{ "meta": { "tracker_site_url": "https://psilocybin-research.com", "publication_tracker_url": "https://psilocybin-research.com/", "generated_at_utc": "2026-07-02 20:49:09", "record_count": 50 }, "papers": [ { "id": 3024, "title": "Sex-Specific Effects of Psilocybin Versus Escitalopram on Anxiety and Anhedonia: A Bayesian Reanalysis of Antidepressant Treatment Outcomes", "normalized_title": "sex specific effects of psilocybin versus escitalopram on anxiety and anhedonia a bayesian reanalysis of antidepressant treatment outcomes", "authors": "Frick A, Blest-Hopley G, Grin M, Erritzoe D, Nutt D, Carhart-Harris R.", "abstract": "Abstract Rationale: Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, women remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. Objectives This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex differences across multiple psychological domains. Methods We reanalyzed data from a six-week, double-blind randomized controlled trial comparing psilocybin with escitalopram in adults with moderate-to-severe MDD. Post-treatment depressive symptoms (MADRS, QIDS-SR-16, BDI), anhedonia (SHAPS), anxiety (STAI), thought suppression (WBSI), and well-being (WEMWBS) were modeled as a function of sex, treatment condition, their interaction, and baseline symptom severity. Sexual dysfunction severity (PRSexDQ-SALSEX), assessed only at the six-week follow-up, was analyzed separately as an ordinal outcome. Results Sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men (STAI: 95% CrI − 17.5 to − 3.29), whereas women receiving escitalopram showed greater reductions in anhedonia than men (SHAPS: 95% CrI − 4.63 to 0.00). For the remaining continuous outcomes, sex differences were generally 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, although the treatment-by-sex interaction was not significant. Conclusions This reanalysis identified domain-specific sex-related patterns in anxiety and anhedonia, suggesting that responses to psilocybin and escitalopram may differ between women and men. These preliminary findings support adequately powered, sex-balanced, and hormone-informed trials of serotonergic treatments for MDD.", "journal": "Research Square", "publication_date": "2026-06-18", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9880403/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9880403/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:45", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1255612\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,Clinical Trial,Randomized Controlled Trial,Drug Interactions", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3367, "title": "Prolonged Grief Symptom Outcomes During At-Home Ketamine-Assisted Therapy: A Real-World Retrospective Analysis of 503 Adults", "normalized_title": "prolonged grief symptom outcomes during at home ketamine assisted therapy a real world retrospective analysis of 503 adults", "authors": "Carter D, Reardon I, Swain J, Vando L.", "abstract": "Abstract Background Prolonged grief disorder (PGD) is a clinically distinguishable bereavement-related condition characterized by persistent yearning, identity disruption, and impaired functioning, formalized in DSM-5-TR and ICD-11 (6L72) and empirically distinguishable from but frequently co-occurring with major depressive disorder. Approximately 7 to 10 percent of bereaved adults meet criteria for PGD, with elevated suicide risk and functional impairment. Complicated grief therapy is the targeted psychotherapy most often referenced for prolonged grief, and existing PGD treatments have been studied primarily in specialty academic and clinical settings without examining at-home telehealth delivery. A small psychedelic-grief literature has emerged in psilocybin and ayahuasca observational and pilot studies. Prior real-world ketamine cohorts have characterized depression outcomes without focusing on prolonged grief. Objective This exploratory, hypothesis-generating analysis describes prolonged grief symptom outcomes among adults with clinically elevated baseline grief who received at-home ketamine-assisted therapy through Mindbloom, a telehealth ketamine therapy platform. Methods We conducted a retrospective cohort analysis of 503 bereaved adults with clinically elevated prolonged grief symptoms (PGD-13 Total grief score ≥ 30 at baseline, a pragmatic severity threshold consistent with the score-based caseness cut used in the Shear randomized trials of complicated grief therapy on the predecessor Inventory of Complicated Grief) who confirmed the loss of a significant person on the PGD-13 gating question and received guided at-home sublingual or subcutaneous ketamine-assisted therapy through Mindbloom. Prolonged grief symptoms were assessed using the PGD-13 (mean baseline = 37.18) at post-session 2 (n = 282), post-session 4 (n = 196), and post-session 6 (n = 121). The primary study-defined response was a ≥ 5-point improvement in PGD-13 Total grief score from baseline. We additionally applied an adapted version of a formal Prolonged Grief Disorder caseness algorithm at baseline and post-session 6 to characterize diagnostic remission. Results Mean PGD-13 Total grief score declined from 37.18 at baseline (95% bootstrap CI36.72-37.63) to 31.07 at post-session 2 (mean change − 6.11), 27.61 at post-session 4 (− 9.57), and 25.81 at post-session 6 (− 11.37). Among the 121 post-session 6 completers (24% of the eligible cohort), study-defined response (≥ 5-point improvement) was achieved by 51.8% at post-session 2 (95% Wilson CI46.0-57.5%), 68.4% at post-session 4 (61.6-74.5%), and 76.0% at post-session 6 (67.7-82.8%); any improvement (≥ 1-point) was achieved by 90.1% of post-session 6 completers (83.5-94.2%). The proportion of post-session 6 completers below the score-based threshold of 30 was 63.6% (95% CI54.8-71.7%); 0.8% reported no change and 9.1% reported any worsening. Applying the adapted PGD caseness algorithm, 42.7% of baseline participants met full diagnostic criteria for Prolonged Grief Disorder under the ICD-11 duration threshold (95% CI38.5-47.1%); 35.6% met DSM-5-TR criteria (95% CI31.5-39.9%). Among completers who met caseness at baseline, 73.2% no longer met ICD-11 criteria at post-session 6 (n = 41/56; 95% CI60.4-83.0%); 71.1% no longer met DSM-5-TR criteria (n = 32/45; 95% CI56.6-82.3%). In a worst-case sensitivity analysis in which all non-completers were assumed to retain full caseness, the confirmed diagnostic remission rates were 19.1% (ICD-11; 95% CI14.4-24.8%) and 17.9% (DSM-5-TR; 95% CI13.0-24.1%). Item-level analysis revealed that the single largest mean change across the 10 PGD-13 symptom items occurred on the identity/role confusion item (mean 4.12 to 2.64; change − 1.48, 95% bootstrap CI − 1.70 to − 1.24, corresponding to a 35.9% reduction from baseline to post-session 6). In contrast, the emotional pain item most closely overlapping major depressive disorder phenomenology improved 26.4% over the same interval, ranking sixth of ten. Side effects of any type were uncommon (7.4% at post-session 2, 5.6% at post-session 4, 4.1% at post-session 6). Subgroup patterns of larger mean change in more recently bereaved patients were observed (largest at post-session 6 in the 6-to-11-months-since-loss band, mean change − 13.83 points; smallest in the 12-months-or-longer band, − 10.40 points). Conclusions In this retrospective cohort of 503 adults with PGD-13 Total grief score ≥ 30 at baseline receiving at-home ketamine-assisted therapy through Mindbloom, prolonged grief symptoms declined monotonically across post-session timepoints; among the 121 post-session 6 completers, 76% achieved the primary study-defined response (≥ 5-point improvement) and 64% dropped below the score-based threshold of 30. Among completers meeting formal PGD caseness at baseline, the majority (73% under ICD-11, 71% under DSM-5-TR) no longer met diagnostic criteria at post-session 6, and item-level patterns showed the largest improvement on a non-depression-overlapping grief-specific symptom. Observed PGD-13 changes cannot be cleanly disentangled from concurrent depression-symptom changes in this uncontrolled design, because the cohort was treated for depression and the PGD-13 shares symptom content with depression instruments. The observed subgroup gradient runs opposite to what a strict mood-mediation account would predict, though concurrent depression improvement remains a compatible explanation. Randomized controlled trials with PGD-13 (or comparable independent grief instrument) as primary outcome, depression-independent comparator arms, and longer follow-up are needed to confirm these findings and to characterize the mechanism and durability of any observed effects.", "journal": "Research Square", "publication_date": "2026-06-01", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9839240/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9839240/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR1243670\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Chronic Pain,Emotional Processing,Randomized Controlled Trial,Observational Study,Safety,Adverse Events", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3022, "title": "Safety and Efficacy of Psilocybin in the Management of Treatment-Resistant Depression: A Systematic Review", "normalized_title": "safety and efficacy of psilocybin in the management of treatment resistant depression a systematic review", "authors": "Walters CK, Chetty S, Rants’o TA, Gossayn S, Lerotholi LJ.", "abstract": "Abstract Background: Conventional pharmacotherapy for treatment-resistant depression (TRD) has been found to provide limited benefit in a subset of patients. Psilocybin-assisted therapy has emerged as a promising modality due to its rapid-acting antidepressant effects and favourable tolerability profile shown in early trials. Despite growing research interest in psilocybin-assisted therapy the evidence for its use remains fragmented. Aim: To systematically review the evidence on the safety and efficacy of psilocybin in adults with TRD. Methods: This review follows the Preferred Reporting Items for Systematic Reviews (PRISMA) and JBI Manual for Systematic Reviews of Effectiveness. PubMed ®, MEDLINE ®, the Cochrane Collaboration's CENTRAL ® trials registry, PsycINFO ® and EMBASE ® were searched between 2014 and 2025 for clinical trials and observational studies that met the inclusion criteria for psilocybin versus other antidepressants for TRD. The JBI Critical Appraisal Checklists were used to assess the quality of the clinical trials. The review protocol was registered on PROSPERO (CRD420251063913) Results: Six trials met the inclusion criteria. Psilocybin showed promising results in lowering depressive scores in participants with TRD. Common adverse events included anxiety, nausea, headache, fatigue and suicidal ideation. No serious safety concerns or cases of physiological toxicity were identified. Study limitations included small sample sizes, open-label designs, and heterogeneous psychotherapy protocols. Conclusions: Psilocybin as a novel therapy for TRD demonstrates promising efficacy and tolerability safety profile. Nonetheless, current evidence remains preliminary, and larger, methodologically robust randomized trials are needed to confirm efficacy, optimize dosing, and standardize psychological support frameworks.", "journal": "Research Square", "publication_date": "2026-05-10", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9283280/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9283280/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:45", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1188752\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Headache / Migraine,Clinical Trial,Systematic Review,Review Article,Observational Study,Treatment-Resistant Depression,Safety,Adverse Events,Toxicity", "study_type": "Systematic Review", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3222, "title": "A128-Channel Wireless Wearable Myolink (W2 Myolink): Functional Characteristics and Multidisciplinary Experiments", "normalized_title": "a128 channel wireless wearable myolink w2 myolink functional characteristics and multidisciplinary experiments", "authors": "Zajaczkowski M, Koutsoftidis S, Sheeraz M, Barsakcioglu DY, Jia T, McGeady CA, Kundu A, Pizzi M, Tatti F, Bashford J, Bhavesh P, Farina D, Drakakis E.", "abstract": "Abstract This paper presents Wireless Wearable Myolink (W2 Myolink), a high-density, battery-powered system for wireless acquisition of surface electromyography(EMG) signals, and demonstrates its practicality across diverse experimentalparadigms. The device features a compact form factor (110x70x35 mm), low weight(160 g), and continuous operation for up to 6 h. It supports low-noise (1.34 µVRMS),high-resolution (24 bit) recordings from 128 EMG channels with real-time wireless datatransmission over Wi-Fi. The capabilities of W2 Myolink have been validated througha series of experiments. Conventional EMG studies included the recording and analysisof muscle activity during various gestures and hand movements, as well as concurrentEMG-EEG measurements for the investigation of cortico-muscular coherence. Thesystem’s suitability for clinical and pathological scenarios was examined using surrogateEMG signals representative of healthy subjects and of conditions such as myopathy,neuropathy, and Amyotrophic Lateral Sclerosis (ALS). More complex experimental usecases involved human-robot interaction with ISYBOT robotic arms, intraoperativeEMG monitoring during different types of surgery with and without exoskeletonassistance for the surgeon, and EMG acquisition during psychedelic experiencesinduced by psilocybin. Collectively, these results demonstrate that W2 Myolink canreliably acquire and wirelessly transmit high-quality, high-density EMG data in a broadrange of research and application contexts.", "journal": "Research Square", "publication_date": "2026-04-27", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9266175/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9266175/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR1183277\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Drug Interactions", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 159, "title": "Methamphetamine-Fentanyl Polysubstance Administration Produces Social Deficits and Corticolimbic Stress-Reward Circuit Adaptations", "normalized_title": "methamphetamine fentanyl polysubstance administration produces social deficits and corticolimbic stress reward circuit adaptations", "authors": "Salinsky LM, Fox JL, Diaz KC, Timmons BC, Ferguson SM.", "abstract": "Abstract Rationale and Objectives: Polysubstance use involving psychostimulants and opioids is increasingly prevalent and