This first RCT (n=25) of vaporised DMT (60mg) demonstrated that DMT significantly increased subjective experience measures while causing only transient, safe physiological changes and predominantly mild adverse events. This suggests that inhaled DMT is safe, well-tolerated, and effective at inducing profound altered states of consciousness. Significant correlations were observed between physiological responses and subjective experiences.
Abstract of Safety, tolerability and subjective effects of vaporized N,N-Dimethyltryptamine
“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 5DASC, 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.“
Authors: Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde, Handersson Barros, Raynara Bolcont, Sérgio Ruschi Silva, Érica 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 Araujo & Fernanda Palhano-Fontes
Summary of Safety, tolerability and subjective effects of vaporized N,N-Dimethyltryptamine
The authors begin by outlining the distinctive pharmacological profile of N,N-dimethyltryptamine (DMT), a classic psychedelic compound known for its extremely rapid onset and short duration of action. Compared to other psychedelics like psilocybin, lysergic acid diethylamide (LSD), and mescaline—which typically induce effects that last several hours—DMT’s effects, when vaporised, generally last under 20 minutes. This brevity offers significant advantages for clinical application, where shorter interventions can be logistically simpler and more appealing to patients and providers.
DMT is naturally found in various plants, fungi, animals, and even in the human body. Its primary pharmacological action involves serotonin receptor agonism, particularly at the 5-HT2A receptor, but it also interacts with sigma-1 receptors—an interaction associated with neuroplasticity and anti-inflammatory effects. Importantly, the researchers point out that DMT may induce only minimal tolerance, making it suitable for repeated use without the need for significant dose escalation. Despite its rapid and intense effects—ranging from visual hallucinations to altered time perception and mystical experiences—DMT has not been widely studied in controlled clinical settings using standardised methodologies.
Building on their prior dose-escalation studies, the authors designed the current investigation to address limitations in earlier research, particularly the potential confounding effects of dosing order. This new trial employs a randomised, double-blind, placebo-controlled crossover design to rigorously assess the safety, tolerability, and subjective effects of inhaled DMT in healthy individuals. A comprehensive battery of physiological and psychological measurements was used, including subjective rating scales, blood pressure monitoring, and biochemical markers.
Methods
Study Design
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https://doi.org/10.1016/j.euroneuro.2025.06.002
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Cite this paper (APA)
Wießner, I., Falchi-Carvalho, M., Laborde, S., Barros, H., Bolcont, R., Silva, S. R., ... & Palhano-Fontes, F. (2025). Safety, tolerability and subjective effects of vaporized N, N-Dimethyltryptamine: A randomized double-blind clinical trial. European Neuropsychopharmacology, 97, 16-27.
Study details
Topics studied
Healthy Subjects
Safety
Study characteristics
Original
Placebo-Controlled
Active Placebo
Double-Blind
Within-Subject
Randomized
Participants
25
Humans
Compound Details
The psychedelics given at which dose and how many times
DMT 60 mg | 1xLinked Clinical Trial
Safety and Tolerability of DMT in Healthy AdultsThis phase I, double-blind, randomized, placebo-controlled crossover trial (n=25) explores the acute and subacute effects of inhaled N,N-Dimethyltryptamine (DMT) in healthy adults.