An antagonist binds to a CB1 receptor and stops or slows the expected response an agonist at the same site would induce (see below).
CB1 Agonism vs Antagonism
CB1 agonism and CB1 antagonism tend to induce opposing effects. For instance, THC is an agonist at CB1 and can cause a dose-dependent euphoria, while THCV and antagonist at CB1 can induce a dose-dependent dysphoria.
CB1 Antagonism Associated Effects
High ECS-based tone or excessive CB1 signaling has been associated with obesity, metabolic syndrome, diabetes (type-2), diabetes-induced cardiomyopathy, and fibrosis of the liver and the lungs (G. Dörnyei et al., 2023).1 More specifically, in people with visceral fat deposits (deep in the abdomen), excessive CB1 signaling increases caloric intake and decreases energy expenditure, which may be corrected by CB1 antagonism (J. Tam et al., 2017).2
Improved glycemic control via SIRT1 (J. Liu et al., 2019)8
Improved diabetes-induced cardiomyopathy (M. Rajesh et al., 2012)9
Improved pulmonary and liver fibrosis (CB1 antagonism has therapeutic potential)(R. Cinar et al., 2020).10
Duchenne muscular dystrophy (CB1 antagonism mitigated locomotor deficits in animals) (F. Iannotti et al., 2018).11
THCV is a CB1 antagonist with a mean Ki of ~84nM using data from 5 trials (J. McPartland et al., 2015).12
Rimonabant (a.k.a. SR-141716) was approved in the EU to treat obesity (2006). However, while effective in reducing signs and symptoms associated with obesity, it was later withdrawn (2008) due to psychiatric adverse effects (A. Samat et al., 2008).13
The synthetic cannabinoid AM4113 is a CB1 receptor antagonist associated with reducing food intake (N. Cluny et al., 2011).14
Dual CB1 antagonists and CB2 agonists include the synthetic cannabinoids GW405833 and AM1710 (A. Dhopeshwarkar et al., 2017).15
Hemopressin (derived from the α1 chain of hemoglobin) is an antagonist at CB1 (A. Heimann et al., 2007).16
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