The interest in this paper is two-fold. One, it is a series of articles promoted by the International Union of Pharmacologists Nomenclature Committee that provides a definitive report on a class of receptors. Second, the topic of cannabinoid research has expanded tremendously in the last few years as the result of 1-the wealth of novel lipid ligands that appear to interact with receptors of this sort, 2-the vast number of CB1 receptors found in the brain compared with the density of receptors for other neuromodulators or neurotransmitters, and 3-the potential for cannabinoid drug therapies via the CB2 receptor within the immune systems.

This review describes within a single overview our understanding of the cannabinoid receptors, their ligands, their signal transduction, and activities in the body. Furthermore, it speculates on the possibility for novel receptors for the endogenous lipid compounds that have been discovered to interact with this class of receptors.

The cannabinoid receptors are the cellular recognition sites for the active compound in marijuana, delta-9-Tetrahydrocannabinol, as well as a wide variety of synthetic pain-relieving compounds. We now know that a number of compounds are made in the body that also activate these recognition sites and cause responses within cells. The target cells for the cannabinoid receptors are brain cells for the receptor termed CB1 and immune cells for the receptor termed CB2. This article describes the various chemical compounds that interact with these receptors, the mechanism of action of these compounds when they interact with the receptors, and the effects that these compounds have in humans and in animal models.

I was studying how another class of compounds worked at the cellular level (the prostaglandins), when I came upon a paper by chemists at Pfizer which hypothesized that their new analgesics based on the cannabinoid structure might work through prostaglandin receptors. I had a simple model system to test that hypothesis, and when tested, I discovered that hypothesis could not be supported. However, upon a literature search, I discovered that very little verifiable information was available concerning the cellular mechanism for cannabinoid compounds. So, I made an effort to investigate this, with the assistance of the Pfizer chemists, who donated samples of 60 of their compounds and offered a precursor for radiolabeling a ligand for a ligand binding assay. All of the other authors on this paper entered the field by very different doorways!

Dr. Allyn Howlett
Principal Investigator
North Carolina Central University
Durham, NC, USA