Acute behavioural effects of low-dose cannabidiol: A randomised crossover trial in healthy volunteers

Cannabidiol (CBD) is widely consumed in low-dose products. However, evidence for its psychotropic effects at non-clinical doses is sparse and inconsistent.

To characterise the acute behavioural effects of low-dose synthetic CBD in healthy volunteers. We hypothesised that 200 mg of CBD would produce a greater peak pleasant drug effect than a placebo.

In a triple-blind, randomised, crossover trial at the CHUM research centre, Montreal, Canada, 70 healthy occasional cannabis users received single oral doses of 20, 50, 100 and 200 mg synthetic CBD and placebo immediately after a high-fat meal. The primary outcome, a participant-rated visual analogue scale of pleasant drug effect (0-100), was assessed at five timepoints post-dosing during each visit. Other measurements included additional participant ratings of drug effects, as well as positive and negative affect, dissociation, anxiety, blood pressure, heart rate, and respiratory rate.

Two hundred milligrams of synthetic CBD dose produced an average 12.8% [95% CI = 3.8% to 21.8%] higher peak pleasant drug effect score compared to placebo (Cohen's d = 0.479 [0.089 to 0.869], p_corr = 0.044). No other dose of CBD showed a significant effect for the primary outcome versus placebo. All adverse events were mild or moderate in severity.

The highest dose of CBD tested produced a slight but perceptible pleasurable subjective drug effect. This effect may differ based on prandial state and in clinical populations and populations with heavier cannabis use. Single doses of 100 mg synthetic CBD or less are unlikely to produce any discernible psychoactive effect in healthy, occasional users.

The study was registered on ClinicalTrials.gov (NCT05407285).