Behavioral sciences (Basel, Switzerland)
April 30, 2026
Dylan Briggs, Thomas B Sease, Ruthie Menou et al.
Mystical experiences—marked by a sense of interconnectedness and transcendence—are linked to lasting positive changes in thoughts, emotions, and behavior. In a sample of 150 adults recruited online, researchers used a machine-learning technique (elastic net regression) to examine how four facets of psychological flexibility (experiential acceptance, present-moment awareness, cognitive defusion, and self-as-context) relate to self-reported mystical experiences, while also accounting for state of surrender, frequency of psychedelic use, and near-death experiences. State of Surrender, experiential acceptance, cognitive defusion, and present-moment awareness were the strongest predictors. The findings suggest that surrender-related processes and psychological flexibility play a key role in predicting mystical experiences.
Psychopharmacology
April 29, 2026
Anne-Fiona Griesfeller, Lotte Kooman, Lilian Kloft-Heller et al.
A scoping review of 53 sources found no coherent explanation for how psychedelics might recover repressed memories, nor consistent evidence that they do so reliably. Most publications focused on LSD, but few defined what they meant by repressed memory. Proposed mechanisms—psychoanalytical reductions of defensive memory blockades and neurobiological alterations of executive control—lacked empirical support. The review concludes that future work should provide clear definitions, test effects across multiple psychedelic substances, use placebo-controlled designs, and account for the potential occurrence of false memories.
medRxiv Preprint Server
April 28, 2026
Sandeep M. Nayak, Nathan D. Sepeda, Matthew Nielsen Dick et al.
preprint
Psilocybin is being studied as a treatment for psychiatric and neurologic conditions, but there is limited comprehensive data on its cardiovascular safety. Current clinical trials typically exclude people with blood pressure of 140/90 mmHg or higher, a cutoff set conservatively without strong empirical evidence.
Current neuropharmacology
April 28, 2026
Hongshuang Wang, Xiaobing Li, Feng Yu et al.
Combining psychedelics with music in therapy may improve mental health outcomes by acting on specific brain mechanisms. Psychedelics like psilocybin activate 5-HT2A receptors and BDNF-TrkB signaling, increase neural plasticity, and desynchronize the default mode network, while music guides emotional processing and amplifies psychological insights. This synergy shows promise for treating depression, PTSD, and addiction. The review provides a mechanistic framework for understanding these interactions and identifies neurobiological targets for optimizing future therapeutic protocols.
Journal of medical Internet research
April 27, 2026
Karilynn M Rockhill, Elizabeth A Bemis, Nicole Schow et al.
2 citations
Combining a large representative survey with a smaller survey focused on psychedelic drugs can produce generalizable estimates of rare behaviors like drug use without adding burdensome questions to the big survey. Researchers used calibration weighting to transport estimates from a psychedelic-enriched survey (two waves, total over 4,300 adults) to a representative anchor survey (two waves, total over 57,000 adults). The method showed good internal consistency, with transport biases under 0.4 percentage points for demographics, health, and substance use. External validity improved for health and substance use estimates after fusion. Using the fused data, recreational use of psilocybin (92.9%), LSD (93.2%), and MDMA (93.3%) was far more common than medical use (30.9%, 26.4%, and 21.1%, respectively). This approach expands surveillance epidemiology for rare behaviors.
Trends in psychiatry and psychotherapy
April 25, 2026
Alberto Barbieri
Personality disorders involve rigid, maladaptive patterns of thinking and relating to others, which are hard to treat. Schema therapy, which targets early maladaptive schemas formed from unmet emotional needs, shows moderate effectiveness mainly for borderline personality disorder. Psilocybin, a psychedelic, may relax deeply held beliefs and increase cognitive flexibility, according to predictive coding models. This theoretical article proposes combining psilocybin with schema therapy—called Psilocybin-Assisted Schema Therapy (PAST)—to help patients revise maladaptive self-beliefs and improve treatment outcomes for Cluster B and C personality disorders. The framework awaits empirical testing.
Communications biology
April 24, 2026
Tatum Askey, Daniel Allen-Ross, Daniil Luzyanin et al.
A single dose of psilocybin produces a sustained anti-nociceptive effect in chronic neuropathic pain models in male and female mice, mediated primarily by 5-HT2A receptors. Psilocybin significantly potentiates the analgesic efficacy of gabapentin, a standard-of-care treatment, representing the first preclinical evidence that a psychedelic can serve as a pain-network primer for existing analgesics. This finding suggests a novel therapeutic strategy, particularly for the 30-50% of neuropathic pain patients who fail gabapentin monotherapy. The data demonstrate that a single psilocybin injection produces sustained month-long changes that enhance gabapentin efficacy in a preclinical model.
AJNR. American journal of neuroradiology
April 24, 2026
Joga Chaganti, Krista J Siefried, Veda S Vyakaranam et al.
