Evidence map›Paper›PMID 39774840›Full record

Trial reportThe international journal of neuropsychopharmacology2024

Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial.

Michael J Mueller, Helena D Aicher, Dario A Dornbierer, Laurenz Marten, Dila Suay, Daniel Meling, Claudius Elsner, Ilhui A Wicki, Jovin Müller, Sandra N Poetzsch and 9 more

Registry-linked trialAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The international journal of neuropsychopharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04716335 (Neurodynamics of Prosocial Emotional Processing Following Serotonergic Stimulation With N,N-Dimethyltryptamine), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT04716335 early_phase1completednot on this map

Neurodynamics of Prosocial Emotional Processing Following Serotonergic Stimulation With N,N-Dimethyltryptamine (DMT) and Harmine in Healthy Subjects

TypeinterventionalSponsorPsychiatric University Hospital, ZurichRan2020 to 2022Enrolled34ConditionsEmotions, Mood, Cognitive Function 1, Social, EmpathyArmsDMT, Harmine, Placebo (Harmine), Placebo (DMT)
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Registered Clinical Trials of Ayahuasca and DMT: A Scoping Review.Clinical pharmacology and therapeutics · 2026
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Michael J MuellerDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.ORCID 0000-0002-9774-9805
Helena D AicherDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Dario A DornbiererDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Laurenz MartenDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Dila SuayDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Daniel MelingDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Claudius ElsnerDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Ilhui A WickiDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Jovin MüllerDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Sandra N PoetzschDepartment of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.
Luzia CaflischDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Alexandra HempeDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Camilla P SteinhartInstitute of Neuroinformatics, University of Zurich, Zurich, Switzerland.
Maxim PuchkovInstitute of Pharmaceutical Technology, University of Basel, Basel, Switzerland.
Jonas KostInstitute of Pharmaceutical Technology, University of Basel, Basel, Switzerland.ORCID 0009-0004-8331-5282
Hans-Peter LandoltDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Erich SeifritzDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.
Boris B QuednowDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.ORCID 0000-0001-7933-2865
Milan ScheideggerDepartment of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.ORCID 0000-0003-1313-2208

Funding

BIAL Foundation 333/20Bioentrepreneur Fellowship UZH BIOEF-18-009Fabian HedigerForschungskredit PostDoc UZH FK-18-052Reconnect FoundationSNSF Swiss National Science Foundation P0ZHP1_191935
6 · The paper itself

Abstract

backgroundRecent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.

methodsThis study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.

resultsN,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2-3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation's suitability for clinical applications.

conclusionsThis study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders. CLINICAL TRIAL REGISTRATION NUMBER: Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335.

Indexed as

HallucinogensHarmineN,N-DimethyltryptamineAdultBanisteriopsisDouble-Blind MethodHealthy VolunteersHumansMaleYoung AdultHallucinogensHarmineN,N-DimethyltryptamineharmineNN-dimethyltryptaminepharmacodynamicspharmacokineticspsychedelics

Identifiers

PMID39774840
PMCPMC11770821

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.