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1-Methylpsilocin structure.png
  • 1-Methyl-3-[2-(N,N-dimethylamino)ethyl]-4-hydroxyindole
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
Formula C13H18N2O
Molar mass 218.300 g·mol−1
3D model (JSmol)
  • CN(C)CCc(cn1C)c2c1cccc2O
  • InChI=1S/C13H18N2O/c1-14(2)8-7-10-9-15(3)11-5-4-6-12(16)13(10)11/h4-6,9,16H,7-8H2,1-3H3

1-Methylpsilocin is a tryptamine derivative which acts as a selective agonist for the 5-HT2C receptor (IC50 of 12 nM, vs 633 nM at 5-HT2A), and an inverse agonist at 5-HT2B (Ki of 38 nM). While 1-methylpsilocin does have higher affinity for 5-HT2C than 5-HT2A, it does produce a head-twitch response in mice that are dependent on 5-HT2A, so it is not entirely free of effects on 5-HT2A in vivo. In contrast to psilocin, 1-methylpsilocin did not activate 5-HT1A receptors in mice. 1-Methylpsilocin has been investigated for applications such as treatment of glaucoma, OCD, and cluster headaches, 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. [1] [2] [3]

See also

Related Research Articles

Psilocybin Chemical compound found in some species of mushrooms

Psilocybin is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. Psilocybin is itself biologically inactive but is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of LSD, mescaline, and DMT. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and perceived spiritual experiences. It can also include possible adverse reactions such as nausea and panic attacks.

Psychedelic drug Hallucinogenic class of psychoactive drug

Psychedelics are a class of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness. This causes specific psychological, visual, and auditory changes, and often a substantially altered state of consciousness. The "classical" psychedelics, the psychedelics with the largest scientific and cultural influence, are mescaline, LSD, psilocybin, and DMT.

Ergotamine Chemical compound in the ergot family of alkaloids

Ergotamine, sold under the brand names Cafergot and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor.

Psilocin Psychedelic substance

Psilocin is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. The mind-altering effects of psilocin are highly variable, subjective, and resemble those of LSD and DMT.


Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and in the treatment of migraine. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.


Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the market in the United States and Canada due to adverse effects. It is taken by mouth.

5-HT<sub>2A</sub> receptor Subtype of serotonin receptor

The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor. 5-HT is short for 5-hydroxy-tryptamine, which is serotonin. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex and the orbitofrontal cortex. This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially the atypical ones.


Ethocybin is a homologue of the mushroom alkaloid psilocybin, and a semi-synthetic psychedelic alkaloid of the tryptamine family. Effects of ethocybin are comparable to those of a shorter LSD or psilocybin trip, although intensity and duration vary depending on dosage, individual physiology, and set and setting.

Serotonin receptor agonist

A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.

5-HT<sub>2B</sub> receptor Mammalian protein found in Homo sapiens

5-Hydroxytryptamine receptor 2B (5-HT2B) also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).

TCB-2 Potent hallucinogenic drug discovered in 2006

TCB-2 is a hallucinogen discovered in 2006 by Thomas McLean working in the lab of David Nichols at Purdue University. It is a conformationally-restricted derivative of the phenethylamine 2C-B, also a hallucinogen, and acts as a potent agonist for the 5-HT2A and 5-HT2C receptors with a Ki of 0.26 nM at the human 5-HT2A receptor. In drug-substitution experiments in rats, TCB-2 was found to be of similar potency to both LSD and Bromo-DragonFLY, ranking it among the most potent phenethylamine hallucinogens yet discovered. This high potency and selectivity has made TCB-2 useful for distinguishing 5-HT2A mediated responses from those produced by other similar receptors. TCB-2 has similar but not identical effects in animals to related phenethylamine hallucinogens such as DOI, and has been used for studying how the function of the 5-HT2A receptor differs from that of other serotonin receptors in a number of animal models, such as studies of cocaine addiction and neuropathic pain.


Aeruginascin or N,N,N-trimethyl-4-phosphoryloxytryptamine is an indoleamine derivative which occurs naturally within the mushroom Inocybe aeruginascens and Pholiotina cyanopus. Aeruginascin is the N-trimethyl analogue of psilocybin. It is closely related to the frog skin toxin bufotenidine (5-HTQ), a potent 5-HT3 receptor agonist, but the aeruginascin metabolite 4-HO-TMT shows strong binding at the 5-HT2 receptors similar to psilocin. The first scientific literature about the pharmacological effects of aeruginascin is from a study published by Gartz in 1989. Across 23 analyzed cases of accidental hallucinogenic mushroom poisonings, people who had ingested the mushroom Inocybe aeruginascens reported only euphoric experiences. This is in contrast to the slight and in some cases extremely dysphoric experiences reported from the accidental ingestion of non aeruginascin containing mushrooms (containing solely psilocybin and psilocin).

