Effect of acute Δ9-tetrahydrocannabinol administration on subjective and metabolic hormone responses to food stimuli and food intake in healthy humans: a randomized, placebo-controlled study

Abstract

The endocannabinoid system (ECS) is considered a key player in the neurophysiology of food reward. Animal studies suggest that the ECS stimulates the sensory perception of food, thereby increasing its incentive-motivational and/or hedonic properties and driving consumption, possibly via interactions with metabolic hormones. However, it remains unclear to what extent this can be extrapolated to humans. We aimed to investigate the effect of oral Δ9-tetrahydrocannabinol (THC) on subjective and metabolic hormone responses to visual food stimuli and food intake. Seventeen healthy subjects participated in a single-blinded, placebo-controlled, 2×2 crossover trial. In each of the 4 visits, subjective "liking" and "wanting" ratings of high- and low-calorie food images were acquired after oral THC or placebo administration. The effect on food intake was quantified in 2 ways: via ad libitum oral intake (half of the visits) and intragastric infusion (other half) of chocolate milkshake. Appetite-related sensations and metabolic hormones were measured at set time points throughout each visit. THC increased "liking" (P=0.031) and "wanting" ratings (P=0.0096) of the high-calorie, but not the low-calorie images, compared with placebo. Participants consumed significantly more milkshake after THC than after placebo during oral intake (P=0.0005), but not intragastric infusion, of milkshake. Prospective food consumption ratings during the food image paradigm were higher after THC than after placebo (P=0.0039). THC also increased plasma motilin (P=0.0021) and decreased octanoylated ghrelin (P=0.023) concentrations before milkshake consumption (i.e., in both oral intake and intragastric infusion test sessions), whereas glucagon-like peptide 1 responses to milkshake intake were attenuated by THC during both oral (P=0.0002) and intragastric (P=0.0055) administration. These findings suggest that the ECS drives food intake by interfering with anticipatory, cephalic phase, and metabolic hormone responses. This trial was registered at clinicaltrials.gov as NCT02310347.