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.
However, many works have repeatedly associated polymorphisms in the CNR1 and FAAH genes with drug-related behaviours; this suggests that these genes should be examined in further genetic studies focusing on drug addiction and other psychiatric disorders.
The relationship between the FAAH A/A genotype and risk for drug dependence in this study was drug class specific, suggesting it is not part of a more general drug abuse effect.
Here, we investigated the relationship of the FAAHP129T variant to a number of linked single nucleotide polymorphisms to establish a haplotyping system, calculate the estimated age and origin of the FAAH 385 C-->A mutation and evaluate its association with clinically significant drug addiction in a case control study.
Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia.
These findings, although preliminary, suggest that the CNR1 1359 G/A and the FAAH cDNA 385C to A gene variants may contribute to the susceptibility to mood disorders.
Owing to the importance of endocannabinoid system in addiction, the Pro129Thr polymorphism in the FAAH gene has reportedly been associated with substance abuse and dependence in a Caucasian population.
Two single nucleotide polymorphisms (SNPs) in the CNR1 (rs2023239) and FAAH (rs324420) genes, associated previously with substance abuse and functional changes in cannabinoid regulation, were examined in a sample of daily marijuana smokers.
Consistent with this, carriers of a low-expressing FAAH variant (385A allele; rs324420) exhibited quicker habituation of amygdala reactivity to threat, and had lower scores on the personality trait of stress-reactivity.
Although a link between the FAAHP129T variant and human drug abuse has been reported, the extent of risk and specific types of substance addiction vulnerability remain to be determined.
We assessed the CB1 receptor gene (CNR1) single nucleotide polymorphism (SNP) rs1049353 (rs1049353" genes_norm="1268">1359 G/A) and the fatty acid amide hydrolase (FAAH) gene rs324420 SNP (cDNA 385C to A) for their associations with MD and/or BD in 83 Caucasian patients with recurrent MD, 134 Caucasian individuals with BD, and 117 Caucasian healthy subjects.
We assessed the CB1 receptor gene (CNR1) single nucleotide polymorphism (SNP) rs1049353 (rs1049353" genes_norm="1268">1359 G/A) and the fatty acid amide hydrolase (FAAH) gene rs324420 SNP (cDNA 385C to A) for their associations with MD and/or BD in 83 Caucasian patients with recurrent MD, 134 Caucasian individuals with BD, and 117 Caucasian healthy subjects.
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.
Here, we designed dual inhibitors targeting the enzymes FAAH and soluble epoxide hydrolase (sEH), which are targets previously shown to synergize at reducing inflammatory and neuropathic pain.
We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity.
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.
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.
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.
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.