Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Healthy Volunteers

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

This open-label study (n=9) found that an encapsulated DMT-harmala alkaloid product (pharmahuasca) produced dose-dependent mystical experiences that exceeded those reported in most previous ayahuasca studies and were associated with beneficial persisting psychological effects in healthy volunteers.

Authors

  • Perkins, D.
  • Halman, A.
  • Urokohara, A.

Published

Scientific Reports
individual Study

Abstract

Acute subjective experiences induced by psychedelics have been identified as important mediators of therapeutic outcomes in many studies. Mystical experiences specifically, have been correlated with a range of therapeutic outcomes including reductions in symptoms of depression, anxiety and addiction. This paper assesses acute subjective experiences induced by an encapsulated DMT-harmala alkaloid product and associations with persisting psychological effects. Botanically derived purified and partially purified formulations containing precise levels of DMT and three harmala alkaloids were administered in 17 dosing sessions to 9 healthy volunteers, with acute subjective experiences data collected via three psychometric instruments (MEQ-30, 5D-ASC, and newly adapted SIME). Pearson’s correlations and linear mixed models investigated dose-response relationships and associations with persisting psychological effects. Further analysis compared acute subjective experience scores in this study to ayahuasca drinkers in various naturalistic contexts. Strong, significant positive correlations were identified between total dose and MEQ and SIME scores. The purified DMT–harmala formulation reliably elicited strong acute subjective experiences, with scores exceeding those reported in most previous studies. These experiences were robustly associated with a range of beneficial persisting psychological effects. Findings suggest that this formulation warrants further investigation in controlled clinical trials with relevant patient populations to assess therapeutic potential and safety.

Available with Blossom Pro

Research Summary of 'Acute experiences and persisting psychological effects associated with an encapsulated DMT-harmala alkaloid combination: results of a phase 1 study'

Introduction

Earlier research has identified the intensity of acute subjective experiences induced by classic psychedelics—particularly mystical-type experiences measured by instruments such as the Mystical Experience Questionnaire (MEQ) and the 5D-ASC—as important mediators of therapeutic outcomes, including reductions in depression and anxiety and changes in attitudes and behaviour. Observational and naturalistic studies of ayahuasca and other DMT-harmala preparations have similarly linked stronger mystical experiences to longer-term wellbeing, reduced substance use risk, and other beneficial life changes, although some studies report associations only for particular subscales. A practical challenge for DMT-harmala products is the wide variability in DMT and harmala alkaloid (harmine, tetrahydroharmine, harmaline) content and ratios in botanical preparations, which may affect reproducibility of acute experiences and downstream effects. This study set out to evaluate whether an encapsulated, standardised DMT-harmala drug product—manufactured to predetermined concentrations and ratios of DMT and the three main harmala alkaloids—could reliably elicit mystical experiences in a clinical setting and whether those acute experiences predicted persisting psychological effects. The researchers assessed acute subjective effects with three psychometric instruments (MEQ-30, 5D-ASC and a newly adapted Short Index of Mystical Experience, SIME) and examined dose-response relationships, formulation effects, and associations with one-week persisting outcomes. The work aimed to provide proof-of-concept data on a purified oral DMT-harmala combination that might inform further clinical investigations.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

See Pro PlansAlready have an account? Sign in

Full Text PDF

Full Paper PDF

Create a free account to open full-text PDFs.

Create Free AccountAlready have an account? Sign in

Study Details

References (39)

Papers cited by this study that are also in Blossom

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)

Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later

Griffiths, R. R. · Journal of Psychopharmacology (2008)

The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects

Yaden, D. B., Griffiths, R. R. · ACS Pharmacology and Translational Science (2020)

Psychotherapeutic and neurobiological processes associated with ayahuasca: A proposed model and implications for therapeutic use

Perkins, D., Ruffell, S. G. D., day, K. et al. · Frontiers in Neuroscience (2023)

Association between mystical-type experiences under psychedelics and improvements in well-being or mental health - A comprehensive review of the evidence

Kangaslampi, S. · Journal of Psychedelic Studies (2023)

58 cited
The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression

Goodwin, G. M., Aaronson, S. T., Alvarez, O. et al. · Journal of Affective Disorders (2025)

28 cited
Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Psychopharmacology (2011)

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: A randomized controlled trial

Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up

Davis, A. K., Streeter Barrett, F., Cosimano, M. P. et al. · Journal of Psychopharmacology (2022)

