Because animal studies show that mOR antagonists block effects of THC, several human laboratory studies have investigated whether the mOR antagonist naltrexone can reduce the subjective effects of cannabinoids in humans. In cannabis users, pretreatment with high doses of naltrexone (50–200 mg) failed to attenuate or enhanced the subjective effects of THC [56, 57] or smoked cannabis [58]. However, a lower, more mOR-selective dose of naltrexone (12 mg) decreased the intoxicating effects of 20 mg, but not 40 mg, of THC [59]. A recent placebo-controlled study in 29 heavy cannabis smokers found that opioid-receptor blockade by naltrexone (12, 25, 50, or 100 mg daily) enhanced the subjective and cardiovascular effects of cannabis [60]. This pattern of human experimental findings is not completely consistent, but suggests that clinically used doses of naltrexone would not be effective as treatment for cannabis dependence, and might actually increase the abuse liability of cannabis.
