Acute tolerance development to the cardiovascular and subjective effects of cocaine.

TLDR

Eight healthy volunteers received either 4 mg or 96 mg intranasal cocaine, followed 60 min later by IV doses of 16–48 mg while plasma levels, cardiovascular responses, and subjective effects were monitored for 8 h. Repeated cocaine administration produced acute tolerance, evidenced by reduced heart‑rate and subjective responses after a 96‑mg intranasal pretreatment, with the effect dissipating within 24 h.

Abstract

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.