EClinicalMedicine
February 1, 2023
Robin von Rotz, Eva M Schindowski, Johannes Jungwirth et al.
345 citations
A single, moderate dose of psilocybin (0.215 mg/kg body weight) significantly reduced depressive symptoms compared to placebo in adults with major depressive disorder. Over two weeks, depression severity scores dropped by 13.0 points on the MADRS and 13.2 points on the BDI in the psilocybin group, with improvements significantly larger than in the placebo group. 54% of participants receiving psilocybin met remission criteria. No serious adverse events occurred. The findings suggest psilocybin offers rapid antidepressant effects, though larger, longer-term trials are needed.
EClinicalMedicine
March 14, 2025
Raoul Bitar, Simon Halm, Christina Rossgoderer et al.
42 citations
A randomized controlled trial investigated whether psilocybin-assisted therapy could reduce relapse in patients with alcohol use disorder. The study compared psilocybin therapy against a control condition, finding that the psilocybin group showed a significantly lower rate of heavy drinking days over the follow-up period. The results suggest that psilocybin, when combined with psychotherapy, may be a promising intervention for relapse prevention in alcohol dependence, though further research is needed to confirm these findings.
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.
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.
Scientific Reports
October 14, 2023
Nathalie M. Rieser, Ladina P Gubser, Flora Moujaes et al.
14 citations
Psilocybin alters cerebral blood flow in the brain, and the magnitude of these changes depends on individual baseline psychological and neurobiological characteristics. In a placebo-controlled study of 70 healthy participants given one of three oral doses of psilocybin, reductions in relative cerebral blood flow correlated with both baseline traits and the intensity of the subjective psychedelic experience. The findings demonstrate that inter-individual heterogeneity in the neural response to psilocybin is linked to pre-existing differences, helping to identify biomarkers for a personalized medicine approach in psychedelic-assisted therapy.
Psychedelic Medicine
January 20, 2025
Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al.
9 citations
Psilocybin and other serotonergic psychedelics are used in research settings with safety measures including controlled environments, staff presence, screening, and psychoeducation. An analysis of study materials from psilocybin trials over the past two decades found that psychoeducation documents varied but commonly emphasized biological and physical safety, psychological safety and well-being, aspects of setting, and the potential for expectancies. The materials prioritized biological and psychological safety across all sites. The authors also identified elements unrelated to safety that may contribute to participant expectancies and suggest these extrapharmacological factors be studied systematically to maximize safety while minimizing extraneous expectancies.
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.
Trends in Cognitive Sciences
August 18, 2025
Flora Moujaes, Nathalie M. Rieser, L. Belinger et al.
5 citations
Serotonergic psychedelics are being investigated as treatments for psychiatric conditions, with promising results in mood disorders suggesting their effects on emotional processing may be central to therapeutic potential. However, mechanistic and clinical studies reveal a complex picture of how psychedelics impact emotions and mood. This review covers recent findings on psychedelics' effects on emotion, emotional empathy, and mood, discussing their influence on long-term emotion management strategies, the role of challenging experiences, and neuroplastic changes. The authors argue that more precise characterization of emotional states and attention to temporal dynamics of psychedelic-induced effects are critical for clarifying mechanisms and optimizing therapeutic impact.
Current Topics in Behavioral Neurosciences
July 31, 2024
Nathalie M. Rieser, Timo T Schmidt, Katrin H. Preller
5 citations
This chapter reviews current knowledge on the neural mechanisms of psychedelic drugs, focusing on human neuroimaging studies. It covers acute and subacute adverse effects and how these may inform psychiatric illness pathophysiology. The chapter examines EEG, fMRI, and PET findings, along with pre- to postdrug changes. Prevailing models discussed include the Cortico-Striato-Thalamo-Cortical feedback loop, the entropic brain hypothesis, the REBUS principle, and the claustrum hypothesis. Neural correlates of visual effects, social and emotional impacts, and ego dissolution are explored. Speculations on how acute effects relate to rare long-term adverse effects are offered, though data scarcity makes these tentative.
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.
Translational Psychiatry
May 26, 2026
Marvin M. Urban, Lea Zillich, Nathalie M. Rieser et al.
1 citation
In a pilot study of 37 detoxified patients with alcohol use disorder, psilocybin (25 mg) produced changes in DNA methylation across the genome compared to placebo. One methylation site in the TLE4 gene and a differentially methylated region in RASGRP4 were linked to psilocybin treatment. Co-methylation networks related to psilocybin were associated with reductions in depressive symptoms and drinking behavior, and gene analysis pointed to involvement in neuroplasticity and immune functions. The primary trial endpoints—duration of abstinence and mean alcohol use—were not reached, so the analysis focused on secondary psychometrics. The findings suggest immunomodulatory actions of psilocybin but are limited by the modest sample size.
Brain and Behavior
July 1, 2026
Lena K L Oestreich, Nathalie M. Rieser
Psychedelic and substance-assisted therapies show promise for mental health disorders like treatment-resistant depression, PTSD, and substance use disorders, but major questions remain as the field moves toward clinical implementation. This editorial introduces a special issue that brings together empirical studies, reviews, and commentaries on these emerging priorities. A central theme is that psychedelic therapy cannot be understood as a pharmacological intervention alone; therapeutic relationships, preparation, integration, music, touch, peer support, cultural context, and patient expectations all shape outcomes. Subjective meaning-making and altered states are potentially central to therapeutic change. Implementation challenges include models of care for veterans, global mental health equity, and culturally responsive access. The field requires greater conceptual precision, attention to safety and consent, and frameworks prioritizing equity and cultural appropriateness.
medRxiv
August 28, 2025
Franziska Stadler, Johan Saelens, Ioline D. Henter et al.
preprint
An international online study of 759 people examined how psychedelic drug use affects cognitive performance and mental health in the short and long term. Participants completed tasks measuring working memory, selective attention, and visual/spatial perception, plus questionnaires on mental health and quality of life. Recent users showed significantly lower accuracy on all cognitive tasks and reported more depressive and dissociative symptoms. Lifetime users had the highest task accuracy without slower reaction times, and their use was not linked to long-term cognitive decline. However, lifetime users scored lower on psychological and social quality of life domains, suggesting possible long-term psychosocial effects.
July 18, 2025
Marvin M. Urban, Eric Zillich, Nathalie M. Rieser et al.
preprint
A single dose of psilocybin (25 mg) was associated with changes in DNA methylation in patients with alcohol use disorder. One methylation site in the TLE4 gene and a region in the RASGRP4 gene showed significant alterations. Co-methylation networks linked to psilocybin treatment were also associated with reduced depressive symptoms and drinking behavior, and involved genes related to neuroplasticity and immune function. Baseline methylation differences between treatment responders and non-responders appeared in genes related to synaptic plasticity and neurotransmitter systems. The findings are preliminary due to the small sample size but align with prior research and suggest possible biological pathways for psilocybin's therapeutic effects.