This may explain the greater vulnerability for addiction and obesity in individuals with C385A genetic variant and by extension, suggest that a D3 antagonism strategy in substance use disorders should consider FAAHC385A polymorphism.
The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence.
The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant phenotype and risk for addictions.
Alterations in expression of a cannabinoid receptor (CNR1, CB1), and of fatty acid amide hydrolase (FAAH) that degrades endogenous ligands of CB1, may contribute to the development of addiction.
Moreover, this mutation appears to have arisen early in human evolution and this study validates the previous link between the FAAHP129T variant and vulnerability to addiction of multiple different drugs.
This SNP, which converts a conserved proline residue in FAAH to threonine (P129T), suggests a potential role for the FAAH-endocannabinoid system in regulating addictive behavior.