Updating the Chemistry and Biology of Cannabinoid CB2 Receptor-Specific Inverse Agonists

The cannabinoid CB2 receptor continues to be an intriguing target for the potential therapeutic benefit of cannabinoids. Because this receptor is significantly found outside the brain, compounds specific for the CB2 receptor may be free of the side effects that have plagued cannabinoid CB1 receptor-based therapeutics. In this review, we will discuss a class of compounds which modulate the constitutive activity of the cannabinoid CB2 receptor, the inverse agonists. We will discuss recent chemical advances that provide new compounds to investigate the biology based on this pharmacology. We will then discuss new biology associated with the cannabinoid CB2 receptor for hints of how these compounds can best be utilized in vivo.