Intranasal Cocaine and Temperature Regulation During Exercise

Assess the effects of intranasal cocaine on temperature regulation and whole-body sweat rate during exercise in warm environmental conditions.

Previously it was shown that intranasal cocaine attenuates skin blood flow and sweating responses during passive heat stress, when compared to placebo. However, nothing is known about the effects of cocaine on whole-body temperature regulation during mild to moderate exercise in warm environmental condition. This project will test the hypothesis that intranasal cocaine attenuates whole-body sweat rate, resulting in greater elevations in core temperature during mild to moderate exercise in warm environmental conditions. Primary data include core temperature, skin temperatures, and whole body sweat rate. Secondary variables include cardiovascular responses, perceptions of exercise exertion and thermal comfort, and metabolic heat production. Intranasal lidocaine will be used as the placebo for cocaine. The selection of the drug administered during the first experimental trial will be randomized, with the other drug administered during the second experimental trial.

We will conduct a double-blind, placebo-controlled, crossover study. Following informed consent and screening, eligible participants will be randomized to complete the cocaine or the lidocaine (placebo) trial first, with the other "agent" administered during the subsequent visit. During these experimental visits, we will first obtain "pre-drug" temperature and cardiovascular data, which will be followed by administer of cocaine or lidocaine intranasally. Participants will then enter the chamber set to warm environmental conditions. After further instrumentation in the warm environment, participants will perform mild to moderate intensity physical activity for 60 minutes. Throughout the 60 minutes of physical activity we will record body temperature and cardiovascular responses. Upon concluding the physical activity, subjects will rest while body temperature and cardiovascular responses are obtained post-physical activity.

Our research nurse will know whether the participant will receive cocaine or lidocaine. All others involved in the protocol, including the participant, will not know which agent they received for which trial.

Prior to entering the warm environmental conditions the participant will receive cocaine intranasally at a dose no higher than 3 mg per kilogram body mass. This dose will be given only once.

Prior to entering the warm environmental conditions the participant will receive lidocaine intranasally at a dose no higher than 3 mg per kilogram body mass. This dose will be given only once.

Cocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise.

Lidocaine will be administered intranasally prior to entering the warm environmental conditions and performing 60 minutes of exercise.

Core body temperature will be measured either from a temperature sensor pill or from a rectal thermometer

Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period.

Skin temperature will be measured from small temperature sensitive electrodes attached to the participant's skin

Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period.

Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period.

Within 30 minutes before exposure to warm environmental conditions and immediately after the 30 minute recovery period.

Within 30 minutes before exposure to warm environmental conditions, throughout 60 minutes of exercise, and during the 30 minute recovery period.

Subjective assessment of how hot the subject feels. Title of Scale: Thermal Sensation Scale; Minimum value: 0 "unbearably cold"; Maximum value: 8: "unbearably hot"

These values will be obtained throughout the 60 minutes of exercise and during the 30 minute recovery period

Subjective assessment of how hard the subject feels they are exercising Title of scale: Rating of Perceived Exertion Borg Scale; Minimum value: 6 "No exertion at all"; Maximum value: 20 "Maximum exertion"

These values will be obtained throughout the 60 minutes of exercise and during the 30 minute recovery period

Inclusion Criteria: 18 to 50 years of age Healthy Body mass index less than 31 kg/m^2 Speak English Systolic blood pressure <140 mmHg Diastolic blood pressure <90 mmHg Exclusion Criteria: Subjects not in the defined age range Participants who have cardiac, respiratory, neurological, and/or metabolic illnesses Any known history of renal or hepatic insufficiency/disease Pregnancy or breast feeding Body mass less than 60 kilograms Current smokers, as well as individuals who regularly smoked within the past 3 years Individuals with a history of drug abuse within the past 5 years Individuals who have an unexplained positive urine drug screen (e.g., some agents cause false-positive results and when agent abstained the drug screen is negative, one example could be an over the counter supplement) Currently taking pain modifying medications