Clinical trial NCT06252506: Molecular Imaging Study of Harmine/DMT: a Basic Research Approach
Official title: Molecular Imaging Study of Harmine/DMT: a Basic Research Approach
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuropharmacological Investigation of Ayahuasca Constituents DMT and Harmine
Keywords: Brain
Glucose
PET
FDG
Metabolism
DMT
Harmine
Ayahuasca
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Psychiatric University Hospital, Zurich
First posted: 2024-02-09
Enrollment: 17
Sex: MALE
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change from baseline in cerebral metabolic rate for glucose (CMRglc)
timeFrame: From enrollment to the second PET scan, up to 6 months
Secondary outcomes:
measure: Blood Glucose levels
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Plasma concentrations of DMT, harmine, and their metabolites
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Aliveness Task
timeFrame: From enrollment to the second PET scan to a maximum of 6 months
measure: Acute Subjective Effects
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Blood pressure
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Heart rate
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Challenging Experiences
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Mystical Experience
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Emotional Breakthrough
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Altered States of Consciousness
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Attribution of Consciousness Questionnaire
timeFrame: From enrollment to the second PET scan, up to 6 months
measure: Individual Differences in Anthropomorphism
timeFrame: From enrollment to the second PET scan, up to 6 months
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Department of Nuclear Medicine, Bern University Hospital
city: Zurich
country: Switzerland
facility: Psychiatric University Hospital Zurich
Study officials:
affiliation: Insel Group AG
name: Paul K Cumming, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.