Mechanism of cocaine-induced hyperthermia in humans.
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.


METHODS
Randomized, double-blind, placebo-controlled crossover trial.


METHODS
A cardiovascular physiology laboratory in Dallas, Texas.


METHODS
7 healthy, cocaine-naive volunteers.


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


METHODS
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).
Crandall
Craig G
CG
Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, 7232 Greenville Avenue, Dallas, TX 75231, USA. CraigCrandall@texashealth.org
Vongpatanasin
Wanpen
W
Victor
Ronald G
RG
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D003042:Cocaine / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004947:Esophagus / Q000502:physiology; D005260:Female; D005334:Fever / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008012:Lidocaine / Q000009:adverse effects; D008297:Male; D012684:Sensory Thresholds / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D013546:Sweating / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D008012:Lidocaine; D003042:Cocaine