Cannabis Use and the Endocannabinoid System: A Clinical Perspective

Abstract

Societal attitudes toward cannabis, both as a drug of abuse and as a potential therapeutic, have undergone a marked shift in the past 25 years, resulting in wide-scale changes in legalization, public policy, and marketing of cannabis and its constituents (cannabinoids, such as cannabidiol). Cannabis has abuse liability, producing positive subjective effects, and repeated use over time can result in a use disorder, which can include withdrawal symptoms (sleep disruption, irritability, anxiety, anorexia, craving), unsuccessful attempts to cut down or quit, and failure to fulfill obligations. The consequences of having a cannabis use disorder are rarely as destructive to individual lives as other drugs of abuse can be, which may lead to the perception that cannabis use disorder is a somewhat minor concern. However, a significant subset (10%−30%) of those using cannabis will develop cannabis use disorder (1), which is both distressing to the individual and not easy to overcome.

The past few decades have also borne witness to a tremendous advancement in our understanding of the endocannabinoid system, beginning with the groundbreaking discoveries of the cannabinoid receptors and endogenous cannabinoids (2). Although cannabis use has been documented for millennia, only relatively recently have we begun to understand the critical role of the endocannabinoid system in a wide array of psychophysiological functions.

Considering both the ubiquity of cannabis and cannabinoid use and the essential function of the endocannabinoid system, my objective in this review is to describe several key clinical issues regarding the interaction between cannabis use and endocannabinoid neurobiology.