In individuals with methamphetamine use disorder, psilocybin administration alongside psychotherapy led to measurable reorganization of large-scale brain networks and local neural synchrony. After the intervention, connectivity within and between attentional, default mode, and salience networks shifted significantly, and local synchrony increased in frontal and sensorimotor regions. Greater reductions in methamphetamine use correlated with recovery of frontostriatal and attentional connectivity, while reduced psychological distress was linked to strengthened integration of attentional and prefrontal-striatal circuits. These findings suggest psilocybin may promote network-level plasticity in stimulant addiction and support the potential of resting-state fMRI metrics as biomarkers of such change.
Research square
April 23, 2026
Leah M Salinsky, Joshua L Fox, Kyra C Diaz et al.
Withdrawal from repeated use of methamphetamine and fentanyl together reduces social preference in rats, confirming earlier findings that polysubstance withdrawal impairs social behavior. A single dose of psilocybin did not restore sociability within 24 hours. In the medial prefrontal cortex, psilocybin had opposite effects on CRHR1 gene expression depending on drug history: it decreased expression in control rats but increased it in polysubstance-treated rats. In the nucleus accumbens, polysubstance treatment reduced CRHR1 expression. OPRM1 expression was sex-dependent, with a marked reduction in the nucleus accumbens of females after polysubstance treatment and sex-dependent effects in the medial prefrontal cortex.
Gaceta Médica de Caracas
April 22, 2026
Psilocybin-assisted therapy shows promise for treating depression and anxiety, especially in cases resistant to conventional treatments. A systematic review of controlled clinical trials from 2020 to 2025, following PRISMA guidelines, included adults aged 18-65 with DSM-5 diagnoses of depression or anxiety who received psilocybin with psychotherapeutic support. Due to methodological differences across studies, a qualitative narrative synthesis was conducted. The review highlights psilocybin's effects on neuroplasticity and brain networks as a potential therapeutic mechanism, but the heterogeneity of the studies prevents a quantitative meta-analysis.
Am J Psychiatry
April 22, 2026
In a nationally representative survey of U.S. adults, past-year psilocybin use was reported by a small but notable percentage of respondents. The study describes the characteristics of those who used psilocybin, including demographic and other substance use correlates. The findings suggest that psilocybin use is associated with certain demographic factors and patterns of other drug use, though the analysis is descriptive and does not establish causation.
bioRxiv : the preprint server for biology
April 22, 2026
Cory A Knox, Samuel C Woodburn, Amelia D Gilbert et al.
Psilocybin, a classic psychedelic, increases dendritic spine density in frontal cortical neurons and facilitates fear extinction after chronic restraint stress in mice, demonstrating its effects in a translationally relevant animal model. Prior studies had largely examined stress-naive animals, so these findings show that psilocybin can promote neural plasticity and behavioral recovery even after chronic stress.
Open Access Indonesian Journal of Medical Reviews
April 21, 2026
Psilocybin-assisted therapy produces a large reduction in depressive symptoms, but the evidence is preliminary and limited by methodological problems. A meta-analysis of nine randomized controlled trials involving 514 participants found a large effect size (SMD = 1.270). However, the certainty of the evidence is rated low due to risk of bias, high heterogeneity, short-term follow-up, and publication bias. Effects were much larger when psilocybin was compared to a waitlist rather than an active placebo, and blinding is compromised by the drug's subjective effects. The authors conclude that robust Phase 3 trials are needed before routine clinical use.
Mental Wellness
April 21, 2026
Mohsen Khosravi, Domenico de Berardis, Massimo Tusconi
A systematic review and meta-analysis of 13 clinical trials with 606 participants found no statistically significant overall antidepressant effect of psilocybin-assisted psychotherapy for major depressive disorder and treatment-resistant depression. The pooled standardized mean difference was -0.79 with a 95% confidence interval from -3.98 to 2.40, and extreme heterogeneity across studies was observed. The type of control group accounted for most of the variation between studies, with waitlist and low-dose comparators exaggerating effect sizes. Session frequency moderated outcomes, with 2 to 5 sessions yielding larger effects and more intensive protocols reducing benefit. Psilocybin's antidepressant efficacy appears highly context-dependent rather than universally robust.
Preprints.org
April 20, 2026
preprint
Medical regulation of psilocybin-assisted therapy has expanded internationally in the past year, with new or clarified regulatory pathways in New Zealand, Germany, Switzerland, the Czech Republic, and at the U.S. federal level. Within the United States, Utah and New Mexico have joined Oregon and Colorado in establishing lawful medical access pathways. These developments build on earlier reforms in Alberta, Canada, and Australia, where structured psychiatric prescribing frameworks were implemented. This update consolidates recent statutory amendments and regulatory decisions to provide a current comparative overview of jurisdictions permitting lawful medical use of psilocybin, distinguishing comprehensive medical regulation from restricted or exceptional access schemes.
Zenodo (CERN European Organization for Nuclear Research)
April 19, 2026
H. Tamba
Psilocybin currently holds six contradictory legal classifications across different jurisdictions, including Schedule I in the US, Breakthrough Therapy designation from the FDA, legal therapeutic use in Oregon and Colorado, Schedule 8 medical use in Australia, and pending rescheduling review. This fragmentation creates a classification cascade—a disruption propagating through administrative, clinical, and economic channels. Analysis of 44 regulatory events across 21 countries (1992–2025) shows a sharp inflection after the 2018 FDA Breakthrough Therapy Designation. Psilocybin-depression research grew at 58.6% annually (2015–2025), and total psilocybin publications increased 54-fold from 12 (2000) to 656 (2025).
