DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers
IntroductionAyahuasca 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 improv...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1545915/full |
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| author | Yvonne A. Bonomo Yvonne A. Bonomo Amanda F. Norman Lisa Collins Margaret Ross Justin Dwyer Daniel Perkins Daniel Perkins Daniel Perkins Jerome Sarris Jerome Sarris Jerome Sarris Jerome Sarris |
| author_facet | Yvonne A. Bonomo Yvonne A. Bonomo Amanda F. Norman Lisa Collins Margaret Ross Justin Dwyer Daniel Perkins Daniel Perkins Daniel Perkins Jerome Sarris Jerome Sarris Jerome Sarris Jerome Sarris |
| author_sort | Yvonne A. Bonomo |
| collection | DOAJ |
| description | IntroductionAyahuasca 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.MethodFormulations 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).ResultsAll 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.DiscussionOur 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.Clinical trial registrationhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384191&isReview=true, identifier ACTRN12622001315707. |
| format | Article |
| id | doaj-art-a3c84840273d4e9fb8cfc27c296cd063 |
| institution | DOAJ |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj-art-a3c84840273d4e9fb8cfc27c296cd0632025-08-20T03:03:19ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-08-011610.3389/fpsyt.2025.15459151545915DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteersYvonne A. Bonomo0Yvonne A. Bonomo1Amanda F. Norman2Lisa Collins3Margaret Ross4Justin Dwyer5Daniel Perkins6Daniel Perkins7Daniel Perkins8Jerome Sarris9Jerome Sarris10Jerome Sarris11Jerome Sarris12Department of Addiction Medicine, St Vincent's Hospital Melbourne, Melbourne, VIC, AustraliaDepartment of Medicine, University of Melbourne, Melbourne, VIC, AustraliaDepartment of Addiction Medicine, St Vincent's Hospital Melbourne, Melbourne, VIC, AustraliaDepartment of Addiction Medicine, St Vincent's Hospital Melbourne, Melbourne, VIC, AustraliaPsychosocial Cancer Care, St Vincent’s Hospital Melbourne, Melbourne, VIC, AustraliaPsychosocial Cancer Care, St Vincent’s Hospital Melbourne, Melbourne, VIC, AustraliaPsychae Institute, Melbourne, VIC, AustraliaSchool of Population and Global Health, University of Melbourne, Melbourne, VIC, AustraliaSwinburne University of Technology, Center for Mental Health and Brain Sciences, Melbourne, VIC, AustraliaPsychae Institute, Melbourne, VIC, AustraliaSwinburne University of Technology, Center for Mental Health and Brain Sciences, Melbourne, VIC, AustraliaNICM Health Research Institute, Western Sydney University, Westmead, NSW, AustraliaFlorey Institute of Neuroscience and Mental Health, Melbourne University, Melbourne, VIC, AustraliaIntroductionAyahuasca 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.MethodFormulations 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).ResultsAll 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.DiscussionOur 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.Clinical trial registrationhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384191&isReview=true, identifier ACTRN12622001315707.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1545915/fullayahuascapsychedelicsplant medicinemental healthdepressionanxiety |
| spellingShingle | Yvonne A. Bonomo Yvonne A. Bonomo Amanda F. Norman Lisa Collins Margaret Ross Justin Dwyer Daniel Perkins Daniel Perkins Daniel Perkins Jerome Sarris Jerome Sarris Jerome Sarris Jerome Sarris DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers Frontiers in Psychiatry ayahuasca psychedelics plant medicine mental health depression anxiety |
| title | DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers |
| title_full | DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers |
| title_fullStr | DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers |
| title_full_unstemmed | DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers |
| title_short | DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers |
| title_sort | dmt and harmala alkaloids an exploratory study of oral acacia based formulations in healthy volunteers |
| topic | ayahuasca psychedelics plant medicine mental health depression anxiety |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1545915/full |
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