokinetic profile. It is theorized that this may be due, in part, to the creation of a stereocenter at the alpha position upon deuteration that affects the ability of enzymes to metabolize the compound (e.g., preventing MAO degradation and / or the ability of enzymes to oxidize the alpha position during metabolic processes).

[0113] In one embodiment, the compounds, methods, and pharmaceutical compositions described herein are used to modulate neurotransmitter receptor activity by administering a therapeutically effective amount of a compound of Formula I and / or Formula V. The methods include administration of a therapeutically effective amount of a compound of Formula I and / or Formula V to prevent or treat a psychiatric disorder, such as those discussed herein. The compounds described herein may be administered neat or as a pharmaceutical composition comprising a compound of Formula I and / or Formula V as discussed herein.

[0114] In some embodiments, the compounds described herein can be used to prevent and / or treat psychiatric disorders. The present disclosure provides a method for preventing and / or treating psychiatric disorders by administering to a subject in need thereof a therapeutically effective amount of a compound of formula I and / or formula V, including the exemplary embodiments discussed herein. The mental disorder may be selected from depression; psychotic disorder; schizophrenia; schizophreniform disorder (acute schizophrenic episode); schizoaffective disorder; bipolar I disorder (mania, manic disorder, manic depression); bipolar II disorder; major depressive disorder; major depressive disorder with psychotic features (psychotic depression); delusional disorder (paranoia); shared psychotic disorder (shared paranoid disorder); brief psychotic disorder (other and unspecified reaction psychosis); psychotic disorder not otherwise specified (unspecified psychosis); paranoid personality disorder; schizotypal personality disorder; schizophreniform personality disorder; anxiety disorder; social phobia; substance-induced anxiety disorder; selective mutism; panic disorder; panic attacks; agoraphobia; attention deficit disorder; post-traumatic stress disorder (PTSD); premenstrual dysphoric disorder (PMDD), and premenstrual syndrome (PMS).

[0115] In some embodiments, the compounds described herein can be used to prevent and / or treat brain disorders. The present disclosure provides a method for preventing and / or treating brain disorders by administering to a subject in need thereof a therapeutically effective amount of a compound of formula I and / or formula V, including the exemplary embodiments discussed above. The brain disorder can be selected from Huntington's disease, Alzheimer's disease, dementia, and Parkinson's disease.

[0116] In some embodiments, the compounds described herein may be used to prevent and / or treat developmental disorders, delirium, dementia, amnesic disorders and other cognitive disorders, psychiatric disorders due to somatic pathology, substance-related disorders, schizophrenia and other psychotic disorders, mood disorders, anxiety disorders, somatic disorders, factitious disorders, dissociative disorders, eating disorders, sleep disorders, impulse control disorders, adjustment disorders, or personality disorders. The present disclosure provides methods for preventing and / or treating these disorders by administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I and / or Formula V, including the exemplary embodiments discussed above.

[0117] In some embodiments, the compounds described herein may be used to prevent and / or treat inflammation and / or pain, such as inflammation and / or pain associated with an inflammatory skeletal or muscular disease or condition. Thus, the present disclosure relates to a method for preventing and / or treating inflammation and / or pain by administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I and / or Formula V, including the exemplary embodiments discussed above. Generally speaking, treatable "pain" includes nociceptive, neuropathic, and mixed types. The methods of the present disclosure may reduce or alleviate symptoms associated with inflammation, including but not limited to treating localized signs of inflammation, in some cases characterized by acute or chronic swelling, pain, redness, elevated temperature, or loss of function. The methods of the present disclosure may reduce or alleviate symptoms of pain, regardless of the cause of the pain, including but not limited to reducing pain of various severity, i.e., mild, moderate, and severe pain, acute pain, and chronic pain. The method of the present disclosure is effective in treating inflammation, such as rheumatoid arthritis-induced joint pain, muscle pain, tendon pain, burn pain, and pain.Skeletal or muscular diseases or conditions that can be treated include, but are not limited to, musculoskeletal sprains, musculoskeletal strains, tendinopathy, peripheral radiculopathy, osteoarthritis, degenerative joint disease, rheumatic polymyalgia, juvenile arthritis, gout, ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, costochondritis, tendonitis, bursitis, such as common lateral epicondylitis (tennis elbow), medial epicondylitis (baseball elbow) and trochanteric bursitis, temporomandibular joint syndrome, and fibromyalgia.

[0118] In other embodiments, the methods and compositions disclosed herein include regulating the activity of neurotransmitter receptors with a formulation comprising a compound described herein, including a compound of Formula I and / or Formula V. In one embodiment, the methods and compositions disclosed herein include administering a first dosage formulation comprising at least one compound of Formula I and / or Formula V, which may include a serotonergic agent (Group A) and a second active compound (Group B). In one embodiment, the second active compound comprises a neurotransmitter activity modulator (e.g., a second serotonergic agent). In one embodiment, the second active compound comprises at least one cannabinoid, at least one terpene, or a second serotonergic agent.

[0119] The present disclosure relates to compositions comprising, consisting essentially of, or consisting of an effective amount of a compound of formula I and / or formula V and an excipient. The terms "composition" and "formulation" are used interchangeably herein. Other embodiments relate to pharmaceutical compositions comprising, consisting essentially of, or consisting of a therapeutically effective amount of a compound of formula I and / or formula V (including those discussed above) and a pharma- ceutically acceptable excipient (also known as a pharma-ceutically acceptable carrier). As discussed above, the compounds of formula I and / or formula V may be therapeutically useful for preventing and / or treating, for example, psychiatric disorders, brain disorders, pain and inflammation, and other disorders, such as those discussed above.

[0120] In some embodiments, the compositions described herein may comprise at least one compound of formula I, which itself comprises a residue of a first active compound comprising a serotonergic agent, and a residue of a second active compound selected from at least one of a second serotonergic agent, a cannabinoid, a terpene, or an MAO inhibitor. In certain embodiments, the second compound may be derived from a natural source, such as fungi (e.g., shiitake mushroom; Yamabushitake mushroom (containing terpenes, e.g., erinacine and hericenones)) and plants (e.g., hemp). Thus, in certain embodiments, the second compound may be derived from or extracted from fungal or plant material, which means that the second compound may or may not be "purified" depending on the method of extraction from which it originates.

[0121] Within the context of the present disclosure, the term "purified" means separated from other compounds or substances, e.g., plant or fungal substances, e.g., proteins, chitin, cellulose, or water. In one embodiment, the term "purified" refers to a compound that is substantially free of other substances. In one embodiment, the term "purified" refers to a compound that is substantially free of a second compound (e.g., an enantiomeric compound of Formula I and / or Formula V that exhibits 99% enantiomeric excess after resolution). In one embodiment, the term "purified" refers to a compound that is substantially free of biological substances, e.g., mold, fungus, plant material, or bacteria.

[0122] In one embodiment, the term "purified" refers to a compound or composition that has been crystallized. In one embodiment, the term "purified" refers to a compound or composition that has been chromatographed, for example, by gas chromatography, liquid chromatography (e.g., LC, HPLC, etc.), etc. In one embodiment, the term "purified" refers to a compound or composition that has been distilled. In one embodiment, the term "purified" refers to a compound or composition that has been sublimated. In one embodiment, the term "purified" refers to a compound or composition that has been subjected to two or more processes selected from crystallization, chromatography, distillation, and sublimation.

[0123] In one embodiment, the term "purified" refers to a compound having a purity in the range of about 80% to about 100%, meaning that the compound comprises about 80% to about 100% of the total mass of the composition. In one embodiment, the term "purified" refers to a compound having a purity in the range of about 90% to about 100%, meaning that the compound comprises about 90% to about 100% of the total mass of the composition. In one embodiment, the term "purified" refers to a compound having a purity in the range of about 95% to about 100%, meaning that the compound comprises about 95% to about 100% of the total mass of the composition. In one embodiment, the term "purified" refers to a compound having a purity in the range of about 99% to about 100% pure, meaning that the compound comprises about 99% to about 100% of the total mass of the composition. In one embodiment, the term "purified" refers to a compound having a purity in the range of about 99.9% to about 100%, meaning that the compound comprises about 99.9% to about 100% of the total mass of the composition.

[0124] As used herein, the term "specific ratio" refers to the amount of one compound relative to the amount of another compound(s). In one embodiment, there is about a 1:1 ratio of 4-acetoxy-3-[2-(dimethylamino)ethyl]-benzo[b]thiophene) to 4-hydroxy-N,N-dimethyltryptamine. In one embodiment, the specific ratio of the compounds is measured by the same units, e.g., grams, kilograms, pounds, ounces, etc. In one embodiment, the specific ratio of the compounds is measured in moles, i.e., molar concentration ratio or molar ratio.

[0125] As used herein, the term "specific amount" refers to a compound or an amount of a compound. In one embodiment, the specific amount is the combined amount of two compounds in a sample. In one embodiment, the specific amount is measured by dry weight. In one embodiment, the specific amount has 1, 2, 3, or 4 significant digits.

[0126] Also disclosed herein are compositions comprising a compound of formula I and / or formula V and an additional compound. In one embodiment, the compositions disclosed herein comprise a molar ratio of a compound of formula I and / or formula V (e.g., a 5-HT2A receptor agonist) to an additional compound (e.g., a 5-HT1A receptor agonist) ranging from about 10:1 to about 1:10. In one embodiment, the compositions disclosed herein comprise a molar ratio of a compound of formula I and / or formula V to an additional compound ranging from about 100:1 to about 1:100. In one embodiment, the compositions disclosed herein comprise a molar ratio of a compound of formula I and / or formula V to an additional compound ranging from about 1,000:1 to about 1:1,000. In one embodiment, the compositions disclosed herein comprise a molar ratio of a compound of formula I and / or formula V to an additional compound ranging from about 10,000:1 to about 1:10,000.

[0127] Within the context of the present disclosure, unless otherwise specified, the serotonergic compounds (e.g., tryptamine compounds) described herein may be present in their protonated or deprotonated (salt or free base) forms or mixtures thereof, depending on the situation, e.g., the pH of the solution or composition. However, in certain embodiments, the serotonergic compounds described herein are lipophilic, which means that they tend to combine with lipids and fats and can easily cross biological membranes (e.g., the blood-brain barrier) in the animal or human body. In certain embodiments, the serotonergic compounds in free base form are lipophilic.

[0128] As used herein, the term "salt" refers to a neutralized ionic compound. In one embodiment, a salt is formed from the neutralization of an acid and a base. In one embodiment, a salt is electrically neutral.

[0129] In one embodiment, the compositions and methods disclosed herein include administering a first cannabinoid. In one embodiment, the first cannabinoid is a first purified cannabinoid.

[0130] As used herein, the term "cannabinoid" refers to compounds and their derivatives from a class of molecules commonly found in plants of the Cannabis genus. In one embodiment, the cannabinoid is endogenous to animals, i.e., endogenous cannabinoids. In one embodiment, the cannabinoid is derived from a plant, e.g., a plant of the Cannabis genus, e.g., a phytocannabinoid. In one embodiment, the cannabinoid is artificially created in a laboratory, i.e., a synthetic cannabinoid. Many cannabinoids can be identified by the letter "cannabi" in their chemical name. There are at least 113 different cannabinoids isolated from Cannabis, which show a variety of (similar and different) effects.

[0131] Examples of cannabinoids within the context of this disclosure include the following molecules: cannabichromene (CBC), cannabichromene acid (CBCA), cannabichromevarin (CBCV), cannabichromevaric acid (CBCVA), cannabicyclol (CBL), cannabicyclo acid (CBLA), cannabicyclovaline (CBLV), cannabidiol (CBD), cannabidiol monomethyl ether (CBDM), cannabidiolic acid (CBDA), cannabidiolcol (CBD-C1), cannabidivarin (CBDV), cannabidivaric acid (CBDVA), cannabielsoic acid B (CBEA-B), cannabielsoin (CBE), cannabielsoic acid A (CBEA-A), cannabigerol (CBG), cannabigerol monomethyl ether (CBGM), cannabigerolic acid (CBGA), cannabigerolic acid monomethyl ether (CBGA M), cannabigerovarin (CBGV), cannabigerovaric acid (CBGVA), cannabinodiol (CBND), cannabinodivarine (CBDV), cannabinol (CBN), cannabinol methyl ether (CBNM), cannabinol-C2 (CBN-C2), cannabinol-C4 (CBN-C4), cannabinolic acid (CBNA), cannabiocool (CBN-C1), cannabivarin (CBV), cannabidiol (CBT), cannabidiol valine (CBTV), 10-ethoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, cannabiditran (CBT), cannabilipsol (CBR), 8,9-dihydroxy-delta-6a-tetrahydrocannabinol, delta-8-tetrahydrocannabinol (.delta.8-THC), delta-8-tetrahydrocannabinolic acid (.delta.8-THCA), delta-9-tetrahydrocannabinol (THC), delta-9-tetrahydrocannabinol-C4 (THC-C4), delta-9-tetrahydrocannabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9-tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabiolchol (THC-C1), delta-9-tetrahydrocannabiolcholic acid (THCA-C1), delta-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydrocannabi These include cannabinoids such as valinic acid (THCVA), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone (CBCF), cannabifuran (CBF), cannabiglendol, delta-9-cis-tetrahydrocannabinol (cis-THC), trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), dehydrocannabifuran (DCBF), and 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trimethyl-9-n-propyl-2,6-methano-2H-1-benzoxin-5-methanol.

[0132] In one embodiment, the term "cannabinoid" refers to a compound selected from THC, THCA, THCV, THCVA, CBC, CBCA, CBCV, CBCVA, CBD, CBDA, CBDV, CBDVA, CBG, CBGA, CBGV, and CBGVA.

[0133] Within the context of this disclosure, the term "THC" includes any derivative of delta-9-tetrahydrocannabinol and / or its salts. In one embodiment, the compound of formula I may contain a THC residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0134] Within the context of this disclosure, the term "THCA" includes any derivative of tetrahydrocannabinolic acid and / or its salts. In one embodiment, a compound of formula I may contain a THCA residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0135] Within the context of this disclosure, the term "THCV" includes any derivative of delta-9-tetrahydrocannabivarin and / or its salts. In one embodiment, the compound of formula I may contain a THCV residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0136] Within the context of this disclosure, the term "THCVA" includes any derivative of delta-9-tetrahydrocannabivarinic acid and / or its salts. In one embodiment, the compound of formula I may contain a THCVA residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0137] Within the context of this disclosure, the term "CBC" includes any derivative of cannabichromene and / or its salts. In one embodiment, a compound of formula I may contain a CBC residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0138] Within the context of the present disclosure, the term "CBCA" includes any derivative of cannabichromenic acid and / or its salts. In one embodiment, a compound of formula I may contain a CBCA residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0139] Within the context of the present disclosure, the term "CBCV" includes any derivative of cannabichromevalin and / or its salts. In one embodiment, a compound of formula I may contain a CBCV residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0140] Within the context of the present disclosure, the term "CBCVA" includes any derivative of cannabichromevarinic acid and / or its salts. In one embodiment, a compound of formula I may contain a CBCVA residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0141] Within the context of the present disclosure, the term "CBD" includes any derivative of cannabidiol and / or its salts. In one embodiment, a compound of formula I may contain a CBD residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0142] Within the context of the present disclosure, the term "CBDA" includes any derivative of cannabidiolic acid and / or its salts. In one embodiment, a compound of formula I may contain a CBDA residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0143] Within the context of the present disclosure, the term "CBDV" includes any derivative of cannabidivarin and / or its salts. In one embodiment, the compound of formula I may include a CBDV residue (i.e., group B) and a serotonergic agent such as psilocin (i.e., group A).

[0144] Within the context of the present disclosure, the term "CBDVA" includes any derivative of cannabidivarinic acid and / or its salts. In one embodiment, a compound of formula I may include a CBDVA residue (i.e., group B) and a serotonergic agent such as psilocin (i.e., group A).

[0145] Within the context of the present disclosure, the term "CBG" includes any derivative of cannabigerol and / or its salts. In one embodiment, the compound of formula I may contain a CBG residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0146] Within the context of the present disclosure, the term "CBGA" includes any derivative of cannabigerolic acid and / or its salts. In one embodiment, a compound of formula I may contain a CBGA residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0147] Within the context of the present disclosure, the term "CBGV" includes any derivative of cannabigerovarin and / or its salts. In one embodiment, a compound of formula I may contain a CBGV residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0148] Within the context of the present disclosure, the term "CBGVA" includes any derivative of cannabigerovarinic acid and / or its salts. In one embodiment, a compound of formula I may contain a CBGVA residue (i.e., Group B) and a serotonergic agent such as psilocin (i.e., Group A).

[0149] In one embodiment, the compositions and methods disclosed herein include a compound of formula I, wherein the compound comprises a first cannabinoid compound (Group A) and a second cannabinoid compound (Group B). In one embodiment, the cannabinoid is selected from THC, THCA, THCV, THCVA, CBC, CBCA, CBCV, CBCVA, CBD, CBDA, CBDV, CBDVA, CBG, CBGA, CBGV, and CBGVA.

[0150] In one embodiment, the compositions and methods disclosed herein include administering a compound of formula I, wherein the compound includes a terpenoid residue (Group B) and a first serotonin agonist (Group A), such as psilocin.

[0151] As used herein, the term "terpene" refers to a compound that belongs to a large class of compounds that are often biosynthesized from five-carbon isoprene units. In one embodiment, the terpene is isolated from plants, such as conifers, hemp, basil, etc. In one embodiment, the terpene is produced by insects, such as termites or swallowtail butterflies. In one embodiment, the terpene is a volatile compound. In one embodiment, the terpene produces an odor. In one embodiment, the terpene is a major component of natural resins, such as turpentine produced from resins. In one embodiment, the terpene is biosynthetically derived from isoprene units, which have the molecular formula C5H8. In one embodiment, the molecular formula of the terpene is (C5H8) n (wherein n is a multiple of the number of linked isoprene units, for example, 1 to 5).

[0152] Within the context of this disclosure, when a terpene is chemically modified, for example, by oxidation or rearrangement of the carbon backbone, the resulting compound is referred to as a "terpenoid." In the relevant art, terpenoids are sometimes referred to as isoprenoids.

[0153] In one embodiment, terpenes are the major component(s) of essential oils from plants and / or flowers. Essential oils are widely used as fragrances in perfumery, medicine, and alternative medicine, e.g., aromatherapy.

[0154] In one embodiment, terpenes are classified according to the number of isoprene (C5H8) units in the compound (e.g., monoterpenes (C 10 H 16 ), sesquiterpenes (C 15 H 24 ), diterpenes (C 20 H 32 ), triterpenes (C 30 H 48 ), or tetraterpenes (C 40 H 64 )).

[0155] Examples of terpenes within the context of the present disclosure include acetanisole, acetyl cedrene, anethole, anisole, benzaldehyde, bornyl acetate, borneol, cadinene, cafestol, caffeic acid, camphene, camphor, capsaicin, carene, carotene, carvacrol, carvone, alpha-caryophyllene, beta-caryophyllene, caryophyllene oxide, cedrene, cedrene epoxide, secanal, cedrol, cembrene, cinnamaldehyde, cinnamic acid, citronellal, citronellol. , cymene, eicosane, elemene, estragole, ethyl acetate, ethyl cinnamate, ethyl maltol, eucalyptol / 1,8-cineole, eudesmol, eugenol, euphor, farnesene, farnesol, fenchone, geraniol, geranyl acetate, guaia-1(10),11-diene, guaiacol, guaiol, guaien, gurjunene, hernialin, hexanaldehyde, hexanoic acid, humulene, ionone, ipsdienol, isoamyl acetate, isoa Myrrh alcohol, isoamylformate, isoborneol, isomyrcenol, isoprene, isopulegol, isovaleric acid, lavandulol, limonene, gamma-linolenic acid, linalool, longifolene, lycopene, menthol, methyl butyrate, 3-mercapto-2-methylpentanal, beta-mercaptoethanol, mercaptoacetic acid, methyl salicylate, methylbutenol, methyl-2-methylvalerate, methylthiobutyrate, beta-myrcene, gamma-myrrholene, nepetalactone, nerol. These include benzoyl, nerolidol, neryl acetate, nonanaldehyde, nonanoic acid, ocimene, octanal, octanoic acid, pentyl butyrate, phellandrene, phenylacetaldehyde, phenylacetic acid, phenylethanethiol, phytol, pinene, propanethiol, pristimerin, pulegone, retinol, rutin, sabinene, squalene, taxadiene, terpineol, terpin-4-ol, terpinolene, thujone, thymol, umbelliferone, undecanal, verdoxane, and vanillin.

