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23 results for "Meta-analysis: what did research on psilocybin find in january 2026?"

Psilocybin-Induced Neuroplasticity and Sustained Antidepressant Effects

Quality in Sport January 31, 2026 Anna Maria Komarczewska, Filip Matusiak, Klaudia Brzoza et al.

Psilocybin-assisted interventions produce rapid reductions in depressive symptoms that can persist for months, including six-month outcomes in treatment-resistant depression protocols with psychological support. Convergent evidence from animal studies shows structural synaptic remodeling in frontal cortex and hippocampal plasticity changes in extinction learning paradigms. Human neuroimaging reveals altered large-scale brain dynamics after psilocybin. These findings support neuroplasticity as a biologically plausible mechanism linking transient serotonergic receptor activation to sustained clinical improvement.

The Use of Psilocybin in the Treatment of Depressive Disorders: A Narrative Review

Cureus January 31, 2026 Lukasz Siwek, Marta Nowocien, Barbara Balajewicz et al.

Psilocybin, a psychoactive compound from Psilocybe mushrooms that activates serotonergic receptors, is being investigated as a treatment for depression, a psychiatric disorder with rising global prevalence projected to become the leading cause of disability by 2030. This narrative review presents recent reports on psilocybin-assisted therapy, which, based on promising results showing higher therapeutic efficacy compared to conventional treatments, offers hope for a modern approach with sustained clinical effects and minimal or no adverse effects.

Regarding “The molecular mechanisms through which psilocybin prevents suicide: evidence from network pharmacology and molecular docking analyses”

Translational Psychiatry January 31, 2026 Jesper L. Kristensen

Psilocybin is a prodrug that is rapidly converted in the body to psilocin, the active compound responsible for its subjective and therapeutic effects. The authors of the reviewed manuscript used computational network pharmacology and molecular docking to investigate how psilocybin might prevent suicide, but they incorrectly treated psilocybin as the active agent. In humans, psilocybin's effects correlate with psilocin plasma concentration and serotonin 2A receptor occupancy, and cryo-EM structures of psilocin bound to that receptor are available. Therefore, discussing psilocybin's binding to proteins is nonsensical for understanding its therapeutic actions in humans.

PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial

Palliative Medicine January 30, 2026 James Downar, Julie Lapenskie, Koby Anderson et al.

A 3-week microdose psilocybin regimen (1 mg daily, increasing to 3 mg) was safe and feasible for adults with advanced, incurable illness and severe psychological distress. Among 13 participants who completed the trial, 69% reported meaningful global improvement, 62% showed more than 50% improvement in depression scores, and 72% reported meaningful improvement in demoralization. No serious adverse events occurred; four participants withdrew due to disease progression or poor response. The findings suggest microdose psilocybin may be a potentially efficacious treatment for psychological distress near the end of life.

Improving access to psilocybin-assisted therapy: barriers, challenges, and recommendations

Frontiers in Public Health January 29, 2026 Vivian W. L. Tsang, Camille Roney, Pamela Kryskow et al.

Psilocybin-assisted therapy (PAT) combines psilocybin with structured psychological support to address psychological, emotional, and existential distress, particularly at end of life. The therapy is relational in nature, recognizing that healing occurs through human connection. Roots to Thrive in Nanaimo, British Columbia, is the only multidisciplinary non-profit healthcare practice in Canada legally offering group PAT, primarily serving terminally ill patients. Between 2022 and late 2024, 471 Special Access Program (SAP) applications were submitted for psilocybin or MDMA in Canada, with about 318 approved.

PSILOCYBIN IN PSYCHIATRIC PRACTICE AND PSYCHEDELIC-ASSISTED THERAPY FOR TREATMENT-RESISTANT DEPRESSION

International Journal of Innovative Technologies in Social Science January 28, 2026 Łukasz Deska, Cezary Kosmecki, Dawid Głaz et al.

Psilocybin-assisted therapy shows rapid, robust, and sustained antidepressant effects for major depressive disorder and treatment-resistant depression, often after one or two sessions. Its safety profile is generally favorable, with transient and mild adverse events. The therapy primarily acts on serotonin 5-HT2A receptors, modulating brain networks and enhancing neuroplasticity. However, high costs, limited accessibility due to the intensive therapeutic model, and regulatory hurdles present significant challenges. Compared with conventional antidepressants and ketamine, psilocybin offers a promising alternative, especially when standard treatments fail, by providing durable symptom reduction through unique neurobiological pathways.