associated with elevated overdose risk, relapse vulnerability, and poor treatment outcomes. However, the neurobehavioral consequences of opioid-stimulant use remain poorly understood. We evaluated whether repeated methamphetamine-fentanyl polysubstance treatment disrupts social preference during withdrawal, whether psilocybin treatment restores sociability, and whether these manipulations alter corticolimbic expression of stress- and opioid-related genes. Methods Male and female rats received injections of methamphetamine and fentanyl or saline and were assessed for social preference at baseline and following 10 days of withdrawal. On withdrawal day 10, rats received psilocybin or saline and were reassessed for sociability 24 h later. CRHR1 and OPRM1 expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) were quantified by RT-qPCR. Results Withdrawal from 14-days of polysubstance treatment reduced social preference, replicating prior findings of withdrawal-associated social dysfunction. Psilocybin pretreatment did not restore social preference at the time point examined. In the mPFC, psilocybin bidirectionally altered CRHR1 expression depending on drug history, decreasing expression in saline-treated controls, while increasing expression following polysubstance treatment. In the NAc, polysubstance administration reduced CRHR1 expression. OPRM1 expression showed sex-dependent regulation with a marked reduction in the NAc of females following polysubstance treatment and evidence of sex-dependent effects in the mPFC. Conclusions Methamphetamine-fentanyl treatment produces persistent social deficits during withdrawal and region- and sex-dependent corticolimbic transcriptional adaptations in vivo. Although psilocybin did not restore sociability, it produced drug history-dependent regulation of cortical CRHR1.", "journal": "Research Square", "publication_date": "2026-04-22", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9306429/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9306429/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR1181545\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3117, "title": "Psilocybin’s Kinematic Effect on Manual Dexterity", "normalized_title": "psilocybin s kinematic effect on manual dexterity", "authors": "Klintefors P, Bhagavan C, Kanaan R, Bryson A, Berlowitz D, Attard Z, Carter O.", "abstract": "Abstract Rationale Clinical interest in psilocybin-assisted rehabilitation for motor disorders is growing. However, psilocybin’s motor effects are under-researched, and quantifying them is essential for assessing treatment risks and outcomes. Objectives This study aims to clarify whether acute effects of psilocybin disrupts established patterns of manual dexterity and coordination. Specifically, we evaluate the impact of psilocybin on velocity, smoothness and kinematic synergies. Methods In a randomised, blinded trial, healthy participants received three doses of psilo-cybin (5-20 mg) administered one week apart. Manual dexterity was assessed using the Box and Block Test (BBT) at baseline and 1.5, 3, and 4.5 hours post-drug administration. Task performance was analysed using a Bayesian mixed-effects model. For kinematic analysis, 21 hand landmarks were tracked from video recordings obtained at baseline and 1.5 hours post-administration. Principal component analysis (PCA) was the basis for evaluating the stability and dimensionality of kinematic synergies. Results BBT performance showed a modest biphasic dose-response pattern at higher doses (10-20 mg), with slight impairment during peak effects and slight improvement 4.5 hours post-administration relative to baseline. Effect sizes were small compared to inter-individual baseline variability. Kinematic analyses revealed no substantial changes in movement smoothness or velocity. Dimensionality metrics indicated a stable coordination structure, although finger movements showed a subtle increase in complexity. Conclusions Low to moderate doses of psilocybin did not meaningfully disrupt manual dexterity or the latent structure of hand coordination. These findings support the feasibility of combining psilocybin administration with active motor rehabilitation. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12621000560897 Date registered: 12 May 2021 URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id= 381526&isReview=true", "journal": "Research Square", "publication_date": "2026-04-14", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9291780/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9291780/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR1177862\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Clinical Trial,Review Article,Healthy Volunteers,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3228, "title": "Age moderates the relationship between psychedelics use and mental health in naturalistic settings", "normalized_title": "age moderates the relationship between psychedelics use and mental health in naturalistic settings", "authors": "Gregorio GD, Basset S, Manmohan H, Nixon WC, Pogaku A, Zhou J, Sanderson DJ, Lengieza ML, Bocchio M.", "abstract": "Abstract Depression and anxiety affect one in five adults, with age affecting prevalence. While clinical trials suggest classic psychedelics (e.g., psilocybin, LSD) and non-classic psychedelics (e.g., MDMA, ketamine) may alleviate these symptoms, it remains unclear how these relationships function in naturalistic settings or how they vary across the lifespan. We conducted a cross-sectional survey of 1,088 adults (18-55 + years) to assess how lifetime psychedelic use - categorized as classic, non-classic, or mixed - relates to mental health. Using structural equation modeling, we found that age significantly moderates the relationship between psychedelic use and mental health outcomes. Specifically, classic psychedelic use was linked to lower depression and anxiety among younger adults, but these effects diminished with age - even reversing for anxiety in older participants. These age-related effects persisted independently of drug-use parameters - including dosage, frequency, and recency of use - and were moderated by mystical experiences for depression, but not for anxiety. Our findings suggest that age may be a meaningful moderator of mental health outcomes from psychedelic use. This underscores the potential value of age-stratified research to optimize the efficacy and safety of psychedelic-assisted interventions, including in aging populations.", "journal": "Research Square", "publication_date": "2026-03-09", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9022170/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9022170/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR1164283\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Aging,Longevity,Mystical Experience,Clinical Trial,Observational Study,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3296, "title": "Substance-induced manic psychosis in which delusions were corroborated by a chatbot - case report", "normalized_title": "substance induced manic psychosis in which delusions were corroborated by a chatbot case report", "authors": "Shah S, Morrin H.", "abstract": "Abstract Background: This case describes a substance-induced manic episode with psychotic features in which interaction with an AI (artificial intelligence) chatbot appeared to corroborate and reinforce the patient’s delusional thought content and to contradict medical advice. Excerpts from the patient’s interactions with the AI chatbot provide novel clinical insight into this phenomenon, which to date has primarily been reported in news media. Case Presentation: A man in his 30s presented to the emergency department with a one-week history of escalating behavioural disturbance, severe insomnia, pressured and overinclusive speech, and grandiose beliefs. Symptom onset followed heavy polysubstance use at a recreational event, including psilocybin (dried mushrooms and liquid preparation), ketamine, cocaine, and alcohol. During this period, the patient reported extensive interaction with an AI chatbot (ChatGPT). The AI chatbot reportedly affirmed his perceived “spiritual awakening,” minimised the possibility that his presentation represented a manic episode, and provided medical advice, including discouragement of prescribed antipsychotic medication. Mental state examination was consistent with a manic episode with psychotic features, without evidence of perceptual disturbance. He was detained under mental health legislation for further assessment and commenced on olanzapine, with adjunctive sleep restoration and psychological interventions. Behavioural management included implementation of a care plan restricting AI chatbot use. Over several weeks, psychotic symptoms and behavioural disinhibition diminished, with subsequent improvement in insight. Conclusions: Concerns regarding potentially harmful interactions between AI chatbots and individuals with mental illness have largely been raised in news media. This case demonstrates that, in patients with psychotic symptoms, AI chatbots may reinforce delusional beliefs and impair the development of insight, and may also interfere with engagement with treatment by providing advice that conflicts with clinical recommendations. These observations raise clinical, ethical, and risk-management considerations regarding AI chatbot use during acute psychiatric illness. As AI chatbot use becomes increasingly widespread, clinicians should consider assessing their use and impact within clinical assessments and, where clinically indicated, implementing interventions to mitigate associated risks, ranging from psychoeducation to use-restriction strategies. Future population-level studies are required to establish the epidemiology of AI-associated mental health harms, and AI companies must bolster efforts to implement harm minimisation strategies and safeguards.", "journal": "Research Square", "publication_date": "2026-03-07", "publication_year": 2026, "doi": "10.21203/rs.3.rs-8919841/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8919841/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:50", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR1163168\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Spirituality,Case Report,Healthcare Workers,Safety,Drug Interactions", "study_type": "Case Report", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3047, "title": "Delayed psilocybin treatment after repeated mild traumatic brain injury recovers chronic behavioural deficits, reduces microglial density, and enhances hippocampal neurogenesis in rats", "normalized_title": "delayed psilocybin treatment after repeated mild traumatic brain injury recovers chronic behavioural deficits reduces microglial density and enhances hippocampal neurogenesis in rats", "authors": "Shultz S, Allen J, O'Regan G, Brand J, Liknaitzky P, O'Brien T, Christie B, McDonald S.", "abstract": "Abstract Repeated mild traumatic brain injury (RmTBI) can produce lasting cognitive, emotional, and social deficits (e.g., persistent post-concussion symptoms; PPCS). Despite the prevalence of RmTBI in sports, military, and domestic violence settings, effective treatments to alleviate the neurological consequences of RmTBI remain limited. Psilocybin, a serotonergic psychedelic, can enhance neuroplasticity and reduce neuroinflammation and has shown efficacy in psychiatric conditions that share overlapping pathophysiological and symptomatic features with RmTBI and PPCS. Here we examined whether delayed administration of psilocybin after RmTBI could improve long-term recovery in rats. Adult male rats received either five mTBIs delivered once daily via a lateral impactor or underwent sham procedures. After an 8-week recovery period, rats were administered psilocybin (1 mg/kg, i.p.) or saline. Behavioural testing began 24 hours later to evaluate psilocybin’s potential therapeutic effects. Afterwards, rats were perfused for immunohistochemical analysis of Cd11b and doublecortin to assess the density and morphology of microglia and newborn neurons, respectively, in the dorsal dentate gyrus. RmTBI produced persistent behavioural deficits across affective, social, and cognitive domains. Psilocybin treatment reversed several of these alterations, exhibiting antidepressant-like effects in the forced swim and sucrose preference tests, promoting pro-social behaviour, and increasing nociceptive thresholds in the hot plate test. Psilocybin also partially recovered RmTBI-induced increases in microglial density and, while RmTBI had minimal impact on the number of newborn neurons, psilocybin increased their abundance and enhanced their dendritic complexity. These results support the potential of psilocybin as a novel intervention for the enduring consequences of RmTBI.", "journal": "Research Square", "publication_date": "2026-02-22", "publication_year": 2026, "doi": "10.21203/rs.3.rs-8555503/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8555503/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1157820\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Neurogenesis,Emotional Processing,Inflammation", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3032, "title": "Safety and Efficacy of Microdosing Psilocybin over 8 Weeks for Major Depressive Disorder: A Randomized Clinical Trial", "normalized_title": "safety and efficacy of microdosing psilocybin over 8 weeks for major depressive disorder a randomized clinical trial", "authors": "Petranker R, Farb N, Syed O, Li E, Shore D, Anderson T, Blackman A.", "abstract": "Abstract IMPORTANCE Microdosing psilocybin may be a novel treatment for major depressive disorder (MDD). OBJECTIVE Assessing the antidepressant effects and safety of repeated low doses of psilocybin in participants diagnosed with MDD. DESIGN This was a Phase II, randomized, double-blind, placebo-controlled clinical trial. SETTING The trial was conducted from July 2022 to December 2024 at two centers: a pediatric clinic and a dedicated psychedelic therapy clinic. PARTICIPANTS were 39 adults aged 27 to 65 years with a diagnosis of MDD and mild to moderate symptom severity. INTERVENTIONS Participants received four weekly doses of placebo or 2 mg psilocybin, followed by four weekly open-label psilocybin doses. MAIN OUTCOMES AND MEASURES Primary outcome: Patient Health Questionnaire with Self-Directed Assessment Scales (PHQ-9) score from baseline week four. Secondary outcome measures were symptom counts measured by the Structured Clinical Interview for DSM-5 (SCID-5) symptom count, Quick Inventory of Depressive Symptomatology (QIDS), and the Dysfunctional Attitudes Scale (DAS-A-17) from baseline to week four. RESULTS 39 participants (mean age 44.4; 56.4% female) reported similar reductions in PHQ-scores regardless of group assignment after four weeks (psilocybin: mean difference -5.4; placebo: -6.0). Similar trends were observed in the QIDS and SCID-5, but participants in the microdose-first group showed more symptoms reduction than those in the placebo-first group (psilocybin: mean difference -1.2; placebo: -0.1) for the DAS-A-17. Symptom reductions persisted through open-label phase, with no serious treatment-emergent adverse events. CONCLUSIONS AND RELEVANCE Repeated low doses of psilocybin were safe and well tolerated but did not demonstrate statistically greater efficacy than placebo. Trial participation itself contributed to clinically significant symptom improvement. