The Persistent Challenge of Developing Addiction Pharmacotherapies

Cold Spring Harb Perspect Med. 2021 Nov 1;11(11):a040311. doi: 10.1101/cshperspect.a040311.


There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the development of eight compounds used in the treatment of drug addiction with an emphasis on pharmacological mechanisms and the utility of preclinical animal models of addiction in therapeutic development. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant use disorder, none of which have proven to be clinically effective. A specific example of an apparently promising pharmacotherapeutic for cocaine that failed clinically will be examined to determine whether this truly represents a challenge to the predictive validity of current models of cocaine addiction. In addition, the development of promising cocaine use disorder therapeutics derived from animal research will be reviewed, with some discussion regarding how preclinical studies might be modified to better inform clinical outcomes.

MeSH terms

  • Acamprosate / therapeutic use
  • Alcohol Deterrents / therapeutic use
  • Alcoholism / drug therapy
  • Bupropion / therapeutic use
  • Central Nervous System Stimulants
  • Cocaine-Related Disorders / drug therapy
  • Drug Therapy*
  • Humans
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / therapeutic use
  • Nicotinic Agonists / therapeutic use
  • Smoking Cessation Agents
  • Substance-Related Disorders / drug therapy*
  • Varenicline / therapeutic use


  • Alcohol Deterrents
  • Central Nervous System Stimulants
  • Narcotic Antagonists
  • Nicotinic Agonists
  • Smoking Cessation Agents
  • Bupropion
  • Naltrexone
  • Acamprosate
  • Varenicline