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

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 crossover to placebo or active naltrexone (50 mg po 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 (IV, 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.