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.
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.
NeuroImage: Clinical
September 19, 2022
Josua Zimmermann, Nicole Friedli, Francesco Bavato et al.
14 citations
Chronic MDMA users show increased fractional anisotropy in white matter tracts, particularly the corpus callosum and corticospinal tracts, with some links to usage intensity. However, blood neurofilament light chain levels did not differ from controls. The absence of reduced fractional anisotropy and elevated NfL—typically seen in conditions with white matter lesions, such as stimulant and ketamine use disorders—suggests MDMA use is not associated with significant white matter damage. Thus, axonal degradation observed in animal models was not replicated in this human sample of 39 chronic users and 39 matched controls.
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.
Frontiers in Behavioral Neuroscience
December 3, 2021
Michael Colla, Hanne Scheerer, Steffi Weidt et al.
9 citations
Ketamine's rapid antidepressant effects challenge traditional theories that focus on monoaminergic pathways. Current research explores mechanisms including glutamatergic disinhibition, neurotrophic, and neuroplastic effects. Despite extensive study, ketamine has not yet led to new therapies beyond itself, and significant knowledge gaps and study limitations remain.
EClinicalMedicine
February 1, 2023
Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al.
8 citations
correction
A correction was issued for a figure in a clinical trial on psilocybin-assisted therapy for major depressive disorder. The colors representing the Psilocybin and Placebo conditions were swapped in Fig. 2; the correction aligns them with the caption and other figures. The error does not affect the results. The trial found that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to placebo for at least two weeks, with no serious adverse events. Larger, multi-centric trials with longer follow-up are needed to optimize this treatment.
Behavioral sciences (Basel, Switzerland)
August 16, 2024
Judith Rohde, Elena Hickmann, Marco Buchmann et al.
7 citations
A pilot case series tested an eight-week program combining nasally administered ketamine (0.5 mg/kg) with trauma-focused psychotherapy for three individuals with chronic, treatment-resistant PTSD. Clinically relevant reductions in PTSD symptoms were observed, with CAPS-5 scores decreasing by an average of 18 points after treatment and 25 points at follow-up. Depressive symptoms also improved, with HAMD scores dropping by an average of 8.3 points after treatment and 9 points at follow-up. Additional benefits included reduced anxiety, fewer dissociations, and better emotion regulation. The ketamine was well tolerated and provided immediate relief from tension, anxiety, and common PTSD symptoms. The authors note that randomized controlled trials are needed to validate these findings.
bioRxiv (Cold Spring Harbor Laboratory)
September 1, 2019
Joanes Grandjean, David Buehlmann, Michaela Buerge et al.
5 citations
preprint
Psilocybin, a serotonin 2A receptor agonist, alters functional connectivity in the brain's default-mode network, which is involved in self-reference and disrupted in depression. In lightly-anesthetized mice, resting-state fMRI showed psilocybin reduced connectivity within the ventral striatum. Using gene expression maps and viral tracer projections, two distinct effects emerged: psilocybin increased connectivity between serotonin-associated networks and parts of the mouse default-mode network, thalamus, and midbrain, while decreasing connectivity within dopamine-associated striatal networks. These findings suggest that interactions between serotonin- and dopamine-regulated neural networks contribute to psilocybin's neural and psychological effects, and show how molecular and structural connectivity data can clarify pharmaco-fMRI results.
Journal of affective disorders
November 22, 2025
Carlos Trenado, Erich Seifritz, Sebastian Olbrich et al.
4 citations
Frontal EEG recordings before treatment with ketamine or esketamine in 43 people with major depressive disorder revealed that those who later responded to the medication had increased functional connectivity (measured by phase locking value and phase lag index) and decreased entropy (Renyi and Tsallis) compared to non-responders. Aperiodic spectral parameters were lower in responders but did not predict response. These EEG measures showed moderate predictive accuracy, with area under the ROC curve values of 0.7065 for Renyi entropy, 0.7101 for Tsallis entropy, and 0.7283 for phase lag index, suggesting frontal EEG patterns may serve as biomarkers for identifying individuals likely to benefit from (es)ketamine treatment.
bioRxiv Preprint Server
November 1, 2022
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
4 citations
preprint
Ketamine is a promising therapy for treatment-resistant depression, but why some people respond better than others remains unclear. The molecular mechanisms of ketamine are not yet connected to its effects on brain activity and behavior.
Psychiatry research. Neuroimaging
July 1, 2025
Anna Monn, Corinne Eicher, Annia Rüesch et al.
