Thomas Thorne
ABSTRACT
Preliminary research in healthy men suggests that the narcolepsy drug modafinil, increasingly used to improve cognitive abilities, affects dopamine activity in the brain in a way that may create potential for abuse and dependence, according to a study published in the journal. March 18 edition. from JAMA.
Modafinil, a wakefulness-promoting drug used in the treatment of sleep disorders, may improve cognition and is used off-label for the treatment of cognitive dysfunction in some psychiatric disorders (i.e., schizophrenia, due to attention deficit hyperactivity disorder [ADHD]). Physicians' Desk Reference warns that it can produce psychoactive and euphoric effects typical of central nervous system stimulant drugs, and there is debate over its potential for abuse, according to background information in the article. Modafinil's mechanisms of action are not well understood, but are thought to differ from those of stimulant medications (such as methylphenidate and amphetamine), which increase dopamine (a neurotransmitter in the brain essential for normal functioning of the central nervous system). ) in the brain by targeting dopamine transporters, a mechanism underlying the abuse potential of these drugs. However, there is increasing evidence that dopamine may also play a role in modafinil's mode of action.
Nora D.Volkow, M.D., of the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., and colleagues at Brookhaven National Laboratory conducted a study to test whether modafinil, at therapeutic doses, would raise the extracellular level (located or occurring outside of the cells). ) dopamine in the brain by blocking the dopamine transporter. The study included 10 healthy men, ages 23 to 46, who received either placebo or modafinil: 200 mg, the recommended dose for narcolepsy; or 400 mg, a dose that has been shown to be beneficial for the treatment of ADHD. The effects of modafinil on extracellular dopamine and on dopamine transporters were measured using positron emission tomography (a radiographic technique used to examine biochemical activity in the tissue).
The researchers found: “In this pilot study, modafinil acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential to lead to abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that the risk of addiction in vulnerable people deserves greater awareness.”
Modafinil also increased dopamine in the nucleus accumbens, a brain region critical for the rewarding effects of drugs of abuse.
“Modafinil was developed with the expectation that a medication could have a non-dopaminergic target for its arousal-promoting effects. However, current findings in humans, along with preclinical studies documenting the indispensable role of dopamine in the wake-promoting effects of modafinil, support the dopamine-enhancing effects of modafinil as a mechanism for its therapeutic actions.”