The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression--and probably also for co-morbid psychiatric conditions such as substance use disorders--through a high neuroticism and low agreeableness phenotype.
As evidence continues to accumulate, neutral CB1R antagonists (such as AM4113), CB2R agonists (JWH133, Xie2-64), and nonselective phytocannabinoids (cannabidiol, β-caryophyllene, ∆<sup>9</sup>-tetrahydrocannabivarin) have shown great therapeutic potential for SUDs, as shown in experimental animals.
Cellular signaling mediated by CB1R is involved in numerous physiological processes, and pharmacological CB1R modulation is considered a tenable therapeutic approach for diseases ranging from substance-use disorders and glaucoma to metabolic syndrome.
A total of 110 adult patients with ASD (n=61) or ADHD (n=49) with or without a lifetime history of SUD participated in a study in which we genotyped polymorphisms in five known candidate genes for (one of) the disorders, i.e. the 5HTTLPR in SLC6A4/5-HTT, rs1800497 (TaqIA C>T) in DRD2, rs7794745 in CNTNAP2, rs1843809 in TPH2, and rs6565113 in CDH13.
Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder.
A single nucleotide polymorphism (SNP) in the gene encoding for fatty acid amide hydrolase (FAAH) has demonstrated association with substance use disorder diagnoses, but has not been studied with respect to these narrower phenotypes.
Since then, much research interest has shifted to other cannabinoid-based strategies, such as peripheral CB1R antagonists/inverse agonists, neutral CB1R antagonists, allosteric CB1R modulators, CB2R agonists, fatty acid amide hydrolase (FAAH) inhibitors, monoacylglycerol lipase (MAGL) inhibitors, fatty acid binding protein (FABP) inhibitors, or nonaddictive phytocannabinoids with CB1R or CB2R-binding profiles, as new therapeutics for SUDs.
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.
Polymorphisms in the gene encoding the brain serotonin synthesis enzyme Tph2 have been identified in mental illnesses, with co-morbidity of substance use disorder.
A total of 110 adult patients with ASD (n=61) or ADHD (n=49) with or without a lifetime history of SUD participated in a study in which we genotyped polymorphisms in five known candidate genes for (one of) the disorders, i.e. the 5HTTLPR in SLC6A4/5-HTT, rs1800497 (TaqIA C>T) in DRD2, rs7794745 in CNTNAP2, rs1843809 in TPH2, and rs6565113 in CDH13.
The finding that lower stress-related NPY is predictive of greater relapse severity provides support for therapeutic development of neuropeptide Y targets in the treatment of substance use disorders.
Although there has been some work examining the effect of human glutamate metabotropic receptor 7 (GRM7) polymorphisms on human substance use disorders, the majority of the work has focused on other psychiatric disorders such as ADHD, major depressive disorder, schizophrenia, bipolar disorder, panic disorder, and autism spectrum disorders.
Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators.