Frontiers in Pharmacology
May 2, 2022
Ilana Berlowitz, Klemens Egger, Paul Cumming
32 citations
Monoamine oxidases (MAOs) are enzymes that break down biogenic amines like serotonin, dopamine, and tyramine in the brain and body. Beta-carboline alkaloids, such as harmine and harmane, are MAO inhibitors found in plants including tobacco and Banisteriopsis caapi, a key ingredient in the Amazonian ayahuasca brew. These beta-carbolines may boost the bioavailability of the hallucinogen DMT and might have antidepressant properties. However, the level of MAO inhibition needed to affect neurotransmitter signaling is not yet known. Unlike synthetic antidepressant MAO inhibitors that cause complete and irreversible inhibition, beta-carbolines are reversible and competitive, making complete inhibition unlikely. Many medicinal plants contain MAO inhibitors, but their pharmacological relevance often remains unclear.
Cellular and molecular life sciences : CMLS
September 10, 2024
Klemens Egger, Helena D Aicher, Paul Cumming et al.
30 citations
The potent hallucinogen N,N-dimethyltryptamine (DMT) alters perception, mood, and cognition, presumably through agonism at serotonin 5-HT1A/2A/2C receptors in the brain. DMT is nearly inactive orally due to rapid first-pass metabolism, but co-administration with β-carbolines or synthetic MAO-A inhibitors—as in the Amazonian brew ayahuasca—greatly increases its bioavailability and duration of action. The synergistic effects of DMT and MAOIs may promote neuroplasticity, which presumably underlies their promising therapeutic efficacy in clinical trials for depression, addiction, and post-traumatic stress disorder. Neuroimaging reveals alterations in brain activity, functional connectivity, and network dynamics during DMT-induced altered states.
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.
Journal of Psychopharmacology
September 27, 2024
Daniel Meling, Klemens Egger, Jovin Mueller et al.
15 citations
In a double-blind, placebo-controlled study over a 3-day meditation retreat, 40 experienced meditators received either DMT-harmine or a placebo. Those who took DMT-harmine reported greater mystical-type experiences, non-dual awareness, and emotional breakthrough during the acute substance effects, and greater psychological insight one day later after adjusting for baseline differences. Mindfulness and compassion did not differ significantly between groups. At one-month follow-up, the DMT-harmine group rated their experience as more personally meaningful, spiritually significant, and well-being-enhancing than the placebo group. The findings suggest specific synergistic effects of DMT-harmine during meditation.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
March 1, 2025
Klemens Egger, Javier Jareño Redondo, Jovin Müller et al.
14 citations
Ayahuasca contains DMT and harmine, but their interactions are not fully understood. In a single-blind, randomized, two-arm, factorial dose-finding study with 16 healthy participants, each received six dose combinations of DMT (0-120 mg) and harmine (0-180 mg) via a transmucosal delivery system. All combinations produced dose-dependent subjective effects lasting 4-5 hours, with peak DMT and harmine levels reaching 33 ng/mL and 49 ng/mL, respectively. The interaction was bidirectional: harmine reduced DMT metabolism, while DMT altered harmine pharmacokinetics. The formulation had a favorable safety profile, supporting further testing for affective disorders.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
July 9, 2025
Angela Äbelö, John W Smallridge, Robin von Rotz et al.
3 citations
The psychedelic compound DMT is often taken with harmine, a monoamine oxidase inhibitor, as in ayahuasca, but how harmine alters DMT's effects was not well understood. In a study of 16 healthy adults, six combinations of buccal DMT (0-120 mg) and harmine (0-180 mg) were given. Harmine increased DMT's bioavailability and prolonged its absorption, leading to higher and more sustained blood levels. The intensity of subjective psychedelic effects rose with dose, and harmine potentiated these effects at higher DMT doses. A mathematical model captured these relationships and individual variability, offering a foundation for more personalized dosing in psychedelic therapy.
International review of neurobiology
January 1, 2025
Paul Cumming, Klemens Egger, Gitte M Knudsen
2 citations
Molecular brain imaging techniques such as PET and SPECT have been used since the 1980s to study psychostimulants, and more recently to investigate psychedelics. Most published research involves SPECT studies of cerebral blood flow and PET studies of metabolism and neuroreceptors, particularly the 5-HT2A receptor, which is primarily responsible for the effects of classical psychedelics. Some evidence documents interactions at dopamine D2/3 receptors in the striatum, but many other potential molecular targets remain unexplored. The growing therapeutic use of psychedelics for neurological and psychiatric disorders highlights the need for broader, systematic investigation of their effects on brain function.
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 D 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 D 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.
medRxiv
Klemens Egger, Daniel Meling, Firuze Polat et al.
preprint
In a double-blind, placebo-controlled pharmaco-fMRI study, 40 meditation practitioners on a three-day retreat received either placebo or buccal DMT-harmine (120 mg each). Meditation alone increased network segregation across several resting-state networks, while DMT-harmine increased functional connectivity within the visual network and between visual and attention networks. Between-group differences showed increased connectivity between visual and salience networks in the DMT-harmine group. No prolonged cortical gradient disruption was observed, indicating a return to typical brain organization shortly after the experience. Meditation reduced connectivity between networks, whereas DMT-harmine increased within- and between-network connectivity, revealing distinct neural mechanisms.