[0156] In one embodiment, the terpene to be purified is selected from bornyl acetate, alpha-bisabolol, borneol, camphene, camphor, carene, beta-caryophyllene, cedrene, cymene, elemene, eucalyptol, eudesmol, farnesene, fenchol, geraniol, guaiacol, humulene, isoborneol, limonene, linalool, menthol, beta-myrcene, nerolidol, ocimene, phellandrene, phytol, pinene, pulegone, sabinene, terpineol, terpinolene, and valencene.

[0157] Within the context of the present disclosure, the term "bornyl acetate" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compound of Formula I and / or Formula V comprises a bornyl acetate residue.

[0158] Within the context of this disclosure, the term "alpha-bisabolol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compound of Formula I and / or Formula V includes an alpha-bisabolol residue.

[0159] Within the context of the present disclosure, the term "borneol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a borneol residue.

[0160] Within the context of the present disclosure, the term "camphene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compound of formula I and / or formula V comprises a camphene residue.

[0161] Within the context of the present disclosure, the term "camphor" includes any derivatives and / or salts thereof, including any isomeric, structural and / or enantiomeric variations thereof. In one embodiment, the compounds of formula I and / or formula V contain a camphor residue.

[0162] Within the context of the present disclosure, the term "carene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a carene moiety.

[0163] Within the context of the present disclosure, the term "beta-caryophyllene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a beta-caryophyllene residue.

[0164] Within the context of this disclosure, the term "cedrene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a cedrene residue.

[0165] Within the context of the present disclosure, the term "cymene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a cymene residue.

[0166] Within the context of the present disclosure, the term "elemene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include an elemene residue.

[0167] Within the context of the present disclosure, the term "eucalyptol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a eucalyptol residue.

[0168] Within the context of the present disclosure, the term "eudesmol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of formula I and / or formula V include a eudesmol residue.

[0169] Within the context of this disclosure, the term "farnesene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a farnesene residue.

[0170] Within the context of the present disclosure, the term "fenchol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of formula I and / or formula V include a fenchol residue.

[0171] Within the context of the present disclosure, the term "geraniol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a geraniol residue.

[0172] Within the context of this disclosure, the term "guaiacol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a guaiacol residue.

[0173] Within the context of the present disclosure, the term "humulene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a humulene residue.

[0174] Within the context of the present disclosure, the term "isoborneol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include an isoborneol residue.

[0175] Within the context of the present disclosure, the term "limonene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a limonene residue.

[0176] Within the context of the present disclosure, the term "linalool" includes any derivative and / or its salt, including any isomeric, structural and / or enantiomeric variations thereof. In one embodiment, the compound of formula I and / or formula V comprises a linalool residue.

[0177] Within the context of the present disclosure, the term "menthol" includes any derivatives and / or salts thereof, including any isomeric, structural and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a menthol residue.

[0178] Within the context of this disclosure, the term "beta-myrcene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compound of Formula I and / or Formula V includes a beta-myrcene residue.

[0179] Within the context of the present disclosure, the term "nerolidol" includes any derivatives and / or salts thereof, including any isomeric, structural and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a nerolidol residue.

[0180] Within the context of the present disclosure, the term "ocimene" includes any derivatives and / or salts thereof, including any isomeric, structural and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include an ocimene residue.

[0181] Within the context of the present disclosure, the term "phellandrene" includes any derivatives and / or salts thereof, including any isomeric, structural and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a phellandrene residue.

[0182] Within the context of the present disclosure, the term "phytol" includes any derivatives and / or salts thereof, including any isomeric, structural and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a phytol residue.

[0183] Within the context of the present disclosure, the term "pinene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a pinene residue.

[0184] Within the context of the present disclosure, the term "pulegone" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of formula I and / or formula V include a pulegone residue.

[0185] Within the context of this disclosure, the term "sabinene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a sabinene residue.

[0186] Within the context of the present disclosure, the term "terpineol" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a terpineol residue.

[0187] Within the context of this disclosure, the term "terpinolene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a terpinolene residue.

[0188] Within the context of the present disclosure, the term "valencene" includes any derivatives and / or salts thereof, including any isomeric, structural, and / or enantiomeric variations thereof. In one embodiment, the compounds of Formula I and / or Formula V include a valencene residue.

[0189] In one embodiment, the compositions and methods disclosed herein include one or more erinacine molecules. In one embodiment, the compositions and methods disclosed herein include erinacine A. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine B residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine C residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine D residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine E residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine F residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine G residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine H residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine I residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine J residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine K residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine L residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine M residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine N residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine O residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine Q residue. In one embodiment, the compounds of formula I and / or formula V disclosed herein include an erinacine R residue.

[0190] The erinacine chemical structure is taken from Li IC, Lee LY, Tzeng TW, et al. Neurohealth properties of Hericium erinaceus mycelia enriched with erinacines. In:Behavioural Neurology. 2018. doi:10.1155 / 2018 / 5802634.

[0191] In one embodiment, the compound of formula I and / or formula V may include a hericenone residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone A residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone B residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone C residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone D residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone E residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone F residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone G residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone H residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone I residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone J residue. In one embodiment, the compound of formula I and / or formula V includes a hericenone K residue.

[0192] In one embodiment, the compound of formula I and / or formula V is selected from the group consisting of Bacopa monnieri (e.g., purified molecule bacoside A3), Centella asiatica (e.g., purified molecule asiaticoside), Gingko biloba (e.g., purified molecule myricetin), Zingiber officinale (e.g., purified molecule zingerone), Ocimum sanctum (e.g., purified molecule linalool), Polygonum cuspidatum (e.g., purified molecule resveratrol), Origanum vulgare (e.g., purified molecule carvacrol), Origanum onites (e.g., purified molecule thymol), Rosmarinus officinalis (e.g., purified molecule rosmarinic acid), Rosmarinus eriocalyx (e.g., purified molecule camphor), Curcuma longa (e.g., purified molecule curcumin), Camellia sinensis (e.g., purified molecule theobromine), Lavandula spica (e.g., purified molecule caryophyllene), Scutellaria lateriflora (e.g., purified molecule baicalin), Avena sativa (e.g., purified molecule avenalin), Avena byzantina (e.g., purified molecule beta-glucan), Salvia divinorum (e.g., purified molecule salvinorin A), Banisteriopsis caapi (e.g., purified molecule harmine), Psychotria species (e.g., purified molecule dimethyltryptamine), Tabernanthe iboga (e.g., purified molecule ibogaine), Voacanga africana (e.g., purified molecule voacangin), Tabernaemontana undulata (e.g., purified molecule ibogamine), Lophophora williamsii (e.g., purified molecule mescaline), Ipomoea tricolor (e.g., purified molecule ergonovine), and Argyreia nervosa (e.g., purified molecule Ergin) may include residues of active compounds obtained from the extraction and subsequent purification of one or more compounds from an organism selected from the

[0193] As used herein, the term "serotonergic agent" refers to a compound that binds to, blocks, or otherwise affects (through allosteric reactions) the activity of a serotonin receptor. In one embodiment, a serotonergic agent binds to a serotonin receptor. In one embodiment, a serotonergic agent indirectly affects a serotonin receptor, e.g., through interactions that affect the reactivity of other molecules at the serotonin receptor. In one embodiment, a serotonergic agent is an agonist, e.g., a compound that activates a serotonin receptor. In one embodiment, a serotonergic agent is an antagonist, e.g., a compound that binds to but does not activate a serotonin receptor, e.g., blocks the receptor. In one embodiment, a serotonergic agent is a compound that binds to an effector molecule, e.g., an enzyme for allosteric control. In one embodiment, a serotonergic agent acts (either directly or indirectly) at multiple types of receptors (e.g., SHT, dopamine, adrenergic, acetylcholine, etc.).

[0194] In one embodiment, the serotonergic agent is an antidepressant.

[0195] In one embodiment, the serotonergic agent is an anti-anxiety agent.

[0196] In one embodiment, the serotonergic agent is a selective serotonin reuptake inhibitor.

[0197] In one embodiment, the serotonergic agent is a selective serotonin norepinephrine reuptake inhibitor.

[0198] In some embodiments, the compound of formula I comprises a first serotonergic residue (Group A, which may be selected from the compounds of formulas II and III) and a second serotonergic residue (Group B, which may be selected from the compounds below and the compounds of formulas II and III).

