title: Dopamine D3 receptors as a therapeutic target for methamphetamine dependence.
abstract: BACKGROUND
  Methamphetamine (MA) use disorders are major public health problems nationally and worldwide and treatment remains an unmet need.
  
  
  OBJECTIVE
  (1) To review preclinical and clinical studies identifying the dopamine D3 receptor as a therapeutic target for substance use disorders (SUDs), including MA dependence, (2) to consider buspirone (Buspar®) as a potential medication based on its dopamine D3 receptor antagonist properties, and (3) to evaluate the safety and initial efficacy of buspirone in a pilot study of MA-dependent individuals.
  
  
  METHODS
  Literature on the dopamine D3 receptor as a therapeutic target and on the potential of buspirone as a novel therapy for MA dependence was reviewed. The cardiovascular and subjective effects of intravenous MA challenge were assessed in five non-treatment seeking individuals. Participants met DSM-IV criteria for MA dependence and were treated subacutely (9 days) with buspirone (60 mg daily).
  
  
  RESULTS
  The literature identified the dopamine D3 receptor as a therapeutic target for MA dependence, a safe and approved medication, and a valuable opportunity to re-purpose buspirone for treating MA dependence and perhaps other SUDs. Pilot data (n = 5) indicated that buspirone is safe in MA-using individuals and comparison against historical placebo data from this laboratory suggested that at least some aspects of the subjective properties of MA may be diminished during buspirone treatment.
  
  
  CONCLUSIONS
  Future studies should include a small-scale, placebo-controlled Phase IIa trial of buspirone in MA dependence.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California , Los Angeles, CA , USA .
authors.forename: Neil E
authors.initials: NE
authors.lastname: Paterson
authors.forename: Frank
authors.initials: F
authors.lastname: Vocci
authors.forename: Rajkumar J
authors.initials: RJ
authors.lastname: Sevak
authors.forename: Eric
authors.initials: E
authors.lastname: Wagreich
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy*; D002065:Buspirone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002319:Cardiovascular System / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D057170:Translational Research, Biomedical
chemical_list: D018492:Dopamine Antagonists; D050637:Receptors, Dopamine D3; D002065:Buspirone