This open-label single ascending dose Phase I trial (n=25) determines the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine (component of ayahuasca brew) in healthy adults. It finds that doses <189mg/70kg can be administered with minimal or no adverse events, while doses >189mg/70kg are associated with vomiting, drowsiness, and limited psychoactivity.
Abstract of A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers
“Background: Harmine is a component of the hallucinogenic brew, Ayahuasca, which also contains the psychoactive compound, N, N-dimethyltryptamine. Whether pharmaceutical-grade harmine hydrochloride (HCl) has psychoactive effects, the doses at which these might occur, and the dose-response relationship to side effects and safety in humans are unknown.
Methods: We conducted a Phase 1, open-label single ascending dose trial in healthy adults with normal body mass index and no prior psychiatric illness. The primary goal was to determine the maximum tolerated dose (MTD) of oral pharmaceutical-grade harmine HCl and to characterize safety and tolerability. A secondary goal was to ascertain whether any oral dose has psychoactive effects.
Results: Thirty-four adult participants, aged 18–55 years, were screened for study eligibility. Twenty-five participants met eligibility criteria and were randomized to a single dose of 100, 200, 300, or 500 mg of harmine HCl, respectively, using a continuous reassessment method. The most common adverse events (AEs) observed were gastrointestinal and/or neurological, dose-related, and of mild to moderate severity. The MTD was determined to be between 100 and 200 mg and is weight-based, with 90% of those participants receiving >2.7 mg/kg experiencing a dose-limiting toxicity. No serious AEs of harmine HCl were identified.
Conclusions: Harmine HCl can be orally administered to healthy participants in doses <2.7 mg/kg with minimal or no AEs. Doses >2.7 mg/kg are associated with vomiting, drowsiness, and limited psychoactivity. This study is the first to systematically characterize the psychoactive effects of pharmaceutical quality harmine in healthy participants.“
Authors: Jessica L. Ables, Leah Israel, Olivia Wood, Usha Govindarajulu, Rachel T. Fremont, Ronjon Banerjee, Hongtao Liu, Jeremy Cohen, Peng Wang, Kunal Kumar, Geming Lu, Robert J. DeVita, Adolfo Garcia-Ocaña, James W. Murroug & Andrew F. Stewart
Summary of A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers
Harmine is a β-carboline alkaloid that has been used by humans for millennia as part of herbal remedies and psychoactive brews like ayahuasca. It is found in plants such as Banisteriopsis caapi and Peganum harmala, which have been used traditionally for various medicinal and spiritual purposes. Ayahuasca, which contains harmine along with the potent hallucinogen N,N-dimethyltryptamine (DMT), has gained popularity in recent years for both recreational and therapeutic use.
The researchers explain that harmine acts as a reversible inhibitor of monoamine oxidase A (MAO-A), which allows orally ingested DMT to avoid degradation and produce psychoactive effects. Harmine has also been studied for its potential neuroprotective properties and ability to induce proliferation of insulin-producing β-cells in the pancreas.
Despite its long history of use and recent scientific interest, there is limited research on the safety, tolerability, and psychoactive effects of pure, pharmaceutical-grade harmine in humans. Previous studies have reported adverse effects such as nausea, vomiting, drowsiness, and cardiovascular changes, but these were often conducted with impure preparations or as part of complex plant mixtures.
Methods
Study participants and design
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A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers
https://doi.org/10.1177/02698811241273772
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Cite this paper (APA)
Ables, J. L., Israel, L., Wood, O., Govindarajulu, U., Fremont, R. T., Banerjee, R., ... & Stewart, A. F. (2024). A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers. Journal of Psychopharmacology, 02698811241273772.
Study details
Compounds studied
Ayahuasca
Topics studied
Healthy Subjects
Safety
Study characteristics
Original
Open-Label
Participants
25
Humans
Compound Details
The psychedelics given at which dose and how many times
Ayahuasca 100 - 500mg | 1x
