DMT, Madness, and Healing: Psychosis Model, Therapy Model, and Their Relations to Mystical Experiences and Positive Emotionality
Isabel Wießner, Marcelo Falchi-Carvalho, Sophie Laborde, Handersson Barros, Raynara Bolcont, Melanie Medina, Daniel C Mograbi, Nicole Galvão-Coelho, Fernanda Palhano-Fontes, Draulio B Araujo
Research Square May 20, 2026 preprint DOI: 10.21203/rs.3.rs-9640916/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, placebo-controlled, double-blind, crossover study |
|---|---|
| Sample size | 25 |
| Population | Healthy participants |
| Intervention | DMT |
| Dose | 60 mg DMT; active placebo 0.6 mg DMT |
| Measures | Aberrant Salience Inventory (ASI), Creative Imagination Scale (CIS), Six Dimensions of Altered States of Consciousness Questionnaire (6D-ASC), Eleven Factors of Altered States of Consciousness Questionnaire (11-ASC), Hallucinogen Rating Scale (HRS), Mystical Experiences Questionnaire (MEQ) |
| Topics | DMT Mystical experience |
| Key points | DMT increased aberrant salience, suggestibility including suggestion-induced mystical experiences, and most altered-states and hallucinogen-rating factors compared with placebo. Aberrant salience correlated with mystical experiences and positive emotionality, while suggestibility correlated with positive emotionality and inversely with negatively valenced measures. The authors propose that DMT supports both psychosis and therapy models, with emotionality playing a more crucial role than mystical experiences in linking them. |
Abstract
Abstract Paradoxically, psychedelics have long been used as models of both psychosis and therapy. After proposing mystical experiences as a link between these models for lysergic acid diethylamide (LSD), we aimed to extend and refine this framework for N,N -Dimethyltryptamine (DMT). In a randomised, placebo-controlled, double-blind, crossover study, 25 healthy participants received DMT (60mg) and an active placebo (0.6mg DMT), separated by two hours. Psychotic-like experiences were assessed via aberrant salience (Aberrant Salience Inventory [ASI]) and therapeutic-like experiences via suggestibility (Creative Imagination Scale [CIS]), including suggestion-induced mystical experiences. Psychedelic experiences were measured via the Six Dimensions and Eleven Factors of Altered States of Consciousness Questionnaire (6D-ASC and 11-ASC), Hallucinogen Rating Scale (HRS), and Mystical Experiences Questionnaire (MEQ). Compared to placebo, DMT increased all aberrant salience factors, most suggestibility modalities, including mystical experiences, and most 6D-ASC and HRS factors. Aberrant salience showed widespread correlations with psychedelic experiences, particularly mystical experiences (MEQ) and positive emotionality (e.g., Joyfulness [6D-ASC], Blissful State [11-ASC]). Suggestibility correlated with the same positive emotionality factors and inversely with negatively valenced aberrant salience (Heightened Emotionality [ASI]), emotionality (Dysphoria [HRS), and mystical experiences (Ineffability [MEQ]). In conclusion, DMT’s effects on aberrant salience and suggestibility support its role both as a psychosis and therapy model. The models’ link may be indirect with respect to mystical experiences, with emotionality playing a more crucial role. Importantly, suggestion-induced mystical experiences after DMT may suggest post-acute perceptual plasticity, informing the development of more tailored psychedelic treatments that induce, amplify, and guide therapeutic experiences.
Comparable studies
Other randomized controlled trials on 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 |
| DMT Models the Near-Death Experience Healthy participants | 2018 | Within-subjects placebo-controlled study | n = 13 |
| Human brain effects of DMT assessed via EEG-fMRI. Healthy volunteers | 2023 | Within-subjects, placebo-controlled design | n = 20 |
| 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 |
Citations in the library
Cites 40
- Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 2003
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
and 35 more in the library