Tuesday, December 5, 2023
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Medical Director, PHYTECS, Los Angeles, California
Professor of Pharmacy & Neurology, University of Wisconsin School of Pharmacy, Madison, Wisconsin
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This activity is intended for neurologists, pharmacists, pediatricians, and primary care physicians.
The goal of this activity is to provide background on the endocannabinoid system and its potential role in investigational therapies.
Upon completion of this activity, participants will have increased knowledge regarding the:
As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.
Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
Medical Director, PHYTECS, Los Angeles, California
Professor of Pharmacy & Neurology, University of Wisconsin School of Pharmacy, Madison, Wisconsin
This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.
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CME / CE Released: 10/31/2017; Reviewed and Renewed: 10/31/2018
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Editor's Note: In June 2018, the United States Food and Drug Administration approved Epidiolex(R) (cannabidiol [CBD]) oral solution for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older. The Department of Justice and Drug Enforcement Administration subsequently placed Epidiolex in schedule V of the Controlled Substances Act, the least restrictive schedule of the Controlled Substances Act.
Discovered after centuries of cannabis plant use by humans for spiritual, medicinal, and recreational purposes, the ECS has in recent decades been revealed to be an integral component of normal physiology. A major contributor to the maintenance of homeostatic balance, the ECS influences nearly every organ and function in the body. This review will include the function of the ECS, its main endogenous components, the exogenous compounds that interact with it, and the current state of research into therapeutic potential of this system, particularly for the treatment of epilepsy.
Though phytocannabinoids (plant-based cannabinoids) have been in use for millennia, identification of the molecules and signaling pathways underlying their efficacy did not progress until the discovery of the main psychoactive compound in Cannabis sativa, ?9-tetrahydrocannabinol (THC).[1] Thereafter, dozens of additional plant-based cannabinoid compounds were identified, their unique chemical structures defined, and their myriad pharmacological profiles described. Later, evidence that ?9-THC was interacting with a particular mammalian target was uncovered in murine neuroblastoma cells, which expressed upregulated adenylate cyclase in response to exposure to the compound or its synthetic analogues. This finding led the way for the isolation and cloning of a G protein-coupled receptor (GPCR) that was subsequently named the cannabinoid receptor type 1 (CB1).[2] A few years after this, the counterpart to CB1, cannabinoid receptor type 2 (CB2), was isolated from human leukemia cells.[3]
The identification of these receptors led to the hypothesis that endogenous ligands may also exist. Indeed, the first such endogenous cannabinoid receptor ligand, or endocannabinoid, was isolated from pig brain and named N-arachidonoylethanolamine (AEA), or anandamide.[4] A second ligand, 2-arachidonoylglycerol (2-AG), was next isolated from canine gut tissue.[5] Of note, these GPCR ligands are lipids, as opposed to the large number of GPCR ligands that are instead protein.[6] In the years since these compounds were identified, the molecules comprising the ECS have expanded to include additional receptors that bind cannabinoids, as well as a number of enzymes that facilitate their synthesis and degradation. Furthermore, the body of research into the system's function has uncovered numerous roles for the ECS in normal mammalian physiology, as well as therapeutic possibilities for multiple diseases and disorders (Figure 1).[1]
Figure 1. The Endocannabinoid System Is Involved in a Variety of Functions[7]
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