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

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

doi:10.3389/fpsyt.2023.1302559

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

Front Psychiatry. 2024 Jan 8:14:1302559. doi: 10.3389/fpsyt.2023.1302559. eCollection 2023.

Authors

Helena D Aicher^#^{1

2

3}, Michael J Mueller^#^{1

3

4}, Dario A Dornbierer^{1

5

6}, Dila Suay^{1

7}, Claudius Elsner¹, Ilhui Wicki¹, Daniel Meling^{1

8}, Luzia Caflisch¹, Alexandra Hempe^{1

9}, Camilla Steinhart¹, Jovin Mueller¹, Robin Von Rotz¹, Birgit Kleim^{2

3

10}, Milan Scheidegger^{1

3}

Affiliations

¹ Psychedelic Research and Therapy Development, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Department of Psychology, University of Zurich, Zurich, Switzerland.
³ Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland.
⁴ Department of Health Science and Technology, ETH, Zurich, Switzerland.
⁵ Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
⁶ Department of Forensic Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
⁷ MoMiLab, IMT School for Advanced Studies Luca, Lucca, Italy.
⁸ Department of Psychosomatic Medicine and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁹ Biopsychology, Department of Psychology, TUD Dresden University of Technology, Dresden, Germany.
¹⁰ Experimental Psychopathology and Psychotherapy, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.

^# Contributed equally.

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 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.

Keywords: DMT; ayahuasca; ayahuasca analog; harmine; psychological processes; psychometrics; subjective effects; therapeutic potential.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We gratefully acknowledge grant funding that supported this publication from the SNSF Swiss National Science Foundation (HA, Doc.CH Grant P0ZHP1_191935; MS, and DM, Spark CRSK-1_196833), from the Bioentrepreneur Fellowship UZH (DD, BIOEF-18-009), from the Forschungskredit PostDoc UZH (MS, Grant No. FK-18-052), from the BIAL Foundation (MS and DM, No. 333/20), from the Reconnect Foundation (DM), and from private donations (MM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.