Increased sensitivity to stress associated with noradrenergic hyperactivity, involving dopaminergic hyperactivity in spontaneous recurrences in methamphetamine psychosis

The study examined the significance of increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes in spontaneous recurrences of methamphetamine (MAP) psychosis (flashbacks). Plasma monoamine metabolite levels were assayed in the subjects: 19 flashbackers, 18 non‐flashbackers with a history of MAP psychosis and 37 controls. Monoaminergic values underwent a square‐root transformation. All flashbackers had been exposed to stressful events plus MAP‐induced fear‐related psychotic symptoms (n = 11) or fear‐related symptoms alone (n = 8). Factors triggering flashbacks met the DSM‐III‐R criteria for mild psychosocial stressors. During flashbacks norepinephrine levels increased markedly and 3‐methoxytyramine, which is indicative of dopaminergic activity, increased to a lesser extent. Among the flashbackers, 11 with a history of stressful events plus fear‐related symptoms displayed further a small increase in 3‐methoxytyramine levels. Thus, stressful events plus fear‐related symptoms, together with MAP use, may induce noradrenergic hyperactivity and some degree of dopaminergic hyperactivity in response to mild stressors. Increased sensitivity to stress associated with a predominance of noradrenergic over dopaminergic hyperactivity may be a precipitating factor in flashbacks.