FASEB J. 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.R2444.
The thermic effect of feeding (the increase in energy expenditure above resting metabolic rate following ingestion of food) is lower in adult humans with overweight and obesity compared to their lean counterparts. In animal models of obesity, the endocannabinoid system is upregulated and is thought to contribute to an unfavorable metabolic phenotype. The influence of cannabidiol, a non-psychoactive component of Cannabis sativa L., on the thermogenic properties of the endocannabinoid system in humans is unclear. Accordingly, the purpose of the current study was to explore the hypothesis that acute administration of cannabidiol would increase the thermic effect of feeding. Metabolic rate, via indirect calorimetry, was determined at rest and over 4-hours following ingestion of a liquid, mixed macronutrient meal (22% fat, 62% carbohydrate, 16% protein) equivalent to 40% of resting metabolism, in 11 adult men with body mass index greater than 25 kg/m2 (age: 26 ± 9 years; body mass: 93.7 ± 13.0 kg; body mass index: 29.8 ± 3.0 kg/m²; body fat: 29.4% ± 4.6% (mean ± SD)) on two separate occasions. Immediately following meal ingestion, participants were administered either 30 mg of cannabidiol or placebo, in a randomized, single-blind crossover fashion. Resting metabolic rate did not differ between trials (1745 ± 311 vs. 1744 ± 288 kcal/day; P=0.98). Compared with rest, energy expenditure was increased after ingestion of the liquid meal (P<0.01) but was unaffected by cannabidiol (Time x Placebo vs. Cannabidiol: P = 0.21). The area under the thermic effect of feeding response curve was also unaffected by cannabidiol (57 ± 24 vs. 58 ± 16 kcal/min x min; P=0.92). Respiratory exchange ratio, an indicator of substrate utilization, was not different between trials at rest (0.81 ± 0.04 vs. 0.79 ± 0.04; P=0.09). Ingestion of the meal increased respiratory exchange ratio (P<0.01), indicative of increased reliance on carbohydrate oxidation, but again this response was unaffected by cannabidiol (Time x Placebo vs. Cannabidiol: P=0.08). These preliminary data suggest that a single 30 mg dose of cannabidiol does not influence the thermic effect of feeding, a significant contributor to total daily energy expenditure, in men with overweight or obesity. Cannabidiol has been purported to have multiple beneficial effects on physiological function, it appears that these effects may be independent of any influence on the thermic effect of feeding.