CannaConsumer Magazine
MEDICAL CANNABIS 23
Figure 1. Anandamide.
Figure 2.
Δ-9-Tetrahydrocannabinol
Figure 3. Cannabidol
As evolution so often does, once the gene for the first cannabinoid receptor existed a second variant was also produced. We now call these cannabinoid receptors CB1 and CB2 – numbered in order of their discovery, not their evolution! Professor Elphick at Queen Mary University of London reported the existence of CB2 farther back in vertebrate evolution than the split between fish and Tetrapoda (mammals, birds, reptiles, amphibians)2. That means that the cannabinoid receptor system is important enough in cellular development that multiple functions were already appearing around the time our friend above was turning into a real fish.
However, this is much more unknown than known regarding the cannabinoid receptor system on a whole. At least two other receptors are likely to function as (endo)cannabinoid receptors based upon both biochemical and bioinformatic studies (https://en.wikipedia.org/wiki/Cannabinoid_receptor) and there may be more variants yet to be discovered.
The Mechanism
What we DO know about the cannabinoid receptors is based upon studies of CB1 and, to a lesser extent, CB2. The full crystal structure of CB1 was published by two separate groups in the last year3, 4. The cannabinoid receptors are members of the larger class of G-Protein Coupled Receptors, or GPCRs. GPCRs (a favorite target for pharmaceutical development) are characterized by a “seven trans-membrane” core. This structural feature consists of seven coiled protein “beams” that form a circle to produce a tunnel through the cell membrane.
Left : schematic of CB1 and CB2 displaying the seven transmembrane barrels, and internal and external tails5. Right : 3D representation of the CB1 core6.