title: Clonidine blocks stress-induced craving in cocaine users.
abstract: BACKGROUND
  Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement.
  
  
  OBJECTIVE
  The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users.
  
  
  METHODS
  Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected.
  
  
  RESULTS
  Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant.
  
  
  CONCLUSIONS
  Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.
authors.affiliation: Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, 251 Bayview Blvd., Suite 200, Baltimore, MD 21224, USA. jobesm@nida.nih.gov
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Jobes
authors.forename: Udi E
authors.initials: UE
authors.lastname: Ghitza
authors.forename: David H
authors.initials: DH
authors.lastname: Epstein
authors.forename: Karran A
authors.initials: KA
authors.lastname: Phillips
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Heishman
authors.forename: Kenzie L
authors.initials: KL
authors.lastname: Preston
mesh_terms: D000284:Administration, Oral; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology / Q000534:rehabilitation*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D013315:Stress, Psychological / Q000150:complications*; D055815:Young Adult
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003000:Clonidine