The Basic Science of Cannabinoids

Abstract

The cannabis plant has been used for centuries to manage the symptoms of various ailments including pain. Hundreds of chemical compounds have been identified and isolated from the plant and elicit a variety of physiological responses by binding to specific receptors and interacting with numerous other proteins. In addition, the body makes its own cannabinoid-like compounds that are integrally involved in modulating normal and pathophysiological processes. As the legal cannabis landscape continues to evolve within the United States and throughout the world, it is important to understand the rich science behind the effects of the plant and the implications for providers and patients. This narrative review aims to provide an overview of the basic science of the cannabinoids by describing the discovery and function of the endocannabinoid system, pharmacology of cannabinoids, and areas for future research and therapeutic development as they relate to perioperative and chronic pain medicine.

Figure 1.

Examples of phytocannabinoids, synthetic cannabinoids, and endocannabinoids. THC and CBD are the most studied phytocannabinoids though there are currently >100 that have been identified to date. Figure created with mindthegraph.com.

Figure 2.

Cannabinoid 1 (CB1) and 2 receptors (CB2) are located in key areas responsible for the generation and propagation of nociceptive signals, and inflammation, respectively. Figure created with mindthegraph.com.

Figure 3.

Endocannabinoid system components at the neuronal synapse and control of neurotransmitter release. Endocannabinoids are synthesized in the postsynaptic neuron in an activity-dependent manner from lipid precursors by enzymes and bind to presynaptically localized CB1 receptors to inhibit the probability of neurotransmitter release; 2-AG is inactivated by MAGL and AEA is inactivated by FAAH. 2-AG indicates 2-arachidonoylglycerol; AEA, anandamide; CB1, cannabinoid 1 receptor; DAGL, diacylglycerol lipase α; FAAH, fatty acid amide hydrolase; MAGL, monoacylglycerol lipase; NAPE-PLD, N-acyl-phosphatidylethanolamine-specific phospholipase D; NAT, N-acyltransferase; PLC, phospholipase C. Figure created using mindthegraph.com.

Figure 4.

Cannabinoid receptor pharmacology. Phyto-, synthetic, and endocannabinoids can act as full, partial, neutral, and inverse agonists and well as positive or negative allosteric modulators (PAM or NAM). NAM indicates negative allosteric modulator; PAM, positive allosteric modulator. Figure created using mindthegraph.com.