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  • Title: Mechanism of cocaine-induced hyperthermia in humans.
    Author: Crandall CG, Vongpatanasin W, Victor RG.
    Journal: Ann Intern Med; 2002 Jun 04; 136(11):785-91. PubMed ID: 12044126.
    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).
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