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Drug addiction is a chronic, relapsing brain disorder. The identification of biomarkers that render individuals vulnerable for the transition from occasional drug use to addiction is of key importance to develop early intervention strategies. The aim of the present study was to prospectively assess brain structural markers for escalating drug use in two independent samples of occasional amphetamine-type stimulant users. At baseline occasional users of amphetamine and 3,4-methylenedioxymethamphetamine (cumulative lifetime use ≤10 units) underwent structural brain imaging and were followed up at 12 months and 24 months (Study 1, n = 38; Study 2, n = 28). Structural vulnerability markers for escalating amphetamine-type drug use were examined by comparing baseline grey matter volumes of participants who increased use with those who maintained or reduced use during the follow-up period. Participants in both samples who subsequently increased amphetamine-type drugs use displayed smaller medial prefrontal cortex volumes and, additionally, in the basolateral amygdala (Study 1) and dorsal striatum (Study 2). In both samples the baseline volumes were significantly negatively correlated with stimulant use during the subsequent 12 and 24 months. Additional multiple regression analyses on the pooled data sets revealed some evidence of a compound-specific association between the baseline volume of the left basolateral amygdala and the subsequent use of amphetamine. These findings indicate that smaller brain volumes in fronto-striato-limbic regions implicated in impulsivity and decision-making might render an individual vulnerable for the transition from occasional to escalating amphetamine-type stimulant use.

Aims It is still unclear if cognitive abnormalities in human 3,4‐methylenedioxymeth‐amphetamine (MDMA) users existed before the beginning of use or if other confounders could explain the deficits. The present study was conducted in order to assess the relationship between beginning MDMA use and subsequent cognitive performance and to overcome previous methodological shortcomings. Design A prospective cohort study in new MDMA users between 2006 and 2009 with a follow‐up duration of 12 months. Setting and Participants Of the 149 almost MDMA‐naive subjects examined at the initial assessment, 109 subjects participated again after 1 year. During this period, 43 subjects did not use any other illicit substance apart from cannabis; 23 subjects used more than 10 pills MDMA (mean = 33.6). These groups then were compared by means of multivariate analyses of variance. Measurements Change scores between the initial examination and follow‐up on a neuropsychological test battery including measures of learning, memory, and frontal executive functions [Auditiv‐Verbaler Lerntest (AVLT), Lern‐ und Gedächtnistest (LGT) 3, digit span test, digit symbol test, Stroop task, Trail‐making test]. In addition, a comprehensive number of possibly relevant confounders including age, general intelligence, cannabis use, alcohol use, cigarette use, medical treatment, participation in sports, nutrition, sleep patterns and subjective wellbeing was assessed. Findings Groups did not differ in any of the potential confounders. However, significant effects of immediate and delayed recall of a visual paired associates learning task between MDMA users and controls were found (respectively, F (1,64) = 11.43, P = 0.001, η2 = 0.136 and F (1,64) = 11.08, P = 0.002, η2 = 0.144). No significant differences on the other neuropsychological tests were found. Conclusions MDMA appears to impair visual paired associates learning in new users, suggesting serotonergic dysfunction in hippocampal regions as a consequence of MDMA use.

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