The effects of methylphenidate (MPH), a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers was studied using PET scans and measurements of D2 receptors at the Brookhaven National Laboratory, the State University of New York at Stony Brook, and New York University, NY. MPH increased metabolism in the superior cingulate, right thalamus, and cerebellum. MPH-induced changes in the right striatum and orbitofrontal cortex were associated with cocaine craving, and those in the prefrontal cortex were associated with mood. Compulsive drug abuse in addicted persons may be related to activation of the right striatum and orbitofrontal cortex, areas known to be abnormal in compulsive disorders. The predominant correlation of craving with right but not left brain regions warrants further investigation of laterality of drug responses. [1]

COMMENT. In normal subjects, these authors have reported variable cerebral metabolic responses to MPH; some showing increased metabolism, some decreases, and some no change. Metabolic responses were correlated with measures of dopamine D2 receptors. Similarly, in cocaine abusers, metabolic responses were correlated with dopamine receptors; those with higher D2 levels had increased metabolism, and those with lower D2 measures had decreased metabolism. MPH, like cocaine, binds to the dopamine transporter, but their effects on metabolism are not identical. The cocaine craving induced by MPH in cocaine abusers is not associated with an MPH addiction. In fact, if substance abuse becomes a problem in adolescence, it is independent of ADHD and does not involve addiction to MPH [2, 3]

The right striato-orbitofrontal regions are thought to be involved in the neuroanatomic and biochemical basis for ADHD. A deficiency in brain dopamine and norepinephrine may explain a loss of inhibition and excessive activity levels in children with ADHD. MPH, by increasing dopamine activity in the right frontal lobe, may normalize motor activity while preserving and heightening the degree of alertness.