2 citations
A higher percentage of EEG vigilance stage A1, a measure of brain activity, is associated with response to intravenous ketamine in major depression. In a phase-2 randomized controlled trial of oral prolonged-release ketamine for treatment-resistant depression, no significant interaction between response and treatment was found for this EEG marker. However, a small-scale meta-analysis showed a significant pooled mean difference between ketamine responders and non-responders. Applying a previously proposed A1 cutoff of 43% yielded chance-level prediction accuracy in the combined ketamine group but 75% accuracy in the 240 mg subgroup. Responders to 240 mg ketamine also showed more stable vigilance over time. These findings support EEG vigilance as a predictive biomarker for treatment outcomes in depression, though further validation is needed.
bioRxiv Preprint Server
January 28, 2019
Thomas Pokorny, Patricia Duerler, Erich Seifritz et al.
2 citations
preprint
A single dose of LSD (100 µg) impaired executive functions, cognitive flexibility, and spatial working memory in 25 healthy adults, but did not affect decision-making or risk-taking. These cognitive deficits were blocked by pretreatment with the 5-HT2A antagonist ketanserin (40 mg), indicating that the serotonin 2A receptor system is involved in specific cognitive processes. The findings suggest that blocking this receptor might help improve cognitive dysfunctions seen in psychiatric disorders.
Brain
October 19, 2025
Rebecca C. Coray, Vincent Beliveau, Josua Zimmermann et al.
1 citation
Regular recreational use of MDMA (Ecstasy) is linked to verbal memory problems, and this study examined the brain changes underlying these deficits. Comparing 61 MDMA users with 61 matched non-users, the researchers found reduced grey matter volume in hippocampal regions and impaired verbal learning, short-term recall after interference, long-term recall, and recognition in users. Self-reported MDMA use over the past six months correlated with several memory scores. Hippocampal volume, especially in the CA1 subregion, was inversely related to verbal long-term memory and to MDMA use intensity measured by hair concentrations. Differences in grey matter between groups correlated with brain serotonin receptor densities, suggesting a serotonergic basis for the structural and memory changes.
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.
European Neuropsychopharmacology
October 1, 2016
O. Grimm, Rainer Krähenmann, Katrin H. Preller et al.
1 citation
No Summary
European Neuropsychopharmacology
September 25, 2014
Rainer Kraehenmann, Katrin H. Preller, Erich Seifritz et al.
1 citation
This work examines the role of the 5-HT1A receptor in mediating the effects of psilocybin on amygdala reactivity. Psilocybin, a serotonergic psychedelic, acts as an agonist at serotonin receptors, including 5-HT1A and 5-HT2A. The study investigates how activation of the 5-HT1A receptor influences emotional processing and neural activity in the amygdala, a brain region central to fear and emotional responses. Findings suggest that 5-HT1A receptor agonism may modulate psilocybin's impact on amygdala function, potentially contributing to its therapeutic effects in psychiatric conditions.
Psychotherapy and psychosomatics
June 19, 2026
Judith Rohde, Tyler M Moore, Kathryn Walker et al.
A systematic review and individual participant data meta-analysis of 12 studies (533 participants) found that higher baseline PTSD severity was the most robust predictor of symptom reduction after combined ketamine and psychotherapy. More psychotherapy sessions, more ketamine sessions, and shorter treatment duration were also associated with greater improvement, but these findings are tentative because most studies were of poor quality. The analysis showed that for each additional psychotherapy session, PTSD symptoms improved by an average of 1.03 points on the PCL-5, and for each additional ketamine session, improvement was 1.15 points. The results require confirmation in well-designed prospective trials.
December 10, 2025
Johannes Jungwirth, Samuel Westenhöfer, Helena Aicher et al.
In a real-world clinical setting in Switzerland, 19 patients with treatment-resistant depression received one to four doses of psilocybin (20–35 mg). Depression severity, measured by the Montgomery–Åsberg Depression Rating Scale and the Beck Depression Inventory II, showed significant and clinically meaningful reductions from before to after treatment. Response rates were 33.3% and remission rates 22.2% on one scale; on the other, both were 27.8%. No serious adverse events occurred, and multiple dosing did not add benefit. These response and remission rates are lower than those seen in earlier controlled trials, but the findings provide some of the first real-world evidence for psilocybin's antidepressant effects.
Scientific Reports
April 23, 2024
Berit Singer, Daniel Meling, Matthias Hirsch-Hoffmann et al.
No Summary
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.