A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers.
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. Murrough, Andrew F Stewart
Journal of Psychopharmacology October 1, 2024 DOI: 10.1177/02698811241273772 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phase 1, open-label single ascending dose trial Randomized Peer reviewed |
|---|---|
| Sample size | 25 |
| Population | Healthy adults aged 18-55 with normal body mass index and no prior psychiatric illness |
| Dose | 100, 200, 300, or 500 mg |
| Topics | Ayahuasca |
| Keywords | Clinical-trials Drug-safety Harmine Phase 1 Psychedelic-medicine Pharmacology Ayahuasca-research |
| Citations | 17 |
| Key findings | The maximum tolerated dose of oral harmine hydrochloride in healthy adults is between 100 and 200 mg, and doses above 2.7 mg/kg produce dose-limiting toxicities such as vomiting and drowsiness with limited psychoactivity. |
Abstract
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. 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. 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. Harmine HCl can be orally administered to healthy participants in 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.
Comparable studies
Other non-randomized and open-label trials on ayahuasca, most cited first.
Citations in the library
Cited by 6
- Examining the pharmacokinetic and pharmacodynamic interaction of N,N-dimethyltryptamine and harmine in healthy volunteers: Α factorial dose-escalation study. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie March 1, 2025
- Clinical pharmacology of ayahuasca: potential applications and future considerations Expert Review of Clinical Pharmacology October 3, 2025
- Enhancing mindfulness and compassion through an ayahuasca-inspired formulation containing N,N-DMT and harmine: A randomized controlled trial in healthy subjects. Journal of Psychopharmacology June 19, 2025
- Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: An [¹⁸F]FDG-PET Study Research Square July 27, 2025
- Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [18F]FDG-PET study. Journal of Cerebral Blood Flow & Metabolism June 1, 2026
and 1 more in the library
Cites 17
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression Journal of Clinical Psychopharmacology December 11, 2015
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
- Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Journal of Pharmacology and Experimental Therapeutics June 18, 2003
and 12 more in the library