A single dose of cannabidiol increases ad libitum energy intake in healthy adults but does not affect postprandial glucose or lipid metabolism

The endocannabinoid system is a potent regulator of energy intake, but effects of cannabidiol (CBD) on appetite/eating behaviour in humans are not documented. We examined whether acute CBD ingestion affects energy intake, subjective appetite, or postprandial glucose and lipid metabolism in fifteen healthy adults (four females). A double-blind, randomized, crossover design was used. Participants ingested 298 mg CBD or placebo, with postprandial metabolic outcomes (blood-based energy substrates/hormones, and indirect calorimetry) assessed following consumption of a mixed-macronutrient breakfast 30 min later. Subjective outcomes were recorded hourly, and an ad libitum lunch provided 180 min post-CBD ingestion. Energy intake was 193 (95%CI: 80 to 306) kcal greater following CBD ingestion (CBD 979 ± 462 kcal; placebo 786 ± 280 kcal; p = 0.003; d_z = 0.94 [0.32 to 1.55]). Ghrelin concentrations were 93 (37 to 148) and 107 (72 to 142) pg/mL less than placebo (p ≤ 0.01) at 120 and 180 min, respectively, following CBD. Minimum ghrelin concentration and AUC were 108 (67 to 150) pg/mL and 10.0 (16.6 to 3.3) ng/mL·180min less after CBD than placebo (p ≤ 0.01). There were no between-conditions differences in plasma glucose, triacylglycerol, non-esterified fatty acids, insulin, Glucagon-like peptide-1, energy expenditure, carbohydrate/lipid oxidation, or any subjective outcome (p > 0.05). Healthy adults ate more at lunch following CBD ingestion, providing the first evidence that CBD isolate can increase energy intake in humans. Energy intake increased despite lesser ghrelin concentrations and no differences in subjective appetite. Future research should explore mechanisms and/or utility in clinical populations.