Search

Background Purpose Classical antiemetics that target the serotonin system may not be effective in treating certain nausea and vomiting conditions like cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS). As a result, there is a need for better therapies to manage the symptoms of these disorders, including nausea, vomiting, and anxiety. Cannabis is often used for its purported antiemetic and anxiolytic effects, given regulation of these processes by the endocannabinoid system (ECS). However, there is considerable evidence that cannabinoids can also produce nausea and vomiting and increase anxiety in certain instances, especially at higher doses. This paradoxical effect of cannabinoids on nausea, vomiting, and anxiety may be due to the dysregulation of the ECS, altering how it maintains these processes and contributing to the pathophysiology of CVS or CHS.The purpose of this review is to highlight the involvement of the ECS in the regulation of stress, nausea, and vomiting. We discuss how prolonged cannabis use, such as in the case of CHS or heightened stress, can dysregulate the ECS and affect its modulation of these functions. The review also examines the evidence for the roles of ECS and stress systems' dysfunction in CVS and CHS to better understand the underlying mechanisms of these conditions. [ABSTRACT FROM AUTHOR]

Background: Amitriptyline (AT) is recommended as first‐line prophylactic therapy in patients with cyclic vomiting syndrome (CVS). However, significant side effects limit its use and dosing is based on trial and error. Though the Clinical Pharmacogenetic Implementation Consortium (CPIC) Guidelines recommend dosing for AT based on CY2D6 and CYP2C19 genotype profile, this is not followed in clinical practice. Methods: This pilot study determined CYP2C19 and CYP2D6 genotypes and ascertained its association with adverse drug reactions (ADRs), clinical response, and serum concentration of AT and nortriptyline in a well‐characterized cohort of adults with CVS. Key Results: Of 46 subjects with CVS, age 33 ± 12 years, 61% female, 85% Caucasian, a third (33%) had normal CYP2C19 metabolizer status, while 4% were poor, and 43% were ultrarapid metabolizers. Most (61%) had normal CYP2D6 genotype while 9% were poor and 2% were ultra‐rapid metabolizers. There was no statistically significant association between genotype and ADRs, clinical response or serum drug concentration. There was a trend towards significance between genotype and clinical response, with 64% of responders having normal CYP2D6 metabolism versus 36% of nonresponders (p = 0.06). ADRs were encountered in 46% of patients with 28% discontinuing the medication as a result. Conclusions and Inferences: A subset of patients with CVS have dysfunctional alleles of CYP2C19 and CYP2D6. Larger prospective studies to evaluate the clinical impact of pharmacogenomic testing in CVS are needed. This has the potential to optimize clinical management, predict ADRs and allow for personalized therapy. [ABSTRACT FROM AUTHOR]

Background: Cyclic vomiting syndrome (CVS) is a disorder of gut–brain interaction (DGBI) characterized by recurrent episodes of nausea and vomiting. Most children outgrow their CVS symptoms and develop migraine headaches, but there are limited data in adults. We thus sought to determine the natural history of CVS in adults. Methods: We conducted a retrospective analysis of patients at a specialized tertiary care clinic. Frequency of CVS episodes, emergency department (ED) visits, and hospitalizations were recorded at the index visit and at follow‐up. Key Results: Of 455 CVS patients with complete data, mean age was 33 ± 13 years, 294 (65%) were female, and 392 (86%) were Caucasian. Mean duration of follow‐up was 47.4 ± 37.2 months. There was a significant reduction in frequency of CVS episodes/year (18 to 6.8), ED visits (6.1 to 2), and hospitalizations (2.3 to 0.7) (all p‐values < 0.001) but only 88 (19%) of patients had complete resolution of episodes at follow‐up. On multivariable regression analysis, non‐white race [0.33 (0.11–0.98) p = 0.01], comorbidity count [0.77 (0.62–0.95) p = 0.01], cannabis use [0.36 (0.2–0.65) p = 0.0007], and aprepitant use [0.2 (0.08–0.005) p < 0.001] were associated with a reduced odds of complete resolution of CVS episodes. Of note, 19 patients (4%) died. Conclusions and Inferences: While most adults with CVS improved with specialized care, in contrast to children, only a small subset (~1 in 5) had complete resolution of symptoms. Reasons for the effects of race, cannabis use, and comorbidity burden on outcomes in CVS are unclear and warrant further investigation. [ABSTRACT FROM AUTHOR]