Frontiers in Pharmacology
January 1, 2023
Klemens Egger, Frederik Gudmundsen, Naja Støckel Jessen et al.
17 citations
Co-administration of harmine with DMT in rats increased brain DMT levels by inhibiting its metabolism to indole-3-acetic acid, yet no significant occupancy of serotonin 5-HT2A receptors by DMT was detected, even at brain DMT concentrations up to 11.3 µM. Low doses of DMT and/or harmine did not significantly alter brain glucose metabolism as measured by [18F]FDG-PET. These preliminary findings suggest that the role of MAO-A inhibition in potentiating DMT's psychedelic effects may be more complex than previously assumed, and further dose-response studies are needed.
The International Journal of Neuropsychopharmacology
December 28, 2024
Michael J Mueller, Helena Aicher, Dario Dornbierer et al.
10 citations
A new pharmaceutical formulation combining pure DMT and harmine produced ayahuasca-like psychological effects lasting 2-3 hours in 31 healthy male volunteers, with consistent drug levels and no serious adverse events. DMT reached peak plasma concentrations of 22.1 ng/mL, while buccal harmine reached 32.5 ng/mL in a sustained-release profile but caused no distinguishable subjective effects on its own. All drug conditions were safe and well tolerated, suggesting the formulation could reduce risks and improve therapeutic outcomes for mental health disorders.
Research Square
July 27, 2025
Klemens Egger, Robert Bozsak, Helena Aicher et al.
1 citation
In healthy volunteers, acute administration of N,N-dimethyltryptamine (DMT) combined with harmine produces global increases in brain glucose metabolism, as measured by [¹⁸F]FDG-PET. This suggests that the compound combination broadly energizes brain activity rather than acting on isolated regions. The findings indicate a neurobiological basis for the altered states of consciousness and mood enhancement reported with these psychoactive compounds, supporting further investigation into their therapeutic potential.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
June 1, 2026
Klemens Egger, Robert Bozsak, Helena Aicher et al.
A psychedelic dose of DMT combined with harmine (mimicking ayahuasca) globally increased cerebral glucose metabolism by 12.5% in 14 healthy males, as measured by FDG-PET scans during peak drug effects. Widespread cortical increases appeared in higher-order brain networks. Global glucose metabolism correlated positively with harmine plasma levels but not with DMT levels or subjective intensity. This recapitulates a classic finding for psilocybin, suggesting a potential metabolic signature of the psychedelic state.
Universität Zürich, ZORA
June 1, 2026
Klemens Egger, Robert Bozsak, Helena Aicher et al.
A psychedelic dose of DMT combined with the MAO-A inhibitor harmine, mimicking ayahuasca, globally increased cerebral glucose metabolism by 12.5% compared to placebo in 14 healthy males. Scans acquired during peak drug effects using FDG-PET showed widespread cortical increases, particularly in higher-order brain networks. Higher harmine plasma levels correlated with greater global glucose metabolism, while DMT levels and subjective intensity did not. This metabolic signature recapitulates a classic finding for psilocybin, suggesting a potential hallmark of the psychedelic state.
Open Access CRIS of the University of Bern
February 9, 2026
Mikael Palner, Elisabeth Kolesnik, Christina Baun et al.
The mammalian brain may contain an endogenous pool of the psychedelic N,N-dimethyltryptamine (DMT), possibly acting as a co-transmitter with serotonin. In rats, inhibiting monoamine oxidase with pargyline did not make endogenous DMT detectable, while probenecid slightly elevated the acidic metabolite 3-indoleacetic acid (3-IAA), suggesting formation from tryptamine, especially in the striatum. After administering DMT plus harmine, peak brain DMT occurred at 45 minutes and peak 3-IAA at 60 minutes, with nearly complete washout by 210 minutes. Escitalopram did not alter exogenous DMT or 3-IAA disposition, and dihydrotetrabenazine slightly increased 3-IAA in some regions. The results do not support an endogenous DMT pool or retention of exogenous DMT in serotonin terminals.
Neuropharmacology
February 9, 2026
Mikael Palner, Elisabeth Kolesnik, Christina Baun et al.
The study tested whether the psychedelic compound N,N-dimethyltryptamine (DMT) exists naturally in the mammalian brain and acts as a co-transmitter with serotonin. In rats, blocking monoamine oxidase with pargyline did not allow detection of endogenous DMT, while blocking acidic metabolite transport with probenecid slightly elevated the DMT metabolite 3-indoleacetic acid, likely from tryptamine. Exogenous DMT was rapidly taken up and cleared from the brain, with peak concentrations at 45 minutes and near-complete washout by 210 minutes. Blocking serotonin reuptake or vesicular monoamine transporters did not alter DMT levels. The results do not support the hypothesis that DMT is an endogenous co-transmitter with serotonin.
Repository for Publications and Research Data (ETH Zurich)
January 1, 2026
Klemens Egger, Robert Bozsak, Helena Aicher et al.
A psychedelic dose of DMT combined with harmine, mimicking ayahuasca, globally increased cerebral glucose metabolism by 12.5% in 14 healthy males, as measured by PET scans during peak drug effects. This increase was widespread across the cortex, particularly in higher-order brain networks, and positively correlated with harmine plasma levels but not with DMT levels or subjective intensity. The finding recapitulates a classic effect seen with psilocybin, suggesting a potential metabolic signature of the psychedelic state.