Psilocybin and the Evolutionary Significance of Altered Neural States: Interaction-Based Perspectives Beyond Deterrence Models

January 28, 2026 Philip Rebensburg

Psilocybin, a psychoactive compound produced by certain fungi, may have evolved not as a simple deterrent against insects but as a molecule that alters neural and behavioral states to influence ecological interactions. The author argues that deterrence-based explanations fail to account for the compound's biosynthetic cost, its conserved effects on serotonin systems across species, and its patchy distribution across fungi. Comparing psilocybin to related tryptamines like DMT, which appear across fungi, plants, and animals, reveals convergent evolutionary patterns. The synthesis proposes an interaction-based framework where such compounds modulate organism–environment relationships through transient neural changes, offering testable predictions for future research.

Psychedelics in psychiatric treatment: a literature review

Quality in Sport January 26, 2026 Adam Wolski, Ewa Szplit, Mikołaj Franciszek Patalong et al.

Psychedelic substances, including psilocybin, LSD, MDMA, and ketamine, show promise for treating psychiatric disorders such as major depressive disorder, PTSD, substance use disorders, and anxiety. Psilocybin produces robust antidepressant effects, reduces anxiety, and benefits substance use disorders after limited dosing sessions. MDMA-assisted psychotherapy yields high remission rates in PTSD. LSD shows promising effects for anxiety and substance use disorders. Ketamine provides rapid antidepressant and anti-suicidal effects in depression and potential benefits in addiction and anxiety, though results in PTSD are mixed. Risks require careful screening and clinical oversight, but evidence supports psychedelic-assisted therapies as adjunctive or alternative interventions for selected patients.

Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience

Journal of Psychopharmacology January 26, 2026 Jess Kerr-Gaffney, Samuel Myrtle, Famia Askari et al. 2 citations

A single dose of psilocybin, compared to an inert placebo, did not alter personality traits, psychiatric symptoms, or cognitive flexibility in healthy participants. However, both the 10 mg and 25 mg psilocybin groups reported greater changes in personal values at both short-term (day 8) and long-term follow-up (day 85). The acute psychedelic experience, particularly the feeling of oceanic boundlessness, partially explained these value changes, with auditory alterations also playing a role in one subscale. These exploratory findings are tentative and require replication in larger samples.

The therapeutic efficacy of psilocybin in major depressive disorder: A review of recent clinical and mechanistic evidence

Zenodo (CERN European Organization for Nuclear Research) January 26, 2026 Fernando Mora López, Johynny Solís Solís, Ekaterina Daniela Hernández Baker et al.

Psilocybin, acting as a 5-HT2A receptor agonist, alters brain connectivity in networks involved in self-referential processing and emotional regulation, accompanied by neuroplastic changes such as enhanced synaptogenesis and functional reorganization. Neuroimaging shows reduced amygdala activity and modifications in default mode and executive networks. Clinical evidence indicates substantial reductions in depressive symptoms, with meta-analyses reporting large effect sizes and durable benefits lasting from weeks to a year. Randomized controlled trials show rapid onset and higher remission rates than conventional treatments, even in treatment-resistant depression. Adverse events are mild, transient, and predictable, though methodological limitations like small samples and high heterogeneity call for larger Phase III trials.

Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure

Journal of Medicinal Chemistry January 26, 2026 Marco Banzato, Martina Colognesi, Lorena Lucatello et al.

A library of fluorinated reversible N-alkyl carbamate derivatives of psilocin was designed and synthesized to reduce acute psilocin exposure and limit hallucinogenic-like effects. By varying the number and positioning of fluorine atoms on the alkyl promoiety, carbamate bond stability was systematically modulated, yielding compounds with finely tuned hydrolysis under physiological conditions. A lead compound (4e) demonstrated favorable oral bioavailability and efficient brain penetration while undergoing partial bioconversion to psilocin. It exhibited intrinsic serotonergic activity at 5-HT2A and 5-HT2C receptors but induced attenuated psychotropic effects compared to psilocybin. Fluorinated carbamate chemistry provides a versatile platform to control psilocin exposure and serotonergic signaling.