AL-34662 Chemical compound

AL-34662 is an indazole derivative drug that is being developed for the treatment of glaucoma. It acts as a selective 5-HT2A receptor agonist, the same target as that of psychedelic drugs like psilocin, but unlike these drugs, AL-34662 was designed specifically as a peripherally selective drug, which does not cross the blood–brain barrier. This means that AL-34662 can exploit a useful side effect of the hallucinogenic 5-HT2A agonists, namely reduction in intra-ocular pressure and hence relief from the symptoms of glaucoma, but without causing the hallucinogenic effects that make centrally active 5-HT2A agonists unsuitable for clinical use. In animal studies, AL-34662 has been shown to be potent and effective in the treatment of symptoms of glaucoma, with minimal side effects.

Osemozotan (MKC-242) is a selective 5-HT1A receptor agonist with some functional selectivity, acting as a full agonist at presynaptic and a partial agonist at postsynaptic 5-HT1A receptors. 5-HT1A receptor stimulation influences the release of various neurotransmitters including serotonin, dopamine, norepinephrine, and acetylcholine. 5-HT1A receptors are inhibitory G protein-coupled receptor. Osemozotan has antidepressant, anxiolytic, antiobsessional, serenic, and analgesic effects in animal studies, and is used to investigate the role of 5-HT1A receptors in modulating the release of dopamine and serotonin in the brain, and their involvement in addiction to abused stimulants such as cocaine and methamphetamine.

LY-293284 Chemical compound

LY-293284 is a research chemical developed by the pharmaceutical company Eli Lilly and used for scientific studies. It acts as a potent and selective 5-HT1A receptor full agonist. It was derived through structural simplification of the ergoline based psychedelic LSD, but is far more selective for 5-HT1A with over 1000x selectivity over other serotonin receptor subtypes and other targets. It has anxiogenic effects in animal studies.

2-Bromo-LSD Chemical compound

2-Bromo-LSD, also known as BOL-148, is a derivative of lysergic acid invented by Albert Hofmann, as part of the original research from which the closely related compound LSD was also derived. 2-Bromo-LSD was found to be inactive as a psychedelic and so was comparatively little researched for many years, although its similar behavior in the body made it useful for radiolabelling studies. It was found to bind to many of the same receptors as LSD, but acting as a neutral antagonist rather than an agonist. However its generally similar behavior to LSD in some respects has shown to be very useful in one specific area, the treatment of cluster headaches. These debilitating attacks have been known for some time to be amenable to treatment with certain hallucinogenic drugs such as LSD and psilocybin, but because of the illegal status of these drugs and the kind of mental changes they induce, research into their medical use has been slow and therapeutic application limited to very specific circumstances under strict supervision. It had been thought that this specific therapeutic action against cluster headaches was limited to hallucinogenic drugs of this type, and would always present a major barrier to their clinical use. However a serendipitous discovery found that 2-bromo-LSD is also able to produce this therapeutic effect, despite lacking the other effects of LSD. This has led to a resurgence of interest and research into 2-bromo-LSD and its possible medical uses. Some isolated incidents of hallucinogenic responses have been reported, but as with other non-hallucinogenic LSD analogues such as lisuride, this appears to be a rare side effect occurring only in individuals with an as yet unexplained susceptibility to this reaction. 2-Bromo-LSD reportedly attenuates the effects of LSD in humans.

Substituted tryptamine

Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.

The head-twitch response (HTR) is a rapid side-to-side head movement that occurs in mice and rats after the serotonin 5-HT2A receptor is activated. The prefrontal cortex may be the neuroanatomical locus mediating the HTR. Many serotonergic hallucinogens, including lysergic acid diethylamide (LSD), induce the head-twitch response, and so the HTR is used as a behavioral model of hallucinogen effects. However while there is generally a good correlation between compounds that induce head twitch in mice and compounds that are hallucinogenic in humans, it is unclear whether the head twitch response is primarily caused by 5-HT2A receptors, 5-HT2C receptors or both, though recent evidence shows that the HTR is mediated by the 5-HT2A receptor and modulated by the 5-HT2C receptor. Also, the effect can be non-specific, with head twitch responses also produced by some drugs that do not act through 5-HT2 receptors, such as phencyclidine, yohimbine, atropine and cannabinoid receptor antagonists. As well, compounds such as 5-HTP, fenfluramine and 1-Methylpsilocin can also produce head twitch and do stimulate serotonin receptors, but are not hallucinogenic in humans. This means that while the head twitch response can be a useful indicator as to whether a compound is likely to display hallucinogenic activity in humans, the induction of a head twitch response does not necessarily mean that a compound will be hallucinogenic, and caution should be exercised when interpreting such results.


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