Molecular Imaging Study of Harmine/DMT: a Basic Research Approach

NCT06252506 | Completed Phase 1 DMC

• 2 other identifiers: HaD-PET320030_204978
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

The few reports on effects of psychedelic substances on cerebral metabolic rate (CMRglc) indicate increases (psilocybin; human FDG-PET) or decreases (LSD, rat autoradiography; 5-MeO-DMT rat autoradiography). There are no reports of effects of DMT and/or harmine on cerebral energy metabolism. The primary objective of this study is thus to assess acute cerebrometabolic effects of harmine/DMT in healthy volunteers using quantitative FDG-PET, that is, to measure CMRglc before and after simultaneous treatment with an oral harmine and DMT formulation developed (and already applied) by the investigators' project partners at the University of Zurich. As a secondary objective, the researchers aim to correlate the time-dependent effects on CMRglc as assessed in the PET images with the time-dependent self-reported intensity of participants' psychedelic experience.

Conditions

Neuropharmacological Investigation of Ayahuasca Constituents DMT and Harmine

Keywords

Brain; Glucose; PET; FDG; Metabolism; DMT; Harmine; Ayahuasca

Outcome Measures

Primary Outcomes (1)

• Change from baseline in cerebral metabolic rate for glucose (CMRglc)

  Differences in CMRglc during a placebo PET scan vs. active-drug PET scan are measured.

  From enrollment to the second PET scan, up to 6 months

Secondary Outcomes (12)

• Blood Glucose levels

  From enrollment to the second PET scan, up to 6 months

• Plasma concentrations of DMT, harmine, and their metabolites

  From enrollment to the second PET scan, up to 6 months

• Aliveness Task

  From enrollment to the second PET scan to a maximum of 6 months

• Acute Subjective Effects

  From enrollment to the second PET scan, up to 6 months

• Blood pressure

  From enrollment to the second PET scan, up to 6 months

Study Arms (2)

Placebo first, intervention second

EXPERIMENTAL

Participants allocated to this arm receive placebo on their first study day and the active drug under investigation on the second study day.

Drug: N,N-dimethyltryptamine (DMT) + harmine; Drug: Placebo

Intervention first, placebo second

EXPERIMENTAL

Participants allocated to this arm receive the active drug under investigation on their first study day and placebo on the second study day.

Drug: N,N-dimethyltryptamine (DMT) + harmine; Drug: Placebo

Interventions

N,N-dimethyltryptamine (DMT) + harmine DRUG

DMT and harmine are the two most abundant chemicals in the Amazonian hallucinogenic plant brew, Ayahuasca, which is used traditionally in spiritual and healing ceremonies. An oral formulation of these two substances will be tested against placebo in the context of an FDG-PET scan.

Intervention first, placebo second; Placebo first, intervention second

Placebo DRUG

Placebo will be administered on one of the study days to compare the effects of DMT and harmine with the effects a placebo administration.

Intervention first, placebo second; Placebo first, intervention second

Eligibility Criteria

• Age: 25 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Between 25-45 years old
• Good command of the German language
• Willing and capable to give consent for the participation in the study after it has been thoroughly explained
• Willing and capable to comply with all study requirements
• Body mass index (BMI) between 18.5 and 35
• Previous experience with psychedelics, but not in the past three months
• Willing to abstain from alcohol, caffeinated drinks, nicotine, food, and sugary drinks for two hours prior to the PET scan on the testing day, and from consuming psychoactive substances for 2 weeks before the first testing day and for the duration of the study

You may not qualify if:

• Previous significant adverse response to a psychedelic drug
• Recent or concurrent participation in another study where pharmaceutical compounds will be given
• Presence of Axis I affective, anxiety, or dissociative disorders
• Present or antecedent diagnosis of bipolar disorder (I, II, not otherwise specified), schizophrenia, schizoaffective disorder, psychosis, or other disorders from the psychotic spectrum
• First-degree relatives with present or antecedent schizophrenia, schizoaffective disorder, or bipolar disorder type I
• History of head trauma, seizures, cancer, or cerebrovascular accidents
• Recent cardiac or brain surgery
• Current abuse of medication or psychotropic substances according to SCID I criteria
• Presence of major internal or neurological disorders (including sepsis, pheochromocytoma, thyrotoxicosis, drug-induced fibrosis, familiar or basilar artery migraine)
• Cardiovascular disease (hypertonia, coronary artery disease, heart insufficiency, myocardial infarction, coronary spastic angina) Version 5, 15/11/2023 16/44
• Peripheral vascular disease (thromboangiitis obliterans, luetic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud's disease)
• Cerebrovascular disease (e.g., stroke, intracranial bleeding / hemorrhage, intracranial aneurysm)
• Diabetes Type 1/2, Metabolic Syndrome
• Serious abnormalities in ECG or blood count/chemistry
• Liver or renal or pulmonary disease

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Psychiatric University Hospital, Zurich: collaborator

Study Sites (2)

Department of Nuclear Medicine, Bern University Hospital

Bern, 3010, Switzerland

Location

Psychiatric University Hospital Zurich

Zurich, 8032, Switzerland

Location

Related Publications (3)

• Vollenweider FX, Leenders KL, Scharfetter C, Maguire P, Stadelmann O, Angst J. Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology. 1997 May;16(5):357-72. doi: 10.1016/S0893-133X(96)00246-1.

  PMID: 9109107 BACKGROUND

• Berlowitz I, Egger K, Cumming P. Monoamine Oxidase Inhibition by Plant-Derived beta-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca. Front Pharmacol. 2022 May 2;13:886408. doi: 10.3389/fphar.2022.886408. eCollection 2022.

  PMID: 35600851 BACKGROUND

• Egger K, Gudmundsen F, Jessen NS, Baun C, Poetzsch SN, Shalgunov V, Herth MM, Quednow BB, Martin-Soelch C, Dornbierer D, Scheidegger M, Cumming P, Palner M. A pilot study of cerebral metabolism and serotonin 5-HT2A receptor occupancy in rats treated with the psychedelic tryptamine DMT in conjunction with the MAO inhibitor harmine. Front Pharmacol. 2023 Sep 28;14:1140656. doi: 10.3389/fphar.2023.1140656. eCollection 2023.

  PMID: 37841918 BACKGROUND

MeSH Terms

Interventions

N,N-Dimethyltryptamine; Harmine

Intervention Hierarchy (Ancestors)

Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Harmala Alkaloids; Indole Alkaloids; Alkaloids; Indolizidines; Indolizines; Carbolines; Heterocyclic Compounds, 3-Ring

Study Officials

• Paul K Cumming, PhD

  Insel Group AG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: January 22, 2024
• Primary Completion: February 17, 2025
• Study Completion: March 5, 2025
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)