The effects of Delta-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis.
OBJECTIVE
Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief. Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Delta(9)-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders. Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis.


METHODS
The 2,4,6-trinitrobenzene sulphonic acid (TNBS) model of acute colitis in rats was used to assess damage, inflammation (myeloperoxidase activity) and in vitro colonic motility. Sulphasalazine was used as an active control drug.


RESULTS
Sulphasalazine, THC and CBD proved beneficial in this model of colitis with the dose-response relationship for the phytocannabinoids showing a bell-shaped pattern on the majority of parameters (optimal THC and CBD dose, 10 mg.kg(-1)). THC was the most effective drug. The effects of these phytocannabinoids were additive, and CBD increased some effects of an ineffective THC dose to the level of an effective one. THC alone and in combination with CBD protected cholinergic nerves whereas sulphasalazine did not.


CONCLUSIONS
In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects.
Jamontt
J M
JM
School of Life Sciences, University of Hertfordshire, Hatfield, Hertfordshire, UK. J.M.Jamontt@herts.ac.uk
Molleman
A
A
Pertwee
R G
RG
Parsons
M E
ME
D000818:Animals; D002185:Cannabidiol / Q000008:administration & dosage* / Q000494:pharmacology; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid
D002185:Cannabidiol; D012460:Sulfasalazine; D013759:Dronabinol; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase