Psilocybin and MAO-B inhibitors
No dataParkinson's disease, selective MAO-B inhibitor · also: rasagiline, azilect, selegiline, eldepryl, zelapar
Psilocybin and MAO-B inhibitors: no data. Not studied. Treated as caution.
Not documented. No study or report of this pairing is cited here. At usual doses the drug acts mainly on MAO-B, while the lab work on psilocin found only a minor role for MAO-A.
Why it happens
Psilocin is cleared mainly by glucuronidation and by conversion to 4-HIAA. In lab studies MAO-A, CYP2D6 and CYP3A4 all contribute, but MAO-A alone produced only small amounts of 4-HIAA. Rasagiline and oral selegiline at usual Parkinson's doses inhibit MAO-B selectively, so a large effect on psilocin is not expected. That selectivity depends on the dose and is lost at higher doses, where MAO-A is inhibited too.
What is known
No study of this pairing. The selectivity at usual doses comes from tyramine challenge studies: rasagiline at 1 mg a day did not raise tyramine sensitivity, while 4 and 6 mg a day reduced a marker of MAO-A inhibition to a degree approaching phenelzine. Oral selegiline at 5 mg twice daily raised tyramine sensitivity only slightly compared with phenelzine. Safinamide is not covered by the sources cited here.
Safety guidance
- Ask the prescriber who manages the Parkinson's treatment before combining anything with this drug. Do not stop it or change the dose on your own. The selegiline skin patch (Emsam) is a different case and is listed under irreversible MAOIs, because at antidepressant doses it inhibits MAO-A as well.
When to seek help
Call emergency services for a seizure, chest pain, loss of consciousness, very high fever or confusion that does not settle. Emergency red flags.
Common questions
Can you take psilocybin mushrooms with MAO-B inhibitors?
Psilocybin and MAO-B inhibitors: no data. Not studied. Treated as caution. Not documented. No study or report of this pairing is cited here. At usual doses the drug acts mainly on MAO-B, while the lab work on psilocin found only a minor role for MAO-A. Ask the prescriber who manages the Parkinson's treatment before combining anything with this drug. Do not stop it or change the dose on your own. The selegiline skin patch (Emsam) is a different case and is listed under irreversible MAOIs, because at antidepressant doses it inhibits MAO-A as well.
Sources
- [1]Goren et al., 'Clinical pharmacology tyramine challenge study to determine the selectivity of the monoamine oxidase type B (MAO-B) inhibitor rasagiline' (2010)
- [2]deMarcaida et al., 'Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline' (2006)
- [3]Chen & Wilkinson, 'The monoamine oxidase type B inhibitor rasagiline in the treatment of Parkinson disease: is tyramine a challenge?' (2012)
- [4]EMSAM (selegiline transdermal system) US prescribing information, DailyMed
- [5]Thomann et al., 'In vitro and in vivo metabolism of psilocybin's active metabolite psilocin' (2024)
How we research this: sources, evidence grading, review and updates.