The acute effects of modafinil on extracellular dopamine and on dopamine transporters in the male human brain were measured by PET study in 10 healthy subjects at Brookhaven National Laboratory and National Institute on Drug Abuse, Bethesda, MD. Modafinil decreased mean [11C]raclopride binding potential in caudate, putamen, and nucleus accumbens, reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in these sites, reflecting blocked dopamine transporters. The changes in dopamine brain levels with modafinil were similar to those reported with methylphenidate. Modafinil in the therapeutic doses (200mg and 400mg) used in this study significantly increased heart rate and systolic blood pressure. Drugs that increase dopamine in the nucleus accumbens have the potential for abuse. The results of this study indicate the need for a heightened awareness for potential abuse and dependency on modafinil in patients who may be vulnerable. [1]

COMMENT. The mechanism of action of modafinil as a wake-promoting agent and cognitive enhancer in patients with narcolepsy and ADHD was believed to differ from that of the stimulants, methylphenidate and amphetamine. Whereas the stimulants are known to increase dopamine and norepinephrine in brain, modafinil was theorized to affect epinephrine, g-aminobutyric acid, and glutamate. The above study is evidence of a dopamine mechanism of modafinil, similar to that of CNS stimulants. The authors advise caution in the use of modafinil in patients with a history of drug abuse or other vulnerable populations. In the treatment of ADHD during childhood and adolescence, researchers find little evidence of abuse or overuse of stimulant medication. [2]