{"rows":[{"id":301,"title":"Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress","normalized_title":"contribution of the serotonin 5 ht2a receptor to the therapeutic effect of psilocin on social behavior deficits in mice repeatedly exposed to social defeat stress","authors":"Ibi Daisuke, Takaba Rika, Yoshida Keisuke, Kawase Ririna, Kitagawa Hiroko, Matsushita Momoko, Ito Kana, Uno Shoya, Nishimura Fumiya, Kitagaki Shinji, Hiramatsu Masayuki","abstract":"ABSTRACT Psychedelics such as psilocybin and lysergic acid diethylamide (LSD) exert hallucinogenic effects through stimulation of serotonin 5-HT2A receptors (5-HT2ARs) in the cerebral cortex. In recent years, numerous reports have demonstrated that psychedelics are effective in treating various psychiatric disorders such as major depressive disorder (MDD), treatment-resistant depression (TRD), and anxiety-related disorders. We have previously reported that administration of psilocin, the active metabolite of psilocybin, produces antidepressant-like effects in mice. Furthermore, we found that this effect is mediated by 5-HT2AR activation. Since depression and other psychiatric disorders often lead to impairments in social behavior (e.g., social avoidance), the present study examined the effects of psilocin on social avoidance behavior in mice subjected to chronic social defeat stress (CSDS), a widely used model that closely models human psychosocial stress. Mice exposed to CSDS exhibited social avoidance behavior, whereas psilocin administration before the onset of CSDS had little effect on this behavior. In contrast, psilocin administration after the completion of CSDS ameliorated social avoidance in CSDS-exposed mice. This effect was blocked by pretreatment with a 5-HT2AR antagonist, indicating that psilocin exerts its therapeutic effects through 5-HT2AR activation. Taken together, psilocin exerts therapeutic effects on social avoidance behavior after stress through activation of 5-HT2AR, but not preventive effects when administered before stress, suggesting that psilocin may promote stress resilience rather than resistance.","journal":"Neuropsychopharmacology Reports","publication_date":"2026-08-31","publication_year":2026,"doi":"10.1002/npr2.70152","pubmed_id":"42379141","source_url":"https://doi.org/10.1002/npr2.70152","keywords":"","substance_tags":"psilocybin,psilocin","source_name":"Crossref","date_added":"2026-07-01 06:48:03","last_checked":"2026-07-07 01:20:41","raw_json":"{\"doi\":\"10.1002/npr2.70152\",\"reference_dois\":[\"10.1016/j.cell.2020.03.020\",\"10.1001/jamapsychiatry.2020.3285\",\"10.1007/s00210‐023‐02778‐x\",\"10.3390/pharmaceutics17040411\",\"10.3389/fphar.2024.1391689\",\"10.1542/peds.2008‐1215\",\"10.1186/s12888‐023‐04681‐4\",\"10.1073/pnas.2312662120\",\"10.1016/j.bpsgos.2021.12.009\",\"10.1016/j.biopsych.2016.06.012\",\"10.1016/j.neuroscience.2021.01.029\",\"10.1016/j.neures.2022.12.015\",\"10.1038/nprot.2011.361\",\"10.1016/s0031‐9384(01)00490‐5\",\"10.1111/ejn.15812\",\"10.1016/j.neuropharm.2018.01.016\",\"10.1021/acschemneuro.9b00493\",\"10.1016/j.neuron.2007.01.008\",\"10.1016/j.bbi.2012.12.017\"],\"reference_count\":19,\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7166665532\",\"openalex_url\":\"https://openalex.org/W7166665532\",\"openalex_relevance_score\":12,\"openalex_relevance_reasons\":[\"abstract:psilocybin\",\"metadata:psilocybin\",\"title:psilocin\",\"abstract:psilocin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[\"https://openalex.org/W1970090557\",\"https://openalex.org/W1977593923\",\"https://openalex.org/W2009134620\",\"https://openalex.org/W2430804118\",\"https://openalex.org/W2783004241\",\"https://openalex.org/W3010499243\",\"https://openalex.org/W3015140823\",\"https://openalex.org/W3096208965\",\"https://openalex.org/W3127490177\",\"https://openalex.org/W4206083694\",\"https://openalex.org/W4293199581\",\"https://openalex.org/W4312054389\",\"https://openalex.org/W4389040484\",\"https://openalex.org/W4396224564\",\"https://openalex.org/W4408808337\"],\"authorships\":[{\"id\":\"https://openalex.org/A5139664214\",\"display_name\":\"Daisuke Ibi\",\"orcid\":null},{\"id\":\"https://openalex.org/A5076092672\",\"display_name\":\"Rika Takaba\",\"orcid\":null},{\"id\":\"https://openalex.org/A5079107661\",\"display_name\":\"Keisuke Yoshida\",\"orcid\":\"https://orcid.org/0000-0002-8384-9418\"},{\"id\":\"https://openalex.org/A5108412221\",\"display_name\":\"R. Kawase\",\"orcid\":null},{\"id\":\"https://openalex.org/A5048244424\",\"display_name\":\"Hiroko Kitagawa\",\"orcid\":null},{\"id\":\"https://openalex.org/A5139661865\",\"display_name\":\"Momoko