[0199] Some exemplary serotonergic agents include the following molecules: 4-hydroxy-N-methyltryptamine (also known as 3[2-(methylamino)ethyl]-1H-indol-4-ol), aeruginacin (also known as [3-[2-(trimethylazaniumyl)ethyl]-1H-indol-4-yl] hydrogen phosphate), baeocystin (also known as [3-[2-(methylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate), bufotenidine (also known as 3-[2-(trimethylazaniumyl)ethyl]-1H-indol-5-ol), , bufotenin (also known as 3-[2-(dimethylamino)ethyl]-1H-indol-5-ol), etosibine (also known as [3-[2-(diethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate), norbeocystin (also known as [3-(2-aminoethyl)-1H-indol-4-yl] dihydrogen phosphate), norpsilocin, psilocin (also known as 3-[2-(dimethylamino)ethyl]-1H-indol-4-ol), psilocybin (also known as [3-[2-(dimethylamino)ethyl]-1H-indol -4-yl]dihydrogen phosphate), serotonin (also known as 3-(2-aminoethyl)-1H-indol-5-ol), 1P-LSD (also known as (6aR,9R)-N,N-diethyl-7-methyl-4-propanoyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide), ALD-52 (also known as (6aR,9R)-4-acetyl-N,N-diethyl-7-methyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide), AL-LAD (also known as (6aR,9 R)-N,N-diethyl-7-prop-2-enyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), BU-LAD (also known as (6aR,9R)-7-butyl-N,N-diethyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), DAL (also known as (6aR,9R)-7-methyl-N,N-bis(prop-2-enyl)-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide),DAM-57 (synonym: (6aR,9R)-N,N,7-trimethyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), EIPLA (synonym: (6aR,9R)-N-ethyl-7-methyl-N-propan-2-yl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), ETH-LAD (synonym: (6aR,9R)-N,N,7-triethyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide) ), LAE-32 (synonym: (6aR,9R)-N-ethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), LPD-824 (synonym: [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-pyrrolidin-1-ylmethanone), LSB (synonym: (6aR,9R)-N-butan-2-yl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), L SA (also known as (6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), LSD-25 (also known as (6aR,9R)-N,N-diethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), LSD-PiP (also known as (7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl)-piperidin-1-ylmethanone), LSM-775 (also known as [(6aR,9R) -7-Methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-morpholin-4-ylmethanone), LSP (also known as (6aR,9R)-7-methyl-N-pentan-3-yl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide), LSZ (also known as [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-[-(2S,4S)-2,4-dimethylazetidin-1-yl]methanone),Methergine (also known as (6aR,9R)-N-(1-hydroxybutan-2-yl)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4-,3-fg]quinoline-9-carboxamide), MiPLA (also known as (6aR,9R)-N,7-dimethyl-N-propan-2-yl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]-quinoline-9-carboxamide), NDTDI, PARGY-LAD, PRO-LAD (also known as (6aR,9R)-N,N-diethyl-7-propyl-6,6a,8,9-tetrahydro-4 H-indolo[4,3-fg]quinoline-9-carboxamide), 2-Me-DET (also known as N,N-diethyl-2-(2-methyl-1H-indol-3-yl)ethanamine), 2-Me-DMT (also known as N,N-dimethyl-2-(2-methyl-1H-indol-3-yl)ethanamine), 2,alpha-DMT (also known as 1-(2-methyl-1H-indol-3-yl)propan-2-amine), 4-AcO-DALT (also known as [3-[2-[bis(prop-2-enyl)amino]ethyl]-1H-indol-4-yl]acetate), 4-A cO-DET (also known as [3-[2-(diethylamino)ethyl]-1H-indol-4-yl]acetate), 4-AcO-DIPT (also known as 3-[2-(diisopropylamino)ethyl]-1H-indol-4-yl acetate), 4-AcO-DMT (also known as [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl]acetate), 4-AcO-DPT (also known as [3-[2-(dipropylamino)ethyl]-1H-indol-4-yl]acetate), 4-AcO-EPT (also known as 3-{2-[ethyl(propyl)amino]ethyl {3-[2-[ethyl(methyl)amino]ethyl]-1H-indol-4-yl]acetate), 4-AcO-MET (also known as [3-[2-[ethyl(methyl)amino]ethyl]-1H-indol-4-yl]acetate), 4-AcO-MIPT (also known as [3-[2-[methyl(propan-2-yl)amino]ethyl]-1H-indol-4-yl]acetate), 4-AcO-MPT, 4-HO-DBT (also known as 3-[2-(dibutylamino)ethyl]-1H-indol-4-ol), 4-HO-DET (also known as 3-[2-(diethylamino)ethyl]-1H-indol-4-ol),4-HO-DIPT (also known as 3-[2-[di(propan-2-yl)amino]ethyl]-1H-indol-4-ol), 4-HO-DPT (also known as 3-[2-(dipropylamino)ethyl]-1H-indol-4-ol), 4-HO-EPT, 4-HO-MCPT, 4-HO-MET (also known as 3-[2-[ethyl(methyl)amino]ethyl]-1H-indol-4-ol), 4-HO-MIPT (also known as 3-[2-[methyl(propan-2-yl)amino]ethyl]-1H-indol-4-ol), 4-HO-MPMI (also known as 3-[(1-methylpyrrolidin-2-yl)methyl]-1H-indol-4-ol), 4-HO-MPT (also known as 3-[2-[methyl(propyl)amino]ethyl]-1H-indol-4-ol), 4-HO-Pyr-T (also known as 3-(2-pyrrolidin-1-ylethyl)-1H-indol-4-ol), 4-MeO-MIPT (also known as N-[2-(4-methoxy-1H-indol-3-yl)ethyl]-N-methylpropan-2-amine), 4,5-MDO-DIPT (also known as N-[2-(6H-[1,3]dioxolo[4,5- e]indol-8-yl)ethyl]-N-propan-2-ylpropan-2-amine-), 4,5-MDO-DMT (also known as 2-(6H-[1,3]dioxolo[4,5-e]indol-8-yl)-N,N-dimethylethanamine), 5-BROMO-DMT (also known as 2-(5-bromo-1H-indol-3-yl)-N,N-dimethylethanamine), 5-Chloro-alpha-MT (also known as 1-(5-chloro-1H-indol-3-yl)propan-2-amine), 5-Fluoro-AMT (also known as 1-(5-fluoro-1H-indol-3-yl)propan-2-amine), 1-(5-methoxy-1H-indol-3-yl)propan-2-amine), 5-MeO-AET (also known as 1-(5-methoxy-1H-indol-3-yl)butan-2-amine), 5-MeO-AMT (also known as 1-(5-methoxy-1H-indol-3-yl)propan-2-amine), 5-MeO-DALT (also known as N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine), 5-MeO-DET (also known as N,N-diethyl-2-(5-methoxy-1H-indol-3-yl)ethanamine),5-MeO-DiPT (also known as N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-propan-2-ylpropan-2-amine), 5-MeO-DMT (also known as 2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine), 5-MeO-DPT (also known as N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-propylpropan-1-amine), 5-MeO-EiPT (also known as N-ethyl-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]propan-2-amine), 5-Me O-MALT (also known as N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine), 5-MeO-MiPT (also known as N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-methylpropan-2-amine), 5-MeO-NMT (also known as 2-(5-methoxy-1H-indol-3-yl)-N-methylethanamine; hydrochloride), 5-MeO-Pyr-T (also known as 4-fluoro-5-methoxy-3-(2-pyrrolidin-1-ylethyl)-1H-indole), 5-MeO-TMT (also known as 2- (5-methoxy-2-methyl-1H-indol-3-yl)-N,N-dimethylethanamine), 5-MeS-DMT (also known as N,N-dimethyl-2-(5-methylsulfanyl-1H-indol-3-yl)ethanamine), 5,6-MDO-DIPT (also known as N-[2-(5H-[1,3]dioxolo[4,5-f]indol-7-yl)ethyl]-N-propan-2-ylpropan-2-amine-), 5,6-MDO-DMT (also known as 2-(5H-[1,3]dioxolo[4,5-f]indol-7-yl)-N,N-dimethylethanamine), 5,6-MDO-MIPT (also known as N-[2-(5H-[1,3]dioxolo[4,5-f]indol-7-yl)ethyl]-N-ethylpropan-2-amine), 5,6-MeO-MIPT (also known as N-[2-(5,6-dimethoxy-1H-indol-3-yl)ethyl]-N-methylpropan-2-amine), 5,N,N-TMT (also known as N,N-dimethyl-2-(5-methyl-1H-indol-3-ethanamine), 6-MeO-THH (also known as 6-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole),Alpha-ET (also known as 1-(1H-indol-3-yl)butan-2-amine), Alpha-MT (also known as 1-(1H-indol-3-yl)propan-2-amine), Alpha-TMT (also known as 1-(1H-indol-3-yl)-N,N-dimethylpropan-2-amine), Alpha,N-DMT (also known as 2-(1H-indol-3-yl)-N,N-dimethylethanamine), Alpha,N,O-TMS (also known as 1-(5-methoxy-1H-indol-3-yl)-N-methylpropan-2-amine), Alpha,O-DMS (also known as 1-(5-methoxy-, 1H-indol-3-yl)propan-2-amine), DALT (also known as N-[2-(1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine), DBT (also known as N-butyl-N-[2-(1H-indol-3-yl)ethyl]butan-1-amine), DET (also known as N,N-diethyl-2-(1H-indol-3-yl)ethanamine), DiPT (also known as N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-propan-2-ylpropan-2-amine), DMT (also known as 2 -(1H-indol-3-yl)-N,N-dimethylethanamine), DPT (also known as N-[2-(1H-indol-3-yl)ethyl]-N-propylpropan-1-amine), EiPT (also known as N-ethyl-N-[2-(1H-indol-3-yl)ethyl]propan-2-amine), harmaline (also known as 7-methoxy-1-methyl-3,4-dihydro-2H-pyrido[3,4-b]indole), harmine (also known as 7-methoxy-1-methyl-9H-pyrido[3,4-b]indole), MALT, MBT (also known as 3H-1,3-benzo[1H-indol-3-yl]ethyl), zothiazole-2-thione), melatonin (also known as N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide), MET (also known as N-ethyl-2-(1H-indol-3-yl)-N-methylethanamine), MiPT (also known as N-[2-(1H-indol-3-yl)ethyl]-N-methylpropan-2-amine), MPT (also known as 3-[2-[methyl(propyl)amino]ethyl]-1H-indol-4-ol), NET (also known as N-ethyl-2-(1H-indol-3-yl)ethanamine), NMT ( 2-(1H-indol-3-yl)-N-methylethanamine), PiPT (N-[2-(1H-indol-3-yl)ethyl]-N-propan-2-ylpropan-1-amine), Pil-T (3-(2-pyrrolidin-1-ylethyl)-1H-indole), T (2-(1H-indol-3-yl)ethanamine), Tetrahydroharmine (7-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), 2-Br-4,5-MDA (1-(6-bromo-1,3-benzodioxol-5-yl)propan-2-amine), 2-TIM (also known as 2-(3,4-dimethoxy-2-methylsulfanylphenyl)ethanamine), 2-TOET (also known as 1-(4-ethyl-5-methoxy-2-methylsulfanylphenyl)propan-2-amine), 2-TOM (also known as 1-(5-methoxy-4-methyl-2-methylsulfanylphenyl)propan-2-amine), 2,4-DMA (also known as 1-(2,4-dimethoxyphenyl)propan-2-amine), 2,5-DMA (also known as 1-(2,5-dimethoxyphenyl)propan-2-amine), 2C-B (also known as 2-(4-bromo-2,5-dimethoxyphenyl)ethanamine), 2C-C (also known as 2-(4-chloro-2,5-dimethoxyphenyl)ethanamine), 2C-D (also known as 2-(2,5-dimethoxy-4-methoxyphenyl)ethanamine), 2C-E (also known as 2-(4-ethyl-2,5-dimethoxyphenyl)ethanamine), 2C-F (also known as 2-(4-fluoro-2,5-dimethoxyphenyl)ethanamine), 2C-G (also known as 2-(2,5-dimethoxy-3,4-dimethylphenyl)ethanamine), 2C-G-3 (also known as 2-(4,7-dimethoxy-2,3-dihydro-1H-inden-5-yl)ethanamine), 2C-G-4 (also known as 2-(1,4-dimethoxy-5,6,7,8-tetrahydronaphthalen-2-yl)ethanamine), 2C-G-5 (also known as CAS 207740-20-3), 2C-GN (also known as 2-(1,4-dimethoxynaphthalen-2-yl)ethanamine), 2C-H (also known as 2-(2,5-dimethoxyphenyl)ethanamine), 2C-I (also known as 2-(4-iodo-2,5-dimethoxyphenyl)ethanamine), 2C-N (also known as 2-(2,5-dimethoxy-4-nitrophenyl)ethanamine), 2C-O-4 (also known as 2-(2,5-dimethoxy-4-propan-2-yloxyphenyl)ethanamine), 2C-P (also known as 2-(2,5-dimethoxy-4-propylphenyl)ethanamine), 2C-SE (also known as 2-(2,5-dimethoxy-4-methylselanylphenyl)ethanamine), 2C-T (also known as 2-(2,5-dimethoxy-4-methylsulfanylphenyl)ethanamine), 2C-T-13 (also known as 2-[2,5-dimethoxy-4-(2-methoxyethylsulfanyl)phenyl]ethanamine), 2C-T-15 (also known as 2-(4-cyclopropylsulfanyl-2,5-dimethoxyphenyl)ethanamine), 2C-T-17 (also known as 2-(4-butan-2-ylsulfanyl-2,5-dimethoxyphenyl)ethanamine), 2C-T-2 (also known as 2-(4-ethylsulfanyl-2,5-dimethoxyphenyl)ethanamine), 2C-T-2 (also known as 2-[4-(2-fluoroethylsulfanyl)-2,5-dimethoxyphenyl]ethanamine), 2C- T-4 (also known as 2-(2,5-dimethoxy-4-propan-2-ylsulfanylphenyl)ethanamine), 2C-T-7 (also known as 2-(2,5-dimethoxy-4-propylsulfanylphenyl)ethanamine), 2C-T-8 (also known as 2-[4-(cyclopropylmethylsulfanyl)-2,5-dimethoxyphenyl]ethanamine), 2C-T-9 (also known as 2-(4-butylsulfanyl-2,5-dimethoxyphenyl)ethanamine), 2C-TFM (also known as 2-[2,5-dimethoxy-4-(trifluoromethyl)phenyl]ethanamine), 2T -MMDA-3a (also known as 1-(4-methylsulfanyl-1,3-benzodioxol-5-yl)propan-2-amine), 3-T-tris (also known as 2-(3,4-diethoxy-5-ethylsulfanylphenyl)ethanamine), 3-TASB (also known as 2-(3-ethoxy-4-ethylsulfanyl-5-methoxyphenyl)ethanamine), 3-TE (also known as 2-(4-ethoxy-3-methoxy-5-methylsulfanylphenyl)ethanamine), 3-TFM (also known as 2-(2,4-dimethoxy-3-methylsulfanylphenyl)ethanamine) ), 3-TM (also known as 2-(3,4-dimethoxy-5-methylsulfanylphenyl)ethanamine), 3-TME (also known as 2-(3-ethylsulfanyl-4,5-dimethoxyphenyl)ethanamine), 3-TSB (also known as 2-(3-ethoxy-5-ethylsulfanyl-4-methoxyphenyl)ethanamine), 3,4-DMA (also known as 1-(3,4-dimethoxyphenyl)propan-2-amine), 3C-BZ (also known as 1-(3,5-dimethoxy-4-phenylmethoxyphenyl)propan-2-amine), 3C-E (also known as 1-(4-ethoxy-3,5-dimethoxyphenyl)propan-2-amine), 4-Br-3,5-DMA (also known as 1-(4-bromo-3,5-dimethoxyphenyl)propan-2-amine), 4-D (also known as CAS 1020518-87-9), 4-MA (also known as 1-(4-methoxyphenyl)propan-2-amine), 4-T- TRIS (also known as 2-(3,5-diethoxy-4-ethylsulfanylphenyl)ethanamine), 4-TASB (also known as 2-(3-ethoxy-4-ethylsulfanyl-5-methoxyphenyl)ethanamine), 4-TE (also known as 2-(4-ethylsulfanyl-3,5-dimethoxyphenyl)ethanamine), 4-TIM (also known as 2-(2,3-dimethoxy-4-methylsulfanylphenyl)ethanamine), 4-TM (also known as 2-(3,5-dimethoxy-4-methylsulf 4-TME (also known as 2-(3-ethoxy-5-methoxy-4-methylsulfanylphenyl)ethanamine), 4-TSB (also known as 2-(3,5-diethoxy-4-methylsulfanylphenyl)ethanamine), 4T-MMDA-2 (also known as 1-(5-methoxy-1,3-benzoxathiol-6-yl)propan-2-amine), 5-TASB (also known as 2-(3,4-diethoxy-5-methylsulfanylphenyl)ethanamine), 5- TME (also known as 2-(3-ethoxy-4-methoxy-5-methylsulfanylphenyl)ethanamine), 5-TOET (also known as 1-(4-ethyl-2-methoxy-5-methylsulfanylphenyl)propan-2-amine), 5-TOM (also known as 1-(2-methoxy-4-methyl-5-methylsulfanylphenyl)propan-2-amine), 25B-NBF (also known as 2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-fluorophenyl)methyl]ethanamine), 25B-NBOH (also known as 2-[[2-(4-bromo-2,5-dimethoxyphenyl)ethylaminolmethyl]phenol), 25B-NBOMe (also known as 2-(4-bromo-2,5-dimethoxyphenyl)-N[(2-methoxyphenyl)methyl]ethanamine-), 25C-NB3OMe (also known as 2-(4-chloro-2,5-dimethoxyphenyl)-N-[((3-methoxyphenyl)methyl]ethanamine), 25C-NB4OMe (also known as 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(4-methoxyphenyl)methyl]ethanamine), 25C-NBF (also known as 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-fluorophenyl)methyl]ethanamine), 25C-NBOH (also known as 2-(4-chloro-2,5-dimethoxyphenyl)ethylaminolmethyl]phenol), 25C-NBOMe (also known as 2-(4-chloro-2,5-dimethoxyphenyl)-N[(2-methoxyphenyl)methyl]ethanamine), 25CN-NBOH (also known as 4-[2-[(2-hydroxyphenyl)methyl]ethanamine), 25CN-NBOMe (also known as CAS 1354632-16-8), 25D-NBOMe (also known as 2-(2,5-dimethoxy-4-methoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine), 25E-NBOMe (also known as 2-(4-ethyl-2,5-dimethoxyphenyl)-N-4(2-methoxyphenyl)methyl]ethanamine), 25G-NBOMe (also known as 2-(2,5-dimethoxy-3,4-dimethylphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine), 25H-NBOMe (alias 2-(2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine), 25H-NB34MD (alias N-(1,3-benzodioxol-5-ylmethyl)-2-(4-iodo-2,5-dimethoxyphenyl)ethanamine), 25I-NB3OMe (alias 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(3-methoxyphenyl)methyl]ethanamine), 25I-NB4OMe (alias 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(3-methoxyphenyl)methyl]ethanamine), 25I-NBF (also known as N-[(2-fluorophenyl)methyl]-2-(4-iodo-2,5-dimethoxyphenyl)ethanamine), 25I-NBMD (also known as N-(1,3-benzodioxol-4-ylmethyl)-2-(4-iodo-2,5-dimethoxyphenyl)ethanamine), 25I-NBOH (also known as 2-[[2-(4-iodo-2,5-dimethoxyphenyl)ethylamino]methyl]phenol), 25I-NBOMe (also known as 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine), 25iP-NBOMe (also known as 2-(2,5-dimethoxy-4-propan-2-ylphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine), 25N-NBOMe (also known as 2-(2,5-dimethoxy-4-nitrophenyl)-N-[(2-methoxyphenyl)methyl]ethanamine), 25P-NBOMe (also known as 2-(2,5-dimethoxy-4-propylphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine), 25TFM-NBOMe (also known as 2-[2,5-dimethoxy-4-(trifluoromethyl)phenyl]-N-[(, 2CBCB-NBOMe (also known as 1-[(7R)-3-bromo-2,5-dimethoxy-7-bicyclo[4.2.0]octa-1(6),2,4-trienyl]-N-[(-2-methoxyphenyl)methyl]methanamine), 2CBFly-NBOMe (also known as 2-(4-bromo-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-8-yl)-N-[(2-methoxyphenyl)methyl]tanamine), AEM (also known as 1-(3,4,5-trimethoxyphenyl)butan-2-amine) amine), AL (also known as 2-(3,5-dimethoxy-4-prop-2-enoxyphenyl)ethanamine), ALEPH (also known as 1-(2,5-dimethoxy-4-methylsulfanylphenyl)propan-2-amine; hydrochloride), ALEPH-2 (also known as 1-(4-ethylsulfanyl-2,5-dimethoxyphenyl)propan-2-amine), ALEPH-4 (also known as 1-(2,5-dimethoxy-4-propan-2-ylsulfanylphenyl)propan-2-amine), ALEPH-6 (also known as 1-(2,5-dimethoxy-4-phenylsulfanylphenyl)propan-2-amine), (2R)-1-(2,5-dimethoxy-4-methoxyphenyl)butan-2-amine), ALEPH-7 (also known as 1-(2,5-dimethoxy-4-propylsulfanylphenyl)propan-2-amine), ARIADNE (also known as (2R)-1-(2,5-dimethoxy-4-methoxyphenyl)butan-2-amine), ASB (also known as 2-(3,4-diethoxy-5-methoxyphenyl)ethanamine), B (also known as 2-(4-butoxy-3,5-dimethoxyphenyl)ethanamine), BEATRICE (also known as 1-(2,5-dimethoxy-4-methoxyphenyl)-N-methylpropan-2-amine), Beta-D (also known as 2,2-dideuterio-2-(3,4,5-trimethoxyphenyl)ethanamine), BIS-TOM (also known as 1-[4-methyl-2,5-bis(methylsulfanyl)phenyl]propan-2-amine), bk-2C-B (also known as 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone), BOB (also known as 2-(4-bromo-2,5-dimethoxyphenyl)-2-methoxyethanamine), BOD (also known as 2-(2,5-dimethoxy-4-methoxyphenyl)-2-methoxyethanamine), BOH (also known as 2-(1,3-Benzodioxol-5-yl)-2-methoxyethanamine), BOHD (also known as 2-amino-1-(2,5-dimethoxy-4-methylphenyl)ethanol), BOM (also known as 2-methoxy-2-(3,4,5-trimethoxyphenyl)ethanamine), Bromo-DragonFLY (also known as 1-(4-bromofuro[2,3-f][1]benzofuran-8-yl)propan-2-amine), Butyrone (also known as 1-(1,3-benzodioxyl-5-yl)-2-(methylamino)butan-1-one), CPM (also known as 2-[4-(cyclopropyl 2-(2,5-dimethoxy-4-methoxyphenyl)cyclopropan-1-amine), DME (2-amino-1-(3,4-dimethoxyphenyl)ethanol), DMDA (1-(4,7-dimethoxy-1,3-benzodioxol-5-yl)propan-2-amine), DMDDA-2 (1-(6,7-dimethoxy-1,3-benzodioxol-5-yl)propan-2-amine), DESOXY (2-(3,5-dimethoxy-4-methylphenyl)ethanamine), DMCPA (2-(2,5-dimethoxy-4-methoxyphenyl)cyclopropan-1-amine), DME (2-amino-1-(3,4-dimethoxyphenyl)ethanol), DMDDA-2 (1-(6,7-dimethoxy-1,3-benzodioxol-5-yl)propan-2-amine), DMPEA (2-(3,4-dimethoxyphenyl)ethanamine), DOAM (1-(2,5-dimethoxy-4-pentylphenyl)propan-2-amine), DOB (1-(4-bromo-2,5-dimethoxyphenyl)propan-2-amine), DOBU (1-(4-butyl-2,5-dimethoxyphenyl)propan-2-amine), DOC (1-(4-chloro-2,5-dimethoxyphenyl)propan-2-amine), DOEF (1-[4-(2-fluoroethyl)-2,5-dimethoxyphenyl)propan-2-amine), dimethoxyphenyl]propan-2-amine), DOET (also known as 1-(4-ethyl-2,5-dimethoxyphenyl)propan-2-amine), DOF (also known as 1-(4-fluoro-2,5-dimethoxyphenyl)propan-2-amine), DOI (also known as 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine), DOM (also known as 1-(2,5-dimethoxy-4-methoxyphenyl)propan-2-amine), DON (also known as 1-(2,5-dimethoxy-4-nitrophenyl)propan-2-amine), DOPR (also known as 1-(2,5-Dimethoxy-4-propylphenyl)propan-2-amine), DOTFM (also known as 1-[2,5-dimethoxy-4-(trifluoromethyl)phenyl]propan-2-amine), E (also known as 2-(4-ethoxy-3,5-dimethoxyphenyl)ethanamine), EBDP (also known as 1-(1,3-benzodioxol-5-yl)-N-ethylpentan-2-amine), EEE (also known as 1-(2,4,5-triethoxyphenyl)propan-2-amine), EEM (also known as 1-(2,4-diethoxy-5-methoxyphenyl)propan-2-amine), amine), EME (also known as 1-(2,5-diethoxy-4-methoxyphenyl)propan-2-amine), EMM (also known as 1-(2-ethoxy-4,5-dimethoxyphenyl)propan-2-amine), ETHYL-J (also known as 1-(1,3-benzodioxol-5-yl)-N-ethylbutan-2-amine), ETHYL-K (also known as 1-(1,3-benzodioxol-5-yl)-N-ethylpentan-2-amine), F-2 (also known as 1-(5-methoxy-2-methyl-2,3-dihydro-1-benzofuran-6-yl)propan-2-amine) ), F-22 (also known as 1-(5-methoxy-2,2-dimethyl-3H-1-benzofuran-6-yl)propan-2-amine), FLEA (also known as N-[1-(1,3-benzodioxol-5-yl)propan-2-yl]-N-methylhydroxylamine), G-3 (also known as 1-(4,7-dimethoxy-2,3-dihydro-1H-inden-5-yl)propan-2-amine), G-4 (also known as 1-(1,4-dimethoxy-5,6,7,8-tetrahydronaphthalen-2-yl)propan-2-amine), G-5 (also known as 3,6-dimethoxy- 4-(2-aminopropyl)benzonorbornane), GN (also known as 1-(1,4-dimethoxynaphthalen-2-yl)propan-2-amine), GANESHA (also known as 1-(2,5-dimethoxy-3,4-dimethylphenyl)propan-2-amine), HOT-17 (also known as N-[2-(4-butan-2-ylsulfanyl-2,5-dimethoxyphenyl)ethyl]hydroxylamine), HOT-2 (also known as N-[2-(4-ethylsulfanyl-2,5-dimethoxyphenyl)ethyl]hydroxylamine), HOT-7 (also known as N-[2-(2,5-Dimethoxy-4-propylsulfanylphenyl)ethyl]hydroxylamine), IDNNA (also known as 1-(4-iodo-2,5-dimethoxyphenyl)-N,N-dimethylpropan-2-amine), IM (also known as 2-(2,3,4-trimethoxyphenyl)ethanamine), IP (also known as 2-(3,5-dimethoxy-4-propan-2-yloxyphenyl)ethanamine), IRIS (also known as 1-(5-ethoxy-2-methoxy-4-methoxyphenyl)propan-2-amine), J (also known as 1-(1,3-benzodioxol-5-yl)butanol), 2-(3,4,5-trimethoxyphenyl)-2-amine), DIMSUCARINE (also known as [(1R)-4,5,6-trimethoxy-2,3-dihydro-1H-inden-1-yl]methanamine), LOPHOPHINE (also known as 2-(7-methoxy-1,3-benzodioxol-5-yl)ethanamine), M (also known as 2-(3,4,5-trimethoxyphenyl)ethanamine), MADAM-6 (also known as N-methyl-1-(6-methyl-1,3-benzodioxol-5-yl)propan-2-amine), MAL (also known as 2-[3,5-dimethoxy-4-(2-methylprop-2-enoxy)phenyl)amine), N-[1-(1,3-benzodioxol-5-yl)propan-2-yl]butan-1-amine), MDA (also known as 1-(1,3-benzodioxol-5-yl)propan-2-amine), MDAL (also known as 1-(1,3-benzodioxol-5-yl)-N-prop-2-enylpropan-2-amine), MDBU (also known as N-[1-(1,3-benzodioxol-5-yl)propan-2-yl]butan-1-amine), MDBZ (also known as 1-(1,3-benzodioxol-5-yl)-N-benzylpropan-2-amine), MDCPM (also known as 1-(3a,7a-dihydro-1,3-benzodioxol-5-yl)propan-2-amine), 1-(1,3-benzodioxol-5-yl)-N-(cyclopropylmethyl)propan-2-amine), MDDM (also known as 1-(1,3-benzodioxol-5-yl)-N,N-dimethylpropan-2-amine), MDE (also known as 1-(1,3-benzodioxol-5-yl)-N-ethylpropan-2-amine), MDHOET (also known as 2-[1-(1,3-benzodioxol-5-yl)propan-2-ylamino]ethanol), MDIP (also known as 1-(1,3-benzodioxol-5-yl)-N-propan-2-ylpropan-2-amine), MDMA (also known as 1-(1,3-benzodioxol-5-yl)-N-methylpropan-2-amine), MDMC (also known as 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-N-methylpropan-2-amine), MDMEO (also known as 1-(1,3-benzodioxol-5-yl)-N-methoxypropan-2-amine), MDMEOET (also known as 1-(1,3-benzodioxol-5-yl)-N-(2-methoxyethyl)propan-2-amine), MDMP (also known as 1-(1,3-benzodioxol-5-yl)-N,2-dimethylpropan-2-amine), -amine), MDOH (also known as N-[1-(1,3-benzodioxol-5-yl)propan-2-yl]hydroxylamine), MDPEA (also known as 2-(1,3-benzodioxol-5-yl)ethanamine), MDPH (also known as 1-(1,3-benzodioxol-5-yl)-2-methylpropan-2-amine), MDPL (also known as 1-(1,3-benzodioxol-5-yl)-N-prop-2-ynylpropan-2-amine), MDPR (also known as 1-(1,3-benzodioxol-5-yl)-N-propylpropan-2-amine), ME (also known as 2-(3-ethoxy-4,5-dimethoxyphenyl)ethanamine), MEDA (also known as 1-(5-methoxy-2,3-dihydro-1,4-benzodioxin-7-yl)propan-2-amine), MEE (also known as 1-(4,5-diethoxy-2-methoxyphenyl)propan-2-amine), MEM (also known as 1-(4-ethoxy-2,5-dimethoxyphenyl)propan-2-amine), MEPEA (also known as 2-(4-ethoxy-3-methoxyphenyl)ethanamine), META-DOB (also known as 1-(5-bromo-2,4- dimethoxyphenyl)propan-2-amine), META-DOT (also known as 1-(2,4-dimethoxy-5-methylsulfanylphenyl)propan-2-amine), METHYL-DMA (also known as 1-(2,5-dimethoxyphenyl)-N-methylpropan-2-amine), METHYL-DOB (also known as 1-(4-bromo-2,5-dimethoxyphenyl)-N-methylpropan-2-amine), METHYL-J (also known as 1-(1,3-benzodioxol-5-yl)-N-methylbutan-2-amine), METHYL-K (also known as 1-(1,3-benzodioxol-5-yl)-N-methylpentan-2-amine), METHYL-MA (also known as 1-(4-methoxyphenyl)-N-methylpropan-2-amine), METHYL-MMDA-2 (also known as 1-(6-methoxy-1,3-benzodioxol-5-yl)-N-methylpropan-2-amine), MMDA (also known as 1-(7-methoxy-1,3-benzodioxol-5-yl)propan-2-amine), MMDA-2 (also known as 1-(6-methoxy-1,3-benzodioxol-5-yl)propan-2-amine), MMDA-3a (also known as 1-(4-methoxy-1,3-benzo, 1-(7-Methoxy-1,3-benzodioxol-4-yl)propan-2-amine), MMDA-3b (also known as 1-(7-Methoxy-1,3-benzodioxol-4-yl)propan-2-amine), MME (also known as 1-(5-ethoxy-2,4-dimethoxyphenyl)propan-2-amine), MP (also known as 2-(3,4-dimethoxy-5-propoxyphenyl)ethanamine), MPM (also known as 1-(2,4-dimethoxy-5-propoxyphenyl)propan-2-amine), NBOMe-mescaline (also known as N-[(2-methoxyphenyl)methyl]-2-(3,4,5-trimethoxyphenyl)ethanamine), ORTHO-DOT (also known as 1-(4,5-dimethoxy-2-methylsulfanylphenyl)propan-2-amine), P (also known as 2-(3,5-dimethoxy-4-propoxyphenyl)propan-2-amine), diphenyl)ethanamine), PE (also known as 2-[3,5-dimethoxy-4-(2-phenylethoxy)phenyl]ethanamine), PEA (also known as 2-phenylethanamine), Propynyl (also known as 2-(3,5-dimethoxy-4-prop-2-ynoxyphenyl)ethanamine), Psi-2C-T-4, Psi-DOM (also known as 1-(2,6-dimethoxy-4-methoxyphenyl)propan-2-amine), SB (also known as 2-(3,5-diethoxy-4-methoxyphenyl)ethanamine), TA (also known as 1-(2,3,4,5-tetramethoxyphenyl)propan-2-amine), TB (also known as 2-(4-butylsulfanyl-3,5-dimethoxyphenyl)ethanamine), TCB-2 (also known as (3-bromo-2,5-dimethoxy-7-bicyclo[4.2.0]octa-1(6),2,4-trienyl)methanamine; hydrobromide), TMA (also known as 1-(3,4,5-trimethoxyphenyl)propan-2-amine), TMA-2 (also known as 1-(2,4,5-trimethoxyphenyl)propan-2-amine), TMA-3 (also known as 1-(2,3,4-trimethoxyphenyl)propan-2-amine), TMA-4 (also known as 1-(2,3,5-trimethoxyphenyl)propan-2-amine), TMA-5 (also known as 1-(2,3,6-trimethoxyphenyl)propan-2-amine), These include TMA-6 (also known as 1-(2,4,6-trimethoxyphenyl)propan-2-amine), TMPEA (also known as 2-(2,4,5-trimethoxyphenyl)ethanamine), TOMSO (also known as 1-(2-methoxy-4-methyl-5-methylsulfinylphenyl)propan-2-amine), TP (also known as 2-(3,5-dimethoxy-4-propylsulfanylphenyl)ethanamine), and Tris (also known as 2-(3,4,5-triethoxyphenyl)ethanamine).

[0200] In one embodiment, the serotonergic agent is alprazolam, amphetamine, aripiprazole, azapirone, barbiturates, bromazepam, bupropion, buspirone, cannabinoids, chlordiazepoxide, citalopram, clonazepam, clorazepate, dextromethorphan, diazepam, duloxetine, escitalopram, fluoxetine, flurazepam, fluvoxamine, lorazepam, lysine, riboflavin ... The active ingredient is selected from the group consisting of glyceryl diethylamide, lysergamide, 3,4-methylenedioxymethamphetamine, milnacipran, mirtazapine, naratriptan, paroxetine, pethidine, phenethylamines, psicaine, oxazepam, reboxetine, selenite, serotonin, sertraline, temazepam, tramadol, triazolam, tryptamine, venlafaxine, vortioxetine, and derivatives thereof.

[0201] In one embodiment, serotonin acts by acting as a ligand at a serotonin receptor, for example, at a 5-HT receptor. In one embodiment, serotonin is produced by an organism for use as a neurotransmitter within the organism. In one embodiment, the compositions and methods disclosed herein increase activity at a serotonin receptor. In one embodiment, the compositions and methods disclosed herein decrease activity at a serotonin receptor.

[0202] As used herein, the term "serotonin receptor" refers to a collection of extracellular proteins capable of receiving a signal and activating an internal signaling pathway that causes a cellular response. In one embodiment, serotonin receptors are found on cells in the central nervous system of an organism. In one embodiment, serotonin receptors are found on cells in the peripheral nervous system of an organism. In one embodiment, serotonin is the natural ligand for serotonin receptors. In one embodiment, serotonin receptors regulate the release of neurotransmitters such as glutamate, gamma-aminobutyric acid, dopamine, epinephrine (also known as norepinephrine), acetylcholine, and the like. In one embodiment, serotonin receptors regulate the release of hormones such as oxytocin, prolactin, vasopressin, cortisol, corticotropin, substance P, and the like.

[0203] Examples of serotonin receptors include 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 2A , 5-HT 2B , 5-HT 2C , 5-HT3, 5-HT4, 5-HT 5A , 5-HT 5B , 5-HT6, and 5-HT7.

[0204] As used herein, the term "adrenergic agonist" refers to a compound that binds to, blocks, or otherwise affects (through an allosteric response) the activity of an adrenergic receptor. In one embodiment, an adrenergic agonist binds to an adrenergic receptor. In one embodiment, an adrenergic agonist indirectly affects an adrenergic receptor, e.g., through an interaction that affects the reactivity of other molecules at the adrenergic receptor. In one embodiment, an adrenergic agonist is an agonist, e.g., a compound that activates an adrenergic receptor. In one embodiment, an adrenergic agonist is an antagonist, e.g., a compound that binds to but does not activate an adrenergic receptor, e.g., blocks the receptor. In one embodiment, an adrenergic agonist is a compound that binds to an effector molecule, e.g., an enzyme for allosteric control. In one embodiment, the adrenergic agent acts (either directly or indirectly) at multiple types of receptors (eg, 5HT, dopamine, adrenergic, acetylcholine, etc.).

[0205] In one embodiment, the adrenergic agent is an antidepressant.

[0206] In one embodiment, the adrenergic agent is a norepinephrine transporter inhibitor.

[0207] In one embodiment, the adrenergic agent is a vesicular monoamine transporter inhibitor.

[0208] In one embodiment, the adrenergic agent is selected from adrenaline, agmatine, amoxapine, aptazapine, atomoxetine, bupropion, clonidine, doxepin, duloxetine, esmirtazpine, mianserin, mianserin, mirtazapine, norepinephrine, phentolamine, phenylephrine, piperoxane, reserpine, ritodrine, setiptiline, tesofensine, timolol, trazodone, trimipramine, and xylazine.

[0209] In one embodiment, the adrenergic agonist acts at an adrenergic receptor, for example, by acting as a ligand at an adrenergic receptor. In one embodiment, adrenaline is produced by an organism for use as a neurotransmitter within the organism. In one embodiment, norepinephrine is produced by an organism for use as a neurotransmitter within the organism. In one embodiment, the compositions and methods disclosed herein increase activity at an adrenergic receptor. In one embodiment, the compositions and methods disclosed herein decrease activity at an adrenergic receptor.

[0210] As used herein, the term "adrenergic receptor" refers to a collection of extracellular proteins that can receive a signal and activate an internal signaling pathway that causes a cellular response. In one embodiment, adrenergic receptors are found on cells in the central nervous system of an organism. In one embodiment, adrenergic receptors are found on cells in the sympathetic nervous system of an organism.

[0211] As used herein, the term "dopaminergic agent" refers to a compound that binds to, blocks, or otherwise affects (through allosteric reactions) the activity of a dopamine receptor. In one embodiment, a dopaminergic agent binds to a dopamine receptor. In one embodiment, a dopaminergic agent indirectly affects a dopamine receptor, e.g., through interactions that affect the reactivity of other molecules at the dopamine receptor. In one embodiment, a dopaminergic agent is an agonist, e.g., a compound that activates a dopamine receptor. In one embodiment, a dopaminergic agent is an antagonist, e.g., a compound that binds to but does not activate a dopamine receptor, e.g., blocks the receptor. In one embodiment, a dopaminergic agent is a compound that binds to an effector molecule, e.g., an enzyme for allosteric control. In one embodiment, a dopaminergic agent acts (either directly or indirectly) at multiple types of receptors (e.g., 5HT, dopamine, adrenergic, acetylcholine, etc.).

[0212] In one embodiment, the dopamine agonist is a dopamine transporter inhibitor.

[0213] In one embodiment, the dopamine agonist is a vesicular monoamine transporter inhibitor.

[0214] In one embodiment, the dopamine agonist is selected from amineptine, apomorphine, benzylpiperazine, bromocriptine, cabergoline, chlorpromazine, clozapine, dihydrexidine, domperidone, dopamine, fluphenazine, haloperidol, ketamine, loxapine, methamphetamine, olanzapine, pemoline, perphenazine, pergolide, phencyclidine, phenethylamines, phenmetrazine, pimozide, piribedil, psychostimulants, reserpine, risperidone, ropinirole, tetrabenazine, and thioridazine.

[0215] In one embodiment, a dopamine agonist acts at a dopamine receptor, for example, by acting as a ligand at a dopamine receptor. In one embodiment, dopamine is produced by an organism for use as a neurotransmitter within the organism. In one embodiment, the compositions and methods disclosed herein increase activity at a dopamine receptor. In one embodiment, the compositions and methods disclosed herein decrease activity at a dopamine receptor.

[0216] As used herein, the term "dopamine receptor" refers to a collection of extracellular proteins capable of receiving a signal and activating an internal signaling pathway that causes a cellular response. In one embodiment, dopamine receptors are found on cells within the central nervous system of an organism.

[0217] In one embodiment, compounds of Formula I and / or Formula V may provide active compounds that modulate the activity of neurotransmitters at their native receptors, such as serotonin at serotonin receptors, dopamine at dopaminergic receptors, norephedrine at adrenergic receptors, etc.

[0218] In one embodiment, the compounds of Formula I and / or Formula V may result in compounds that are active at one or more receptors, such as serotonin receptors, adrenergic receptors, dopamine receptors, GABAergic receptors, glutaminergic receptors, histaminergic receptors, cholinergic receptors, opioid receptors, or glycinergic receptors.

[0219] In one embodiment, the compositions disclosed herein comprise a monoamine oxidase inhibitor.

[0220] As used herein, the term "monoamine oxidase inhibitor" refers to a molecule that binds to monoamine oxidase enzyme, thereby reducing the activity of monoamine oxidase enzyme.In the context of the present disclosure, examples of monoamine oxidase inhibitors include aurorix, deprenyl, eldepryl, emsam, humoril, hydracarbazine, isocarboxazid, linezolid, manerix, nidrazide, phenelzine, pyrazidol, procarbazine, rasagiline, and tranylcypromine.In one embodiment, monoamine oxidase catalyzes the oxidation of monoamines, such as serotonin, dopamine, norepinephrine, amphetamine, adrenaline, etc.

[0221] In one embodiment, the compositions disclosed herein include a stabilizer. As used herein, the term "stabilizer" refers to a compound useful for preventing the decomposition of an active ingredient, such as a compound of formula I and / or formula V, a psilocybin derivative, a cannabinoid, a terpene, etc. In one embodiment, the stabilizer prevents the active ingredient from decomposing. In one embodiment, the stabilizer prevents the serotonergic agent from reacting with other compounds in the composition, such as a cannabinoid, a terpene, a base, an acid, etc. In one embodiment, the stabilizer prevents the serotonergic agent from reacting with the surrounding atmosphere, such as heat, light, water, and / or oxygen. In one embodiment, the stabilizer includes an antioxidant. In one embodiment, the stabilizer includes a pH buffer.

[0222] In one embodiment, the methods and compositions disclosed herein include an antioxidant. As used herein, the term "antioxidant" refers to a compound and / or composition useful for preventing oxidation. In one embodiment, the antioxidant protects the active ingredient from "free radicals." Within the context of this disclosure, a "free radical" is an atom, molecule, or ion that has an unpaired valence electron. In one embodiment, the antioxidant is an electron donor.

[0223] In one embodiment, the antioxidant is selected from ascorbic acid, lycopene, tocopherol, melatonin, retinol, astaxanthin, lutein, apigenin, carnosine, selenium, zinc, curcumin, and salts or derivatives thereof.

[0224] In one embodiment, the antioxidant is ascorbic acid and / or its salts or derivatives. Within the context of the present disclosure, the term "ascorbic acid" includes vitamin C and / or its salts or derivatives.

[0225] In one embodiment, the antioxidant prevents oxidation of a composition comprising one or more compounds disclosed herein, e.g., compounds of Formula I and / or Formula V, psilocybin derivatives, cannabinoids, terpenes, and / or mixtures thereof, e.g., by preventing oxidation of phenolic groups attached to the psilocybin derivatives.

[0226] As used herein, the term "oxidation" refers to the formal loss of electrons and / or an increase in formal oxidation state and / or the addition of oxygen atom(s). As used herein, "reduction" refers to the formal gain of electrons and / or a decrease in formal oxidation state. Zumdahl, Steven S., et al. Chemistry, 7th. Cengage Learning, 2018.

[0227] In one embodiment, the methods and compositions disclosed herein comprise a pH buffer.

[0228] As used herein, the term "pH buffer" refers to a compound or composition useful for maintaining the pH of a composition. In one embodiment, the pH buffer comprises a weak acid and a corresponding conjugated base. In one embodiment, the pH buffer comprises a weak base and a corresponding conjugated acid. In one embodiment, the pH buffer does not change the pH of the composition upon addition of a strong acid and / or base.

[0229] In one embodiment, the pH buffer maintains the pH of the composition at about 7. In one embodiment, the pH buffer maintains the pH of the composition less than about 7. In one embodiment, the pH buffer maintains the pH of the composition greater than about 7. In one embodiment, the pH buffer maintains the pH of the composition in the range of about 2 to about 6. In one embodiment, the pH buffer maintains the pH of the composition in the range of about 5 to about 7. In one embodiment, the pH buffer maintains the pH of the composition in the range of about 6 to about 8. In one embodiment, the pH buffer maintains the pH of the composition in the range of about 7 to about 10.

[0230] In one embodiment, the pH buffer comprises citric acid, acetic acid, monosodium phosphate, N-cyclohexyl-2-aminoethanesulfonic acid, borate, hydrochloric acid, and / or sodium hydroxide.

[0231] In one embodiment, the methods disclosed herein include administering a composition comprising an acid.

[0232] As used herein, the term "acid" refers to an acid that contains a proton, i.e., H + In one embodiment, "acid" refers to a molecule or ion capable of donating and / or accepting electrons. In one embodiment, "acid" refers to a Lewis acid. In one embodiment, "acid" refers to a Bronsted acid. In one embodiment, the acid is determined by the pH of the composition. In one embodiment, a pH of less than 7 indicates the presence of an acid.

[0233] In one embodiment, the compositions and methods disclosed herein include administering a formulation that includes a base.

[0234] As used herein, the term "base" refers to a proton, i.e., H + In one embodiment, "base" refers to a molecule or ion capable of accepting an electron pair, i.e., a Lewis base. In one embodiment, the presence of a base is determined by the pH of the compound. In one embodiment, a pH greater than 7 indicates the presence of a base.

[0235] In one embodiment, the compositions and methods disclosed herein involve administering a non-aqueous composition.

[0236] In some embodiments, the compositions described herein are non-aqueous.

[0237] As used herein, the term "water-soluble" refers to a compound or composition that can be dissolved in water at standard temperature and pressure. In one example, 1 g of a compound dissolves in 1 L of water. In one example, 2 g of a compound dissolves in 1 L of water. In one example, 5 g of a compound dissolves in 1 L of water. In one example, 10 g of a compound dissolves in 1 L of water. In one embodiment, the solubility of a compound in water is an inherent property of the compound. In one embodiment, the solubility of a compound in water can be promoted by another compound, e.g., an excipient.

[0238] In one embodiment, the compositions and methods disclosed herein include administering a compound of Formula I and / or Formula V present as a homogenous mixture in a dosage formulation and / or present in a homogenous mixture.

[0239] In one embodiment, the compositions and methods disclosed herein include administering a compound of Formula I and / or Formula V and at least one additional compound (e.g., a serotonergic agent, a cannabinoid, a terpene, an excipient, a stabilizer, an antioxidant, etc.) present as a homogenous mixture in a dosage formulation and / or present within a homogenous mixture.

[0240] As used herein, the term "homogeneous mixture" refers to a solid, liquid, or gas composition having two or more compounds present in one state or thing, e.g., a clear, colorless solution. In an embodiment, the homogeneous mixture disclosed herein has the same proportions, concentrations, and / or ratios of its components across different samples. In an embodiment, the components in a homogeneous mixture are in the same state of matter. In an embodiment, the homogeneous mixture comprises one or more compounds in solution, e.g., a compound of formula I and / or formula V and a cannabinoid in a clear solution. In an embodiment, the compositions disclosed herein exist as homogeneous mixtures, e.g., solutions without particulate matter, solutions with comparable concentrations between samples, powders with similar particle sizes, etc.

[0241] Provided herein is a method for modulating activity at a neurotransmitter receptor, comprising: Methods are disclosed that include administering to a person in need of treatment a dosage formulation comprising a compound of Formula I and / or Formula V, where the dosage formulation modulates activity at a neurotransmitter receptor.

[0242] As used herein, the term "modulating the activity of a neurotransmitter activity modulating agent" refers to altering, manipulating, and / or regulating the ability of a compound or composition to affect a neurotransmitter receptor. In one embodiment, modulating the activity of a neurotransmitter activity modulating agent comprises administering an agonist at the neurotransmitter receptor. In one embodiment, modulating the activity of a neurotransmitter activity modulating agent comprises administering an antagonist at the neurotransmitter receptor.

[0243] As used herein, the term "administering" (e.g., administering a drug) refers to dosing, treating, giving, and / or providing. In one embodiment, administering a neurotransmitter activity modulating agent includes providing a neurotransmitter activity modulating agent to an organism (e.g., a human) having a neurotransmitter receptor. In one embodiment, administering a neurotransmitter activity modulating agent includes providing a neurotransmitter activity modulating agent together with a compound of formula I and / or formula V, e.g., a formulation having a neurotransmitter activity modulating agent and each of the compounds of formula I and / or formula V in a single dosage amount. In one embodiment, administering a neurotransmitter activity modulating agent includes applying a transdermal composition, e.g., applying a topical composition having a neurotransmitter activity modulating agent and each of the compounds of formula I and / or formula V to the skin. In one embodiment, administering a neurotransmitter activity modulating agent includes providing a transmucosal preparation, e.g., providing a fast dissolving tablet having an absorption enhancer having a neurotransmitter activity modulating agent and each of the compounds of formula I and / or formula V.

[0244] In one embodiment, the methods disclosed herein include administering the composition by inhalation to cross the blood-brain barrier.

[0245] As used herein, the term "neurotransmitter activity modulating agent" refers to a compound or composition that reacts at or affects the activity of a neurotransmitter receptor, such as, for example, a compound of Formula I and / or Formula V, a serotonergic agent, an adrenergic receptor, a dopamine receptor, a GABAergic receptor, a glutaminergic receptor, a histaminergic receptor, a cholinergic receptor, an opioid receptor, or a glycinergic receptor. In one embodiment, the neurotransmitter activity modulating agent binds to the neurotransmitter receptor. In one embodiment, the neurotransmitter activity modulating agent indirectly affects the neurotransmitter receptor, for example, through an interaction that affects the reactivity of other molecules at the neurotransmitter receptor. In one embodiment, the neurotransmitter activity modulating agent is an agonist. In one embodiment, the neurotransmitter activity modulating agent is an antagonist. In one embodiment, the neurotransmitter activity modulating agent acts (either directly or indirectly) at multiple types of neurotransmitter receptors.

[0246] In one embodiment, the neurotransmitter activity modulator is selected from aripiprazole, bupropion, citalopram, clomipramine, dextroamphetamine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, quetiapine, reboxetine, risperidone, sertraline, and venlafaxine.

