Background: Novel psychoactive substances (NPS) have shown increasing prevalence worldwide, yet their relationship with psychotic disorders remains incompletely characterized despite growing clinical concern. Objective: To systematically evaluate the epidemiological evidence, clinical characteristics, neurobiological mechanisms, vulnerability factors, and management approaches for NPS-associated psychosis. Methods: A comprehensive systematic review following PRISMA guidelines was conducted across five major databases from January 2005 through December 2022. Quality assessment was performed using the Newcastle-Ottawa Scale and Joanna Briggs Institute checklist. Of 684 initially identified records, 85 studies met inclusion criteria, comprising case reports/series (n = 38), retrospective cohort studies (n = 25), cross-sectional studies (n = 10), case-control studies (n = 7), experimental studies (n = 3), and prospective cohort studies (n = 2). Results: Epidemiological evidence consistently suggested higher psychosis risk with NPS compared to traditional substances (OR 4.4–5.2 for synthetic cannabinoids versus cannabis). Distinctive clinical profiles emerged: synthetic cannabinoid-induced “spiceophrenia” featured visual hallucinations (73–84 %), agitation (79–91 %), and anxiety (62–76 %); cathinone-induced psychosis presented with extreme agitation (81–94 %) and stereotyped behaviors (47–63 %); phenethylamine-induced states showed perceptual disturbances including synesthesia (37–54 %). Neurobiological investigations indicated different mechanisms across substance classes. Key vulnerability factors included pre-existing psychiatric conditions, adolescent exposure, and polysubstance use. Conclusion: NPS use is associated with elevated psychosis risk and distinctive clinical presentations across substance classes. Standardized assessment approaches and rigorous longitudinal investigations are needed to better establish causality, refine substance-specific treatment protocols, and develop targeted prevention strategies.
Novel psychoactive substances and psychosis: A comprehensive systematic review of epidemiology, clinical features, neurobiology, and treatment
Ricci, Valerio;Maina, Giuseppe
2025-01-01
Abstract
Background: Novel psychoactive substances (NPS) have shown increasing prevalence worldwide, yet their relationship with psychotic disorders remains incompletely characterized despite growing clinical concern. Objective: To systematically evaluate the epidemiological evidence, clinical characteristics, neurobiological mechanisms, vulnerability factors, and management approaches for NPS-associated psychosis. Methods: A comprehensive systematic review following PRISMA guidelines was conducted across five major databases from January 2005 through December 2022. Quality assessment was performed using the Newcastle-Ottawa Scale and Joanna Briggs Institute checklist. Of 684 initially identified records, 85 studies met inclusion criteria, comprising case reports/series (n = 38), retrospective cohort studies (n = 25), cross-sectional studies (n = 10), case-control studies (n = 7), experimental studies (n = 3), and prospective cohort studies (n = 2). Results: Epidemiological evidence consistently suggested higher psychosis risk with NPS compared to traditional substances (OR 4.4–5.2 for synthetic cannabinoids versus cannabis). Distinctive clinical profiles emerged: synthetic cannabinoid-induced “spiceophrenia” featured visual hallucinations (73–84 %), agitation (79–91 %), and anxiety (62–76 %); cathinone-induced psychosis presented with extreme agitation (81–94 %) and stereotyped behaviors (47–63 %); phenethylamine-induced states showed perceptual disturbances including synesthesia (37–54 %). Neurobiological investigations indicated different mechanisms across substance classes. Key vulnerability factors included pre-existing psychiatric conditions, adolescent exposure, and polysubstance use. Conclusion: NPS use is associated with elevated psychosis risk and distinctive clinical presentations across substance classes. Standardized assessment approaches and rigorous longitudinal investigations are needed to better establish causality, refine substance-specific treatment protocols, and develop targeted prevention strategies.
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