Cannabinoid Receptor Type 1 and mu-Opioid Receptor Polymorphisms Are Associated With Cyclic Vomiting Syndrome

Abstract

Our results show for the first time that the variations in CNR1 and OPRM1 genes are associated with CVS and that different genotypes may contribute to the risk of CVS.

Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults

“…27 Finally, recent insights have shown that polymorphisms in the cannabinoid receptor type 1 and m-opioid receptor genes are associated with CVS. 28 The description of cannabinoid hyperemesis syndrome, a variant of CVS, is intriguing given that cannabis traditionally has been used as an anti-emetic and appetite stimulant. The major psychoactive component in cannabis is 9-tetrahydrocannabinol, which after binding to cannabinoid type-1 receptors in the brain and gut activates the endocannabinoid system, an integral component in regulating nausea, vomiting, and gastrointestinal motility.…”

Cyclic vomiting syndrome is a prevalent and under‐recognized condition in the gastroenterology outpatient clinic

“…We did not address underlying pathophysiological mechanisms, another poorly studied area in CVS, although there have been a number of potential theories hypothesized previously. These include activation of the corticotrophin‐releasing factor signaling system, abnormal gastric motility, mitochondrial DNA mutations, and other genetic factors including variants in the RYR2 gene, which is involved in stress‐induced calcium channels in autonomic neurons, and polymorphisms in genes encoding endogenous cannabinoid and opioid receptors . In addition, we did not evaluate the subsequent management of these patients, an issue that has been highlighted in the literature as problematic for gastroenterologists, although we have reported data from our center regarding the treatment of CVS previously …”

“…These include activation of the corticotrophin-releasing factor signaling system, 41,42 abnormal gastric motility, 12,43 mitochondrial DNA mutations, 44,45 and other genetic factors including variants in the RYR2 gene, which is involved in stress-induced calcium channels in autonomic neurons, 46 and polymorphisms in genes encoding endogenous cannabinoid and opioid receptors. 47 In addition, we did not evaluate the subsequent management of these patients, an issue that has been highlighted in the literature as problematic for gastroenterologists, 13 although we have reported data from our center regarding the treatment of CVS previously. 48 In conclusion, the prevalence of CVS among adult patients in secondary care gastroenterology clinics in this study was 10.8%, but the diagnosis was considered in fewer than one-in-twenty individuals with typical symptoms, who had no structural explanation for these, and who likely had CVS.…”

Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions

“…27 Recently, the AG and GG genotypes of CB 1 receptor rs806380 were associated with an increased risk of CVS while the CC genotype of CB 1 receptor rs806368, and AG and GG genotypes of mu-opioid receptor rs1799971 were associated with a decreased risk of CVS. 28 This highlights a potential genetic basis for ECS dysregulation at the receptor level rather than an absolute deficiency of endocannabinoids in CVS and may indicate that some individuals may be genetically predisposed to develop cyclical emesis when chronically exposed to cannabis. Taken together, these observations suggest a role for the ECS in CVS and CHS with both genetic (ie, CB 1 receptor SNPs) and environmental (ie, exposure to high potency cannabis products) factors altering stress responses that may contribute to the development of core CVS/CHS symptoms.…”