{"rows":[{"id":5678,"title":"α2-Adrenergic receptor modulates 5-HT2A-mediated behavioral effects of MDMA and psilocybin in mice.","normalized_title":"α2 adrenergic receptor modulates 5 ht2a mediated behavioral effects of mdma and psilocybin in mice","authors":"Rosado AF, Yu AL, Yang JH, Rondeau J, Floris G, Basu A, Staszko S, Dibbs M, Feng J, Li Y, Warner-Schmidt J, Kelmendi B, Krystal JH, Pittenger C, Kwan AC, Kaye AP.","abstract":"Classic serotonergic psychedelics such as psilocybin act as agonists at cortical serotonin (5-HT) 2A receptors (5-HT2AR), inducing psychedelic effects in humans and head-twitch responses (HTRs) in rodents. Another class of psychedelic drugs called entactogens, exemplified by MDMA, function primarily as monoamine releasers and typically evoke minimal HTR despite causing serotonin release. The polypharmacology of psychedelic drugs at receptors other than 5-HT2AR may modulate their behavioral effects. Here, we report that MDMA, but not psilocybin, induces robust elevations of both 5-HT and norepinephrine (NE) in the medial prefrontal cortex. Blocking the release of extracellular NE unmasks MDMA-evoked HTR, suggesting that polypharmacology involving noradrenergic receptors may oppose the 5-HT2A-mediated effects of MDMA. Artificially elevating NE also attenuates psilocybin-induced HTR, supporting this hypothesis. Selective agonism of the noradrenergic α2 receptor (α2R) is sufficient to suppress 5-HT2A-mediated HTR, and also suppresses the HTR in locus coeruleus-ablated mice, suggesting that this effect is mediated by heteroreceptors. Moreover, psilocybin-induced effects in the forced swim test persisted in the presence of α₂R activation. Thus, these findings support a model in which some forms of 5-HT2A signaling can be attenuated by α2R activation without interfering with antidepressant-like effects. The ability to reduce potential side effects of 5-HT2A activation while preserving antidepressant-like effects via α2R and other analogous receptors may be relevant to therapeutic development.","journal":"Molecular Psychiatry","publication_date":"2026-07-06","publication_year":2026,"doi":"10.1038/s41380-026-03713-1","pubmed_id":"42414551","source_url":"https://doi.org/10.1038/s41380-026-03713-1","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-08 01:20:22","last_checked":"2026-07-09 01:20:16","raw_json":"{\"europe_pmc_id\":\"42414551\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7167607963\",\"openalex_url\":\"https://openalex.org/W7167607963\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[\"https://openalex.org/W1572907996\",\"https://openalex.org/W1836264777\",\"https://openalex.org/W1842480878\",\"https://openalex.org/W1897852281\",\"https://openalex.org/W1966733439\",\"https://openalex.org/W1968883863\",\"https://openalex.org/W1974195654\",\"https://openalex.org/W1983048332\",\"https://openalex.org/W1996618171\",\"https://openalex.org/W2009134620\",\"https://openalex.org/W2013923425\",\"https://openalex.org/W2021048027\",\"https://openalex.org/W2029122479\",\"https://openalex.org/W2043018270\",\"https://openalex.org/W2062822713\",\"https://openalex.org/W2063277419\",\"https://openalex.org/W2067481209\",\"https://openalex.org/W2069500038\",\"https://openalex.org/W2080123927\",\"https://openalex.org/W2082642884\",\"https://openalex.org/W2089306255\",\"https://openalex.org/W2090826913\",\"https://openalex.org/W2101795926\",\"https://openalex.org/W2120113858\",\"https://openalex.org/W2121872553\",\"https://openalex.org/W2122453635\",\"https://openalex.org/W2131184913\",\"https://openalex.org/W2139127187\",\"https://openalex.org/W2140901931\",\"https://openalex.org/W2147123664\",\"https://openalex.org/W2151488696\",\"https://openalex.org/W2153615886\",\"https://openalex.org/W2159032443\",\"https://openalex.org/W2168836105\",\"https://openalex.org/W2176880930\",\"https://openalex.org/W2218174899\",\"https://openalex.org/W2508048853\",\"https://openalex.org/W2576763726\",\"https://openalex.org/W2725596576\",\"https://openalex.org/W2739337936\",\"https://openalex.org/W2789541163\",\"https://openalex.org/W2802418317\",\"https://openalex.org/W2867834500\",\"https://openalex.org/W2914255920\",\"https://openalex.org/W2979144408\",\"https://openalex.org/W2988140114\",\"https://openalex.org/W3008141248\",\"https://openalex.org/W3014121938\",\"https://openalex.org/W3044771279\",\"https://openalex.org/W3113989724\",\"https://openalex.org/W3154620846\",\"https://openalex.org/W3155245221\",\"https://openalex.org/W3160990818\",\"https://openalex.org/W3217377467\",\"https://openalex.org/W4200256404\",\"https://openalex.org/W4205362358\",\"https://openalex.org/W4221078879\",\"https://openalex.org/W4291398459\",\"https://openalex.org/W4293729162\",\"https://openalex.org/W4296759713\",\"https://openalex.org/W4309269582\",\"https://openalex.org/W4321238244\",\"https://openalex.org/W4323825498\",\"https://openalex.org/W4362596352\",\"https://openalex.org/W4386740988\",\"https://openalex.org/W4390755783\",\"https://openalex.org/W4395069371\",\"https://openalex.org/W4400449392\",\"https://openalex.org/W4401212791\",\"https://openalex.org/W4406062303\",\"https://openalex.org/W4409987664\",\"https://openalex.org/W4410200405\",\"https://openalex.org/W4411302754\",\"https://openalex.org/W4412520959\",\"https://openalex.org/W4412626160\",\"https://openalex.org/W4414747399\",\"https://openalex.org/W7118979083\"],\"authorships\":[{\"id\":\"https://openalex.org/A5140175434\",\"display_name\":\"Axel F. Rosado\",\"orcid\":null},{\"id\":\"https://openalex.org/A5047632425\",\"display_name\":\"Abigail L. Yu\",\"orcid\":\"https://orcid.org/0009-0000-2194-5028\"},{\"id\":\"https://openalex.org/A5080588826\",\"display_name\":\"J. Yang\",\"orcid\":\"https://orcid.org/0009-0005-1220-4312\"},{\"id\":\"https://openalex.org/A5140189588\",\"display_name\":\"Jocelyne Rondeau\",\"orcid\":null},{\"id\":\"https://openalex.org/A5032092254\",\"display_name\":\"Gabriele Floris\",\"orcid\":\"https://orcid.org/0000-0002-5818-774X\"},{\"id\":\"https://openalex.org/A5023986617\",\"display_name\":\"Aakash Basu\",\"orcid\":\"https://orcid.org/0000-0002-8257-7393\"},{\"id\":\"https://openalex.org/A5140193039\",\"display_name\":\"Stephanie Staszko\",\"orcid\":null},{\"id\":\"https://openalex.org/A5022935279\",\"display_name\":\"Mark Dibbs\",\"orcid\":\"https://orcid.org/0000-0002-4341-361X\"},{\"id\":\"https://openalex.org/A5103001401\",\"display_name\":\"Jiesi Feng\",\"orcid\":\"https://orcid.org/0000-0003-3635-2625\"},{\"id\":\"https://openalex.org/A5100428710\",\"display_name\":\"Yulong Li\",\"orcid\":\"https://orcid.org/0000-0002-9166-9919\"},{\"id\":\"https://openalex.org/A5140193611\",\"display_name\":\"Jennifer Warner-Schmidt\",\"orcid\":null},{\"id\":\"https://openalex.org/A5110948308\",\"display_name\":\"Benjamin Kelmendi\",\"orcid\":\"https://orcid.org/0000-0002-3141-1326\"},{\"id\":\"https://openalex.org/A5071039477\",\"display_name\":\"John H. Krystal\",\"orcid\":\"https://orcid.org/0000-0001-6952-1726\"},{\"id\":\"https://openalex.org/A5001094886\",\"display_name\":\"Christopher Pittenger\",\"orcid\":\"https://orcid.org/0000-0003-2117-9321\"},{\"id\":\"https://openalex.org/A5014605321\",\"display_name\":\"Alex C. Kwan\",\"orcid\":\"https://orcid.org/0000-0003-2169-1667\"},{\"id\":\"https://openalex.org/A5008798564\",\"display_name\":\"Alfred P. Kaye\",\"orcid\":\"https://orcid.org/0000-0002-3153-1221\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S71149355\",\"source_display_name\":\"Molecular Psychiatry\",\"landing_page_url\":\"https://doi.org/10.1038/s41380-026-03713-1\",\"is_oa\":true}}}","topic_tags":"Pharmacology,Mechanism of Action,Receptor Pharmacology,Animal Study,Adverse Events","study_type":"Animal Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W7167607963"},{"id":5677,"title":"CSF galanin and noradrenaline downregulation by psilocybin therapy in major depressive disorder.","normalized_title":"csf galanin and noradrenaline downregulation by psilocybin therapy in major depressive disorder","authors":"Paslawski W, Doyon D, Ekman CJ, Yngwe H, Mamula D, Zareba-Paslawska J, Beckman M, Xu ZD, Hökfelt T, Tiger M, Lundberg J, Svenningsson P.","abstract":"Psilocybin is a rapid-acting antidepressant, but its mechanism of action in major depressive disorder remains unclear. In this secondary analysis of randomized, placebo-controlled trial with multimodal CSF and blood biomarker measurements, psilocybin selectively reduced CSF galanin and noradrenaline, implicating that normalization of these co-transmitters is a key pharmacodynamic signature.","journal":"Neuropsychopharmacology","publication_date":"2026-07-06","publication_year":2026,"doi":"10.1038/s41386-026-02490-3","pubmed_id":"42414566","source_url":"https://doi.org/10.1038/s41386-026-02490-3","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-08 01:20:22","last_checked":"2026-07-09 