Amphetamine metabolism in amphetamine psychosis

The metabolism of 3 H‐d,l‐amphetamine was investigated in 11 subjects with amphetamine psychosis. In 3 patients with acidic urine (pH < 6.6), renal elimination of unchanged amphetamine (67% to 73%) was associated with plasma half‐life of 7 to 14 hours and rapid clearing of psychotic symptoms. In 4 patients with alkaline urinary pH metabolism became the dominant route of elimination and plasma half‐life increased to 18 to 34 hours. In these subfects the psychosis was also more long‐lasting. Parahydroxyamphetamine, p‐hydroxynorephedrine, and norephedrine constituted 3% to 8% and hippuric acid 14% to 16% of the metabolites in acidic urine, and 6.8% to 13% and 22% to 52%, respectively, in alkaline urine. The intensity of the psychosis was positively correlated to the amount of basic polar metabolites of amphetamine excreted in urine but not to the amphetamine level in the plasma. Our results indicate that amphetamine metabolites may be of importance in the development of the paranoid psychosis in chronic amphetamine abusers.