1-Methylpsilocin
Chemical compound
From Wikipedia, the free encyclopedia
1-Methylpsilocin (developmental code name CMY or CMY-16), also known as 1-methyl-4-hydroxy-N,N-dimethyltryptamine (1-Me-4-HO-DMT), is a serotonin receptor agonist and putative psychedelic drug of the tryptamine and 4-hydroxytryptamine families related to psilocin.[1][2][3] It is the 1-methyl derivative of psilocin.[1][2][3] The drug shows much greater selectivity as a serotonin 5-HT2C receptor agonist than psilocin, but still robustly induces psychedelic-like effects in animals, albeit with lower potency.[2][3][4]
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| Other names | CMY; CMY-16; CMY16; 1-Methyl-psilocin; 1-Methyl-4-hydroxy-N,N-dimethyltryptamine; 1-Methyl-4-HO-DMT; 1-Me-4-HO-DMT; 1-Me-4-OH-DMT |
| Drug class | Serotonin receptor agonist; Serotonin 5-HT2C receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen |
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| Formula | C13H18N2O |
| Molar mass | 218.300 g·molâ1 |
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Use and effects
According to Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved), 1-methylpsilocin is known to have been assessed in clinical studies by Sandoz (code name CMY or CMY-16) but its activity has not been reported.[5][6][7] As such, its properties and effects in humans are unknown.[5]
Interactions
Pharmacology
Pharmacodynamics
The affinities (Ki) of 1-methylpsilocin for serotonin receptors have been reported to be 900 nM for the serotonin 5-HT2A receptor, 38 nM for the serotonin 5-HT2B receptor, and 7.0 nM for the serotonin 5-HT2C receptor (unedited/INI isoform).[2] Its activational potencies and efficacies (EC50 (Emax)) were 633 nM (31%) at the serotonin 5-HT2A receptor, inverse agonism at the serotonin 5-HT2B receptor (values not given), and 12 nM (45%) at the serotonin 5-HT2C receptor.[2] As a result, it was concluded that 1-methylpsilocin is a selective serotonin 5-HT2C receptor agonist.[2]
In subsequent research however, 1-methylpsilocin has been reported to have activational potencies and efficacies in terms of Gq dissociation BRET assays of 86 nM (73%) at the serotonin 5-HT2A receptor, 32 nM (40%) at the serotonin 5-HT2B receptor, and 9.5 nM at the serotonin 5-HT2C receptor (92%).[4] It was about 10-fold less potent than psilocin at the serotonin 5-HT2A receptor and 30-fold less potent at the 5-HT2B receptor but had similar potency at the serotonin 5-HT2C receptor.[4] Besides at the serotonin 5-HT2 receptors, 1-methylpsilocin has shown affinity for the serotonin 5-HT1A receptor (Ki = 358 nM), albeit approximately 7-fold lower than that of psilocin.[3]
Despite showing much greater potency at the serotonin 5-HT2C receptor than at the 5-HT2A receptor, 1-methylpsilocin produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.[1][8][3] This effect was absent in serotonin 5-HT2A receptor knockout mice.[1][3] The median effective dose (ED50) of 1-methylpsilocin for induction of the head-twitch response was about 2.3-fold lower than that of psilocin (0.3 mg/kg and 0.7 mg/kg, respectively), and hence 1-methylpsilocin was somewhat less potent than psilocin.[8][1][3] The two drugs showed similar maximal responses in terms of head twitch counts.[3] Due to its induction of the head-twitch response, it is very likely that 1-methylpsilocin would produce hallucinogenic effects in humans, but may have reduced potency in comparison.[3]
The fact that 1-methylpsilocin is able to robustly induce the head-twitch response similarly to psilocin suggests that serotonin 5-HT2C receptor agonism does not suppress the head-twitch response mediated by the serotonin 5-HT2A receptor.[9] Accordingly, the serotonin 5-HT2C receptor antagonist SB-242084 did not significantly reduce the head-twitch response induced by 1-methylpsilocin in rodents.[8] On the other hand, 1-methylpsilocin was found to strongly suppress the head-twitch response induced by the phenethylamine psychedelic DOI (by up to 82%) in rodents.[10] It was hypothesized that these paradoxical findings might be accounted for by differences in functional selectivity between the drugs and/or by 1-methylpsilocin possibly additionally activating certain serotonin 5-HT1 receptors.[10]
Unlike psilocin, which produced hypolocomotion mediated by serotonin 5-HT1A receptor activation, 1-methylpsilocin showed no effects in locomotor activity in rodents.[1][3] These findings suggest that 1-methylpsilocin may be inactive as a serotonin 5-HT1A receptor agonist.[1][3] 1-Methylpsilocin has shown anti-obsessional-like effects in rodents.[2] In addition, it has shown antidepressant-, antianhedonic-, and anxiolytic-like effects in rodents.[11][12] In contrast to psilocin and DOI, 1-methylpsilocin did not show anti-inflammatory effects in preclinical research, which was attributed to its selectivity for the serotonin 5-HT2C receptor and reduced activity at the serotonin 5-HT2A receptor.[13]
1-Methylpsilocin was shown to be a substantially biased agonist of the serotonin 5-HT2C receptor at different downstream signaling pathways similarly to many other psychedelics in 2025.[14] For instance, it was a high-efficacy agonist of the Gq and G11 pathways (89â95%), a moderate-efficacy agonist of the Gz pathway (66%), and a low-efficacy agonist or inactive at the G12, G13, GoA, GoB, Gi1, Gi2, Gi3, β-arrestin1, and β-arrestin2 pathways (0â28%).[14]
Chemistry
Synthesis
The chemical synthesis of 1-methylpsilocin has been described.[15]
Analogues
Various analogues and derivatives of 1-methylpsilocin, including prodrugs, have been studied and described.[16][2][4]
Some notable analogues of 1-methylpsilocin include 1-methyltryptamine, 1-methyl-DMT, lespedamine (1-methoxy-DMT), 1-propyl-5-MeO-AMT, O-4310 (1-isopropyl-6-fluoropsilocin), and CP-132,484 (4,5-dihydropyrano-1-methyltryptamine), among others. In addition, 1-methyl lysergamides like MLD-41 (1-methyl-LSD) and methysergide (1-methylmethylergometrine) are cyclized tryptamines and hence have some structural similarity to 1-methylpsilocin.
History
1-Methylpsilocin was originally developed by Albert Hofmann and colleagues at Sandoz in the late 1950s.[15][5] Subsequently, it was studied by Sard and colleagues at Organix in the mid-2000s[16][2] and by other researchers such as Adam Halberstadt and colleagues in the 2010s and thereafter.[3][8][10][14][4]
1-Methylpsilocin has been investigated for potential medical applications such as treatment of glaucoma, obsessiveâcompulsive disorder (OCD), cluster headaches, and obesity, as these conditions are amenable to treatment with psychedelic drugs but are not generally treated with such agents due to the hallucinogenic side effects they produce, which are considered undesirable. 1-Methylpsilocin therefore represents a potential alternative treatment to psilocin that may be less likely to produce hallucinogenic effects.[2][3][17]