Browsing by Author "Svendsen, Kristofer"

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    Non-Psychotropic cannabinoids attenuate visceral pain in colitis
    (2023-05-25) Svendsen, Kristofer; Altier, Christophe; Sharkey, Keith; Nasser, Yasmin; Trang, Tuan; Ma, Chris
    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.