CBD Can Help to Heal Oral Ulcers, Study Suggests
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Cannabidiol (CBD) is well-known for its potential as an anti-inflammatory agent. For this reason, it has already been investigated as a way of tackling a whole host of different conditions, from arthritic pain to inflammatory bowel disease (IBS).
Now, new research presented at the virtual 99th General Session & Exhibition of the International Association for Dental Research (IADR) suggests that CBD can also help to speed up healing and reduce the pain associated with oral ulcers.
The researchers from the West China Hospital of Stomatology at Sichuan University demonstrated these healing effects in lab mice and have now characterized the mechanism behind this action using published RNA-sequencing datasets. The study results have been published in the Journal of Dental Research.
The researchers say that these new findings may help to shed light on the development of new therapeutics for oral ulcers.
CBD reduces inflammatory pain and promotes wound healing
Oral ulcers are a relatively common, but there are few effective treatments currently available. Given CBD’s promise as an anti-inflammatory agent, the Sichuan University researchers set out to evaluate whether the cannabinoid could also benefit the inflammatory pain that occurs with oral ulcers.
To do this, the researchers created mouse models of oral ulcers by acid etching or mechanical trauma inside the mouths of the lab mice, then applying a CBD oral spray. After macroscopic and histological evaluation, the researchers concluded that CBD was indeed able to alleviate the inflammatory pain associated with the ulcers in a dose-dependent manner. Topical application of the CBD oral spray to the ulcers was also seen to result in faster wound closure and ameliorated the expected loss of body weight in a similarly dose-dependent way.
CBD alters NLPR3 expression to combat inflammation in ulcers
After having established experimentally that CBD can accelerate healing and treat inflammatory pain in oral ulcers, the research team set out to investigate the underlying mechanisms for this action.
“Here we applied a CBD oral spray on ulcers in mice tongues, and found that CBD could greatly inhibit inflammation, relieve pain, and accelerate lesion closure. To dissect the mechanism, we analyzed the published RNA-sequenced datasets with recurrent aphthous ulcer, and found NLPR3 expression is notably upregulated in human oral ulcers,” said lead study author Xingying Qi during a virtual research presentation session.
The NLRP3 inflammasome is an important part of the body’s immune system and is responsible for producing the pro-inflammatory cytokines that typically respond to microbial infections and cell damage. High NLRP3 expression has previously been linked to the cause of recurrent aphthous ulcer (RAU) in humans.
“We performed RNA-sequencing using inflammation-stimulated RNA oral keratinocytes and revealed that CBD significantly inactivates NLRP3 inflammasome activation. In addition, CBD could also inhibit inflammasome-induced pyroptosis [cell death associated with inflammation], which is very helpful for ulcer healing,” said Qi.
Mechanically, the researchers also found that CBD was able to decrease the expression of CMPK2, which in turn reduced the new synthesis of mitochondrial DNA and led to the suppression of NLRP3 inflammasome activation.
“Notably, we identified a significant decrease of CMPK2 after CBD treatment – CMPK2 being the greatly limiting enzyme in the mitochondria that controls mitochondrial DNA synthesis,” Qi explained. “So we confirmed that in ulcers, CBD treatment suppressed CMPK2 expression and consequently attenuated mitochondrial DNA synthesis and inactivated the inflammasome.”
CBD ulcer healing mediated by PPAR-γ and CB1 receptor
From experiments using various receptor antagonists, the researchers determined that CBD’s beneficial effect on ulcer healing is mediated mostly by the PPAR-γ nuclear receptor and partially through the CB1 endocannabinoid receptor in plasma membrane.
“Cannabinoids can signal through various receptor targets. Here, we demonstrated that the CB1 receptor was partially involved in the inhibitory effects of CBD on inflammasome activation,” said Qi.
“In addition, CBD has been shown to exert immunomodulation properties through other receptors, like the nuclear receptor PPAR-γ. The application of a PPAR-γ receptor antagonist significantly and totally blocked the inhibitory effect of CBD on CMPK2-mediated inflammasome and pyroptosis.”
The researchers believe this is explained by PPAR-γ acting as a transcription factor for the CMPK2 gene. CBD treatment disrupts this process and inhibits the transcriptional modulation of PPAR-γ on CMPK2, resulting in the inhibition of the NLRP3 inflammasome.
With this new understanding of the mechanism behind CBD’s beneficial effects, the researchers hope that their results will go on to inform the development of new therapeutic strategies for managing oral ulcers in humans.