Clinical uses of naltrexone: a review of the evidence.

The implication of the opioidergic system in the pathogenesis of various substance use disorders has led to renewed interest in expanding the clinical uses of naltrexone, an opioid antagonist. This article examines the evidence for the efficacy of naltrexone in a variety of substance use and psychiatric disorders. Naltrexone can be an effective treatment for alcohol and opioid dependence if issues of compliance are adequately addressed. Thus far, no definitive role has been found for naltrexone in the treatment of other psychiatric disorders. Further research needs to be done in self-injurious behavior, gambling, cocaine, and nicotine dependence.

Adrenocorticotropin and cortisol responses to a naloxone challenge and risk of alcoholism.

BACKGROUND: Because abnormalities in opioid neurotransmission appear to underlie some of the inherited risk for alcoholism, we examined the effects of naloxone, an opioid antagonist, on corticotropin and cortisol responses in nonalcoholic subjects differentiated by paternal history of alcoholism. METHODS: Placebo-controlled, balanced, within-subject design involving 2 test days over a period of 3 to 7 days. Thirty-six subjects (67% male; 53% paternal-history-positive; mean age = 25.0 years) were screened to exclude substance abuse or dependence. Subjects received intravenous naloxone 125 microg/kg or placebo, with sessions in random order. Plasma corticotropin and cortisol were measured for up to 120 min post infusion. RESULTS: Corticotropin responses at baseline and following naloxone did not differ by paternal history of alcoholism; however, paternal-history-positive subjects exhibited greater cortisol concentrations at baseline, and at 15 and 30 min after naloxone administration. Paternal-history-positive subjects also had an earlier and greater peak cortisol response to naloxone and a nonsignificant trend for a greater area under the cortisol time curve than paternal-history-negative subjects. CONCLUSIONS: These findings suggest that individuals with greater vulnerability to alcoholism may have altered Hypothalamic-pituitary axis (HPA) dynamics, a finding that is consistent with a growing body of data on the role of opioidergic neurotransmission in the inherited risk of alcoholism.

Mecamylamine modifies the pharmacokinetics and reinforcing effects of alcohol.

BACKGROUND: Central nicotinic cholinergic receptors modify alcohol-induced mesolimbic dopamine activation, which seems to be important in the reinforcing properties of alcohol. Consistent with this model, acute administration to rats of the tertiary nicotinic receptor antagonist mecamylamine blocks both alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens. This study was conducted to test the hypothesis that, during the ascending limb of the blood alcohol concentration curve, mecamylamine would reduce the stimulating and pleasurable effects of an intoxicating dose of alcohol in humans. METHODS: Ten female and 10 male volunteers with no history of alcohol or substance use disorders, including nicotine dependence, completed the study. During two laboratory sessions, subjects consumed three aliquots of an alcohol-containing drink, with a total ethanol content of 0.7 g/kg (in women) or 0.8 g/kg (in men), over a 30-min period. Two hours before the first drink, subjects were pretreated with mecamylamine or placebo, with the order of sessions counterbalanced. Primary outcome measures included the Drug Effect Questionnaire, the central stimulation subscale of the Alcohol Sensation Scale, and the stimulant subscale of the Biphasic Alcohol Effects Scale. Breath alcohol level (BAL) was examined to identify the ascending and descending limbs of the blood alcohol curve and to assess pharmacokinetic interactions between alcohol and mecamylamine. RESULTS: Significant effects of time, study drug, and their interaction were observed. Compared with placebo, mecamylamine reduced BAL. After controlling for BAL at each time point, mecamylamine also reduced the Drug Effect Questionnaire and Alcohol Sensation Scale stimulant subscale scores, with a trend for a similar effect on the Biphasic Alcohol Effects Scale score. CONCLUSIONS: Mecamylamine seems to modify both the pharmacokinetic profile of alcohol and the rewarding effects of alcohol in healthy volunteers.