Safety, tolerability and subjective effects of vaporized N,N-Dimethyltryptamine: A randomized double-blind clinical trial.
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde, Handersson Barros, Raynara Bolcont, Sérgio Ruschi B Silva, Érica J. Pantrigo, Melanie Medina, Flávia Arichelle, Raissa Almeida, Rosana Aires, Luis Fernando Nunes Ferreira, Luísa Dantas Corrêa, Romária Bárbara da Costa Bezerra, Kaike Thie, Natan Silva-Costa, Luiz Antonio de Araújo Costa Neto, Marcos Vinícius Jales Lima de Queiroz, Nicole Galvão-Coelho, Draulio B Araujo, Fernanda Palhano-Fontes
European Neuropsychopharmacology June 17, 2025 DOI: 10.1016/j.euroneuro.2025.06.002 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled crossover trial Peer reviewed |
|---|---|
| Sample size | 25 |
| Population | Healthy participants |
| Interventions | Vaporized N N-Dimethyltryptamine (DMT) |
| Dose | 60 mg DMT or 0.6 mg DMT |
| Duration | Two treatment sessions with a two-hour interval between sessions |
| Topics | 5-MeO-DMT Altered states of consciousness DMT Psychedelic-assisted therapy |
| Keywords | N,N-Dimethyltryptamine Placebo-controlled study Psychedelics Mood disorders DMT Research Compound Randomized study Clinical potential Therapeutic applications Treatment Experience Clinical trial methodology Healthy participants Safety and tolerability Safely Safe limits Well-tolerated Mild adverse events Physiological changes Transient |
| Citations | 7 |
| Registration | NCT05901012 |
| Key findings | Inhaled DMT is safe, well-tolerated, and induces profound altered states of consciousness in healthy adults. |
Abstract
Vaporized N,N-Dimethyltryptamine (DMT) has a short duration and simple application, prompting this technique as a new approach for psychedelics' clinical use. Building on our initial dose-ascending studies and addressing potential confounding effects of dosing order, this study is the first to evaluate inhaled DMT in a randomized, placebo-controlled, double-blind design. Given DMT's therapeutic potential, we aimed to assess its safety, tolerability, and subjective effects compared to an active placebo. Twenty-five healthy participants completed two treatment sessions, receiving DMT (60 mg) or active placebo (0.6 mg DMT) in a crossover design with a two-hour interval between the sessions. Subjective experiences were evaluated using measures of intensity and valence, the Five Dimensions of Altered States of Consciousness Questionnaire (5D-ASC), the Hallucinogen Rating Scale (HRS), and the Mystical Experiences Questionnaire (MEQ). Physiological parameters were monitored, including systolic and diastolic blood pressure, heart rate, respiratory rate, and peripheral oxygen saturation. Biological responses were analysed through various biochemical biomarkers. Adverse events were recorded. Compared to placebo, DMT significantly increased subjective measures of intensity, as well as most 5D-ASC, HRS, and MEQ factors, except for 5D-ASC Anxiety, Audio-Visual Synaesthesia and Vigilance Reduction subscales. DMT transiently increased physiological parameters within safe limits. Biochemical changes were not clinically relevant. The adverse events were predominantly mild and transient. Physiological increases were significantly correlated with subjective experiences, providing insights into the interaction between physiological responses and altered states of consciousness. Our findings suggest that inhaled DMT is safe, well-tolerated, and capable of inducing profound altered states of consciousness. Clinicaltrials.gov NCT05901012.
Comparable studies
Other randomized controlled trials on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Healthy volunteers | 2005 | Double-blind crossover study | n = 9 |
| Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Experienced hallucinogen users | 1996 | Randomized controlled trial | n = 13 |
| Pharmacokinetics of N,N-dimethyltryptamine in Humans. Healthy adults | 2023 | Phase I component of a phase I/IIa randomised, double-blind, placebo-controlled, parallel-group, dose-escalation trial | n = 24 |
| Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis Healthy volunteers | 2007 | Double-blind crossover study | n = 15 |
Citations in the library
Cited by 4
- Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression Journal of Psychopharmacology July 8, 2026
- Registered Clinical Trials of Ayahuasca and DMT: A Scoping Review. Clinical Pharmacology & Therapeutics July 1, 2026
- Overcoming Pharmacokinetic and Peripheral Safety Challenges in Psychedelic Therapies: The Promise of Advanced Drug Delivery Systems. ACS Pharmacology & Translational Science June 12, 2026
- Predicting and exploring ayahuasca effects: Perception, mind-wandering, and EEG oscillations Journal of Psychopharmacology December 4, 2025
Cites 37
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Psychedelics and the essential importance of context. Journal of Psychopharmacology February 15, 2018
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
and 32 more in the library