Matsushita\",\"orcid\":null},{\"id\":\"https://openalex.org/A5139634014\",\"display_name\":\"Kana Ito\",\"orcid\":null},{\"id\":\"https://openalex.org/A5030080970\",\"display_name\":\"Shoya Uno\",\"orcid\":null},{\"id\":\"https://openalex.org/A5139632842\",\"display_name\":\"Fumiya Nishimura\",\"orcid\":null},{\"id\":\"https://openalex.org/A5014830673\",\"display_name\":\"Shinji Kitagaki\",\"orcid\":\"https://orcid.org/0000-0001-7496-7773\"},{\"id\":\"https://openalex.org/A5139711108\",\"display_name\":\"Masayuki Hiramatsu\",\"orcid\":null}],\"primary_location\":{\"source_id\":\"https://openalex.org/S4210189692\",\"source_display_name\":\"Neuropsychopharmacology Reports\",\"landing_page_url\":\"https://doi.org/10.1002/npr2.70152\",\"is_oa\":true}}}","topic_tags":"Depression,Anxiety,Receptor Pharmacology,Resilience,Animal Study,Treatment-Resistant Depression","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/W7166665532"},{"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":5674,"title":"Psilocybe Poisoning: Pathophysiology, Classification and Treatment. A Clinical Case Review","normalized_title":"psilocybe poisoning pathophysiology classification and treatment a clinical case review","authors":"Omar Azuara-Antonio, Erika Rubí De La Cruz-Elizaldeb, José Eduardo Carmona-Rodriguez, Lesly Idaliht Hernandez-Martinez","abstract":"The Psilocybe cubensis mushroom is recognized as the primary source of psilocybin in the Americas, occurring naturally across various regions. This fungus has a long history of use in Mesoamerican rituals due to its capacity to induce altered states of consciousness. The defining characteristic of Psilocybe mushrooms is their psilocybin content. Following ingestion, psilocybin is metabolized into psilocin, which acts as a potent serotonergic agonist by interacting with serotonin receptors. The resulting physiological and psychoactive effects are linked to the activity at 5-HT receptors within the central nervous system, along with the release of glutamate. Throughout history, diverse Mesoamerican cultures incorporated hallucinogenic mushroom consumption into their ritual ceremonies. The Aztecs, for example, revered them as Teonanácatl, or \" flesh of the gods,\" valuing their ability to shift the perception of reality. Interest in psilocybin has seen a resurgence in the scientific community, spanning from the ethnobotanical studies of R. Gordon Wasson in the 1950s to contemporary research into its therapeutic applications for depression. Studies have indicated that psilocybin can sustainably alleviate depressive symptoms, often with fewer side effects compared to conventional pharmacological treatments. The combination of the ancient ceremonial and religious use of Psilocybe mushrooms with their demonstrable therapeutic potential is prompting a reevaluation of their legal status as a Schedule I drug. Ongoing research is actively exploring the impact of psilocybin on various psychiatric disorders, yielding promising results, particularly in the treatment of major depressive disorder. As the evidence supporting its therapeutic benefits continues to accumulate, it suggests a future where these psychedelic compounds could play a vital role in global mental health.","journal":"Mexican Journal of Medical Research ICSA","publication_date":"2026-07-04","publication_year":2026,"doi":"10.29057/mjmr.v14i28.16493","pubmed_id":null,"source_url":"https://doi.org/10.29057/mjmr.v14i28.16493","keywords":"Psilocybin, Serotonergic, Hallucinogen, Trance, Psychology, Pharmacology, Traditional medicine, Medicine, Neuroscience, Serotonin Agonist, Ayahuasca, Agonist, Amphetamine, Psychiatry, 5-HT2 receptor, Psychedelics and Drug Studies, Forensic Toxicology and Drug Analysis, Chemical synthesis and alkaloids","substance_tags":"psilocybin,psilocin","source_name":"OpenAlex","date_added":"2026-07-07 01:20:41","last_checked":"2026-07-09 01:20:16","raw_json":"{\"openalex_id\":\"https://openalex.org/W7167422156\",\"openalex_url\":\"https://openalex.org/W7167422156\",\"openalex_relevance_score\":10,\"openalex_relevance_reasons\":[\"abstract:psilocybin\",\"metadata:psilocybin\",\"abstract:psilocin\",\"contextual-mushroom-match\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[],\"authorships\":[{\"id\":\"https://openalex.org/A5051415806\",\"display_name\":\"Omar Azuara-Antonio\",\"orcid\":\"https://orcid.org/0000-0002-8648-4573\"},{\"id\":\"https://openalex.org/A5140086242\",\"display_name\":\"Erika Rubí De La Cruz-Elizaldeb\",\"orcid\":null},{\"id\":\"https://openalex.org/A5140068470\",\"display_name\":\"José Eduardo