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. 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 degreesC for cocaine vs. 37.06 +/- 0.07 degreesC for lidocaine; P = 0.01) and sweating (37.38 +/- 0.09 degreesC for cocaine vs. 37.07 +/- 0.06 degreesC 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).