Acute tolerance development to the cardiovascular and subjective effects of cocaine.
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.
D000328:Adult; D002319:Cardiovascular System / Q000187:drug effects*; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004644:Emotions / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000378:metabolism
D003042:Cocaine; D009638:Norepinephrine