June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Mihai Avram, Felix Müller, Katrin H Preller et al.
13 citations
In a double-blind, placebo-controlled, crossover study with 25 healthy participants, LSD, MDMA, and d-amphetamine all increased effective connectivity from the thalamus to specific unimodal cortices while reducing the influence of those cortices back onto the thalamus, indicating stronger bottom-up and weaker top-down information flow. For transmodal cortices, including parts of the salience network, amphetamines showed opposite effects. LSD uniquely increased effective connectivity from the thalamus to both unimodal and transmodal cortices, suggesting a breakdown in the hierarchical organization of brain activity. These findings refine models of how psychedelics alter brain connectivity.
Psychiatry Research
January 29, 2025
Felix Müller, Thomas Sauer, Corina Hänny et al.
11 citations
A 60-year-old man with recurrent depression and a history of delusions died after psilocybin-assisted therapy. Psilocybin-triggered delusions and emotional dysregulation may have contributed to the death. A weak therapeutic alliance hindered assessment of the patient's internal state. Delusional symptoms may contraindicate psychedelic interventions. The case emphasizes the need for thorough assessment and close follow-up in complex cases.
JAMA network open
January 2, 2026
Gianluca Andri Florineth, Isabell Klima, Anna Laura Boeker et al.
5 citations
In a systematic review and meta-analysis of 12 controlled clinical trials involving 733 adults with depressive symptoms, psychedelic-assisted therapy (PAT) with psilocybin or LSD produced a large overall reduction in depressive symptoms compared to control conditions. More hours of preparation therapy before the psychedelic session were significantly linked to greater symptom reduction. However, the number of post-dosing integration therapy hours, total therapy sessions, and longer follow-up periods were not associated with better outcomes. Most studies had high risk of bias due to ineffective blinding. The findings suggest that preparation therapy may be a key component in optimizing PAT outcomes, but further research is needed.
Current topics in behavioral neurosciences
July 31, 2024
Friederike Holze, Matthias E. Liechti, Felix Müller
4 citations
Psychedelics, including phenethylamines (e.g., mescaline), tryptamines (e.g., psilocybin), and ergolines (e.g., LSD), bind to the serotonin 5-HT2A receptor, causing profound alterations in sensation, cognition, emotions, and self-perception. While generally considered physiologically safe compared to other recreational drugs, they carry risks of lasting psychological adverse reactions such as persisting anxiety, dissociation, or flashbacks. This chapter provides a comprehensive overview of their pharmacology, origins, psychological and autonomic effects, interactions, risks, dosing, and consumption methods, distinguishing them from other psychoactive drugs like MDMA and ketamine based on distinct receptor profiles.
Cell Reports Medicine
May 7, 2026
Mihai Avram, Aurore Menegaux, Felix Müller et al.
1 citation
Lysergic acid diethylamide (LSD) may alleviate depression by altering white matter microstructure in the brain, potentially reflecting enhanced neuroplasticity. In a clinical trial of 61 patients with major depressive disorder, those receiving moderate-to-high doses (100 μg then 200 μg) showed increased fractional anisotropy in several white matter tracts, including the internal and external capsule, sagittal stratum, and fornix/stria terminalis. These microstructural changes correlated with improvements in depressive symptoms measured at 2, 6, and 12 weeks. The findings suggest that LSD-induced white matter changes are linked to antidepressant effects.
Psychedelics as Psychiatric Medications
March 1, 2023
Mihai Avram, Felix Müller, Stefan Borgwardt
1 citation
Lysergic acid diethylamide (LSD) is a potent perception-altering chemical that has been both revered and demonized since its discovery. Before its ban in the late 1960s, it was used to model aspects of psychosis and treat alcohol addiction and anxiety. Recent clinical trials show LSD can be administered safely in clinical settings to healthy volunteers and clinical groups. Small studies suggest potential therapeutic uses for anxiety. LSD's perception-altering effects involve agonism at the 5-HT2A receptor. Neuroimaging reveals LSD enhances signal diversity and complexity, decreases resting-state connectivity within intrinsic brain networks, and increases between-network connectivity, including thalamocortical connectivity.
Neuroscience and biobehavioral reviews
July 1, 2022
Drummond E-Wen Mcculloch, Gitte Moos Knudsen, Frederick Streeter Barrett et al.
A large group of psychedelic imaging researchers reviewed 42 articles from 17 unique studies that used resting-state functional magnetic resonance imaging (rs-fMRI) to examine psychedelic effects. They found that nearly all studies varied in data processing and analysis methods, two datasets underpin over half of the published literature, and key outcome terms are used ambiguously. The authors recommend guidelines to improve consistency and replicability in future research, arguing that the field must balance novel methods with standardized approaches to reliably understand the neural mechanisms of psychedelics.