Translational Psychiatry
November 13, 2025
Bruna Giribaldi Cunha, David Nutt, Marieke Martens et al.
In a double-blind randomized trial, patients with long-standing moderate-to-severe depression received either two doses of 25 mg psilocybin plus daily placebo or two doses of 1 mg psilocybin plus daily escitalopram over six weeks. Both treatments comparably reduced negative bias in recognizing facial emotions, a measure of emotional information processing. However, changes in this bias were not linked to concurrent depression score changes. Only in the escitalopram group did a decrease in misclassifying positive faces as negative correlate with lower depression scores at a one-month follow-up. The findings suggest overlapping cognitive mechanisms between psilocybin and escitalopram, notable given psilocybin's short dosing regimen.
Neuropsychopharmacology
October 31, 2025
Natalie Ertl, Imran Ashraf, Lisa Azizi et al.
LSD and MDMA, two psychoactive drugs being explored for psychiatric use, alter how the striatum—a brain region involved in reward and motivation—communicates with other areas. Using resting-state fMRI data from prior studies, researchers examined striatal connectivity after acute drug administration. Neither drug changed connectivity within the striatum's own networks. However, MDMA reduced connections between the limbic striatum and the amygdala, while LSD increased connections between the associative striatum and frontal, sensorimotor, and visual cortices. These changes occurred mostly outside standard striatal networks, supporting the idea that psychedelics reduce the brain's usual network segregation, potentially explaining their therapeutic and psychological effects.
PsyArXiv
September 30, 2025
Christopher Timmermann, Tommaso Barba, James Sanders et al.
preprint
In an advanced meditator and Lama from the Mahāmudrā tradition, nondual meditation and a low dose (5 mg) of 5-MeO-DMT both produced timelessness, reduced labeling of sensory content, and diminished narrative self and thoughts. Both states showed increased alpha power and decreased gamma power in the brain, with neural overlap driven by posterior and right frontal gamma reductions. Nondual meditation uniquely emphasized recognition of nonduality and clarity of mind, while low-dose 5-MeO-DMT was characterized by visual imagery. High-dose (12 mg) 5-MeO-DMT produced sensory disconnection, seeing a 'white-light', and broad increases in gamma power. The findings suggest two distinct routes to self-dissolution: a 'saturation' route with increased neural firing and entropy (high-dose 5-MeO) and a 'subtractive' route with reduced firing and entropy (nondual meditation and low-dose 5-MeO).
Psychol Med
August 26, 2025
Michael Angyus, Sarah Osborn, Eline Haijen et al.
No Summary
Mol Psychiatry
July 1, 2025
Rebecca Harding, Neomi Singer, Matthew B. Wall et al.
correction
In a study comparing psilocybin therapy (PT) to escitalopram for depression, brain responses to unexpected musical notes were measured. After PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. This suggests PT alters brain processing of unexpected events differently than escitalopram, potentially contributing to its therapeutic effects.
bioRxiv Preprint Server
May 1, 2025
Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al.
preprint
A single psychedelic dose of ketamine (1 mg/kg, intravenous) alters brain chemistry and connectivity in healthy people for at least one to eight days. After the dose, glutamate levels in the anterior cingulate cortex rose significantly. Functional connectivity decreased within high-order networks such as the default mode network, while integration between low- and high-order networks increased. Increases in a PET marker of synaptic plasticity correlated with reduced intrinsic activity in default mode network regions and a diminished influence of the posterior cingulate cortex on global network dynamics. The posterior cingulate cortex appears to be a central hub through which ketamine may reshape brain hierarchies over the long term.
Cureus
January 1, 2025
Sorcha O'Connor, Kate Godfrey, Sara Reed et al.
correction
A protocol describes a planned study testing whether a low-moderate dose of psilocybin (10 mg), combined with non-interventional therapy, can improve cognitive flexibility and neuroplasticity in people with obsessive-compulsive disorder (OCD). Twenty blinded participants will receive an active placebo (1 mg psilocybin) in a first session and 10 mg in a second session four weeks later. Cognitive flexibility will be measured with the intradimensional-extradimensional shift task two days after each session, and neuroplasticity will be assessed via electroencephalography immediately after each session. Secondary outcomes include OCD symptom severity and patient-reported measures. The results are expected to clarify neural mechanisms and guide a future randomized controlled trial.
October 14, 2024
Terence J. Lyons, Merle Spriggs, Leevi Kerkelä et al.
preprint
A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.
Journal of Psychopharmacology
July 14, 2019
Livia Ng, Luca Pani, Anaïs Soula et al.
Claims about the positive effects of microdosing psychedelics on mood and cognition have entered public discussion, but scientific studies are scarce and no consensus on what microdosing means exists. This critique identifies questions future research must answer and offers guidelines, focusing on psilocybin due to its potential clinical approval and short-lasting effects. While anecdotal reports emphasize benefits, the paper concludes that future studies should also investigate potential risks of repeated low-dose administrations. Preclinical and clinical research examining biological measures like heart rate and receptor turnover, as well as cognitive parameters such as memory and attention, is needed to uncover possible negative consequences.
