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Milan Scheidegger

Department of Adult Psychiatry and Psychotherapy, Psychiatric University Clinic Zurich and University of Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland; Reconnect Labs, Winterthur, Switzerland. Electronic address: milan.scheidegger@bli.uzh.ch.

36 papers in the library · 1,333 citations · publishing 2014-2026

Papers

Enhancing mindfulness and compassion through an ayahuasca-inspired formulation containing N,N-DMT and harmine: A randomized controlled trial in healthy subjects.

Journal of psychopharmacology (Oxford, England) June 19, 2025 Helena D Aicher, Ilhui A Wicki, Daniel Meling et al. 2 citations

A single dose of an ayahuasca-inspired DMT/harmine formulation increased mindfulness and compassion in 31 healthy participants one day after administration. The randomized, double-blind, placebo-controlled trial found significant effects on mindfulness, self-compassion, and compassion with others, with larger effects in participants who reported higher sensitivity to the drug. These results suggest the formulation may have therapeutic potential for enhancing traits relevant to mood disorders, though further research in clinical settings is needed.

Psychedelic Experiences and the Enactive Approach

The Oxford Handbook of Psychedelic, Religious, Spiritual, and Mystical Experiences May 22, 2024 Daniel Meling, Milan Scheidegger 2 citations

Two competing views on psychedelic experiences—realism, which sees them as revealing a pre-given world, and idealism, which sees them as projections of a pre-given mind—both rely on grasping and representations. An enactive approach offers an alternative that moves beyond these assumptions, emphasizing observer relativity and context dependency without grounding experience in either the world or the self. The chapter argues for this perspective and discusses its implications for understanding the common core of psychedelic experiences, the role of hallucinogens in enactive theory, and the relationship between direct experience and belief.

N, N-Dimethyltryptamine and harmine formulation shifts metastable topography sequences in the cortex

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.

Combined DMT-harmine formulation reduces negative self-referential emotions during social self-evaluation: a randomized placebo-controlled trial in healthy volunteers.

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.

Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [ 18 F]FDG-PET study

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.

Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [18F]FDG-PET study.

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.

Mixed-methods analysis on psychedelic-augmented meditation experiences from a randomized controlled mindfulness retreat

Scientific Reports March 18, 2026 Jonas T. T. Schlomberg, Daniel Meling, Robin Grylka et al.

The acute subjective effects of psychedelics are thought to be key to their therapeutic benefits, but conventional measurement methods may be biased. Using natural language processing to analyze phenomenological interviews from a randomized trial of DMT/harmine versus placebo during meditation in experienced meditators, the study found that meditation under DMT/harmine produced different thematic content and greater experiential diversity than meditation under placebo, though semantic overlap existed. The analysis detected well-known primary effects and subtle language patterns, including frequent use of Buddhist concepts and spiritual jargon regardless of condition. Findings suggest shared features between meditative and psychedelic states, a strong drug-context interconnection, and potential synergistic effects.

The translational potential of salvinorin A: systematic review and meta-analysis of preclinical studies

Universität Zürich, ZORA October 10, 2025 Wolfgang Emanuel Zürrer, Lionel Wettstein, Helena Aicher et al.

Salvinorin A, the main psychoactive compound in Salvia divinorum and a potent kappa opioid receptor agonist, has been tested in animal models of pain, stroke, addiction, and depression. It shows anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects. However, findings on depression are inconsistent, with both antidepressant and depressogenic outcomes reported. Toxicity data indicate anxiogenic effects and motor and cognitive impairment, with minimal impact on vital parameters. Pharmacokinetic data show rapid onset, fast peak, and a half-life of about one hour. Sixteen structurally distinct analogues were identified with potentially improved safety and pharmacokinetic profiles.

Ayahuasca-inspired DMT/harmine formulation alters creative thinking dynamics during artistic creation.

Journal of psychopharmacology (Oxford, England) August 16, 2025 Dila Suay, Helena D Aicher, Berit Singer et al.

A psychedelic formulation combining DMT and harmine, but not harmine alone, impaired convergent thinking—the ability to find a single correct solution—in 30 healthy men, especially those with higher baseline reasoning. Divergent thinking, the generation of many ideas, showed no overall effect but trended toward reduced fluency and elaboration. In a real-world painting task, both DMT/HAR and harmine reduced transitions associated with incubation, and DMT/HAR uniquely decreased the shift from incubation to illumination, indicating altered pathways to insight. Subjective experiences like altered meaning and insightfulness predicted divergent but not convergent thinking. The effects of DMT/HAR on creativity are not uniform, affecting both cognitive performance and the dynamic creative process.

Meditation, Psychedelics, and Brain Connectivity: A Randomised Controlled Resting-State fMRI Study of N,N -Dimethyltryptamine and Harmine in a Meditation Retreat

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.