European Archives of Psychiatry and Clinical Neuroscience
January 12, 2022
Matti Gärtner, Anne Weigand, Milan Scheidegger et al.
13 citations
Ketamine's rapid antidepressant effects involve the glutamatergic system. A multimodal imaging study of 23 healthy volunteers used resting state fMRI and proton magnetic resonance spectroscopy to examine links between metabolic and functional brain changes during intravenous ketamine infusion. The pregenual anterior cingulate cortex (pgACC) was the focus. Functional connectivity changed from the pgACC to the right frontal pole and anterior mid cingulate cortex (aMCC). Absolute glutamate and glutamine concentrations in the pgACC did not differ significantly from baseline. Stronger pgACC activation during ketamine was linked to lower glutamine concentration, and reduced connectivity between pgACC and aMCC was related to increased pgACC activation and reduced glutamine.
CNS drugs
December 1, 2023
Niloufar Pouyan, Farnaz Younesi Sisi, Alireza Kargar et al.
12 citations
A review of 28 clinical studies with 477 participants examined how lysergic acid diethylamide (LSD) affects reward processing, using the National Institute of Mental Health's Research Domain Criteria (RDoC) framework. LSD produced dose-dependent mood improvement in 20 short-term and 3 long-term studies. Its subjective and neural effects were linked to the 5-HT2A receptor. Animal studies suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential enhancements in associative learning. Reward valuation measures indicated possible reductions in effort expenditure for other reinforcers. The review identified areas for future research but noted limitations including diverse study designs not initially RDoC-oriented and potential bias from open-label human studies.
The World Journal of Biological Psychiatry
January 5, 2022
Matti Gärtner, Mischa de Rover, Lena Václavů et al.
11 citations
In patients with Major Depressive Disorder, increased blood flow in the thalamus one day after a single low-dose ketamine infusion is linked to greater improvement in depressive symptoms. Lower thalamus blood flow before treatment predicts both a larger increase in flow after ketamine and stronger symptom reduction. The study used arterial spin labelling, a brain imaging technique that directly measures cerebral blood flow, avoiding the ambiguity of standard BOLD imaging. These findings suggest that measuring regional blood flow could help guide ketamine treatment decisions.
The international journal of neuropsychopharmacology
December 28, 2024
Michael J Mueller, Helena D Aicher, Dario A Dornbierer et al.
10 citations
A new pharmaceutical formulation combining pure DMT and harmine produced ayahuasca-like psychological effects lasting 2-3 hours in 31 healthy male volunteers, with consistent drug levels and no serious adverse events. DMT reached peak plasma concentrations of 22.1 ng/mL, while buccal harmine reached 32.5 ng/mL in a sustained-release profile but caused no distinguishable subjective effects on its own. All drug conditions were safe and well tolerated, suggesting the formulation could reduce risks and improve therapeutic outcomes for mental health disorders.
Journal of Psychoactive Drugs
March 6, 2019
Ansgar Rougemont-Bücking, Henrik Jungaberle, Milan Scheidegger et al.
6 citations
Among 4,475 young adult men in Switzerland, those who used psychedelics in the past year showed no significant difference in mental health (depressive symptoms, overall mental health, perceived stress, life satisfaction) compared to those who used no drugs. In contrast, users of MDMA, psychostimulants, and cannabis had poorer mental health. These effects were influenced by stressful life events and past family functioning. The findings suggest that some men may use substances to cope with life adversity, and the lack of a negative mental health association with psychedelics warrants further research in both men and women.
European Neuropsychopharmacology
September 1, 2015
Katrin H. Preller, Thomas Pokorny, Rainer Krähenmann et al.
6 citations
No Summary
NeuroImage
June 1, 2025
Dila Suay, Helena D Aicher, Micheal Kometer et al.
4 citations
A psychedelic formulation combining DMT and harmine, inspired by ayahuasca, altered brain responses to faces in 30 healthy men. It increased early visual reactivity (P1 wave) and disrupted face-structural encoding (N170 wave) for all face types. Crucially, it reduced the neural distinction between self and other faces in the P300 wave, while familiar-face processing remained stable. Harmine alone did not produce these effects. The findings suggest psychedelics can reorganize self-related neural dynamics, potentially promoting cognitive flexibility and offering therapeutic benefits for conditions involving rigid self-focus, such as depression and social anxiety.
Translational psychiatry
October 10, 2025
Wolfgang Emanuel Zürrer, Lionel Wettstein, Helena D Aicher et al.
3 citations
Salvinorin A, the main psychoactive compound in Salvia divinorum, shows therapeutic potential for pain, addiction, and stroke in animal models, but its side effects—including anxiety, motor and cognitive impairment—may limit clinical use. A systematic review and meta-analysis of 82 studies found anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects, though depression results were inconsistent. Doses ranged from 0.1 to 10 mg/kg, with rapid onset and a half-life of about one hour. Sixteen structurally distinct analogues were identified with potentially improved safety and pharmacokinetic profiles. Findings support further development of analogues to overcome the side effect profile.
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.
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.
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.
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.
Imaging Neurosci (Camb)
September 29, 2025
Klemens Egger, Daniel Meling, Firuze Polat et al.
1 citation
A randomized controlled trial investigated how the psychedelic compounds N,N-dimethyltryptamine (DMT) and harmine, administered during a meditation retreat, affect brain connectivity. Using resting-state fMRI, the study found that these compounds altered functional connectivity in neural networks, particularly in regions associated with self-referential thought and sensory integration. The changes in brain communication patterns were linked to enhanced psychological well-being and mental flexibility, suggesting that combining psychedelics with contemplative practices may promote neuroplasticity and cognitive enhancement. The results indicate that DMT and harmine can reorganize brain networks in ways that support meditative experiences and long-term benefits for brain health.
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.
medRxiv
November 1, 2024
Dila Suay, Helena D. Aicher, Micheal Kometer et al.
1 citation
preprint
A psychedelic formulation combining DMT and harmine, inspired by ayahuasca, blurs the brain's distinction between self and other faces. In a double-blind, placebo-controlled experiment with 31 healthy men, the DMT/harmine combination increased early visual brain responses (P1 amplitude) and disrupted the structural encoding of faces (reduced N170 amplitude) for all face types. It also specifically reduced the brain's later response (P300) to one's own face, making the neural reaction to self-faces more similar to that for familiar or unknown faces. Harmine alone did not produce these effects. The findings suggest psychedelics may reduce attentional focus on self-referential information, potentially explaining feelings of unity and enhanced empathy.
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.
Psychedelics
June 28, 2026
Joost J. Breeksema, Ulf Bremberg, Jens H. van Dalfsen et al.
Psychedelic therapies face layered complexity from interactions between pharmacological and extra-pharmacological factors, and their embeddedness in societal, legal, and regulatory systems. This is compounded by epistemic fragmentation: dominant biomedical paradigms often clash with knowledge from social sciences, humanities, or Indigenous traditions. Though interdisciplinary engagement is increasingly recognized as necessary, existing calls rarely specify structural or pedagogical conditions for operationalizing it. Addressing these complexities requires moving beyond superficial collaboration; genuine interdisciplinary progress needs researchers capable of productive friction across epistemic cultures. The authors propose cultivating T-shaped competencies and intersectoral training as a structural response to these systemic challenges.
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.
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.
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.
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
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.
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.
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.