The Effect of Cannabidiol on Subjective Responses to Endurance Exercise: A Randomised Controlled Trial.

BACKGROUND: Exercise is known to improve health. However, it can be unpleasant, often inducing negative feelings, or 'affect'. Cannabidiol (CBD), a non-intoxicating constituent of the cannabis plant, has been reported to enhance the subjective experience of exercise; specifically, in trained individuals performing fixed-intensity endurance activity. Here, we investigated the effects of CBD on subjective responses to exercise under more ecologically valid conditions; namely, in recreationally active individuals performing self-paced endurance activity. METHODS: A randomised, double-blind, placebo-controlled, crossover trial was conducted at Griffith University between July 17 and August 28, 2023. Griffith University students studying sports nutrition were invited to take part, with eligible volunteers ≥ 18 years of age and able to perform endurance exercise. Participants ingested placebo or 150 mg CBD in two soft-gel capsules 90 min before completing a self-paced 25-lap (10 km) run around an outdoor athletics track (400 m, synthetic). The primary outcomes were affective valence during exercise, assessed on completion of laps 6, 12, 18 and 24 using the 'Feelings Scale', and positive and negative affect, assessed at baseline, pre-run and post-run using the 'Positive and Negative Affect Schedule'. Exercise enjoyment, motivation and self-efficacy, the core features of the 'runner's high' (i.e., euphoria, pain, anxiety, sedation), perceived exertion and run time were also assessed. RESULTS: Fifty-two participants were randomised and 51 were included in the final sample (n = 22 female; 22 [21-25] years). Exercise induced negative affect (i.e., at the time of undertaking) and increased pain. CBD did not counteract either response. In fact, CBD had no significant effects on any of the outcomes measured. In contrast, exercise, once completed, increased positive affect, and decreased negative affect and anxiety. CONCLUSIONS: CBD (150 mg, oral) does not appear to enhance the subjective experience of self-paced endurance exercise in recreationally active individuals. Nor, however, does it appear to compromise it. These findings suggest that CBD use is safe under exercise conditions and unlikely to impede physical activity participation. Our study also reaffirms the powerful mood-enhancing effects of exercise. TRIAL REGISTRATION: Registered with the Australian New Zealand Clinical Trials Registry ( www.anzctr.org.au ) on May 31, 2023 (Trial ID: ACTRN12623000593639).

How long does a single oral dose of cannabidiol persist in plasma? Findings from three clinical trials.

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 (R2 m = 0.44; R2 c = 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.

Effects of Cannabidiol on Exercise Physiology and Bioenergetics: A Randomised Controlled Pilot Trial.

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-1ß, 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).