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.
Keywords: CBD; cannabinoids; cannabis; clinical trials; washout period.
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