ArticleFrontiers in pharmacology2023
Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine.
Article in Frontiers in pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- 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 (Oxford, England) · 2026Trial
- Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial.The international journal of neuropsychopharmacology · 2024Trial
- Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat.Journal of psychopharmacology (Oxford, England) · 2024Trial
- A Phase 1 single ascending dose study of pure oral harmine in healthy volunteers.Journal of psychopharmacology (Oxford, England) · 2024Trial
- Combined DMT-harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers.Psychopharmacology · 2026Article
- Registered Clinical Trials of Ayahuasca and DMT: A Scoping Review.Clinical pharmacology and therapeutics · 2026Article
- Overcoming Pharmacokinetic and Peripheral Safety Challenges in Psychedelic Therapies: The Promise of Advanced Drug Delivery Systems.ACS pharmacology & translational science · 2026Review
- Pharmacodynamic effects and plasma pharmacokinetics of N, N-dimethyltryptamine after intranasal versus subcutaneous administration in male rats.Psychopharmacology · 2026Article
- Review
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning-Based Advanced Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers.Frontiers in psychiatry · 2025Article
- Meditation, psychedelics, and brain connectivity: A randomized controlled resting-state fMRI study ofImaging neuroscience (Cambridge, Mass.) · 2025Article
- Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors.Cellular and molecular life sciences : CMLS · 2024Review
- Research progress on the antitumor effects of harmine.Frontiers in oncology · 2024Review
- Potential therapeutic effects of an ayahuasca-inspired N,N-DMT and harmine formulation: a controlled trial in healthy subjects.Frontiers in psychiatry · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, the Amazonian plant medicine "ayahuasca"-containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous β-carboline alkaloids, such as harmine-has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.