Cannabidiol can affect morphology, morphometry, enzymatic and microbial activity of rabbit digestive system

The present research aimed to evaluate the effects of the continuative dietary administration of a hemp oil extract containing cannabinoids (cannabidiol, CBD) on the macroscopic morphology, morphometry, and enzymatic activity of different intestinal tracts as well as on the production of short-chain fatty acids (SCFAs) in the cecum of growing rabbits. The research was performed on 16 rabbits randomly selected from 2 experimental groups (8 per group). In detail, 42 sixty-day-old New Zealand White × California rabbits (sex ratio 1:1, average weight 1621.3 ± 46.2 g) were homogeneously divided into 2 groups (21 animals/group), namely control and CBD. Both groups were fed the same commercial diet, but the CBD one was supplemented with 0.1 mL of hemp extract in coconut-based oil corresponding to 10 mg of CBD/animal/d. Up to 92 d of age (for 27 d), individual live weight and feed intake were measured weekly. At 92 d of age, 8 rabbits/group (sex ratio 1:1) were moved to a specialized slaughterhouse, and the gastrointestinal tract was separated from the carcass. Samples from 8 rabbits per dietary treatment were used for the histomorphological analysis of small and large intestines. In addition, duodenum, jejunum, ileum, and cecum were processed for enzymatic analysis. The caecal contents were used for the SCFAs determination. The administration of CBD did not affect feed intake and the final rabbits' whole body weight (P > 0.05), but some changes were detected in the gastrointestinal tract of the animals. CBD seemed to interfere with protein digestion, with a significantly lower activity of the enzymes related to peptides in the small intestine and a consequent increase of the fermentative activity of caecal microbiota. This effect, in combination with a general decrease of fermentative activity in the caecal content of rabbits submitted to CBD treatment, was responsible for a change in the SCFA proportion mainly regarding the reduction of butyrate production (P < 0.01) that resulted significant higher in CTR group compared to CBD. This last result is very important for intestinal health. Such fermentation activity modification was coupled with changes in the relative abundance of goblet cells in the colon. Overall, our findings suggest that a relatively long-term administration of CBD may affect digestion in rabbits, in particular at enzymatic and fermentative levels.