The Evaluation of the Efficacy and Safety of the Use of Psilocybin in the Treatment of Adults with Treatment-Resistant Depression

Emerging Minds Journal for Student Research January 25, 2026 Rishika Scott, James Smith

A systematic review and meta-analysis of seven studies (five open-label and two randomized controlled trials) found that a single 25 mg dose of psilocybin per clinical session is effective for treatment-resistant depression. The 25 mg dose significantly reduced depressive severity compared to 10 mg and 1 mg doses, with two-dose studies showing greater benefit than single-dose studies. The evidence suggests psilocybin is a promising therapeutic, though more research is needed due to limitations in the available studies.

Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis

Neuroscience & Biobehavioral Reviews January 24, 2026 Omer A. Syed, Benjamin Tsang, Sean M. Nestor et al.

Psilocybin-assisted therapy (PAT) shows a large and significant antidepressant effect in treating major depressive disorder, based on a meta-analysis of seven randomized controlled trials involving 522 participants. Larger effects were associated with bodyweight-adjusted dosing, longer preparation, dosing, and integration sessions, and non-manualized psychotherapy, though subgroup differences were not statistically significant. The review provides preliminary guidance for clinicians designing PAT protocols.

Consistency of protocol and safety data reporting in clinical trial registrations and corresponding publications of interventions involving MDMA and psilocybin.

Journal of clinical epidemiology January 23, 2026 Marija Franka Žuljević, Antonija Mijatović, Renata Orhanović et al. 4 citations

A cross-sectional analysis of 336 clinical trials on MDMA or psilocybin registered on ClinicalTrials.gov found that 17.6% made major changes to primary outcome measures and 28.6% changed eligibility criteria, most after recruitment began. Among completed trials, 72.0% did not post results on the registry, and most that did exceeded the one-year reporting window. Only 3 of 29 trials with both posted results and publications had fully concordant adverse event reporting; most showed qualitative and quantitative discrepancies. These inconsistencies undermine the credibility and safety evaluation of these trials, and the authors advise greater transparency and stricter adherence to reporting standards.

THE PSYCHEDELIC RENAISSANCE: A SYSTEMATIC REVIEW OF PSILOCYBIN AND LSD IN THE TREATMENT OF PSYCHIATRIC DISORDERS

International Journal of Innovative Technologies in Social Science January 23, 2026 Jakub Klepacz, Radosław Swędrak, Marzena Swojnóg et al.

Classical serotonergic hallucinogens like psilocybin and LSD are being re-evaluated in clinical research. A systematic review traces their history from indigenous use through prohibition to current trials. The compounds act via 5-HT2A receptor agonism and disrupt the Default Mode Network, which may help alleviate rigid cognitive patterns in depression and anxiety. Clinical data show significant therapeutic potential for Treatment-Resistant Depression, end-of-life distress, and substance use disorders. The review emphasizes that psychedelic-assisted therapy requires a specific psychotherapeutic framework, integration processes, and attention to cost-effectiveness and access equity. This approach suggests a shift from chronic symptom management to rapid, episodic curative interventions if regulatory and ethical challenges are addressed.

No evidence of immediate or persistent analgesic effect from a single dose of psilocybin in three mouse models of pain

Nature Communications January 22, 2026 Nicholas Gregory, Tyler Girard, Akila Ram et al. 5 citations

Psilocybin, a psychedelic compound, was tested for direct pain-relieving effects in mice with inflammatory, nerve injury, and muscle pain. Across a range of doses (0.3, 2, and 10 mg/kg) in both sexes, using multiple sensory and functional pain tests, psilocybin showed no analgesic effect except for reduced cold sensitivity. That reduction likely resulted from psilocybin-induced hypothermia rather than true pain relief. The findings suggest that any lasting therapeutic benefits of psilocybin for chronic pain are not due to direct analgesic action.

Is psilocybin only effective as part of psychotherapy?

