British Journal of Clinical Pharmacology
December 11, 2015
Matthias E. Liechti, Boris B. Quednow, Evangelia Liakoni et al.
57 citations
Gamma-hydroxybutyrate (GHB) produced mixed stimulant-sedative effects in healthy men, with higher doses causing more sedation and dizziness but no changes in heart rate or blood pressure. Plasma exposure to GHB rose disproportionately with dose—a 40% greater increase than expected from dose alone—indicating nonlinear pharmacokinetics. The psychotropic effects were closely tied to plasma concentrations, and no acute tolerance developed over time.
Molecules
April 22, 2021
Paul Cumming, Milan Scheidegger, Dario Dornbierer et al.
45 citations
Hallucinogens such as LSD, psilocybin, and mescaline are being re-evaluated for their psychotherapeutic potential. This narrative review covers in vitro and ex vivo binding studies and molecular imaging using PET or SPECT. Early PET work with [11C]-MBL showed that most specific binding is to serotonin 5-HT2A receptors, but interactions with 5-HT1A receptors and other pathways may contribute to the unique experiences. Other important factors include blood-brain barrier permeability, metabolism, and active metabolites. Only a few PET or SPECT studies of radiolabeled hallucinogens exist, most recently using [11C]Cimbi-36. Hybrid imaging combining PET with fMRI is expected to advance future research.
Psychoneuroendocrinology
July 17, 2015
Oliver G. Bosch, Christoph Eisenegger, Jürg Gertsch et al.
42 citations
Gamma-hydroxybutyrate (GHB), a GHB-/GABAB-receptor agonist, produces euphoric, disinhibiting, and vitality-enhancing effects in healthy men. In a randomized, placebo-controlled crossover trial with 16 males, a single 20 mg/kg dose increased charitable donations and prosocial money distributions among participants who initially showed low prosociality. However, GHB did not alter emotion recognition, empathy, theory-of-mind, or basic cognitive functions. The drug raised plasma progesterone levels but left oxytocin, testosterone, cortisol, aldosterone, DHEA, and ACTH unchanged. These findings suggest that GHB's mood and prosocial effects may involve GHB-/GABAB-receptors and progesterone rather than typical social hormones like oxytocin or testosterone.
Psychopharmacology
July 1, 2017
Robin Rotz, Michael Kometer, Dario Dornbierer et al.
19 citations
Gamma-hydroxybutyrate (GHB) increases theta oscillations in the posterior cingulate cortex and alpha1 oscillations in the anterior cingulate cortex, while decreasing the global omega complexity of alpha1 oscillations. Higher blood plasma levels of GHB are linked to increased delta oscillation connectivity between the posterior cingulate cortex and the right inferior parietal lobulus. These neural changes in the posterior cingulate cortex may explain the paradoxical dissociation between EEG patterns and behavior that GHB produces, where brain activity resembles sleep during wakefulness. The reduced number of independent neuronal processes is similar to effects seen with other anesthetics.
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.
Scientific reports
March 26, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
15 citations
Brain activity patterns during meditation shift after a psilocybin-assisted retreat, especially when open-monitoring meditation is practiced. Using functional MRI and a topological data analysis method (Mapper), researchers compared experienced meditators who received psilocybin or placebo over five days. The psilocybin group showed a link between positive derealization—an altered perception that can foster insight—and a greater geometric distance between open-monitoring meditation and resting-state brain activity, as measured by optimal transport distance. This suggests that combining psilocybin with open-monitoring practice enhances meta-awareness and insight. The findings point to possible brain markers for synergistic effects between mindfulness and psychedelics.
bioRxiv (Cold Spring Harbor Laboratory)
December 9, 2025
Maria Niedernhuber, Dila Suay, Michael J. Mueller et al.
1 citation
Classic serotonergic psychedelics strongly alter conscious awareness, but how they change the temporal structure of brain activity has been unclear. In a double-blind, placebo-controlled study with 25 participants using high-density EEG, an ayahuasca-inspired formulation (intranasal N,N-DMT and buccal harmine) accelerated neural dynamics: microstate duration decreased and state transitions became more frequent. Surprisingly, the sequence of microstates became less random, showing higher first-order Markov structure. This restructuring involved reduced transitions into one state (M2) and increased prevalence and accessibility of two others (M3 and M5). The psychedelic state thus produces a syntactically reconfigured, highly metastable neural dynamic, not mere randomization.
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.
Psychopharmacology
July 14, 2026
Helena D Aicher, Joëlle Dornbierer, Luzia Caflisch et al.
A combination of harmine and DMT, the active ingredients in ayahuasca, reduces feelings of embarrassment and shame in healthy men. In a randomized trial with 28 participants, those who received the combination reported significantly less embarrassment when listening to recordings of their own singing compared to those who received a placebo. The treatment also lowered overall shame scores. Harmine alone did not produce these effects. The findings suggest that this compound may help treat psychiatric disorders where negative self-focused emotions play a key role.
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.
Repository for Publications and Research Data (ETH Zurich)
January 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 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.
Universität Zürich, ZORA
August 16, 2025
Dila Suay, Helena Dorothea Aicher, Berit Singer et al.
A psychedelic formulation combining DMT and harmine impaired convergent thinking, especially in people with higher baseline reasoning, while harmine alone had no such effect. Divergent thinking showed no overall change, though there were trend-level reductions in fluency and elaboration under the combined formulation. In a real-world painting task, both the combined formulation and harmine alone reduced incubation-related transitions, and the combined formulation uniquely decreased transitions from incubation to illumination, suggesting altered pathways to insight. Subjective experiences like altered meaning perception and increased insightfulness predicted divergent, but not convergent, thinking outcomes. The effects of psychedelics on creativity are not uniform and depend on the cognitive stage and individual differences.
Universität Zürich, ZORA
June 19, 2025
Helena Dorothea Aicher, Ilhui Wicki, Daniel Meling et al.
A single dose of an ayahuasca-inspired DMT/harmine formulation increased mindfulness, self-compassion, and compassion toward others in 31 healthy participants one day after treatment, compared with placebo. The effects were larger in participants who reported higher sensitivity to the drug. The findings suggest that such formulations may have therapeutic potential for mood disorders by enhancing mindfulness and compassion, though further studies in clinical settings are needed.
Scientific Reports
April 23, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
No Summary
January 4, 2023
Klemens Egger, Frederik Gudmundsen, Naja Støckel Jessen et al.
preprint
Co-administration of harmine with N,N-dimethyltryptamine (DMT) in rats inhibited the formation of the DMT metabolite indole-3-acetic acid in the brain and increased cerebral availability of DMT, confirming harmine's role in making oral DMT bioavailable. However, no significant occupancy by DMT at serotonin 5-HT2A receptors was detected ex vivo, despite brain DMT concentrations reaching 11.3 µM at moderate doses. Low doses of DMT and/or harmine did not strongly influence brain glucose metabolism measured with [18F]FDG-PET. The results call for further experiments on dose-dependent effects of harmine/DMT on receptor occupancy and cerebral metabolism.