Agonist-like pharmacotherapy for stimulant dependence: preclinical, human laboratory, and clinical studies

Ann N Y Acad Sci. 2010 Feb;1187:76-100. doi: 10.1111/j.1749-6632.2009.05145.x.


A variety of natural and synthetic agents have long been used for stimulant properties, with nontherapeutic use producing multiple waves of stimulant abuse and dependence. The multitude of effects of stimulants exist on continua, and accordingly, here we characterize stimulant abuse/dependence and candidate pharmacotherapies in this manner. Behavioral therapy and medications have been investigated for treatment of stimulant abuse/dependence. Effectiveness of some behavioral interventions has been demonstrated. Most medications studied have been found to lack efficacy. However, an expanding literature supports use of agonist-like medications to treat stimulant abuse/dependence, a strategy effective for nicotine and opiate dependence. The agonist-like conceptualization for stimulant dependence posits that medications with properties similar to that of the abused drug, but possessing lesser abuse liability, will normalize neurochemistry and stabilize behavior, thus reducing drug use. Data suggest use of a range of medications, from l-dopa/carbidopa to amphetamine preparations, depending on the severity of use. This report reviews preclinical, human laboratory, and clinical trial data supporting the agonist-like approach, including risks and benefits. Future directions for development of agonist-like medications are also discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Behavior Therapy
  • Benzhydryl Compounds / therapeutic use
  • Bupropion / therapeutic use
  • Central Nervous System Stimulants / therapeutic use*
  • Central Nervous System Stimulants / toxicity*
  • Clinical Trials as Topic
  • Cognition / drug effects
  • Dextroamphetamine / therapeutic use
  • Humans
  • Levodopa / therapeutic use
  • Methylphenidate / therapeutic use
  • Modafinil
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / psychology
  • Substance-Related Disorders / therapy


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Bupropion
  • Methylphenidate
  • Levodopa
  • Modafinil
  • Dextroamphetamine