[0247] As used herein, the term "first dosage formulation" refers to a compound(s) selected for the purpose of causing a reaction, effect, and / or result in an organism, e.g., causing activity at a neurotransmitter receptor, reacting with another compound, enhancing the effect of another active ingredient, inhibiting the biosynthesis of a compound, etc. In one embodiment, the first dosage formulation comprises a compound of Formula I and / or Formula V.

[0248] In one embodiment, the second dosage formulation comprises a compound of Formula I and / or Formula V. In one embodiment, the second dosage formulation comprises a second compound of Formula I and / or Formula V. In one embodiment, the second dosage formulation comprises an additional serotonergic agent.

[0249] In one embodiment, the method disclosed herein comprises administering a second dosage formulation. In one embodiment, the method disclosed herein comprises administering a third dosage formulation. In one embodiment, the method disclosed herein comprises administering a fourth dosage formulation. In one embodiment, the method disclosed herein comprises administering more than four dosage formulations.

[0250] In certain embodiments, the dosage formulation contains a desired amount of at least one compound of Formula I and / or Formula V. In certain embodiments, the dosage formulation contains about 0.01 to about 1,000 mg, e.g., about 0.1 to about 500 mg, about 0.5 to about 100 mg, or about 1 to about 50 mg of compound. In certain embodiments, the dosage formulation is calculated to contain an amount of compound of Formula I and / or Formula V based on mg of compound per kg of subject (mg / kg). In certain embodiments, the mg / kg range can be about 0.001 to about 10 mg / kg, e.g., about 0.01 to about 5, about 0.05 to about 4, about 0.05 to about 3, about 0.05 to about 3, about 0.05 to about 2, or about 0.05 to about 1 mg / kg. In some embodiments, the compound is administered in an amount of less than about 1 mg / kg, e.g., about 0.001 to about 0.99, about 0.01 to about 0.85, about 0.05 to about 0.75, about 0.01 to about 0.50, about 0.01 to about 0.25, or about 0.01 to about 0.10 mg / kg.

[0251] In one embodiment, the methods disclosed herein include administering a compound of Formula I and / or Formula V that upon metabolism in vivo provides one or more active ingredients, such as a cannabinoid, a terpene, a serotonergic agent, a neurotransmitter activity modulator, etc.

[0252] Provided herein is a method for treating a psychiatric problem, comprising: Methods are disclosed that include administering a compound of Formula I and / or Formula V to a person in need of treatment. In one embodiment, the method further includes identifying a person in need of treatment prior to administering the compound of Formula I and / or Formula V. In one embodiment, the compound of Formula I and / or Formula V provides one or more active compounds that modulate activity at neurotransmitter receptors in vivo.

[0253] As used herein, the term "identifying a person in need of treatment" refers to analyzing, diagnosing, and / or determining whether a person needs treatment for a disease or condition. In one embodiment, identifying a person in need of treatment includes diagnosing a person with a medical condition, e.g., a neurological disorder, a chemical imbalance, a genetic condition, etc. In one embodiment, identifying a person in need of treatment includes performing a psychiatric evaluation. In one embodiment, identifying a person in need of treatment includes performing a blood test. In one embodiment, identifying a person in need of treatment includes determining whether a person has obsessive-compulsive disorder. In one embodiment, identifying a person in need of treatment includes self-identifying as having obsessive-compulsive disorder.

[0254] As used herein, the term "mental disorder" refers to a condition in which a person exhibits a pattern of behavioral and / or psychological symptoms that affect multiple areas of life and cause distress to the person experiencing these symptoms. In one embodiment, the mental disorder is caused by a genetic disorder. In one embodiment, the mental disorder is caused by a biological condition, such as excess hormone production, lack of activity at a neurotransmitter receptor, lack of neurotransmitter production, etc. In one embodiment, the neurotransmitter receptor is a serotonin receptor.

[0255] In one embodiment, the mental problem is an anxiety disorder. In one embodiment, the mental problem is a depressive disorder. In one embodiment, the mental problem is an obsessive-compulsive disorder. In one embodiment, the mental problem is characterized by neurodegeneration.

[0256] As used herein, the term "anxiety disorder" refers to a state of worry, uncertainty, and / or fear resulting from the expectation of an event and / or situation. Anxiety disorder can disrupt a person's physical and mental functions. These disruptions can cause minor to debilitating handicaps in a person's daily life. Anxiety disorder can cause physiological symptoms, such as muscle tension, heart palpitations, sweating, dizziness, shortness of breath, etc. Anxiety disorder can also cause mental symptoms, such as fear of dying, fear of distress or humiliation, fear of the occurrence of an event, etc.

[0257] In one embodiment, the anxiety disorder comprises acute stress disorder, anxiety due to a medical condition, generalized anxiety disorder, panic disorder, panic attacks, phobias, post-traumatic stress disorder, separation anxiety disorder, social anxiety disorder, substance-induced anxiety disorder, or selective mutism.

[0258] As used herein, the term "acute stress disorder" refers to a condition that develops after exposure to one or more traumatic events. Examples of traumatic events include, but are not limited to, war, rape or sexual assault, physical attack, robbery, childhood physical or sexual assault, kidnapping or hostage taking, terrorist attack, torture, natural disaster, and / or critical self. In one embodiment, acute stress disorder occurs within one day of experiencing the traumatic event. In one embodiment, acute stress disorder occurs within three days of experiencing the traumatic event. In some examples, acute stress disorder occurs within one week of experiencing the traumatic event. In some examples, acute stress disorder occurs within one month of experiencing the traumatic event.

[0259] As used herein, the term "anxiety due to another medical condition" refers to a condition in which anxiety symptoms develop due to the physiological and psychological consequences of an unrelated illness, injury, and / or disease, such as an endocrine disorder, cardiovascular disorder, respiratory disease, metabolic disorder, neurological disease, etc.

[0260] As used herein, the term "generalized anxiety disorder" refers to persistent and excessive anxiety and worry about a variety of areas that an individual perceives as difficult to control, such as work, school, the social environment, etc. The individual also experiences physical symptoms including restlessness, vigilance, and / or nervousness; easily tiring, difficulty concentrating or clearing the mind, irritability, muscle tension, and sleep disturbances.

[0261] As used herein, the term "panic disorder" refers to a condition in which an individual experiences recurrent and unexpected panic attacks. The individual persistently worries about having more panic attacks, and these panic attacks cause him or her to change his or her behavior in maladaptive ways (e.g., avoiding exercise, unfamiliar places, new people, etc.).

[0262] As used herein, the term "panic attack" refers to a sudden surge of intense fear or intense discomfort that peaks within a short period of time, e.g., within seconds, minutes, hours, etc. In some instances, a panic attack refers to physical and / or cognitive symptoms. A panic attack may be predictable, e.g., in response to a typically feared object or situation. In some instances, a panic attack occurs for no apparent reason.

[0263] As used herein, the term "phobia" refers to a condition of fear, anxiety, or avoidance of a specific object and / or situation. In some instances, a phobia includes a fear, anxiety, or avoidance induced by a situation that is persistent and out of proportion to the actual risk. Examples of phobias include, but are not limited to, fear or anxiety of animals, natural environments, injection injuries, etc.

[0264] As used herein, the term "post-traumatic stress disorder" refers to a condition that develops after experiencing and / or witnessing a traumatic event, or after learning that a traumatic event has occurred to a loved one. In some instances, a person exhibits symptoms of post-traumatic stress disorder within one week of experiencing the traumatic event. In some instances, a person exhibits symptoms of post-traumatic stress disorder within one month of experiencing the traumatic event. In some instances, a person exhibits symptoms of post-traumatic stress disorder within one year of experiencing the traumatic event. In some instances, a person exhibits symptoms of post-traumatic stress disorder more than one year after experiencing the traumatic event. In some instances, post-traumatic stress disorder involves a person reliving the traumatic event through intrusive and distressing recollections of the event, flashbacks, and / or nightmares. In some instances, symptoms of post-traumatic stress disorder include emotional numbing and avoidance of places, people, and activities that remind one of the trauma. In some instances, symptoms of post-traumatic stress disorder include increased arousal, such as difficulty sleeping and concentrating, anxiety, and being irritable and angry.

[0265] As used herein, the term "neurodegeneration" refers to the progressive loss of neuronal structure or function, including but not limited to neuronal death. Many neurodegenerative diseases (including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease) result from neurodegenerative processes. Such diseases are incurable and result in the progressive degeneration and / or death of neuronal cells. Several attempts have been made to treat such diseases and conditions using fungal and plant extracts. However, all of these methods suffer from a common shortcoming that fungal and / or plant extracts cannot provide consistent or reliable amounts of therapeutic compounds because they rely on the highly variable chemical composition of specific naturally occurring organisms.

[0266] As used herein, the term "separation anxiety disorder" refers to a condition in which an individual is fearful and / or anxious about separation from an attachment figure to a degree that is developmentally inappropriate. In some instances, separation anxiety disorder includes fear or anxiety about harm coming to an attachment figure. In some instances, separation anxiety disorder includes fear of events that result in loss or separation from an attachment figure and unwillingness to leave the attachment figure. In some instances, separation anxiety disorder includes distressing nightmares and / or psychotic symptoms.

[0267] As used herein, the term "social anxiety disorder" refers to a condition in which an individual fears, is anxious about, or avoids social interactions and situations that involve the possibility of being observed. These social interactions and situations include meeting unknown people, situations in which the individual may be observed eating or drinking, situations in which the individual performs in front of others, etc. In some instances, social anxiety disorder is caused by fear of being negatively evaluated by others, embarrassed, humiliated, rejected, and / or making others uncomfortable.

[0268] As used herein, the term "substance-induced anxiety disorder" refers to a condition in which anxiety is caused by substance addiction and / or withdrawal or by medical treatment. In some instances, withdrawal from the substance increases anxiety.

[0269] As used herein, the term "selective mutism" refers to a condition characterized by an individual's consistent inability to speak in social situations where speech is expected, e.g., school, lectures, meetings, etc., even though the individual speaks in other situations. The inability to speak has significant consequences for achievement in academic, professional settings, and / or otherwise interferes with normal social communication.

[0270] In some instances, the anxiety disorder comprises a medical diagnosis based on criteria and classifications from the Diagnostic and Statistical Manual of Medical Disorders, 5th Ed. In some instances, the anxiety disorder comprises a medical diagnosis based on an independent medical evaluation. In some instances, the anxiety disorder comprises a medical diagnosis based on self-assessment.

[0271] In one embodiment, the methods and compositions disclosed herein comprise administering an anti-anxiety medication.

[0272] As used herein, the term "anxiolytic agent" refers to a compound or composition that reacts at or affects the activity of a neurotransmitter receptor, such as, for example, a compound of Formula I and / or Formula V, a serotonergic receptor, an adrenergic receptor, a dopamine receptor, a GABAergic receptor, a glutaminergic receptor, a histaminergic receptor, a cholinergic receptor, an opioid receptor, or a glycinergic receptor. In one embodiment, the anxiolytic agent binds to a neurotransmitter receptor. In one embodiment, the anxiolytic agent indirectly affects a neurotransmitter receptor, for example, through an interaction that affects the reactivity of other molecules at the neurotransmitter receptor. In one embodiment, the anxiolytic agent is an agonist. In one embodiment, the anxiolytic agent is an antagonist. In one embodiment, the anxiolytic agent acts (either directly or indirectly) at multiple types of neurotransmitter receptors.

[0273] In one embodiment, the anti-anxiety agent is selected from alprazolam, alpha blockers, antihistamines, barbiturates, beta blockers, bromazepam, carbamates, chlordiazepoxide, clonazepam, clorazepate, diazepam, flurazepam, lorazepam, opioids, oxazepam, temazepam, and triazolam.

[0274] As used herein, the term "depressive disorder" refers to a condition of low mood and aversion to activities that lasts for a period of time and can affect a person's thoughts, behaviors, emotions, and sense of well-being. In one embodiment, a depressive disorder disrupts a person's physical and mental functioning. In one embodiment, a depressive disorder causes physiological symptoms, such as weight loss, aches or pains, headaches, cramps, digestive problems, and the like. In one embodiment, a depressive disorder causes mental symptoms, such as persistent sadness; anxiety; feelings of hopelessness and irritability; feelings of guilt, worthlessness, or helplessness; loss of interest or enjoyment in hobbies and activities; difficulty concentrating, remembering, or making decisions, and the like.

[0275] In one embodiment, the depressive disorder is selected from atypical depression, bipolar disorder, catatonic depression, depression due to a medical condition, major depressive disorder, postpartum depression, premenstrual dysphoric disorder, and seasonal affective disorder.

[0276] As used herein, the term "atypical depression" refers to a condition in which an individual shows signs of mood reactivity (i.e., mood brightens in response to actual or potential positive events), significant weight gain, increased appetite, hypersomnia, heavy lead-like sensations in the arms or legs, and / or a long-standing pattern of interpersonal rejection sensitivity (leading to significant social or occupational impairment). Exemplary symptoms of atypical depression include, but are not limited to, daily sadness or depressed mood; loss of enjoyment in things that were once enjoyable; major weight changes (gain or loss) or appetite changes; nearly daily insomnia or hypersomnia; physical restlessness or fatigue that can be noticed by others; daily fatigue or loss of energy; nearly daily feelings of hopelessness, worthlessness, or excessive guilt; nearly daily concentration or decision-making problems; recurrent thoughts of death or suicide, suicide plans, or suicide attempts.

[0277] As used herein, the term "bipolar disorder" refers to a condition that causes an individual to experience abnormal changes in mood, energy, activity level, and ability to perform daily tasks. Individuals with bipolar disorder experience periods of abnormally intense emotions, changes in sleep patterns and activity levels, and abnormal behavior. These distinct periods are called "mood episodes." Mood episodes are dramatically different from the person's typical mood and behavior. Exemplary symptoms of manic excessive behavior include, but are not limited to, abnormally cheerful, nervous, or irritable behavior; increased activity, energy, or agitation; exaggerated happiness and self-confidence; decreased desire for sleep; abnormal talkativeness; racing thoughts; distractibility; and inappropriate decisions, such as spending too much, taking sexual risks, or making poor investments. Exemplary symptoms of a depressive episode, low mood, include, but are not limited to, depressed mood, e.g., feelings of sadness, emptiness, hopelessness, or crying; marked loss of interest or lack of pleasure in all or nearly all activities; significant weight loss, weight gain, or decreased or increased appetite; insomnia or hypersomnia; restlessness or slowed behavior; fatigue or loss of energy; feelings of worthlessness or excessive or inappropriate guilt; decreased ability to think or concentrate, or indecisiveness; and suicidal thoughts, plans, or attempts.

[0278] As used herein, the term "catatonic depression" refers to a condition that causes an individual to remain silent and immobile for long periods of time.Exemplary symptoms of catatonic depression include, but are not limited to, feelings of sadness that may occur daily, loss of interest in most activities, sudden weight gain or loss, changes in appetite, difficulty falling asleep, difficulty waking up, feelings of restlessness, irritability, feelings of worthlessness, feelings of guilt, fatigue, difficulty concentrating, difficulty thinking, difficulty making decisions, thoughts of suicide or death, and / or suicide attempts.

[0279] As used herein, the term "depressive disorder due to medical condition" refers to a condition in which an individual experiences depressive symptom(s) caused by another disease. Examples of medical conditions known to cause depressive disorders include, but are not limited to, HIV / AIDS, diabetes, arthritis, stroke, brain disorders such as Parkinson's disease, Huntington's disease, multiple sclerosis, and Alzheimer's disease, metabolic conditions (e.g., vitamin B12 deficiency), autoimmune conditions (e.g., lupus and rheumatoid arthritis), viral or other infectious diseases (hepatitis, mononucleosis, herpes), back pain, and certain cancers (e.g., pancreatic).

[0280] As used herein, the term "major depressive disorder" refers to a condition characterized by periods of depressed mood that are present across most circumstances. Major depressive disorder is often accompanied by low self-esteem, loss of interest in normally enjoyable activities, little energy, and pain without obvious cause. In some instances, major depressive disorder is characterized by 2 weeks. In some instances, an individual experiences periods of depression that are years apart. In some instances, an individual experiences symptoms of depression that are nearly always present. Major depressive disorder can adversely affect a person's personal, work, or school life, as well as sleep, eating habits, and general health. 2-7% of adults with major depressive disorder attempt suicide, and up to 60% of people who attempt suicide had major depressive disorder or another related mood disorder. Dysthymia is a subtype of major depressive disorder that consists of the same cognitive and physical problems as major depressive disorder, with less severe but longer-lasting symptoms. Exemplary symptoms of major depressive disorder include, but are not limited to, sadness, crying, feelings of emptiness, or hopelessness; angry outbursts, irritability, or frustration, even over small things; loss of interest or pleasure in most or all normal activities; sleep disorders, including insomnia or hypersomnia; fatigue and lack of energy; loss of appetite, weight loss or gain; anxiety, agitation, or restlessness; slowed thinking, speech, or physical movements; feelings of worthlessness or guilt, preoccupation with past failures or self-blame; problems thinking, concentrating, making decisions, and remembering; frequent thoughts of death, suicidal thoughts, suicide attempts, or suicide; and unexplained physical problems, such as back pain or headaches.

[0281] As used herein, the term "postpartum depression" refers to a condition resulting from childbirth and hormonal changes, psychological adjustment to parenthood, and / or fatigue. Although postpartum depression is often associated with women, men can suffer from postpartum depression as well. Exemplary symptoms of postpartum depression include, but are not limited to, feelings of sadness, despair, emptiness, or overwhelm; crying more often than usual or for no apparent reason; worrying or feeling excessive anxiety; feeling moody, irritable, or restless; hypersomnia or inability to sleep even when the baby is sleeping; having problems concentrating, remembering details, and making decisions; experiencing anger or rages; losing interest in normally enjoyed activities; suffering from physical aches and pains, including frequent headaches, stomach problems, and muscle aches; eating too little or too much; withdrawing or avoiding friends and family; having problems bonding or forming an emotional attachment with the baby; persistently doubting his or her ability to care for the baby; and thoughts of harming themselves or the baby.

[0282] As used herein, the term "premenstrual dysphoric disorder" refers to a condition in which an individual experiences mood lability, irritability, restlessness, and anxiety symptoms that occur repeatedly during the premenstrual phase of the cycle and remit around the onset of menstruation or shortly thereafter.Exemplary symptoms of premenstrual dysphoric disorder include, but are not limited to, lability (e.g., mood swings), irritability or anger, depressed mood, anxiety, and tension, decreased interest in normal activities, difficulty concentrating, lethargy and lack of energy, changes in appetite (e.g., overeating or craving certain foods), excessive or insomnia, feeling overwhelmed or out of control, physical symptoms (e.g., breast tenderness or swelling, joint or muscle pain, feeling of "fullness" and weight gain), self-deprecating thoughts, feelings of agitation or irritability, decreased interest in normal activities (e.g., work, school, friends, hobbies), subjective difficulty concentrating, and easy fatigue.

[0283] As used herein, the term "seasonal affective disorder" refers to a condition in which an individual experiences mood changes based on the time of year. In some instances, an individual experiences low mood, low energy, or other depressive symptoms during the fall and / or winter seasons. In some instances, an individual experiences low mood, low energy, or other depressive symptoms during the spring and / or summer seasons. Exemplary symptoms of seasonal affective disorder include, but are not limited to, feeling depressed most or almost every day of the day; losing interest in activities that were once enjoyed; having low energy; having sleep problems; experiencing changes in appetite or weight; feeling sluggish or agitated; having difficulty concentrating; feeling hopeless, worthless, or guilty; and having frequent thoughts of death or suicide.

[0284] In one embodiment, a depressive disorder comprises a medical diagnosis based on criteria and classifications from the Diagnostic and Statistical Manual of Medical Disorders, 5th Ed. In one embodiment, a depressive disorder comprises a medical diagnosis based on an independent medical evaluation.

[0285] In one embodiment, the methods and compositions disclosed herein comprise administering an antidepressant.

