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 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.
Rosen
M I
MI
Yale University School of Medicine, VA Connecticut Healthcare System, Psychiatry Service, West Haven, CT 06516, USA.
Kosten
T R
TR
Kreek
M J
MJ
D000328:Adult; D001046:Aphrodisiacs / Q000378:metabolism*; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000175:diagnosis; D005260:Female; D006304:Health Status; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D012725:Sexual Behavior / Q000187:drug effects; D013997:Time Factors; D015016:Yohimbine / Q000378:metabolism*
D001046:Aphrodisiacs; D009292:Narcotic Antagonists; D015016:Yohimbine; D009271:Naltrexone; D006854:Hydrocortisone