{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T10:13:41Z","timestamp":1787912021062,"version":"build-2784847793"},"reference-count":53,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Substance-induced psychosis is a recognized clinical entity, commonly linked to cannabinoids, stimulants, hallucinogens, alcohol, and polysubstance use. These agents may provoke transient or persistent psychotic symptoms during intoxication or withdrawal. Opioids, however, constitute a noteworthy exception: psychosis is rarely observed during opioid intoxication, and emerging data suggest that opioid agonists might even exert antipsychotic-like effects. This article examines the paradoxical interaction between opioids and psychosis, with attention to clinical reports of psychotic symptoms arising following abrupt discontinuation of methadone or buprenorphine. In numerous cases, symptoms resolved swiftly after reintroduction of the opioid agonist, implying a neuromodulatory role. Opioids, unlike other substances of abuse, seem to lack intrinsic psychotogenic effects and may influence dopaminergic activity via kappa-opioid receptor antagonism and endorphinergic mechanisms. This challenges standard models of substance-induced psychosis and calls for a refined understanding of opioid pharmacodynamics in psychiatric contexts. In psychotic presentations among polysubstance users who also use opioids, restoring opioid agonist therapy should be prioritized, with antipsychotics reserved as second-line options\u2014preferably agents with favorable receptor profiles. Where opioids are not involved, antipsychotics remain first-line, but should be applied judiciously, with efforts to taper when clinically appropriate.<\/jats:p>","DOI":"10.3390\/jcm14155596","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T09:56:42Z","timestamp":1754647002000},"page":"5596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antipsychotic Potential of Opioids: Rethinking Substance-Induced Psychosis and Treatment Stratification"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7728-3705","authenticated-orcid":false,"given":"Angelo G. I.","family":"Maremmani","sequence":"first","affiliation":[{"name":"UniCamillus, International Medical University in Rome, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"},{"name":"VP Dole Research Group, PISA-School of Addiction Medicine, G. De Lisio Institute of Behavioural Sciences, Via di Pratale 3, 56121 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7935-3524","authenticated-orcid":false,"given":"Filippo","family":"Della Rocca","sequence":"additional","affiliation":[{"name":"UniCamillus, International Medical University in Rome, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"},{"name":"VP Dole Research Group, PISA-School of Addiction Medicine, G. De Lisio Institute of Behavioural Sciences, Via di Pratale 3, 56121 Pisa, Italy"},{"name":"Addiction Unit, Department of Mental Health and Addictions, ASL5 Liguria NHS, Via Dalmazia 1, 19124 La Spezia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bacciardi","sequence":"additional","affiliation":[{"name":"UniCamillus, International Medical University in Rome, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"},{"name":"VP Dole Research Group, PISA-School of Addiction Medicine, G. De Lisio Institute of Behavioural Sciences, Via di Pratale 3, 56121 Pisa, Italy"},{"name":"Department of Psychiatry and Addictions, Section of Psychiatry, North-Western Tuscany Local Health Unit, Tuscany NHS, Versilia Zone, Via Aurelia 335, 55041 Lido di Camaiore, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-6008","authenticated-orcid":false,"given":"Manuel Glauco","family":"Carbone","sequence":"additional","affiliation":[{"name":"UniCamillus, International Medical University in Rome, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"},{"name":"VP Dole Research Group, PISA-School of Addiction Medicine, G. De Lisio Institute of Behavioural Sciences, Via di Pratale 3, 56121 Pisa, Italy"},{"name":"Division of Psychiatry, Department of Medicine and Surgery, University of Insubria, Viale Luigi Borri 57, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-0576","authenticated-orcid":false,"given":"Icro","family":"Maremmani","sequence":"additional","affiliation":[{"name":"UniCamillus, International Medical University in Rome, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"},{"name":"VP Dole Research Group, PISA-School of Addiction Medicine, G. De Lisio Institute of Behavioural Sciences, Via di Pratale 3, 56121 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.schres.2017.11.001","article-title":"Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-induced psychotic disorders: A systematic review","volume":"197","author":"Wilson","year":"2018","journal-title":"Schizophr. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fiorentini, A., Cantu, F., Crisanti, C., Cereda, G., Oldani, L., and Brambilla, P. (2021). Substance-Induced Psychoses: An Updated Literature Review. Front. 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