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New Study Reveals How CBD Blocks Pain Signalling Pathways

While the therapeutic applications of cannabidiol (CBD) are extremely broad, the cannabinoid’s ability to reduce pain has become one of its major attractions. A recent survey of medical cannabis users found that some 53 percent use marijuana specifically for pain relief[i], and research is still ongoing in order to determine exactly how the various compounds in cannabis produce this effect.

On that front, a team of scientists from Imperial College London have just published a new study in the Journal of Pain Research, revealing how CBD desensitises certain neurons that are involved in pain signalling[ii].

Blocking The Pain Pathway

Previous studies have found that the painkilling effects of CBD can be weakened by blocking serotonin receptors in the brains of mice, indicating that the cannabinoid’s analgesic capacity is mediated at least in part by these receptors[iii]. However, to gain a more rounded idea of how the cannabinoid works, the authors of this latest study decided to focus on a different receptor known as the transient receptor potential vanilloid 1 (TRPV1), which is known to play a key role in pain signalling.

The researchers began by culturing neurons in a petri dish and adding capsaicin, the compound in chillies which gives them their spicy heat. In response, TRPV1 receptors in these neurons became activated, sending out pain signalling molecules that would normally lead to the kind of burning sensation that results from eating food that’s a bit too spicy.

When these neurons were treated with CBD, however, they became noticeably less sensitive to capsaicin, and transmitted fewer pain signals after coming into contact with the fiery compound. Closer analysis revealed that this occurred because CBD inhibited a secondary molecule called cyclic adenosine monophosphate (cAMP), which is known to control the sensitivity of TRPV1 receptors.

In short, then, CBD blocked cAMP, which in turn caused the TRPV1 receptors to become desensitised, resulting in less pain signalling in the presence of capsaicin.

A Safe Painkiller

Part of the reason for the popularity of cannabis as a painkiller is its excellent safety profile in comparison with other prescription medications, especially opioids. While many of these drugs are effective at relieving pain in the short term, they have been found to increase pain sensitivity if taken over a long period. As a consequence, pain signalling is amplified in the brain, meaning things start to hurt a lot more than they used to, leading to a greater need to increase the frequency and dosage of medication.

This is particularly dangerous in the case of opioids, as these drugs come with a risk of addiction and overdose, so the last thing anyone wants is to find themselves in a situation where they need to be taking more and more pills just to stay pain-free.

Fortunately, a new study in the Clinical Journal of Pain reveals that regular cannabis use does not cause any increase in pain sensitivity, which means that there is no danger of having to increase frequency or dosage over time[iv]. To investigate, the study authors tested the pain sensitivity, tolerance and intensity of 40 regular cannabis smokers and 40 non-smokers, finding no differences between the two groups.

Based on these findings, it’s easy to understand why so many people are now turning to cannabis as their painkiller of choice.

[i] Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: a survey of authorized medical cannabis patients. International Journal of Drug Policy. 2017 Apr 1;42:30-5. – https://www.sciencedirect.com/science/article/abs/pii/S0955395917300130

[ii] Anand U, Jones B, Korchev Y, Bloom SR, Pacchetti B, Anand P, Sodergren MH. CBD Effects on TRPV1 Signaling Pathways in Cultured DRG Neurons. Journal of Pain Research. 2020;13:2269. – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494392/

[iii] Ward SJ, McAllister SD, Kawamura R, Murase R, Neelakantan H, Walker EA. Cannabidiol inhibits paclitaxel‐induced neuropathic pain through 5‐HT1A receptors without diminishing nervous system function or chemotherapy efficacy. British Journal of Pharmacology. 2014 Feb;171(3):636-45. – https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.12439

[iv] St Pierre M, Russo EB, Walsh Z. No Evidence of Altered Reactivity to Experimentally Induced Pain Among Regular Cannabis Users. The Clinical Journal of Pain. 2020 Aug 8;36(8):589-93. – https://journals.lww.com/clinicalpain/Abstract/2020/08000/No_Evidence_of_Altered_Reactivity_to.4.aspx

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Ben Taub