Psilocybin: interactions

Interactions

Combining MAOIs (monoamine oxidase inhibitors — ayahuasca is one example) with SSRIs can lead to serotonin syndrome, as with psychedelics generally [1]. True serotonin toxicity typically occurs with a serotonergic drug overdose or with an MAOI combined with a drug that raises intrasynaptic serotonin, as with psychedelics generally [2]. Watch for myoclonus (muscle jerks), wildly fluctuating vital signs, agitation or a comatose state, muscle rigidity, severe hyperthermia, or seizures — any of these warrants immediate medical attention [2]. Interactions between classic psychedelics and antidepressants generally remain under-researched [1], and any serotonergic medication should be screened for before combining [3].

As with psychedelics generally: in collected reports of a classic psychedelic taken alongside lithium, 47% described seizures [4], 18% described bad trips [4], and 39% involved medical attention [4]. Psychedelic use may carry a significant seizure risk for people on lithium [4].

As with psychedelics generally, most reports of lamotrigine combined with a psychedelic described no real effect on the experience [4], and none of 34 such reports involved seizures [4] — though this is anecdotal data, not a guarantee.

Escitalopram pretreatment reduced bad drug effects, anxiety, and adverse cardiovascular effects from psilocybin compared with placebo [5], without blunting the positive mood effects [5] or changing psilocin's pharmacokinetics [5]; psilocin's half-life after escitalopram pretreatment was 1.8 hours (range 1.1–2.2 hours) [5]. Serotonergic psychotropics that don't contain MAOIs are, as a class, considered low risk in combination with psychedelics that also don't contain MAOIs [2].

Separately from drug-drug effects, adulterants such as methamphetamine or fentanyl have turned up in a small number of submitted psychedelic samples [6], which is a real risk in its own right; drug checking services can help identify these [6].

References

1. Drug–drug interactions involving classic psychedelics: A systematic review — Journal of Psychopharmacology
2. Serotonin toxicity of serotonergic psychedelics — PubMed
3. Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms — PubMed
4. Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports — Pharmacopsychiatry (Thieme)
5. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects — Clinical Pharmacology & Therapeutics (Wiley)
6. Harm reduction practises for users of psychedelic drugs: a scoping review — Harm Reduction Journal