Modafinil: a useful medication for cocaine addiction? Review of the evidence from neuropharmacological, experimental and clinical studies

Curr Drug Abuse Rev. 2008 Jun;1(2):213-21. doi: 10.2174/1874473710801020213.


Cocaine addiction is a chronic relapsing disorder associated with severe medical and psychosocial complications. However, there are no approved medications for cocaine dependent individuals. Modafinil, a medication that differs chemically and pharmacologically from other central nervous system stimulants, has been suggested to be potentially useful for this complex disorder. The present paper aims to critically review the published evidence from laboratory and clinical studies on modafinil for cocaine addiction, including discussion of its pharmacological characteristics and how it may relate with cocaine neurobiology. Whilst its exact mechanism of action remains to be elucidated, different neurotransmitter systems have been implicated, including modulation on dopamine, glutamate/GABA, noradrenaline and the hypocretin/orexin system, but it is possible that modafinil acts by a synergistic combination of mechanisms. With a favourable pharmacokinetic profile, it appears to have a low abuse potential. Laboratory and clinical studies provide consistent, albeit preliminary, evidence of the potential usefulness of modafinil for cocaine dependent patients. Not only there is no evidence of pharmacokinetic interactions between modafinil and cocaine, but in addition cocaine induced euphoria and cardiovascular effects appear to be attenuated by modafinil. Furthermore, modafinil has been shown to decrease cocaine self-administration. In addition, modafinil treated patient are more likely to achieve protracted abstinence than placebo treated patients. However, further research is needed to confirm these findings.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / pharmacokinetics
  • Benzhydryl Compounds / therapeutic use*
  • Brain / drug effects*
  • Brain / physiopathology
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / pharmacokinetics
  • Central Nervous System Stimulants / therapeutic use*
  • Cocaine / adverse effects
  • Cocaine / pharmacokinetics
  • Cocaine-Related Disorders / physiopathology
  • Cocaine-Related Disorders / rehabilitation*
  • Cognitive Behavioral Therapy
  • Combined Modality Therapy
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / physiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enzyme Induction / drug effects
  • Enzyme Induction / physiology
  • Humans
  • Metabolic Clearance Rate
  • Modafinil
  • Motivation
  • Neurotransmitter Agents / physiology*
  • Randomized Controlled Trials as Topic
  • Substance Withdrawal Syndrome / physiopathology
  • Substance Withdrawal Syndrome / rehabilitation
  • Treatment Outcome


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Neurotransmitter Agents
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Cocaine
  • Modafinil