Psychiatry and Clinical Neurosciences
February 26, 2026
Kengo Yonezawa, M. Hirata, Hiroaki Takano et al.
1 citation
Psilocybin, a classic psychedelic compound, is being reexamined as a treatment for psychiatric disorders after decades of legal restrictions. Clinical trials report therapeutic effects for major depressive disorder, depressive symptoms in life-threatening illnesses, and some substance use disorders, with phase III trials for depression underway. Short-term side effects are generally mild and transient, but long-term effects need investigation. Neuroimaging research, mainly using MRI and EEG, is limited and focused on MDD, though ongoing trials include broader studies. Regulatory frameworks vary; controlled use is permitted in Switzerland, parts of the US, Canada, and Australia. Challenges remain, including the need for larger blinded trials and standardized protocols.
Scientific Reports
February 25, 2026
Albert Garcia-Romeu, Gideon P. Naudé, Alison W. Rebman et al.
2 citations
An estimated 10–20% of Lyme disease patients develop post-treatment Lyme disease (PTLD), a chronic syndrome with no established treatments. In an open-label pilot study of 20 participants with PTLD, two sessions of psilocybin (15 mg then 15 or 25 mg) with psychological support led to significant improvements in symptom burden and quality of life from enrollment through one month after the second dose, with benefits sustained at six months. At six months, general PTLD symptom burden decreased 40% from baseline, and mental and physical quality-of-life scores improved 13%. Mood, fatigue, sleep, and pain also improved. No serious adverse events occurred; common side effects were transient hypertension, headache, and tachycardia. The findings suggest psilocybin-assisted treatment is feasible and well-tolerated, warranting further research.
Research Square
February 23, 2026
Rotem Petranker, Norman Farb, Omer A. Syed et al.
Repeated low doses of psilocybin were safe and well tolerated in adults with major depressive disorder but did not show greater antidepressant effects than placebo. In a randomized, double-blind trial, 39 participants received either 2 mg psilocybin or placebo weekly for four weeks. Both groups reported similar reductions in depression scores on the PHQ-9 (psilocybin: -5.4; placebo: -6.0) and other measures. The microdose-first group showed slightly more improvement on a dysfunctional attitudes scale than the placebo-first group. No serious adverse events occurred, and symptom reductions continued during an open-label phase. Trial participation itself contributed to clinically meaningful improvement.
medRxiv
February 19, 2026
Amanda Gow, Emily Shih, Ryan Reid et al.
Under Oregon's regulated psilocybin program, adults who consumed an average of 27.8 mg of psilocybin showed significant improvements in depression, anxiety, and well-being 30 days after a session, including those concurrently using psychiatric medication. Of 88 participants (median age 43, 52% male, 64.8% with prior psychedelic experience), two reported symptoms of hallucinogen persisting perception disorder one day after the session, but none at 30 days. The findings suggest that legal psilocybin services can produce clinically meaningful mental health benefits.
MacEwan University Student eJournal
February 18, 2026
Jordan Mcdowell, Jada Middleton, Alanna Bluett et al.
Over 126,000 Canadians may be experiencing interactions between antidepressants like fluoxetine and psychedelics like psilocybin, a number expected to grow as psychedelic therapy and recreational use become more accepted. Fluoxetine appears to attenuate the mind-altering effects of psilocybin, likely due to modulation of serotonin receptor activity. Benzodiazepine use, including alprazolam, ranges from 5% to 10% nationwide, with higher usage among older adults. Little direct research exists on psilocybin-alprazolam interactions, but small interactive effects are indicated. Understanding these interactions may improve harm-reduction strategies and clinical decision-making.
BMJ Supportive & Palliative Care
February 18, 2026
Luca Magnani, Luca Ghirotto, Fabio Fesce et al.
Psilocybin-assisted psychotherapy shows promise as a therapeutic option for palliative care, and further rigorous, interdisciplinary research is needed to ensure its implementation is grounded in anthropological and ethical considerations, extending its potential beyond oncology to other palliative settings.
