{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:51:53Z","timestamp":1790189513545,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anti-Drug Policies Department, Presidency of the Council of Ministers, Italy"},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["FAR 2024"],"award-info":[{"award-number":["FAR 2024"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["FAR 2025"],"award-info":[{"award-number":["FAR 2025"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FAR 2024"],"award-info":[{"award-number":["FAR 2024"]}],"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FAR 2025"],"award-info":[{"award-number":["FAR 2025"]}],"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Novel psychoactive substances (NPSs) exhibit extremely strong pharmaco-toxicological activity, often leading to severe adverse effects that pose a serious risk to consumers\u2019 health. Among these, synthetic cannabinoids (SCs) currently represent the majority of drug seizures in Europe. One such compound, AKB-48 (also known as APINACA), was first identified in Japanese herbal smoking blends in 2012. Although it mimics the effects of \u03949-THC, the primary psychoactive component of Cannabis sativa, AKB-48 can induce more severe and potentially life-threatening outcomes. Several in vivo studies investigating the acute administration of AKB-48 have reported profound behavioral, neurological, and neurochemical alterations, including disruptions of neurotransmission across multiple brain regions, thus confirming its neurotoxic potential. Given the recognized vulnerability of the cerebellum to NPS, and its critical role in integrating neural circuits affected by psychostimulant drugs, the present study evaluated the toxic effects of repeated AKB-48 exposure on the cerebellar cortex of adult male and female ICR-CD1\u00ae mice. Particular attention was paid to the modulation of cell death pathways, alongside assessments of sensorimotor responses. The results demonstrate, for the first time, that repeated AKB-48 administration induces significant morphological, immunohistochemical, and ultrastructural changes in both male and female mice. These alterations included pronounced disruption of cerebellar architecture and marked modulation of cell death pathways, further corroborated by TEM-detected ultrastructural damage and a substantial reduction in the basal visual placing response. Overall, the findings provide clear evidence of AKB-48\u2019s sex-independent neurotoxicity, leading to cerebellar alterations that ultimately result in neuroplasticity impairment.<\/jats:p>","DOI":"10.3390\/ijms27093867","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Synthetic Cannabinoid AKB-48 Induces Cell Death in Murine Cerebellum Through Different Signaling Pathways"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6462-2373","authenticated-orcid":false,"given":"Fabrizio","family":"De Luca","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-2446","authenticated-orcid":false,"given":"Giorgia","family":"Corli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3753-4627","authenticated-orcid":false,"given":"Marta","family":"Bassi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrine","family":"Bilel","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Merli","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia, Italy"},{"name":"INFN Sezione di Milano-Bicocca, Piazza della Scienza 3, 20126 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-3445","authenticated-orcid":false,"given":"Davide","family":"Lonati","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Toxicology, and Poison Control Centre and National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-8750","authenticated-orcid":false,"given":"Azzurra","family":"Schicchi","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Toxicology, and Poison Control Centre and National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-8785","authenticated-orcid":false,"given":"Maria Grazia","family":"Bottone","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2154-5897","authenticated-orcid":false,"given":"Carlo Alessandro","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Toxicology, and Poison Control Centre and National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8751-2882","authenticated-orcid":false,"given":"Matteo","family":"Marti","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Collaborative Center for the Italian National Early Warning System, NEWS-D, Department of Anti-Drug Policies and Other Addictions, Presidency of the Council of Ministers, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Roda","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Toxicology, and Poison Control Centre and National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","unstructured":"United Nations Office on Drugs and Crime (UNODC) (2025, June 20). 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