4-HO-MET
4-HO-MET is a synthetic psychedelic tryptamine first synthesized by Alexander Shulgin and documented in his 1997 book TiHKAL.1 Structurally related to psilocin, it produces effects through serotonin receptor agonism.2 Users typically describe it as more recreational than psilocybin mushrooms, characterized by vivid colorful visuals with a less mentally intense headspace. Reports of human use emerged in the late 2000s following its appearance on the research chemical market. Very little data exists regarding its toxicity profile.
Contents
Dosage & Duration
Dosage
Reported active doses vary widely between individuals; some report heavy effects near 17 mg while others report light effects at 30 mg, which has been attributed to differences in metabolism, batch quality, and salt form. Nausea is reported to be less prominent than with psilocybin mushrooms and may be reduced by dosing on an empty stomach.
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
The physical effects of 4-HO-MET can be broken down into several components which progressively intensify proportional to dosage. These are described below and generally include:
Cognitive
The cognitive effects of 4-HO-MET are described by many as somewhat relaxing yet fast-paced in style with similarities to psychedelics such as LSD or 2C-B which tend to be cognitively energetic and stimulating. The drug contains a large number of typical and unique psychedelic cognitive effects. The most prominent of these typical effects generally include:
Visual
A noteworthy aspect regarding this compound is that at sub-psychedelic doses, it appears to still produce visual effects without any accompanying cognitive effects or "head space."
Distortions
As for visual distortions and alterations, the effects experienced are detailed below:
Enhancements
4-HO-MET presents a full and complete array of possible visual enhancements which generally includes:
Geometry
The visual geometry that is present throughout this trip can be described as somewhat similar in appearance to that of psilocin (4-HO-DMT) and 4-HO-MiPT but with far stronger synthetic digital undertones reminiscent of LSD or 2C-B. 4-HO-MET can be comprehensively described through its variations as intricate in complexity, abstract in form, equally synthetic and organic in style, structured in organization, extremely brightly lit and multicoloured in scheme, glossy in shading, sharp in edges, large in size, fast in speed, smooth in motion, angular in corners, non-immersive in depth and consistent in intensity. The visuals have a contradictory natural and synthetic feel to them which is reminiscent of both LSD and psilocybin.
Hallucinatory States
4-HO-MET and its various other forms produce a full range of high level hallucinatory states in a fashion that is more consistent and reproducible than that of many other commonly used psychedelics. These effects generally include:
Auditory
The auditory effects of 4-HO-MET are common in their occurrence and exhibit a full range of effects which commonly include:
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
4-HO-MET primarily acts as a partial agonist at the serotonin 5-HT2A receptor2 with high affinity and a maximum activation of 72%, an interaction believed to underlie its psychedelic effects. It also acts as an agonist at 5-HT1A, 5-HT2B, and 5-HT2C receptors and shows high affinity for the serotonin transporter with modest reuptake inhibition, though direct receptor agonism is considered the more significant contributor to its effects. Additional lower-affinity binding has been observed at histamine H1, TAAR1, dopamine D2 and D3, and α1A and α2A adrenergic receptors.2 4-HO-MET does not possess monoamine releasing properties.2
Pharmacokinetics
4-HO-MET is metabolized hepatically. In vivo studies in humans have identified four metabolites3 resulting from hydroxylation, glucuronidation of the parent compound, and glucuronidation of an N-oxide metabolite. In vitro analysis using pooled human liver microsomes has revealed a broader metabolic profile of twelve metabolites3, with additional transformation pathways including dihydroxylation, N-oxide formation, demethylation, desethylation, and carboxylic acid formation. Three of the monohydroxylated metabolites were modified at the benzene ring of its indole structure. 4-AcO-MET is believed to function as an ester prodrug that is hydrolyzed to 4-HO-MET in the body.
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
All psychedelics
Harm Potential
Addiction & Dependence
Psychological
Extremely Low4-HO-MET is not habit-forming and the desire to use it can actually decrease with use. It is most often self-regulating and is not known to be associated with compulsive use.
Physical
Extremely LowPhysical dependence is extremely unlikely.4
Toxicity
Tachycardia and elevated blood pressure may occur during acute intoxication; serious cardiovascular complications are hypothetical and would be expected primarily at overdose levels.
Kidney damage is a hypothetical risk at overdose levels based on pharmacological considerations; no documented cases of renal toxicity from typical use.
