CB2 cannabinoid (CB2) receptors are found through out the human body, concentrating in the immune system. Activating these receptors can result in anti- and pro-inflammatory effects, analgesia, and anti-cancer effects. These effects are modulated through the recruitment of beta-arrestin. While most drugs also activate the g-protein, which has a possible psychosis link, finding a drug that has a bias toward the recruitment of beta-arrestin could increase the anti-cancer effects and decrease any adverse effects that might be cause though g-protein activation.<br/>The bias for the drug tested, PNR-4- 20 (PNR), was determined by measuring its g-protein activation in CHO-H2- CB2 membrane and the beta-arrestin recruitment in CHO-H2- CB2 cells. The same assays were preformed on a classical non-biased cannabinoid, CP-55,940 (CP), for a comparison. To ensure the beta-arrestin recruitment internalized the receptors, down-regulation assays were preformed.<br/>PNR activated g-protein less potently and efficaciously compared to CP. PNR recruited beta-arrestin more potently, but with equal affinity compared to CP. Chronic treatment of cells with PNR produced a more rapid down regulation of the CB2 receptor compared to CP. The bias of PNR to recruit beta-arrestin could aid in producing anti-cancer effects, while minimizing adverse effects that g-protein activation might cause, such as psychosis.

Biased agonism at CB2 cannabinoid receptors: Implications for drug development

253rd National Meeting (2017)

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