Pharmacology, biochemistry, and behavior
June 30, 2026
Lucie Ladislavová, Viera Kútná, Kristýna Mazochová et al.
Chronic microdosing of psilocin (0.05 or 0.075 mg/kg) in adult male Wistar rats over five weeks did not alter locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase cell proliferation in the dentate gyrus of the hippocampus. A small anxiogenic effect was detected in the Elevated Plus Maze. The findings suggest that, under this dosing schedule, psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation.
Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater
June 30, 2026
Cielo A Estela-Fernandez, Reem Mohamed Yousif Elsheikh, Dal Bianco Beatrice et al.
Psychedelics show significant potential for treatment-resistant depression (TRD) by promoting neuroplasticity, corticolimbic function, and epigenetic changes beyond serotonergic agonism. Psilocybin-assisted therapy induces short-term symptom improvement lasting weeks to months. Ketamine, in intravenous, subcutaneous, and oral forms, produces rapid and robust reductions in depressive symptoms and relapses without impairing cognitive function. Esketamine yields early, clinically meaningful improvements in function and productivity. Ayahuasca demonstrates fast and sustained effects with higher remission rates and good safety. Despite encouraging findings, large, well-designed studies are needed before psychedelics become standard recommendations for TRD.
Journal of Psychopharmacology
June 28, 2026
Yiğit Özaydın, Buket Canlan Ozaydin
An umbrella review of systematic reviews and meta-analyses on psychedelic microdosing (repeated low doses of LSD or psilocybin) for mood and cognitive effects found that the only statistically significant pooled result was a small decrease in cognitive control, contrary to popular claims of enhancement. Self-reported mood benefits were largely not replicated under placebo-controlled conditions, suggesting expectancy effects. Short-term tolerability was acceptable, but cardiovascular signals and long-term risks remain uncharacterized. The evidence base is limited by high overlap among primary studies and methodological heterogeneity.
J Psychopharmacol
June 28, 2026
In a mouse model of posttraumatic stress disorder, a single dose of psilocybin reduced fear responses to a conditioned cue measured 1, 6, and 7 days later. Psilocybin also reversed the fear conditioning-induced reductions in neuroplasticity in the hippocampus and medial prefrontal cortex, increasing dendritic branches and spine density, upregulating GluR1 and synapsin-1, enhancing brain-derived neurotrophic factor and mammalian target of rapamycin signaling, and promoting neurogenesis. These results suggest that psilocybin may have therapeutic potential for PTSD and other disorders involving fear memory by restoring neuroplasticity in these brain regions.
The Brown University Psychopharmacology Update
June 28, 2026
Repeated high doses of psilocybin reduced obsessive-compulsive disorder symptoms more effectively than low doses or placebo in a Phase 1 trial with 15 patients. Psilocybin was generally well-tolerated, with no serious adverse events reported.
bioRxiv (Cold Spring Harbor Laboratory)
June 26, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Robin Carhart‐Harris et al.
A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual.
Open MIND
June 26, 2026
Max Courtney
Substance use disorders remain a major public health challenge, and existing treatments often have limited long-term success. Psilocybin-assisted therapy (PAT) has recently attracted renewed research interest as a potential treatment for addictions including alcohol, tobacco, and opioids. Most prior studies have been observational or non-randomized, but the number of randomized controlled trials (RCTs) has grown rapidly. This systematic review will examine only RCTs to evaluate the safety, efficacy, and blinding integrity of PAT for substance use disorders. It will assess changes in substance use, adverse events, and how well double-blinding works given psilocybin's strong psychoactive effects. A narrative synthesis is planned, organized by substance type, safety outcomes, and blinding, using the SWiM reporting guideline.
Journal of psychopharmacology (Oxford, England)
June 25, 2026
Pavan S Brar, Rebecca B Price, Stephen Ross et al.
Psychedelic compounds like psilocybin and LSD are being studied again as potential treatments, but research usually excludes people at risk for psychosis. This narrative review examines the historical and theoretical links between psychedelics and schizophrenia spectrum disorders (SSDs), including the psychotomimetic hypothesis. The authors compare the phenomenological experiences induced by psychedelics with those of SSDs, finding both overlap and important qualitative differences that challenge a simple equivalence. They review neural mechanisms involving serotonin, dopamine, and glutamate. Clinical evidence shows psychedelics can worsen existing psychotic illness and may trigger psychosis in vulnerable individuals, though the risk magnitude is not well quantified. The authors suggest potential therapeutic applications for carefully selected symptoms in stable patients using low-dose, controlled approaches and provide recommendations for managing psychosis-related risk.
