Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study

As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 ± 0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug × time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug × time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.