Background Cannabidiol (CBD) has demonstrated anti-inflammatory, analgesic, anxiolytic and neuroprotective effects that have the potential to benefit athletes. This pilot study investigated the effects of acute, oral CBD treatment on physiological and psychological responses to aerobic exercise to determine its practical utility within the sporting context. Methods On two occasions, nine endurance-trained males (mean ± SD V̇O2max: 57.4 ± 4.0 mL·min−1·kg−1) ran for 60 min at a fixed intensity (70% V̇O2max) (RUN 1) before completing an incremental run to exhaustion (RUN 2). Participants received CBD (300 mg; oral) or placebo 1.5 h before exercise in a randomised, double-blind design. Respiratory gases (V̇O2), respiratory exchange ratio (RER), heart rate (HR), blood glucose (BG) and lactate (BL) concentrations, and ratings of perceived exertion (RPE) and pleasure–displeasure were measured at three timepoints (T1–3) during RUN 1. V̇O2max, RERmax, HRmax and time to exhaustion (TTE) were recorded during RUN 2. Venous blood was drawn at Baseline, Pre- and Post-RUN 1, Post-RUN 2 and 1 h Post-RUN 2. Data were synthesised using Cohen’s dz effect sizes and 85% confidence intervals (CIs). Effects were considered worthy of further investigation if the 85% CI included ± 0.5 but not zero. Results CBD appeared to increase V̇O2 (T2: + 38 ± 48 mL·min−1, dz: 0.25–1.35), ratings of pleasure (T1: + 0.7 ± 0.9, dz: 0.22–1.32; T2: + 0.8 ± 1.1, dz: 0.17–1.25) and BL (T2: + 3.3 ± 6.4 mmol·L−1, dz: > 0.00–1.03) during RUN 1 compared to placebo. No differences in HR, RPE, BG or RER were observed between treatments. CBD appeared to increase V̇O2max (+ 119 ± 206 mL·min−1, dz: 0.06–1.10) and RERmax (+ 0.04 ± 0.05 dz: 0.24–1.34) during RUN 2 compared to placebo. No differences in TTE or HRmax were observed between treatments. Exercise increased serum interleukin (IL)-6, IL-1β, tumour necrosis factor-α, lipopolysaccharide and myoglobin concentrations (i.e. Baseline vs. Post-RUN 1, Post-RUN 2 and/or 1-h Post-RUN 2, p’s < 0.05). However, the changes were small, making it difficult to reliably evaluate the effect of CBD, where an effect appeared to be present. Plasma concentrations of the endogenous cannabinoid, anandamide (AEA), increased Post-RUN 1 and Post-RUN 2, relative to Baseline and Pre-RUN 1 (p’s < 0.05). CBD appeared to reduce AEA concentrations Post-RUN 2, compared to placebo (− 0.95 ± 0.64 pmol·mL−1, dz: − 2.19, − 0.79). Conclusion CBD appears to alter some key physiological and psychological responses to aerobic exercise without impairing performance. Larger studies are required to confirm and better understand these preliminary findings. Trial Registration This investigation was approved by the Sydney Local Health District’s Human Research Ethics Committee (2020/ETH00226) and registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12620000941965).

A growing number of clinical trials (CTs) are investigating the therapeutic potential of cannabidiol (CBD), a non‐intoxicating phytocannabinoid found in Cannabis sativa. These CTs often use crossover experimental designs requiring ‘washout’ (clearance) periods. However, the length of time CBD persists in plasma (its ‘window of detection’) is unclear and could be significant. Indeed, the structurally related phytocannabinoid, Δ9‐tetrahydrocannabinol (THC), has a long window of detection in plasma. We investigated the extent to which CBD and its major metabolites persist in plasma. Data from three CTs that measured plasma cannabinoid concentrations ≥7 days after administering a single oral dose of CBD were pooled. The CBD doses were as follows: CT #1: 300 mg; CT #2: 200 mg (and 10 mg THC); and CT #3: 15, 300 and 1500 mg (one per treatment session). Thirty‐two participants were included in the analysis, 17 of whom (from CT #3) provided repeated measures. Overall, 0% (15 mg), 60% (200 mg), 28% (300 mg) and 100% (1500 mg) of participants had detectable concentrations (i.e., >0.25 ng·ml−1) of CBD in plasma ≥7 days post‐treatment (some, several weeks post‐treatment). A zero‐inflated negative binomial mixed‐effects regression analysis (R2m = 0.44; R2c = 0.73) predicted that, on average, a 13 day washout period would reduce plasma CBD concentrations to ‘zero’ (i.e., <0.25 ng·ml−1) if a single oral dose of 300 mg was consumed. Higher doses require longer washout periods; concomitant medications may also affect clearance. In conclusion, CBD has a long window of detection in plasma. Crossover studies involving CBD should, therefore, be conducted with caution, particularly when higher doses and/or chronic dosing regimens are used.

CONCLUSION: Bitter solutions may not be effective in improving functional performance in older adults. Lack of significant findings could be due to 1) inappropriately low dosages of caffeine to produce an ergogenic effect 2) caffeine is not as effective quinine in stimulating oral receptors in the mouth 3) decreased chemosensitivity and oral receptor function due to age related changes. Further research is needed to assess the effects of bitter solution mouthwashes in older adults as a way to effect acutely change performance measures. PURPOSE: Cannabidiol (CBD) may exert physiological and psychological effects that benefit athletes (e.g. protect against neurological damage; reduce inflammation, anxiety and pain) (McCartney et al. 2020). This pilot study investigated the effects of CBD on physiological responses to exercise to determine its practical utility within the sporting context. METHODS: On two occasions, nine endurance-trained males (VO2max: 57.4±4.0 mL•min -1 •kg -1 ) ran for 60 mins at a fixed, moderate-intensity (70% VO2max) (RUN 1) before completing an incremental run to exhaustion (RUN 2) on an indoor treadmill (21.4±0.4°C). Participants received an oral dose of CBD (300 mg) or placebo 1.5 hrs prior to exercise in a randomised, doubleblind, crossover design. Respiratory gases were sampled continuously between 24-32, 37-45 and 50-58 mins of submaximal exercise; heart rate (HR), ratings of perceived exertion (RPEs), ratings of pleasure-displeasure, blood glucose (BG) and lactate (BL) concentrations were measured at 20-min intervals. Blood was drawn at baseline, pre-and post-RUN 1, post-RUN 2 and 1 hr post-RUN 2. RESULTS: CBD tended to increase submaximal oxygen consumption (+24±13 mL•min -1 , p=0.094). No differences in HR, RPE, BG, BL, or respiratory exchange ratio were observed during submaximal exercise (p's>0.10); VO2max (CBD: 3987±462; Placebo: 3868±577 mL•min -1 ; p=0.121) and time to exhaustion (CBD: 1286±150; Placebo: 1246±197 sec; p=0.204) were also similar during the incremental run. CBD tended to increase ratings of pleasure at 20-(p=0.050) and 40-mins (p=0.065) of submaximal exercise. Serum interleukin (IL)-6, IL-1β, tumor necrosis factor-α, lipopolysaccharide and myoglobin concentrations increased from baseline with exercise (i.e., post-RUN 1, post-RUN 2 and/or 1 hr post-RUN 2, p's<0.05); however, the change was too small to reliably evaluate the effect of CBD. Plasma CBD concentrations were 0±0, 3±2, 77±18, 164±35 and 99±26 ng.mL -1 at each respective time point. CONCLUSIONS: These preliminary findings suggest that CBD has potential to alter physiological responses during exercise. Further research involving a larger participant sample is required to confirm and better understand these effects.