A laboratory study found that modafinil increases levels of dopamine in the human brain, including in an area of the brain associated with potential for abuse.

Modafinil is used for treatment of narcolepsy and was originally thought to have a low abuse potential; its apparent effects on wakefulness and cognition are resulting in increasing non-licensed use and diversion as a cognition enhancer in healthy individuals. It was initially not thought to act via dopaminergic systems, however experimental studies suggest that it does cause significant alterations in brain dopamine levels. This is of concern as drugs that increase dopamine levels in the brain, particularly in the nucleus accumbens, have a potential for abuse.

This placebo-controlled study in ten healthy volunteers aimed to determine whether modafinil blocked the dopamine transporter in the brain and thus increased extracellular dopamine levels. Dopamine levels and transporter activity in the presence of modafinil were assessed using positron emission tomography with [11C]raclopride (a D2 / D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand). Modafinil doses reflected those used in clinical practice. Primary outcomes were changes in dopamine D2 / D3 receptor and dopamine transporter availability after modafinil compared with after placebo.

The results showed that in the presence of modafinil, dopamine binding potential was reduced when compared to placebo in various brain regions, reflecting increased extracellular dopamine; this included the nucleus accumbens where the reduction in binding potential was 19.4% (SD, 20%; 95% CI, 5% to 35%; P = 0.02). [11C]cocaine binding potential was also decreased in the presence of modafinil, indicating increased occupancy of dopamine receptors.

Based on their results, the authors conclude that at clinically relevant doses modafinil blocks dopamine transporters and increases dopamine levels in the human brain, including in the nucleus accumbens. This provides increasing support for the role of dopamine in modafinil’s actions. Because drugs that increase dopamine in the brain have a potential for abuse, there is a need for increased awareness of the possibility for abuse of and dependence on modafinil in vulnerable people.