Spontaneous Recurrence of Methamphetamine-lnduced Paranoid-Hallucinatory States in Female Subjects: Susceptibility to Psychotic States and Implications for Relapse of Schizophrenia

Abstract

In this study, we examined the relationship between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). The subjects were 81 physically healthy females. Plasma monoamine metabolite levels were assayed in: 19 flashbackers, of whom 11 experienced a single flashback and 8 exhibited subsequent flashbacks; 20 non-flashbackers with a history of MAP psychosis; 8 subjects with persistent MAP psychosis; and 23 MAP users and 11 non-user controls. All 19 flashbackers had undergone frightening and stressful experiences during previous MAP use. Mild psychosocial stressors then triggered their flashbacks. During flashbacks, plasma norepinephrine levels increased, with a small increase in plasma levels of 3-methoxytyramine, which is an index of dopamine release. Among the 19 flashbackers, the 8 with subsequent episodes had increased NE levels and slightly increased 3-methoxytyramine levels, while the 11 with a single episode displayed small increases in norepinephrine and 3-methoxytyramine levels. Thus, noradrenergic hyperactivity and increased dopamine release in response to mild psychosocial stressors may be responsible for the development of flashbacks. Robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may induce susceptibility to subsequent flashbacks. Flashbacks and schizophrenia may share the pathophysiology of susceptibility to recurrence of paranoid-hallucinatory states such as stress sensitization, and also noradrenergic hyperactivity and enhanced DA release. Thus, flashbacks may provide an appropriate model of susceptibility to paranoid-hallucinatory states of schizophrenia. The model psychosis is a potential tool for validating basic neurobiological concepts thought to be related to the schizophrenia. A better understanding of the neurobiological mechanisms of susceptibility to recurrence could provide useful information in the development of strategies for preventing relapse.

A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia

“…There is substantial evidence for a DA involvement in psychosis: (1) DA agonists are known to exacerbate psychosis in schizophrenia (Curran et al, 2004;Yui et al, 2002), (2) DA antagonist antipsychotic drugs are more effective at treating the positive psychotic symptoms of this disorder (Seeman et al, 1976;Strange, 2001), (3) and PET imaging studies show higher amphetamine-induced raclopride displacement in schizophrenia subjects, indicative of increased DA release that correlates with a worsening of psychosis (Breier et al, 1997;Laruelle et al, 1999). It has already been established that the HPC regulates DA population activity in the VTA via a multisynaptic pathway (vHPCFnucleus accumbensF ventral pallidumFVTA) (Floresco et al, 2001;Floresco et al, 2003).…”

Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine

“…Methamphetamine is a highly addictive drug of abuse, and chronic methamphetamine users show psychotic signs such as hallucinations and delusions, which are indistinguishable from paranoid schizophrenia (78,79). Chronic use of methamphetamine also causes long-term cognitive deficits (80).…”

Chronic khat use and psychotic disorders: A review of the literature and future prospects

“…It is unclear whether moderate use or only excessive, chronic or prolonged chewing might have the adverse effects. Of special importance in this context is the question of whether sensitization to the effects of khat is associated with relapses or deterioration of symptoms (Yui et al, 2002). The longitudinal assessment of patient data (e.g.…”