Increased sensitivity to stress in spontaneous recurrence of methamphetamine psychosis: Noradrenergic hyperactivity with contribution from dopaminergic hyperactivity

The significance of increased sensitivity to stress associated with noradrenergic hyperactivity involving dopaminergic change in spontaneous recurrences of methamphetamine (MAP) psychosis (flashbacks) was examined. Plasma monoamine metabolite levels were assayed in 18 subjects with flashbacks who had been exposed to stressful events plus MAP-induced frightening psychotic symptoms (N = 11) or frightening psychotic symptoms alone (N = 7) during previous MAP use, in 15 nonflashbackers with a history of MAP psychosis, in 8 subjects with persistent MAP psychosis, and in 27 control subjects. Monoaminergic values were subjected to a square-root transformation, rendering the distribution normal. The numbers of stressful events (mostly threatening events) and frightening psychotic symptoms were significantly higher in the flashbackers than in the nonflashbackers. Factors triggering flashbacks were mild psychosocial stressors (mostly a mild fear of other people). During flashbacks, plasma norepinephrine levels increased, and the flashbackers, II of whom had experienced stressful events plus frightening psychotic symptoms, had an additional small increase in plasma levels of 3-methoxytyramine, which is indicative of dopamine release. Thus, threatening stressful events, together with MAP use, may induce noradrenergic hyperreactivity to subsequent mild stressors. Threatening, stressful events plus frightening psychotic symptoms may further induce increased dopamine release in response to mild stressors. Increased sensitivity to stress associated with noradrenergic hyperactivity involving increased dopamine release may have elicited memories of MAP psychosis related to frightening, stressful experiences. The increased sensitivity may be critical for the development of flashbacks.