4-HO-MET, also known as metocin, is a synthetic 4-hydroxy tryptamine related to psilocin. It has a hydroxy group at the 4-position of the indole ring and a methyl-ethyl substitution on the terminal nitrogen. It is one of the better-described compounds in the newer tryptamine group: laboratory studies have measured its activity at several serotonin receptors, and forensic literature includes analytically confirmed exposure cases.
Chemistry and relationship to psilocin
4-HO-MET is 4-hydroxy-N-methyl-N-ethyltryptamine. It shares the 4-hydroxyindole motif of psilocin (4-HO-DMT), but has an ethyl group in place of one of psilocin’s methyl groups. This seemingly small change affects receptor affinity and functional activity.
Its acetylated analogue is 4-AcO-MET, also known as metacetin. The two should not be treated as interchangeable: 4-HO-MET has a free hydroxy group, whereas 4-AcO-MET carries an acetate ester.
Receptor pharmacology
A 2023 study measured the activity of 4-HO-MET at human 5-HT1A, 5-HT2A and 5-HT2C receptors and at the serotonin transporter. It showed notable activity at 5-HT2A, with a binding affinity of approximately 46 nM and a functional EC50 of about 87 nM in the assay used. Its efficacy was lower than the serotonin reference response, illustrating the distinction between receptor potency and efficacy (Kozell and colleagues, 2023).
Reported effects
Descriptions in the literature and user reports include changes in visual perception, mood and thought patterns. A review of psychoactive tryptamines also summarises reports of anxiety, nervousness, paranoia, tiredness and insomnia in some contexts. These accounts are not controlled clinical observations and do not establish how frequently each effect occurs (Toxicology and analysis of psychoactive tryptamines, 2020).
Clinical and forensic evidence
4-HO-MET has been identified in forensic toxicology investigations, including cases where several psychoactive substances were present. Such detections confirm exposure but do not, by themselves, establish that 4-HO-MET caused a particular symptom or outcome. A reliable human concentration-toxicity relationship has not been established.
Research limitations
Although receptor activity is better characterised than for many newer tryptamines, human pharmacokinetic data remain limited. There is no robust clinical evidence defining the acute toxic range, dependence potential or long-term effects. Results for 4-AcO-MET or psilocin offer useful comparisons, without replacing direct evidence about 4-HO-MET.
Related tryptamines
4-HO-MET is related to 4-AcO-MET, 4-HO-DMT, 4-HO-MiPT and 4-HO-DET. Its N-methyl-N-ethyl substitution distinguishes it from the dimethyl and diisopropyl analogues.
