Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun;239(6):1945-1976.
doi: 10.1007/s00213-022-06083-y. Epub 2022 Mar 7.

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review

Affiliations

Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review

Aryan Sarparast et al. Psychopharmacology (Berl). 2022 Jun.

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.

Keywords: Depression; Drug interactions; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine; Psilocybin; Psychopharmacology; Serotonin uptake inhibitors; Stress disorders, Post-traumatic.

PubMed Disclaimer

Conflict of interest statement

Declarations

Conflict of interest CSS has received payment from the MAPS Public Benefit Corporation for Training clinicians in MAP. BM runs www.spiritpharmacist.com, which offers a monthly membership service for access to drug interactions guides, courses, and consultation services. AS and KT have no conflicts of interest to report.

Figures

Fig. 1
Fig. 1
PRISMA study selection flow diagram

References

    1. Abraham TT, Barnes AJ, Lowe RH, Spargo EAK, Milman G, Pirnay SO, Gorelick DA, Goodwin RS, Huestis MA (2009) Urinary MDMA, MDA, HMMA, and HMA Excretion Following Controlled MDMA Administration to Humans. J Anal Toxicol 33(8):439–446 - PMC - PubMed
    1. Akhondzadeh S, Hampa AD (2005) Topiramate prevents ecstasy consumption: A case report. Fundam Clin Pharmacol 19(5):601–602. 10.1111/j.1472-8206.2005.00355.x - DOI - PubMed
    1. Artin H, Zisook S, Ramanathan D (2021) How do serotonergic psychedelics treat depression: The potential role of neuroplasticity. World J Psychiatr 11(6):201–214. 10.5498/wjp.v11.i6.201 - DOI - PMC - PubMed
    1. Baggott MJ, Kirkpatrick MG, Bedi G, de Wit H (2015) Intimate insight: MDMA changes how people talk about significant others. J Psychopharmacol 29(6):669–677. 10.1177/0269881115581962 - DOI - PMC - PubMed
    1. Barrett FS, Bradstreet MP, Leoutsakos JMS, Johnson MW, Griffiths RR (2016) The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms. J Psychopharmacol 30(12):1279–1295 - PMC - PubMed

Publication types

MeSH terms