Rat studies have indicated that high doses of amphetamines in adolescence produced significant declines in working memory as adults, and that amphetamines and cocaine can damage the brain’s ability to learn from new experiences. A human twin study also found long-term cocaine or amphetamine abuse affected attention and motor skills. Another human study suggests that cocaine use particularly affects prospective memory — which of course is heavily dependent on executive function.
One important mechanism for these effects involves the neurotransmitter dopamine. Methamphetamine abuse damages neurons that respond to dopamine. And a small imaging study found that people with different variants of the COMT gene (which affects dopamine responsiveness) were differently affected by amphetamine in regards to their performance on tasks involving working memory and executive functioning (this may explain why some people respond better to ADHD drugs).
Prenatal exposure to methamphetamine or cocaine has been found to produce structural abnormalities in the brain. For cocaine, the damage seems to lie mainly in regions regulating attention and memory. Mental retardation, according to one study, is dramatically (nearly five times) higher in cocaine-exposed children. Nevertheless, a review of 32 major studies of school-age children concludes that, with the exception of attention problems, the low IQ and poor academic and language achievement often found in those whose mothers used cocaine during pregnancy is more related to home environment than to the drug exposure.
Among those exposed to methamphetamine, the damage appears to be primarily to the striatum (significantly smaller) and the limbic system (significantly bigger). The striatum is involved in skill learning and habit formation, and motor coordination is likely to be affected.