Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: An [¹⁸F]FDG-PET Study
Klemens Egger, Robert Bozsak, Helena Aicher, Hasan Sari, Sandra N. Poetzsch, Axel Rominger, Chantal Martin-Soelch, Dario Dornbierer, Boris B. Quednow, Milan Scheidegger, Paul Cumming
Research Square July 27, 2025 preprint DOI: 10.21203/rs.3.rs-7099164/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Single-blind, placebo-controlled, crossover study |
|---|---|
| Sample size | 14 |
| Population | Healthy males |
| Interventions | DMT harmine |
| Dose | 90 mg DMT, 120 mg harmine |
| Duration | Scans acquired 100–170 min post-administration |
| Measures | [18F]FDG-PET, serotonin-2A receptor (5-HT2AR) density PET atlas |
| Topics | 5-MeO-DMT DMT |
| Keywords | Psychoactive compounds n Harmine Brain activity Energize your brain Brain function Altered consciousness consciousness Mood enhancement Well-being Positive findings |
| Citations | 1 |
| Key points | DMT plus harmine increased global cerebral glucose metabolism by 12% compared with placebo, with relatively greater right-hemisphere activation and widespread cortical increases in the default mode, frontoparietal, and attentional networks. Global metabolism correlated positively with harmine plasma levels but not with DMT levels, subjective intensity ratings, or serotonin-2A receptor density. The authors propose increased brain glucose metabolism as a potential metabolic signature of the psychedelic state. |
Abstract
Abstract Classical psychedelics such N,N -dimethyltryptamine (DMT), psilocybin, and lysergic acid diethylamide (LSD) 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 hours. While neuroimaging studies have examined changes in brain activity, connectivity, and cerebral perfusion under psychedelics, their effects on cerebral glucose metabolism remain largely unexplored. Here, we used positron emission tomography with [ 18 F]fluorodeoxyglucose ([¹⁸F]FDG-PET) to assess the cerebral metabolic rate for glucose consumption (CMRglc) following buccal DMT + harmine (90 mg DMT, 120 mg harmine) versus placebo in a single-blind, placebo-controlled, crossover design in (n = 14) healthy males. Scans were acquired during peak drug effects, i.e., 100–170 min post-administration. Global CMRglc increased by 12% under DMT + harmine compared to placebo ( t = 2.57, p < 0.05), with relatively greater activation in the right hemisphere. Vertex- and network-wise analyses revealed widespread cortical increases, with localized effects in the default mode, frontoparietal, and attentional networks. Exploratory correlational analyses found a significant positive correlation between global CMRglc and harmine plasma levels (area under the curve (AUC); r = 0.61, p = 0.021) in the DMT + harmine condition, but not with DMT AUC, subjective intensity ratings, or regional serotonin-2A receptor (5-HT2AR) density derived from a publicly available PET atlas. These findings advance the mechanistic understanding of psychedelics by demonstrating that DMT + harmine increases cerebral glucose metabolism, particularly in higher-order networks, and augment pioneering work indicating increased brain glucose metabolism as a potential metabolic signature of the psychedelic state.
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 |
Citations in the library
Cites 45
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
- Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression Journal of Clinical Psychopharmacology December 11, 2015
and 40 more in the library