Psilocybin and Moclobemide and other RIMAs
CautionAntidepressant, reversible MAO-A inhibitor · also: moclobemide, manerix, aurorix, rima, linezolid
Psilocybin and moclobemide: caution, the effect is unpredictable and may be stronger or longer, though the MAO-A inhibition is reversible and short-lived.
Stronger and longer effects than expected, to a lesser degree than with an irreversible MAOI.
Claims re-checked against the cited sources:
Why it happens
Moclobemide reversibly inhibits MAO-A, about 80% at a 300 mg dose, and the inhibition lasts at most about 24 hours. MAO-A plays only a small part in breaking down psilocin in lab work, so any change to psilocin levels is likely smaller than with irreversible MAOIs, but it has not been measured in people. The antibiotic linezolid and intravenous methylene blue are also reversible inhibitors of monoamine oxidase, according to their FDA labels (linezolid is nonselective, and the methylene blue label bases this on literature reports); no study of either with psilocybin is cited here.
What is known
Based on the mechanism, plus scattered self-reports. No controlled data.
- 2016
- Moclobemide inhibits MAO-A by about 80% at 300 mg (MAO-B 20 to 30%); the inhibition is short-lasting (maximum 24 hours) and reversible; elimination half-life is about 1.5 hours after a single 100 mg dose. Dom-Moclobemide Canadian product monograph (Dominion Pharmacal, revised 12 Aug 2016)
- 2016
- The monograph says moclobemide does not require special dietary restrictions when taken after meals, but asks patients to report sudden occipital headache, palpitations, neck stiffness or unusual heart rate. Dom-Moclobemide Canadian product monograph (Dominion Pharmacal, revised 12 Aug 2016)
- 2024
- MAO-A converted psilocin into only minimal amounts of 4-HIAA in vitro; CYP2D6 and CYP3A4 also metabolise psilocin. Thomann et al., 'In vitro and in vivo metabolism of psilocybin's active metabolite psilocin', Front Pharmacol
- 2024
- No human study of psilocybin with moclobemide was identified in a 2024 systematic review of psychedelic drug interactions. Halman et al., 'Drug-drug interactions involving classic psychedelics: a systematic review', J Psychopharmacol
Safety guidance
- Assume any dose may hit differently from last time you took it without moclobemide; start well below your usual amount.
- Not a reason to stop your medication; changes go through your prescriber.
- Avoid adding stimulants or other serotonergic drugs on the same day.
When to seek help
Get urgent help for a sudden severe or back-of-the-head headache, pounding or very slow heartbeat, or stiff neck, which can signal a blood-pressure reaction. Emergency red flags.
Common questions
Is moclobemide as risky as phenelzine or tranylcypromine?
Less so on current knowledge: its MAO-A inhibition is reversible and lasts at most about 24 hours. But the combination with psilocybin has not been studied.
Will the trip be stronger?
Possibly, but it is not known. MAO-A is only a minor route for psilocin in lab studies.
Should I skip a day of moclobemide?
Do not change your dose without talking to your prescriber.
Sources
- [1]Thomann et al., 'In vitro and in vivo metabolism of psilocybin's active metabolite psilocin' (2024)
- [2]Linezolid injection US prescribing information (NDA 206473), FDA: 'a reversible, nonselective inhibitor of monoamine oxidase' (2026)
- [3]Linezolid safety-related labeling changes (serotonin syndrome with serotonergic agents), FDA
- [4]PROVAYBLUE (methylene blue) injection US prescribing information, FDA (2024)
How we research this: sources, evidence grading, review and updates.