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT05259943", "journal": "Research Square", "publication_date": "2026-02-22", "publication_year": 2026, "doi": "10.21203/rs.3.rs-8319478/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8319478/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1157780\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Microdosing,Clinical Trial,Safety,Adverse Events", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 275, "title": "Time-Dependent Effects of Rapid-Acting Antidepressants in iPSC-Derived Neurons from Treatment-Resistant Depression and Healthy Volunteers", "normalized_title": "time dependent effects of rapid acting antidepressants in ipsc derived neurons from treatment resistant depression and healthy volunteers", "authors": "Johnston J, Jones G, Peng S, Yuan P, Yavi M, Kadriu B, Henter I, Quintanilla B, Elkahloun AG, Moaddel R, Schulmann A, Akula N, Kvarta M, McMahon F, Zarate C.", "abstract": "Abstract Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relevant system. Here, iPSCs from individuals with TRD and healthy volunteers (HVs) were differentiated into mature cortical-like neurons and treated for six and 24 hours with agents being investigated as rapid-acting antidepressants, including (2 R,6 R )-hydroxynorketamine (HNK), psilocybin, lysergic acid diethylamide (LSD), and 2,5-Dimethoxy-4-iodoamphetamine (DOI). Bulk and single-cell RNA sequencing assessed global and cell-type-specific transcriptomic responses. Synaptic proteins were evaluated via Western blotting and immunocytochemistry. To validate translational relevance, transcriptomic results were compared to CSF proteomics from ketamine-treated HVs. Despite differing initial pharmacological targets, overall gene expression across all compounds was highly correlated at matched timepoints compared to vehicle control, suggesting shared downstream effects. Both glutamatergic and serotonergic drugs converged on pathways involving inflammation, mTORC1 signaling, and cellular growth. At the single-cell level, HNK showed distinct cell-type specific alterations: upregulation in excitatory neurons and concomitant downregulation of inhibitory neuron populations. Differentially expressed genes from HNK-treated neurons also overlapped with CSF proteomic signatures from ketamine-treated individuals, supporting the model’s translational relevance. This study is the first to assess multiple putative rapid-acting antidepressants in parallel using an iPSC-derived neuron model. Both convergent and drug-specific changes in gene expression and pathway enrichment were observed across diverse compounds, supporting the use of human iPSC-derived neurons in antidepressant drug discovery. Clinical Trial Registry: www.clinical trials.gov, NCT02484456", "journal": "Research Square", "publication_date": "2026-02-11", "publication_year": 2026, "doi": "10.21203/rs.3.rs-8733841/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8733841/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR1154314\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Neuroplasticity,Mechanism of Action,Clinical Trial,Healthy Volunteers,Treatment-Resistant Depression,Transcriptomics,Proteomics,Inflammation", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3272, "title": "Can LLMs Get High? A Dual-Metric Framework for Evaluating Psychedelic Simulation and Safety in Large Language Models", "normalized_title": "can llms get high a dual metric framework for evaluating psychedelic simulation and safety in large language models", "authors": "Ben-Zion Z, Simon G, Lazebnik T.", "abstract": "Abstract Large language models (LLMs) are increasingly consulted by individuals for support during psychedelic experiences (\"trip sitting\"), yet no framework exists to evaluate whether these models can accurately simulate or safely respond to altered states of consciousness. We aimed to determine if LLMs can be induced to generate narratives resembling human psychedelic experiences and to quantify this behavior using psychometric and linguistic metrics. We developed a dual-metric evaluation framework comparing 3,000 LLM-generated narratives (from Gemini 2.5, Claude Sonnet 3.5, ChatGPT-5, Llama-2 70B, and Falcon 40B) against 1,085 human trip reports sourced from Erowid.org. Models were prompted under neutral and psychedelic-induction conditions across five substances (psilocybin, LSD, DMT, ayahuasca, and mescaline). We assessed outcomes using semantic similarity (Sentence-BERT embeddings) to human reports and the Mystical Experience Questionnaire-30 (MEQ-30). Psychedelic induction prompts produced a significant shift in model outputs compared to neutral conditions. Semantic similarity to human reports increased from a mean of 0.156 (neutral) to 0.548 (psychedelic), and mystical-experience scores rose from 0.046 to 0.748. While models demonstrated substance-specific linguistic styles (e.g., generating distinct semantic profiles for substances like LSD versus ayahuasca), they exhibited uniformly high mystical intensity across all substances. Contemporary LLMs can be \"dosed\" via text prompts to generate convincingly realistic psychedelic narratives. However, the dissociation between their high linguistic mimicry and lack of genuine phenomenology suggests they simulate the form of altered states without the experiential content. This capability raises significant safety concerns regarding anthropomorphism and the potential for AI to inadvertently amplify distress or delusional ideation in vulnerable users.", "journal": "Research Square", "publication_date": "2026-02-01", "publication_year": 2026, "doi": "10.21203/rs.3.rs-8682370/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8682370/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR1149771\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Mystical Experience,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3014, "title": "Psilocin fosters neuroplasticity in iPSC-derived human cortical neurons", "normalized_title": "psilocin fosters neuroplasticity in ipsc derived human cortical neurons", "authors": "Koch P, Schmidt M, Hoffrichter A, Davoudi M, Horschitz S, Lau T, Meinhardt M, Spanagel R, Ladewig J, Köhr G.", "abstract": "Abstract Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated human cortical neurons derived from induced pluripotent stem cells with the 5-HT2A receptor agonist psilocin - the psychoactive metabolite of psilocybin. We analyzed how exposure to psilocin affects 5-HT2A receptor localization, gene expression, neuronal morphology, synaptic markers and neuronal function. Upon exposure of human neurons to psilocin, we observed a decrease of cell surface-located 5-HT2A receptors first in the axonal- followed by the somatodendritic-compartment. Psilocin further provoked a 5-HT2A-R-mediated augmentation of BDNF abundance. Transcriptomic profiling identified gene expression signatures priming neurons to neuroplasticity. On a morphological level, psilocin induced enhanced neuronal complexity and increased expression of synaptic proteins, in particular in the postsynaptic-compartment. Consistently, we observed an increased excitability and enhanced synaptic network activity in neurons treated with psilocin. In conclusion, exposure of human neurons to psilocin might induces a state of enhanced neuronal plasticity which could explain why psilocin is beneficial in the treatment of neuropsychiatric disorders where synaptic dysfunctions are discussed.", "journal": "Research Square", "publication_date": "2026-01-06", "publication_year": 2026, "doi": "10.21203/rs.3.rs-4242829/v3", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4242829/v3", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:45", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1140594\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Neuroplasticity,Receptor Pharmacology,Biomarkers,Treatment-Resistant Depression,Transcriptomics", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3048, "title": "Real-World Psilocybin Therapy for Treatment-Resistant Depression: a Retrospective Observational Study", "normalized_title": "real world psilocybin therapy for treatment resistant depression a retrospective observational study", "authors": "Jungwirth J, Westenhöfer S, Aicher H, Provaznikova B, Kronenberg G, Seifritz E, Prinz S, Olbrich S.", "abstract": "Abstract Psilocybin has demonstrated promising antidepressant effects in depression and treatment-resistant depression (TRD) in controlled clinical trials. However, its effectiveness and safety in real-world therapeutic settings remain largely unknown. Although psilocybin is not yet approved as an antidepressant treatment, Switzerland’s unique legal framework allows its limited medical use for TRD. We conducted a retrospective analysis of medical records from 19 TRD patients treated with psilocybin (20-35mg) across one to four dosing sessions at the Psychiatric University Hospital Zurich. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory II (BDI). Changes from baseline to interim and post-treatment were analyzed, including response, remission, and the reliable change index. MADRS scores significantly decreased from baseline ( M = 30.78) to post-treatment ( M = 19.89), with a large effect size (Hedges’ g = 1.37, p", "journal": "Research Square", "publication_date": "2025-12-09", "publication_year": 2025, "doi": "10.21203/rs.3.rs-8079137/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8079137/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1132641\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Clinical Trial,Observational Study,Treatment-Resistant Depression,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3166, "title": "Limited prognostic value of early maladaptive schemas for acute psychedelic experience and symptom improvement", "normalized_title": "limited prognostic value of early maladaptive schemas for acute psychedelic experience and symptom improvement", "authors": "Buchard A, Seragnoli F, Sabe M, Eskinazi M, Aboulafia T, Furtado L, Briefer J, Roediger E, Penzenstadler L, Zullino D, Thorens G.", "abstract": "Abstract Early maladaptive schemas (EMS) are highly prevalent in patients seeking psychedelic-assisted psychotherapy and correlate strongly with baseline depression and anxiety. This study characterized EMS in 192 adults and longitudinally followed 74 patients receiving psilocybin- or LSD-assisted therapy. We found that baseline schema burden, particularly related to failure and defectiveness, was linked to cognitive-depressive symptoms but did not predict the quality of the acute psychedelic experience or moderate overall symptom improvement. While patients experienced significant reductions in both depression and anxiety symptoms with each session, these changes were dependent on initial symptom severity, not their schema profile. Treatment effects were comparable between psilocybin and LSD. These findings suggest the clinical utility of EMS lies not in patient selection or outcome prediction, but in identifying key cognitive-emotional themes, such as core beliefs about failure, to be targeted during psychotherapeutic integration.", "journal": "Research Square", "publication_date": "2025-11-30", "publication_year": 2025, "doi": "10.21203/rs.3.rs-8214817/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8214817/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR1128933\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Emotional Processing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3049, "title": "Standardization of Psilocybin Dosing in a Natural Product-Based Retreat Setting: A Practical Method for Dose Quantification and Adjustment Across Sessions", "normalized_title": "standardization of psilocybin dosing in a natural product based retreat setting a practical method for dose quantification and adjustment across sessions", "authors": "Rosal SRP, Faber SC.", "abstract": "Abstract Natural variation in psilocybin content across mushroom samples presents a significant challenge to consistent dosing in both research and retreat settings. In this observational report, we describe a pragmatic approach for quantifying psilocybin content in naturally sourced material to ensure more standardized dosing across participants. Eleven individuals participated in a 7-day psilocybin retreat, receiving two doses of psilocybin-containing mushrooms. The psilocybin content was chemically analyzed rather than inferred from weight, revealing large variability across samples. Standardization based on measured psilocybin concentration allowed for dose adjustments, including a planned increase of the second dose to approximately twice the first to compensate for known acute tolerance effects. This method provides a model for responsible natural product use in community or retreat settings and can inform future translational research.", "journal": "Research Square", "publication_date": "2025-11-16", "publication_year": 2025, "doi": "10.21203/rs.3.rs-8000629/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-8000629/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1120883\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Observational Study", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3067, "title": "Psilocybin reduces depressive-like behavior and improves cognition in healthy aging mice via epigenetic regulation of plasticity- and immune-related genes", "normalized_title": "psilocybin reduces depressive like behavior and improves cognition in healthy aging mice via epigenetic regulation of plasticity and immune related genes", "authors": "Mennenga S, Hanson T, Semple M, Lifshitz D, Flores B, Balducci J, Harker S, Ford A, Lewis C.", "abstract": "Abstract For many, cognitive and affective health declines through typical aging. Although cognitive and affective symptoms are often studied in isolation, they share substantial overlap, and arise, in part, from common biological processes. Aging is accompanied by diminished neural plasticity, heightened neuroinflammation, and widespread