International Journal of Innovative Technologies in Social Science
June 24, 2026
Aleksandra Łoś, Kacper Szkodziński, Inga Jakubczyk et al.
Depressive disorders affect up to 16% of the population over a lifetime and are a leading cause of disability. For 20–50% of patients, standard treatments fail, leading to treatment-resistant depression (TRD). A review of studies on psilocybin-assisted therapy (PAT) for major depressive disorder (MDD) and TRD found that PAT offers a faster onset of action than traditional antidepressants, with symptom reduction often occurring within the first week and lasting 6–12 months. Many patients also improved in anhedonia, anxiety, and psychosocial functioning. Psilocybin represents a promising alternative for severe depression and TRD, with rapid and lasting effects.
Journal of Psychopharmacology
June 23, 2026
Lenka Seillier, Alexandre Seillier, Morgan A. Zvolska et al.
Psilocybin produces rapid and sustained antidepressant-like effects in rats, as measured by reduced immobility and increased climbing in the forced swim test. Blocking the 5-HT2B receptor with the antagonist RS-127445 dose-dependently reversed these behavioral effects, indicating that 5-HT2B receptors are necessary for psilocybin's antidepressant-like activity. However, the same antagonist did not affect psilocybin-induced head-twitch responses, a proxy for psychedelic effects, suggesting that the antidepressant-like and psychedelic effects of psilocybin can be dissociated via different serotonin receptor subtypes.
Monash University
June 23, 2026
Sheida Shadani
Psilocybin, the active ingredient in magic mushrooms, alters social behavior differently in male and female mice, with effects changing over time. Female mice became more social and showed increased brain reward signals, while males displayed reduced stress behaviors and dampened brain responses. Psilocybin also affected inflammation differently depending on whether mice were exercising. These findings highlight that males and females respond very differently to psilocybin, which is crucial for developing treatments for anorexia nervosa, a condition affecting primarily women where current medications are limited.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Agnieszka Bysiek, Izabela Szpręgiel, Adam Wojtas et al.
Two doses of psilocybin (0.6 mg/kg, given subcutaneously seven days apart) reversed anhedonia, produced antidepressant-like effects in the forced swim test, and reduced anxiety in the light/dark box, elevated plus maze, and open field tests in rats exposed to chronic unpredictable mild stress. Psilocybin also increased hippocampal neurogenesis, shown by higher numbers of BrdU-positive, DCX-positive, and Ki-67-positive cells in stressed animals. Stress-induced reductions in brain-derived neurotrophic factor (BDNF) expression appeared linked to normalization of hypothalamic-pituitary-adrenal (HPA) axis activity. The findings highlight psilocybin-induced neuroplasticity as a key mechanism for its antidepressant and anxiolytic effects.
Research Square
June 19, 2026
Aline Frick, Grace Blest‐hopley, Manesh Grin et al.
In a reanalysis of a six-week randomized controlled trial comparing psilocybin with escitalopram for moderate-to-severe major depressive disorder, sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men, while women receiving escitalopram showed greater reductions in anhedonia than men. For other depressive symptoms, thought suppression, and well-being, sex differences were small and uncertain. Sexual dysfunction severity was lower overall in the psilocybin group than in the escitalopram group and lower in women than in men, though the treatment-by-sex interaction was not significant. These preliminary findings suggest that responses to these serotonergic treatments may differ between women and men, supporting the need for adequately powered, sex-balanced trials.
Annals of Medicine and Surgery
June 18, 2026
Astrit Sabani, Adnan Khatak
Psilocybin-assisted therapy shows promise for treatment-resistant depression (TRD), defined as depression persisting after at least two adequate antidepressant trials. Early randomized trials report rapid symptom reduction and encouraging short-term remission, primarily in major depressive disorder, with limited evidence in TRD populations. However, key questions remain: whether benefits last beyond several weeks, the safety of repeated dosing, and comparisons with established treatments like esketamine, electroconvulsive therapy, and transcranial magnetic stimulation. Current evidence is limited by small samples, short follow-up, blinding challenges, and few active comparators. Implementation requires substantial therapeutic infrastructure, raising concerns about scalability, cost, and equitable access. Future research needs standardized definitions, longer outcomes, rigorous comparators, and cost-effectiveness analyses.
bioRxiv : the preprint server for biology
June 18, 2026
Jacob J Baker, Emily Kogan, Shaorong Ma et al.
Psilocybin promotes the formation and maturation of synapses while accelerating the elimination of pre-existing synapses. Signaling through serotonin 2A receptors in cortical layer 5 pyramidal neurons is necessary and sufficient for this synaptic remodeling but is not required for the head-twitch response, a rodent proxy for hallucination.