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

Meltzer A.; Cooper Z.; Heidish R.; Loganathan A.; Loganathan T.; Bolden T.; Lagunazad I.; Perkins J.; Jaatinen K.; Adelman J. et al. · Journal of cannabis research · 2026

**Background & Methods** This pilot study employed whole-blood RNA sequencing to investigate transcriptomic differences in cannabinoid hyperemesis syndrome (CHS), a paradoxical disorder characterized by recurrent vomiting despite chronic cannabis use. Seven patients with suspected CHS presenting to the emergency department were compared with seven matched controls, with differential gene expression analysis supplemented by digital HLA isotyping. **Key Findings** - Suspected CHS was associated with marked adaptive immune system activation, including upregulation of B-cell-related immunoglobulin transcripts and altered expression of T cell, monocyte, and neutrophil-related transcripts - Differentially expressed genes suggested increased matrix degradation alongside reduced adhesion and protease inhibitor transcripts, potentially explaining the gastrointestinal complications observed in CHS - Digital HLA isotyping revealed increased MHC Class I expression, Class II allele restriction, and downregulation of IgE receptor transcripts, consistent with patterns seen in allergic hypersensitivity responses **Dosage & Administration** Not reported. The study did not specify cannabis dosage, frequency, or route of administration in enrolled patients. **Safety & Adverse Effects** Not reported. The study focused on transcriptomic characterization rather than formal safety monitoring or adverse effect documentation. CHS itself is characterized by recurrent vomiting, which represents the defining clinical manifestation under investigation. **Evidence Quality** This pilot study carries significant limitations that restrict evidence quality. The extremely small sample size (n=7 per group) severely limits statistical power and generalizability. The study is cross-sectional and observational, precluding causal inference regarding the relationship between identified transcriptomic changes and CHS pathogenesis. Patient phenotyping was described as "suspected" rather than confirmed CHS, introducing diagnostic uncertainty. The authors acknowledge these limitations and explicitly state findings are preliminary, laying groundwork for future studies. No information regarding control matching criteria specificity, potential confounding variables, or statistical correction for multiple comparisons is provided. The study represents exploratory research rather than confirmatory evidence, suitable for hypothesis generation but insufficient for clinical decision-making or therapeutic development without substantial additional validation in larger, prospectively characterized cohorts.

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