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Purpose: Exertional heat stress can induce systemic endotoxin exposure and a pro-inflammatory cascade, likely impairing thermoregulation. Cannabidiol (CBD) is protective in pre-clinical models of tissue ischaemia and inflammation. Therefore, this study examined the effects of CBD ingestion on exercise-induced thermoregulatory and inflammatory responses., Methods: In a randomised, double-blinded study, thirteen active males (age 25 ± 5 y; peak oxygen uptake [V̇O2peak] 50.4 ± 3.2 mL/kg/min) ingested 298 mg CBD or placebo 105 minutes before 1 h treadmill exercise (60-65% V̇O2peak) 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, 20- and 90-min post-exercise., Results: Core temperature (∆ 1.69 ± 0.48 °C [CBD] and 1.79 ± 0.53 °C [Placebo]) and I-FABP increased during exercise, with no differences between conditions (p > 0.050). Mean (95% CI) CD14 was 1776 (463 to 3090) pg/mL greater 90 min post-exercise in placebo (p = 0.049). Median (interquartile range) peak IL-6 concentration was -0.8 (-1.1, -0.3) pg/mL less in CBD (p = 0.050), whilst the between-conditions difference in IL-6 area under curve was -113 (-172, 27) pg/mL·270 min (p = 0.054)., Conclusions: 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 pro-inflammatory scenarios., Competing Interests: Conflict of Interest and Funding Source: This project was funded by Bridge Farm Nurseries Ltd, Spalding, UK. Drusus A. Johnson was a doctoral researcher funded by Loughborough University and Bridge Farm Nurseries ltd. (Spalding, UK) during the data collection and analysis period. Stephen J. Bailey has current/previous funding from KIRIN Central Research Institute, Fitoplancton Marino SL, Kaneka Medical Europe, Bio-gen Extracts and Herbalife Europe Ltd. In all cases, monies have been paid to SJB’s institution and not directly to SJB. Tom Clifford has current/previous funding from Rousselot BV; all funds were paid directly to TC’s institution. Lewis J. James has current/previous funding from Entrinsic Beverage Company LLP, Herbalife Europe Ltd, Bridge Farm Nurseries ltd., Decathlon SA, PepsiCo Inc. and Volac International, has performed consultancy for PepsiCo Inc. and Lucozade, Ribena Suntory, and has received conference fees from PepsiCo Inc. and Danone Nutricia. In all cases, monies have been paid to LJJ’s institution and not directly to LJJ. LJJ is part of the National Institute for Health Research’s Leicester Biomedical Research Centre, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University, and the University of Leicester. No other authors have any conflicts of interest to declare., (Copyright © 2024 by the American College of Sports Medicine.)

Introduction: Cannabidiol (CBD) is a nonintoxicating phytocannabinoid used in clinical treatments and sold widely in consumer products. CBD products may be designed for sublingual or oral delivery, but it is unclear whether either is advantageous for CBD absorption. This study compared CBD pharmacokinetics after providing CBD oil as sublingual drops and within orally ingested gelatin capsules, at a dose relevant to consumer products. Materials and Methods: Eight males completed three conditions in a participant-blinded, randomized crossover design. Participants received the following combinations of placebo and CBD-containing (69 mg/mL) hemp oil in capsules and as sublingual drops: placebo capsules/placebo drops ( Placebo ), CBD capsules/placebo drops ( CBD-Caps ), and placebo capsules/CBD drops ( CBD-Drops ). Blood samples, blood pressure, and subjective scales were obtained/completed hourly for 6 h and at 24 h. Discussion: Plasma CBD concentrations were not different between CBD-Caps and CBD-Drops (interaction effect p =0.76). Peak CBD concentration (28.0±15.6 vs. 24.0±22.2 ng/mL), time of peak CBD concentration (4±1 vs. 4±2 h), and area under the concentration curve (45.3±20.3 vs. 41.8±23.3 ng/mL·6 h) were not different between conditions ( p ≥0.25). Cardiometabolic outcomes (plasma glucose/triacylglycerol, heart rate, blood pressure), liver function (plasma alanine aminotransferase/aspartate aminotransferase), kidney function (plasma creatinine), and subjective feelings/symptoms were not different between conditions ( p ≥0.07). Conclusions: Plasma CBD profiles were comparable between CBD-Caps and CBD-Drops , suggesting that there were not meaningful differences in routes of CBD absorption between conditions. This implies that CBD oil delivered sublingually is swallowed before oral mucosal CBD absorption occurs, which may have implications for research design, CBD product design, and consumer product choice.