Qualitative Health Research
February 17, 2026
Zaynab Khan, Sterre Weaver, Rachael V. Dando et al.
1 citation
Seven women in the United Kingdom with a current or previous cancer diagnosis were interviewed about their attitudes toward using psilocybin for mental health. Four had used psilocybin and three had considered it. Participants viewed psilocybin as a needed alternative to traditional treatments for depression and anxiety linked to their cancer diagnosis, but they felt its illegal status was a major barrier to access. Three themes emerged: somatic healing needs, illegality as both a burden and boundary, and reconnecting self, nature, and mortality. The authors suggest a compassionate access scheme in the UK could transform mental health care for people with cancer.
Journal of Psychopharmacology
February 16, 2026
Marten Kase, Karl Kristjan Kaup, Jaan Aru
1 citation
A systematic review of 32 placebo-controlled studies from 1990 to 2025 examined the acute and post-acute effects of LSD, DMT, and psilocybin on cognitive and psychological functions. Psychedelics tended to enhance emotional empathy but had no effect on cognitive empathy. Effects on memory varied by task and timing, with some impairments, enhancements, or no change. Dose-dependent impairments occurred in reaction time, attention, and inhibition tasks, though some studies found no effects. Recognition of negative stimuli was impaired under acute effects. Findings on cognitive flexibility were mixed. Many studies had small samples, and finding a reliable placebo is challenging due to psychedelics' unique subjective effects.
Scientific Reports
February 14, 2026
Zurika Murray, Angélique Lewies, Johannes F. Wentzel et al.
3 citations
Whole mushroom extracts containing psilocybin may be more effective than isolated psilocybin for treating psychiatric disorders, possibly due to an entourage effect from additional bioactive compounds. Using computational methods including network pharmacology, molecular docking, and molecular dynamics, researchers identified fifteen compounds from psilocybin-producing mushrooms, eight with favorable pharmacokinetic profiles. Target prediction revealed 44 brain-localized proteins with biological connectivity. The compounds showed strong docking to neurological targets, with several forming stable salt bridges with the Asp155 residue of HTR2A, similar to serotonin. Molecular dynamics simulations confirmed high residence stability within HTR2A and MAOA binding pockets, supporting a mechanistic rationale for enhanced efficacy of whole mushroom extracts.
Neuropsychopharmacology
February 13, 2026
Fabrizio Ascone, Valeria Buzzelli, Francesca Mottarlini et al.
2 citations
In a rat model of Fragile X Syndrome (FXS), psilocybin microdosing rescued deficits in novel object recognition memory. This benefit persisted even when serotonin receptors (5HT2AR or 5HT1AR) were blocked, but was abolished by blocking the TrkB receptor, indicating that the effect depends on BDNF/TrkB signaling rather than classical serotonergic pathways. At the molecular level, psilocybin normalized mature BDNF, increased TrkB, and restored downstream AKT signaling in the prefrontal cortex—pathways linked to synaptic plasticity and cognition. These results suggest psilocybin microdosing could be a promising therapeutic strategy for neurodevelopmental disorders like FXS and autism spectrum disorder, potentially dissociating therapeutic benefits from hallucinogenic effects.
Journal of Affective Disorders
February 12, 2026
Erica Kaczmarek, Nelson Rodriguez, Noah Chisamore et al.
Anhedonia, a core symptom of depression that often resists standard treatments, may be reduced by psilocybin-assisted psychotherapy (PAP). In a secondary analysis of a randomized, waitlist-controlled trial, 30 adults with treatment-resistant depression (major depressive disorder or bipolar II disorder) received one 25 mg dose of oral psilocybin plus psychotherapy. Anhedonia severity, measured by the Snaith-Hamilton Pleasure Scale, decreased significantly at the 2-week primary endpoint, with clinically meaningful improvements persisting at 3 and 6 months. The analysis adjusted for sex and age. These preliminary results suggest PAP could be a promising intervention for anhedonia in treatment-resistant depression, though larger placebo-controlled trials are needed to confirm the findings and clarify underlying mechanisms.
