Diclofenac and dexamethasone modulate the effect of cannabidiol on the rat colon motility ex vivo.

Introduction: Due to the growing interest in the use of cannabinoids in supportive therapies, they are increasingly used together with anti-inflammatory drugs. Cannabinoids inhibit gastrointestinal motility, while steroidal and nonsteroidal anti-inflammatory drugs influence motility in other ways. The aim of the research was to study the interactions between cannabidiol (CBD) and these two classes of anti-inflammatory drugs in the context of gastrointestinal motility. Dexamethasone (DEX) was selected as a steroidal drug and diclofenac (DCF) as a nonsteroidal counterpart.

Material and methods: The experiments were performed on isolated rat colon strips in isometric conditions. The contractile response to acetylcholine (ACh) (1 μM) was measured with no substance applied as a control value and was measured after application of CBD (80 μM), DEX (100 μM), DCF (100 μM), or a combination of these substances.

Results: Cannabidiol strongly inhibited intestinal motility mediated by ACh application, DCF inhibited it non-significantly, while DEX intensified it. When CBD was co-administered with DEX, the combination inhibited intestinal motility non-significantly relative to the ACh-only control. Co-administration of CBD with DCF inhibited motility more than when these substances were administered separately.

Conclusion: Inhibition of the intestinal response to ACh is likely due to the synergistic effect of CBD and endogenous cannabinoids. Dexamethasone lessened the inhibitory effect of CBD, likely because of diminished availability of the arachidonic acid necessary for endogenous cannabinoid synthesis. However, diclofenac may increase endogenous cannabinoid synthesis, because of the greater availability of arachidonic acid caused by DCF blocking the cyclooxygenation pathway.