Carmona-Rodriguez\",\"orcid\":\"https://orcid.org/0009-0002-9952-3356\"},{\"id\":\"https://openalex.org/A5140080438\",\"display_name\":\"Lesly Idaliht Hernandez-Martinez\",\"orcid\":\"https://orcid.org/0009-0002-2027-9574\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S4210193124\",\"source_display_name\":\"Mexican Journal of Medical Research ICSA\",\"landing_page_url\":\"https://doi.org/10.29057/mjmr.v14i28.16493\",\"is_oa\":true}}","topic_tags":"Depression,Pharmacology,Receptor Pharmacology,Consciousness,Review Article,Adverse Events,Toxicity","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W7167422156"},{"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":58,"title":"MFCC-DFT mapping of ligand recognition at the 5-HT2A receptor: energetic analysis of the interactions between serotonin, psychedelics, and antipsychotics.","normalized_title":"mfcc dft mapping of ligand recognition at the 5 ht2a receptor energetic analysis of the interactions between serotonin psychedelics and antipsychotics","authors":"Junior WSC, Bezerra KS, Matias EGC, Oliveira JIN, Fulco UL.","abstract":"Mental disorders represent a major global health problem, with depression being one of the most prevalent and disabling conditions worldwide. Growing evidence suggests that the serotonergic system, particularly the 5-HT2A receptor, plays an important role in modulating mood and cognitive processes, constituting a key pharmacological target for several psychoactive compounds. In this study, we investigated the molecular interaction profile between the 5-HT2A receptor and four pharmacologically relevant ligands, serotonin (5-HT), psilocybin/psilocin (PSILO), lysergic acid diethylamide (LSD), and lumateperone (LMTP). Interaction energies were evaluated using the molecular fragmentation with conjugated caps (MFCC) method combined with density functional theory (DFT) calculations. Crystallographic structures were used as initial models, and residue-level interaction energies were calculated to identify the amino acids that contribute most to ligand stabilization at the receptor binding site. The results reveal that the complexes exhibit total interaction energies ranging from -35.38 to -71.98 kcal mol-1 under dielectric conditions representative of the protein environment. Key residues such as Asp155, Phe339, Leu229, and Val366 were identified as the main contributors to ligand stabilization in the studied systems, highlighting their role as structural anchors within the orthosteric binding pocket. Energy decomposition further revealed distinct interaction patterns associated with different regions of the ligand. Therefore, this study provides a detailed energetic characterization of ligand recognition in the 5-HT2A receptor and offers details that may contribute to the rational design of new serotonergic agents with potential for therapeutic applications.","journal":null,"publication_date":"2026-06-30","publication_year":2026,"doi":"10.1039/d6cp00943c","pubmed_id":"42300394","source_url":"https://doi.org/10.1039/d6cp00943c","keywords":"Humans, Serotonin, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Antipsychotic Agents, Hallucinogens, Ligands, Binding Sites, Thermodynamics, Psilocybin, Heterocyclic Compounds, 4 or More Rings, Density Functional Theory","substance_tags":"psilocybin,psilocin","source_name":"Europe PMC","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:23","raw_json":"{\"europe_pmc_id\":\"42300394\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Receptor Pharmacology,Drug Interactions","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":18,"title":"Neuropsychopharmacology of hallucinogenic and non-hallucinogenic 5-HT receptor agonists.","normalized_title":"neuropsychopharmacology of hallucinogenic and non hallucinogenic 5 ht receptor agonists","authors":"Sharp T, Ippolito A","abstract":"Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry based on increasing evidence that they can produce long-lasting improvements in health across a wide variety of mental illnesses, including major depression, addictions and anxiety disorders. These drugs interact with many different 5-HT receptor subtypes but the powerful psychedelic experience, which (depending on set and setting) includes profound alterations in perception, mood and cognition, accompanied by vivid hallucinations, is now widely considered mediated by an agonist action at 5-HT receptors. However, the link between the psychedelic experience, 5-HT receptor agonism and therapeutic effects is currently uncertain. Indeed, recent research has revealed a new class of 5-HT receptor agonists which appear to retain the therapeutic potential of psychedelics drugs without inducing disorienting hallucinatory experiences. Biased signalling, partial agonism and non-selectivity at the 5-HT receptor are amongst the possible explanations for the differential properties of these drugs, whereas increased neuroplasticity offers a likely account of their common therapeutic effects. This article explores the neuropsychopharmacological properties of hallucinogenic and non-hallucinogenic 5-HT receptor agonists in the context of their promise as novel drug treatments in psychiatry. 