Changing the tone of clinical study design in the cannabis industry

Abstract: Cannabis (also known as marijuana) is the most frequently used psychoactive substance globally. Cannabis exerts therapeutic functions for many indications and has vast potential as a health and wellness product. Advances in our understanding of the composition and pharmacological properties of cannabis have revealed interactions between cannabis, an individuals’ circadian rhythms and their endocannabinoid signaling. Exogenously administered cannabinoids can bidirectionally entrain central and peripheral clocks that comprise circadian rhythms, and malfunctions in the endocannabinoid system are reported to impact neurological processes. Therefore, it is necessary to account for the circadian rhythm when designing clinical trials examining the pharmacological properties of cannabis-based products for health and wellness to limit its potential confounding impact on results. Consideration of the entrainment capabilities of the endocannabinoid system is warranted when designing clinical trials.