01:20:16","raw_json":"{\"europe_pmc_id\":\"42414566\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7167637338\",\"openalex_url\":\"https://openalex.org/W7167637338\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[\"https://openalex.org/W1981734883\",\"https://openalex.org/W2014887176\",\"https://openalex.org/W2040649786\",\"https://openalex.org/W2092170736\",\"https://openalex.org/W2175268588\",\"https://openalex.org/W2201607793\",\"https://openalex.org/W2461590308\",\"https://openalex.org/W2560044495\",\"https://openalex.org/W3156937150\",\"https://openalex.org/W4205208574\",\"https://openalex.org/W4308146982\",\"https://openalex.org/W4386305655\",\"https://openalex.org/W4386504040\",\"https://openalex.org/W4405890096\",\"https://openalex.org/W7161294763\"],\"authorships\":[{\"id\":\"https://openalex.org/A5026281113\",\"display_name\":\"Wojciech Pasławski\",\"orcid\":\"https://orcid.org/0000-0003-2141-4547\"},{\"id\":\"https://openalex.org/A5026248580\",\"display_name\":\"D Doyon\",\"orcid\":null},{\"id\":\"https://openalex.org/A5045856839\",\"display_name\":\"Carl Johan Ekman\",\"orcid\":\"https://orcid.org/0000-0002-3770-9385\"},{\"id\":\"https://openalex.org/A5095379592\",\"display_name\":\"Hampus Yngwe\",\"orcid\":null},{\"id\":\"https://openalex.org/A5086436715\",\"display_name\":\"Dejan Mamula\",\"orcid\":\"https://orcid.org/0000-0002-8215-7794\"},{\"id\":\"https://openalex.org/A5027605872\",\"display_name\":\"Justyna Zarȩba-Pasławska\",\"orcid\":\"https://orcid.org/0000-0001-6193-5908\"},{\"id\":\"https://openalex.org/A5065682565\",\"display_name\":\"Maria Beckman\",\"orcid\":\"https://orcid.org/0000-0002-9370-1863\"},{\"id\":\"https://openalex.org/A5024639719\",\"display_name\":\"Qing Xu\",\"orcid\":\"https://orcid.org/0000-0002-0387-7559\"},{\"id\":\"https://openalex.org/A5140192339\",\"display_name\":\"Tomas Hökfelt\",\"orcid\":null},{\"id\":\"https://openalex.org/A5063179816\",\"display_name\":\"Mikael Tiger\",\"orcid\":\"https://orcid.org/0000-0001-8495-8125\"},{\"id\":\"https://openalex.org/A5082468471\",\"display_name\":\"Johan Lundberg\",\"orcid\":\"https://orcid.org/0000-0002-4298-3936\"},{\"id\":\"https://openalex.org/A5036364090\",\"display_name\":\"Per Svenningsson\",\"orcid\":\"https://orcid.org/0000-0001-6727-3802\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S175030738\",\"source_display_name\":\"Neuropsychopharmacology\",\"landing_page_url\":\"https://doi.org/10.1038/s41386-026-02490-3\",\"is_oa\":true}}}","topic_tags":"Depression,Pharmacology,Mechanism of Action,Biomarkers","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W7167637338"},{"id":3587,"title":"Neurobehavioral Mechanisms of Psilocybin-assisted Treatment for Alcohol Use Disorder","normalized_title":"neurobehavioral mechanisms of psilocybin assisted treatment for alcohol use disorder","authors":"NYU Langone Health","abstract":"This is a double-blind, randomized, placebo-controlled Phase 2 mechanistic clinical trial designed to evaluate the therapeutic neural mechanisms of psilocybin in patients with alcohol use disorder (AUD), and to determine whether further studies are warranted to study the relationship of any such effects to clinical improvement in AUD symptoms. The primary aims are to evaluate the effects of psilocybin on AUD; measures will include 1) fMRI neural activation and functional connectivity, using a well-validated task to characterize neural and subjective response to negative affective and alcohol visual stimuli; 2) alcohol use data (self-report and blood biomarkers); and 3) self-report measures related the NE, IS, and EF domains.","journal":"ClinicalTrials.gov","publication_date":"2026-07-06","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT06349083","keywords":"Alcohol Use Disorder, Psilocybin, Inactive Placebo, Supportive therapy sessions, RECRUITING","substance_tags":"psilocybin","source_name":"ClinicalTrials.gov","date_added":"2026-07-01 11:04:28","last_checked":"2026-07-09 01:22:31","raw_json":"{\"nct_id\":\"NCT06349083\",\"overall_status\":\"RECRUITING\",\"phase\":[\"PHASE2\"]}","topic_tags":"Addiction,Brain Imaging,Mechanism of Action,Biomarkers,Clinical Trial","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"clinical trial","openalex_id":null},{"id":5673,"title":"The need for another tool: Australian healthcare professionals on the use of psilocybin for existential distress in people with cancer.","normalized_title":"the need for another tool australian healthcare professionals on the use of psilocybin for existential distress in people with cancer","authors":"Adler H, Filipic R, Gonzalez M, Kwon K, Lacey J, McDonald G, Sarris J, Chmiel K, Low M, Sinclair J, Grant S.","abstract":"BackgroundExistential distress is commonly experienced by people with cancer, yet there are limited treatment options. The therapeutic potential for psychedelic-assisted therapy (PAT) utilising psilocybin for this cohort is underexplored, with emerging literature showing clinical improvements in wellbeing. In Australia there is limited knowledge on healthcare professionals' (HCPs') attitudes, beliefs, and perceptions of the use of PAT for existential distress in people with cancer, and their opinions on components of delivery.MethodsQualitative semi-structured interviews were used to investigate the attitudes of 11 HCPs across specialties, largely from cancer treatment centres such as Chris O'Brien Lifehouse and Peter MacCallum Cancer Centre. The interviews were analysed using reflexive thematic analysis.ResultsFour key themes were identified: (1) A spectrum of knowing: The varied space of PAT knowledges, (2) Conceptualising and thinking through PAT in practice, (3) Navigating nuances territory: The complexity of providing and engaging with PAT, (4) Visualising potential future for PAT. Findings from the themes include that despite HCPs remaining interested in the potential of PAT, there are clear barriers being faced, knowledge gaps, and a desire for more research. HCPs also indicated a preference for PAT to be delivered in multidisciplinary teams, and for modes of delivery to be culturally sensitive and ethically rigorous. While some positioned this treatment as a last resort, others noted that there is a need for another 'tool' in the treatment of existential distress in cancer.ConclusionsAs evidence for PAT grows, expanded clinical and qualitative research will be needed to develop delivery models that are ethically sound, culturally sensitive and informed by clinical evidence, as well as traditional knowledges While small in sample size, this present study offers preliminary insights into how HCPs perceive the potential role of PAT in cancer populations, specifically for existential distress. Thus, this study contributes to a growing qualitative evidence base to understand implementation pathways for PAT in oncology settings, and the complexity of managing the need for another tool with existing barriers, limitations, and knowledge bases.","journal":"BMC Medicine","publication_date":"2026-07-05","publication_year":2026,"doi":"10.1186/s12916-026-05024-2","pubmed_id":"42410597","source_url":"https://doi.org/10.1186/s12916-026-05024-2","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-07 01:20:35","last_checked":"2026-07-09 01:20:16","raw_json":"{\"europe_pmc_id\":\"42410597\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7167496298\",\"openalex_url\":\"https://openalex.org/W7167496298\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[],\"authorships\":[{\"id\":\"https://openalex.org/A5014161444\",\"display_name\":\"Hannah Adler\",\"orcid\":\"https://orcid.org/0000-0002-4226-582X\"},{\"id\":\"https://openalex.org/A5140149775\",\"display_name\":\"Rebecca Filipic\",\"orcid\":null},{\"id\":\"https://openalex.org/A5113198437\",\"display_name\":\"Dr Maria Gonzalez\",\"orcid\":null},{\"id\":\"https://openalex.org/A5129392464\",\"display_name\":\"Ki Kwon\",\"orcid\":null},{\"id\":\"https://openalex.org/A5040937885\",\"display_name\":\"Judith Lacey\",\"orcid\":\"https://orcid.org/0000-0002-3751-406X\"},{\"id\":\"https://openalex.org/A5077777065\",\"display_name\":\"Geraldine McDonald\",\"orcid\":\"https://orcid.org/0000-0003-4417-2974\"},{\"id\":\"https://openalex.org/A5114087434\",\"display_name\":\"Jerome Sarris\",\"orcid\":null},{\"id\":\"https://openalex.org/A5140106837\",\"display_name\":\"Katarzyna Chmiel\",\"orcid\":null},{\"id\":\"https://openalex.org/A5108015801\",\"display_name\":\"Mitchell Low\",\"orcid\":\"https://orcid.org/0000-0002-3770-535X\"},{\"id\":\"https://openalex.org/A5140140174\",\"display_name\":\"Justin Sinclair\",\"orcid\":null},{\"id\":\"https://openalex.org/A5136366624\",\"display_name\":\"S Grant\",\"orcid\":null}],\"primary_location\":{\"source_id\":\"https://openalex.org/S135560524\",\"source_display_name\":\"BMC Medicine\",\"landing_page_url\":\"https://doi.org/10.1186/s12916-026-05024-2\",\"is_oa\":true}}}","topic_tags":"Mechanism