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.70050","pubmed_id":"40405723","source_url":"https://pubmed.ncbi.nlm.nih.gov/40405723/","keywords":"5-HT, 5-HT2A receptor, antidepressant, hallucinogens, psychedelics, serotonin","substance_tags":"psilocin","source_name":"PubMed","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:06","raw_json":"{\"pubmed_id\":\"40405723\"}","topic_tags":"Depression,Anxiety,Addiction,Neuroplasticity,Pharmacology,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":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":15,"title":"Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?","normalized_title":"are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation","authors":"Qureshi O, Cowley J, Pegg A, Cooper AJ, Gordon J, Brady CA, Belli A, Butterworth S, Upthegrove R, Andrews N, Barnes NM","abstract":"Psychedelic drugs that activate 5-HT receptors have been long used for cultural, medicinal and recreational purposes. Interest in psychedelics for treating psychiatric disorders has resurged recently and is well documented; less well recognised are their anti-inflammatory properties. Growing evidence now demonstrates that psychedelics modulate immune responses, including inhibiting pro-inflammatory cytokine release. Furthermore, in vivo studies demonstrate that psychedelics, like (R)-DOI, reduce inflammation in animal models of acute and chronic inflammatory disease such as asthma. Likewise, some clinical studies with psychedelic drugs (e.g. psilocybin) demonstrate an impact upon circulating cytokine levels, supporting a translation from the animal models to the clinical arena. Such data emphasise the promise of therapeutic approaches targeting inflammation. Interestingly, recent research has also uncovered compounds that maintain therapeutic potential without likely causing psychedelic effects. These discoveries suggest that drugs informed by psychedelic drugs, but which do not evoke psychedelic experiences, which we term PIPI drugs (Psychedelic drug Informed but Psychedelic experience Inactive), could offer effective treatments for mental health and inflammation, presenting new avenues for therapeutic development. 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.70138","pubmed_id":"40726049","source_url":"https://pubmed.ncbi.nlm.nih.gov/40726049/","keywords":"5-HT2A receptor, immune system, inflammation, neuroinflammation, psychedelic drugs","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\":\"40726049\"}","topic_tags":"Receptor Pharmacology,Animal Study,Inflammation,Immune Function","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":13,"title":"Correction: The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice.","normalized_title":"correction the serotonin 1b receptor is required for some of the behavioral effects of psilocybin in mice","authors":"Fleury S, Nautiyal KM.","abstract":"","journal":null,"publication_date":"2026-06-30","publication_year":2026,"doi":"10.1038/s41380-026-03488-5","pubmed_id":"41680332","source_url":"https://doi.org/10.1038/s41380-026-03488-5","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-08 01:20:23","raw_json":"{\"europe_pmc_id\":\"41680332\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"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":"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":1921,"title":"The relevance of the 5HT2A-mGlu2 heterodimer in explaining the clinical ambivalence of psilocybin","normalized_title":"the relevance of the 5ht2a mglu2 heterodimer in explaining the clinical ambivalence of psilocybin","authors":"Escobar-Cornejo Guillermo, Corredor-Gamba Julián, Rodriguez-Rojas Yoly, Cárdenas F. P.","abstract":"","journal":"Revista de Neuro-Psiquiatría","publication_date":"2026-06-29","publication_year":2026,"doi":"10.20453/rnp.v89i2.7539","pubmed_id":null,"source_url":"https://doi.org/10.20453/rnp.v89i2.7539","keywords":"","substance_tags":"psilocybin","source_name":"Crossref","date_added":"2026-07-01 06:49:23","last_checked":"2026-07-07 