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 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).