P084 Cannabis use promotes lymphocyte responsiveness and modifies T-cell signalling in adolescent IBD patients

M. Sanctuary1, C. Wilkinson2, A. Jones2, B. Murphy3, E. Hoffenberg3, C. Collins4

1University of Colorado Denver, Mucosal Inflammation Program, Pediatrics, Aurora, USA, 2University of Colorado, Mucosal Inflammation Program, Pediatrics, Aurora, USA, 3Children’s Hospital Colorado, Pediatrics, Aurora, USA, 4University College Dublin, Pharmacology, Dublin, Ireland

Background

The prevalence of inflammatory bowel disease (IBD) has increased dramatically in recent years, particularly in paediatric populations. The efficacy of available therapies is limited and often transient, leading patients to seek alternative therapies for symptom relief, including the use of medical marijuana (Cannabis sativa). There is some evidence to suggest that cannabinoids exert anti-inflammatory effects in preclinical colitis models. In addition, a number of small studies have reported improvements in non-empirical disease measures and reductions in visceral pain in response to cannabis use. However, associations between cannabis use in IBD and increased need for surgical interventions have also been reported.

Methods

Therefore, determining the direct impact of cannabis use on immune modulation in IBD patients is of critical importance. Blood samples collected from paediatric IBD patients who reported cannabis use for symptom control were analysed for cytokine expression and T-cell signalling pathway activation compared with non-users. Concentrations of serum phytocannabinoids were determined by HPLC and correlated with subsequent ex vivo assay parameters.

Results

Results demonstrated elevated levels of a myriad of pro-inflammatory cytokines in users vs. non-users upon ex vivo restimulation. This coincided with an expansion of pathogenic Th17 cells in the periphery. Differences in signalling cascades of activated T cells between users and non-users were also observed.

Conclusion

These results suggest that cannabis exposure, which can desensitise cannabinoid receptors, may prime pro-inflammatory pathways in paediatric IBD patients. Future studies should address the limitations of observational studies through the use of randomised controlled trials of cannabis use in paediatric IBD populations.

This research was funded by the Colorado Department of Public Health and Environment.