Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review
This review (2022) explores the drug-drug interactions between MDMA or psilocybin and conventional psychiatric medications. Publications of studies describe interactions between MDMA (n=24) or psilocybin (n=5) and medications from several psychiatric drug classes: adrenergic agents, antipsychotics, anxiolytics, mood stabilizers, NMDA antagonists, psychostimulants, and several classes of antidepressants.
Authors
- Christopher Stauffer
- Benjamin Malcolm
Published
Abstract
Rationale $ objectives: ± 3,4-Methylenedioxymethamphetamine (MDMA) and psilocybin are currently moving through the US Food and Drug Administration’s phased drug development process for psychiatric treatment indications: posttraumatic stress disorder and depression, respectively. The current standard of care for these disorders involves treatment with psychiatric medications (e.g., selective serotonin reuptake inhibitors), so it will be important to understand drug-drug interactions between MDMA or psilocybin and psychiatric medications.
Methods
In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the MEDLINE database via PubMed for publications of human studies in English spanning between the first synthesis of psilocybin (1958) and December 2020. We used 163 search terms containing 22 psychiatric medication classes, 135 specific psychiatric medications, and 6 terms describing MDMA or psilocybin.
Results
Forty publications were included in our systematic review: 26 reporting outcomes from randomized controlled studies with healthy adults, 3 epidemiologic studies, and 11 case reports. Publications of studies describe interactions between MDMA (N = 24) or psilocybin (N = 5) and medications from several psychiatric drug classes: adrenergic agents, antipsychotics, anxiolytics, mood stabilizers, NMDA antagonists, psychostimulants, and several classes of antidepressants. We focus our results on pharmacodynamic, physiological, and subjective outcomes of drug-drug interactions.
Conclusions
As MDMA and psilocybin continue to move through the FDA drug development process, this systematic review offers a compilation of existing research on psychiatric drug-drug interactions with MDMA or psilocybin.
Research Summary of 'Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review'
Introduction
Sarparast and colleagues situate this review within a renewed clinical interest in MDMA and psilocybin as adjuncts to psychotherapy for disorders such as post‑traumatic stress disorder and major depressive disorder. Both compounds differ from typical psychiatric medications in being administered only a few times during a treatment course and have advanced in the US FDA pipeline (MDMA with Breakthrough Therapy designation for PTSD; psilocybin for depression). Because current standard care for these indications frequently involves ongoing use of psychiatric medications and because MDMA and psilocybin both modulate serotonergic (and in MDMA's case noradrenergic and dopaminergic) systems, there is a plausible risk of pharmacokinetic and pharmacodynamic drug‑drug interactions that could alter safety, subjective effects, or therapeutic efficacy. This paper aims to systematically summarise human data on interactions between psychiatric medications and either MDMA or psilocybin. The stated objective was to compile evidence on pharmacokinetic measures (for example plasma drug and metabolite levels), physiological outcomes (for example vital signs, circulating catecholamines), and subjective effects when MDMA or psilocybin are co‑administered with drugs prescribed in psychiatry. The authors emphasise that prior reviews of MDMA interactions were not systematic and that no prior systematic review addressed psilocybin drug‑drug interactions, motivating the present work.
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Study Details
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- APA Citation
Sarparast, A., Thomas, K., Malcolm, B., & Stauffer, C. S. (2022). Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review. Psychopharmacology, 239(6), 1945-1976. https://doi.org/10.1007/s00213-022-06083-y
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