of Action,Aging,Wellbeing,Observational Study,Cancer Patients","study_type":"Observational Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W7167496298"},{"id":3976,"title":"Psilocybin as a Transdiagnostic Treatment for Eating Disorders and Comorbid Psychopathology: Implications for Clinical Nosology and Research Directions.","normalized_title":"psilocybin as a transdiagnostic treatment for eating disorders and comorbid psychopathology implications for clinical nosology and research directions","authors":"Koning E, Richard J, Keshen A.","abstract":"ObjectiveEating disorders (EDs) are characterized by high rates of psychiatric comorbidity and suboptimal treatment outcomes. There remain critical gaps in research, including the exploration of effective transdiagnostic interventions. This forum article examines the potential of psilocybin treatment (PT) as a transdiagnostic intervention for EDs and common comorbidities, including the implications for alternative nosological frameworks, trial design, and clinical care.MethodA narrative review was conducted synthesizing clinical, mechanistic, and conceptual literature on PT for EDs and common psychiatric comorbidities. Searches of academic databases were supplemented by hand-searching and clinical trial registries. Thematic synthesis focused on transdiagnostic clinical evidence, mechanistic theories, and implications for the Hierarchical Taxonomy of Psychopathology (HiTOP), Research Domain Criteria (RDoC), treatment development, and clinical trial design.ResultsPreliminary clinical evidence supports the feasibility, safety, and therapeutic effects of PT for EDs, with robust transdiagnostic effects observed across comorbid conditions. Proposed mechanisms (i.e., serotonergic receptor agonism, psychoplastogenic effects, neural network desynchronization) target shared vulnerabilities that map onto dimensional constructs in HiTOP (Emotional Dysfunction superspectrum, Internalizing spectrum) and RDoC (negative/positive valence, cognitive, and social process domains) nosologies. Future research should explore pragmatic trial designs and dimensional outcome measures to capture the real-world complexities of PT for EDs.DiscussionPT demonstrates transdiagnostic therapeutic potential for EDs, and the advancement of dimensional nosologies, complex intervention frameworks, and personalized treatment protocols may address existing gaps in research and clinical care.","journal":"International Journal of Eating Disorders","publication_date":"2026-07-01","publication_year":2026,"doi":"10.1002/eat.70164","pubmed_id":"42393007","source_url":"https://doi.org/10.1002/eat.70164","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-04 01:20:05","last_checked":"2026-07-09 01:20:16","raw_json":"{\"europe_pmc_id\":\"42393007\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7167014213\",\"openalex_url\":\"https://openalex.org/W7167014213\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[\"https://openalex.org/W1191653087\",\"https://openalex.org/W1931781407\",\"https://openalex.org/W1944481685\",\"https://openalex.org/W1968733266\",\"https://openalex.org/W1969577526\",\"https://openalex.org/W1972883514\",\"https://openalex.org/W1976624064\",\"https://openalex.org/W1985513874\",\"https://openalex.org/W1986348004\",\"https://openalex.org/W2006378117\",\"https://openalex.org/W2007644698\",\"https://openalex.org/W2026832357\",\"https://openalex.org/W2030842831\",\"https://openalex.org/W2043197532\",\"https://openalex.org/W2052565335\",\"https://openalex.org/W2052804935\",\"https://openalex.org/W2080055550\",\"https://openalex.org/W2093203605\",\"https://openalex.org/W2095960650\",\"https://openalex.org/W2115430216\",\"https://openalex.org/W2118540296\",\"https://openalex.org/W2120654343\",\"https://openalex.org/W2140540881\",\"https://openalex.org/W2298540806\",\"https://openalex.org/W2339503814\",\"https://openalex.org/W2567379065\",\"https://openalex.org/W2599264051\",\"https://openalex.org/W2623228771\",\"https://openalex.org/W2733159797\",\"https://openalex.org/W2740567311\",\"https://openalex.org/W2795870103\",\"https://openalex.org/W2807534705\",\"https://openalex.org/W2888612576\",\"https://openalex.org/W2892307734\",\"https://openalex.org/W2896480657\",\"https://openalex.org/W2900604419\",\"https://openalex.org/W2908155319\",\"https://openalex.org/W2914496888\",\"https://openalex.org/W2914520605\",\"https://openalex.org/W2949457836\",\"https://openalex.org/W2979620240\",\"https://openalex.org/W2986368852\",\"https://openalex.org/W2996870046\",\"https://openalex.org/W3007835064\",\"https://openalex.org/W3031144616\",\"https://openalex.org/W3049509808\",\"https://openalex.org/W3084249337\",\"https://openalex.org/W3087859780\",\"https://openalex.org/W3112525124\",\"https://openalex.org/W3120551831\",\"https://openalex.org/W3134803076\",\"https://openalex.org/W3135628799\",\"https://openalex.org/W3135635133\",\"https://openalex.org/W3136402846\",\"https://openalex.org/W3148497253\",\"https://openalex.org/W3153796079\",\"https://openalex.org/W3166604621\",\"https://openalex.org/W3194472989\",\"https://openalex.org/W3200757480\",\"https://openalex.org/W3204019137\",\"https://openalex.org/W4200408156\",\"https://openalex.org/W4205400385\",\"https://openalex.org/W4210332402\",\"https://openalex.org/W4280584826\",\"https://openalex.org/W4281891940\",\"https://openalex.org/W4292262959\",\"https://openalex.org/W4307093712\",\"https://openalex.org/W4310942020\",\"https://openalex.org/W4318933953\",\"https://openalex.org/W4319765908\",\"https://openalex.org/W4362656963\",\"https://openalex.org/W4376279493\",\"https://openalex.org/W4381548553\",\"https://openalex.org/W4384154266\",\"https://openalex.org/W4385664009\",\"https://openalex.org/W4386504040\",\"https://openalex.org/W4386606492\",\"https://openalex.org/W4387019277\",\"https://openalex.org/W4387521434\",\"https://openalex.org/W4389139111\",\"https://openalex.org/W4389975182\",\"https://openalex.org/W4390794276\",\"https://openalex.org/W4391893692\",\"https://openalex.org/W4396229906\",\"https://openalex.org/W4397049758\",\"https://openalex.org/W4398195443\",\"https://openalex.org/W4398782381\",\"https://openalex.org/W4399572299\",\"https://openalex.org/W4400364503\",\"https://openalex.org/W4401212791\",\"https://openalex.org/W4402221705\",\"https://openalex.org/W4403216984\",\"https://openalex.org/W4403509916\",\"https://openalex.org/W4404160271\",\"https://openalex.org/W4404286681\",\"https://openalex.org/W4404836981\",\"https://openalex.org/W4405376152\",\"https://openalex.org/W4406338182\",\"https://openalex.org/W4408186822\",\"https://openalex.org/W4408221975\",\"https://openalex.org/W4408328158\",\"https://openalex.org/W4409313347\",\"https://openalex.org/W4409449345\",\"https://openalex.org/W4409687073\",\"https://openalex.org/W4409729252\",\"https://openalex.org/W4411355052\",\"https://openalex.org/W4411969620\",\"https://openalex.org/W4412489091\",\"https://openalex.org/W4412570375\",\"https://openalex.org/W4413411862\",\"https://openalex.org/W4413839750\",\"https://openalex.org/W4414072214\",\"https://openalex.org/W4414745665\",\"https://openalex.org/W4415622018\",\"https://openalex.org/W4417031290\",\"https://openalex.org/W4417397706\",\"https://openalex.org/W7125961702\",\"https://openalex.org/W7128441230\",\"https://openalex.org/W7133234785\",\"https://openalex.org/W7134072318\",\"https://openalex.org/W7134891055\",\"https://openalex.org/W7135170485\",\"https://openalex.org/W7148242223\"],\"authorships\":[{\"id\":\"https://openalex.org/A5060209926\",\"display_name\":\"Elena Koning\",\"orcid\":\"https://orcid.org/0000-0001-5241-0288\"},{\"id\":\"https://openalex.org/A5006203775\",\"display_name\":\"Jérémie Richard\",\"orcid\":\"https://orcid.org/0000-0001-9893-1353\"},{\"id\":\"https://openalex.org/A5023552725\",\"display_name\":\"Aaron Keshen\",\"orcid\":\"https://orcid.org/0000-0003-0462-9749\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S74080386\",\"source_display_name\":\"International Journal of Eating Disorders\",\"landing_page_url\":\"https://doi.org/10.1002/eat.70164\",\"is_oa\":false}}}","topic_tags":"Eating Disorders,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Clinical Trial,Review Article,Safety","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W7167014213"},{"id":3813,"title":"Convergent biosynthesis of psilocybin in an ectomycorrhizal lineage: is the psychoactive end-product the selected trait?","normalized_title":"convergent biosynthesis of psilocybin in an ectomycorrhizal lineage is the psychoactive end product the selected trait","authors":"Askari M, Surapaneni V.","abstract":"The fungivore-deterrence hypothesis, that psilocybin evolved as a chemical defence against arthropod fungivores via 5-HT receptor agonism, has become the working consensus in fungal chemical