How Does CBD Affect TRPV1 Pain Signalling Pathways

How Does CBD Affect TRPV1 Pain Signalling Pathways?

Cannabidiol (CBD) has become of increasing interest in recent years as the scientific and medical community continues to build on their understanding of cannabinoid science. The cannabis derivative has been shown to effectively reduce seizures in childhood cases of treatment-resistant epilepsy. In addition, a combination of CBD and THC has been used for treating spasticity and pain associated with multiple sclerosis.

It is believed that CBD primarily acts through endocannabinoid receptors – CB1 and CB2. However, the compound has also been implicated in other receptor interactions including the 5-HT1a serotonin receptor, a3, and a1 glycine receptors, and the TRPV1 receptor.

The vanilloid subtype 1 receptor (TRPV1) is thought to play an important role in pain signaling. As numerous studies have revealed that CBD may have promising potential to reduce inflammation and pain, the interaction between CBD and TRPV1 receptors is an area of particular interest. In a recent study, published in the Journal of Pain Research, researchers aimed to understand how CBD affects TRPV1 signalling pathways.

About the Study

In order to assess how CBD interacts with TRPV1 receptors, the researchers harvested dorsal root ganglion (DRG) neurons from adult rats. These were applied with CBD at varying dosages. Separate samples of DRG neurons were stimulated with capsaicin with or without CBD for a functional calcium assay. Capsaicin directly activates TRPV1 receptors. It is via this mechanism that capsaicin is responsible for the heat sensation associated with spicy foods such as chilies.

Calcium imaging was used to assess neuronal activation in response to the application of CBD. This study demonstrated that CBD stimulated calcium influx in DRG neurons at concentrations of 10 and 50 µMol/L. This research also showed than on exposure to higher concentrations of CBD, more neurons demonstrated an associated rise in intracellular calcium concentrations. These findings both demonstrate that CBD is a TRPV1 agonist.

This study also established a desensitisation effect of low-dose CBD on capsaicin-evoked calcium influx in DRG neurons which may underlie its role in reducing neuropathic pain. Furthermore, the researchers aimed to understand the underlying mechanisms behind these interactions. CBD-induced TRPV1 desensitisation was seen to be reversed in the presence of forskolin – a chemical which is known to activate the adenylyl cyclase – cAMP pathway. This implies that this desensitisation may be accounted for by CBD-induced inhibition of intracellular pathways associated with cAMP in DRG cells. A second pathway was also uncovered suggest a role of CBD in calcineurin-mediated TRPV1 inhibition.

What do these results mean?

The findings of this study identify CBD as an agonist of TRPV1 receptors with calcium-dependant effects of subsequent desensitisation. This is supported by previous in vivo evidence which has demonstrated the potential for TRPV1 desensitisation through inhibition of cAMP.

The authors of this study conclude that these findings demonstrate that physiological concentrations of CBD are able to inhibit TRPV1 signalling through a dual mechanism. These physiological concentrations were equivalent to plasma CBD concentrations seen during pharmacokinetic trials of orally administered CBD.

This paper serves to greater elucidate the mechanism behind the efficacy of CBD in models of acute and chronic pain.