Effects of Cannabidiol Ingestion on Thermoregulatory and Inflammatory Responses to Treadmill Exercise in the Heat in Recreationally Active Males

Exertional heat stress can induce systemic endotoxin exposure and a proinflammatory cascade, likely impairing thermoregulation. Cannabidiol (CBD) is protective in preclinical models of tissue ischemia and inflammation. Therefore, this study examined the effects of CBD ingestion on exercise-induced thermoregulatory and inflammatory responses. In a randomized, double-blinded study, 13 active males (age 25 ± 5 yr; peak oxygen uptake (V̇O 2peak ) 50.4 ± 3.2 mL·kg -1 ·min -1 ) ingested 298 mg CBD or placebo 105 min before 1 h treadmill exercise (60%-65% V̇O 2peak ) in 32°C and 50% relative humidity. Core temperature, skin temperature, heart rate, subjective outcomes, and sweat loss were assessed during/after exercise. Plasma osmolality, plasma volume changes, and plasma markers of intestinal damage (I-FABP), monocyte activation (CD14), and inflammatory cytokine responses (IL-6, IL-8, and TNF-α) were assessed at baseline, pre-exercise, and 20 and 90 min post-exercise. Core temperature (∆ 1.69°C ± 0.48°C (CBD) and 1.79°C ± 0.53°C (Placebo)) and I-FABP increased during exercise, with no differences between conditions ( P > 0.050). Mean (95% confidence interval) CD14 was 1776 (463 to 3090) pg·mL -1 greater 90 min post-exercise in placebo ( P = 0.049). Median (interquartile range) peak IL-6 concentration was -0.8 (-1.1 to -0.3) pg·mL -1 less in CBD ( P = 0.050), whereas the between-condition difference in IL-6 area under curve was -113 (-172 to 27) (pg·mL -1 )·270 min ( P = 0.054). CBD did not affect thermoregulation during exertional heat stress but appeared to elicit minor immunosuppressive effects, reducing CD14 and IL-6 responses, warranting investigation in humans under more severe heat strain and other proinflammatory scenarios.