alterations in the epigenome. These molecular changes mirror behavioral decline, linking the erosion of cellular adaptability to the decline of cognitive function and emotional well-being in aging. Here, we show that psilocybin reverses age-related behavioral and epigenetic alterations in aged mice. Male and female C57BL/6 mice (11 months old) received two intraperitoneal doses of psilocybin (1mg/kg) or saline one week apart and were evaluated for memory and affective behaviors. Psilocybin improved learning and memory in females and reduced depressive-like behavior across sexes. Genome-wide DNA methylation profiling in the prefrontal cortex and bilateral hippocampus revealed widespread, sex- and region-specific effects, with the right hippocampus of females showing the most extensive gene-level changes. Differentially methylated loci were enriched for pathways related to synaptic organization, axon guidance, and neuroimmune signaling. Notably, psilocybin reversed age-associated methylation at CpG sites linked to typical aging, including within the Tbr1 promoter, a transcription factor essential for excitatory neuron development and synapse formation. Moreover, methylation at Tbr1 mediated psilocybin’s pro-cognitive effects on Y-Maze performance in females. Together, these findings demonstrate that psilocybin induces coordinated behavioral and epigenetic remodeling in the aging brain, with lateralized and sex-dependent signatures implicating neuroimmune and neuroplasticity transcriptional networks. Psilocybin thus emerges as a candidate compound for promoting aging resilience.", "journal": "Research Square", "publication_date": "2025-11-04", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7890051/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7890051/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1114471\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Neuroplasticity,Mechanism of Action,Aging,Epigenetics,Wellbeing,Resilience,Emotional Processing,Animal Study,Genomics,Inflammation,Immune Function", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3160, "title": "Psilocybin’s effect on human brain synaptic plasticity", "normalized_title": "psilocybin s effect on human brain synaptic plasticity", "authors": "Johansen A, Plavén-Sigray P, Madsen MK, Søndergaard A, Messel C, Geisler M, Nasser A, McCulloch DE, Beliveau V, Vassilieva A, Lund A, Lehel S, Ozenne B, Stenbæk DS, Fisher PM, Svarer C, Knudsen GM.", "abstract": "Abstract Psychedelics such as psilocybin have been linked to enhanced neuroplasticity and symptom relief in affective disorders, but the neurobiological mechanisms and impact of environmen-tal context remain unclear. Here, we tested whether a single dose of psilocybin alters synap-tic density in healthy individuals and whether setting-dependent subjective experience shapes this effect. Fifteen healthy participants had a psilocybin-induced psychedelic experi-ence either inside an MRI scanner or in a therapeutic-like room. We assessed synaptic densi-ty changes by measuring the Synaptic Vesicle glycoprotein 2A in the frontal cortex and hip-pocampus with [¹¹C]UCB-J PET at baseline and one-week post-dose, and assessed subjective experiences immediately afterwards and at three months. Participants treated in the thera-peutic-like setting exhibited more intense mystical-type experiences, longer-lasting psycho-logical benefits, and greater increases in synaptic density than those dosed in the MRI scan-ner. These findings indicate that psilocybin’s neuroplastic effects are modulated by envi-ronmental context, with important implications for psychedelic-assisted therapies.", "journal": "Research Square", "publication_date": "2025-10-09", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7469144/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7469144/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR1099975\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Mechanism of Action,Mystical Experience,Healthy Volunteers", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3065, "title": "Towards Novel Antidepressant Strategies: A Comparative Study of Ketamine, Psilocybin, and Fluoxetine in a Chronic Stress Model", "normalized_title": "towards novel antidepressant strategies a comparative study of ketamine psilocybin and fluoxetine in a chronic stress model", "authors": "Domzalska M, Kwiatkowska J, Cichon I, Sokolowska E.", "abstract": "Abstract Depression is a debilitating mental disorder affecting millions worldwide, yet current pharmacological treatments, such as selective serotonin reuptake inhibitors (SSRIs), often exhibit delayed onset and limited efficacy. The chronic social defeat (CSD) stress model in mice is a well-established preclinical paradigm for inducing depression-like behaviors and evaluating antidepressants effectiveness. This study compared the efficacy of both acute and chronic fluoxetine with acute ketamine and psilocybin treatment in male C57BL/6J mice subjected to CSD. Fluoxetine showed no significant effects 24 hours after a single dose or following 7 days of repeated administration; antidepressant-like effects only appeared after 14 days of continuous treatment. In contrast, a single dose of either ketamine or psilocybin significantly reversed social avoidance behavior at 24 hours, with sustained effects observed at 7- and 14-days post-treatment. These findings suggest that ketamine and psilocybin elicit rapid and durable, antidepressant-like responses in this preclinical model, in contrast to traditional SSRIs, like fluoxetine, which requires extended treatment duration, mirroring clinical efficacy patterns. The results support the utility of the CSD model in evaluating antidepressant efficacy and highlight the therapeutic potential of fast-acting agents such as ketamine and psilocybin as alternatives to conventional treatments for major depressive disorder.", "journal": "Research Square", "publication_date": "2025-10-06", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7269356/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7269356/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1096443\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3064, "title": "Regional Specificity of the Cingulate Cortex Thickness Association with the Intensity of Psilocybin Experience: A Replication Study", "normalized_title": "regional specificity of the cingulate cortex thickness association with the intensity of psilocybin experience a replication study", "authors": "Greguš D, Hlinka J, Tylš F, Viktorin V, Viktorinová M, Bravermanová A, Androvičová R, Andrashko V, Korčák J, Nikolič M, Adámek P, Beneš M, Páleníček T, Horáček J.", "abstract": "Abstract Rationale: Individual variability in psilocybin response is a major challenge for psychedelic-assisted therapy, with structural brain features potentially serving as predictive biomarkers. Lewis et al. (2020) reported that rostral anterior cingulate cortex thickness predicted emotional experiences under psilocybin, suggesting cortical morphometry as a marker of psychedelic responsivity. Objectives: This study sought to replicate and extend these findings by examining associations between cingulate thickness and psilocybin-induced altered states of consciousness using comprehensive assessment and rigorous statistical control. Methods: Twenty-five healthy participants underwent a double-blind, placebo-controlled crossover design with psilocybin (0.26 mg/kg) and placebo. High-resolution T1-weighted magnetic resonance imaging (MRI) measured cortical thickness across cingulate subregions. Subjective effects were assessed with the Altered States of Consciousness (ASC) questionnaire. Analyses applied false discovery rate (FDR) correction for multiple comparisons. Results: The primary Lewis et al. finding-that rostral anterior cingulate cortex thickness predicts emotional psilocybin responses-was not replicated. Instead, we identified a robust anterior-posterior gradient in cingulate thickness that significantly predicted global psychedelic intensity (r = 0.549, FDR p = 0.013). Moreover, general cingulate thickness was associated with the balance between anxiety-dominated and visionary states (r = 0.495, FDR p = 0.016). Conclusions: Findings indicate that structural organization of the cingulate cortex provides a neuroanatomical marker of variability in psychedelic response, with implications for personalized dosing and anticipatory management in psychedelic-assisted therapy. Results highlight the importance of broad cortical organizational patterns, rather than focal regional measures, when predicting psychedelic effects.", "journal": "Research Square", "publication_date": "2025-09-24", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7544401/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7544401/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1090728\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Anxiety,Brain Imaging,Consciousness,Biomarkers,Aging,Emotional Processing,Healthy Volunteers", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3089, "title": "Mindset Over Molecule: Comparing Self-Transcendent and Mystical Experiences Across Recreational Psilocybin, MDMA, and Cannabis Use", "normalized_title": "mindset over molecule comparing self transcendent and mystical experiences across recreational psilocybin mdma and cannabis use", "authors": "Chwyl C, Spata A, Lucas W, Luoma JB.", "abstract": "Abstract Background Self-transcendent and mystical experiences may be key mechanisms underlying psychedelics’ therapeutic effects, yet how these experiences differ across substances remains unclear. This study compared mystical and self-transcendent experiences across psilocybin, 3,4-Methylenedioxymethamphetamine (MDMA), and cannabis in a diverse, community-based sample, while accounting for covariates. Additionally, we examined the relative contributions of pharmacological versus psychological factors in shaping self-transcendent and mystical experiences. Methods Adults aged 18 years and older ( N = 397) were recruited with general, non-psychedelic-targeted advertisements on a crowdsourcing platform, and randomized to report on their most intense use experience with either cannabis, psilocybin or MDMA in the past five years. Participants completed measures of self-transcendent and mystical experiences, emotions, and variables previously found to predict mystical experiences (e.g., personality traits, motivations for use, intentions/expectations for the experience). Hierarchical multiple linear regressions examined the effects of substance type (cannabis/psilocybin/MDMA) on outcomes, both alone and while adjusting for contextual (set/setting) variables. Results Most of the sample reported recreational reasons for use (83%) and concurrently used other substances (75%). Psilocybin and MDMA corresponded to greater self-transcendent and mystical experiences than cannabis, even after controlling for contextual factors. However, effect sizes were generally small (standardized regression coefficients β =.14-34, p s.33). Notably, mindset-particularly surrendering to the experience and having spiritual/prosocial motivations-emerged as the strongest predictors, with models including these variables accounting for up to 58% of variance (compared to ≤ 10% for substance alone). Conclusions Findings indicate a “mindset-over-molecule” pattern wherein psychological context (“set”) is more strongly associated with psychedelic outcomes than substance type alone.", "journal": "Research Square", "publication_date": "2025-09-11", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7266162/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7266162/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1084679\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Mechanism of Action,Personality Change,Emotional Processing,Spirituality,Mystical Experience", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 560, "title": "Psychedelic Therapy, Positive Emotional Experiences, and the Central Role of Self-Compassion", "normalized_title": "psychedelic therapy positive emotional experiences and the central role of self compassion", "authors": "Zeifman R, Danias G, Agin-Liebes G, Pagni B, Kettner H, Bhat V, Ross S, Erritzoe D, Carhart-Harris R.", "abstract": "Abstract Background: Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional experiences and their association with improvements in mental health. Methods: Study 1 was an observational study of naturalistic psychedelic use. Study 2 used data from a clinical trial that compared psilocybin with escitalopram in individuals with major depressive disorder. In this trial, participants completed two dosing sessions, where they received either 25mg or 1mg of psilocybin. In both studies, following their psychedelic experience or psilocybin dosing sessions, participants rated their acute experiences of seven specific positive emotional experiences (self-compassion, compassion toward others, gratitude, love, awe, ecstasy, and peace). Results: Relative to low-dose psychedelic, medium and high-dose psychedelic use were associated with greater positive emotional experiences. Relative to 1mg psilocybin, 25mg psilocybin was associated with greater positive emotional experiences. Several positive emotional experiences predicted improvements in mental health and mediated treatment outcomes, with the strongest evidence for the effect of self-compassion (over and above mystical experience and positive mood). Discussion: Positive emotional experiences, especially self-compassion, appear to play an important role within psychedelic therapy. Based on these findings, we highlight key considerations surrounding psychotherapeutic approaches to, and optimization of, psychedelic therapy. Future research should move beyond retrospective, self-reports of emotional experiences to fully capture their role within psychedelic therapy.", "journal": "Research Square", "publication_date": "2025-08-21", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7420529/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7420529/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR1071953\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Emotional Processing,Mystical Experience,Clinical Trial,Observational Study", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3307, "title": "Attitudes Toward Psychedelic-Assisted Therapies for Cancer-Related Psychosocial Symptoms: A Multi- Stakeholder Analysis", "normalized_title": "attitudes toward psychedelic assisted therapies for cancer related psychosocial symptoms a multi stakeholder analysis", "authors": "Schuman HD, Deleemans JM, Nguyen T, Savard C, Mina R, Carlson LE.", "abstract": "Abstract Background Psychedelic-assisted therapy (PAT) is