Acute tolerance to cocaine in humans

It has been shown that there is a dose-response relationship between blood levels of intravenously injected cocaine and magnitude of evoked heat rate (Javaid et al. 1978). This relationship also holds for inhaled cocaine while plasma levels are increasing, but the cardiovascular effects of the drug dissipate more rapidly than cocaine disappears from the plasma. This suggests that the repeated administration or sustained blood level of cocaine might produce an acute tolerance. Using an intranasal route of administration it is possible to maintain cocaine blood levels for a substantial period of time after heart rate begins to decrease from its peak levels. If an intravenous dose is then administered on top of this preexisting blood level, the effects of this second dose can be compared to the same dose administered to subjects with no preexisting blood level.