01:20:41","raw_json":"{\"doi\":\"10.20453/rnp.v89i2.7539\",\"reference_dois\":[],\"reference_count\":0,\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7166853822\",\"openalex_url\":\"https://openalex.org/W7166853822\",\"openalex_relevance_score\":6,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[],\"authorships\":[{\"id\":\"https://openalex.org/A5024191030\",\"display_name\":\"Guillermo Saúl Escobar Cornejo\",\"orcid\":\"https://orcid.org/0000-0001-5936-3023\"},{\"id\":\"https://openalex.org/A5119218852\",\"display_name\":\"Julián Corredor-Gamba\",\"orcid\":null},{\"id\":\"https://openalex.org/A5139724047\",\"display_name\":\"Yoly Rodriguez-Rojas\",\"orcid\":\"https://orcid.org/0009-0009-9984-1777\"},{\"id\":\"https://openalex.org/A5029069026\",\"display_name\":\"Fernando P. Cárdenas\",\"orcid\":\"https://orcid.org/0000-0002-8826-6211\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S4210210805\",\"source_display_name\":\"Revista de Neuro-Psiquiatría\",\"landing_page_url\":\"https://doi.org/10.20453/rnp.v89i2.7539\",\"is_oa\":true}}}","topic_tags":"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":"https://openalex.org/W7166853822"},{"id":302,"title":"Chronic psilocin microdosing produces limited behavioral effects and does not enhance neurogenesis in rats.","normalized_title":"chronic psilocin microdosing produces limited behavioral effects and does not enhance neurogenesis in rats","authors":"Ladislavová L, Kútná V, Mazochová K, Šíchová K, Danda H, Lhotková E, Uttl L, Brejtr V, Syrová K, Mazoch V, Horsley R, Páleníček T.","abstract":"Psilocin (4-hydroxy-N, N-dimethyltryptamine) is a substituted tryptamine alkaloid and a nonselective serotonergic agonist acting predominantly at 5-HT2A/C receptors, with substantial binding to 5-HT1A and 5-HT2B receptors. Microdosing is the practice of taking a very small, sub-perceptual dose, typically 5% to 10% of a full recreational dose, to improve mood, creativity, and focus without hallucinogenic effects. However, rigorous preclinical evidence for its behavioral and neurobiological effects remains limited. We therefore examined whether chronic psilocin microdosing alters behavior and dentate gyrus (DG) cell proliferation in adult male Wistar rats. Psilocin was administered subcutaneously at 0.05 or 0.075 mg/kg. Animals received six doses of psilocin or saline on alternate days over 18 days prior to the first behavioral assessment, and microdosing on alternate days continued between behavioral tasks for five weeks. To minimize acute drug effects, all behavioral assessments were performed 48 h after the preceding dose. Animals were tested sequentially in the Elevated Plus Maze, Hole-Board, Open Field, Social Interaction, and modified Forced Swim Test, with six-day intervals between tests. DG cell proliferation was quantified by BrdU and Ki-67 immunohistochemistry. Across this regimen, psilocin microdosing did not measurably affect locomotor activity, depressive-like behavior, sociability, or novelty seeking, and it did not increase DG proliferation by either marker. A small anxiogenic effect was detected in the Elevated Plus Maze. These data indicate that, under the present dosing schedule and endpoints, chronic psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation in rats.","journal":null,"publication_date":"2026-06-29","publication_year":2026,"doi":"10.1016/j.pbb.2026.174231","pubmed_id":"42379524","source_url":"https://doi.org/10.1016/j.pbb.2026.174231","keywords":"","substance_tags":"psilocin","source_name":"Europe PMC","date_added":"2026-07-01 06:48:03","last_checked":"2026-07-07 01:20:35","raw_json":"{\"europe_pmc_id\":\"42379524\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Neurogenesis,Receptor Pharmacology,Biomarkers,Microdosing,Creativity,Animal Study,Drug Interactions","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":3595,"title":"Acute Effects of MDMA Co-administration on the Response to Psilocybin in Healthy Subjects","normalized_title":"acute effects of mdma co administration on the response to psilocybin in healthy subjects","authors":"University Hospital, Basel, Switzerland","abstract":"The acute subjective effects of serotonin (5-HT)2A receptor stimulation with psilocybin in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking, or loss of trust towards other people are common effects, depending on the dose administered, the personality traits of the person consuming it (set), or the environment in which psilocybin is taken (setting). Negative psychedelic effects may cause acute distress to the subject and acute anxiety has been linked to less favorable long-term outcomes in patients