The subjective effects of △9-tetrahydrocannabinol: A systematic review and dose-response meta-regression

Global shifts towards the liberalisation of cannabis policies have increased the potency of cannabis products, alongside their accessibility, diversity, and the number of inexperienced cannabis consumers. There is a lack of systematic evidence on the subjective effects of cannabis' main psychoactive compound, Δ9-tetrahydrocannabinol (THC). We systematically reviewed and meta-analysed data from 41 randomised, double-blind, and placebo-controlled experimental studies on the acute subjective effects of THC in 1020 healthy individuals with infrequent cannabis use (<2 weekly; <100 lifetime). Pairwise meta-analyses estimating the mean difference of peak subjective effects between THC and placebo showed greater feelings of high, anxiety, and tiredness (all p < 0.001), lower alertness and contentedness (both p < 0.01), and no difference on calmness (p = 0.414). Meta-regressions of dose were stratified by inhaled and oral administration. Greater inhaled THC dose increased feeling high (b=1.06, p = 0.0024) and contentedness (b=1.06, p = 0.025), and decreased calmness (b=-0.96, p = 0.048); with no change in anxiety (b=-0.03, p = 0.845), tiredness (b=0.39, p = 0.129), or alertness (b=0.11, p = 0.837). Variability meta-analyses showed that greater inhaled dose of THC produced greater consistency between individuals in feeling high (b=-0.05, p = 0.021) and contentedness (b=-0.04, p < 0.0001). On a 100-point scale, inhaling 5 mg THC resulted in: increased high, anxiety, tiredness, and calmness by 34.3 (95%CI: 30.8-37.7), 14.4 (95%CI: 12.8-16.0), 26.3 (95%CI: 23.8-28.8), 4.5 (95%CI: -0.3-9.3), respectively; decreased alertness and contentedness by 40.2 (95%CI: -45.4--34.9) and 71.0 (95%CI: -75.7--66.4), respectively. Oral dose was not associated with any subjective effects (p > 0.05), although variability meta-analyses showed that greater oral dose of THC produced greater consistency between individuals in alertness (b=-0.13, p = 0.049). This evidence can inform public health efforts to guide consumers on the expected subjective effects of THC.