osteoarthritis (Whyte et al. 2009). In prostate cancer cells, increase in the phosphor-

ylation of AKT and ERK1/2 and mobilization of calcium ions are reduced by GPR55

silencing (Pineiro et al. 2011). Thus, this shows that GPR55 provides additional

benefit to CB1 and CB2 receptor functioning.

This chapter reviews the current knowledge of ECS and elucidate the physiologi-

cal and pathophysiological roles of cannabinoid receptors. We will further discuss

about various cannabinoid receptor agonists and antagonists and their putative use as

adjunctive anticancer agents.

12.4

Cannabinoid Receptor Ligands

12.4.1 Classification of Ligands and Their Affinities Toward

Receptors

In the classification according to the chemical structures, ligands fall into four major

classes: classical, nonclassical, aminoalkylindole, and eicosanoid (Howlett et al.

2002) (Fig. 12.1).

1. Classical cannabinoids: Classical group of cannabinoids consist of ABC tricyclic

dibenzopyran derivatives. The most investigated among classical cannabinoids

have been Δ⁹THC, Δ⁸THC, HU-210, and desacetyl-L-nantradol. These

cannabinoids are not selective and can bind both the receptors. Δ⁹-THC has

notably lower CB1 and CB2 affinity as compared to HU-210.

2. Non-classical group: This group contains analogs of Δ⁹THC and is mostly found

to have bicyclic and tricycling structures that lack a pyran ring. The most

extensively studied member belonging to this group is CP55940. It has slightly

lower affinities for both the cannabinoid receptors (CB1 and CB2) than HU-210

but does have the same intrinsic activity.

Cannabinoid Ligands

Classical

Cannabinoids

Non Classical

Cannabinoids

Aminoalkylindole

Eicosanoid

1. CP 55940

1. WIN 55212

1. Anandamide

2. 2-AG

3. Virodhamine

4. N-arachidonoyl

dopamine

1.

2.

3. HU-210

THC

THC

∆⁹

∆⁸

Fig. 12.1 Classifications of the cannabinoid ligands

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S. Singh et al.