Journal of Psychedelic Studies
February 12, 2026
Matthew Hicks, Olivia Hicks, Ryan Bradley et al.
2 citations
Group psilocybin therapy is feasible for low-income adults with depression in Oregon's regulated psilocybin program. In an open-label study, 20 participants began treatment and 19 completed two psilocybin administration sessions one week apart, with preparation and integration sessions online. No severe adverse events occurred; participants rated satisfaction 4.8 out of 5, reporting moderate to high benefit and no harm. Exploratory outcomes showed a significant decrease in Hamilton Depression scores with a strong effect size (Cohen's d = 1.89), and all eight domains of the PROMIS-29 significantly improved with effect sizes from 0.667 to 1.774. Further research with comparator groups is warranted.
Molecular Psychiatry
February 12, 2026
Sixtine Fleury, Katherine M. Nautiyal
correction
Research in mice implicates the 5-HT1BR, a nonhallucinogenic serotonin receptor, as a potential mediator of the behavioral and neural effects of psilocybin. The 5-HT1BR influences brain-wide neural changes following psilocybin administration and may contribute to its enduring antidepressant-like effects in mice. However, the data do not address whether 5-HT1BR is sufficient for these effects.
February 11, 2026
Sarah Shnayder, Gabrielle Agin-Liebes, Troy Hubert et al.
preprint
In people with treatment-resistant obsessive-compulsive disorder (OCD), greater mystical-type experiences during psilocybin sessions—especially feelings of unity, sacredness, and transcendence—were linked to lower OCD symptom severity at 1-week and 12-week follow-ups, even after accounting for baseline severity and treatment condition. The Mystical subscale of the Mystical Experience Questionnaire showed the strongest and most consistent associations. The Space–Time subscale was related to lower OCD severity only at 12 weeks. Positive mood, ineffability, and challenging experiences were not significantly tied to post-treatment OCD severity. These results suggest that the quality of subjective experience during psilocybin sessions may help optimize treatment outcomes.
Zenodo (CERN European Organization for Nuclear Research)
February 6, 2026
Zen Revista
Psilocybin, a psychedelic compound, triggers activity-dependent rewiring of large-scale cortical networks. Using monosynaptic rabies viral tracing in mice, researchers mapped brain-wide inputs to pyramidal neurons in the dorsal medial frontal cortex. Psilocybin strengthened pathways routing sensory and retrosplenial inputs to subcortical targets while weakening cortico-cortical recurrent loops. This reorganization depends on neural activity during drug administration, shown through chemogenetic silencing. These findings offer insights into psychedelic mechanisms and suggest combining targeted neuromodulation with psychedelic treatment to enhance therapeutic outcomes for mental health disorders.
Zenodo (CERN European Organization for Nuclear Research)
February 6, 2026
Zen Revista
Psilocybin, the psychoactive compound in magic mushrooms, triggers network-specific neural rewiring that is activity-dependent and programmable. Using genetically modified rabies virus for monosynaptic circuit tracing, researchers discovered that psilocybin strengthens sensory-motor pathways while weakening cortical-cortical feedback loops linked to rumination and depression. Sensory regions showed up to 10% increases in connectivity, and self-referential regions exhibited up to 15% decreases. Neural activity during the psilocybin window determines which circuits are strengthened or weakened, suggesting therapeutic interventions could be optimized by controlling sensory and cognitive experiences during treatment. These findings provide mechanistic insights into psilocybin’s rapid antidepressant effects.
Journal of psychopharmacology (Oxford, England)
February 5, 2026
Benjamin R Lewis, Matthew J Reid, Andrew M Novick et al.
Clinical trials of classical psychedelics like psilocybin for mental health conditions face unique challenges that may persist if these treatments enter clinical practice. Four categories of challenges with trial participants are identified: treatment nonresponse, expectancy effects and functional unblinding, post-session psychological difficulties, and contagion effects. Management strategies for study teams to mitigate these risks are described. The National Network of Depression Centers and similar organizations can guide best practices to responsibly advance this promising field.