Cannabinoids are the main biologically active constituents of marijuana and cannabis derivatives. They have psychoactive effects. There are at least three CB receptors in human tissues: (i) CB₁ receptors, (ii) CB₂ receptors, and (iii) GPR55 receptors. High expression of CB₁ receptors in the brain suggests that endocannabinoid system plays an important role in the function of CNS. Cannabinoids’ intoxication attenuates learning and memory processes in both humans and animals. In addition, CB₁ shows relations with skin fibrosis and scar tissue formation in mice. Therefore, the topical use of cannabinoids may have a role in the prevention or treatment of local fibrotic and wound healing diseases such as hypertrophic scars or keloids. In this study, AM251 is a selective cannabinoid 1 (CB₁) receptor antagonist (IC₅₀=8 nM). It also acts as a potent GPR55 agonist (EC₅₀=39 nM).

AM251 is an inverse agonist of the CB₁ receptor that can exert ‘off-target’ effects in vitro. It is also potent at modulating tumor cell growth. AM251 shows a concentration-dependent effect over collagen deposition with a pIC₅₀ of 5.5. It regulates the expression of the EGF receptor and its ligands via destabilization of oestrogen-related receptor α protein. In addition, AM251 (1.0 mg/kg) significantly improves recognition memory. Moreover, AM251 does not affect anxiety but in the highest dose significantly attenuates psychomotor activity in rats. In a word, AM251, at the dose of 1.0 mg/kg, improves recognition memory in rats without alteration of their psychomotor activity and anxiety. Moreover, It prevents human fibroblasts differentiation and collagen deposition induced by TGF-β.

In summary, AM251 is a selective CB₁ receptor antagonist. CB1 may be a molecular target for wound healing disorders.

Reference:

Bialuk I, et al. Pharmacol Rep. 2011;63(3):670-679.; Correia-Sá IB, et al. Eur J Pharmacol. 2021;892:173738.