Other · 2026
Review of MAOI antidepressants mixed with psychedelics and other psychoactive drugs
- Original title
- Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data.
- Authors
- Rached G, Campana A, Fiani D, et al.
- Journal
- CNS drugs, 2026
- Molecules
- MDMA, DMT, 5-MeO-DMT, Psilocybin, 2C-B, Other
- Conditions
- Treatment-resistant depression, Substance use disorder
- Evidence grade
- Very low
- Source
- Read the original paper
The question
What is known about the safety of monoamine oxidase inhibitor (MAOI) antidepressants when patients also use psychoactive substances, including psychedelics, and can MAOIs treat substance use disorders?
What they did
The authors carried out a narrative review, meaning they gathered and summarized existing literature rather than pooling it statistically. They drew on 219 peer-reviewed publications from 1955 to 2025, including 20 randomized controlled trials, 18 non-randomized trials, 32 observational studies or case series, 56 case reports, 85 preclinical (animal or laboratory) studies and 8 reviews. They also included 28 non-peer-reviewed user reports from drug-use and harm-reduction forums.
What they found
Suspected serotonin toxicity (a dangerous build-up of serotonin activity) was reported when MAOIs were combined with amphetamine, dextromethorphan, MDMA, meperidine, methadone or tramadol. Dangerously high blood pressure was reported with alcohol high in tyramine, amphetamine, cocaine, dextroamphetamine, khat, methamphetamine and psilocybin mushrooms. Other reported events included agitation (2C-B, 5-MeO-DMT, DMT), delirium or confusion (DMT), mania or psychosis (DMT), and muscle breakdown known as rhabdomyolysis (5-MeO-DMT, DMT). Deaths were reported in combinations involving 5-MeO-DMT, amphetamine, dextroamphetamine, dextromethorphan in overdose, MDMA, methamphetamine, meperidine and tramadol in overdose. The authors found no robust human data showing MAOIs effectively treat substance use disorders.
The fine print
This is a narrative review, not a systematic analysis, so the authors chose and weighed the literature by judgment. Most of the harm signals come from individual case reports, older publications and even unverified online forum posts, which cannot establish how often these events happen or prove the drug combination caused them. Many included studies were preclinical. Dose and route of use varied widely, and this summary is based on the abstract only.
What it means
The available evidence, though low quality, points to real and sometimes fatal risks when MAOI antidepressants are combined with certain stimulants, opioids and MDMA, while MAOIs show no proven benefit for treating addiction. It underlines why people taking these medications need careful medical oversight around any other psychoactive substance use.
Evidence grade: Very low. A narrative review whose safety signals come mainly from case reports, observational data and even non-peer-reviewed forum posts, rather than controlled trials.
This summary is based on the study’s published abstract.