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 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 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.
Translational Psychiatry
May 21, 2026
Francesco Bavato, Andrea E. Steuer, Anna M. Jacobsen et al.
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct alterations in blood levels of tryptophan-related metabolites, which may help explain their different clinical effects. In a study of 36 chronic MDMA users, 33 chronic METH users, and 71 healthy controls, METH use was linked to depleted serum tryptophan and serotonin and broad activation of kynurenine pathways, whereas MDMA use was associated with selective activation of the OH-kynurenine branch. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that persistent changes in peripheral tryptophan metabolism may contribute to the substances' contrasting addiction and psychiatric profiles.
Brain
May 15, 2026
Boris B. Quednow, Rebecca C Coray
The authors argue that the consequences of MDMA use cannot be easily separated from the effects of other drug use or lifestyle factors, highlighting the difficulty in attributing specific outcomes solely to MDMA.
Neuroscience and Biobehavioral Reviews
April 1, 2026
Yanfang Xia, Boris B. Quednow, Dominik R Bach
A systematic review of 100 publications found that 36 pharmacological compounds have been tested for their effects on aversive memory in healthy humans. The most studied drugs were hydrocortisone, propranolol, and D-cycloserine. Solid evidence supports propranolol's impact on memory reconsolidation, while weak evidence suggests effects of several compounds on memory encoding, consolidation, or extinction. Fifteen compounds showed significant effects in single studies without replication. The review highlights the need for greater comparability across studies.
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.
bioRxiv Preprint Server
August 25, 2025
Francesco Bavato, Andrea E. Steuer, Anna M. Jacobsen et al.
preprint
Chronic users of methamphetamine (METH) and MDMA (Ecstasy) show distinct changes in blood metabolites derived from tryptophan, a building block for serotonin and other signaling molecules. METH use was linked to lower serotonin levels and broad activation of the kynurenine pathway, while MDMA use was associated with a specific increase in a different branch of that pathway. These metabolite changes correlated with the severity of depression and psychosis symptoms. The findings suggest that lasting alterations in tryptophan metabolism may help explain the different clinical effects of the two drugs and could point to new therapeutic targets.
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.
BMJ Open
July 16, 2025
Golo Kronenberg, Anna Bankwitz, Barbora Provaznikova et al.
Nitrous oxide (N2O) may offer rapid antisuicidal effects across mental health conditions, with its pharmacological action thought to involve NMDA antagonism and opioid effects. This protocol describes a single-centre pilot study of 85 psychiatric inpatients. In a double-blind, randomized, placebo-controlled design, the first 45-minute inhalation session delivers either 50% N2O with 50% oxygen or 50% oxygen plus air. Suicidal ideation is measured by the Beck Scale for Suicidal Ideation before and after inhalation. A second N2O inhalation one week later ensures all participants receive active treatment. A nested biomarker substudy using hair, blood, and EEG will explore mechanisms and prediction.