Science Letters
April 17, 2026
Beatriz P. Senra, Ricardo Jorge Dinis-Oliveira, Carlos J. A. Ribeiro
Psilocybe cubensis mushrooms contain psilocybin (0.5%–1.5% in dried mushrooms) and psilocin, which have therapeutic potential and are used recreationally. An optimized extraction method using cold methanol with 10% water and kinetic maceration yielded 1.98% psilocybin and 0.10% psilocin. A thin-layer chromatography (TLC) method with Ehrlich's reagent was developed for rapid identification of these tryptamines, suitable for forensic applications.
bioRxiv : the preprint server for biology
April 17, 2026
Pasha A Davoudian, Quan Jiang, Cory A Knox et al.
Psilocybin, a classic psychedelic, alters the activity of specific inhibitory neurons in the mouse medial frontal cortex. It reduces firing of somatostatin-expressing interneurons while increasing activity of parvalbumin-expressing interneurons. This cell type-specific response depends on the 5-HT1A receptor on somatostatin interneurons, and contributes to the drug's long-term behavioral effects. The findings reveal that psilocybin changes cortical inhibition in a targeted manner, highlighting a mechanism beyond the commonly studied pyramidal cells.
medRxiv Preprint Server
April 17, 2026
Chiranth Bhagavan, Orwa Dandash, Olivia Carter et al.
preprint
Psilocybin, a classic psychedelic, acutely alters brain functional connectivity, and these changes are linked to therapeutic doses and subjective effects. Some evidence indicates that such changes persist beyond the acute drug administration period. However, the effects of lower doses on sustained connectivity changes remain unclear.
Science Letters
April 17, 2026
Francisco Sacadura, Cláudia Marques, Andreia Machado Brito-Da-Costa et al.
Both pure psilocybin and a Psilocybe cubensis extract altered the gut microbiota of male Wistar Han rats over two weeks. Fecal samples analyzed by 16S rRNA amplicon sequencing showed that microbial community structure shifted away from baseline and control profiles at day 7 and diverged further by day 14. The effect was more pronounced in rats given pure psilocybin than in those given the whole mushroom extract, suggesting the extract's additional compounds may modulate the impact. The results indicate a time-dependent modulation of gut microbiota by both treatments, with differential magnitude between the pure compound and the whole extract.
Science Letters
April 17, 2026
Diana Dias Da Silva, Andreia Machado Brito-Da-Costa, Francisco Sacadura et al.
Pure psilocybin and whole Psilocybe cubensis extract produce distinct behavioral and toxicological effects in male Wistar Han rats. Pure psilocybin decreased conditioned place preference scores at days 1 and 7, indicating aversive or non-reinforcing effects, and reduced exploratory activity. The extract did not significantly alter preference but transiently increased exploratory behavior at day 7. Peripherally, pure psilocybin increased relative liver weight, suggesting hepatic stress, while the extract reduced renal lipid peroxidation, indicating a protective or antioxidant effect likely from other compounds. These differences highlight the importance of matrix effects in psychedelic research.
Preprints.org
April 15, 2026
preprint
This review examines the potential therapeutic use of psilocybin in older adults for inflammation-driven disorders of aging, including depression and neurodegeneration. It discusses how psilocybin may modulate inflammatory pathways and promote neuroplasticity, offering benefits for age-related conditions where inflammation plays a key role. The authors suggest that psilocybin-assisted therapy could address both mood disorders and cognitive decline in this population, though they note the need for further research to establish safety and efficacy in older adults.
Journal of Psychedelic Studies
April 15, 2026
In a convenience sample of 343 adults in Puerto Rico recruited online, 52.6% reported having used psilocybin (magic mushrooms) at least once. Most users considered the substance non-addictive (61%) and safe (57%), and 88% reported pleasant or very pleasant experiences. Curiosity was the most common motivation (43%). Factors associated with higher odds of use included male sex, bisexual or non-heterosexual identity, non-Christian religious affiliation, and higher scores on openness and agreeableness; identifying as gay was associated with lower odds. The authors caution that these findings are preliminary and not generalizable to the broader population.
Translational psychiatry
April 14, 2026
Ryan J Keenan, Rifa T Haque, Xiangjun Jin et al.
A single dose of psilocybin worsened diet-induced weight loss over four weeks in obese mice switched to low-fat chow, making them more likely to lose more weight. The effect came mainly from reducing food intake, not from changing energy expenditure. In obese mice kept on a high-fat diet, psilocybin did not affect body weight or food intake, suggesting it does not directly cause weight loss or reduce eating. Instead, it may help enable weight loss when combined with other weight-loss interventions. The findings support further research into psychedelic compounds as an add-on therapy for obesity, though more work is needed to understand the mechanisms.