Acute experiences and persisting psychological effects associated with an encapsulated DMT-harmala alkaloid combination: results of a phase 1 study (2025)

November 2025

Daniel Perkins Andreas Halman Anna Urokohara Joeseph Palumbo Mitchell Low Simon Ruffell Nicole Galvão-Coelho Lisa Collins Amanda Norman Jerome Sarris

An encapsulated, precisely standardised combination of DMT and harmala alkaloids, the active compounds found in ayahuasca, reliably produced strong mystical experiences in healthy volunteers, and these experiences were associated with a range of lasting psychological benefits, in new research published in Scientific Reports.

Why mystical experiences matter in psychedelic research

Across many psychedelic studies, the intensity of the acute "mystical experience", with its feelings of unity, sacredness, transcendence of time and space, and ineffability, has been linked to therapeutic outcomes, including reductions in depression, anxiety and addiction. For any standardised psychedelic medicine to be effective in a clinical setting, it needs to reliably produce this kind of experience.

A first: standardising DMT and all three harmala alkaloids

Traditional ayahuasca brews vary widely in their chemical makeup, depending on the plants used, how they are grown and how the brew is prepared. This study is believed to be the first clinical trial to standardise not only DMT, but also the three main harmala alkaloids (harmine, tetrahydroharmine and harmaline) to precise, predetermined levels. DMT was extracted from Australian native Acacia species and the harmala alkaloids from Peganum harmala seeds, with formulations developed with CSIRO, Australia's national science agency, and manufactured to pharmaceutical (GMP) standards at NICM Health Research Institute, Western Sydney University.

A phase 1 study with experienced volunteers

Nine healthy volunteers, all with previous ayahuasca experience, took part in 17 dosing sessions in a clinical setting. Participants received partially purified or highly purified formulations at a standard or higher dose. The acute experience was measured using three instruments:

The Mystical Experience Questionnaire (MEQ-30) and the Five Dimensions of Altered States of Consciousness scale (5D-ASC)

A newly adapted Short Index of Mystical Experience (SIME)

Persisting effects on mood, attitudes, behaviour and personal insight were assessed one week later.

Mystical experiences among the strongest reported in psychedelic research
At the higher dose, the highly purified formulation produced mystical experience scores exceeding those reported in most other published studies across a range of psychedelics, and 5D-ASC scores higher than any other study compared. Higher total doses were significantly associated with stronger mystical experiences on the MEQ and SIME.

A capsule in a clinic, comparable to ceremony
When compared with data from the Global Ayahuasca Survey, the strength of mystical experiences was similar to that reported by people drinking ayahuasca in churches, traditional shamanic ceremonies and other settings. Around 62% of sessions were rated among the five most spiritually significant experiences of participants' lives, in line with the 56-63% reported by people drinking ayahuasca in naturalistic settings.

Mystical experiences linked to lasting benefits, not lasting harm
Stronger mystical experiences predicted a wide range of positive persisting effects, including greater personal insight, meaningfulness, spiritual significance, wellbeing, positive mood and behaviour change, and more positive attitudes about life and self. With one minor exception, mystical experiences did not predict any negative persisting effects.

The Onaya Science take: Promising, but early days
This was a small, proof-of-concept study without a placebo group, and all participants were healthy and already familiar with ayahuasca, which may not reflect how patients or psychedelic-naïve people would respond. More detailed statistical models did not confirm a clear dose-response relationship, likely due to the small sample. Qualitative findings will be shared in a future paper. The researchers conclude that this formulation now warrants investigation in controlled clinical trials with relevant patient populations, to assess both its therapeutic potential and its safety.