Research Status on Cannabinoid Hyperemesis Syndrome
Research on CHS is limited but growing, with the evidence base consisting primarily of case reports, case series, and small observational studies rather than high-quality randomized controlled trials. 1
Current State of the Evidence
The research landscape for CHS reveals significant gaps in high-quality evidence:
Management evidence is limited to case series and small clinical trials, not robust randomized controlled trials that would provide definitive treatment guidance 1
A 2017 systematic review identified only 2,178 articles initially, with just 183 meeting inclusion criteria after screening—and among these, there were only 4 prospective level-2 studies, 3 retrospective level-3 studies, 12 level-4 case series, and 44 level-5 case reports involving 205 total subjects 2
No large-scale randomized controlled trials exist for acute or long-term pharmacologic management of CHS 2
What Research Does Exist
Diagnostic and Epidemiologic Studies
One systematic review compiled 271 cases of CHS to characterize the typical patient profile (mean age 30 years, 69% male, 6.6 years of cannabis use before onset) 1
CHS was first reported in 2004, making it a relatively recently recognized condition with an evolving evidence base 3
Pathophysiology Research
Research has identified potential mechanisms involving CB1 receptor dysregulation in the dorsal vagal complex and loss of negative feedback on the hypothalamic-pituitary-adrenal axis 1, 4
A 2022 genomic investigation examined only 28 CHS patients and 12 controls, identifying potential genetic mutations in COMT, TRPV1, CYP2C9, DRD2, and ABCA1 genes—but acknowledged the sample size was smaller than desired 5
Treatment Studies
Preliminary evidence from 2 small placebo-controlled randomized studies suggests fatty acid amide hydrolase inhibitors and CBD may reduce cannabis use, but larger studies are necessary 1
Most treatment recommendations are based on case reports and small case series rather than controlled trials 1, 2
Critical Knowledge Gaps
The pathophysiology of CHS remains unclear with a dearth of research dedicated to investigating its underlying mechanism 6
Prevalence data is unknown because of symptomatic overlap with other disorders and lack of awareness among clinicians and patients 7
CHS is frequently underdiagnosed or misdiagnosed due to limited clinician awareness 8
Future prospective trials are greatly needed to evaluate and define optimal pharmacologic treatment 2
Clinical Implications of Limited Research
Despite limited high-quality evidence, clinical guidelines have been developed:
CHS was included in the Rome IV classification of functional gastrointestinal disorders in 2016, providing formal diagnostic recognition 1
The American Gastroenterological Association published clinical practice updates in 2024 synthesizing available evidence into practical recommendations 1, 9
Treatment recommendations rely heavily on expert consensus and clinical experience rather than robust trial data 1
The bottom line: Research on CHS is sparse and of limited quality, consisting mainly of case reports and small observational studies, with an urgent need for large-scale prospective trials to establish evidence-based diagnostic criteria and treatment protocols. 6, 2, 7