An antagonist binds that to a CB2 receptor and stops or slows the expected response an agonist at the same site would induce (see below).
CB2 Antagonism Associated Effects
Blocked CBD-induced weight loss (B. Ignatowska-Jankowska et al., 2011).1
CB2 inverse agonism increased CB2 expression associated with mitigating colitis pathologies (S. Kiran et al., 2022).2
CB2 Antagonists
One of the first reported potent, selective antagonists of CB2 includes the synthetic cannabinoid SR-144528. The researchers report a Ki of 0.6 nM (M. Rinaldi-Carmona et al., 1998).3 The authors posit that research into the effects of SR-144528 will provide novel insights into ECS-based effects on the immune system.
AM-630 (K. Hosohata et al., 1997).4 AM630 blocked CBD-induced weight loss (B. Ignatowska-Jankowska et al., 2011).5
SMM-189, a CB2 inverse agonist, increased the expression of CB2 receptor sites in colon lamina propria lymphocytes and reversed colitis-associated pathogenesis (S. Kiran et al., 2022).6
CBD displays inverse agonism at CB2. Furthermore, the authors also report that CBD has high potency (in vitro) as an antagonist of both CB1 and CB2 receptor agonists (A. Thomas et al., 2007).7
Endnotes:
1. Ignatowska-Jankowska B, Jankowski MM, Swiergiel AH. Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors. Neurosci Lett. 2011 Feb 18;490(1):82-4.
2. Kiran S, Rakib A, Moore BM, Singh UP. Cannabinoid Receptor 2 (CB2) Inverse Agonist SMM-189 Induces Expression of Endogenous CB2 and Protein Kinase A That Differentially Modulates the Immune Response and Suppresses Experimental Colitis. Pharmaceutics. 2022 Apr 26;14(5):936.
3. Rinaldi-Carmona M, Barth F, Millan J, Derocq JM, Casellas P, Congy C, Oustric D, Sarran M, Bouaboula M, Calandra B, Portier M, Shire D, Brelière JC, Le Fur GL. (1998). SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J Pharmacol Exp Ther. 284(2):644-50.
4. Hosohata K, Quock RM, Hosohata Y, Burkey TH, Makriyannis A, Consroe P, Roeske WR, Yamamura HI. (1997) AM630 is a competitive cannabinoid receptor antagonist in the guinea pig brain. Life Sci. 61(9):PL115-8.
5. Ignatowska-Jankowska B, Jankowski MM, Swiergiel AH. Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors. Neurosci Lett. 2011 Feb 18;490(1):82-4.
6. Kiran S, Rakib A, Moore BM, Singh UP. Cannabinoid Receptor 2 (CB2) Inverse Agonist SMM-189 Induces Expression of Endogenous CB2 and Protein Kinase A That Differentially Modulates the Immune Response and Suppresses Experimental Colitis. Pharmaceutics. 2022 Apr 26;14(5):936.
6. Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. (2007). Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 150(5):613-23.