experimentally treated with psilocybin or similar substances for the treatment of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA) reliably induces positive mood, euphoria, comfort, empathy, and feelings of trust. If administered in combination with psilocybin, MDMA may increase positive subjective drug effects including positive mood, empathy, and trust and reduce negative emotions and anxiety associated with psilocybin and overall produce a more positive over negative experience. The present study will assess subjective and autonomic effects of psilocybin alone and in combination with MDMA. Psilocybin is a classic serotonergic psychedelic. Clinically, the acute effects of psilocybin last shorter than those of lysergic acid diethylamide (LSD) but are qualitatively very similar. Currently, psilocybin is the most investigated psychedelic substance among the classic psychedelics including LSD, psilocybin, mescaline, and dimethyltryptamine (DMT). Psilocybin is capable of inducing exceptional subjective effects such as a dream-like alteration of consciousness, affective changes, psychological insight, visual imagery, pseudo-hallucinations and ego-dissolution. The acute subjective effects elicited by psilocybin are mostly positive in humans. However, psychedelic substances like psilocybin may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of psilocybin used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize the effects of psilocybin by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.","journal":"ClinicalTrials.gov","publication_date":"2026-06-24","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT06884514","keywords":"Healthy, Psilocybin, 3,4-Methylenedioxymethamphetamine, Psilocybin placebo, 3,4-Methylenedioxymethamphetamine placebo, COMPLETED","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\":\"NCT06884514\",\"overall_status\":\"COMPLETED\",\"phase\":[\"PHASE1\"]}","topic_tags":"Depression,Anxiety,Addiction,Receptor Pharmacology,Consciousness,Wellbeing,Personality Change,Emotional Processing,Safety","study_type":"Qualitative Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"clinical trial","openalex_id":null},{"id":3525,"title":"Psilocybin Administration With 5-HT1a Blockade","normalized_title":"psilocybin administration with 5 ht1a blockade","authors":"Johns Hopkins University","abstract":"The purpose of this study is to assess the effects of 5-HT1A receptor blockade on the acute subjective effects of psilocybin, as measured through subjective survey measures and acute electroencephalography (EEG). Further, the investigators will assess the effects of psilocybin on post-acute sleep and dreaming through the use of sleep EEG and sleep and dream diaries. This double-blind, randomized, cross-over study (N = 18) will administer a moderate dose of psilocybin trihydrate (18 mg, equivalent to 15 mg psilocybin anhydrate), with pindolol (30 mg), or placebo to assess the effects of 5-HT1A receptor blockade on the acute subjective effects and the acute neurophysiological effects of psilocybin through the use of self-report measures and acute EEG. Participants will also complete sleep and dream diaries 10 days prior to and 10 days following each drug administration session as well as wear an at-home sleep EEG device for 5 days prior to and 5 days following each drug session. This study aims to understand the mechanistic basis of the perceptual changes in the altered state of consciousness induced by psilocybin as well as its effects on post-acute sleep and dreaming.","journal":"ClinicalTrials.gov","publication_date":"2026-06-24","publication_year":2026,"doi":null,"pubmed_id":null,"source_url":"https://clinicaltrials.gov/study/NCT07565493","keywords":"Psychedelic Effects in Healthy Volunteers, Pindolol, Placebo, Microcrystalline cellulose placebo, Psilocybin, RECRUITING","substance_tags":"psilocybin","source_name":"ClinicalTrials.gov","date_added":"2026-07-01 11:04:27","last_checked":"2026-07-01 23:13:10","raw_json":"{\"nct_id\":\"NCT07565493\",\"overall_status\":\"RECRUITING\",\"phase\":[\"EARLY_PHASE1\"]}","topic_tags":"Brain Imaging,Receptor Pharmacology,Consciousness,Observational Study,Healthy Volunteers","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}],"total":1062,"page":1,"per_page":20,"pages":54,"resource":"papers","filters":{"q":null,"author":null,"substances":["psilocybin","psilocin"],"topic":"Receptor Pharmacology","study_type":null,"cited_doi":null,"sources":[],"publication_statuses":[],"year":null,"journal":null,"from":null,"to":null,"added_from":null,"added_to":null,"sort":"newest","page":1,"per_page":"20"}}