iScience
May 19, 2023
Andres Ort, John W Smallridge, Simone Sarasso et al.
47 citations
Classical psychedelic drugs like psilocybin induce profound changes in consciousness, including heightened sensory-emotional awareness and arousal, accompanied by increased spontaneous EEG signal diversity. By combining Transcranial Magnetic Stimulation (TMS) with EEG, this work shows that psilocybin creates a state of increased chaotic brain activity, which is not due to altered complexity in causal interactions between brain regions. The study also maps regional effects of psilocybin on TMS-evoked activity, identifying changes in frontal brain structures that may relate to the phenomenology of psychedelic experiences.
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.
Progress in Neuro-psychopharmacology and Biological Psychiatry
January 1, 2026
Cheng-Teng Ip, Sebastian Olbrich, Mateo de Bardeci et al.
1 citation
In a double-blind, randomized, crossover, placebo-controlled trial with 25 healthy adults, psilocybin (10–20 mg oral) decreased EEG power in slow frequency bands (theta and alpha) and increased power in fast frequency bands (beta, gamma1, gamma2) compared to placebo. Connectivity within the default-mode network and localized parietal network increased under psilocybin. Changes in EEG power and connectivity correlated positively with subjective experiences measured by the Altered States of Consciousness Questionnaire. Baseline EEG features predicted subjective alterations, suggesting that specific brain activity patterns could serve as biomarkers for tailoring psilocybin therapy.
iScience
May 19, 2024
Andres Ort, John W Smallridge, Erich Seifritz et al.
1 citation
Psilocybin, a serotonergic psychedelic being studied for psychiatric treatment, preserved reinforcement learning in a probabilistic cue-reward task using emotional faces presented consciously or subconsciously. Across dosages, psilocybin was statistically noninferior to placebo and suggested higher exploratory behavior. The 20 mg group showed significantly better learning rates than placebo. Psilocybin led to inferior learning with subconscious cues compared to placebo, but better results with conscious neutral cues in some conditions. The findings indicate that modulating serotonin signaling with psilocybin sufficiently preserves reinforcement learning.
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.
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.