111,116-122 However, it is not clear whether these deficits are a consequence of the use of stimulants or whether they reflect pre-existing low cognitive abilities in people who become drug users later in life. Nevertheless, reduced DAT densities and longer duration of METH use were associated with poorer performance in both Inhibitors,research,lifescience,medical fine motor and memory tasks in 15 currently abstinent METH users.106 Also, the normalization

of rMRGlu in the thalamus was associated with an improvement of motor and memory performance after long-term abstinence of 1 year and more.109 Finally, reduced attentional control (ie, increased Stroop interference) was shown to correlate with levels of NAA-Cr within the anterior cingulate in METH users, Inhibitors,research,lifescience,medical but not in controls.111 In conclusion, the limited evidence to date suggests that persisting neurotoxic brain damage is conceivable in METH users, PCI-32765 especially in heavy users with binge use patterns. More studies with longitudinal and prospective designs are clearly needed. Conclusions Ecstasy (MDMA) and stimulant amphetamines (METH and AMPPI) are Inhibitors,research,lifescience,medical popular drugs of abuse and they are neurotoxic in animal studies. High and repeated doses of MDMA cause selective and long-lasting degeneration of 5-HT axon terminals in several brain regions, whereas

METH and AMPH damage both serotonergic and dopaminergic neurons. Although the doses taken recreationally are considerably lower than the doses typically given in animal studies, some users exhibit compulsive binge use behaviors that may well correspond Inhibitors,research,lifescience,medical to the animal doses. In addition, polydrug use and the typical environment of use (hot, overcrowded, and noisy rooms, extensive physical exercise in the form of dancing) may well Inhibitors,research,lifescience,medical potentiate the neurotoxic effects of the drugs. Studies with drug users demonstrated associations of subtle alterations in brain structure and 5-HT brain parameters

with MDMA use, Similarly, subtle cognitive dysfunctions, particularly in the memory and learning domain, were also found to be associated with ecstasy use, Although the results are not entirely consistent, these associations were replicated aminophylline in many welldesigned, controlled studies including longitudinal and one prospective investigation. Moreover, the only prospective study to date demonstrated structural brain alterations and subtle memory dysfunction, even after minimal exposure to MDMA.59,103 Although most ecstasy users do not suffer cognitive impairment of clinically relevant proportions, and even heavy users initially appear mostly unimpaired in their everyday life, several cases with severe deficits have also been reported.