ecology, despite resting on a phylogenomic pattern of horizontal gene transfer among saprotrophs and remarkably little direct experimental evidence. Recent biochemistry shows that the ectomycorrhizal Inocybe corydalina assembles psilocybin through a convergently evolved, non-homologous ips cluster whose branched pathway yields baeocystin, not psilocybin, as the primary end-product. We argue that psilocybin's psychoactivity at vertebrate 5-HT2A receptors is plausibly incidental, with selection most likely acting on the injury-triggered polymerized indoloquinoid end-state of the blueing reaction (with psilocybin functioning as its stable storage precursor) and only secondarily on the monomeric congeners baeocystin or aeruginascin. We propose a five-tier comparative experimental program to adjudicate among these alternatives.","journal":"EcoEvoRxiv","publication_date":"2026-06-30","publication_year":2026,"doi":"10.32942/x2fd49","pubmed_id":null,"source_url":"https://doi.org/10.32942/x2fd49","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-02 20:31:02","last_checked":"2026-07-08 01:20:28","raw_json":"{\"europe_pmc_id\":\"PPR1263823\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"EcoEvoRxiv\",\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7166796269\",\"openalex_url\":\"https://openalex.org/W7166796269\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[],\"authorships\":[{\"id\":\"https://openalex.org/A5139727248\",\"display_name\":\"Mellica Askari\",\"orcid\":\"https://orcid.org/0009-0005-1876-7714\"},{\"id\":\"https://openalex.org/A5135689316\",\"display_name\":\"Varun Surapaneni\",\"orcid\":null}],\"primary_location\":{\"source_id\":null,\"source_display_name\":null,\"landing_page_url\":\"https://doi.org/10.32942/x2fd49\",\"is_oa\":true}}}","topic_tags":"Mechanism of Action,Receptor Pharmacology,Genomics","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":"https://openalex.org/W7166796269"},{"id":3002,"title":"Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits.","normalized_title":"modeled long term effects of psilocybin on dynamic activity and effective connectivity of fronto striatal thalamic circuits","authors":"Pasquini L, Vohryzek J, Escrichs A, Perl YS, Ponce-Alvarez A, Idesis S, Girn M, Roseman L, Mitchell JM, Gazzaley A, Kringelbach M, Nutt DJ, Lyons T, Carhart-Harris RL, Deco G.","abstract":"Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we performed secondary analyses and applied computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first showed that dynamic FST activity increased 4 weeks after a full dose of psilocybin. We then proceeded to mechanistically account for these changes by providing tentative model-based support that reductions in the structure-function coupling contribute to increased dynamic FST activity postpsilocybin. Finally, we used computational approaches to show that psilocybin induces longitudinal increases in bottom-up and reduced top-down modulation of FST circuits. We then used publicly available receptor maps to show that cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, while increased information outflow via subcortical and limbic regions relates to local D2 receptor availability. Together, these findings suggest that increased FST flexibility weeks after a high dose of psilocybin is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism contributing to the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia nervosa.","journal":null,"publication_date":"2026-06-30","publication_year":2026,"doi":"10.1002/hbm.70596","pubmed_id":"42381187","source_url":"https://doi.org/10.1002/hbm.70596","keywords":"Thalamus, Corpus Striatum, Frontal Lobe, Nerve Net, Neural Pathways, Humans, Hallucinogens, Magnetic Resonance Imaging, Longitudinal Studies, Models, Neurological, Adult, Female, Male, Young Adult, Connectome, Psilocybin","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 11:03:06","last_checked":"2026-07-08 01:20:22","raw_json":"{\"europe_pmc_id\":\"42381187\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Eating Disorders,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Healthy Volunteers","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":101,"title":"Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms.","normalized_title":"psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5 hydroxytryptamine mechanisms","authors":"Akbar RJ, Stringer AD, Wiah S, Dachepalli M, Daws SE, Inan S, Rawls SM.","abstract":"Psilocybin is a serotonergic 5-HT2A R agonist that causes psychedelic and anxiolytic effects in human users. To delineate conservation of psilocybin pharmacology, we investigated behavioral effects of psilocybin in planarians ( Dugesia dorotocephala ), the simplest living animal with cephalization that also has a well defined serotonin (5-hydroxytryptamine [5-HT]) system. We quantified stereotyped movements (e.g. head bops, twists, scrunches, and C-shapes) and defensive responding (negative phototaxis) and probed a 5-HT2A R mechanism for psilocybin using a selective 5-HT2A R antagonist (volinanserin). Psilocybin (0.01, 0.1, 1, and 10 nM) increased all stereotyped movements and, at higher concentrations, reduced motility. Volinanserin (1, 10, and 100 nM) did not induce any stereotyped movements or reduce motility. For combination experiments, volinanserin reduced cumulative stereotyped movements produced by psilocybin (0.01 nM) and specifically reduced psilocybin-evoked twists and head bops. Concentrations (","journal":null,"publication_date":"2026-06-30","publication_year":2026,"doi":"10.1097/fbp.0000000000000879","pubmed_id":"42186402","source_url":"https://doi.org/10.1097/fbp.0000000000000879","keywords":"Animals, Planarians, Serotonin, Hallucinogens, Stereotyped Behavior, Dose-Response Relationship, Drug, Psilocybin, Phototaxis","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:22","raw_json":"{\"europe_pmc_id\":\"42186402\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Pharmacology,Mechanism of Action,Receptor Pharmacology","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":21,"title":"Chemistry/structural biology of psychedelic drugs and their receptor(s).","normalized_title":"chemistry structural biology of psychedelic drugs and their receptor s","authors":"Gumpper RH, Nichols DE","abstract":"This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.17361","pubmed_id":"39354889","source_url":"https://pubmed.ncbi.nlm.nih.gov/39354889/","keywords":"5-HT2A agonists, 5-HT2A receptor, LSD, Psychedelic chemotypes, crystal structures, docking, ergolines, phenethylamines, psilocybin, structural biology, structure-activity relationships, therapeutic potential, tryptamines","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:06","raw_json":"{\"pubmed_id\":\"39354889\"}","topic_tags":"Mechanism of Action,Receptor Pharmacology,Review Article","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":20,"title":"Psilocybin as a novel treatment for chronic pain.","normalized_title":"psilocybin as a novel treatment for chronic pain","authors":"Askey T, Lasrado R, Maiarú M, Stephens GJ","abstract":"Psychedelic drugs are under active consideration for clinical use and have generated significant interest for their potential as anti-nociceptive treatments for chronic pain, and for addressing conditions like depression, frequently co-morbid with pain. This review primarily explores the utility of preclinical animal models in investigating the potential of psilocybin as an anti-nociceptive agent. Initial studies involving psilocybin in animal models of neuropathic and inflammatory pain are summarised, alongside areas where further research is needed. The potential mechanisms of action, including targeting serotonergic pathways through the activation of 5-HT receptors at both spinal and central levels, as well as neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain, are considered. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Also discussed is psilocybin's profile as an ideal anti-nociceptive agent, with a wide range of effects against chronic pain and its associated inflammatory or emotional components. