Inhaling high THC cannabis acutely increases inflammation but not insulin sensitivity: a quasi-randomized trial

Cannabis is linked with increased appetite, raising concern about obesity‐related disease and type 2 diabetes. Yet data suggest metabolic benefits of cannabis through inflammatory processes and insulin sensitivity. This was a quasi‐randomly assigned experimental study comparing acute effects of a CBD‐dominant versus THC‐dominant versus CBD + THC cannabis flower product. Data were collected from community participants through a mobile pharmacology laboratory and a clinical research center. Participants smoked their assigned pre‐rolled cannabis flower cigarette ad libitum. Primary outcomes were IL‐10, chemokine MCP‐1, a composite of pro‐inflammatory cytokines (TNF‐α, IL‐6, IL‐1β, IL‐12, IFNG, and IL‐4), and insulin sensitivity (Matsuda index). Outcomes were predicted by peak blood levels of THC and CBD immediately after cannabis use. Hypotheses were that inflammation and insulin sensitivity would vary as a function of CBD and THC exposure, and that inflammatory changes would be associated with insulin sensitivity. Participants (n = 108) were 25 to 45 (Mage = 29.7, sd = 5.4), 56.5% Female, and 88.0% white. Mixed effect models indicated a time X peak THC blood level interaction (B = 0.003, SE = 0.001, p = 0.037). As THC blood levels increased, inflammation increased more after acute use. There was a THC X CBD X time interaction on IL‐10 (B=‐0.001, SE = 0.000, p < 0.001). Higher than average peak blood THC was related to increasing IL‐10 over time while lower than average peak THC was related to decreasing IL‐10 over time but only at average or lower peak CBD levels. Cannabis use decreased MCP‐1 acutely (effect for time: B=‐48.757, SE = 15.061, p = 0.002), while there was no effect on the Matsuda Index. Acute cannabis use is associated with increases in both pro‐ and anti‐inflammatory circulating cytokines, but not with insulin sensitivity. Additional research on the possible mediating mechanisms involved in the connection between cannabis use and type 2 diabetes is required.Trial registration: Gov NCT04114903, https://clinicaltrials.gov/study/NCT04114903, Registration date 11/08/2019.