Psychosis Risk
There are reports of very high doses leading to drug-induced psychosis. A formal case report described a teenager who used approximately 100 mg, resulting in severe psychotic symptoms including visual hallucinations, paranoid delusions, sensation of insects under the skin, and dangerous behavior requiring week-long hospitalization. Psychotic symptoms typically resolve with supportive care, though paranoid ideation may persist for several days. At common doses, psychotic reactions are uncommon.
Seizure Risk
Like other psychedelics, 4-HO-MET is believed to lower the seizure threshold and may increase the likelihood of seizures in those with personal susceptibility or family history of epilepsy. This is not considered a risk in healthy people at typical doses. Seizures at overdose levels are conceivable but remain hypothetical.
History & Culture
Trip Reports
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Legality
International
1961 Single Convention: 4-HO-MET is not individually scheduled.
1971 Convention on Psychotropic Substances: 4-HO-MET is not individually scheduled.
1988 Convention: 4-HO-MET is not listed in precursor Tables I or II.
By Country
References
Source Pages
Citations
- Alexander Shulgin, & Ann Shulgin. (1997). TiHKAL: The Continuation — Entry #21: 4-HO-MET. Transform Press. https://www.erowid.org/library/books_online/tihkal/tihkal21.shtml123
- Anna Rickli, Matthias C. Hoener, & Markus E. Liechti. (2016-08). Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology, 26(8), 1327–1337. https://doi.org/10.1016/j.euroneuro.2016.05.0011234567891011121314151617181920212223
- Pia Simona Bruni, K. E. Grafinger, S. Nussbaumer, S. König, S. Schürch, & W. Weinmann. (2018-09). Study of the in vitro and in vivo metabolism of 4-HO-MET. Forensic Science International, 290, 103–110. https://doi.org/10.1016/j.forsciint.2018.06.03712
- (April 2016). Psychedelics. Pharmacol Rev, 68(2), 264–355. https://doi.org/10.1124/pr.115.0114781
- (1981). Psilocin analogs II. Synthesis of 3-[2-(dialkylamino)ethyl]-, 3-[2-( N -methyl- N -alkylamino)ethyl]-, and 3-[2-(cycloalkylamino)ethyl]indol-4-ols. Journal of Heterocyclic Chemistry, 18(1), 175–179. https://doi.org/10.1002/jhet.55701801311
- Álvaro José Palma-Conesa, Mireia Ventura, Laia Galindo, Francina Fonseca, Marc Grifell, Pol Quintana, Iris Fornís, Carlos Gil, Magí Farré, & Marta Torrens. (2017). Something New about Something Old: A 10-Year Follow-Up on Classical and New Psychoactive Tryptamines and Results of Analysis. 49(4), 297–305. https://doi.org/10.1080/02791072.2017.13207321
- Débora González, Mireia Ventura, Fernando Caudevilla, Marta Torrens, & Magí Farré. (2013). Consumption of new psychoactive substances in a Spanish sample of research chemical users. 28(4), 332–340. https://doi.org/10.1002/hup.23231
- Helander A, Beck O, Hägerkvist R, & Hultén P. (2013). Identification of novel psychoactive drug use in Sweden based on laboratory analysis--initial experiences from the STRIDA project. 73(5), 400-406. https://doi.org/10.3109/00365513.2013.793817123
- Anders Helander, Matilda Bäckberg, Peter Hultén, Yasir Al-Saffar, & Olof Beck. (2014). Detection of new psychoactive substance use among emergency room patients: results from the Swedish STRIDA project. 243, 23–29. https://doi.org/10.1016/j.forsciint.2014.02.0221
- (2019-07-17). Anlage 1 des Neue-psychoaktive-Stoffe-Gesetzes (NpSG), Gruppe 5: Indol-3-alkylaminen abgeleitete Verbindungen. Bundesministerium für Gesundheit / Bundesgesetzblatt. https://www.gesetze-im-internet.de/npsg/anlage_1.html1
- (n.d.). Misuse of Drugs Act 1971 generic tryptamine control. gov.uk. https://www.gov.uk/government/publications/forensic-early-warning-system-fews-annual-report/annual-report-on-the-home-office-forensic-early-warning-system-fews-2021-to-20221
- (n.d.). 21 U.S.C. § 813 — Treatment of controlled substance analogues. Legal Information Institute, Cornell Law School. https://www.law.cornell.edu/uscode/text/21/8131
Further Reading
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