Most substance abusers simultaneously use and abuse more than one substance, even when there is a clear drug of choice. This pattern creates a great challenge in relating neuropsychological findings in drug users to a certain drug. This review aims to: (i) discuss results from neuropsychological studies using different research methodologies that may improve our understanding of specific vs. generalized effects of different drugs on neuropsychological performance; and (ii) determine which neuropsychological mechanisms are impaired in the same way by the use of different drugs, and which impairments are specific to certain substances, including cannabis, psychostimulants, opioids and alcohol. We review evidence from human studies in chronic substance abusers using three methodologies: (i) studies on 'pure' users of one particular substance, (ii) studies that methodologically control the effects of drugs co-abused, and (iii) studies contrasting subgroups of polysubstance users with different drugs of choice. Converging evidence from these approaches indicates that all the drugs studied are commonly associated with significant alterations in the neuropsychological domains of episodic memory, emotional processing, and the executive components of updating and decision-making. However, there is evidence of a greater reliability in the association of certain substances with specific neuropsychological domains. Specifically, there are relatively more robust effects of psychostimulants and alcohol use on impulsive action and cognitive flexibility, of alcohol and MDMA use on spatial processing, perceptual speed and selective attention, cannabis and methamphetamine on prospective memory deficits, and cannabis and MDMA on processing speed and complex planning. The magnitude of both generalized and specific neuropsychological effects is overall attenuated in samples achieving long-term abstinence, but there are persistent psychostimulant-related effects on updating, inhibition, flexibility and emotional processing, and opioid-related effects on updating and decision-making.
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