Cocaine tolerance: behavioral, cardiovascular, and neuroendocrine function in men.

Cocaine tolerance was assessed by comparing the acute effects of cocaine in drug-abstinent men who reported occasional cocaine use (n = 6) and in men who met DSM-III-R diagnostic criteria for dependence on both cocaine and opiates (n = 6). Peak plasma cocaine levels were equivalent in the two groups, and pharmacokinetic analyses revealed no significant differences in cocaine levels at any time. Cocaine induced a significantly greater increase in ACTH in the occasional cocaine users than in the cocaine dependent men (p < .01). Heart rate and systolic and diastolic blood pressure increases after cocaine were also significantly greater in the occasional cocaine users than in the cocaine-dependent men (p < .05). These neuroendocrine and physiologic differences were paralleled by significantly greater subjective reports of "high" and "euphoria" by the occasional cocaine users (p < .03 to .0001). These data are consistent with the conclusion that tolerance to cocaine's physiologic, neuroendocrine, and subjective effects may occur as a function of chronic use.