ChemRxiv
Vito Federico Palmisano, Claudio Agnorelli, Andrea Fagiolini et al.
The ability of classic psychedelics to permeate neuronal membranes and reach intracellular 5-HT2A receptors is critical for their therapeutic effects. Using molecular dynamics simulations, this computational study examined how structural modifications to tryptamines affect membrane permeability. Dimethylation of the primary amine group and adding a methoxy group at position 5 increased permeability. In contrast, substitutions at other positions on the indole ring and protonation of the molecules raised the energy barrier at the bilayer center, making the compounds highly impermeable. These findings can guide future drug design to develop psychedelics with enhanced activity.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
March 21, 2026
Claudio Agnorelli, Joseph Peill, Gabriela Sawicka et al.
A single intravenous dose of ketamine (1 mg/kg) in eleven healthy men altered brain chemistry and connectivity days later. Glutamate levels rose in the anterior cingulate cortex (ACC). Functional coupling between the ACC and the dorsolateral prefrontal cortex decreased, while coupling between the ACC and the amygdala increased. Participants whose PET scans indicated increased synaptic plasticity showed reduced intrinsic activity in default mode network (DMN) regions. The findings suggest the DMN is a central hub where ketamine may reshape brain hierarchies, offering clues to its therapeutic mechanisms.
Neuroscience of consciousness
January 1, 2026
James W Sanders, Raphaël Millière, Ema Demšar et al.
The psychedelic compound DMT induces highly immersive experiences that often include encounters with seemingly sentient presences. Using micro-phenomenology, immersion under DMT was characterized as a structured continuum from subtle to gross forms. Twenty-three participants received 20 mg intravenous DMT during fMRI-EEG, followed by detailed interviews. Analysis yielded 125 phenomenological categories describing structural dimensions like sensory faculties, spatial organization, and self-world configuration. Bodily effects typically preceded visual and auditory ones, and perceived presences emerged only after multisensory integration and 3D spatial characteristics had developed, illustrating a hierarchical relationship between subtle and gross immersion. Perceived presences varied widely in sensory modality, semantic complexity, and relational mode, showing immersion as a dynamic, constructive process.
Psychedelic Medicine
December 15, 2025
M. Mehmood, Rebecka Bremler, M. Spriggs et al.
People who experienced more adverse childhood experiences (ACEs) showed greater improvements in mental well-being, reductions in experiential avoidance, and lower trait anxiety after participating in psychedelic ceremonies compared to those with fewer ACEs. Higher ACE scores were also linked to stronger emotional breakthrough and mystical experiences during the psychedelic session. Among individuals with four or more ACEs, those who reported stronger mystical or emotional breakthrough experiences had better well-being at two and four weeks afterward, and mystical experiences were linked to less experiential avoidance while emotional breakthrough was linked to less anxiety at four weeks. However, the acute experiences did not significantly change how ACEs affected mental health outcomes overall.
arXiv Preprint Archive
March 28, 2025
Marcus J. Glennon, Catherine I. V. Bird, Prateek Yadav et al.
Setting up a psychedelic study is a long and complex process that presents unique challenges not yet standardized. This review brings together major UK research teams to formalize these considerations, identify ongoing debates, and provide a practical guide for researchers and policymakers. It addresses challenges to existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. The paper can be read end-to-end or used as a manual with sections for specific needs.
Frontiers in psychiatry
January 1, 2025
Rayyan Raja Zafar, Patrick Kleine, Danielle Kurtin et al.
Only 1.8% of people with substance use disorders receive effective treatment, revealing a gap between neuroscience research and clinical care. This paper argues that addiction neuroscience should shift from a diagnostic focus to a theragnostic framework that uses biomarkers to guide treatment decisions. Integrating fMRI, EEG, and PET biomarkers within psychedelic addiction research offers an opportunity for this change. Psychedelics like psilocybin engage neuroplasticity and reward networks central to addiction. The authors review neuroimaging paradigms for indexing drug effects and propose a roadmap for embedding biomarkers in clinical trials. They outline ongoing work at Imperial College London co-developing biomarkers for gambling and opioid use disorders to identify biotype-specific responses, aiming for regulatory-grade tools similar to those in oncology.
arXiv Preprint Archive
November 29, 2024
Claudio Agnorelli, Meg Spriggs, Kate Godfrey et al.
Psychedelics like LSD and psilocybin can rewire brain connections after just one dose, unlike traditional psychiatric medications. These compounds boost the brain's natural plasticity, helping neurons form new pathways and adapt to change. Studies show they create a window of enhanced learning and adaptation, leading to lasting improvements in mood and behavior.