Mechanism of cocaine-induced hyperthermia in humans

Ann Intern Med. 2002 Jun 4;136(11):785-91. doi: 10.7326/0003-4819-136-11-200206040-00006.

Abstract

Background: The lethal effects of cocaine are unique among those of other illicit drugs because cocaine has the propensity to cause hyperthermia. The traditional view is that cocaine causes a hypermetabolic state with increased heat production. However, because cocaine-induced hyperthermia occurs primarily in hot weather, it is hypothesized that cocaine also impairs thermoregulatory adjustments that mediate heat dissipation.

Objective: To test the effects of cocaine on body temperature regulation in humans.

Design: Randomized, double-blind, placebo-controlled crossover trial.

Setting: A cardiovascular physiology laboratory in Dallas, Texas.

Participants: 7 healthy, cocaine-naive volunteers.

Intervention: Progressive passive heat stress, during which each participant received intranasal cocaine (2 mg/kg of body weight) or placebo (lidocaine, 2 mg/kg).

Measurements: Esophageal temperature, skin blood flow, sweat rate, and perceived thermal sensation.

Results: Three major new findings were noted. First, cocaine substantially augmented the progressive increase in esophageal temperature during heat stress (P < 0.001). Second, this augmentation was explained by a rightward shift in the esophageal temperature threshold for the onset of both cutaneous vasodilation (37.37 +/- 0.09 degrees C for cocaine vs. 37.06 +/- 0.07 degrees C for lidocaine; P = 0.01) and sweating (37.38 +/- 0.09 degrees C for cocaine vs. 37.07 +/- 0.06 degrees C for lidocaine; P = 0.002). Third, cocaine paradoxically impaired the perception of heating by attenuating the progressive increase in thermal discomfort associated with heat stress.

Conclusions: In humans, impaired heat dissipation is a major mechanism by which cocaine elevates body temperature. When healthy, cocaine-naive persons are subjected to passive heating, pretreatment with even a small dose of intranasal cocaine impairs sweating and cutaneous vasodilation (the major autonomic adjustments to thermal stress) and heat perception (the key trigger for behavioral adjustments).

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Body Temperature Regulation / drug effects*
  • Cocaine / adverse effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Esophagus / physiology
  • Female
  • Fever / chemically induced*
  • Heart Rate / drug effects
  • Humans
  • Lidocaine / adverse effects
  • Male
  • Sensory Thresholds / drug effects
  • Skin / blood supply
  • Sweating / drug effects
  • Vasodilation / drug effects

Substances

  • Lidocaine
  • Cocaine