Understanding the Biochemical Pathways of Cannabinoids

Written by Antonio DeRose

Cannabinoids are a class of diverse chemical compounds that act on cannabinoid receptors in cells that alter neurotransmitter release in the brain. Cannabinoids can be produced in the body (endogenous cannabinoids) or introduced from outside the body (exogenous cannabinoids). The most notable exogenous cannabinoid is delta-9-tetrahydrocannabinol (THC) one of the primary psychoactive components of cannabis.


The Biochemical Pathways of Cannabinoids

Cannabinoids interact with the endocannabinoid system (ECS), which is a collection of cell receptors and corresponding neurotransmitters. The ECS regulates various physiological functions including pain, appetite, mood, and memory. There are two main types of receptors in the ECS, CB1 and CB2 receptors. CB1 receptors are predominantly found in the brain and central nervous system. CB2 receptors are mostly found in the peripheral nervous system.

These receptors are stimulated by endocannabinoids and exogenous cannabinoids. The most extensively studied endocannabinoid is anandamide. “Other endogenous ligands for cannabinoid receptors are 2arachidonoylglycerol (2-AG), noladin ether, virodhamine, and N-arachidonoyldopamine (NADA) and 2-arachidonoylglycerol (2-AG)”. [1]

In recent years, researchers have begun to understand more about how cannabinoids modulate physiological processes by binding to cannabinoid receptors. For example, THC binds to both CB1 and CB2 receptors, while cannabidiol (CBD) works with the receptors indirectly as a CB2 receptor inverse antagonist. “The ability of cannabidiol to behave as a CB2 receptor inverse agonist may contribute to its documented anti-inflammatory properties.”


CB1 receptors are found primarily in the brain and are responsible for mediating the psychoactive effects of cannabinoids. CB2 receptors are found primarily in the peripheral nervous system and are involved in mediating inflammation. When THC binds to CB1 receptors it alters neurotransmitter release and leads to the high associated with consuming cannabis.

CBD does not bind directly to CB1 receptors but instead inhibits the enzyme that breaks down the  endogenous cannabinoid anandamide. This leads to an increase in anandamide levels and contributes to CBD’s therapeutic effects. [1]

The ECS is a complex network, and its role in human health and disease is only beginning to be better understood. However, the available evidence suggests that cannabinoids, either endogenous or exogenous, modulate various biochemical pathways involved in maintaining homeostasis within the body. Understanding how cannabinoids interact with the ECS is critical for developing new therapeutic treatments for various conditions.




1- Manzanares J, et al. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006 Jul;4(3):239-57. doi: 10.2174/157015906778019527. Journal Impat Factor: 7.363 Times Cited: 67

2- Thomas A, et al. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007 Mar;150(5):613-23. doi: 10.1038/sj.bjp.0707133. Journal Impact Factor: 8.739 Times Cited: 253


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Antonio DeRose

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