Acute tolerance development to the cardiovascular and subjective effects of cocaine
Fischman, M.W.; Schuster, C.R.; Javaid, J.; Hatano, Y.; Davis, J.
Journal of Pharmacology and Experimental Therapeutics 235(3): 677-682
1985
ISSN/ISBN: 0022-3565 PMID: 4078729 Document Number: 247317
Eight normal adult volunteer subjects received an intranasal pretreatment of either 4 (placebo) or 96 mg of cocaine. Sixty minutes later 16, 32 or 48 mg of cocaine was injected i.v. Cocaine plasma levels were determined periodically over a 2-hr period and both cardiovascular effects and verbal report of drug effects were monitored for 8 hr daily. The plasma concentrations of cocaine were always related to the dose administered. When i.v. cocaine was given after a 96-mg intranasal pretreatment, the increase in heart rate was not as great as when an i.v. injection followed a 4-mg inhalation. Comparable changes were obtained in subjective effects as measured on the Addiction Research Center Inventory, the Profile of Mood States and a subjective effects questionnaire. These results suggest that there is a decrease in physiological and subjective effects of cocaine when administered repeatedly in humans. This acute tolerance appeared to have dissipated within 24 hr.