Journal of Psychedelic Studies
May 29, 2026
Alex Hood, Gary Elkins
A systematic review of 25 studies found that psilocybin-assisted psychotherapy (PAP) produces a large reduction in anxiety symptoms within groups (Hedge's g = 0.96) and a small reduction compared to control groups (Hedge's g = 0.48). However, the studies varied widely in psychotherapy format, dosing, session structure, and outcome timing, and high heterogeneity persisted even after accounting for these differences. The authors conclude that PAP shows promise for treating anxiety across different diagnoses but caution that variability in study quality, design, sample representativeness, and high heterogeneity limit confidence in the findings. More rigorous trials with diverse populations are needed.
Cell Discov
May 29, 2026
The authors propose a spatiotemporal gating hypothesis to resolve a paradox in how psilocybin produces lasting neural plasticity. Psilocybin activates 5-HT₂A receptors, but the plasticity it induces requires TrkB signaling, even though psilocybin does not directly bind TrkB. The hypothesis suggests that 5-HT₂A activation creates a specific pattern of neural activity—a spatiotemporal gate—that indirectly engages TrkB signaling, reconciling the two mechanisms. This framework aims to explain how a brief psychedelic experience can lead to sustained changes in brain structure and function.
Journal of psychopharmacology (Oxford, England)
May 29, 2026
Kristoffer Brendstrup-Brix, Brice Ozenne, Patrick M Fisher et al.
Patients with chronic cluster headache (CCH) suffer from poor sleep, which may affect brain microstructure and waste clearance. In 11 CCH patients, subjective sleep quality—measured by the Pittsburgh Sleep Quality Index—improved one week after three doses of psilocybin (0.14 mg/kg) given one week apart, with a mean PSQI change of -2.50 points. Before treatment, CCH patients had poorer sleep and differences in brain microstructure and water diffusivity compared to 24 healthy controls, primarily in grey matter. Psilocybin intervention was not associated with statistically significant changes in brain microstructure or water diffusivity on average, though most patients showed lower white matter diffusivity and neurite volume. Subjective sleep quality showed borderline significant correlations of moderate effect size with brain microstructure and water diffusivity.
Zenodo (CERN European Organization for Nuclear Research)
May 29, 2026
Andrew Stewart Caldin
A high-dimensional geometric framework called E8 can encode the coupled dynamics of serotonin-2A receptor activation and dopamine pathways relevant to cocaine addiction. Embedding clinical data on psilocybin and cocaine into this model allows rapid classical simulations that predict therapeutic outcomes, potentially enabling faster optimization of dosing protocols. The original finding suggests that psilocybin could be an effective treatment for cocaine addiction.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
May 28, 2026
L Belinger, N M Rieser, E J E Engeli et al.
In a double-blind randomized trial with 120 healthy volunteers who received psilocybin, MDMA, or methylphenidate (active placebo), overall blinding was insufficient. Psilocybin had the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological effects. Prior substance experiences did not influence accuracy of forced-choice guesses. These findings offer empirical guidance for designing and reporting blinding procedures in psychedelic trials.
Journal of Raman Spectroscopy
May 28, 2026
A new detection method using surface-enhanced Raman spectroscopy with silver-coated gold nanoparticles can identify psilocybin and psilocin in human urine at extremely low concentrations. The technique achieved detection limits of 1.11 × 10⁻¹⁰ mol·L⁻¹ for psilocybin and 6.75 × 10⁻¹² mol·L⁻¹ for psilocin. In tests with real urine samples, recovery rates ranged from 80.79% to 109.53% for psilocybin and 83.98% to 106.78% for psilocin, with relative standard deviations below 9%, indicating good accuracy and stability. This approach may be useful for drug enforcement, clinical toxicology, and monitoring psychoactive substances.
Psychopharmacology
May 28, 2026
Mazen A Atiq, Eli Weisman, Rodrigo B Guerra et al.
A healthy 35-year-old man experienced a rare hypotensive adverse event—neurocardiogenic syncope (fainting)—about 60 minutes after taking 25 mg of oral psilocybin in a clinical trial. His blood pressure dropped to 93/51 mmHg, with rapid heart rate and sweating, but he stabilized quickly with leg elevation and oral hydration. The episode may have been triggered by upright seated posture, restrictive EEG equipment, and anxiety about upcoming transcranial magnetic stimulation. Fewer than one-quarter of contemporary psychedelic trials report systematic adverse event assessment, highlighting the need for transparent documentation of both hypertensive and hypotensive events as psilocybin moves toward potential FDA approval.
Psychotherapy and psychosomatics
May 27, 2026
Lea J Mertens, Felix Betzler, Manuela Brand et al.
