Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation
Open accessAbstract
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 ATP-binding 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.
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Long-term use is associated with risk of cannabis use disorder, hyperemesis syndrome, as well as withdrawal symptoms including insomnia, anxiety, depression, and tremulousness.
“Long-term use is associated with risk of cannabis use disorder, hyperemesis syndrome, as well as withdrawal symptoms including insomnia, anxiety, depression, and tremulousness.125,126”
From Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions (2024) · cites this paper as [126]
The Introduction describes cannabinoid hyperemesis syndrome in the context of heavy, chronic THC exposure. The Results (Survey findings) report cannabis dependency or addiction diagnoses and withdrawal symptoms including anxiety, depression, and insomnia. The paper does not identify tremulousness as a withdrawal symptom, so that part of the claim is unsupported. (LLM, conf=0.86)
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- Authors
- Russo, E. B., Spooner, C., May, L., Leslie, R., & Whiteley, V. L.
- Affiliations
- CReDO Science, Vashon, Washington, USA.
- Paradigm Naturopathic Medicine, Vernon, Canada.
- Endocanna Health, Los Angeles, California, USA.
- Corresponding author
- Russo, Ethan B.
- ORCID
- Russo, Ethan B.
- Venue
- Cannabis & Cannabinoid Research
- Publisher
- SAGE Publications
- Published
- 2022-06-01
- Volume
- 7
- Issue
- 3
- Pages
- 336-344
- ISSN
- 2378-8763 (ISSN-L)
- 2578-5125
- PMC
- PMC9225400
- OpenAlex
- W3181384455
- Cited by
- 42
- References
- 42
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 11 · 2023: 4 · 2022: 9 · 2021: 1
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cannabis and Cannabinoid Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
- Keywords
- cannabinoid hyperemesis syndrome, tetrahydrocannabinol, cannabis use, genetic mutations, catechol-O-methyltransferase, TRPV1, CYP2C9, DRD2, ABCA1, endocannabinoid system, cytochrome P450, cannabis withdrawal, cannabis cessation, nausea and vomiting, cannabis concentrates, cannabis flower
- MeSH terms
- Cannabinoids, Cannabis, Female, Hallucinogens, Humans, Hyperemesis Gravidarum, Pregnancy, Surveys and Questionnaires, Dronabinol, Genomics, Cannabinoid Receptor Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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