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.