A single 25 mg dose of psilocybin, or two such doses given six weeks apart, combined with psychotherapy produced a stable and clinically meaningful reduction in depression symptoms for up to twelve months in people with treatment-resistant depression. The average improvement on the Hamilton Rating Scale for Depression was about 7.9 points at six months and 7.7 points at twelve months, with no significant difference between dosing groups. Restarting standard antidepressant medication during follow-up was strongly linked to higher depression scores. This naturalistic follow-up of a phase 2b trial is the largest and most complete long-term assessment of psilocybin for depression to date.
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.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 25, 2026
Sheida Shadani, Kaspar McCoy, Lina Ong et al.
A single dose of psilocybin (1.5 mg/kg) in C57BL/6 J mice produces sex-specific effects on social behavior and dopamine signaling. In females, psilocybin acutely increased huddling and induced hypothermia, and post-acutely enhanced novelty-seeking and grooming, with no comparable effects in males. By 24 hours, males showed reduced grooming and rearing but increased sociability toward a cage-mate, accompanied by blunted novelty-evoked nucleus accumbens dopamine responses lasting up to 7 days. At 7 days, females shifted social preference toward familiarity, associated with prolonged dopamine release during familiar interactions, while males increased grooming. Both 5-HT1A and 5-HT2A receptors contributed to these sex-specific behavioral effects.
Scientific data
May 21, 2026
Leonardo Novelli, Devon Stoliker, Tamrin Barta et al.
PsiConnect is a large-scale neuroimaging study that investigates how psilocybin affects brain activity and subjective experience depending on context. Sixty-two participants received a 19 mg dose of psilocybin and underwent functional, structural, and diffusion-weighted MRI, as well as EEG, before and after administration. Scans included resting-state and three naturalistic conditions: guided meditation, music listening, and movie watching. Half of the participants completed an 8-week meditation training program, allowing examination of interactions between meditation, psilocybin, and brain function. Multi-echo fMRI improved signal quality. Behavioral and self-report measures captured acute and long-term effects, with follow-ups up to one year. Data is openly shared to support future research.
Palliative Medicine
May 19, 2026
1 citation
Most palliative care stakeholders in Canada view psilocybin-assisted therapy favorably, with 95% of physicians reporting positive attitudes. A cross-sectional online survey of 121 adults involved in palliative care found that the lack of trained healthcare providers is the primary barrier to implementation, while further research and standardized protocols are key facilitators. Sixty-eight percent of stakeholders support introducing this therapy early in the illness trajectory. The findings highlight significant divergence in perspectives between clinical and non-clinical groups, suggesting tailored interprofessional education could build shared understanding. The study's Canadian context may limit transferability to other regulatory frameworks.
Aust N Z J Psychiatry
May 18, 2026
correction
A corrigendum corrects errors in a previously published article about psilocybin's regulatory, ethical, and operational challenges in Australia's clinical landscape. The original article discussed issues surrounding the real-world use of psilocybin, a psychedelic substance, in therapeutic settings. The corrigendum does not present new findings or arguments but amends specific inaccuracies in the original text.
bioRxiv
May 18, 2026
A single dose of psilocybin (1.5 mg/kg) in female rats enhanced cognitive flexibility in several learning tasks by amplifying dopamine signals in the nucleus accumbens. The drug increased learning rates and reduced reliance on prior expectations, leading to faster reversal learning. However, calorie restriction and prior exposure to activity-based anorexia (ABA) reduced these benefits. Calorie restriction shifted the timing of psilocybin's effect on reversal learning and increased neural activity in the nucleus accumbens. Prior ABA exposure eliminated improvements in discrimination accuracy and trended toward worsening reversal learning, likely due to reduced cortical 5-HT2A receptor availability. The results show that nutritional state and history of anorexia-like behavior critically moderate psilocybin's cognitive effects.
Religions
May 18, 2026
Geoffrey Ready, Ron Cole‐turner
Orthodox Christianity offers distinctive resources for evaluating psychedelic spirituality that both challenge and enrich existing Western Christian approaches. The tradition's insistence that profound spiritual experience is a universal Christian vocation rather than reserved for an elite reframes discussions of mystical experience. Orthodoxy's recognition of diverse catalysts for spiritual awakening, its understanding of ascetical preparation as receptive, and its doctrine of divine energies provide frameworks for evaluating psychedelic experiences that sometimes resemble mystical experience by their orientation and fruits. The emphasis on ongoing formation within communities situates spiritual experience within broader transformation, and traditions of spiritual discernment offer criteria for evaluating authenticity. Engagement with psychedelic experiences can occur within established frameworks when guided by discernment, formation, and communal accountability.
JAMA Network Open
May 15, 2026
1 citation
A single 25 mg dose of psilocybin, combined with psychotherapeutic support, produced rapid antidepressant effects in people with moderate to severe recurrent major depressive disorder. Depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale, improved significantly more in the psilocybin group than in the placebo group by day 8, with benefits lasting through day 42 but not at one year. Self-reported depressive symptoms showed improvement as early as day 2 and persisted for over three months. The treatment was generally well tolerated, though two participants experienced persistent severe anxiety requiring medical attention. These findings suggest psilocybin may offer a rapid and relatively durable antidepressant effect.
