title: Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals.
abstract: BACKGROUND
  In laboratory animals, the biological stressor yohimbine (α(2)-noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory studies have demonstrated that psychological stressors can increase drug craving but not that stressors alter drug seeking.
  
  
  OBJECTIVE
  This clinical study tested whether yohimbine increases opioid-seeking behavior.
  
  
  METHODS
  Ten heroin-dependent, buprenorphine-stabilized (8 mg/day) volunteers sampled two doses of hydromorphone [12 and 24 mg IM in counterbalanced order, labeled drug A (session 1) and drug B (session 2)]. During each of six later sessions (within-subject, double-blind, randomized crossover design), volunteers could respond on a 12-trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled hydromorphone dose (drug A or B) vs money ($2) following different oral yohimbine pretreatment doses (0, 16.2, and 32.4 mg).
  
  
  RESULTS
  Behavioral economic demand intensity and peak responding (O (max)) were significantly higher for hydromorphone 2 than 1 mg. Relative to placebo, yohimbine significantly increased hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (P (max) = 909, 3,647, and 3,225 for placebo, 16.2, and 32.4 mg yohimbine doses, respectively) than hydromorphone 2-mg units (P (max) = 2,656, 3,193, and 3,615, respectively). Yohimbine produced significant but clinically modest dose-dependent increases in blood pressure (systolic ≈ 15 and diastolic ≈ 10 mmHg) and opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated mood.
  
  
  CONCLUSIONS
  These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose.
authors.affiliation: Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2761 East Jefferson Ave., Detroit, MI 48207, USA. mgreen@med.wayne.edu
authors.forename: Mark K
authors.initials: MK
authors.lastname: Greenwald
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Lundahl
authors.forename: Caren L
authors.initials: CL
authors.lastname: Steinmiller
mesh_terms: D000328:Adult; D016739:Behavior, Addictive / Q000139:chemically induced* / Q000523:psychology; D002047:Buprenorphine / Q000627:therapeutic use*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006556:Heroin Dependence / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D015016:Yohimbine / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D009292:Narcotic Antagonists; D015016:Yohimbine; D002047:Buprenorphine