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.17420","pubmed_id":"39614355","source_url":"https://pubmed.ncbi.nlm.nih.gov/39614355/","keywords":"neuropathic pain, neuroplasticity, nociplastic pain, psilocybin, psychedelic drugs, serotonergic signalling","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:06","raw_json":"{\"pubmed_id\":\"39614355\"}","topic_tags":"Depression,Chronic Pain,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Review Article,Animal Study,Inflammation","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":19,"title":"The Australia story: Current status and future challenges for the clinical applications of psychedelics.","normalized_title":"the australia story current status and future challenges for the clinical applications of psychedelics","authors":"Nutt DJ, Hunt P, Schlag AK, Fitzgerald P","abstract":"The past decade has seen a huge increase in clinical research with psychedelic drugs and 3,4-methylenedioxymethamphetamine (MDMA), which have revealed great potential for treating mental health conditions. Given this progress in research, as well as the current unmet clinical need of millions of patients, in 2023, the Australian Therapeutic Goods Administration (TGA) approved the use of psilocybin for treatment-resistant depression and MDMA for PTSD to take effect from 1 July 2023. The campaign for TGA approval was led by a coalition comprising the Australian charity Mind Medicine Australia with support from Professor David Nutt, Drug Science, Professor Arthur Christopolous, Professor Chris Langmead (both from Monash University) and from large numbers of clinical, academic and patient groups. Under the rescheduling, current prescribing rights are limited to psychiatrists who have become authorised prescribers under the TGA's Authorised Prescriber Scheme, and psilocybin can only be used for treatment resistant depression and MDMA can only be used for PTSD. This paper reviews the background for this decision, its implications for approvals in other jurisdictions, as well as for the development pathways for other psychedelic drugs. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.17398","pubmed_id":"39701143","source_url":"https://pubmed.ncbi.nlm.nih.gov/39701143/","keywords":"3,4-methylenedioxymethamphetamine (MDMA), Australia, psilocybin, psychedelics, therapeutic goods administration (TGA)","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:06","raw_json":"{\"pubmed_id\":\"39701143\"}","topic_tags":"Depression,PTSD,Mechanism of Action,Review Article,Treatment-Resistant Depression","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":17,"title":"Psychedelics, entactogens and psychoplastogens for depression and related disorders.","normalized_title":"psychedelics entactogens and psychoplastogens for depression and related disorders","authors":"Hoyer D","abstract":"Currently, the most actively investigated rapidly acting antidepressants, anxiolytics and/or anti PTSD agents, include psychedelics e.g. psilocybin, LSD, N,N-dimethyltryptamine, ayahuasca; non-hallucinogenic entactogens, e.g. MDMA; psychoplastogens which rapidly promote neuroplasticity, e.g. ibogaine, ketamine and esketamine; and other atypicals e.g. dextromorphan/bupropion, esmethadone. Late-stage clinical trials support psychedelics and/or MDMA-assisted psychotherapy as rapidly acting treatments for major depressive disorder (MDD), treatment-resistant depression (TRD), PTSD or generalised anxiety disorders (GAD). Psilocybin, MDMA and LSD were granted FDA breakthrough status for TRD/MDD, PTSD and GAD, respectively, although FDA recently rejected the new drug application of MDMA in PTSD. Most of these drugs target the 5-HT and monoamine systems. Classical psychedelics act as 5-HT receptor agonists, although LSD, DMT and psilocybin target other 5-HT and/or dopamine receptors. Psychedelic-dependent 5-HT receptor agonism also has profound anti-(neuro)inflammatory effects. Advanced imaging studies suggest that brain 5-HT levels are reduced in depression. Functional magnetic resonance studies show that neural networks (cortico thalamic, salience, default mode) are profoundly impaired in depression. Such network defects are corrected upon psychedelic/entactogen treatment, offering a unique opportunity to serve as biomarkers for depression, anxiety and PTSD precision medicine trials. Psychedelics and entactogens target common end pathways, namely neuroplasticity/synaptogenesis, either directly via monoamine or glutamate receptors and/or indirectly, via BDNF and mTORC1 pathways. Together, these findings strongly support a biological basis for MDD, GAD, PTSD and related conditions, which can be considered as mixed biochemical, neurological and neuroimmune disorders, and are profoundly modified by psychedelics, entactogens and the newly developed psychoplastogens. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.70088","pubmed_id":"40518133","source_url":"https://pubmed.ncbi.nlm.nih.gov/40518133/","keywords":"5-HT (serotonin), Brain-derived neurotrophic factor (BDNF), Empathogens, Entactogens, LSD (lysergic acid diethylamide), MDMA (3,4-methylenedioxy methamphetamine), Post-traumatic stress disorders (PTSD), Psychedelics, Psychoplastogens, Treatment resistant depression (TRD)","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:06","raw_json":"{\"pubmed_id\":\"40518133\"}","topic_tags":"Depression,Anxiety,PTSD,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Biomarkers,Aging,Clinical Trial,Treatment-Resistant Depression,Inflammation,Immune Function","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":14,"title":"Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology.","normalized_title":"psychedelics as pharmacotherapeutics for substance use disorders a scoping review on clinical trials and perspectives on underlying neurobiology","authors":"Wittenkeller L, Gudelsky G, Winhusen TJ, Amato D","abstract":"Psychedelics have garnered great attention in recent years as treatments for major depressive disorder (MDD) and treatment-resistant depression because of their ability to alter consciousness and afflicted cognitive processes with lasting effects. We aimed to characterise how psychedelics are currently being investigated to treat substance use disorders (SUDs). Additionally, we aimed to summarise the available literature on the dopaminergic consequences of classic psychedelics in the nucleus accumbens (NAc), a foundational component of SUDs, to understand how psychedelics may be therapeutically relevant for SUDs from a neurobiological perspective. Two scoping review approaches adhering to PRISMA-SCR guidelines were conducted. The first screened for ongoing clinical trials utilising psychedelics for SUD treatment registered at ClinicalTrials.gov. The second screened for in vivo microdialysis studies measuring psychedelic-induced changes in extracellular NAc dopamine in rats, found using PubMed, SCOPUS or Google Scholar. Thirty-four unique clinical trials were identified targeting alcohol, cannabis, cocaine, methamphetamine, nicotine, and opioid use disorders and mostly consisting of open-label trials lacking placebo-treated controls. The most common SUD investigated was alcohol use disorder (AUD). Following stringent exclusion criteria, four publications were identified that measured extracellular dopamine in the NAc following systemic administration of psilocybin or 3,4-methylenedioxymethamphetamine (MDMA). A sustained mild increase of dopamine was observed that was unique to high-dose psilocybin. In addition to known therapeutic mechanisms of psychedelics, findings herein suggest that psilocybin may support dopamine homeostasis through restoration of tonic dopamine levels. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.","journal":"British journal of pharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1111/bph.70181","pubmed_id":"40891276","source_url":"https://pubmed.ncbi.nlm.nih.gov/40891276/","keywords":"MDMA, addiction, psilocybin, psychedelics, psychedelic-assisted therapy, substance use disorders","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:06","raw_json":"{\"pubmed_id\":\"40891276\"}","topic_tags":"Depression,Addiction,Mechanism of Action,Consciousness,Clinical Trial,Review Article,Treatment-Resistant Depression","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":12,"title":"Psilocybin improves novel object recognition in a rat model of Fragile X Syndrome through the modulation of the BDNF/TrkB signaling pathway.","normalized_title":"psilocybin improves novel object recognition in a rat model of fragile x syndrome through the modulation of the bdnf trkb signaling pathway","authors":"Ascone F, Buzzelli V, Mottarlini F, Di Trapano M, Miglioranza P, Rava A, Feo A, Spano F, Hausman M, Sugaya K, Caffino L, Fumagalli F, Trezza V","abstract":"Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a synaptic disorder, FXS involves the loss of Fragile X messenger ribonucleoprotein 1 (FMRP), leading to abnormal dendrite development and immature dendritic spines. Serotonergic signaling, essential for neuronal development and circuit remodeling, has been implicated in ASD and related conditions, including FXS, raising the possibility that serotonergic modulation could ameliorate neurodevelopmental impairments. This study investigated the therapeutic potential of psilocybin, a serotonergic compound, in the validated Fmr1-exon 8 rat model of FXS. Psilocybin microdosing rescued deficits in NOR. Importantly, its benefits on recognition memory persisted despite pretreatment with the 5HT2AR antagonist, volinanserin, or the 5HT1AR