Transcriptomic Evidence of Acquired Cannabis Hypersensitivity in Cannabinoid Hyperemesis Syndrome
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ABSTRACT:
PROVIDER: PRJNA1298242 | ENA |
REPOSITORIES: ENA
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Project description: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. Contrary to prevailing hypotheses implicating the endogenous cannabinoid system (ECS), we found no significant changes in ECS-related transcripts. Instead, 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, consistent with impaired gut barrier function. 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. Together, these findings suggest that CHS may represent an acquired, gut-restricted, immune-mediated hypersensitivity response to cannabis. This transcriptomic analysis provides new mechanistic insights into CHS and lays groundwork for future studies to identify biomarkers, clarify immune triggers, and develop targeted therapies.
2025-08-01 | GSE303922 | GEO
Project description:We evaluated cutaneous contact hypersensitivity (CHS) in Cnr1-/-/Cnr2-/- animals using the obligate contact allergen 2,4-dinitrofluorobenzene (DNFB), which generates a specific cutaneous T-cell mediated allergic response upon repeated allergen contact. Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated whereas receptor agonists attenuated allergic inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin, and suggest a novel target for therapeutic intervention. Experiment Overall Design: Three wildtype mice (Wt) and three Cnr1-/-/Cnr2-/- (Ko) mice were used. Contact hypersensitivity was determined always at the right ears, which therefore were treated with DNFB (Tr). Left ears of mice were kept untreated and served as control ears (C). A total of 12 hybridizations were performed (2 strains x 2 treatments X 3 biological replicates) in this experiment.
2009-04-23 | E-GEOD-7694 | biostudies-arrayexpress
Project description:We evaluated cutaneous contact hypersensitivity (CHS) in Cnr1-/-/Cnr2-/- animals using the obligate contact allergen 2,4-dinitrofluorobenzene (DNFB), which generates a specific cutaneous T-cell mediated allergic response upon repeated allergen contact. Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated whereas receptor agonists attenuated allergic inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin, and suggest a novel target for therapeutic intervention. Keywords: Strain (Wt versus Ko) and disease state (DNFB treated versus control).
2007-06-11 | GSE7694 | GEO
Project description:In this study, we evaluated the common proteomic profile, as well as, the exclusively deregulated proteins in ON cells from healthy controls cannabis users (HC/c), SCZ patients non-cannabis users (SCZ/nc) and SCZ patients cannabis users (SCZ/c) as compared to healthy controls non-cannabis users (HC/nc). Moreover, we investigated quantitative and functional differences between HC/c and SCZ, and we characterized the distinct effect of cannabis in SCZ comparing SCZ/nc and SCZ/c.
2021-09-09 | PXD020739 | Pride
Project description:Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. Nonetheless, until now, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, has been unexplored. Here, we report that adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in the mouse model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings highlight the importance of microglial Cnr1 to produce the adverse effect of cannabis exposure in genetically vulnerable individuals.
2023-10-03 | GSE242892 | GEO
Project description:Cannabis sativa L. is a dioecious, annual herbaceous crop (2n = 20) known for its diverse applications across textile, food, cosmetic, and medicinal industries. Recent increases in global temperatures have raised concerns about the impact of heat stress on hemp physiology. Although previous studies have demonstrated reductions in photosynthetic efficiency and cannabinoid levels under heat stress, transcriptome-wide insights into molecular responses remain limited. In this study, we performed a genome-wide transcriptomic analysis to investigate the molecular mechanisms of heat stress response in C. sativa cv. Pink Pepper. This dataset provides a high-resolution transcriptomic resource to explore thermotolerance in C. sativa and contributes to a better understanding of its molecular adaptation to heat stress. The findings can aid future breeding and biotechnology efforts aimed at enhancing stress resilience in hemp.
2025-05-26 | GSE296859 | GEO
Project description:Cannabis use has been controversial, largely having been designated a controlled substance over the last century. The link between cannabis smoking and disease pathogenesis may best be explored through DNA methylation, an epigentic mechanism. We investigated the relationship between epigenetic age and cannabis smoking in participants within the Canadian Cohort of Obstructive Lung Disease (CanCOLD) cohort (n=93) (ClinicalTrials.gov identifier NCT00920348). Blood samples were profiled for DNA methylation using the Illumina MethylationEPIC BeadChipv1 at two separate laboratories and the blood epigenetic age of each sample was calculated using the Clock Foundation tool (https://dnamage.clockfoundation.org). An ANOVA was used to identify differences in the age acceleration residuals associated with cannabis smoking status (never, former, and current), adjusted for chronological age, sex, body mass index (BMI), batch, cigarette smoking status, and the first two principal components of blood cell proportions. Our observations indicated that current cannabis smoking and higher joint-years exposure are associated with epigenetic age acceleration; cessation, however, may help to normalize in part this age acceleration.
2024-07-01 | GSE255929 | GEO
Project description:Purpose: Globally, many jurisdictions are legalizing or decriminalizing cannabis, creating a potential public health issue that would benefit from experimental evidence to inform policy, government regulations, and user practices. Tobacco smoke exposure science has created a body of knowledge that demonstrates the conclusive negative impacts on respiratory health; similar knowledge remains to be established for cannabis. To address this unmet need, we performed in vitro functional and transcriptomic experiments with a human airway epithelial cell line (Calu-3) exposed to cannabis smoke, with tobacco smoke as a positive control. Results: We demonstrate that cannabis smoke induced functional and transcriptional responses that overlapped with tobacco smoke. Ontology and pathway analysis revealed that cannabis smoke induced DNA replication and oxidative stress responses. Functionally, cannabis smoke impaired epithelial cell barrier function, antiviral responses, and increased inflammatory mediator production. Our study reveals striking similarities between cannabis and tobacco smoke exposure on impairing barrier function, suppressing antiviral pathways, potentiating of pro-inflammatory mediators, and inducing oncogenic and oxidative stress gene expression signatures. LABA/GC intervention in airway epithelial cells exposed to cannabis smoke reduces levels of pro-inflammatory (CXCL8) and antiviral (CXCL10) mediators, while transcriptomic signatures of neutrophil mediated immunity and oxidative stress remain elevated. Conclusions: Collectively our data suggest that cannabis smoke exposure is not innocuous and may possess many of the deleterious properties of tobacco smoke, warranting additional studies to support public policy, government regulations, and user practices.
2020-01-28 | GSE125259 | GEO
Project description:Even if a large amount of high-throughput functional genomic data exists, most researchers feature a strong background in molecular biology but lack advanced bioinformatics skills. In this work, publicly available gene expression datasets have been analyzed giving rise to a total of 40,224 gene expression profiles within different Cannabis tissues/developmental stages. The resource here proposed will provide researchers with a starting point for future investigations of Cannabis sativa.
2017-01-13 | GSE93201 | GEO
Project description:DNaseI sensitivity/hypersensitivity
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