Mechanism of Cocaine-Induced Hyperthermia in Humans

  1. Craig G. Crandall, PhD;
  2. Wanpen Vongpatanasin, MD; and
  3. Ronald G. Victor, MD
  1. From University of Texas Southwestern Medical Center and Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, Texas.

    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 °C for cocaine vs. 37.06 ± 0.07 °C for lidocaine; P = 0.01) and sweating (37.38 ± 0.09 °C for cocaine vs. 37.07 ± 0.06 °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).

    Article and Author Information

    • Grant Support: By the National Institutes of Health (HL-61388) (Dr. Crandall); the American Heart Association, Texas Affiliate (0060010Y) (Dr. Vongpatanasin); and the National Institute on Drug Abuse (RO-1 DA10064) (Dr. Victor).

    • Requests for Single Reprints: Craig G. Crandall, PhD, Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, 7232 Greenville Avenue, Dallas, TX 75231; e-mail, CraigCrandall{at}texashealth.org.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Current Author Addresses: Dr. Crandall: Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, 7232 Greenville Avenue, Dallas, TX 75231.

    • Drs. Vongpatanasin and Victor: Divisions of Hypertension and Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, J4.134, Dallas, TX 75390-8586.

    • Author Contributions: Conception and design: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

    • Analysis and interpretation of the data: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

    • Drafting of the article: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

    • Critical revision of the article for important intellectual content: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

    • Final approval of the article: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

    • Provision of study materials or patients: C.G. Crandall, W. Vongpatanasin.

    • Statistical expertise: C.G. Crandall.

    • Obtaining of funding: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

    • Administrative, technical, or logistic support: C.G. Crandall, W. Vongpatanasin, R.G. Victor.

    • Collection and assembly of data: C.G. Crandall.

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    1. Ann Intern Med June 4, 2002 vol. 136 no. 11 785-791
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