antagonist, WAY-100635, indicating that classical serotonergic receptor activation is not required. In contrast, pretreatment with the TrkB receptor antagonist, ANA-12, abolished psilocybin's effects, implicating BDNF/TrkB signaling as essential. At the molecular level, psilocybin normalized mature BDNF (mBDNF), increased TrkB, and restored downstream AKT signaling in the prefrontal cortex of Fmr1-exon 8 rats, pathways strongly linked to synaptic plasticity and cognitive function. These findings demonstrate that psilocybin rescues object recognition memory deficits in this rat model of FXS via BDNF/TrkB-AKT signaling rather than serotonergic receptor mechanisms. By dissociating therapeutic effects from hallucinogenic pathways, our results highlight psilocybin microdosing as a promising therapeutic strategy for neurodevelopmental disorders such as FXS and ASD.","journal":"Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1038/s41386-026-02361-x","pubmed_id":"41688761","source_url":"https://pubmed.ncbi.nlm.nih.gov/41688761/","keywords":"","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:06","raw_json":"{\"pubmed_id\":\"41688761\"}","topic_tags":"Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Microdosing,Animal Study","study_type":"Animal Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":3494,"title":"5-HT2A Agonist Psilocybin in the Treatment of Tobacco Use Disorder","normalized_title":"5 ht2a agonist psilocybin in the treatment of tobacco use disorder","authors":"Johns Hopkins University","abstract":"This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. Four sites with experience in conducting psilocybin research will be involved in this trial: Johns Hopkins University (JHU), the University of Alabama at Birmingham (UAB), and New York University (NYU). The proposed study will treat 66 participants (22 at each site), randomized to receive either: 1) oral psilocybin (30 mg in session 1 and either 30 mg or 40 mg in session 2); or 2) oral niacin (150 mg in session 1 and either 150 mg or 200 mg in session 2), with sessions 1 week apart. This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. The investigators previously conducted an open-label pilot trial (N = 15) of psilocybin paired with cognitive behavior therapy (CBT). Data showed a biologically-verified 7-day point-prevalence abstinence rate of 67% at 12 months and 60% at 2.5 years (continuous abstinence rates: 53% and 47%, respectively). The investigators are now conducting an open-label randomized comparative efficacy trial of psilocybin vs. nicotine patch, both in combination with CBT. Interim results (N = 44; 22 per group) show greater biologically-verified abstinence rates at 12 months for psilocybin: 7-day point-prevalence: 59% vs. 27%; continuous abstinence: 36% vs. 9%. Despite these promising findings, the investigators have yet to conduct a double-blind study of psilocybin for smoking cessation. Furthermore, previous psilocybin study samples have been largely White with higher socioeconomic status (SES). The current trial will address these issues across four sites with experience in conducting psilocybin research: Johns Hopkins, the University of Alabama at Birmingham (UAB), and New York University (NYU). A diverse sample with regard to ethno-racial identity and SES will be recruited at each site. The proposed double-blind study will treat 66 participants (22 at each site), randomized to receive either: 1) psilocybin; 30 mg in session 1 and either 30 or 40 mg in session 2, with sessions 1 week apart; or 2) niacin; 150 mg in session 1 and either 150 mg or 200 mg in session 2, with sessions 1 week apart. Niacin was selected because it has been used as an active placebo in two previous randomized therapeutic trials of psilocybin, and the FDA has informed the investigators that niacin is the FDA's preferred active placebo for psilocybin. CBT will be administered to both groups and will allow the investigators to test psilocybin's efficacy above and beyond an established treatment approach. Biochemically-confirmed 7-day point-prevalence abstinence will be assessed throughout for up to 12 months. The investigators hypothesize that psilocybin (compared to niacin) will cause increased biologically-confirmed 7-day point-prevalence abstinence at 12-month follow-up. Based on pilot data, the investigators will test cognitive/psychological mediators of treatment response. The investigators hypothesize that psilocybin will be associated with improved cognitive control and decreased anticipation of withdrawal relief (from smoking) 1 day after the target quit date, which will be associated with greater 7-day point-prevalence abstinence at 12- month follow-up. This trial will provide a rigorous test of efficacy in a diverse study sample, and test relevant mechanisms, for an innovative smoking cessation treatment showing potential for substantial efficacy.","journal":"ClinicalTrials.gov","publication_date":"2026-06-28","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT05452772","keywords":"Tobacco Use Disorder, Psilocybin, Active Experimental Group, Niacin, Active Comparator Group, RECRUITING","substance_tags":"psilocybin","source_name":"ClinicalTrials.gov","date_added":"2026-07-01 11:04:27","last_checked":"2026-07-05 01:22:40","raw_json":"{\"nct_id\":\"NCT05452772\",\"overall_status\":\"RECRUITING\",\"phase\":[\"PHASE2\"]}","topic_tags":"Addiction,Mechanism of Action,Receptor Pharmacology,Clinical Trial","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"clinical trial","openalex_id":null},{"id":24,"title":"Psilocybin reduces fear memory and restores neuroplasticity in the hippocampus and medial prefrontal cortex.","normalized_title":"psilocybin reduces fear memory and restores neuroplasticity in the hippocampus and medial prefrontal cortex","authors":"Du Y, Zhao X, Yao Y, Li Y, Wang G, Zhang L.","abstract":"BackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder are often comorbid in humans. Psilocybin reportedly has beneficial therapeutic effects on depression, possibly by promoting neuroplasticity. PTSD is associated with the dysregulation of neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC). We hypothesized that psilocybin might reduce fear memory by promoting neuroplasticity in the hippocampus and mPFC.AimsWe investigated the effects of psilocybin on fear memory and explored its underlying mechanisms. We generated a mouse model of PTSD via auditory-cued fear conditioning and treated the mice with either vehicle or psilocybin (2.5 mg/kg, intraperitoneal) on day 0. Fear memory was assessed by the percentage of freezing time in response to conditioned stimuli. Fear memory tests were conducted on days 1, 6, and 7, after which the mice were sacrificed. To investigate the role of neuroplasticity in mediating the effects of psilocybin on fear memory, we assessed structural neuroplasticity and neuroplasticity-associated marker protein levels in the hippocampus and mPFC 7 days after a single dose of psilocybin.ResultsPsilocybin reduced the cue-induced fear response on days 1, 6, and 7. Psilocybin ameliorated the fear conditioning-induced decreases in neuroplasticity in the hippocampus and mPFC. Through Golgi-Cox staining, Western blotting, and immunofluorescence staining, we found that psilocybin increased dendritic branches and spine density, upregulated GluR1 and synapsin-1, enhanced brain-derived neurotrophic factor and mammalian target of rapamycin signaling, and promoted neurogenesis.ConclusionsA single dose of psilocybin reduces both the rapid and sustained fear memory in mice, at least in part by restoring neuroplasticity in the hippocampus and mPFC. These findings indicate that psilocybin has significant potential for use in the treatment of PTSD and other mental disorders characterized by fear memory.","journal":"Journal of Psychopharmacology","publication_date":"2026-06-27","publication_year":2026,"doi":"10.1177/02698811261453819","pubmed_id":"42365496","source_url":"https://doi.org/10.1177/02698811261453819","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-05 