Methamphetamine-associated difficulties in cognitive control allocation may normalize after prolonged abstinence

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Abstract

Chronic heavy methamphetamine use likely causes dopaminergic neurotoxicity, which is commonly thought to result in cognitive control deficits. Both of these alterations may persist even after the use is discontinued, but tend to (partly) improve with increasing duration of abstinence. While several studies have demonstrated that the reinstatement of comparatively normal dopaminergic signaling may take months, if not years, the amelioration of cognitive deficits has predominantly been investigated in much shorter intervals of several weeks to less than half a year. Against this background, we set out to investigate the effects on prolonged abstinence in n = 27 abstinent former methamphetamine users in a cross-sectional design using behavioral and neurophysiological measures of cognitive control.

Our behavioral results suggest that former users struggled to identify and adapt to different degrees of cognitive control requirements, which made their behavioral performance less expedient than that of healthy controls. On the neurophysiological level, this was reflected by reduced modulations of the N2-N450 amplitude in response to high vs. low cognitive control requirements. Yet, those effects could only be observed in methamphetamine users who had been abstinent for a relatively short time (mean 9.9; max. 18 months), but not in former users who had been abstinent two years or longer.

While this finding alone does not allow for causal inferences, it suggests that the amelioration of control deficits may take longer than what is commonly investigated (1–6 months). Hence, some of the statements about permanent/irreversible dopamine-dependent executive dysfunctions in former methamphetamine users should be interpreted with caution.

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