Non-Psychotropic cannabinoids attenuate visceral pain in colitis

The inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are complex chronic diseases that affect an increasing proportion of the population. Abdominal pain is a major clinical symptom, but current treatments are limited and a source of frustration for patients, many of whom seek alternatives such as cannabis. Cannabis contains many compounds with therapeutic potential that do not have the prohibitive psychotropic effects of tetrahydrocannabinol (THC). These non-psychotropic cannabinoids (npCBs) have a variety of effects including analgesia and anti-inflammatory actions and show potentiating effects when administered in combination. This project explored the analgesic effects of cannabichromene (CBC), cannabidiol (CBD), cannabidivarin (CBDV), and cannabigerol (CBG), individually and in combination, in the treatment of colitis-evoked visceral hypersensitivity use the acute dextran sulfate sodium model. Abdominal pain was quantified by electromyographic recordings of the reflexive contraction of the external oblique muscle in response to colorectal distension using an animal of experimental colitis. Activation of the spinal cord was assessed using immunohistochemistry to the neuronal activity marker c-Fos in neurons of the lumbosacral dorsal horn. A single injection intraperitoneal injection of 10 mg/kg of either CBD or CBG was found to reduce both nocifensive behaviors in the functional assay and c-Fos activity in spinal cord in animals with colitis. Similarly, a combination of npCBs consisting of 5 m/kg CBD with 1 m/kg each CBC, CBDV, and CBG—all sub-therapeutic dosages—reduced both measures to the level of untreated control animals. Investigations of mechanism of actions via whole-cell patchclamp electrophysiology of primary dorsal root ganglia neurons revealed CBD to act via a voltage-gated calcium channel with preliminary evidence indicating a high-voltage activated isoform. Preliminary data also suggest that the mixture of npCBs may act through a similar mechanism. These results suggest CBD, CBG, and a mixture of npCBs may be beneficial in managing pain associated with IBD.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Medicine – Neuroscience

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2023

Author dc:creator

• Svendsen, Kristofer

Advisors dc:contributor.advisor

• Altier, Christophe
• Sharkey, Keith

Committee members dc:contributor.committeemember

• Nasser, Yasmin
• Trang, Tuan
• Ma, Chris

• Cannabis
• Cannabinoids
• Cannabidiol
• Cannabigerol
• Pain
• Colitis

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

en

DOI

https://dx.doi.org/10.11575/PRISM/41430

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:1880/116587