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The authors critically review key findings from the neuropsychological literature related to the long-term sequelae of alcohol, cannabis, inhalant, opiates, psychostimulants and ecstasy use. Leading electronic databases such as PubMed were searched to identify relevant studies published in the past 20 years. References identified from bibliographies of pertinent articles and books in the field were also collected and selectively reviewed. Across substances, individuals with long-term abuse consistently demonstrate neuropsychological impairments of executive (inhibitory) control, working memory and decision making, together with neurobiological abnormalities involving frontotemporal and basal ganglia circuits. In some instances these deficits are dose dependent, implying that they are a direct consequence of prolonged drug exposure. However, comorbid behavioural, personality and mental health problems are common among drug-using populations and are associated with similar neuropsychological deficits. 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