This open-label exploratory study (n=9) tested three Acacia-based ayahuasca-like formulations in healthy volunteers with prior ayahuasca experience. In a cross-over design, two formulations (1 mg/kg DMT + 4 mg/kg harmalas) were given to five adults, while a third (ACL-010) was given to four adults at two dosages. All formulations were safe and well-tolerated, with no serious adverse events. Subjective experiences were similar to traditional ayahuasca, and ACL-010 was rated as comparable or more beneficial.
Abstract of DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers
“Introduction: Ayahuasca is a psychedelic compound of N, N, Dimethyltryptamine (DMT) and harmala alkaloids used for spiritual and medicinal applications in traditional settings. A range of potential psychotherapeutic mechanisms have been proposed for ayahuasca. These are thought to contribute to improvements in various psychiatric conditions including mood disorders and substance dependence. This open label exploratory study explored safety, tolerability, physical, mental health and psychedelic effects of three Acacia based formulations in 9 healthy volunteers with prior use of Ayahuasca.
Method: Formulations derived from two Acacia species (1mg/kg DMT and 4mg/kg of harmalas) were tested in a cross-over design in 5 adults; a third formulation (ACL-010) was tested in 4 adults at two dosages (1mg/kg DMT and 4mg/kg of harmalas, and then 1.4mg/kg DMT and 5.6mg of harmalas).
Results: All formulations had a good safety profile. No serious adverse events were reported. Physical examination, vital signs, and pathology revealed no clinically significant changes across the course of the study. The subjective experience of all formulations was generally rated similar to Ayahuasca. Four-week follow-up measures of psychological wellbeing and perceptual effects showed little difference between formulations. The strength and quality of the psychedelic experience elicited with ACL-010 was rated as similar or more beneficial than Ayahuasca.
Discussion: Our results indicate DMT formulations derived from the Acacia species represent a feasible alternative to traditional Ayahuasca for future clinical trials and possibly clinical contexts. The small sample size and open label design limit generalizability of results.“
Authors: Yvonne A. Bonomo, Amanda F. Norman, Lisa Collins, Margaret Ross, Justin Dwyer, Daniel Perkins & Jerome Sarris
Summary of DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers
Ayahuasca is a traditional Amazonian brew containing DMT (N,N-dimethyltryptamine) and harmala alkaloids (notably harmine, harmaline and tetrahydroharmine). DMT is a psychedelic that, when taken orally, is normally broken down in the gut; harmala alkaloids act as reversible monoamine oxidase inhibitors (MAOIs), temporarily slowing that breakdown so DMT reaches the brain and activates serotonin (5-HT) receptors—especially 5-HT2A, the main target that mediates classic psychedelic effects. The brew has migrated far beyond its Amazonian origins into religious and neo-shamanic contexts. Earlier research and widespread anecdotal reports suggest possible benefits in mood, anxiety, substance dependence, grief, and traits such as openness and acceptance, often alongside “purging” (vomiting) and vivid visionary states.
The authors set out to explore whether encapsulated, Acacia-derived DMT paired with Peganum harmala (harmala alkaloids) could offer a practical alternative to liquid ayahuasca, with attention to safety, tolerability, and the quality of the psychedelic experience in people already familiar with ayahuasca. Beyond cultural and ecological reasons (avoiding pressure on Amazonian plant stocks), the team aimed for pharmaceutical-style standardisation and purity to support future trials. The study specifically compared two Acacia sources and, after an interim review, a third, more highly purified formulation (ACL-010), in healthy volunteers with prior ayahuasca use. Findings were intended to inform a planned Phase I pharmacokinetic/pharmacodynamic study and later Phase II work in depression and alcohol use disorder.
Materials and Methods
Trial oversight
Find this paper
https://doi.org/10.3389/fpsyt.2025.1545915
Open Access | Google Scholar | Backup | 🕊
Cite this paper (APA)
Bonomo, Y. A., Norman, A. F., Collins, L., Ross, M., Dwyer, J., Perkins, D., & Sarris, J. (2025). DMT and harmala alkaloids: An exploratory study of oral Acacia based formulations in healthy volunteers. Frontiers in Psychiatry, 16, 1545915.
Study details
Compounds studied
Ayahuasca
DMT
Topics studied
Healthy Subjects
Safety
Study characteristics
Open-Label
Within-Subject
Theory Building
Participants
9
Humans
Linked Clinical Trial
An open label study to evaluate the safety, tolerability, and subjective effects of two dimethyltryptamine (DMT) and harmala alkaloid containing formulations in healthy volunteersThis small open-label trial (n=8) will test the safety of two doses of the ayahuasca brew containing DMT (1.0mg to 1.4mg/kg). The trial is sponsored by Psychae and is done in collaboration with St. Vincent's Hospital in Melbourne Australia.