01:20:22","raw_json":"{\"europe_pmc_id\":\"42365496\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7166436963\",\"openalex_url\":\"https://openalex.org/W7166436963\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[\"https://openalex.org/W170792860\",\"https://openalex.org/W1980452424\",\"https://openalex.org/W1994547251\",\"https://openalex.org/W2036499082\",\"https://openalex.org/W2051271111\",\"https://openalex.org/W2084108505\",\"https://openalex.org/W2112188963\",\"https://openalex.org/W2396675581\",\"https://openalex.org/W2558412547\",\"https://openalex.org/W2559739670\",\"https://openalex.org/W2592144218\",\"https://openalex.org/W2808301300\",\"https://openalex.org/W2901904956\",\"https://openalex.org/W2927237494\",\"https://openalex.org/W2936046802\",\"https://openalex.org/W2963792090\",\"https://openalex.org/W2992679405\",\"https://openalex.org/W2997242667\",\"https://openalex.org/W3003581149\",\"https://openalex.org/W3011668650\",\"https://openalex.org/W3094714065\",\"https://openalex.org/W3096208965\",\"https://openalex.org/W3100215548\",\"https://openalex.org/W3108222140\",\"https://openalex.org/W3112503127\",\"https://openalex.org/W3112535936\",\"https://openalex.org/W3126370177\",\"https://openalex.org/W3156937150\",\"https://openalex.org/W3157927787\",\"https://openalex.org/W3161556967\",\"https://openalex.org/W3165027302\",\"https://openalex.org/W3169261903\",\"https://openalex.org/W3178121559\",\"https://openalex.org/W3179469168\",\"https://openalex.org/W3210509042\",\"https://openalex.org/W4212903385\",\"https://openalex.org/W4214649547\",\"https://openalex.org/W4231265947\",\"https://openalex.org/W4283070601\",\"https://openalex.org/W4308146113\",\"https://openalex.org/W4308146982\",\"https://openalex.org/W4318755662\",\"https://openalex.org/W4362457938\",\"https://openalex.org/W4394693583\",\"https://openalex.org/W4396588878\",\"https://openalex.org/W4400729513\",\"https://openalex.org/W4401212791\"],\"authorships\":[{\"id\":\"https://openalex.org/A5134867509\",\"display_name\":\"Y J Du\",\"orcid\":null},{\"id\":\"https://openalex.org/A5103220890\",\"display_name\":\"Xinyi Zhao\",\"orcid\":\"https://orcid.org/0009-0007-6483-6148\"},{\"id\":\"https://openalex.org/A5127702000\",\"display_name\":\"Yishan Yao\",\"orcid\":null},{\"id\":\"https://openalex.org/A5139523749\",\"display_name\":\"Yunfeng Li\",\"orcid\":null},{\"id\":\"https://openalex.org/A5088725738\",\"display_name\":\"Guyan Wang\",\"orcid\":\"https://orcid.org/0000-0003-3098-5472\"},{\"id\":\"https://openalex.org/A5101545617\",\"display_name\":\"Liming Zhang\",\"orcid\":\"https://orcid.org/0000-0002-9071-8985\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S136368880\",\"source_display_name\":\"Journal of Psychopharmacology\",\"landing_page_url\":\"https://doi.org/10.1177/02698811261453819\",\"is_oa\":false}}}","topic_tags":"Depression,PTSD,Neuroplasticity,Neurogenesis,Mechanism of Action,Biomarkers,Animal Study","study_type":"Animal Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W7166436963"},{"id":3560,"title":"A Pilot Mechanistic RCT of Psilocybin With Mindfulness-based Therapy vs Support for Posttraumatic Stress Disorder (PTSD)","normalized_title":"a pilot mechanistic rct of psilocybin with mindfulness based therapy vs support for posttraumatic stress disorder ptsd","authors":"Anthony P King","abstract":"The goal of this study is to learn how psilocybin delivered with mindfulness-based therapy may help symptoms of posttraumatic stress disorder (PTSD). This is an assessor-blinded, randomized, controlled study in participants with PTSD. The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using EEG/EMG and multimodal MRI measures after administration of one oral dose of psilocybin, accompanied either with standard \"psychological support\" only; or with standard support plus Mindfulness-based Cognitive Therapy (MBCT). Many patients with PTSD do not respond or have an incomplete response to treatment with currently available medications that are FDA-approved for PTSD, and/or do not respond to psychotherapies for PTSD. The use of psychedelics (e.g. psilocybin) is being investigated as a new approach to improve symptoms in patients with PTSD and depression, however their mechanism of action is still not well understood. Furthermore, while psychedelics are usually administered in the context of psychological support (\"psychedelic assisted therapy\", PAT) the kinds of support therapy used and possible interactions with drug with therapy effects is not well understood. This study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity, assessed using electroencephalography (EEG) / electromyography (EMG) and functional magnetic resonance imaging (fMRI) /diffusion-weighted magnetic resonance imaging (DWI), after administration of one oral dose of 25 mg synthetic Psilocybin delivered in the context of either non-directive psychological support only (the most common approach for PAT) or in combination with psychological support plus an active form of psychotherapy called Mindfulness-based Cognitive Therapy (MBCT). Up to 30 participants will be enrolled altogether. The initial phase of this study will be an open label administration of 25 mg synthetic Psilocybin combined with standard \"PAT psychological support\" plus MBCT in ten participants with PTSD, to allow us to pilot this new intervention package. In the next phase of the study, we will randomly assign twenty participants with PTSD into two groups: one group receiving 25 mg of synthetic Psilocybin (open label) combined with standard \"PAT support\" only, and one group receiving 25 mg of synthetic Psilocybin (open label) combined with standard \"support\" plus active form MBCT psychotherapy. In both groups, psychological support will be provided before, during and after the administration session. The MBCT group will also receive bi-weekly individual MBCT sessions and will be invited to complete daily homework, as per the MBCT protocol. Assessments performed at Baseline and on Day 2 and Day 28 after administration will include EEG/EMG, MRI, clinician-administered scales (CAPS-5, MADRS, C-SSRS) and self-report questionnaires to assess PTSD, depression and anxiety symptoms, cognitive testing, self-report questionnaires to evaluate the psychedelic effects of synthetic Psilocybin administration, and blood collection for the Gsα-AC biomarker assay.","journal":"ClinicalTrials.gov","publication_date":"2026-06-24","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT07104916","keywords":"Post Traumatic Stress Disorder, Depression - Major Depressive Disorder, Psilocybin + MBCT therapy, Active Comparator: Psilocybin with Support Only, RECRUITING","substance_tags":"psilocybin","source_name":"ClinicalTrials.gov","date_added":"2026-07-01 11:04:28","last_checked":"2026-07-01 23:13:10","raw_json":"{\"nct_id\":\"NCT07104916\",\"overall_status\":\"RECRUITING\",\"phase\":[\"PHASE2\"]}","topic_tags":"Depression,Anxiety,PTSD,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Randomized Controlled Trial,Healthcare Workers,Drug Interactions","study_type":"Randomized Controlled Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"clinical trial","openalex_id":null},{"id":30,"title":"The intersection between psychedelics and schizophrenia spectrum disorders: Reevaluating risk and therapeutic potential.","normalized_title":"the intersection between psychedelics and schizophrenia spectrum disorders reevaluating risk and therapeutic potential","authors":"Brar PS, Price RB, Ross S, Tofighi B, Sarpal DK","abstract":"In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and schizophrenia spectrum disorders (SSDs). In this narrative review, we examine the historical and theoretical relationship between psychedelic drugs and SSDs, including the origins of the psychotomimetic hypothesis. For key psychedelic compounds, we review their phenomenological manifestations in relation to the experiential alterations characteristic of SSDs, revealing both areas of overlap and important qualitative differences that challenge the uniform psychotomimetic classification. We also review putative neural mechanisms underlying altered experiential states associated with psychedelic use and SSDs, with attention to serotonergic, dopaminergic, and glutamatergic contributions. Clinical evidence demonstrates that psychedelics can exacerbate pre-existing psychotic illness and may trigger psychosis in vulnerable individuals, though the magnitude of these risks remains inadequately quantified. However, phenomenological and mechanistic distinctions suggest that potential therapeutic applications may exist for carefully selected symptoms (negative symptoms, depression) in stable patients using low-dose, controlled approaches. Based on published work, we provide recommendations regarding psychosis-related risk and potential avenues for the treatment of SSDs as psychedelics gain traction as therapeutics.","journal":"Journal of psychopharmacology (Oxford, England)","publication_date":"2026-06-24","publication_year":2026,"doi":"10.1177/02698811261456191","pubmed_id":"42345450","source_url":"https://pubmed.ncbi.nlm.nih.gov/42345450/","keywords":"DMT, LSD, mescaline, phenomenology, psilocybin, psychedelics, psychosis, schizophrenia","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-02 23:03:18","raw_json":"{\"pubmed_id\":\"42345450\"}","topic_tags":"Depression,Mechanism of Action,Review Article,Safety","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":3705,"title":"Effects of Psilocybin Microdosing on Cognition, Mood and Quality of Life: A Pilot Study","normalized_title":"effects of psilocybin microdosing on cognition mood and quality of life a pilot study","authors":"Yale University","abstract":"This study is being conducted to evaluate how of 30 days of intermittently microdosed psilocybin affects mood, cognition, subjective well-being and structural/functional MRI results compared to a placebo. