Drug-drug interactions between classic psychedelics and psychoactive drugs: a systematic review
Andreas Halman, Geraldine Kong, Jerome Sarris, Daniel Perkins
medRxiv June 1, 2023 preprint DOI: 10.1101/2023.06.01.23290811 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review |
|---|---|
| Population | Humans |
| Topics | Ayahuasca LSD MDMA Mescaline Psilocybin |
| Keywords | Hallucinogen Psychoactive drug Pharmacology Psychotropic drug Recreational drug Mood |
| Citations | 17 |
| Key findings | Combining classic psychedelics with other psychoactive drugs can attenuate, potentiate, or produce no change in effects, with no serious adverse events reported except in a few case reports. |
Abstract
Abstract Classic psychedelics, lysergic acid diethylamide, psilocybin, mescaline and N,N-dimethyltryptamine, are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes of using these substances are used in combination with other psychoactive drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other psychoactive drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 8,487 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other psychoactive drugs were included. In total, we identified 50 studies from 34 reports published before April 20, 2023, encompassing 31 studies on LSD, 11 on psilocybin, 4 on mescaline, 3 on DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. In-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.
Comparable studies
Other systematic reviews and meta-analyses on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids Humans (ritual ayahuasca use) | 2006 | Systematic review | |
| Drug–drug interactions involving classic psychedelics: A systematic review | 2023 | Systematic review | |
| Psychedelic‐assisted treatment for substance use disorder: A narrative systematic review Participants in studies of psychedelic-assisted treatment for alcohol, tobacco, and... | 2025 | Systematic review | n = 2,035 |
| The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies Preclinical animal and in vitro studies | 2024 | Systematic review | |
| A Systematic Review of the Neurocognitive Effects of Psychedelics in Healthy Populations: Implications for Depressive Disorders and Post-Traumatic Stress Disorder Healthy individuals and patients with PTSD or MDD | 2024 | Systematic review | n = 43 |
Citations in the library
Cited by 11
- Pharmacokinetics of Psilocybin: A Systematic Review Pharmaceutics March 25, 2025
- The psychedelic call: analysis of Australian Poisons Information Centre calls associated with classic psychedelics. Clinical Toxicology April 1, 2024
- EMBARK Psychedelic Therapy for Depression March 6, 2024
- An Overview of Psychedelic-Assisted Therapy EMBARK Psychedelic Therapy for Depression April 23, 2024
- EMBARK Mechanisms of Change in the Treatment of Depression EMBARK Psychedelic Therapy for Depression April 23, 2024
and 6 more in the library
Cites 56
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology December 1, 2011
and 51 more in the library