Sensitization to the cardiovascular but not subject-rated effects of oral cocaine in humans

Background: Despite a substantial nonhuman literature in the area, few studies have experimentally evaluated the effects of repeated stimulant administration in human participants. This study examined the effects of repeated cocaine in individuals with histories of abuse and dependence. Methods: Twenty-two individuals with recent histories of cocaine abuse received under double-blind conditions, in pseudorandom order, four administrations of oral cocaine (150 mg [n = 14] or 200 mg [n = 8]) and two administrations of placebo. All administrations were given on separate days. Cardiovascular measures were collected and included heart rate, systolic pressure, diastolic pressure, mean arterial pressure, and pressure rate product. Subject-rated effects were assessed using the Addiction Research Center Inventory (ARCI) and a 15-item drug-effect questionnaire. Results: There were significant differences between placebo days and cocaine days in both cardiovascular and subject-rated effects. Moreover, three of five cardiovascular measures analyzed revealed a significant main effect for day of cocaine administration. A planned follow-up contrast revealed a significant increasing linear trend for each of these variables across days. No significant effects were found for day of administration for the subject-rated items. Conclusions: These results indicate that, under controlled laboratory conditions, repeated oral cocaine administration may result in sensitization to the cardiovascular effects, but not subject-rated effects.