gaining attention as a potential treatment for cancer-related psychosocial symptoms. While growing evidence highlights its promise, little is known about how different stakeholder groups perceive its use in oncology and palliative care. Objectives This study aimed to assess stakeholder-specific perspectives on PAT, including attitudes, perceived knowledge, agent-specific beliefs, safety and effectiveness, implementation barriers, and interest in training and access. Predictors of positive attitudes were also examined. Methods A national cross-sectional survey was conducted across Canada. Measures included the Attitudes to Psychedelics Questionnaire (APQ), self-rated knowledge, perceived effectiveness and safety of psychedelic agents, implementation barriers, and views on appropriate patient populations. Group comparisons were conducted using Kruskal-Wallis tests, ANOVA, and post hoc analyses; multivariate linear regression identified predictors of attitudes. Results A total of 742 participants were included: cancer patients (PLWC; n = 519), healthcare providers (HCP; n = 187), and policymakers (PM; n = 36). PLWC reported the most favourable attitudes toward PAT, significantly higher than both HCP and PM. Despite their positive views, PLWC self-reported the lowest knowledge. PM reported the highest perceived knowledge but also the greatest safety concerns. Across all groups, psilocybin was viewed as the most effective agent. PLWC and HCP supported PAT use across the cancer continuum, while most PM favoured restricting use to advanced-stage cases. Conclusion Stakeholder perspectives on PAT reveal high interest tempered by role-specific concerns about safety, legitimacy, and readiness. Effective and ethical integration of PAT into oncology will require stakeholder-informed education, regulatory guidance, and attention to contextual implementation needs.", "journal": "Research Square", "publication_date": "2025-08-18", "publication_year": 2025, "doi": "10.21203/rs.3.rs-6941009/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-6941009/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:50", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR1070146\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "End-of-Life Distress,Observational Study,Cancer Patients,Safety", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3316, "title": "Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: An [¹⁸F]FDG-PET Study", "normalized_title": "global increases in brain glucose metabolism following acute n n dimethyltryptamine and harmine administration in healthy volunteers an ¹⁸f fdg pet study", "authors": "Egger K, Bozsak R, Aicher H, Sari H, Poetzsch S, Rominger A, Martin-Soelch C, Dornbierer D, Quednow B, Scheidegger M, Cumming P.", "abstract": "Abstract Classical psychedelics such N,N -dimethyltryptamine (DMT), psilocybin, and lysergic acid diethylamide (LSD) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine-mimicking the pharmacological profile of ayahuasca-oral DMT induces a psychedelic experience lasting 4-5 hours. While neuroimaging studies have examined changes in brain activity, connectivity, and cerebral perfusion under psychedelics, their effects on cerebral glucose metabolism remain largely unexplored. Here, we used positron emission tomography with [ 18 F]fluorodeoxyglucose ([¹⁸F]FDG-PET) to assess the cerebral metabolic rate for glucose consumption (CMRglc) following buccal DMT + harmine (90 mg DMT, 120 mg harmine) versus placebo in a single-blind, placebo-controlled, crossover design in (n = 14) healthy males. Scans were acquired during peak drug effects, i.e., 100-170 min post-administration. Global CMRglc increased by 12% under DMT + harmine compared to placebo ( t = 2.57, p", "journal": "Research Square", "publication_date": "2025-07-26", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7099164/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7099164/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:50", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR1056074\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness,Aging,Healthy Volunteers", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3088, "title": "Psilocybin Mitigates Behavioral Despair and Cognitive Impairment in Treatment-resistant Depression Model using Wistar Kyoto Rats", "normalized_title": "psilocybin mitigates behavioral despair and cognitive impairment in treatment resistant depression model using wistar kyoto rats", "authors": "Wang Z, Robbins B, Zhuang R, Bruggen Rv, Sandini T, Li X, Zhang Y.", "abstract": "Abstract Major depressive disorder (MDD) is a leading cause of disability that affects over 300 million people globally. Despite multiple antidepressant trials, approximately one-third of MDD patients remain symptomatic, progressing to treatment-resistant depression (TRD). This persistence possibly is due to the multifaceted etiology of TRD, encompassing biological, psychological, and environmental factors. Chronic stress, prevalent in modern life, significantly contributes to mental health disorders and complicates TRD treatment. This study investigated psilocybin as a potential TRD treatment using a diathesis-stress animal model. Twenty-two male Wistar-Kyoto (WKY) rats were divided into control and stress groups, with the stress group further subdivided to receive either sham treatment or psilocybin as early intervention. Behavioral assessments demonstrated a significant and sustained beneficial effect of psilocybin on behavioral despair and cognitive impairment. Biochemical analyses revealed psilocybin-induced increases in thyroid-stimulating hormone (TSH) levels without significant changes in the hypothalamic-pituitary-adrenal (HPA) axis. The ability of psilocybin to counter stress-induced TSH reductions suggested that TSH may serve as a proxy marker of therapeutic response, although its causal role in mood regulation remains unclear. Additionally, following psilocybin administration, changes in cannabinoid receptor type I (CB1R) suggest a potential modulation of psilocybin intervention on the component of the endocannabinoid system (ECS), though causal links remain unconfirmed without antagonist studies. These findings highlight the potential of psilocybin to treat TRD through the targeting of previously unexplored biological pathways.", "journal": "Research Square", "publication_date": "2025-05-05", "publication_year": 2025, "doi": "10.21203/rs.3.rs-5493661/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-5493661/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1015165\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3286, "title": "Calcium Activation Mechanism of a Noncanonical Aromatic L-Amino Acid Decarboxylase from Psilocybin Mushroom", "normalized_title": "calcium activation mechanism of a noncanonical aromatic l amino acid decarboxylase from psilocybin mushroom", "authors": "Wang Y, Li T, Reynolds E, Wang Z, Torrens-Spence M, Weng J.", "abstract": "Abstract PcncAAAD is a calcium-activatable noncanonical aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. In this study, we establish an in silico RMSD-based evaluation model through molecular dynamics simulations, validated by in vitro enzyme assays, to decipher the enzyme’s calcium activation mechanism. Between the two metal-binding sites, the site at the N-terminal domain/CTD interface (site A) is found to play a primary role in the calcium activation of PcncAAAD, whereas the secondary site within the unique CTD (site B) contributes to the calcium-mediated stabilization of enzyme structure. Binding of calcium, but not sodium, exerts a profound influence on PcncAAAD activity by stabilizing a \"lid-rim\" structure underlying site A, which in turn maintains the integrity of the substrate-binding environment. In silico mutations disrupting site A or the “lid-rim” structure show severe structural distortion of the active site, leading to reduced or even eliminated activity as demonstrated by in vitro assays. Collectively, our computational and experimental analyses pinpoint the molecular mechanism underlying the noncanonical activation of PcncAAAD by calcium. These findings deepen our understanding of metal-activatable enzymes and hold promise for the rational design of engineered enzymes for the synthesis of aromatic amino acid derivatives.", "journal": "Research Square", "publication_date": "2025-04-27", "publication_year": 2025, "doi": "10.21203/rs.3.rs-6329392/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-6329392/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR1011162\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "End-of-Life Distress,In Vitro Study", "study_type": "In Vitro Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3092, "title": "Effects of a single dose of psilocybin on diet-induced weight loss in obese mice", "normalized_title": "effects of a single dose of psilocybin on diet induced weight loss in obese mice", "authors": "Keenan R, Haque R, Jin X, Mustafa T, Homman-Ludiye J, Elysee K, Wee ZS, Simonds S, Foldi C, Cowley M.", "abstract": "Abstract Prolonged obesity induces enduring structural changes within neural circuits that contribute to maintaining the body at an elevated/obese body weight. These circuits regulate various mechanisms which can inhibit extreme or persistent weight loss. Therefore, a potential therapeutic strategy to facilitate weight loss is to promote structural plasticity within the brain. Psychedelic compounds, such as psilocybin, promote neural plasticity caused by a rapid and persistent growth of dendritic spines, which can facilitate the remodelling of neural circuits. Preclinical and clinical studies using psychedelic compounds have demonstrated efficacy for various neuropsychiatric disorders, which are often comorbid with obesity, and share underlying neural mechanisms. Here, we evaluate the effects of a single dose of psilocybin on body weight, food intake and energy expenditure in diet-induced obese (DIO) mice switched onto a low-fat chow. Psilocybin exacerbated diet-induced weight loss over a four-week period in DIO mice and increased the susceptibility for mice to exhibit more profound weight loss. Psilocybin appears to exert these effects predominantly through modulating food intake, with no influence on energy expenditure. No differences were observed in body weight or food intake in DIO mice maintained on a high-fat diet, indicating psilocybin does not necessarily directly promote weight loss or reduce food intake. Rather, it may help facilitate weight loss, provided it is administered in combination with other weight loss promoting interventions. Additional experimentation is required to examine the precise mechanisms involved; however, this data supports further investigation into the use of psychedelic compounds as an adjunct therapy for obesity.", "journal": "Research Square", "publication_date": "2025-03-30", "publication_year": 2025, "doi": "10.21203/rs.3.rs-6225000/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-6225000/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR996923\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Mechanism of Action,Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3099, "title": "Ketamine and Psilocybin Differentially Impact Sensory Learning During the Mismatch Negativity", "normalized_title": "ketamine and psilocybin differentially impact sensory learning during the mismatch negativity", "authors": "Allohverdi S, Soltanzadeh M, Schmidt A, Charlton C, Hauke D, Karvelis P, Vollenweider F, Diaconescu A.", "abstract": "Abstract Ketamine and psilocybin show potential as therapies for various mental illnesses, including major depressive disorder. However, further investigation into their neural mechanisms is required to understand their effects on the brain. By combining computational modelling with electroencephalography (EEG), we examine the effects of ketamine and psilocybin on hierarchical sensory precision-weighted prediction error (pwPE) learning in the context of the auditory mismatch negativity, an event-related potential consistently shown to be reduced under psychotomimetic interventions. We employed a Bayesian framework and re-analyzed a previously acquired EEG dataset (Schmidt et al., 2012) by modelling single-trial EEG data using the Hierarchical Gaussian Filter. Using a placebo-controlled within-subject crossover design, healthy subjects were administered either S-ketamine or psilocybin during an auditory roving paradigm of pure sinusoidal tones. Our findings elucidate distinct neural impacts of ketamine and psilocybin on sensory learning: ketamine led to a larger reduction in the effect of sensory precision compared to placebo from 207 to 316 ms peaking at 277 ms in the frontal central channels, while psilocybin showed no significant effect. Both drugs reduced the expression of belief precision between 160 to 184 ms, peaking at 172 ms. For higher-level volatility pwPEs, ketamine reduced the expression while psilocybin had null effect at 312 ms. For perception of elementary imagery, ketamine had a greater effect than psilocybin on sensory and volatility precision, while psilocybin had a greater effect on volatility pwPEs. Our findings suggest hallucinogens have distinct effects on sensory learning that could inform tailored therapies for major depression.", "journal": "Research Square", "publication_date": "2024-09-25", "publication_year": 2024, "doi": "10.21203/rs.3.rs-4492873/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4492873/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR916682\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Mechanism of Action", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3115, "title": "Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates the gabapentin-mediated analgesia", "normalized_title": "psilocybin ameliorates neuropathic pain like behaviour in mice and facilitates the gabapentin mediated analgesia", "authors": "Askey T, Allen-Ross D, Lasrado R, Gilmour G, Hunt S, Tamagnini F, Ahmed M, Stephens G, Maiarú M.", "abstract": "Abstract Chronic pain states are challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin can produce a sustained anti-nociceptive effect in a mouse model of chronic neuropathic pain. Beyond this, the single dose of psilocybin caused a dramatic increase in the anti-nociceptive potential of gabapentin, a widely used treatment for neuropathic pain, such data are suggestive of establishment of longer lasting changes in network processing.", "journal": "Research Square", "publication_date": "2024-09-19", "publication_year": 2024, "doi": "10.21203/rs.3.rs-5026806/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-5026806/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR913343\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Chronic