[0286] As used herein, the term "antidepressant" refers to a compound that reacts at or affects the activity of neurotransmitter receptors, such as compounds of Formula I and / or Formula V, serotonergic receptors, adrenergic receptors, dopamine receptors, GABAergic receptors, glutaminergic receptors, histaminergic receptors, cholinergic receptors, opioid receptors, or glycinergic receptors. In one embodiment, the antidepressant binds to the neurotransmitter receptor. In one embodiment, the antidepressant indirectly affects the neurotransmitter receptor, for example, through interactions that affect the reactivity of other molecules at the neurotransmitter receptor. In one embodiment, the antidepressant is an agonist. In one embodiment, the antidepressant is an antagonist. In one embodiment, the antidepressant acts (either directly or indirectly) at multiple types of neurotransmitter receptors.

[0287] In one embodiment, the antidepressant is selected from bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine.

[0288] Disclosed herein are methods of treating headaches and / or migraines, the methods comprising identifying a person in need of treatment and administering a composition disclosed herein to the person in need of treatment.

[0289] Disclosed herein is a method of treating nicotine addiction, comprising identifying a person in need of treatment and administering a composition disclosed herein to the person in need of treatment.

[0290] Disclosed herein is a method of treating drug addiction comprising identifying a person in need of treatment and administering a composition disclosed herein to the person in need of treatment.

[0291] Disclosed herein is a method of treating alcoholism comprising identifying a person in need of treatment and administering a composition disclosed herein to the person in need of treatment.

[0292] The compositions disclosed herein are useful for the treatment of obsessive-compulsive disorder, various intractable psychiatric disorders, chronic depression, post-traumatic stress disorder, and drug or alcohol addiction in humans. The compositions disclosed herein are also useful in the context of meditative, spiritual, and religious practices in a variety of contexts.

[0293] As used herein, the term "obsessive-compulsive disorder" refers to a condition in which an individual has obsessions that cause feelings of anxiety, fear, anxiety, and the like, and a compulsion to perform tasks to alleviate the feelings of anxiety. Obsessions are thoughts that recur and persist despite the individual's efforts to ignore or confront them. In some instances, obsessions are relatively vague, with a general feeling of confusion or tension accompanied by the idea that life will not go on as usual while the uncertainty remains. In other instances, obsessions may be more intense, preoccupied with thoughts or images of someone close to them dying, or intrusions related to the correctness of relationships. Other obsessions concern the possibility that someone or something other than oneself (e.g., God, the Devil, or disease) will harm the individual, either the people or things the individual cares about. In some instances, individuals perform compulsive rituals because they inexplicably feel they must. In some instances, individuals perform compulsive rituals to relieve anxiety resulting from a particular obsession. The person feels that these actions somewhat prevent the frightening event from happening or remove the event from their thoughts.

[0294] In one embodiment, the obsessive-compulsive disorder is selected from addiction, body dysmorphic disorder, skin picking disorder, hoarding disorder, obsessive-compulsive disorder, and trichotillomania.

[0295] As used herein, the term "addiction" refers to a physical and / or mental dependency on a substance, an activity, and / or any other habit. In one embodiment, addiction is caused by an individual's altered brain chemistry in response to a stimulant, e.g., a substance that releases high amounts of serotonin, an activity that releases high amounts of adrenaline, etc. In one embodiment, addiction is a dependency on a substance, e.g., drugs, alcohol, nicotine, food, etc. In one embodiment, addiction is a dependency on an activity, e.g., gambling, eating, shopping, etc.

[0296] As used herein, the term "body dysmorphic disorder" refers to a condition characterized by an obsessive belief that some aspect of an individual's appearance is severely flawed and necessitates extraordinary measures to conceal or correct it. Exemplary symptoms of body dysmorphic disorder include, but are not limited to, being extremely preoccupied with perceived flaws in appearance that others do not see or see as minor; the belief that the flaws in appearance disfigure or deform the individual; the belief that others negatively singularize or ridicule the individual's appearance; engaging in behaviors aimed at correcting or hiding the perceived flaws that are difficult to resist or control, such as frequently checking in the mirror, grooming, or picking at skin; attempting to hide the perceived flaws with styling, makeup, or clothing; constantly comparing one's appearance with others; constantly seeking reassurance from others about one's appearance; having perfectionist tendencies; frequently seeking unsatisfying cosmetic procedures; avoiding social situations; and being so preoccupied with one's appearance that it causes great distress or problems in one's social life, work, school, or other areas of functioning.

[0297] As used herein, the term "skin picking disorder" refers to a condition in which a person has a recurrent urge to pick at their skin. In some instances, skin picking disorder causes people to pick at their skin, often to the point where damage is caused.

[0298] As used herein, the term "hoarding disorder" refers to a condition in which possessions are persistently difficult to discard or part with, regardless of their value.Exemplary symptoms of hoarding disorder include, but are not limited to, being unable to throw away possessions; severe anxiety when trying to discard items; great difficulty in sorting or arranging possessions; indecisiveness about what to keep or where to put things; distress such as feeling overwhelmed or embarrassed by possessions; doubts about other people touching items; obsessive thoughts and behaviors; fear of missing or needing items in the future; checking the trash for items that have been discarded by mistake; and functional impairment, such as loss of living space, social isolation, family or marital discord, financial difficulties, health crisis, etc.

[0299] As used herein, the term "obsessive-compulsive disorder" refers to a condition in which an individual has uncontrollable recurrent thoughts and behaviors that he or she feels the urge to repeat over and over again. In some instances, obsessive-compulsive disorder manifests itself as an individual needing to clean to reduce the fear that germs, dirt, or chemicals will contaminate the individual, and the individual spends a lot of time washing themselves or cleaning their surroundings. In some instances, obsessive-compulsive disorder manifests itself as an individual needing relief from anxiety. An individual may say a name, phrase, or repeat an action several times. The individual knows that these repetitive behaviors do not actually prevent harm, but fears that harm will occur if they do not perform the repetitive behavior. In some instances, obsessive-compulsive disorder manifests itself as an individual creating checking rituals, for example, that require reducing the fear of harming themselves or others by forgetting to lock a door or turning off an appliance. In some instances, OCD manifests as an individual needing to organize and arrange his or her surroundings to reduce discomfort, for example, placing things in a certain order, arranging household items in a certain way or symmetrical fashion, etc. In some instances, OCD manifests as an individual needing to respond to intrusive obsessions, for example, praying or saying phrases to reduce anxiety or prevent future frightening events. In some instances, OCD is caused by another medical condition. In some instances, OCD is caused by a substance.

[0300] As used herein, the term "trichotillomania" refers to a condition in which the individual self-induced and recurrent loss of hair, e.g., pulling out one's own hair. In some instances, trichotillomania involves an individual who pulls out their hair at one location. In some instances, trichotillomania involves an individual who pulls out their hair at multiple locations. Exemplary symptoms of trichotillomania include, but are not limited to, recurrent pulling out of one's own hair, resulting in noticeable hair loss; increased tension just before or when resisting the act of pulling out hair; feelings of enjoyment, satisfaction, or relief when pulling out hair; the disorder is not explained by another psychiatric disorder and is not due to a general medical condition (i.e., skin lesion); repeated attempts are made to reduce or stop pulling out hair; the disorder has caused significant distress or dysfunction in social, occupational, or other important areas of functioning; distress, including feelings of loss of control, financial difficulties, and embarrassment; and dysfunction due to avoidance of work, school, or other public situations.

[0301] In one embodiment, obsessive-compulsive disorder comprises a medical diagnosis based on criteria and classifications from the Diagnostic and Statistical Manual of Medical Disorders, 5th Ed. In one embodiment, obsessive-compulsive disorder comprises a medical diagnosis based on an independent medical evaluation.

[0302] In some embodiments, the compositions described herein further comprise at least one compound that does not act on serotonin receptors.

[0303] In some embodiments, the compositions described herein comprise a compound of Formula I and / or Formula V. In some embodiments, the compound of Formula I and / or Formula V comprises one active serotonergic agent.

[0304] Although the compounds disclosed herein are described with reference to various exemplary embodiments, it should be understood that these embodiments are merely illustrative of the principles and applications of the present disclosure. Those skilled in the art will recognize that various modifications can be made to the exemplary embodiments without departing from the scope of the present disclosure.

[0305] It should be understood that when a specific compound is referred to, the disclosure also contemplates the salts and derivatives of that compound, as well as the decomposition products, such as oxidized versions of the explicitly disclosed molecule.

[0306] Moreover, it should be understood that various features and / or characteristics of different embodiments herein may be combined with one another. As such, it is to be understood that numerous modifications may be made to the exemplary embodiments and other arrangements may be devised without departing from the scope of the present disclosure.

[0307] Moreover, other embodiments of the present disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. It is intended that the specification and examples be considered as exemplary only, with the scope and spirit being indicated by the claims.

[0308] Any concentration range, percentage range, ratio range, or integer range herein should be understood to include any integer value within the stated range, and fractions thereof, where appropriate (such as tenths and hundredths of integers), unless otherwise indicated. As used herein, the terms "about" and "approximately" mean ±20%, ±10%, ±5%, or ±1% of the indicated range, value, or structure, unless otherwise indicated. EXAMPLES

[0309] Example 1. Dispsilocin™ L-10 Dimer [ka] To a suspension of sebacic acid (0.5 mmol) and PyBOP (1.0 mmol) in DCM (0.15 M) was added Hunig's base (1.0 mmol) and the mixture was stirred at room temperature until the solution was homogenous (approximately 30 min). To this solution was added psilocin (1.0 mmol) and DMAP (0.15 mmol) as mixed solids in one portion. The resulting heterogeneous solution was stirred at room temperature. After 16 h, the reaction mixture was diluted with an equal volume of hexane. The supernatant was decanted, leaving a reddish oil. The red oil was washed three times with chloroform to give a crude red-brown oil.

[0310] CPC purification The crude material was dissolved in CHCl.sub.3 then partitioned between ethyl acetate and hexanes on a Quattro CPC Lab Prep (250 mL) to give a white crystalline solid in 68% yield after concentration.

[0311] General information about CPC Centrifugal partition chromatography (CPC) is a subtype of countercurrent chromatography that applies liquid-liquid chromatography. CPC extrapolates small differences in partition coefficients by repeated partitioning in many small chambers connected in series called cells. The components of a mixture are separated by partitioning between two immiscible liquid phases. In operation, the liquid stationary phase is retained in the centrifuge rotor by centrifugal force and then eluted by passing the mobile phase through the stationary phase. The mobile phase is collected into fractions containing the resolved analytes, most commonly detected by UV-diode array detection. The mobile phase containing the target component(s) is collected and concentrated to recover the target analyte(s). Non-target analytes may also be recovered from the mobile phase, and strongly retained non-target analytes are recovered from the stationary phase by purging the device.

[0312] Example 2 [ka] To a cooled solution of 4-acetoxyindole (6.8 mmol) in anhydrous THF (3 mL) at -78 °C, 1.6 M nBuLi in hexane (7.0 mL, 11.0 mmol) was added dropwise and the temperature was raised to -10 °C. After 15 min, the reaction mixture was cooled to -50 °C and TIPSCl (1.64 g, 11.0 mmol) was added. The solution was warmed to 0 °C, stirred for 3 h, and poured into water (10 mL). The mixture was extracted three times with DCM and the combined organic extracts were dried, filtered, and concentrated under vacuum. The crude 1-(triisopropylsilyl)-1H-indol-4-yl acetate was used without further purification.

[0313] To 5 mL of anhydrous THF at 0° C. under an inert atmosphere was added oxalyl chloride (0.865 mL, 10.2 mmol). A solution of crude 1-(triisopropylsilyl)-1H-indol-4-yl acetate (estimated 6.8 mmol, 1 equiv.) in THF was added dropwise via addition funnel and stirred at 0° C. for 1 h. The reaction mixture was diluted with anhydrous hexane. The resulting solid was filtered, washed several times with a (3 / 1) hexane / diethyl ether mixture, and used without further purification.

[0314] The filtered acid chloride (estimated 6.8 mmol, 1 equiv.) was dissolved in THF (10 mL) under an inert atmosphere and 2.0 M dimethylamine in THF (11.5 mmol, 1.7 equiv.) was added via syringe followed by triethylamine (1.39 mL, 10.2 mmol, 1.5 equiv.). The reaction mixture was stirred at room temperature for 3 h. Anhydrous hexane (10 mL) was then added and stirred at 40° C. for 30 min. The resulting hydrochloride salt was filtered off and the ketoamide was precipitated from the mother liquor and collected to give an off-white solid in 51% yield over three steps.

[0315] Example 3. [ka] To a solution of ketoamide prepared according to the procedure of Example 2 (1.0 g, 2.32 mmol) in THF (50 mL) at 0° C. under inert atmosphere, LiAlH4 (12.7 mmol, 5.5 equiv.) was added as a 2.0 M solution in THF and the mixture was heated under reflux for 8 h. The reaction was quenched by the addition of water (10 mL) and the aqueous layer was extracted three times with diethyl ether. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude solid was purified by SiO2 column chromatography to give the desired product in about 64% yield.

[0316] Example 4. [ka] The procedure according to Example 1 was repeated using the TIPS-protected phenol prepared according to Example 3 to give the desired TIPS-protected dimer.

[0317] Example 5. [ka] A 1.0 M solution of Bu4NF (0.6 mmol) in THF was added to a 0.2 M solution of purified TIPS-protected Dipsilocin™ dimer in anhydrous THF, prepared according to the procedure in Example 4 (0.5 mmol). The mixture was stirred at room temperature for 10 min. After quenching with saturated aqueous sodium carbonate, the mixture was extracted with DCM and the combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was passed through a silica plug to afford analytically pure bis(3-(2-(dimethylamino)ethyl)-1H-indol-4-yl) decanedioate as a crystalline white solid in 89% yield.

[0318] Example 6. [ka] To a heated solution of buspirone (2.00 mmol, 1 equiv.) in toluene (5 mL) at 50° C. was added triethylamine (0.52 mL, 4 mmol, 2 equiv.), followed by the slow addition of sebacoyl chloride (1.9 mmol, 0.95 equiv.) in toluene (5 mL) via an addition funnel. After 2 h, the solution was quenched with water and diluted with ethyl acetate before being washed with saturated sodium bicarbonate. The organic layer was then dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude residue was purified by column chromatography on silica gel (30% ethyl acetate in hexanes) to give 10-oxo-10-((9-oxo-8-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)-8-azaspiro[4.5]dec-6-en-7-yl)oxy)decanoic acid.

[0319] Example 7. [ka] To a suspension of 10-oxo-10-((9-oxo-8-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)-8-azaspiro[4.5]dec-6-en-7-yl)oxy)decanoic acid (0.5 mmol) prepared according to the procedure of Example 6 and PyBOP (0.6 mmol) in DCM (0.15 M) is added Hunig's base (0.6 mmol) and the mixture is stirred at room temperature until homogenous (around 30 min). To this, psilocin (0.5 mmol) and DMAP (0.15 mmol) are added in one portion as mixed solids. The reaction mixture is stirred at room temperature for 16 h and then diluted with an equal volume of hexane. The supernatant is then decanted, leaving the crude material, which is washed three times with chloroform to give the crude product, which is purified by HPLC to give 1-(3-(2-(dimethylamino)ethyl)-1H-indol-4-yl)10-(9-oxo-8-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)-8-azaspiro[4.5]dec-6-en-7-yl)decanedioate.

[0320] Example 8. [ka] To a solution of delta-9-tetrahydrocannabinol (1.0 mmol) in anhydrous THF (5 mL), sebacic anhydride (1.0 mmol) is added in one portion and then refluxed for 16 h. The crude reaction mixture is then concentrated under vacuum to give the target 10-oxo-10-((6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-yl)oxy)decanoic acid as crude material.

[0321] Example 9. [ka] The procedure of Example 7 is repeated using the starting material produced according to Example 8 to give the desired THC-psilocin L-10 dimer product in good yield, which is purified by silica gel chromatography and / or the HPLC or CPC methods described herein.

[0322] biological research Head twitch response (HTR) experiment. Dose-Response Studies. Dose-response studies for compounds of Formula I and / or Formula V are carried out in four sequential steps: (a) Formulation Process: Identify a suitable (non-toxic) vehicle that can be used to dissolve the compound. (b) Pilot dose-finding studies. HTR-inducing drugs typically have a biphasic bell-shaped (inverted U-shaped) dose-response function, with an ascending and descending phase. To quantify the efficacy of a drug in an HTR dose-response study, doses covering the full range of the ascending phase and at least one dose falling into the descending phase should be included. A pilot dose-finding study is conducted to identify a set of doses that match those conditions. For the pilot, male C57BL / 6J mice are injected with various doses (typically 0.3-30 mg / kg) by IP or SC route, and behavior is then recorded in a magnetometer chamber for up to 150 min. (c) Dose-response studies. Groups of male C57BL / 6J mice with magnet implants are injected with vehicle or 4-5 doses of compound (n=5-7 mice / group) by IP or SC route, and behavior is then recorded for at least 30 min in a magnetometer chamber. (d) Repeated testing. Efficacy can typically be quantified on the basis of a single dose-response study, but in some cases, repeated testing may be necessary. For example, the dose selected for testing may not have been ideal for calculating the median effective dose (ED50 value). If necessary, a second or third dose-response study is performed.

[0323] Analyses: The following analyses are performed on dose-response studies: HTR counts are analyzed using one-way ANOVA followed by post-hoc testing (Dunnett's test).

[0324] Median effective dose (ED 50 Values ​​(mg / kg or mol / kg) will be calculated by non-linear regression using a Gaussian or sigmoidal model. The potencies of compounds and other reference compounds can also be statistically compared using the extra sum of squares F test.

[0325] HTR counts can be binned (e.g., 1, 2, 5, or 10 min blocks) and analyzed using two-way ANOVA (drug x time) followed by post-hoc tests (Dunnett's test or Tukey's test).

[0326] 5-HT 2A Antagonist Blockade Studies. Four groups of male C57BL / 6J mice with magnet implants were treated with selective 5-HT antagonist blockade. 2A Pre-treat SC with antagonist M100907 (vehicle, 0.001, 0.01, or 0.1 mg / kg). Twenty minutes later, all of the animals are injected IP or SC with one dose of compound (n = 5-7 mice / group), and then behavior is recorded for 30 min in the magnetometer chamber.

[0327] 5-HT1A Antagonist Blockade Studies. Four groups of male C57BL / 6J mice (n = 5–7 mice / group) with magnet implants were treated with selective 5-HT antagonist blockade. 1A Animals are pretreated SC with the antagonist WAY-100635 (vehicle or 1 mg / kg). Twenty minutes later, animals are injected IP or SC with vehicle or a dose of compound, and then behavior is recorded for at least 30 minutes in the magnetometer chamber.

[0328] Extended time course studies. Male C57BL / 6J mice with magnet implants are injected IP or SC with up to three different treatments (n=5-6 mice / group) and behavior is then recorded in a magnetometer chamber for up to 5 hours (the exact evaluation period used depends on the duration of action of the substance being tested).

[0329] Brain penetration studies. Use these studies to test whether 5-HT2A ligands that do not induce HTR are brain penetrant in mice. Male C57BL / 6J mice with magnet implants are pretreated IP or SC with vehicle or three doses of 5-HT2A ligand (n=5-7 mice / group); 20 min later, all of the mice are injected with 1 mg / kg (±)-DOI HCl, and then behavior is recorded for 20-30 min in the magnetometer chamber.

[0330] hERG inhibition studies. All experiments are performed manually at room temperature using a HEKA EPC-10 amplifier in whole-cell mode of the patch clamp technique. HEK293 cells stably expressing hKv11.1 (hERG) under G418 selection can be procured from the University of Wisconsin, Madison. Cells are cultured in DMEM containing 10% fetal bovine serum, 2 mM glutamine, 1 mM sodium pyruvate, 100 U ml-1 streptomycin, and 500 mg ml-1 penicillin, 100 μg ml-1 G418. Cell lines have not been authenticated or tested for mycoplasma contamination. Prior to the experiments, cells are grown to 60-80% confluence, suspended using TrypLE, and seeded onto poly-l-lysine coated coverslips. Patch pipettes are pulled from soda-lime glass (micro-hematocrit tubes) and should exhibit a resistance of 2-4 MΩ. For the external solution, regular sodium Ringer's is used (160 mM NaCl, 4.5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, pH 7.4 and 290-310 mOsm). The internal solution used is potassium fluoride with ATP (160 mM KF, 2 mM MgCl2, 10 mM EGTA, 10 mM HEPES, 4 mM NaATP, pH = 7.2 and 300-320 mOsm). hERG currents are evoked using a two-step pulse (applied every 10 s) first from -80 mV to 40 mV for 2 s and then -60 mV for 4 s. The percentage reduction in tail current amplitude by the compounds of formula I and / or formula V tested is determined and data are presented as mean ± sd (n = 3-4 per data point). For all experiments, solutions of drugs are freshly prepared from 10 mM stocks in DMSO. The final DMSO concentration does not exceed 1%.

