Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [¹⁸F]FDG-PET study
Klemens Egger, Robert Bozsak, Helena Aicher, Hasan Sari, Sandra N. Poetzsch, Axel Rominger, Chantal Martin-Soelch, John W Smallridge, Dario Dornbierer, Boris B. Quednow, Milan Scheidegger, Paul Cumming
Repository for Publications and Research Data 2026 DOI: 10.3929/ethz-c-000801722 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Single-blind, crossover design Randomized Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Healthy males |
| Interventions | buccal DMT + harmine placebo |
| Dose | 90 mg DMT, 120 mg harmine |
| Topics | 5-MeO-DMT DMT |
| Keywords | Harmine Placebo Neuroimaging Metabolite Electroencephalography Positron emission tomography Crossover study Monoamine oxidase Pharmacology Endocrinology Type 2 diabetes Ictal Pharmacodynamics |
| Registration | NCT06252506 |
| Key points | Global cerebral glucose metabolism increased by 12.5% under DMT+harmine versus placebo, with widespread cortical increases particularly in higher-order brain networks. |
Abstract
Classical psychedelics such as N,N-dimethyltryptamine (DMT) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine—mimicking the pharmacological profile of ayahuasca—oral DMT induces a psychedelic experience lasting 4–5 h. While some neuroimaging studies have characterized effects of DMT on functional connectivity and electroencephalography its impact on cerebral energy metabolism remains largely unexplored. We assessed the cerebral metabolic rate for glucose consumption (CMRglc) with [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) and linear graphic analysis following buccal DMT + harmine (90 mg DMT, 120 mg harmine) versus placebo in a single-blind, crossover design in 14 healthy males. Scans were acquired during peak drug effects (100–170 min post-administration). Global CMRglc increased by 12.5% under DMT+harmine versus placebo (t = 2.58, p = 0.011). Vertex- and network-wise analyses revealed widespread cortical increases, particularly in higher-order brain networks. Exploratory analyses found a significant positive correlation between global CMRglc and harmine plasma levels, but not with DMT plasma levels, subjective intensity ratings. A psychedelic dose of DMT + harmine globally increased cerebral glucose metabolism, recapitulating a classic finding for psilocybin, and suggesting a potential metabolic signature of the psychedelic state. Clinical trial registry name and URL incl. registration number: Molecular Imaging Study of Harmine/DMT: a Basic Research Approach (HaD-PET) https://clinicaltrials.gov/study/NCT06252506.
Comparable studies
Other randomized controlled trials on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Healthy volunteers | 2005 | Double-blind crossover study | n = 9 |
| Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Experienced hallucinogen users | 1996 | Randomized controlled trial | n = 13 |
| Pharmacokinetics of N,N-dimethyltryptamine in Humans. Healthy adults | 2023 | Phase I component of a phase I/IIa randomised, double-blind, placebo-controlled, parallel-group, dose-escalation trial | n = 24 |
| Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis Healthy volunteers | 2007 | Double-blind crossover study | n = 15 |