ABSTRACT
This chapter provides a summary, as of late 2020, of the state of knowledge of cannabis pharmacokinetics and pharmacodynamics. First, the absorption, distribution, metabolism, and elimination of both THC and CBD are described. Then follows a summary of the existing pharmacokinetic models for both substances. The section ends with the presentation of a new model for THC that includes the elimination of both carboxy-THC and its glucuronide conjugate. Many endogenous and exogenous substances are conjugated with glucuronic acid, a highly polar moiety, to enhance both biliary and urinary excretion. Humans have a high capacity for glucuronidation to foster the elimination of bilirubin, the toxic by-product of hemoglobin degradation and the cause of jaundice, a yellowing of the skin and eyes in those with compromised liver function. The chapter continues with a review of the endocannabinoid system. Endocannabinoids are molecules produced within the body that bind to cannabinoid receptors. The two primary endocannabinoids are 2-arachidonoylglycerol and anandamide. The function of these molecules and the associated receptors is to modulate synaptic transmission at GABAergic and glutamatergic synapses. THC acts at the CB1 receptor and CBD acts at the CB2 receptor. The endocannabinoid system itself likely includes other components and the understanding of this system’s normal functioning is still developing. The chapter concludes with three examples of cannabinoid effects: the impairing effect of THC on driving ability by modulation of attention; the effect of THC on the heart and the relation to sudden heart attacks; and the reduction of anxiety brought on by the use of CBD. The glimpse of cannabis science presented here will likely be supplanted as continuing interest in both endogenous and exogenous cannabinoids is driving additional research.