[0331] Serotonin and opioid receptor functional assays. Functional assay screens at 5-HT and opioid receptors are performed in parallel using the same compound dilutions and a high-throughput assay platform in a 384-well format. 2AExcept where receptors are mentioned, the assay is used to evaluate activity on all human isoforms of the receptor. Receptor constructs in pcDNA vectors are generated from the Presto-Tango GPCR library 39 with minor modifications. All test compounds of Formula I and / or Formula V are serially diluted in drug buffer (HBSS, 20 mM HEPES, pH 7.4 (supplemented with 0.1% bovine serum albumin and 0.01% ascorbic acid)) and dispensed into 384-well assay plates using a FLIPR Tetra automated dispenser head (Molecular Devices). All plates include positive controls, e.g., 5-HT (for all 5-HT receptors), DADLE (DOR), Salvinorin A (KOR), and DAMGO (MOR). 5-HT 2A , 5-HT 2B , and 5-HT 2C For measurements of Gq-mediated calcium flux function, HEK Flp-In 293, T-Rex stable cell lines (Invitrogen) were loaded with Fluo-4 dye for 1 hour, stimulated with compounds, and read for baseline (0-10 seconds) and peak fold over base fluorescence (5 minutes) on a FLIPR Tetra system at 25°C. 7a For functional assay measurements, mediated cAMP accumulation is detected using a split luciferase GloSensor assay in HEKT cells measuring luminescence with a Microbeta Trilux (Perkin Elmer) at 15 min during drug incubation at 25° C. 1A , 5-HT 1B , 5-HT 1F For MOR, KOR and DOR functional assays, Gi / o-mediated cAMP inhibition was achieved with 0.3 μM isoproterenol (5-HT 1A , 5-HT 1B , 5-HT 1F ) or 1 μM forskolin (MOR, KOR and DOR) to stimulate endogenous cAMP accumulation and detect 5-HT using a split luciferase GloSensor assay in HEKT cells, performed similarly to the above except that 5-HT is combined with either 1 μM 5-HT or 1 μM forskolin (MOR, KOR and DOR).1D , 5-HT 1E , 5-HT4, and 5-HT 5A For functional assay measurements, β-arrestin2 recruitment is measured by Tango assay using HTLA cells expressing Tobacco Etch Virus (TEV)-fused β-arrestin2 as previously described with minor modifications. Cell lines are not authenticated, but are purchased mycoplasma-free and tested for mycoplasma contamination. Data for all assays are plotted and nonlinear regression performed using "log(agonist) vs. response" in GraphPad Prism to derive estimates of efficacy (Emax and half-maximal effective concentration (EC 50 )).

[0332] Pharmacokinetic studies. Male and female C57 / BL6J mice (12 weeks old) are administered the compounds of formula I and / or formula V via intravenous infusion at doses of either 50 mg kg-1, 10 mg kg-1 or 1 mg kg-1. Mice are euthanized by cervical dislocation 15 minutes or 3 hours after injection. Two males and two females are used per dose and time point. Brains and livers are collected, flash frozen in liquid nitrogen and stored at -80°C until metabolomic processing. Whole brains and liver sections are lyophilized overnight until completely dry and then homogenized with 3.2 mm diameter stainless steel beads using a GenoGrinder at 1,500 rpm for 50 seconds. The ground tissue is then extracted using 225 μl cold methanol, 190 μl water, 750 μl methyl tert-butyl ether (MTBE). Seven method blanks and seven quality control samples (pooled human serum, BioIVT) are sampled simultaneously. The non-polar fraction of MTBE is dried under vacuum and reconstituted in 60 μl of 90:10 (v / v) methanol:toluene containing 1-cyclohexyldodecanoic acid urea as an internal standard. Samples are then vortexed, sonicated, and centrifuged before analysis.

[0333] For analysis of test compounds in liver and brain, samples are randomized before injection with a method blank and quality control samples are analyzed between every 10 study samples. A 6-point calibration curve is analyzed after column equilibration using a blank injection and then after every study sample. A blank is injected after the calibration curve to ensure that none of the test compounds are retained on the column and carried over into the sample. Reconstituted samples (5 μl) are injected onto a Waters Acquity UPLC CSH C18 column (100 mm×2.1 mm, 1.7 μm particle size) with an Acquity UPLC CSH C18 VanGuard precolumn (Waters) using a Vanquish UHPLC coupled to a TSQ Altis triple quadrupole mass spectrometer (Thermo Fisher Scientific). Mobile phase A consists of 60:40 v / v acetonitrile / water with 10 mM ammonium formate and 0.1% formic acid. Mobile phase B consists of 90:10 v / v isopropanol / acetonitrile with 10 mM ammonium formate and 0.1% formic acid. The gradient is run 0-2 min at 15% B; 2-2.5 min at 30% B; 2.5-4.5 min at 48% B; 4.5-7.3 min at 99% B; 7.3-10 min at 15% B. The flow rate is 0.600 ml / min and the column is heated to 65 °C. Mass spectrometer conditions are optimized for the target compound by direct infusion. Selected reaction monitoring is performed for the top 5 ions with collision energy, source fragmentation, and radio frequency optimized for the test compound. Data are processed with TraceFinder 4.1 (Thermo Fisher Scientific). Organ weights are reported. The concentration in the brain is calculated using an empirically determined number of moles of the target compound in the whole organ divided by the organ weight.

[0334] 5-HT receptor functional assay. Various assays for measuring serotonin receptor activation are known to those skilled in the art, including those methods described in Olsen et al., Nat. Chem. Biol., 2020 Aug.; 16(8):841-49, which is incorporated herein by reference in its entirety for all purposes. The assays described herein may be utilized to measure the functional activity of any of the serotonin receptor subtypes described herein, including 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C. In certain embodiments, serotonin (5-hydroxytryptamine) is used as the reference compound.

[0335] cell culture HEK293T cells are maintained, passaged, and transfected in DMEM medium containing 10% FBS, 100 units / mL penicillin, and 100 μg / mL streptomycin (Gibco-ThermoFisher, Waltham, Mass.) at 37° C. and 5% CO2 in a humidified atmosphere. After transfection, cells are seeded in DMEM containing 1% dialyzed FBS, 100 units / mL penicillin, and 100 μg / mL streptomycin for BRET2, calcium, and GloSensor assays.

[0336] BRET2 assay Cells are seeded at a density of either 700,000-800,000 cells / well in 6-well dishes or 7-8 million cells / dish in 10 cm dishes. Cells are transfected 2-4 h later using a 1:1:1:1 ratio of receptor:Gα-RLuc8:Gβ:Gγ-GFP2 DNA (100 ng / construct for 6-well dishes and 750 ng / construct for 10 cm dishes) (except for the Gγ-GFP2 screen, where an ethanol-precipitated mixture of Gβ1-4- is used at twice its usual ratio (1:1:2:1). Transit 2020 (Mirus Biosciences, Madison, WI) is used to complex DNA at a ratio of 3 µL of Transit / µg DNA in OptiMEM (Gibco-ThermoFisher, Waltham, MA) at a concentration of 10 ng DNA / µL of OptiMEM. The next day, cells are harvested from the plates using Versene (0.1 M PBS + 0.5 mM EDTA, pH 7.4) and plated at a density of 30,000-50,000 cells / well in poly-D-lysine coated white clear bottom 96-well assay plates (Greiner Bio-One, Monroe, NC).

[0337] One day after seeding in 96-well assay plates, a white backing (Perkin Elmer, Waltham, MA) is affixed to the plate bottom, and the growth medium is carefully aspirated and immediately replaced with 60 μL of assay buffer (1xHBSS+20 mM HEPES, pH 7.4), followed by the addition of 10 μL of freshly prepared 50 μM coelenterazine 400a (Nanolight Technologies, Pinetop, AZ). After a 5-minute equilibration period, cells are treated with 30 μL of drug for an additional 5 minutes. Plates are then read on an LB940 Mithras plate reader (Berthold Technologies, Oak Ridge, TN) with emission filters of 395 nm (RLuc8-coelenterazine 400a) and 510 nm (GFP2) at an integration time of 1 sec / well. Plates are read six times in succession, and measurements from the six reads are used in all analyses. BRET2 ratios are calculated as the ratio of GFP2 emission to RLuc8 emission.

[0338] Calcium mobilization assay Cells are seeded in 10 cm plates and co-transfected with receptor (1 μg) and Gα-subunit (1 μg) cDNA as described in the BRET2 protocol. The next day, cells are seeded at 15,000 cells / well in poly-D-lysine coated black clear bottom 384-well plates (Greiner Bio-One, Monroe, NC). The next day, growth medium is aspirated and replaced with 20 μL of assay buffer containing 1x Fluo-4 Direct Calcium Dye (ThermoFisher Scientific, Waltham, MA) and incubated for 60 minutes at 37°C (no CO2). Plates are allowed to come to room temperature in the dark for 10 minutes before being loaded onto a FLIPR Tetra® liquid handling robot and plate reader (Molecular Devices, San Jose, CA). A baseline fluorescence measurement is taken for 10 seconds, followed by robotic drug addition (10 μL) and 60 seconds of measurement (1 measurement / second). For antagonist assays, cells are first treated with antagonist and kept in the dark at room temperature for 10 minutes before adding agonist by FLIPR Tetra® robot. The maximum response during this time is used to calculate the amplitude of calcium transients. Measurement results are analyzed as a percentage of the maximum signal amplitude for the construct.

[0339] Glosensor cAMP Assay Cells are seeded in 10 cm plates as previously described. Cells are transfected with plasmids encoding cDNAs for Glosensor reporter (Promega, Madison, WI), receptor, and Gα-subunits in a 2:1:1 ratio (2 μg:1 μg:1 μg). The next day, cells are seeded in black clear-bottom 384-well white plates. On the day of the assay, after aspirating the medium, cells are incubated with 20 μL of 5 mM luciferin substrate (GoldBio, St. Louis, MO) freshly prepared in assay buffer for 60 min at 37° C. For Gαs activity, 10 μL of drug is added using a FLIPR Tetra® liquid handling robot and read after 15 min in a Spectramax luminescence plate reader (Molecular Devices, San Jose, CA) with a signal integration time of 0.5 s. For Gαi activity, 10 μL of drug is added for a 15 min incubation period. Then 10 μL of isoproterenol (200 nM final concentration) is added and incubated for a further 15 minutes before reading.

[0340] Exemplary embodiments Embodiment 1: A compound of formula I: [ka] (In the formula, Group A is a residue of a first active compound that comprises a serotonergic agent; Group B is a residue of a second active compound; L is a covalent bond between group A and group B. and salts, solvates, hydrates, and prodrugs thereof.

[0341] Embodiment 2: At least one of Group A or Group B is a serotonergic agent selected from formula II and III: [ka] (In the formula, X and Y are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl, or Y together with X and the nitrogen atom therebetween forms a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; W1 is selected from NR1, O, S, S(O), SO2, Se, Se(O), and SeO2; W2 is selected from -CD2-, -CHD-, -(CD2)2-, -CH2-, and -(CH2)2-; Z4 is selected from N and CR4; Z5 is selected from N and CR5; Z6 is selected from N and CR6; Z7 is selected from N and CR7; R1 is selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, -C(O)R8, -C(O)OR8, -P(O)(OR9), -C(O)N(R9), -SOR8, and -SOR8; R2, R3, R 3’ R6 and R7 are each independently selected from hydrogen, deuterium, -N(R9)2, -SR9, halo, optionally substituted C1-C8 alkyl, -C1-C8 alkoxy, and optionally substituted C2-C8 alkenyl; or Y is absent and R3, taken together with the carbon to which it is attached and the nitrogen atom to which X is attached, forms a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; or Y is absent and R2, taken together with the carbon to which it is attached and the nitrogen atom to which X is attached, forms a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; R4 and R5 are each independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -N(R9)2, -SR9, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8; each R8 is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; Each R9 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl. and salts, solvates, hydrates, and prodrug residues thereof.

[0342] Embodiment 3: R and R 3’ is hydrogen for each occurrence.

[0343] Embodiment 4: A compound of embodiment 2 or 3, wherein X and Y at each occurrence are independently selected from C1-C8 alkyl.

[0344] Embodiment 5: The compound of embodiment 4, wherein X is methyl.

[0345] Embodiment 6: The compound of embodiment 4, wherein X is ethyl.

[0346] Embodiment 7: The compound of embodiment 4, wherein X is n-propyl.

[0347] Embodiment 8: The compound of embodiment 4, wherein X is isopropyl.

[0348] Embodiment 9: The compound of any one of embodiments 2-3, wherein X is hydrogen.

[0349] Embodiment 10: The compound of any one of embodiments 2-9, wherein Y is methyl.

[0350] Embodiment 11: The compound of any one of embodiments 2-9, wherein Y is ethyl.

[0351] Embodiment 12: The compound of any one of embodiments 2-9, wherein Y is n-propyl.

[0352] Embodiment 13: The compound of any one of embodiments 2-9, wherein Y is isopropyl.

[0353] Embodiment 14: A compound of any one of embodiments 2-13, wherein W2, for each occurrence, is independently selected from -CD2, -CHD-, and -CH2-.

[0354] Embodiment 15: A compound of any one of embodiments 2 to 14, wherein R2, for each occurrence, is hydrogen.

[0355] Embodiment 16: R and R in each occurrence 3’ The compound of any one of embodiments 2 and 4-15, wherein is independently selected from hydrogen, deuterium, and C1-C4 alkyl.

[0356] Embodiment 17: R and R 3’ is each independently selected from methyl and hydrogen.

[0357] Embodiment 18: A compound according to any one of embodiments 2 to 17, wherein R7 is selected from hydrogen and C1-C4 alkyl.

[0358] Embodiment 19: The compound of embodiment 18, wherein R7 is methyl.

[0359] Embodiment 20: A compound of embodiment 18, wherein R7 is hydrogen.

[0360] Embodiment 21: A compound according to any one of embodiments 2 to 20, wherein R6 is selected from hydrogen, -C1-C8 alkoxy, and halo.

[0361] Embodiment 22: A compound according to embodiment 21, wherein R6 is selected from halo and methoxy.

[0362] Embodiment 23: A compound of embodiment 21, wherein R6 is fluoro.

[0363] Embodiment 24: A compound of embodiment 21, wherein R6 is chloro.

[0364] Embodiment 25: A compound of embodiment 21, wherein R6 is bromo.

[0365] Embodiment 26: A compound according to any one of embodiments 2 to 25, wherein at least one of R4 and R5 is hydroxyl.

[0366] Embodiment 27: The compound of embodiment 26, wherein the linker "L" is linked to the residue of the compound of formula II via a hydroxyl group.

[0367] Embodiment 28: A compound according to any one of embodiments 2 to 21 and 26 to 27, wherein Z6 is N.

[0368] Embodiment 29: A compound according to any one of embodiments 2 to 17 and 21 to 28, wherein Z7 is N.

[0369] Embodiment 30: A compound according to any one of embodiments 2 to 29, wherein W1 is NR1.

[0370] Embodiment 31: A compound of any one of embodiments 2 to 29, wherein W1 is O.

[0371] Embodiment 32: A compound of any one of embodiments 2 to 29, wherein W1 is S.

[0372] Embodiment 33: A compound of any one of embodiments 2 to 29, wherein W1 is Se.

[0373] Embodiment 34: A compound according to any one of claims 2 to 33, wherein Group A is a residue of a compound of formula II.

[0374] Embodiment 35: The compound of any one of claims 2 to 33, wherein Group A is a residue of a compound of formula III.

[0375] Embodiment 36: A compound of any one of the preceding embodiments, wherein Group B is a residue of a cannabinoid.

[0376] Embodiment 37: The compound of embodiment 36, wherein the cannabinoid is selected from delta-8-THC, delta-9-THC, THCA, THCV, THCVA, CBC, CBCA, CBCV, CBCVA, CBD, CBDA, CBDV, CBDVA, CBG, CBGA, CBGV, and CBGVA.

[0377] Embodiment 38: A compound according to any one of the preceding embodiments, wherein Group B is a residue of an active compound which is a serotonin receptor 5-HT2A agonist.

[0378] Embodiment 39: The compound of embodiment 38, wherein the serotonin receptor 5-HT1A agonist is a full agonist.

[0379] Embodiment 40: The compound of any one of embodiments 38-39, wherein the serotonin receptor 5-HT1A agonist is a compound of formula II.

[0380] Embodiment 41: The serotonin receptor 5-HT2A agonist is selected from the group consisting of buspirone (8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione), 5-OH-buspirone, 6-OH-buspirone, tandospirone ((1R,2R,6S,7S)-4-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}-4-azatricyclo[5.2.1.02,6]decane-3,5-dione), gepirone (4,4-dimethyl-1-[4-(4-pyrimidin-2-ylpiperazin- 1-yl)butyl]piperidine-2,6-dione), alnespirone ((+)-4-dihydro-2H-chromen-3-yl]-propylamino]butyl]-8-azaspiro[4.5]decane-7,9-dione), binospirone (8-[2-(2,3-dihydro-1,4-benzodioxin-2-ylmethylamino)ethyl]-8-azaspiro[4.5]decane-7,9-dione), ipsapirone (9,9-dioxo-8-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-9.6-thia-8-azabicyclo[4.3]lambda-6.0]nona-1,3,5-trien-7-one), perospirone (3aR,7aS)-2-{4-[4-(1,2-benzisothiazol-3-yl)piperazin-1-yl]butyl}hexahydro-1H-isoindole-1,3(2H)-dione, befiladol (F-13,640) (3-chloro-4-fluorophenyl-[4-fluoro-4-([(5-methylpyridin-2-yl)methylamino]methyl)piperidine) zymidine-1-yl]methanone, repinotan ((R)-(-)-2-[4-[(chroman-2-ylmethyl)-amino]-butyl]-1,1-dioxo-benzo[d]isothiazolone), piclozotan (3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one), osemozotan (5-(3-[((2S)-1,4- Benzodioxan-2-ylmethyl)amino]propoxy)-1,3-benzodioxole), flesinoxan (4-fluoro-N-[2-[4-[(3S)-3-(hydroxymethyl)-2,3-dihydro-1,4-benzodioxin-8-yl]piperazin-1-yl]ethyl]benzamide), flibanserin (1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1,3 39. The compound according to embodiment 38, wherein the compound is selected from 1-[(2R)-3,4-dihydro-2H-benzimidazol-2-one), 8-OH-DPAT (7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol), and sarizotan (EMD-128,130) (1-[(2R)-3,4-dihydro-2H-chromen-2-yl]-N-([5-(4-fluorophenyl)pyridin-3-yl]methyl)methanamine).

[0381] Embodiment 42: The compound of any one of embodiments 1-35 and 38-40, wherein the compound of formula I is a compound of formula IA: [ka]

[0382] Embodiment 43: The compound of any one of embodiments 1 to 35, 38 to 40, and 42, wherein the compound of formula I is a compound of formula IB: [ka]

[0383] Embodiment 44: A compound according to any one of the preceding embodiments, wherein the linker "L" is selected from formula IV: [ka] (In the formula, L1 and L5 in each occurrence are independently a covalent bond, O, NR 10 , and S; L2 and L4 in each occurrence are independently O, C(R 10 )2, NR 10 , and S; L3 in each occurrence is independently O, NR 10 , S, C(R 10 )2, C(R 10 )=C(R 10 ), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl; R at each occurrence 10 are independently hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, NO2, -N(R9)2, -SR9, halo, hydroxyl, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, OP(O)(OR9)2, -OSO2R8, and residues of formula IVB: [ka] is selected from R8 is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; R9 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; n, p, and q in each occurrence are integers independently selected from 0 to 10.

