NALTREXONE EFFECTS ON DIAZEPAM INTOXICATION AND PHARMACOKINETICS IN HUMANS

The opiate antagonist naltrexone (NTX) blocks relapse drinking in alco holics and modifies some of the subjective effects of alcohol intoxica tion, Benzodiazepines have demonstrated cross-dependence and cross-tol erance to alcohol. Furthermore, benzodiazepine intoxication has effect s on mood and psychomotor performance that are similar to alcohol into xication. The effects of NTX on diazepam intoxication were investigate d in non-drug abusing individuals. Eighteen men and eight women were r andomly assigned to receive either 50 mg NTX or placebo PO, on two dif ferent occasions in a within-subjects: crossover, double-blind protoco l. Diazepam was taken by mouth, 90 min after NTX. At -90, 45, 75, 135, 210 min, subjects were tested with repeated assessments of several mo od and sensation scales and a computer-generated psychomotor test batt ery (CTB). Blood samples were also obtained and analyzed for serum dia zepam levels. Diazepam induced several sensations and mood effects sim ilar to those induced by alcohol. Negative mood states such as sedatio n, fatigue, and anxiety were higher for NTX than for placebo. Positive mood states such as friendliness, vigor, liking the effects of diazep am? and feeling high from diazepam were all lower for NTX than for pla cebo. There were no group differences on the CTB performance. NTX dela yed the time to reach peak diazepam levels, so that peak levels occurr ed at 75 min for placebo compared to 135 min for NTX. A sub-analysis w as conducted with 14 subjects who were FHP for alcoholism, but no diff erences were found on these outcome measures.