Molecular Imaging Study of Harmine/DMT: a Basic Research Approach (HaD-PET)

Insel Gruppe AG, University Hospital Bern

Status and phase: Completed; Phase 1

Conditions: Neuropharmacological Investigation of Ayahuasca Constituents DMT and Harmine

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06252506

320030_204978 (Other Grant/Funding Number)

HaD-PET

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: Male

Ages: 25 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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
• Inability to lie still in the scanner for about 90 minutes (e.g., because of sneezing, itching, tremor, pain)
• Left-handedness
• Significant radiation exposure (either X-ray or nuclear medicine studies) in the last 12 months
• Presence of claustrophobia or other contraindications to PET scanning
• Presence of contraindications to MRI investigations: Magnetic parts in the body (piercings, brain aneurysm clip, implanted neural stimulator/cardiac pacemaker/defibrillator/Swan Ganz catheter/insulin pump, cochlear implant); metal shrapnel or bullet, ocular foreign body (e.g., metal shavings); current or previous job in metalworking industry
• Current use of medications with significant interaction potential with MAO inhibitors (e.g., antidepressants, antipsychotics, psychostimulants, dopaminergic/serotonergic agents, anticonvulsants)
• High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, serious current stressors, lack of social support).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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17 participants in 2 patient groups

Placebo first, intervention second

Experimental group

Description:

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

Treatment:

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

Drug: Placebo

Intervention first, placebo second

Experimental group

Description:

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

Treatment:

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

Drug: Placebo