[0384] Embodiment 45: A compound according to embodiment 44, wherein L1 and L5 are O.

[0385] Embodiment 46: L2 and L4, for each occurrence, are independently O and C(R 10 46. ​​The compound of any one of embodiments 44-45, wherein said compound is selected from:

[0386] Embodiment 47:R 10 is, for each occurrence, independently selected from hydrogen and C1-C4 alkyl.

[0387] Embodiment 48: The compound of any one of embodiments 44-47, wherein n and q are integers independently selected from 1, 2, 3, and 4.

[0388] Embodiment 49: L3 at each occurrence is independently selected from O, S, and C(R 10 49. The compound of any one of embodiments 44-48, wherein said compound is selected from:

[0389] Embodiment 50: R 10 The compound of any one of embodiments 44-49, wherein for each occurrence, is hydrogen.

[0390] Embodiment 51: A compound according to any one of embodiments 44 to 50, wherein p is an integer selected from 1, 2, 3 and 4.

[0391] Embodiment 52: The compound of any one of embodiments 2-35, 42, and 44-51, wherein Group B is a residue of buspirone enolate, 6-OH-buspirone, or 8-OH-DPAT.

[0392] Embodiment 53: The compound of embodiment 52, wherein the compound is selected from the following: [ka]

[0393] Embodiment 54: The compound of embodiments 42-51, wherein the compound is a Dipsilocin™ analog selected from formula IF: [ka]

[0394] Embodiment 55: The compound of any one of embodiments 1 to 54, wherein the compound is a salt.

[0395] Embodiment 56: The compound of any one of embodiments 1 to 55, wherein the compound is crystalline.

[0396] Embodiment 57: A composition comprising, consisting essentially of, or consisting of a compound according to any one of embodiments 1 to 56 and 62 to 117 and excipients.

[0397] Embodiment 58: The composition of embodiment 57, wherein the composition is a pharmaceutical composition comprising, consisting essentially of, or consisting of a therapeutically effective amount of a compound of any one of embodiments 1 to 56 and 62 to 117 and a pharma- ceutically acceptable excipient.

[0398] Embodiment 59: A method for preventing or treating a psychiatric disorder, comprising administering a therapeutically effective amount of a compound according to any one of embodiments 1 to 56 and 62 to 117, or a composition according to any one of embodiments 57 to 58, to a subject in need thereof.

[0399] Embodiment 60: A method for preventing or treating inflammation and / or pain, comprising administering a therapeutically effective amount of a compound according to any one of embodiments 1 to 56 and 62 to 117, or a composition according to any one of embodiments 57 to 58, to a subject in need thereof.

[0400] Embodiment 61: A method of modulating activity at a neurotransmitter receptor, comprising: The method comprises administering to a subject in need thereof a compound according to any one of embodiments 1-56 and 62-117, or a composition according to any one of embodiments 57-58.

[0401] Embodiment 62: A compound of formula IDe: [ka] (In the formula, X, X1, Y and Y1 in each occurrence are independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl, or Y or Y1 together with X or X1, respectively, and the nitrogen atom therebetween form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; W1 and W 1a is independently selected from NR1, O, S, S(O), SO2, Se, Se(O), and SeO2; W2 and W 2a is independently selected from -CD2-, -CHD-, -(CD2)2-, -CH2-, and -(CH2)2-; Z4 and Z 4a is independently selected from N and CR4; Z5 and Z 5a is independently selected from N and CR5; Z6 and Z 6a is independently selected from N and CR6; Z7 and Z 7a is independently selected from N and CR7; R1 in each occurrence is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, -C(O)R8, -C(O)OR8, -OP(O)(OR9), -C(O)N(R9), -SOR8, and -SOR8; R2, R3, R6, R7, R 2a , R 3a , R 3’ and R 3a’ is independently selected from hydrogen, deuterium, -N(R9)2, -SR9, halo, optionally substituted C1-C8 alkyl, -C1-C8 alkoxy, and optionally substituted C2-C8 alkenyl; Or Y or Y1 is absent, and R3 or R 3a taken together with the carbon to which it is attached and the nitrogen atom to which X or X1 is attached, respectively, form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; Or X or X1 is absent and R2 or R 2a each taken together with the carbon to which it is attached and the nitrogen atom to which Y or Y1 is attached forms a 5-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; R4 and R5 in each occurrence are independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -N(R9)2, -SR9, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8; R8 at each occurrence is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; R9 at each occurrence is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; L1 and L5 in each occurrence are independently a covalent bond, O, NR 10, and S; L2 and L4 in each occurrence are independently O, C(R 10 )2, NR 10 , and S; L3 in each occurrence is independently O, NR 10 , S, C(R 10 )2, C(R 10 )=C(R 10 ), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl; R at each occurrence 10 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl; n, p, and q in each occurrence are integers independently selected from 0 to 10; L1 can replace a hydrogen in an R4 group when Z4 is CR4, a hydrogen in an R5 group when Z5 is CR5, a hydrogen in an R6 group when Z6 is CR6, or a hydrogen in an R7 group when Z7 is CR7; or L1 can replace a hydrogen atom in the X or R2 group; L5 can replace hydrogen, Z 4a When is CR4, hydrogen in the R4 group is replaced by Z 5a When R5 is CR5, hydrogen in the R5 group is replaced by Z 6a When is CR6, hydrogen in the R6 group is replaced by Z 7a When is CR7, hydrogen in the R7 group can be replaced; Or L5 can replace a hydrogen atom in X or R2 group. or salts, solvates, hydrates, and prodrugs thereof.

[0402] Embodiment 63: A compound of embodiment 62, wherein X is hydrogen.

[0403] Embodiment 64: A compound according to embodiment 62, wherein X, X1, Y and Y1 are selected from optionally substituted C1-C8 alkyl and optionally substituted C2-C8 alkenyl.

[0404] Embodiment 65: A compound of embodiment 62 or 64, wherein X is methyl.

[0405] Embodiment 66: A compound according to any one of embodiments 62 to 65, wherein X1 is methyl.

[0406] Embodiment 67: A compound according to any one of embodiments 62, 64, and 66, wherein X is ethyl.

[0407] Embodiment 68: A compound according to any one of embodiments 62 to 65, and 67, wherein X1 is ethyl.

[0408] Embodiment 69: A compound according to any one of embodiments 62-63 and 65-68, wherein Y is hydrogen.

[0409] Embodiment 70: A compound according to any one of embodiments 62-63 and 65-69, wherein Y1 is hydrogen.

[0410] Embodiment 71: A compound according to any one of embodiments 62-68, and 70, wherein Y is methyl.

[0411] Embodiment 72: A compound according to any one of embodiments 62 to 69 and 70, wherein Y1 is methyl.

[0412] Embodiment 73: A compound according to any one of embodiments 62-68, and 70, wherein Y is ethyl.

[0413] Embodiment 74: A compound according to any one of embodiments 62-69, 71, and 73, wherein Y1 is ethyl.

[0414] Embodiment 75: W2 and W 2ais each independently selected from -CD2-, -CHD-, and -CH2-.

[0415] Embodiment 76: R3 and R 3’ are each independently selected from hydrogen, deuterium, and C1-C4 alkyl.

[0416] Embodiment 77: R 3a and R 3a’ are each independently selected from hydrogen, deuterium, and C1-C4 alkyl.

[0417] Embodiment 78: R2 and R 2a The compound of any one of embodiments 62-77, wherein is hydrogen.

[0418] Embodiment 79: Z6, Z 6a , Z7 or Z 7a The compound of any one of embodiments 62-78, wherein at least one of is N.

[0419] Embodiment 80: Z7 or Z 7a The compound of any one of embodiments 62-79, wherein at least one of is N.

[0420] Embodiment 81: Z6 and Z 6a and each of the following is CR6:

[0421] Embodiment 82: A compound of embodiment 81, wherein each R6 is independently selected from C1-C8 alkoxy, hydrogen, and halo.

[0422] Embodiment 83: A compound according to embodiment 82, wherein each R6 is independently selected from methoxy, fluoro, chloro, and bromo.

[0423] Embodiment 84: Z6 or Z6a The compound of any one of embodiments 62-80, wherein at least one of is N.

[0424] Embodiment 85: Z7 and Z 7a and R 1 and R 2 are each independently CR7.

[0425] Embodiment 86: A compound according to embodiment 85, wherein each R7 is independently selected from C1-C4 alkyl and hydrogen.

[0426] Embodiment 87: A compound of embodiment 86, wherein each R7 is methyl.

[0427] Embodiment 88: A compound according to any one of embodiments 62 to 87, wherein at least one of Z4 or Z5 is CR4 and CR5, respectively.

[0428] Embodiment 89: Z 4a or Z 5a The compound according to any one of embodiments 62-88, wherein at least one of is CR4 and CR5, respectively.

[0429] Embodiment 90: A compound according to any one of embodiments 62 to 89, wherein Z4 is CR4, wherein R4 is replaced by L1.

[0430] Embodiment 91: A compound according to any one of embodiments 62 to 89, wherein Z5 is CR5, wherein R5 is replaced by L1.

[0431] Embodiment 92: Z 4a is CR4, where R 4a The compound according to any one of embodiments 62-91, wherein is replaced by L5.

[0432] Embodiment 93: Z 5a is CR5, where R 5aThe compound according to any one of embodiments 62-91, wherein is replaced by L5.

[0433] Embodiment 94: A compound according to any one of embodiments 62 to 93, wherein L1 is O.

[0434] Embodiment 95: A compound according to any one of embodiments 62 to 94, wherein L5 is O.

[0435] Embodiment 96: A compound according to any one of embodiments 62 to 95, wherein W1 is NR1.

[0436] Embodiment 97: A compound according to any one of embodiments 62 to 96, wherein R1 is selected from hydrogen and C1-C4 alkyl.

[0437] Embodiment 98: A compound according to any one of embodiments 62 to 95, wherein W1 is O.

[0438] Embodiment 99: A compound according to any one of embodiments 62 to 95, wherein W1 is S.

[0439] Embodiment 100: A compound according to any one of embodiments 62-95, wherein W1 is Se.

[0440] Embodiment 101: W 1a The compound according to any one of embodiments 62-100, wherein is NR1.

[0441] Embodiment 102: A compound according to embodiment 101, wherein R1 is selected from hydrogen and C1-C4 alkyl.

[0442] Embodiment 103: W 1a The compound according to any one of embodiments 62-100, wherein

[0443] Embodiment 104: W 1a The compound of any one of embodiments 62-100, wherein is S.

[0444] Embodiment 105: W 1a The compound according to any one of embodiments 62-100, wherein is Se.

[0445] Embodiment 106: L2 and L4 at each occurrence are independently O and C(R 10 ) 2. The compound of any one of embodiments 62-105, wherein

[0446] 107. R in each occurrence 10 is independently selected from hydrogen and C1-C4 alkyl.

[0447] 108. R in each occurrence 10 is independently selected from hydrogen and methyl.

[0448] Embodiment 109: A compound according to any one of embodiments 62 to 108, wherein n and q are independently selected from 1, 2, 3, and 4.

[0449] Embodiment 110: L3 at each occurrence is independently selected from O, S and C(R 10 ) 2. The compound of any one of embodiments 62-109, wherein

[0450] Embodiment 111: R in each occurrence with respect to L3 10 is independently selected from hydrogen and C1-C4 alkyl.

[0451] Embodiment 112: R in each occurrence with respect to L3 10 The compound of embodiment 111, wherein is hydrogen.

[0452] Embodiment 113: A compound according to any one of embodiments 62 to 112, wherein p is selected from 1, 2, 3 and 4.

[0453] Embodiment 114: The compound according to any one of embodiments 62-78, 81-83, 85-97, 101-102, and 106-113, wherein the compound of formula IDe is selected from formula IEa: [ka]

[0454] Embodiment 115: A compound according to embodiment 114, wherein L1 and L5 are O.

[0455] Embodiment 116: A compound according to embodiment 114 or 115, wherein L1 replaces R4 on the first indole scaffold.

[0456] Embodiment 117: A compound according to any one of embodiments 113-114, wherein L5 replaces R4 on the second indole scaffold.

[0457] 1. Embodiment 118: Compound of formula IG: [ka] (In the formula, X, X1, Y and Y1 in each occurrence are independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl, or Y or Y1 together with X or X1, respectively, and the nitrogen atom therebetween form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; W1 and W 1a is independently selected from NR1, O, S, S(O), Se, Se(O), and SeO2; W2 and W 2a is independently selected from -CD2-, -CHD-, -(CD2)2-, -CH2-, and -(CH2)2-; Z5 and Z 5a is independently selected from N and CR5; Z6 and Z 6a is independently selected from N and CR6; Z7 and Z 7a is independently selected from N and CR7; R1 at each occurrence is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, -C(O)R8, -C(O)OR8, -P(O)(OR9), -C(O)N(R9), -SOR8, and -SOR8; R2, R3, R6, R7, R 2a , R 3a , R 3’ and R 3a’ is independently selected from hydrogen, deuterium, -N(R9)2, -SR9, halo, optionally substituted C1-C8 alkyl, -C1-C8 alkoxy, and optionally substituted C2-C8 alkenyl; Or Y or Y1 is absent, and R3 or R 3a taken together with the carbon to which it is attached and the nitrogen atom to which X or X1 is attached, respectively, form a 3-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; Or X or X1 is absent and R2 or R 2a each taken together with the carbon to which it is attached and the nitrogen atom to which Y or Y1 is attached forms a 5-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from O, S, S(O), SO2, and NR9; R5 in each occurrence is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, halo, hydroxyl, -N(R9)2, -SR9, -C1-C8 alkoxy, -OC(O)R8, -OC(O)OR8, -OP(O)(OR9)2, and -OSO2R8; R8 at each occurrence is independently selected from optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; R9 at each occurrence is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted aryl; L1 and L5 in each occurrence are independently a covalent bond, O, NR 10 , and S; L2 and L4 in each occurrence are independently O, C(R 10 )2, NR 10 , and S; L3 in each occurrence is independently O, NR 10 , S, C(R 10 )2, C(R 10 )=C(R 10 ), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl; R at each occurrence 10 is independently selected from hydrogen, deuterium, optionally substituted C1-C8 alkyl, and optionally substituted C2-C8 alkenyl; n, p, and q in each occurrence are integers independently selected from 0 to 10; or Salts, solvates, hydrates, and prodrugs thereof.

[0458] Finally, it is noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents, and vice versa, unless expressly and unambiguously limited to one referent. As used herein, the terms "include" or "comprising" and grammatical variations thereof are intended to be open-ended such that the description of an item(s) does not exclude other similar items that may be substituted for or added to the described item(s).

Claims

1. Compound of formula IG: 【Chemistry 1】 (In the formula, X, X in each occurrence １ , Y and Y １ are independently hydrogen, deuterium, optionally substituted C １ -C ８ Alkyl, and optionally substituted C ２ -C ８ alkenyl, or Y or Y １ are X or X respectively. １ and together with the nitrogen atom therebetween, O, S, S(O), SO ２ , and N.R. ９ forming a 3- to 7-membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from W １ and W １ａ are independently NR １ , O, S, S(O), Se, Se(O), and SeO ２ Selected from: W ２ and W ２ａ are independently -CD ２ -, -CHD-, -(CD ２ ) ２ -, -CH ２ - and -(CH ２ ) ２ - selected from; Z ５ and Z ５ａ are independently N and CR ５ Selected from: Z ６ and Z ６ａ are independently N and CR ６ Selected from: Z ７ and Z ７ａ are independently N and CR ７ Selected from: R at each occurrence １ are independently hydrogen, deuterium, optionally substituted C １ -C ８ Alkyl, optionally substituted C ２ -C ８ Alkenyl, —C(O)R ８ , -C(O)OR ８ , -P(O)(OR ９ ) ２ , -C(O)N(R ９ ) ２ , -SOR ８ , and -SO ２ R ８ Selected from: R at each occurrence ２ , R ３ , R ６ , R ７ , R ２ａ , R ３ａ , R ３’ and R ３ａ’ are independently hydrogen, deuterium, -N(R ９ ) ２ , -SR ９ , halo, optionally substituted C １ -C ８ Alkyl, -C １ -C ８ Alkoxy, and optionally substituted C ２ -C ８ alkenyl, or Y or Y １ is non-existent, and R ３ Or R ３ａ is the carbon to which it is attached and X or X １ The nitrogen atoms to which these are attached together form O, S, S(O), SO ２ , and N.R. ９ forming a 3- to 7-membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from or X or X １ is non-existent, and R ２ Or R ２ａ each represents the carbon to which it is attached and Y or Y １ The nitrogen atoms to which these are attached together form O, S, S(O), SO ２ , and N.R. ９ forming a 5-7 membered heterocyclic ring optionally containing 1-2 additional ring hetero moieties selected from R at each occurrence ５ are independently hydrogen, deuterium, optionally substituted C １ -C ８ Alkyl, optionally substituted C ２ -C ８ Alkenyl, halo, hydroxyl, -N(R ９ ) ２ , -SR ９ , -C １ -C ８ Alkoxy, —OC(O)R ８ , -OC(O)OR ８ , -OP(O)(OR ９ ) ２ , and -OSO ２ R ８ Selected from: R at each occurrence ８ are independently optionally substituted C １ -C ８ Alkyl, optionally substituted C ２ -C ８ selected from alkenyl, and optionally substituted aryl; R at each occurrence ９ are independently hydrogen, deuterium, optionally substituted C １ -C ８ Alkyl, optionally substituted C ２ -C ８ selected from alkenyl, and optionally substituted aryl; L in each occurrence １ and L ５ are independently a covalent bond, O, NR １０ and S; L in each occurrence ２ and L ４ are independently O, C(R １０ ) ２ , N.R. １０ and S; L in each occurrence ３ are independently O, NR １０ , S, C(R １０ ) ２ , C(R １０ ) = C(R １０ ), optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocyclyl; R at each occurrence １０ are independently hydrogen, deuterium, optionally substituted C １ -C ８ Alkyl, and optionally substituted C ２ -C ８ alkenyl; n, p, and q in each occurrence are integers independently selected from 0 to 10; or Salts, solvates, hydrates, and prodrugs thereof.

2. X and X １ But independently, C １ -C ８ 2. The compound of claim 1, wherein the alkyl is selected from the group consisting of aryl, aryl, arylsulfonyl ...

3. Y and Y １ But independently, C １ -C ８ 3. The compound of claim 2, wherein the aryl group is selected from alkyl.

4. W ２ and W ２ａ But independently, -CD ２ -, -CHD-, and -CH ２ The compound of claim 1, wherein the compound is selected from:

5. R ２ａ and R ２ The compound of claim 1 , wherein is hydrogen.

6. R ３ , R ３’ , R ３ａ and R ３’ 10. The compound of claim 1, wherein each is independently selected from hydrogen, deuterium, and methyl.

7. R ３ , R ３’ , R ３ａ and R ３’ 10. The compound of claim 1, wherein each is independently selected from hydrogen and deuterium.

8. Z at each occurrence ５ and Z ５ａ But independently, CR ５ 2. The compound of claim 1, wherein:

9. R at each occurrence ５ 9. The compound of claim 8, wherein is independently selected from hydrogen and halogen.

10. Z ６ , Z ６ａ , Z ７ and Z ７ａ The compound of claim 1 , wherein at least one of

11. Z ６ and Z ６ａ The compound of claim 10, wherein is N.

12. Z ７ and Z ７ａ The compound of claim 10, wherein is N.

13. Z ６ and Z ６ａ However, both are CR ６ 11. The compound of claim 10, wherein:

14. R at each occurrence ６ But independently, C １ -C ４ 14. The compound of claim 13, wherein the alkyl group is selected from alkoxy, halo, and hydrogen.

15. W １ and W １ａ However, both are NR １ 2. The compound of claim 1, wherein:

16. L １ and L ５ and R are each O.

17. L in each occurrence ２ and L ４ are independently O and C(R １０ ) ２ 17. The compound of claim 16, selected from:

18. 18. The compound of claim 17, wherein n and q are independently selected from 1, 2, 3 and 4.

19. L in each occurrence ３ are independently O, S and C(R １０ ) ２ 18. The compound of claim 17, selected from:

20. 18. The compound of claim 17, wherein p is selected from 1, 2, 3 and 4.

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