Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects

This crossover RCT (n=31) investigates the effects of a novel ayahuasca-inspired formulation containing harmine and DMT in healthy male subjects. It finds that the combination of DMT and harmine, but not harmine alone, leads to a psychedelic experience with psychological insights, emotional breakthroughs, and low challenging experiences. The study reports positive persisting effects at 1- and 4-month follow-ups, with no changes in personality traits, psychological flexibility, general well-being, or increases in psychopathology.

Abstract of Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation

“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 Conclusion: 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.”

Authors: Helena D. Aicher, Michael J. Mueller, Dario A. Dornbierer, Dila Suay, Claudius Elsner, Ilhui Wicki, Daniel Meling, Luzia Caflisch, Alexandra Hempe, Camilla Steinhart, Jovin Mueller, Robin Von Rotz, Birgit Kleim & Milan Scheidegger

Summary of Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation