Effects of Intranasal Cocaine on Thermoregulatory Responses During Exercise in a Hot and Dry Environment

The lethal effects of cocaine are unique because of its propensity to cause hyperthermia. Previously we showed relatively small, but significantly greater (0.11°C; CI, 0.02 to 0.24) elevations in core temperature when individuals exercised in a hot and humid environment (38°C and 40% relative humidity) after receiving cocaine. However, the effects of cocaine on core temperature responses when individuals exercise in a hot and dry environment are unknown. Objective: The objective of this study was to test the effects of cocaine on thermoregulatory responses to exercise in a hot and dry environment in humans. HYPOTHESIS: We hypothesized that when compared to a placebo, a single sub-euphoric dose of intranasal cocaine would augment the increase in core temperature during exercise heat stress in a hot and dry environment, secondary to impairments in sweating and skin blood flow. In addition, we hypothesized that cocaine would alter the thermal perception in exercising humans in that environment. Methods: 10 healthy participants (5 males/5 females age: 25 ± 5 years) participated in a randomized, crossover, double-blinded, placebo (lidocaine) controlled trial. Following intranasal administration (3mg/kg) of cocaine (cocaine hydrochloride 4% nasal solution) or lidocaine (lidocaine hydrochloride 4% nasal solution), participants exercised on a semi-recumbent cycle ergometer for 60 minutes at a metabolic heat production of 4.98 ± 0.72 Watts/kg body mass in an environmental chamber set to 41°C and 15% relative humidity. We analyzed data using linear mixed effect models with main effects of time (within factor), drug (within factor), and the time by drug interaction or paired t-tests (one-tailed), as appropriate. Results: When compared to lidocaine, the increase in core temperature was greater in the cocaine trial (cocaine: 1.20 ± 0.27°C vs. lidocaine: 0.90 ± 0.22°C, p<.001). When indexed to changes in mean body temperature, whole body sweat rate was 0.44 L/hr/°C (CI, -0.73 to -0.14) lower with cocaine compared to lidocaine. Likewise, the increase in forearm blood flow indexed to changes in mean body temperature was 189 mL/min/°C (CI, -332 to -47) lower with cocaine compared to lidocaine. End-trial heart rate was greater in the cocaine trial (cocaine: 147 ± 20 bpm vs. lidocaine 134 ± 18 bpm, p<.001). Interestingly, end-trial thermal comfort (cocaine: 4 ± 2 vs. lidocaine: 4 ± 2, p=.09) and thermal sensation (cocaine: 26 ± 12 vs. lidocaine: 27 ± 15, p=.46) were not different between trials. Conclusion: These data show that intranasal cocaine impairs thermoregulatory responses to exercise in a hot and dry environment resulting in greater elevations in core temperature. However, the perception of heat was not different between trials, though this occurred despite heightened elevations in core temperature with cocaine. Funding sources for this study did not play any role in the design, conduct or analysis of the study or in the decision to submit the manuscript for publication. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.