Whole-blood transcriptomic findings in emergency department patients with suspected cannabinoid hyperemesis syndrome: a pilot study

Abstract Background Cannabinoid hyperemesis syndrome (CHS) is a paradoxical and increasingly prevalent disorder characterized by recurrent vomiting in people with chronic cannabis use. Despite its growing clinical impact, the underlying mechanisms remain poorly understood. Methods Genome-wide RNA sequencing was used to characterize transcriptomic differences and identify potential pathways involved in CHS pathogenesis. In this pilot study, whole blood RNA sequencing was performed on 7 patients with suspected CHS and 7 matched controls. Differentially expressed genes (DEGs) were identified, annotated and analyzed by automated and manual analysis. RNA sequences were further analyzed by digital isotyping for HLA Class I and II allele usage. Results Suspected CHS was associated with marked activation of the adaptive immune system, including upregulation of B-cell related immunoglobin transcripts and altered expression of T cell, monocyte, and neutrophil-related transcripts. DEGs also suggested increased matrix degradation, and reduced adhesion and protease inhibitor transcripts. Digital HLA isotyping revealed increased MHC Class I expression, Class II allele restriction, and down-regulation of IgE receptor transcripts, a known response to elevated IgE levels in allergic hypersensitivity. Conclusions Together, these preliminary findings identify immune-related signals in ED patients with suspected CHS, and lay the groundwork for future studies with larger, prospectively phenotyped cohorts to identify biomarkers, clarify immune triggers, and develop targeted therapies.