Zenodo (CERN European Organization for Nuclear Research) January 22, 2026

Current evidence mainly shows psilocybin's effectiveness when combined with psychotherapy, but there is also evidence suggesting it can have beneficial effects with less intensive psychological support. Further research is needed to clarify its efficacy as a standalone treatment.

Psilocin mediates long-term synaptic depression in the prelimbic cortex through 5-HT2A receptor-independent mechanisms

Neuropharmacology January 21, 2026 Ana Domi, Erika Lucente, Davide Cadeddu et al. 1 citation

Psilocin, the active metabolite of psilocybin, induces a long-lasting decrease in excitatory synaptic strength in the prefrontal cortex of rats, an effect that is independent of sex. This synaptic depression originates presynaptically and is not mediated by 5-HT2A or metabotropic glutamate group 2 receptors, but instead involves enhanced GABAergic inhibition. The effect is partially blocked by a 5-HT1A receptor antagonist and fully blocked by a TrkB receptor antagonist. These sustained changes in synaptic activity may relate to reduced prefrontal connectivity observed in humans and could affect cognitive function.

[Clinical application and mechanistic studies of psychedelics for treatment of depression: progress and future challenges].

Nan fang yi ke da xue xue bao = Journal of Southern Medical University January 20, 2026 Ke Xia, Tianming Gao

Classic psychedelics, especially psilocybin, show promise for treating depression, with several randomized controlled trials indicating that one or a few sessions of psychedelic-assisted psychotherapy can produce rapid and lasting antidepressant effects in patients with treatment-resistant depression. Mechanistically, these substances quickly increase neurotrophic factors, enhance neuroplasticity, and reorganize brain networks, creating a window for psychotherapy. However, the specific molecular and circuit-level mechanisms remain unclear, with debate between the 5-HT2A receptor-dependent hypothesis and the TrkB neurotrophic pathway-dependent hypothesis. Key challenges include psychedelic-related risks, incomplete mechanistic understanding, lack of standardized protocols, and insufficient long-term safety data.

Insights into psilocybin use among people with bipolar disorder: A thematic analysis of Reddit posts

Journal of Affective Disorders January 20, 2026 Laura Mills, Susan L. Rossell, Sean Carruthers

Psilocybin use among people with bipolar disorder is associated with both benefits and risks. Analysis of 354 Reddit posts and comments revealed four themes: mania, depression, mixed experiences, and broader perspectives. Some users reported reduced depression symptoms and shifts in perspective, but others described increased or new mania, psychosis, and worsened depression. The findings suggest that while psilocybin may help some individuals with bipolar disorder, it also carries potential for adverse mental health effects.

Group Retreat Psilocybin Therapy for People with Metastatic Cancer with Symptoms of Anxiety and Depression: Safety and Efficacy Outcomes of a Phase 1/2 Study

Psychedelic Medicine January 18, 2026 Anthony L. Back, Bonnie A. Mcgregor, Leslie Lazar Thorn et al. 1 citation

A group retreat model of psilocybin therapy for people with metastatic cancer and anxiety or depression was safe and well tolerated. Fifty-two participants attended a 3-day retreat with 25 mg psilocybin, supported by virtual and in-person sessions. No episodes of unattended distress occurred during the psilocybin sessions. Anxiety and depression symptoms, measured by the Hospital Anxiety and Depression Scale, decreased by an average of 7.3 points from baseline to 28 days after the retreat, a statistically significant reduction. The findings suggest that a group configuration of eight participants with four core facilitators can be safe for future studies in people with serious medical illness.

Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols.

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology January 16, 2026 Damian Swieczkowski, Aleksander Kwaśny, Krzysztof Sadko et al. 1 citation

Psilocybin-assisted therapies are being tested for major depressive disorder and treatment-resistant depression, but rigorous research requires not only measuring the drug's effects but also consistently reporting non-pharmacological factors—such as the physical and social environment (set and setting)—that can influence outcomes. To address this, the ReSPCT guidelines were developed as a 30-item framework for standardized reporting. This review evaluated 13 clinical trial protocols (11 Phase II and 2 Phase III) from ClinicalTrials.gov and the EU Clinical Trials Information System. Using the ReSPCT checklist, only 15.6% of 390 item-level assessments showed full compliance; 64.6% had partial compliance, and 19.