Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine in human subjects: a systematic review of clinical trials.
Aleksander Kwaśny, Alina Wilkowska, Wiesław Jerzy Cubała
Frontiers in Psychiatry 2024 DOI: 10.3389/fpsyt.2024.1477996 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 78 |
| Population | Healthy volunteers and patients with treatment-resistant depression |
| Intervention | 5-MeO-DMT |
| Topics | 5-MeO-DMT DMT |
| Keywords | Psychedelics entheogens Hallucinogens Tolerability Medical research Behavioral health 5-Methoxy-N,N-Dimethyltryptamine Adverse events Safety Side effects |
| Citations | 10 |
| Key findings | 5-MeO-DMT has a favorable short-term safety and tolerability profile with no serious adverse events or drop-outs reported in clinical trials. |
Abstract
Psychedelic agents have regained the attention of pharmaceutical companies as promising treatments for depressive episodes. 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), an atypical psychedelic, is emerging as a potentially effective, novel rapid-acting antidepressant. In this systematic review, we analyze the safety and tolerability evidence from clinical trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, electronic databases (PubMed, SCOPUS, Web of Science, EMBASE, and EBSCO) were searched from inception until 15 May 2024 to identify clinical trials (regardless of phase) reporting on short-term safety and tolerability profile of 5-MeO-DMT using the following keywords in various combinations: 5-methoxy-N, N-dimethyltryptamine, 5-MeO-DMT, safety, adverse, adverse reaction, side effects, tolerability, dropout, healthy volunteer, healthy participant, depression, major depressive disorder. Only studies written in English were considered. Initial search yielded 100 records, out of which 3 met the inclusion criteria. These studies reported on the results from clinical trial phases I and I/II, with a total of 78 participants included; two studies involved healthy volunteers, and one included patients with treatment-resistant depression. Although the data is limited, it confirms a good short-term safety and tolerability profile for 5-MeO-DMT, with no serious adverse events (SAEs) reported. Furthermore, no drop-outs were reported. 5-MeO-DMT administration in human subjects presents favorable short-term safety and tolerability profile. Importantly, no SAEs have been documented, and no adverse events led to participant withdrawal from the studies There is a need for future randomized, double-blind, placebo-controlled trials with larger samples and follow-up to assess potential chronic adverse events.
Comparable studies
Other systematic reviews and meta-analyses on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. | 2012 | Systematic review | |
| Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis. Humans | 2025 | Systematic review | |
| Efficacy of N, N-dimethyltryptamine (DMT) psychedelic therapy for substance misuse: A systematic review and meta-analysis Individuals with substance misuse | 2026 | Systematic review and meta-analysis | |
| Clinical pharmacokinetics of N,N-dimethyltryptamine (DMT): a systematic review and post-hoc analysis Humans | 2025 | Systematic review | |
| Pharmacological, clinical, and translational evidence for N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and zalsupindole: a systematic review. | 2026 | Systematic review |
Citations in the library
Cited by 10
- Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 7, 2025
- Application of microarray patches for the transdermal administration of psychedelic drugs in micro-doses. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V February 1, 2025
- Innovative Psychedelic Therapies: Harnessing 5-MeO-DMT and DMT for Mental Health Treatment. ACS Medicinal Chemistry Letters November 14, 2024
- Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols. European Neuropsychopharmacology January 16, 2026
- Serotonergic psychedelics for depression: A comprehensive overview. International review of neurobiology 2025
and 5 more in the library
Cites 18
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology February 2, 2022
- Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study. Biological Psychiatry February 1, 2023
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current Drug Metabolism October 1, 2010
- Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. Neuropsychopharmacology September 1, 2022
and 13 more in the library