{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:16:07Z","timestamp":1781237767007,"version":"3.54.1"},"posted":{"date-parts":[[2024,6,29]]},"group-title":"Pharmacology and Toxicology","reference-count":38,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg\/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 4 and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety and other behavioral features. Mice treated with vehicle (n=18) manifested a 118.71\n                  <jats:underline>+<\/jats:underline>\n                  95.96 % increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60%\n                  <jats:underline>+<\/jats:underline>\n                  17.90% in mice treated with psilocybin (n=16) and by 19.20\n                  <jats:underline>+<\/jats:underline>\n                  20.05% in mice treated with psychedelic mushroom extract (n=16) (p=.001 for effect of time; p=.0001 for time X treatment interaction). 5 mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n=12) and psychedelic mushroom extract (n=13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"600634v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                  <jats:p>\n                    Prepared with BioRender (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.biorender.com\/\">https:\/\/www.biorender.com\/<\/jats:ext-link>\n                    )\n                  <\/jats:p>\n                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Self-Grooming"],"prefix":"10.64898","author":[{"given":"Michal","family":"Brownstien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Lazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Botvinnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Shevakh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Blakolmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-4991","authenticated-orcid":false,"given":"Leonard","family":"Lerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzuri","family":"Lifschytz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9914-632X","authenticated-orcid":false,"given":"Bernard","family":"Lerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024070220401381000_2024.06.25.600634v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.94"},{"key":"2024070220401381000_2024.06.25.600634v1.2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.20111601"},{"key":"2024070220401381000_2024.06.25.600634v1.3","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145711001829"},{"key":"2024070220401381000_2024.06.25.600634v1.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012959"},{"key":"2024070220401381000_2024.06.25.600634v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature06104"},{"key":"2024070220401381000_2024.06.25.600634v1.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.18.11943"},{"key":"2024070220401381000_2024.06.25.600634v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/35039075"},{"key":"2024070220401381000_2024.06.25.600634v1.8","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.3.669"},{"key":"2024070220401381000_2024.06.25.600634v1.9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133339"},{"key":"2024070220401381000_2024.06.25.600634v1.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2533-11.2011"},{"issue":"1","key":"2024070220401381000_2024.06.25.600634v1.11","doi-asserted-by":"crossref","first-page":"12061","DOI":"10.1038\/s41598-019-48637-9","article-title":"Aberrant 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