306 cited
Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)

Show all 39 references
Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression

Murphy, R., Murphy-Beiner, A., Kettner, H. et al. · Frontiers in Pharmacology (2022)

162 cited
Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study

Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)

Long-term follow-up of psilocybin-facilitated smoking cessation

Johnson, M. W., Garcia-Romeu, A., Griffiths, R. R. · The American Journal of Drug and Alcohol Abuse (2016)

562 cited
Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness

Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Palhano-Fontes, F., Barreto, D., Onias, H. et al. · Psychological Medicine (2018)

Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression

Falchi-Carvalho, M., Palhano-Fontes, F., Wießner, I. et al. · Neuropsychopharmacology (2025)

Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial

Schindowski, E. M., Jungwirth, J., Schuldt, A. et al. · EClinicalMedicine (2023)

Investigating the relationship between changes in metaphysical beliefs and death anxiety following a significant psychedelic experience

Moreton, S. G., Barr, N., Giese, K. J. · Death Studies (2024)

Associations between ayahuasca consumption in naturalistic settings and current alcohol and drug use: Results of a large international cross-sectional survey

Perkins, D., Opaleye, E. S., Simonová, H. et al. · Drug and Alcohol Review (2021)

Changes in mental health, wellbeing and personality following ayahuasca consumption: Results of a naturalistic longitudinal study

Perkins, D., Pagni, B. A., Sarris, J. et al. · Frontiers in Pharmacology (2022)

40 cited
DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers

Bonomo, Y. A., Norman, A. F., Collins, L. et al. · Frontiers in Psychiatry (2025)

Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Journal of Psychopharmacology (2017)

393 cited
Influence of Context and Setting on the Mental Health and Wellbeing Outcomes of Ayahuasca Drinkers: Results of a Large International Survey

Perkins, D., Schubert, V., Simonová, H. et al. · Frontiers in Pharmacology (2021)

45 cited
Acute subjective effects in LSD- and MDMA-assisted psychotherapy

Schmid, Y., Gasser, P., Oehen, P. et al. · Journal of Psychopharmacology (2020)

72 cited
Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study

Barsuglia, J. P., Davis, A. K., Palmer, R. et al. · Frontiers in Psychology (2018)

Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants

Rucker, J., Roberts, C. A., Seynaeve, M. et al. · Journal of Psychopharmacology (2024)

20 cited
Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants

Erne, L., Vogt, S. B., Müller, L. et al. · Neuropsychopharmacology (2024)

9 cited
Alterations of consciousness and mystical-type experiences after acute LSD in humans

Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)

190 cited
The influence of ceremonial settings on mystical and challenging experiences occasioned by ayahuasca: A survey among ritualistic and religious ayahuasca users

Pontual, A. A. D. D., Tófoli, L. F., Corradi-Webster, C. M. et al. · Frontiers in Psychology (2022)

Ketanserin reverses the acute response to LSD in a randomized, double-blind, placebo-controlled, crossover study in healthy subjects

Becker, A. M., Klaiber, A., Holze, F. et al. · International Journal of Neuropsychopharmacology (2022)

73 cited
Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects.

Holze, F., Vizeli, P., Müller, F. et al. · Neuropsychopharmacology (2019)

214 cited
Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants

Vogt, S. B., Ley, L., Erne, L. et al. · Translational Psychiatry (2023)

64 cited
Comparative acute effects of mescaline, lysergic acid diethylamide, and psilocybin in a randomized, double-blind, placebo-controlled cross-over study in healthy participants

Ley, L., Holze, F., Arikci, D. et al. · Neuropsychopharmacology (2023)

138 cited
A phase 1, dose-ranging study to assess safety and psychoactive effects of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in healthy volunteers

Reckweg, J., Mason, N. L., van Leeuwen, C. et al. · Frontiers in Pharmacology (2021)

Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects

Holze, F., Ley, L., Müller, F. et al. · Neuropsychopharmacology (2022)

169 cited
Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca

Riba, J., Mcilhenny, E. H., Valle, M. et al. · Drug Testing and Analysis (2012)

Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

Valle, M., Maqueda, A. E., Rabella, M. et al. · European Neuropsychopharmacology (2016)

145 cited
Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial

Zeifman, R. J., Dos Santos, R. G., Sanches, R. F. et al. · Psychopharmacology (2020)

67 cited

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.

See Pro PlansSign in