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.
Project description:Accessible in vitro models recapitulating the human airway that are amenable to study whole cannabis smoke exposure are needed for immunological and toxicological studies that inform public health policy and recreational cannabis use. In the present study, we developed and validated a novel 3D printed In Vitro Exposure System (IVES) that can be directly applied to study the effect of cannabis smoke exposure on primary human bronchial epithelial cells. Using commercially available design software and a 3D printer, we designed a four-chamber Transwell® insert holder for exposures to whole smoke. Software was used to model gas distribution, concentration gradients, velocity profile and shear stress within IVES. Following simulations, primary human bronchial epithelial cells cultured at air-liquid interface on Transwell® inserts were exposed to whole cannabis smoke. IVES represents an accessible, open-source, exposure system that can be used to model varying types of cannabis smoke exposures with human airway epithelial cells grown under air-liquid interface culture conditions.
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.
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.
Project description:Primary glioma stem cells cultured as neurospheres in NBL media with growth factors were subjected to treatment with the non-toxic, non-psychoactive cannabis compound cannabidiol (CBD). Control and CBD- treated cultures were used to generate RNA used to hybridize on Affymetrix DNA arrays Fluorescence intensities data were RMA-normalized using Partek software.
Project description:Medical cannabis has been increasingly prescribed for a range of conditions including epilepsy, chronic neuropathic pain, and chemotherapy-induced nausea and vomiting. The benefits and possible adverse events of medical-grade cannabis products vary between patients, suggesting that genetics may play a role in the pharmacokinetics of the cannabinoids, yet regulatory restrictions have led to limited clinical studies. This study is aimed at identifying a genetic signature that is predictive of the pharmacokinetics of tetrahydrocannabinol (THC), the principal intoxicating chemical compound derived from cannabis. We have identified 55 variants among 38 genes that were overrepresented in either the Low-THC or High-THC groups.
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.
Project description:<p>Cannabis and stimulants are among the most widely used illicit drug in the United States, and their use is associated with substantial physical and psychiatric sequelae. Twin studies have shown a substantial genetic component to the etiology of cannabis and stimulant use disorders, but, genome-wide association studies using genotype data obtained from microarrays have yielded few robust results. The advent of increasingly economical whole genome sequencing provides new opportunities to identify trait-associated sequence variations. The present study proposes to identify sequence variants that affect stimulant and cannabis dependence in three cohorts. The three study cohorts were ascertained as part of the Mission Indian Study (PI Cindy Ehlers), the combined Yale-University of Connecticut Addiction Study samples (PI Joel Gelernter) and the San Francisco Family Study (PI Kirk Wilhelmsen). Because three populations with different continental origins were studied, the present study will also ascertain whether the major genetic risk factors for the traits of interest are shared or population-specific. </p>