Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects.
Helena Aicher, Michael J Mueller, Dario Dornbierer, Dila Suay, Claudius Elsner, Ilhui A Wicki, Daniel Meling, Luzia Caflisch, Alexandra Hempe, Camilla P Steinhart, Jovin Mueller, Robin von Rotz, Birgit Kleim, Milan Scheidegger
Frontiers in Psychiatry 2023 DOI: 10.3389/fpsyt.2023.1302559 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 31 |
| Population | Healthy male subjects |
| Interventions | Harmine DMT |
| Dose | 100 mg harmine orodispersible tablet; incremental intranasal DMT up to 100 mg |
| Duration | 1- and 4-months follow-up |
| Topics | Ayahuasca DMT |
| Keywords | Ayahuasca analog Harmine Psychological processes Psychometrics Subjective effects Therapeutic potential Psychedelic medicine Psychopharmacology Mental health therapeutics Ethnobotany |
| Citations | 34 |
| Key findings | A standardized DMT plus harmine formulation induced a phenomenologically rich psychedelic experience with good psychological safety and tolerability, while harmine alone did not produce psychedelic effects. |
Abstract
There is growing scientific evidence for the therapeutic benefits of the Amazonian plant-based psychedelic "ayahuasca" for neuropsychiatric disorders such as depression and anxiety. However, there are certain challenges when incorporating botanical ayahuasca into biomedical research and clinical therapy environments. Formulations inspired by ayahuasca, which contain specific and standardized active components, are a potential remedy. We investigated subjective acute and persisting effects of a novel formulation containing the reversible monoamine oxidase inhibitor harmine (orodispersible tablet containing 100 mg MAO-I) and N,N-dimethyltryptamine (incremental intranasal dosing of up to 100 mg DMT), compared with two other conditions, namely harmine alone and placebo, in a crossover RCT in 31 healthy male subjects. DMT + harmine, but not harmine alone, induced a psychedelic experience assessed with the 5D-ASC rating scale [global score: F(2,60) = 80.21, p < 0.001] and acute experience sampling items over time, characterized by psychological insights [PIQ, F(2,58.5) = 28.514, p < 0.001], emotional breakthroughs [EBI, F(2,60) = 26.509, p < 0.001], and low scores on the challenging experience questionnaire [CEQ, F(2,60) = 12.84, p < 0.001]. Participants attributed personal and spiritual significance to the experience (GSR) with mainly positive persisting effects (PEQ) at 1- and 4-months follow-up. Acute drug effects correlated positively with persisting effects. We found no changes in trait measures of personality, psychological flexibility, or general well-being, and no increases in psychopathology (SCL-90-R) were reported. Our results suggest that the experience induced by the standardized DMT + harmine formulation induces a phenomenologically rich psychedelic experience, demonstrates good psychological safety and tolerability, is well tolerated, and induces beneficial psychological processes that could possibly support psychotherapy. Further studies are required to investigate the psychotherapeutic potential in patients.
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
Cited by 31
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
- Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression American Journal of Psychiatry 2025
- A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers. Journal of Psychopharmacology October 1, 2024
- Insights on psychedelics: A systematic review of therapeutic effects. Neuroscience & Biobehavioral Reviews June 1, 2025
- Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat Journal of Psychopharmacology September 27, 2024
and 26 more in the library
Cites 68
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- 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
and 63 more in the library