Opioid-sparing effects of cannabinoids: Myth or reality?

A converging line of evidence is indicating that cannabinoids may have an opioid-sparing effect. This property, well validated in preclinical studies, allow when both drugs are co-administered to reduce the dose of opioids without loss of analgesic effects. A meta-analysis of pre-clinical studies indicated in 2017 that the median effective dose (ED₅₀) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower than the ED₅₀ of morphine alone (Nielsen et al., 2017). However, very few studies have been conducted in humans to validate this effect. This narrative review provides an update on whether or not cannabinoid drugs can be used to produce an opioid sparing effect. For this, various lines of evidence ranging from preclinical, epidemiological and human studies will be summarized. Overall, this review indicates that the preclinical results are strongly and consistently supportive of the presence of an opioid sparing effect of cannabinoid drugs. However, to date the clinical studies have been mostly negative; and, the evidence collected in humans so far is so limited that it is premature to conclude. Therefore, prospective high quality controlled clinical trials are still required to validate this. Priorities for future research are also discussed.