Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation

Abstract

Background: Cannabinoid hyperemesis syndrome (CHS) is a diagnosis of exclusion with intractable nausea, cyclic vomiting, abdominal pain, and hot bathing behavior associated with ongoing tetrahydrocannabinol (THC) exposure. Increasing cannabis use may elevate CHS prevalence, exacerbating a public health issue with attendant costs and morbidity. Objective, Design, and Data Source: This study, the largest contemporaneous database, investigated genetic mutations underlying CHS. Patients with CHS diagnosis and ongoing symptoms were compared with current cannabis users lacking symptoms. Target Population: A screening questionnaire was posted online. Of 585 respondents, 205 qualified as the CHS pool and 54 as controls; a reduced pool of 28 patients and 12 controls ultimately completed genomic testing. Results: Patients and controls were high-frequency users of cannabis flower or concentrates (93%), using multiple grams/day of THC-predominant material. Among patients, 15.6% carried diagnoses of cannabis dependency or addiction, and 56.6% experienced withdrawal symptoms. About 87.7% of patients improved after cannabis cessation, most suffering recurrence rapidly after resumption. Findings in patients included mutations in genes COMT {odds ratio, 12 (95% confidence limit [CL], 1.3-88.1) p = 0.012}, transient receptor potential vanilloid receptor 1 (TRPV1) (odds ratio, 5.8 [95% CL, 1.2-28.4] p = 0.015), CYP2C9 (odds ratio, 7.8 [95% CL, 1.1-70.1] p = 0.043), gene coding dopamine-2 receptor (DRD2) (odds ratio, 6.2 [95% CL, 1.1-34.7] p = 0.031), and ATPbinding cassette transporter gene (ABCA1) (odds ratio, 8.4 [95% CL, 1.5-48.1] p = 0.012). Limitations: Some participants were reluctant to undergo genetic testing; only 28 of 99 CHS patients who agreed to testing ultimately returned a kit. Conclusion: This is the largest patient cohort of CHS examined to date, and first to note associated mutations in genes affecting neurotransmitters, the endocannabinoid system, and the cytochrome P450 complex associated with cannabinoid metabolism. Although the sample size was smaller than desired, these preliminary findings may contribute to the growing body of knowledge, stimulate additional investigation, help elucidate the pathophysiology of CHS, and, ultimately, direct future treatment.

Cannabinoid Conference 2022

“…Dental Plaque CBD/CBG • Transdermal/ sublingual (mouthwash) [8] [9] karger@karger.com www.karger.com/mca Introduction: Genetics may influence experience with cannabis and CBD. With increased access to legal cannabis and the research community expanding their focus on the medicinal uses of cannabinoids, more and more consumers are seeking cannabis for health and wellness.…”

“…A peer reviewed approved study was published as a partial example of study findings. Western IRB, peer reviewed, and first to note associated mutations in genes affecting the ECS and neurotransmitter systems that may elucidate the pathophysiology of these adverse events [8]. Keywords: DNA, genomics, genotyping, personalization, endocannabinoid, terpenes, cannabinoids.…”

Cannabinoid hyperemesis syndrome and cannabis withdrawal syndrome: a review of the management of cannabis-related syndrome in the emergency department

“…Unfortunately, in addition to these tests, many patients undergo more invasive diagnostic tests such as CT, endoscopy, and occasionally exploratory laparoscopy, which often fail to find an alternative cause and expose the patient to potential complications [ 15 , 18 ]. Screening of genetic predispositions may also provide some benefit in differential diagnosing, though this would not be of use in the acute setting; as of publication, 5 mutations have been identified as potentiators of CHS (COMT, TRPV1, CYP2C9, DRD2, and ABCA1) [ 7 ].…”

“…This overstimulation is thought to be multifactorial and relates in part to the lipophilic properties of cannabinoids, which store in body fat and are subsequently released in chronic users (whose reserves are elevated from continuous intake) [5,6]. The fact that not all chronic users develop CHS suggests genetic predisposition, a feature recently described, via the identification of five gene mutations which seem to confer some level of protection from paradoxical effects of overstimulation of the endocannabinoid system [7].…”

The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?

“…The components of the ECS are found in many cell types within the GI tract, including the ENS. Not surprisingly, exogenously administered cannabinoids have profound effects that may be beneficial for the treatment of some GI conditions [ 14 , 17 , 18 , 19 ], and adverse GI effects of their use have also been recognized (i.e., cannabinoid hyperemesis [ 20 , 21 ] and small bowel intussusception, [ 22 ]). However, the relationship between the components of the ECS and EGCs and the mechanism by which nutraceuticals may act through them have not been well established yet.…”