Pain,Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3122, "title": "Exploring U.K. cancer doctors’ attitudes toward psilocybin-assisted psychotherapy for cancer-related distress", "normalized_title": "exploring u k cancer doctors attitudes toward psilocybin assisted psychotherapy for cancer related distress", "authors": "Mageean S, Daniel A, Tai S.", "abstract": "Abstract Background A diagnosis of cancer is often associated with significant psychological distress. Current approaches to cancer-related distress predominantly fall short of meeting the needs of patients. Recent investigations have shown that administering psilocybin in combination with psychotherapy might be effective at reducing distress in cancer patients. Oncologists are often ‘gatekeepers’, who oversee cancer patient care; if this intervention were to become more routinely available, it is important to understand doctors’ attitudes toward psilocybin-assisted psychotherapy. Method Nine oncologists who worked across two National Health Service Trusts in England were interviewed using a semi-structured interview approach. Thematic analysis was used to analyse the interviews and guide the development of overarching themes and subthemes. Results The analysis revealed five overarching themes relating to oncologists’ experiences of cancer-related distress and attitudes towards psilocybin-assisted psychotherapy: current approaches to distress; attitudes towards psychedelics and psilocybin; quality research; service design and delivery; distress and patients from different backgrounds. Limitations: Future research should aim to explore the experiences and attitudes of other professionals, such as specialist cancer nurses, who are more likely to broach the subject of distress with cancer patients. Conclusions Oncologists are open to novel interventions for supporting patients experiencing cancer-related psychological distress. Future research should aim to address their concerns regarding the safety and potential interactions of psilocybin with anticancer treatments and should stratify trials with different patient groups, owing to the idiosyncratic nature of specific types of cancer.", "journal": "Research Square", "publication_date": "2024-09-17", "publication_year": 2024, "doi": "10.21203/rs.3.rs-4862438/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4862438/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR911306\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Cancer Patients,Safety,Drug Interactions", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3075, "title": "­­­­Single-Dose Psilocybin Therapy for Alcohol Use Disorder: Pharmacokinetics, Feasibility, Safety, and Efficacy in an Open-Label Study", "normalized_title": "single dose psilocybin therapy for alcohol use disorder pharmacokinetics feasibility safety and efficacy in an open label study", "authors": "Jensen ME, Stenbæk DS, Messell CD, Poulsen ED, Varga TV, Fisher PM, Nielsen MKK, Johansen SS, Volkow ND, Knudsen GM, Fink-Jensen A.", "abstract": "Abstract Background Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects a single dose have not been investigated. Aims To investigate the pharmacokinetics, feasibility, safety, and efficacy of single-dose psilocybin therapy in AUD. Methods This open-label, single-group study investigated single-dose psilocybin therapy in ten treatment-seeking adults (eight men and two women; median age 44 years) with severe AUD. The treatment involved two preparation sessions, a high-dose psilocybin session (25 mg), and two integration sessions. Pharmacokinetics were determined by noncompartmental analysis, and changes in alcohol consumption, craving and self-efficacy, were assessed with a linear mixed model. Results Notable between-participant pharmacokinetic variations were observed, with peak plasma psilocin concentrations ranging from 14-59 µg/L. Alcohol consumption significantly decreased over the 12 weeks following psilocybin administration. Heavy drinking days were reduced by 37.5 percentage points (95% CI, -61.1, -13.9, p = 0.005), and drinks per day decreased by 3.4 units (95% CI: -6.5, -0.3), p = 0.035). This was corroborated by reports of rapid and sustained reductions in craving and increases in self-efficacy. Conclusions Despite pharmacokinetic variations, a single 25 mg psilocybin dose was safe and effective in reducing alcohol consumption in AUD patients. Larger randomised, placebo-controlled, single-dose AUD trials are warranted. Funding This work was supported by The Novo Nordisk Foundation (NNF19OC0058412), The Lundbeck Foundation (R-355-2020-945), The Health Foundation(21-B-0358) and The Ivan Nielsen Foundation. Clinical trial registration: NCT05347849", "journal": "Research Square", "publication_date": "2024-08-22", "publication_year": 2024, "doi": "10.21203/rs.3.rs-4947184/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4947184/v1", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR899973\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Pharmacology,Receptor Pharmacology,Clinical Trial,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3337, "title": "Prevalence and Correlates of Psychedelic Use in Poland: A Study on a Representative Sample of Polish Adults", "normalized_title": "prevalence and correlates of psychedelic use in poland a study on a representative sample of polish adults", "authors": "Holas P, Kaminska J.", "abstract": "Abstract Objective Recent years have witnessed a resurgence in research exploring the therapeutic potential of classic psychedelics like psilocybin and LSD for treating mental disorders. However, there is a limited knowledge regarding the epidemiology of classic psychedelics consumption and the factors associated with their recreational use in Poland. Methods A representative sample of Polish citizens (N=1051 adults) completed an internet-based survey encompassing demographic inquiries, evaluations of psychedelic substance consumption including motivations and contexts, subjective assessments of psychedelics experience and evaluation of attitudes towards psychodelics and psychedelic-assisted therapy. Results Our study revealed that approximately 4% to 8% of Polish individuals, equivalent to around 2 million people, have experimented with psychedelic substances at least once in their lives. Men exhibited a higher likelihood of psychedelic use compared to women, with the largest cohort of users falling within the 25-34 age bracket and residing in urban areas. The most common motivation for reaching them was curiosity. The psychedelic experience was commonly described as a mixture of pleasant and unpleasant sensations. A significant portion of participants expressed a negative attitude towards psychedelics and psychedelic-assisted therapy, but previous experience with psychodelics was associated with more positive attitudes. Conclusions In this representative sample of Poles, we found a substantial percentage of adults who recreationally used classic psychedelics, with majority of them being young men coming from big cities. More studies are needed as well as educational programs that may foster scientific research into psychedelic therapy in Poland and the attitudes of Poles toward it.", "journal": "Research Square", "publication_date": "2024-08-14", "publication_year": 2024, "doi": "10.21203/rs.3.rs-4860906/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4860906/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR896775\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Observational Study", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3322, "title": "Latin American adults who regularly use macrodoses of psychedelics: a cross-sectional study", "normalized_title": "latin american adults who regularly use macrodoses of psychedelics a cross sectional study", "authors": "Véliz-García O, Domic M.", "abstract": "Abstract Psychedelics have a complex history marked by traditional use among indigenous cultures, early scientific interest, and subsequent prohibition. Despite their classification as controlled substances, recent decades have witnessed a resurgence of research into their therapeutic potential for various mental health conditions. However, most studies have focused on controlled clinical settings, leaving a significant gap in understanding how these substances are used in naturalistic contexts, particularly in Latin America. This study investigates the regular use of macrodoses of psychedelics among Latin American adults. We aimed to characterize the sociodemographic profiles, consumption practices, and subjective effects experienced by individuals who use psychedelics regularly. Data were collected via an online survey from 4,270 participants across several Latin American countries. Results indicated a diverse user base with varied motivations, predominantly psychological and spiritual well-being. The most frequently used substance was psilocybin mushrooms, with significant associations found between demographic variables and specific psychedelics used. The study provides new insights into the naturalistic use of psychedelics in Latin America, highlighting the need for informed, safe, and legal use frameworks.", "journal": "Research Square", "publication_date": "2024-07-31", "publication_year": 2024, "doi": "10.21203/rs.3.rs-4706910/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4706910/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:50", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR889998\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Wellbeing,Spirituality,Observational Study", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3345, "title": "Quantitative Natural Language Processing Markers of Psychoactive Drug Effects: A Pre-Registered Systematic Review", "normalized_title": "quantitative natural language processing markers of psychoactive drug effects a pre registered systematic review", "authors": "Ahuja S, Zaher F, Palaniyappan L.", "abstract": "Abstract Psychoactive substances used for recreational purposes have mind-altering effects, but systematic evaluation of these effects is largely limited to self-reports. Automated analysis of expressed language (speech and written text) using Natural Language Processing (NLP) tools can provide objective readouts of mental states. In this pre-registered systematic review, we investigate findings from the emerging field of computational linguistics in substance use with specific focus on identifying short-term effects of psychoactive drugs. From the literature identified to date, we note that all the studied drugs - stimulants, MDMA, cannabis, ketamine, and psychedelics - affect language production. Based on two or more studies per substance, we note some emerging patterns: stimulants increase verbosity; LSD reduces the lexicon; MDMA increases semantic proximity to emotional words; psilocybin increases positive sentiment; and cannabis affects speech stream acoustics. Ketamine and other drugs are understudied regarding NLP features (one or no studies). One study provided externally validated support for NLP and machine learning-based identification of MDMA intoxication. We could not undertake a meta-analysis due to the high degree of heterogeneity among outcome measures and the lack of sufficient number of studies. We identify a need for harmonised speech tasks to improve replicability and comparability, standardisation of methods for curating and analysing speech and text data, theory-driven inquiries, and the need for developing a shared Substance Use Language Corpus for data mining. The growing field of computational linguistics can be leveraged in the service of human behavioural pharmacology to study psychoactive substances through concerted efforts to achieve consistency in research methods.", "journal": "Research Square", "publication_date": "2024-07-09", "publication_year": 2024, "doi": "10.21203/rs.3.rs-4534997/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4534997/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR879311\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Pharmacology,Biomarkers,Emotional Processing,Meta-Analysis,Systematic Review,Review Article", "study_type": "Meta-Analysis", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3350, "title": "Psychedelics Use and the Risk of Reduced Formal Mental Health Care", "normalized_title": "psychedelics use and the risk of reduced formal mental health care", "authors": "Viña S.", "abstract": "Abstract Background: Due to increasing cultural and legal acceptance of psychedelics, there is a need to understand their potential influence on formal mental health care. This paper examines the connection between psychedelics, distress, and treatment utilization. Are psychedelic users less likely to use formal mental health care? Methods This study tests the relationship between psychedelics use (MDMA, Psilocybin, DMT, Ayahuasca, Peyote/Mescaline, and LSD) on stigma, psychological distress (K6), and formal mental health care use (medication, outpatient, and any use). This project also tests the impact of one measure of classic psychedelics (LCPU) use on distress and care. This project uses pooled data from the National Survey of Drug Use and Health (NSDUH) (2010 to 2018) (N=458,372). Results The analysis involved conducting a series of nested logistic regression models in Stata 18. The results provided evidence of an independent association between psychedelics use and a decreased likelihood of using mental health medication, outpatient treatment, and any formal mental health care. Additionally, the interaction terms revealed that as distress levels increase, psychedelics users are even less inclined to seek formal mental health care compared to non-psychedelic users. Conclusion Overall, the results suggest psychedelic users are less likely to use formal mental health care, even when they are particularly distress, indicating a heightened societal risk of self-medication as these drugs become more widely available.", "journal": "Research Square", "publication_date": "2024-05-12", "publication_year": 2024, "doi": "10.21203/rs.3.rs-4378944/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-4378944/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR852229\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Observational Study,Safety,Drug Interactions", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3282, "title": "The Temporal Trajectory of the Psychedelic Mushroom Experience Mimics the Narrative Arc of the Hero’s Journey", "normalized_title": "the temporal trajectory of the psychedelic mushroom experience mimics the narrative arc of the hero s journey", "authors": "Brouwer A, Brown JK, Erowid E, Erowid F, Thyssen S, Raison CL, Carhart-Harris RL.", "abstract": "Abstract Psychedelic therapy has the potential to become a revolutionary and transdiagnostic mental health treatment, yielding enduring benefits that are often attributed to the experiences that coincide with peak psychedelic effects. However, there may be an underrecognized temporal structure to this process that helps explain why psychedelic and related altered states of consciousness can have a initially distressing but ultimately a distress-resolving effect. Here we present a qualitative analysis of the self-reported ‘comeup’ or onset phase, and ‘comedown’ or falling phase, of the psychedelic experience. Focusing on psilocybin or psilocybin-containing mushrooms, we show that the comeup is more often characterized by negatively valenced feeling states, while the comedown phase is more often characterized by positively valenced feeling states of the sort often observed following recovery from illness or adversity. In this way, the temporal trajectory of the psychedelic experience could be seen to mimic the narrative arc of the monomythical ‘Hero’s Journey’.", "journal": "Research Square", "publication_date": "2024-02-22", "publication_year": 2024, "doi": "10.21203/rs.3.rs-3941205/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3941205/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR810141\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3280, "title": "Prefrontal Electrophysiological Biomarkers and Mechanism-Based Drug Effects in a Rat Model of Alcohol Addiction", "normalized_title": "prefrontal electrophysiological biomarkers and mechanism based drug effects in a rat model of alcohol addiction", "authors": "Habelt B, Afanasenkau D, Schwarz C, Domanegg K, Kuchar M, Werner C, Minev IR, Spanagel R, Meinhardt MW, Bernhardt N.", "abstract": "Abstract Current treatments for alcohol use disorder (AUD) show large heterogeneity in response and thus limited effectiveness and high relapse rates. