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Substance-induced psychotic disorders (SIPD) are frequent and account for about 25% of the first admissions to a psychiatric hospital. From a clinical point of view the differential diagnosis of SIPD vs. primary (genuine or cryptogenic) psychotic disorders is often a challenge due to the similar psychopathology. This is complicated by the fact that SIPDs associated with cannabis, hallucinogens and amphetamines have a significant risk of transition to manifest psychotic disorder (e.g. schizophrenia). In the first section of this paper two case reports from general psychiatric and forensic practice are presented. Then, in a narrative review the relevance of the differential diagnostic distinction between both disorders is examined from the perspective of general and forensic psychiatry with respect to therapy, prognosis and judicial decisions regarding the placement in forensic commitment (§ 63 vs. § 64 German Penal Code, StGB). The last section aims to develop a structured procedure for the differentiation between SIPD and primary psychotic disorders. The concepts and findings presented and discussed in this paper are intended to help psychiatrists and psychologists make a diagnosis in a general and a forensic context., (© 2021. The Author(s).)