The effects of naltrexone maintenance on the response to yohimbine in healthy volunteers

Biol Psychiatry. 1999 Jun 15;45(12):1636-45. doi: 10.1016/s0006-3223(98)00259-5.


Background: Preclinical research suggests that opiate antagonists may alter stress responsiveness. This study describes the effect of pretreatment with the opioid antagonist naltrexone on the response to a noradrenergic stressor, the alpha-2-receptor-antagonist, yohimbine, in healthy subjects. The current study was designed to compare the change in responses to yohimbine after 2 weeks of treatment with naltrexone to the response after at least 2 weeks of treatment with placebo.

Methods: After a week of placebo naltrexone treatment, ten subjects were randomized into a double-blind cross-over to placebo or active naltrexone (50 mg p.o. daily) on weeks 2 to 4, and the converse condition for weeks 5 to 7. Subjects received challenges in a random, fixed sequence with placebo and active yohimbine (i.v., 0.2 mg/kg) on weeks 1, 4, and 7. The active-active combination generally had the strongest drug effects.

Results: There were statistically significant (p < .05) interactions of naltrexone condition X yohimbine condition for subject ratings of "nervous," "not liking the drug effect," "talkative," and "urge to urinate," and a trend (p < .10) for cortisol levels.

Conclusions: The results suggest that clinically used naltrexone doses alter sensitivity to yohimbine.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aphrodisiacs / metabolism*
  • Double-Blind Method
  • Drug Hypersensitivity / diagnosis
  • Female
  • Health Status
  • Humans
  • Hydrocortisone / blood
  • Injections, Intravenous
  • Male
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Sexual Behavior / drug effects
  • Time Factors
  • Yohimbine / metabolism*


  • Aphrodisiacs
  • Narcotic Antagonists
  • Yohimbine
  • Naltrexone
  • Hydrocortisone