Frontiers in pharmacology
January 1, 2023
Dario A Dornbierer, Laurenz Marten, Jovin Mueller et al.
32 citations
Ayahuasca, an Amazonian plant medicine containing DMT and harmine, shows promise for mental health disorders but its oral use causes gastrointestinal side effects and unpredictable drug levels. This study tested new ayahuasca-analogue formulations in 10 healthy men: an oral capsule of purified DMT and harmine versus a combined oromucosal harmine tablet with intranasal DMT spray. The combined buccal/intranasal route significantly reduced variations in systemic exposure and attenuated common side effects like nausea, vomiting, and diarrhea compared to traditional oral ayahuasca. All preparations were well tolerated. This approach may enable safer, patient-friendly DMT/harmine administration for affective disorders.
Clinical Neurophysiology
March 14, 2021
Torsten M. Meyer, Martin Brunovský, Jiřı́ Horáček et al.
25 citations
In patients with major depressive disorder, heart rate and heart rate variability measured before and during ketamine infusion can predict who will respond to treatment. Among 51 patients, those who responded to ketamine had a higher heart rate throughout the study, including at baseline, compared to non-responders. Ketamine infusion increased both heart rate and heart rate variability power during and after infusion. Heart rate and heart rate variability power, but not normalized frequency bands, discriminated between responders and non-responders. These findings suggest that autonomic nervous system markers may help optimize treatment selection for major depressive disorder.
eLife
April 17, 2024
Flora Moujaes, Jie Lisa Ji, Masih Rahmati et al.
23 citations
Ketamine is a promising treatment for treatment-resistant depression, but why people respond differently is poorly understood. In a single-blind placebo-controlled study, 40 healthy participants received acute ketamine. Using data-driven global brain connectivity, the neural and behavioral effects of ketamine were found to be multi-dimensional, reflecting robust inter-individual variability. Ketamine's principal neural gradient matched somatostatin and parvalbumin cortical gene expression patterns, while the mean effect did not. Behavioral symptom variation mapped onto distinct neural gradients resolvable at the single-subject level. These results highlight the importance of individual variation for developing precise pharmacological biomarkers in psychiatry.
The International Journal of Neuropsychopharmacology
August 10, 2022
Anne Weigand, Matti Gärtner, Milan Scheidegger et al.
22 citations
Activity in the pregenual anterior cingulate cortex (pgACC) during emotional stimulation can predict how well a single intravenous infusion of ketamine will relieve depression symptoms in people with major depressive disorder. In 24 patients, pgACC activity was linked to an increase in glutamate in the same brain region 24 hours after the infusion, and this glutamate increase was associated with greater symptom improvement. The findings suggest pgACC activity may serve as a neuroimaging biomarker for early treatment response to ketamine.
European Neuropsychopharmacology
March 8, 2017
Oliver G. Bosch, Michael M. Havranek, A Baumberger et al.
22 citations
Gamma-hydroxybutyrate (GHB), a drug used for narcolepsy and abused recreationally, has prosexual effects in healthy men. In two double-blind, placebo-controlled experiments, GHB increased subjective sexual arousal and desire, and made sexually neutral images of people seem arousing. Brain scans showed that GHB boosted activity in reward regions like the nucleus accumbens when viewing erotic pictures, and increased connectivity between the nucleus accumbens and the ventromedial prefrontal cortex. The findings indicate GHB enhances hedonic sexual functioning and lowers the threshold for perceiving erotic cues by sensitizing mesolimbic reward pathways.
Biological Psychiatry Cognitive Neuroscience and Neuroimaging
July 17, 2023
Flora Moujaes, Nathalie M. Rieser, Christophe Phillips et al.
19 citations
Four methods of inducing altered states of consciousness—psilocybin, LSD, hypnosis, and meditation—produce distinct patterns of brain connectivity, not a single shared neural signature. Pharmacological and nonpharmacological interventions showed connectivity patterns that could predict which method a person had used. Hypnosis and meditation differed from each other and from the drugs. Psilocybin and LSD did not differ in brain connectivity but showed different relationships between brain activity and behavior. The findings clarify how each method works in the brain and suggest they may offer different therapeutic avenues for psychiatric disorders.
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.
Schizophrenia Bulletin
October 8, 2019
Julian Rössler, Wulf Rössler, Erich Seifritz et al.
16 citations
Dopamine reduces functional connectivity between the right anterior insula, a central hub of the salience network, and the left auditory cortex planum polare. In healthy men given a placebo, higher psychotic-like experiences correlated with weaker connectivity between these regions; in those given L-DOPA, higher psychotic-like experiences correlated with stronger connectivity. The score on a measure of psychotic-like experiences explained about 30% of the variation in connectivity between the two groups. These results suggest that psychotic-like experiences are linked to dopamine-induced disruption of auditory input to the salience network, potentially leading to aberrant attribution of salience.
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.
Frontiers in Human Neuroscience
December 19, 2023
Nuno M.p. de Matos, Philipp Staempfli, Erich Seifritz et al.
8 citations
Hypnosis alters functional connectivity in brain networks involving parieto-occipital-temporal areas, cuneal/precuneal and occipital cortices, lingual gyri, and the occipital pole. Comparing two hypnotic states revealed depth-dependent connectivity changes in left superior temporal/supramarginal gyri, cuneus, planum temporale, and lingual gyri. Respiration rate slowed significantly during hypnosis. These findings provide insights into the neurobiology of altered consciousness.
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.
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.
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
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