PsyArXiv
May 14, 2026
preprint
A double-blind randomized controlled trial will test whether low doses of psilocybin, given alongside virtual reality exposure therapy, can reduce symptoms of social anxiety disorder. The protocol describes the planned methods but does not yet report results.
Current psychiatry reports
May 14, 2026
Jamarie A Geller, Rachel Pacilio, Amanda E Downey et al.
Psilocybin-assisted therapy may hold promise for anorexia nervosa, a serious and often treatment-resistant illness. Although research has focused on adults, anorexia frequently begins in adolescence, and early onset is linked to more severe illness, greater psychiatric comorbidity, and more life difficulties. The authors argue that exploring the theoretical potential of this therapy for adolescents is warranted, considering biological implications, developmental stage, and consent. They propose adaptations to adult treatment models and discuss emerging models that address the unique challenges of adolescent patients.
The Journal of clinical psychiatry
May 13, 2026
Andrew van der Vaart, Jeffrey LaPratt, Kimberly Swartz et al.
A single 25-mg dose of a synthetic psilocybin formulation, combined with psychological support, rapidly and durably reduced chronic suicidal ideation and depressive symptoms in 20 adults with major depressive disorder who had not responded to at least two prior antidepressant treatments. Suicidal ideation scores dropped significantly by week 1, remained reduced at week 3 (the primary endpoint), and were still lower at week 12, when 70% of participants had minimal or no suicidal ideation. Depressive symptoms also improved substantially. No serious adverse events occurred. The findings are preliminary and require confirmation in larger randomized trials.
BJPsych Open
May 13, 2026
This is a correction notice for a previously published study protocol. The original protocol describes a phase II double-blind placebo-controlled randomised partial crossover trial investigating microdosing psilocybin for major depressive disorder. No new findings or data are presented.
Frontiers in Psychiatry
May 13, 2026
2 citations
In the first year of Oregon's regulated psilocybin program, 5,935 clients participated in 5,375 sessions. Utilization peaked in the second quarter before stabilizing. About a third of participants lived outside Oregon. The largest age group was 35–49; women and LGBTQ+ individuals were well represented, but racial diversity was limited, with White participants making up 84–92% quarterly and African American participation at 2.1%. Adverse events were rare, with behavioral and medical rates of 2.42 and 2.79 per 1,000 sessions. The program serves as both a wellness modality and an alternative for mental health distress, though racial disparities and socioeconomic barriers persist.
Neuroethics
May 13, 2026
Christina Chwyl, Alissa Bazinet, Adrianne R. Wilson-Poe et al.
Informed consent in psychedelic-assisted services is ethically complex and lacks standardization. Expert recommendations from 36 participants (71% white, 53% female, average 15.2 years of experience in clinical trial, underground, or ceremonial settings) emphasized that consent should be an ongoing process built on a strong therapeutic relationship and client empowerment. Comprehensive disclosure of risks and benefits is needed, including long-term psychological and social changes and the possibility of disappointing experiences. Detailed consent around touch and boundaries is crucial, with explicit boundary-setting before administration and attention to non-verbal cues. Provider training should cultivate deep respect for client agency and experiential learning of relational and boundary skills.
Research Square
May 11, 2026
Psilocybin-assisted therapy shows promise as a treatment for adults with treatment-resistant depression, with early trials reporting rapid antidepressant effects and a favorable tolerability profile. A systematic review of six trials found that psilocybin lowered depressive scores in participants, while common adverse events included anxiety, nausea, headache, fatigue, and suicidal ideation; no serious safety concerns or physiological toxicity were identified. However, the evidence remains preliminary due to small sample sizes, open-label designs, and varied psychotherapy protocols. Larger, more rigorous randomized trials are needed to confirm efficacy, optimize dosing, and standardize psychological support.
International journal of molecular sciences
May 9, 2026
Marta Jóźwiak-Bębenista, Anna Stasiak, Monika Sienkiewicz et al.
Aging involves chronic low-grade inflammation that contributes to depression and neurodegenerative diseases like Alzheimer's and Parkinson's. Psilocybin, acting through its active metabolite psilocin as a partial agonist at the 5-HT2A receptor, may address these challenges by modulating cortical glutamate transmission, enhancing TrkB/BDNF pathways, and influencing neuroimmune cascades including NF-κB. Human studies report acute reductions in TNF-α with variable effects on IL-6 and CRP. Psilocybin's rapid onset, short half-life, and phase-II glucuronidation reduce drug interaction risks, making it potentially advantageous for older adults. Controlled studies show rapid antidepressant and anxiolytic effects in major depressive disorder, treatment-resistant depression, and existential distress, with emerging signals in neurodegeneration. The review integrates current evidence and calls for targeted studies in older adults.