Literature describes conflicting effects of opiate antagonists on many stress responses-gastric ulceration, adrenergic sensitivity, and suppression of different immune responses. Many of the side effects noted with naltrexone treatment-anxiety, insomnia, feelings of unreality-are consistent with increased adrenergic sensitivity. The investigators propose to determine the effects of the standard clinical dose of naltrexone, administered over a 21 day period to healthy volunteers, on adrenergic sensitivity, as assessed by the neuroendocrine, physiological and behavioral response to challenge with the alpha-2 antagonist, yohimbine. Healthy subjects will be randomized into a double-blind, placebo-controlled crossover with placebo or active naltrexone (5Omg po daily) for 3 weeks, followed by the converse condition, with active and placebo yohimbine challenges after each naltrexone phase. In a collateral study, blood samples from these healthy subjects will be collected and analyzed in a Flourescence Activated Cell Sorter to determine if the numbers of CD4 and NK cells are altered by active naltrexone maintenance; other proliferative and cytolytic capacities will be evaluated in pilot studies. Another study will compare adrenergic sensitivity at different naltrexone doses. Healthy subjects will be assigned in a random sequence in a 2X3 design to 6 challenges involving pre-treatment with either naltrexone placebo, 25mg, or 150mg, followed by challenges with active or placebo yohimbine. Understanding naltrexone's adrenergic effects has important implications for naltrexone dosing, management of naltrexone side effects, and naltrexone's effects in patients sensitive to noradrenergic effects.
