ABCB1 polymorphisms are associated with clinical response to nabiximols in patients with multiple sclerosis-related spasticity

Genetic factors represent crucial contributors to variability in drug.In particular, single nucleotide polymorphisms (SNPs) may predict drug, efficacy and safety in many clinical settings (Reviewed in Owusu Obeng et al. 2021).Both THC and CBD act on cannabinoid receptors (CBR) 1 and 2, which are encoded by the cannabinoid receptor genes (CNR) 1 and 2 (Martini et al. 2023).SNPs in CNR1, such as rs1049353 and rs2023239 and in CNR2 (rs2501431), influence various receptor functions, including depression (Mitjans et al. 2012), happiness perception (Matsunaga et al. 2014) and childhood obesity (Col Araz et al. 2012).THC and CBD are substrates for P-glycoprotein (P-gp), an efflux pump encoded by the ATP Binding Cassette Subfamily B Member 1 (ABCB1) gene (Martini et al. 2023).SNPs in the ABCB1, such as rs1128503 and rs1045642, have been associated with interindividual variability in drug response (Brambila-Tapia 2013), including response to cannabinoids (Babayeva et al., 2023).These polymorphisms have also been proposed as potential predictors of individual responses to analgesics, including opioids (Fernandez et al., 2012) and cannabisbased treatments (Poli et al. 2022).Additionally, THC and CBD are metabolized by the CYP450 enzyme family, by CYP2C9, CYP2C19, and CYP3A4 (Martrini at al.,