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| ID | Type | Description | Link |
|---|---|---|---|
| 320030_204978 | Other Grant/Funding Number | Swiss National Science Foundation (SNSF) |
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| Name | Class |
|---|---|
| Psychiatric University Hospital, Zurich | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Glucose levels | Glucose levels in blood are measured before and after PET scans to correct PET data to changes in glucose during the scans. | From enrollment to the second PET scan, up to 6 months |
| Plasma concentrations of DMT, harmine, and their metabolites |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul K Cumming, PhD | Insel Group AG | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Nuclear Medicine, Bern University Hospital | Bern | 3010 | Switzerland | |||
| Psychiatric University Hospital Zurich |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9109107 | Background | 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. | |
| 35600851 | Background |
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| ID | Term |
|---|---|
| D004130 | N,N-Dimethyltryptamine |
| D006247 | Harmine |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D000588 | Amines |
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| 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. |
|
Plasma concentrations of DMT, harmine and their main metabolites are assessed at several timepoints, i.e. at baseline, 20, 40, 60, 80, 100, and 180 min after drug or placebo administration. These concentrations serve as a combined outcome measure, as harmine directly influences the metabolism of DMT. |
| From enrollment to the second PET scan, up to 6 months |
| Aliveness Task | Behavioral experiment designed to assess the attribution of consciousness and intentionality to animate and inanimate objects. | From enrollment to the second PET scan to a maximum of 6 months |
| Acute Subjective Effects | Acute substance effects are measured with a questionnaire named APsych and consists of 8 items (i.e. ratings of intensity, challenging, acceptance, clarity, visual hallucinations, emotionality, liking, arousal) rated from 1-10 with 10 being the highest and assessment if bodily or psychiatric symptoms are present are assessed at several timepoints, i.e. at baseline, 20, 40, 60, 80, 100, 120, 140, 160, 180, 240, and 300 min after drug or placebo administration. | From enrollment to the second PET scan, up to 6 months |
| Blood pressure | Blood pressure is assessed at several timepoints, i.e. at baseline, 20, 40, 80, 180, and 300 min after drug or placebo administration. | From enrollment to the second PET scan, up to 6 months |
| Heart rate | Heart rate is assessed at several timepoints, i.e. at baseline, 20, 40, 80, 180, and 300 min after drug or placebo administration. | From enrollment to the second PET scan, up to 6 months |
| Challenging Experiences | Challenging Experiences Questionnaire is administered 240 min after drug or placebo administration. The questionnaire consists of 26 items that are rated from 0 (not at all) to 5 (extreme). | From enrollment to the second PET scan, up to 6 months |
| Mystical Experience | Mystical Experience Questionnaire is administered 240 min after drug or placebo administration. The questionnaire consists of 30 items that are rated from 0 (not at all) to 5 (extreme). | From enrollment to the second PET scan, up to 6 months |
| Emotional Breakthrough | Emotional Breakthrough Inventory is administered 240 min after drug or placebo administration. The questionnaire consists of 6 items that are rated from 0 (not at all) to 100 (very much). | From enrollment to the second PET scan, up to 6 months |
| Altered States of Consciousness | Altered States of Consciousness Questionnaire is administered 240 min after drug or placebo administration. The questionnaire consists of 94 items that are rated from 0 (no, not more than usual) to 100 (yes, much more than usual). | From enrollment to the second PET scan, up to 6 months |
| Attribution of Consciousness Questionnaire | The Attribution of Consciousness Questionnaire is assessed at baseline (medical screening) and 240 min after drug or placebo administration. The questionnaire consists of 10 items that are rated from 0 (strongly disagree) to 6 (strongly agree). | From enrollment to the second PET scan, up to 6 months |
| Individual Differences in Anthropomorphism | The Individual Differences in Anthropomorphism Questionnaire is assessed at baseline (medical screening) and 240 min after drug or placebo administration. The questionnaire consists of 30 items that are rated from 0 (not at all) to 10 (very much). | From enrollment to the second PET scan, up to 6 months |
| Zurich |
| 8032 |
| Switzerland |
| 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. |
| 37841918 | 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. |
| 42220002 | Derived | Egger K, Bozsak R, Aicher HD, Sari H, Poetzsch SN, Rominger A, Martin-Soelch C, Smallridge JW, Dornbierer D, Quednow BB, Scheidegger M, Cumming P. Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [18F]FDG-PET study. J Cereb Blood Flow Metab. 2026 Jun 1:271678X261454172. doi: 10.1177/0271678X261454172. Online ahead of print. |
| D009930 |
| Organic Chemicals |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000077290 | Harmala Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D002243 | Carbolines |
| D006575 | Heterocyclic Compounds, 3-Ring |