Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects
In a crossover RCT of 31 healthy male volunteers, an ayahuasca‑inspired formulation combining intranasal N,N‑DMT (up to 100 mg) with an orodispersible 100 mg harmine tablet produced robust, phenomenologically rich psychedelic experiences characterised by psychological insights and emotional breakthroughs, low challenging effects, and mainly positive persisting effects at 1 and 4 months. The compound showed good psychological safety and tolerability with no increases in psychopathology or changes in trait measures, indicating potential to support psychotherapeutic applications.
Authors
- Milan Scheidegger
- Dominik Dornbierer
- Anne Aicher
Published
Abstract
Background
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.
Methods
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.
Results
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.Discussion and ConclusionOur 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.
Research Summary of 'Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects'
Introduction
Interest in ayahuasca, the Amazonian brew containing N,N-dimethyltryptamine (DMT) plus reversible monoamine oxidase inhibitors (MAO-Is) such as harmine, has grown because of signals that it can reduce symptoms of depression, anxiety and addiction. The brew’s combination of β-carbolines and DMT produces orally active, multi-hour psychedelic states characterised by increased introspection, vivid imagery, emotional release and reported psychological insights. However, botanical ayahuasca poses challenges for clinical research and therapy: batch-to-batch variability in alkaloid content, variable oral bioavailability due to first-pass MAO metabolism, common side effects such as nausea/vomiting, cultural and ecological concerns, and difficulty in standardising dosing and delivery for biomedical settings. Aicher and colleagues developed an ayahuasca-inspired, standardised formulation combining harmine and intranasal DMT with incremental dosing to improve controllability and tolerability. The study aimed to characterise the acute subjective phenomenology, psychological mechanisms (insight, emotional breakthrough), safety/tolerability, and persisting effects of the combined DMT + harmine (DMT/HAR) formulation compared with harmine-only (HAR) and placebo (PLA) in healthy male participants. The authors hypothesised that DMT/HAR—but not harmine alone—would produce psychedelic phenomena and foster psychological insights and emotional breakthroughs with low levels of challenging experiences and no lasting increases in psychopathology, and that acute effects would relate to positive persisting outcomes.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
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- APA Citation
Aicher, H. D., Mueller, M. J., Dornbierer, D. A., Suay, D., Elsner, C., Wicki, I., Meling, D., Caflisch, L., Hempe, A., Steinhart, C., Mueller, J., Von Rotz, R., Kleim, B., & Scheidegger, M. (2024). Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects. Frontiers in Psychiatry, 14. https://doi.org/10.3389/fpsyt.2023.1302559
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