Substance-induced schizophrenia: possible pathogenetic mechanisms

This brief report presents a narrative literature review describing potential pathogenetic mechanisms underlying the transformation of drug-induced psychoses into chronic psychotic disorders of the schizophrenic spectrum. The central role of hyperdopaminergia in the development of productive psychotic symptoms is discussed, along with the possibility of dopamine D2 receptor sensitization resulting from prolonged use of stimulant drugs. Attention is drawn to the previously described phenomenon of reverse tolerance, the study of which at genetic, molecular, neurotransmitter, and clinical levels may offer a promising approach for clinical assessment of prognosis and prevention of schizophrenia in individuals with a history of substance use.