Preliminary research in healthy men suggests that the drug modafinil (used to treat attention-deficit/hyperactivity disorder and narcolepsy) affects the activity of dopamine in the brain in a way that may create the potential for abuse and dependence.
The wake-promoting drug may enhance cognition and is used for the treatment of cognitive dysfunction in some psychiatric disorders such as schizophrenia and ADHD. The Physicians’ Desk Reference warns that it can produce psychoactive and euphoric effects typical of drugs that stimulate the central nervous system.
It is not completely understood how modafinil works, but it was previously believed that it acted differently from similar stimulant drugs (such as amphetamine) that increase dopamine in the brain, which can lead to abuse and dependence. However, there is growing evidence that dopamine does indeed play a role in the action of modafinil.
Nora D. Volkow of the National Institute on Alcohol Abuse and Alcoholism and colleagues tested whether modafinil (at therapeutic doses) would elevate extracellular dopamine in the brain by blocking the dopamine transporter. The study included ten healthy men between ages 23-46 who received either placebo or modafinil at 200 mg (the dose used to treat narcolepsy) or 400 mg (a dose used to treat ADHD). The researchers measured the effects of modafinil on extracellular dopamine and dopamine transporters using positron emission tomography (a radiographic technique used to examine biochemical activity in tissue).
The researchers found that modafinil “acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential for abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that risk for addiction in vulnerable persons merits heightened awareness."
They also found that modafinil increased dopamine in the nucleus accumbens, a brain region critical for the rewarding effects of abused substances.