Repeated intranasal cocaine administration: lack of tolerance to pressor effects.

Three healthy adult male volunteers were allowed to self-administer 96 mg or 4 mg (a dose without measurable effects) of inhaled cocaine approximately once every 35 min during experimental sessions lasting up to 6 h. Heart rate (HR), blood pressure and self-report of drug effects were measured. After inhaling, on average, four doses of 4 mg, subjects voluntarily ended the session. Five out of the six sessions of 96 mg cocaine availability, however, were terminated due to consistent elevated diastolic blood pressure (DP), rather than by subject request. During 96 mg sessions, HR and self-report data either rapidly reached an asymptote or showed a slow rate of increase. Blood pressure, on the other hand, increased throughout the session, generally to the point where the session had to be terminated. These findings suggest the possibility that the rate of development of tolerance to the effects of cocaine may vary as a function of the dependent variable. In addition, the consistent increase in pressor effects may well be a mechanism for the increased cardiovascular toxicity reported for cocaine abusers.