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences. This study is being conducted to evaluate the effects of 30 days of intermittently microdosed psilocybin in a parallel arm double-blind manner on mood, cognition, subjective well-being and structural/functional MRI compared to placebo, using validated psychological assessments and cognitive tests. Investigators hypothesize that compared to placebo, 30 days of intermittently microdosed psilocybin will produce observable changes in mood, cognition, subjective well-being and MRI, in the absence of psychedelic experiences. Demonstrating significant results in a population of healthy psychedelic non-users will establish a strong precedent for studying the effects of microdosing psychedelics in patient populations, such as those with treatment-resistant depression. Showing that microdosing minimizes risk of adverse outcomes with psychedelic treatment while maintaining beneficial effects would provide useful information relevant to clinical research in psychedelic-assisted psychotherapy. In addition to investigating claims that microdosing psychedelics may improve cognition and mood, this study also aims to test the hypothesis that these effects including those measurable at a brain level may persist beyond the course of the 30 days of the study. There are few to no studies that assessed the longevity of psychedelic effects on the majority of the above measures, so the proposed study may further establish the longer-term benefits of microdosing. The use of structural and functional magnetic resonance imaging (fMRI) will elucidate the mechanisms by which microdosing may be exerting its effects on mood and cognition. Because this is a relatively understudied area, information gleaned from this study will provide service in informing the field in general.","journal":"ClinicalTrials.gov","publication_date":"2026-06-22","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT07449351","keywords":"Psychedelic Microdosing Effects on Mood, Cognition, Subjective Well-being and MRI, Psliocybin, Placebo, NOT_YET_RECRUITING","substance_tags":"psilocybin","source_name":"ClinicalTrials.gov","date_added":"2026-07-01 11:04:28","last_checked":"2026-07-01 11:22:34","raw_json":"{\"nct_id\":\"NCT07449351\",\"overall_status\":\"NOT_YET_RECRUITING\",\"phase\":[\"EARLY_PHASE1\"]}","topic_tags":"Depression,Brain Imaging,Mechanism of Action,Aging,Longevity,Microdosing,Wellbeing,Treatment-Resistant Depression,Safety","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"clinical trial","openalex_id":null},{"id":34,"title":"Blocking 5-HT2B receptors abolishes psilocybin’s efficacy in the rat forced swim test","normalized_title":"blocking 5 ht2b receptors abolishes psilocybin s efficacy in the rat forced swim test","authors":"Lenka Seillier, Alexandre Seillier, Morgan A. Zvolska, Romana Šlamberová","abstract":"BACKGROUND: Major depressive disorder is one of the most debilitating psychiatric disorders worldwide. First-line treatments such as selective serotonin reuptake inhibitors have significant limitations, including delayed onset of therapeutic effects and treatment resistance in about 30% of patients. Increasing evidence suggests that acute administration of serotonergic psychedelics, such as psilocybin, produces rapid and long-lasting antidepressant effects, including in treatment-resistant patients. However, it remains unknown which specific 5-HT receptor subtype mediates psilocybin's antidepressant activity. METHODS: We examined in Wistar rats whether pretreatment with the 5-HT2B receptor (5-HT2BR) antagonist RS-127445 (0.32, 1.0, or 3.2 mg/kg) blocked the rapid (day 1) and sustained (day 21) behavioral effects of a single psilocybin administration (0.32 mg/kg) in the forced swim test (FST), a test with predictive validity for antidepressant efficacy. We also measured the impact of RS-127445 on psilocybin-induced head-twitch response (HTR), a behavioral proxy in rodents for psychedelic properties. RESULTS: Our data showed that psilocybin produced both a rapid and sustained decrease in immobility and an increase in climbing behavior in the FST and significantly increased HTR counts. Although RS-127445 did not affect HTR counts at any tested dose, it dose-dependently reversed both the rapid and sustained psilocybin-induced reductions in immobility and increases in climbing behavior. CONCLUSION: These findings indicate that 5-HT2BRs are required for psilocybin's behavioral effects in the FST, but are not required for its HTR. The results add to evidence that psilocybin's predictive validity in the FST can be dissociated from its 5-HT2A-mediated psychedelic effects.","journal":"Journal of Psychopharmacology","publication_date":"2026-06-22","publication_year":2026,"doi":"10.1177/02698811261458349","pubmed_id":"42334341","source_url":"https://doi.org/10.1177/02698811261458349","keywords":"Behavioural despair test, Serotonergic, Antidepressant, Psilocybin, Pharmacology, Antagonist, Tricyclic antidepressant, Serotonin, Psychology, Reuptake inhibitor, Imipramine, Receptor antagonist, Receptor, 5-HT receptor, Internal medicine, Major depressive disorder, Serotonin reuptake inhibitor, Agonist, Endocrinology, Medicine, Anxiogenic, Pindolol, 5-HT1A receptor, Reuptake, Hallucinogen, Mechanism of action, Neurotransmitter, Psychedelics and Drug Studies, Forensic Toxicology and Drug Analysis, Neurotransmitter Receptor Influence on Behavior","substance_tags":"psilocybin","source_name":"OpenAlex","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-04 07:00:31","raw_json":"{\"openalex_id\":\"https://openalex.org/W7165643590\",\"openalex_url\":\"https://openalex.org/W7165643590\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[\"https://openalex.org/W1961364466\",\"https://openalex.org/W1974074998\",\"https://openalex.org/W1989757811\",\"https://openalex.org/W2007107398\",\"https://openalex.org/W2009134620\",\"https://openalex.org/W2012975576\",\"https://openalex.org/W2013598219\",\"https://openalex.org/W2031733304\",\"https://openalex.org/W2047129003\",\"https://openalex.org/W2054695075\",\"https://openalex.org/W2067481209\",\"https://openalex.org/W2089299823\",\"https://openalex.org/W2091064555\",\"https://openalex.org/W2091363925\",\"https://openalex.org/W2126685404\",\"https://openalex.org/W2134518716\",\"https://openalex.org/W2154105276\",\"https://openalex.org/W2166952073\",\"https://openalex.org/W2170915041\",\"https://openalex.org/W2173531201\",\"https://openalex.org/W2287930331\",\"https://openalex.org/W2319365136\",\"https://openalex.org/W2396675581\",\"https://openalex.org/W2412428225\",\"https://openalex.org/W2511250611\",\"https://openalex.org/W2564232286\",\"https://openalex.org/W2590821743\",\"https://openalex.org/W2596798372\",\"https://openalex.org/W2788337440\",\"https://openalex.org/W2806419184\",\"https://openalex.org/W2914255920\",\"https://openalex.org/W2999364864\",\"https://openalex.org/W3006905788\",\"https://openalex.org/W3010499243\",\"https://openalex.org/W3042758594\",\"https://openalex.org/W3087095811\",\"https://openalex.org/W3093375227\",\"https://openalex.org/W3094714065\",\"https://openalex.org/W3096208965\",\"https://openalex.org/W3127186731\",\"https://openalex.org/W3179469168\",\"https://openalex.org/W3213007658\",\"https://openalex.org/W3216485471\",\"https://openalex.org/W4206134470\",\"https://openalex.org/W4211211437\",\"https://openalex.org/W4211263234\",\"https://openalex.org/W4293729162\",\"https://openalex.org/W4308146982\",\"https://openalex.org/W4309269582\",\"https://openalex.org/W4315620747\",\"https://openalex.org/W4319067008\",\"https://openalex.org/W4321033185\",\"https://openalex.org/W4353017554\",\"https://openalex.org/W4385628167\",\"https://openalex.org/W4386504040\",\"https://openalex.org/W4390755783\",\"https://openalex.org/W4394693583\",\"https://openalex.org/W4396229906\",\"https://openalex.org/W4400335852\",\"https://openalex.org/W4402327722\",\"https://openalex.org/W4409449430\",\"https://openalex.org/W4410735628\",\"https://openalex.org/W4410737616\",\"https://openalex.org/W4411302754\",\"https://openalex.org/W4415713367\",\"https://openalex.org/W7118172518\",\"https://openalex.org/W7152959768\"],\"authorships\":[{\"id\":\"https://openalex.org/A5067927693\",\"display_name\":\"Lenka Seillier\",\"orcid\":\"https://orcid.org/0000-0002-1041-2290\"},{\"id\":\"https://openalex.org/A5002414770\",\"display_name\":\"Alexandre Seillier\",\"orcid\":\"https://orcid.org/0000-0003-1859-2561\"},{\"id\":\"https://openalex.org/A5139127821\",\"display_name\":\"Morgan A. 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