Drugs that are addictive tend to exert a strong influence on the pleasure-creating neurotransmitter dopamine, particularly in a region of the brain called the nucleus accumbens. Other stimulant medications, such as Ritalin or Adderall, work directly by increasing dopamine in the brain, but since Modafinil didn't seem to work via dopamine, it was touted in some circles as a new and non-addictive stimulant medication.

Could Modafinil Really Be a Non-Addictive Stimulant?

Nora D. Volkow of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and her team at Brookhaven National Laboratory decided to take a closer look at the increasingly used “smart” drug's path of action.

They ran a study with 10 adult male subjects. Some of the subjects were given a placebo and the others were administered either 200 mg or 400 mg doses (typical therapeutic doses) of Modafinil. The researchers then ran PET scans on all subjects, comparing the levels of extracellular dopamine between them.

The researchers found that Modafinil caused an increase in dopamine levels in extracellular space, increasing dopamine levels by blocking the transporters that would normally remove and clean up this extracellular dopamine. Significantly, extracellular dopamine levels increased in all areas of the brain, including the nucleus accumbens.

Since the dopamine transporters remove and recycle released dopamine from the spaces between brain cells, blocking the activity of these transporters causes released dopamine to stick around longer between the cells, resulting in an increase in overall levels of dopamine. Both cocaine and methamphetamine also work in part by blocking dopamine transporters, but these drugs also increase the amount of dopamine released – greatly increasing dopamine levels and thus addictiveness.

Study Leaders Warn Against Off-Label Use

The study authors acknowledge the increase in illicit use of Modafinil, writing, "Modafinil is increasingly being diverted for nonmedical use by healthy individuals with the expectation that it will improve cognitive performance." But they caution, "This drug is not safe to use the way people are using it."

Dr. Volkow concludes that although Modafinil was initially developed as a non-dopaminergic stimulant, it relies at least partially on increased levels of dopamine for its effects. Since drugs that cause increased dopamine levels in the nucleus accumbens have abuse potential, she warns that, "These results suggest that risk for addiction in vulnerable persons merits heightened awareness."