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR) and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.", "journal": "Research Square", "publication_date": "2024-02-21", "publication_year": 2024, "doi": "10.21203/rs.3.rs-3905152/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3905152/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR809495\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3145, "title": "MicroRNAs underlying the antidepressant effect of psilocybin - Establishing an nCounter pipeline for microRNA-quantification in the pig brain", "normalized_title": "micrornas underlying the antidepressant effect of psilocybin establishing an ncounter pipeline for microrna quantification in the pig brain", "authors": "Kaadt E, Søkilde R, Hansen H, Raval N, Lundgaard L, Just J, Knudsen G, Elfving B.", "abstract": "Abstract Novel treatment strategies are needed to overcome some of the current challenges related to treatment resistance and treatment latency within the psychiatric field. Recently, psilocybin has shown promise as a novel treatment of major depressive disorder. A single dose of psilocybin is associated with lasting changes in personality and mood. In parallel, various studies have indicated that microRNAs (miRNAs) are regulated after antidepressive interventions. Here, pigs were used to study the transcriptional profiles of miRNAs in the prefrontal cortex (PFC) and hippocampus (HIP), 1 day and 1 week after a single dose of psilocybin. A streamlined process was developed to adapt the Nanostring nCounter technology, specifically the Human v3b miRNA Assay panel, for compatibility with pig tissue samples. The mirmachine tool was used to select miRNAs with complete human-pig sequence conservation to make a conservative reannotation of pig microRNAs. Furthermore, different normalization strategies were employed. Utilizing this pipeline, dysregulation of 12 miRNAs in the PFC and 2 miRNAs in the HIP was ∂identified 1 day after psilocybin administration. Seven days after psilocybin administration, only 4 dysregulated miRNAs were observed in the HIP. Among the 18 identified miRNAs, 9 have previously been linked to depression. Notably, miR-212-3p and miR-107 displayed robust acute regulation across all four normalization strategies in the PFC. The two miRNAs are known to exert anti-inflammatory effects, mirroring previously reported effects of psilocybin. These results suggest that psilocybin may exert its acute and sustained molecular effects through the regulation of specific miRNAs in core brain areas of depression.", "journal": "Research Square", "publication_date": "2024-01-11", "publication_year": 2024, "doi": "10.21203/rs.3.rs-3787179/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3787179/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR786762\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Personality Change,Inflammation", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3174, "title": "Psilocybin-Assisted Therapy for Severe Alcohol Use Disorder: Protocol for a Double-Blind, Randomized, Placebo-Controlled, 7-month Parallel-Group Phase II Superiority Trial", "normalized_title": "psilocybin assisted therapy for severe alcohol use disorder protocol for a double blind randomized placebo controlled 7 month parallel group phase ii superiority trial", "authors": "Vanderijst L, Hever F, Buot A, Dauré C, Benoit J, Hanak C, Veeser J, Morgiève M, Campanella S, Kornreich C, Mallet L, Leys C, Noël X.", "abstract": "Background: A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction. Methods:: In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21-64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in 1) drinking behavior parameters up to six months posthospital discharge, 2) symptoms of depression, anxiety, trauma, and global functioning, 3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and 4) psychological processes and alcohol-related parameters. Discussion: The discussion outlines issues that might arise from our design. Trial registration: EudraCT 2022-002369-14 and NCT06160232", "journal": "Research Square", "publication_date": "2024-01-03", "publication_year": 2024, "doi": "10.21203/rs.3.rs-3829237/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3829237/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR782504\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Addiction,Neuroplasticity,Mechanism of Action,Clinical Trial,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3164, "title": "Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, proof-of-principle, placebo-controlled and crossover, neuroimaging trial in depression", "normalized_title": "engaging mood brain circuits with psilocybin embrace a study protocol for a randomized proof of principle placebo controlled and crossover neuroimaging trial in depression", "authors": "Poulin JM, Bigford GE, Lanctot KL, Giacobbe P, Schaffer A, Sinyor M, Rabin JS, Masellis M, Singnurkar A, Pople CB, Lipsman N, MacIntosh BJ, Nestor SM.", "abstract": "Abstract Background: Major Depressive Disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. Methods: Thirty-six participants diagnosed with MDD or Persistent Depressive Disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or active placebo (100 mg niacin) for the first treatment. Three weeks later, those in the control arm will cross over and all participants will receive 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in 1) cerebral blood flow and 2) functional brain activity in networks associated with mood regulation and depression when compared to placebo. Secondary outcomes include changes in MADRS score over time compared to placebo, and changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline to examine relationships with clinical response, and neuroimaging measures. Discussion: This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. Trial registration: ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.", "journal": "Research Square", "publication_date": "2023-12-27", "publication_year": 2023, "doi": "10.21203/rs.3.rs-3474764/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3474764/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR779931\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Inflammation", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3364, "title": "Aesthetic Chills Mitigate Maladaptive Cognition In Depression", "normalized_title": "aesthetic chills mitigate maladaptive cognition in depression", "authors": "Schoeller F, Jain A, Adrien V, Maes P, Reggente N.", "abstract": "Background: Depression is a major global health challenge, affecting over 300 million people worldwide. Current pharmacological and psychotherapeutic interventions have limited efficacy, underscoring the need for novel approaches. Emerging evidence suggests that peak emotional experiences characterized by awe, transcendence, and meaning hold promise for rapidly shifting maladaptive cognitive patterns in depression. Aesthetic chills, a peak positive emotion characterized by physical sensations such as shivers and goosebumps, may influence reward-related neural pathways and hold promise for modifying core maladaptive beliefs rooted in early adverse experiences. Methods We enrolled 96 patients diagnosed with major depressive disorder. A validated database of multimedia known to elicit chills responses (ChillsDB) was used for stimulus presentation. Participants' emotional responses were assessed using the Emotional Breakthrough Inventory (EBI), while shifts in self-schema were measured via the Young Schema Questionnaire (YSQ). Results The study found that chill-inducing stimuli have the potential to positively influence the core schema of individuals with depression, impacting areas of self-related beliefs. The associated phenomenology triggered by chills appears to share similarities with the altered states of consciousness induced by psychedelic substances like psilocybin. Conclusions These preliminary results suggest that the biological processes involved in aesthetic chills could be harnessed as a non-pharmacological intervention for depression. However, further investigation is necessary to comprehensively understand the neurophysiological responses to chills and to evaluate the practicality, effectiveness, and safety of utilizing aesthetic chills as a preventive measure in mental health care.", "journal": "Research Square", "publication_date": "2023-11-13", "publication_year": 2023, "doi": "10.21203/rs.3.rs-3582420/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3582420/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR759273\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Consciousness,Emotional Processing,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3279, "title": "“Why would you open someone’s brain up?” Lived experience insights inform a psilocybin-assisted psychotherapy treatment manual for body image disturbance", "normalized_title": "why would you open someone s brain up lived experience insights inform a psilocybin assisted psychotherapy treatment manual for body image disturbance", "authors": "Finkelstein C, Soha O, Roy A, Phillipou A, Rossell S.", "abstract": "Abstract Background: Body Image Disturbance (BID) is the distorted experience of one’s body. BID presents a risk for the onset, maintenance and relapse of body dysmorphic disorder and eating disorders, including anorexia nervosa (AN). Current treatments tend to focus on the cognitive and behavioural aspects while overlooking the perceptual symptoms and BID frequently persists beyond physical recovery. Psilocybin-assisted psychotherapy (PAP) may bridge the gap in current BID treatments by addressing perceptual and affective symptoms. This study sought to inform the development of a PAP treatment manual for BID in AN, through a co-design process informed by individuals with lived/living experience of AN. Methods: A Lived Experience Panel (LEAP) comprising six adult women who had a lived or living experience of AN and associated BID were presented with the proposed treatment protocol, including therapeutic interventions, and invited to provide feedback. An experiential, relativist framework informed reflexive thematic analysis of the LEAP data. Results: Reflexive thematic analysis of the LEAP data identified three central themes: enduring uncertainty; managing internal experience, and ambivalence in recovery. The LEAP also proposed strategies to address the challenges they identified and enhance the treatment manual more broadly. Conclusions: The LEAP identified challenges associated with intolerance of uncertainty, harm avoidance, alexithymia, and interoceptive impairment. The LEAP provided feedback that directly informed adaptations to the PAP treatment manual, including graduated interventions, the inclusion of nominated supports, and comprehensive psychoeducation for participants and their supports. Accordingly, a PAP treatment manual to treat BID for individuals with AN has been developed through lived experience co-design.", "journal": "Research Square", "publication_date": "2023-07-26", "publication_year": 2023, "doi": "10.21203/rs.3.rs-3189970/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3189970/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR698832\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Eating Disorders,Aging,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3168, "title": "Distinctive Molecular and Metabolic Profiles of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract", "normalized_title": "distinctive molecular and metabolic profiles of chemically synthesized psilocybin and psychedelic mushroom extract", "authors": "Shahar O, Botvinnik A, Shwartz A, Lerer E, Buko A, Hamid E, Kahn D, Guralnick M, Blakolmer K, Wolf G, Lerer L, Lerer B, Lifschytz T.", "abstract": "Abstract Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or “full spectrum” (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice. HTR measurement showed similar effects of PSIL and PME over 20 minutes. Brain specimens (frontal cortex, hippocampus, amygdala, striatum) were assayed for the synaptic proteins, GAP43, PSD95, synaptophysin and SV2A, using western blots. These proteins are indicators of synaptic plasticity. Three days after treatment, there was minimal increase in synaptic proteins. After 11 days, nested analysis of variance (ANOVA) showed a significant increase in each of the 4 proteins over all brain areas studied for PME versus vehicle control, while significant PSIL effects were observed only in the hippocampus and amygdala and were limited to PSD95 and SV2A. Metabolomic analyses of the pre-frontal cortex were performed by untargeted polar metabolomics utilizing capillary electrophoresis - Fourier transform mass spectrometry (CE-FTMS) and showed a differential metabolic separation between PME and vehicle groups. The purines guanosine, hypoxanthine and inosine, associated with oxidative stress and energy production pathways, showed a progressive decline from VEH to PSIL to PME. In conclusion, our synaptic protein findings suggest that PME has a more potent and prolonged effect on synaptic plasticity than PSIL. Our metabolomics data support a gradient of effects from inert vehicle via chemical psilocybin to PME further supporting differential effects. Further studies are needed to confirm and extend these findings and to identify the molecules that may be responsible for the enhanced effects of PME as compared to psilocybin alone.", "journal": "Research Square", "publication_date": "2023-07-19", "publication_year": 2023, "doi": "10.21203/rs.3.rs-3146433/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3146433/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR694814\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Mechanism of Action,Oxidative Stress,Animal Study,Metabolomics", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3217, "title": "Administration effects of four psilocybin mushroom extracts on serotonin levels and endothelial nitric oxide synthase activity levels in vivo and in vitro after one hour", "normalized_title": "administration effects of four psilocybin mushroom extracts on serotonin levels and endothelial nitric oxide synthase activity levels in vivo and in vitro after one hour", "authors": "Nkadimeng SM, Hay L, Steinmann CM, Eloff JN.", "abstract": "Abstract Background Psilocybin-containing mushrooms induce antidepressant and momentary increase in blood pressure (BP) with potential risk to users with cardiovascular diseases. Irregularities in nitric oxide (NO) levels play a key role in endothelial dysfunctions leading to increases in BP. Mushrooms species show large variation in potency which may potentially induce different outcomes and mechanisms of action. Effects of the mushrooms on the endothelial nitric oxide synthase activity is not known. Aim To investigate safety and effects of administration of four psilocybin-containing mushroom species, Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis and Psilocybe cubesis leucistic A + strain, on acute haemodynamic and LV parameters in normal Wistar rat and on serotonin, NO levels and endothelial NO synthase (eNOS) activity in vivo and in vitro on H9C2 cardiomyocytes. Methods Mushrooms were extracted with hot-boiling water and administered (5 mg/kg) through a direct catheterization in anaesthetized rats. Nuzak (0.2 mg/kg) and Nω-Nitro-L-arginine methyl ester hydrochloride (LNAME) were used as positive controls and negative control group given saline. Levels of serotonin, NO and eNOS activities were measured after 1-hour treatment. Results Mushroom treatments incited non-significant increase in LV parameters peaks only after 20 minutes and not immediate like with LNAME. Mushrooms induced a significant increase in serotonin levels and a suppressing effect on the eNOS activity in vivo in rats and in vitro in cardiomyocytes. Conclusion Mushroom treatments were safe on the LV function and induced a significant serotonin level with the concentration investigated. Disturbance in eNOS pathways may be the underlying mechanism involved in the psilocybin-mushroom extracts to inducing temporary BP increase. The four mushrooms exhibited different cardiac effects indicating variations depending on mushroom species.", "journal": "Research Square", "publication_date": "2023-07-17", "publication_year": 2023, "doi": "10.21203/rs.3.rs-3088850/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3088850/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR693606\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Mechanism of Action,Receptor Pharmacology,Animal Study,In Vitro Study,Safety", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1156, "title": "Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice", "normalized_title": "ethopharmacological evaluation of antidepressant like effect of serotonergic psychedelics in c57bl 6j male mice", "authors": "Takaba R, Ibi D, Yoshida K, Hosomi E, Kawase R, Kitagawa H, Goto H, Achiwa M, Mizutani K, Maede K, González-Maeso J, Kitagaki S, Hiramatsu M.", "abstract": "Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic-and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice 24 h post-treatment. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than an anxiolytic effects.", "journal": "Research Square", "publication_date": "2023-07-06", "publication_year": 2023, "doi": "10.21203/rs.3.rs-3138705/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3138705/v1", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR688165\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Receptor Pharmacology,Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3135, "title": "Psilocybin decelerates cellular senescence", "normalized_title": "psilocybin decelerates cellular senescence", "authors": "Hecker L, kato k, Kleinhenz JMK, Shin Y, Papageorgiou J, Zarrabi A.", "abstract": "Abstract Psilocybin is the psychoactive substance contained in the psilocybe(hallucinogenic) mushroom, which has received considerable attention among the scientific community in recent years. Human studies have demonstrated that even a single-dose of psilocybin can improve debilitating physical and psychological symptoms with durable long-term effects. >136 clinical studies with psilocybin have been completed or are ongoing for various indications, including psychiatric, neurodegenerative, chronic pain, and more. However, despite considerable clinical evidence for the therapeutic effects, the underlying molecular mechanisms responsible for its beneficial actions remain enigmatic. Studies with psilocybin have overwhelmingly focused on neurological impacts and/or behavioral outcomes; however, few studies have evaluated other mechanisms by which it exerts beneficial effects. It has recently been hypothesized that psilocybin may exert beneficial effects on aging; however, no studies have experimentally investigated the impact of psilocybin on senescence/aging. Using a previously validated human cell model of replicative senescence in vitro, cells were treated with psilocybin continuously throughout their replicative cellular lifecycle. Psilocybin treatment led to a dose-dependent decrease in cell-cycle arrest markers, increased markers of DNA replication and proliferation, reduced senescence-associated secretory phenotype (SASP), and reduced oxidative stress levels. Further, psilocybin did not demonstrate senolytic activity. Overall, these data are the first experimental evidence suggesting that psilocybin may decelerate the process of cellular senescence. Given that senescence and inflammation contribute to the pathogenesis of numerous age-related diseases, these studies could lay the foundation for the use of psilocybin as a therapeutic strategy for many age-related disease indications and/or as a geroprotective agent.", "journal": "Research Square", "publication_date": "2023-06-26", "publication_year": 2023, "doi": "10.21203/rs.3.rs-2921423/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-2921423/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR682607\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Chronic Pain,Mechanism of Action,Biomarkers,Aging,Cellular Senescence,Oxidative Stress,In Vitro Study,Inflammation", "study_type": "In Vitro Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3167, "title": "Exposure therapy under psilocybin for general anxiety disorder and claustrophobia", "normalized_title": "exposure therapy under psilocybin for general anxiety disorder and claustrophobia", "authors": "THORENS G, PENZENSTADLER l, FURTADO LCDC, SERAGNOLI F, ROTHEN S, MABILAIS C, ZULLINO D.", "abstract": "Case report of a patient with GAD and claustrophobia who underwent exposure therapy using psilocybin-assisted psychotherapy. The patient had failed to respond to conventional psychotherapeutic treatment. After three sessions of psilocybin-assisted psychotherapy, the patient experienced a reduction in anxiety and fear associated with closed spaces, elevators, and planes. The protocol included both an imaginary exposure exercise and a classic exposure therapy in an elevator during the psilocybin-assisted psychotherapy. the patient experienced a significant improvement in his score on the Beck Depression Inventory-II (BDI-II), the State-Trait Anxiety Inventory (STAI), and the Fear Questionnaire before and after therapy. He reported a generalization of the treatment effects, feeling more relaxed and having a greater willingness to confront fearful situations. He also described a shift in his perception of fearful stimuli, which may be explained as the development of new memory representations and a major disconfirmatory experience.", "journal": "Research Square", "publication_date": "2023-05-11", "publication_year": 2023, "doi": "10.21203/rs.3.rs-2859973/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-2859973/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR659477\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Case Report", "study_type": "Case Report", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3126, "title": "Brain dynamics predictive of response to psilocybin for treatment-resistant depression", "normalized_title": "brain dynamics predictive of response to psilocybin for treatment resistant depression", "authors": "Vohryzek J, Cabral J, Lord L, Fernandes H, Roseman L, Nutt D, Carhart-Harris R, Deco G, Kringelbach M.", "abstract": "Abstract Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (> 50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.", "journal": "Research Square", "publication_date": "2022-09-19", "publication_year": 2022, "doi": "10.21203/rs.3.rs-2060381/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-2060381/v1", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR548038\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3189, "title": "Effect of psilocybin on marble-burying in ICR mice: Role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder", "normalized_title": "effect of psilocybin on marble burying in icr mice role of 5 ht1a receptors and implications for the treatment of obsessive compulsive disorder", "authors": "Lerer B, Singh S, Botvinnik A, Shahar O, Wolf G, Yakobi C, Saban M, Salama A, Lotan A, Lifschytz T.", "abstract": "Abstract Preliminary clinical findings, supported by preclinical studies employing behavioral paradigms such as marble-burying, suggest that psilocybin may be effective in treating obsessive-compulsive disorder. On this background, we set out to explore 1) the role of 5-HT2A and 5-HT1A receptors in the effect of psilocybin on marble-burying; 2) the effect of staggered versus bolus psilocybin administration and persistence of the effect; 3) the effect of the 5-HT1A partial agonist, buspirone, on marble-burying and the head-twitch response (HTR) induced by psilocybin, a rodent correlate of psychedelic effects. Male ICR mice were administered psilocybin 4.4 mg/kg, escitalopram 5 mg/kg, 8-OH-DPAT2 mg/kg, M100907 2 mg/kg, buspirone 5 mg/kg, WAY100635 2 mg/kg or combinations, intraperitoneally, and were tested on the MBT. HTR was examined in a magnetometer-based assay. The results show that 1) Psilocybin and escitalopram significantly reduced marble-burying. The effect of psilocybin was not attenuated by the 5-HT2A antagonist, M100907. The 5-HT1A agonist, 8-OH-DPAT reduced marble-burying as did the 5-HT1A partial agonist, buspirone. The effect of 8-OH-DPAT was additive to that of psilocybin but that of buspirone was not. The 5-HT1A antagonist, WAY100635, attenuated the effect of 8-OH-DPAT and buspirone but not the effect of psilocybin. 2) Psilocybin injections over 3.5 hours had no effect on marble-burying and the effect of bolus injection was not persistent. 3) Co-administration of buspirone with psilocybin blocked its effect on HTR. These data suggest that neither 5-HT2A nor 5-HT1A receptors are pivotally implicated in the effect of psilocybin on marble-burying. Co-administration with buspirone may block the psychedelic effects of psilocybin without impeding its anti-obsessional effects.", "journal": "Research Square", "publication_date": "2022-09-07", "publication_year": 2022, "doi": "10.21203/rs.3.rs-2001983/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-2001983/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR541577\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "OCD,Receptor Pharmacology,Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3198, "title": "Psilocybin Combines Rapid Synaptogenic And Anti-Inflammatory Effects In Vitro", "normalized_title": "psilocybin combines rapid synaptogenic and anti inflammatory effects in vitro", "authors": "Smedfors G, Glotfelty E, Kalani N, Hjelle CP, Horntvedt O, Wellfelt K, Brodin A, von Kieseritzky F, Olson L, Karlsson T.", "abstract": "Abstract Psilocybin is a psychedelic substance approaching clinical use. The drug has long-lasting effects after single or multiple administrations and enhances structural plasticity in the brain. Little is known if the plasticity inducing effects of psilocybin could be timed to other treatments and promote a larger effect. We investigated the effect of psilocybin on cultured mouse hippocampal neurons, examining the plasticity promoting effects from 5 min to 72 h post-treatment. We found robust effects on pre- and postsynaptic (Piccolo and Homer1) protein expression 1-3 h following treatment. Presynaptic Synapsin-1 expression mirrored these findings, with peak expression 72 h post-treatment. Our studies suggest psilocybin opens a window of plasticity that rapidly normalizes. As psilocybin has been shown to have an effect treating diseases (e.g. depression and cluster headache) linked with inflammation, we used an immortalized microglia cell line (IMG) to demonstrate its anti-inflammatory effects against a lipopolysaccharide (LPS) challenge (we show reduced tumor necrosis factor-alpha (TNF-α) secretion). Altogether, our studies show discrete and acute cell type specific effects of psilocybin that provides insight into its mechanisms of action and potential therapeutic value.", "journal": "Research Square", "publication_date": "2022-03-07", "publication_year": 2022, "doi": "10.21203/rs.3.rs-1321542/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-1321542/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR465041\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Headache / Migraine,Neuroplasticity,Mechanism of Action,Animal Study,In Vitro Study,Inflammation", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" } ] }