“Aim: Effective treatment for neuropathic pain remains an unmet clinical need. The therapeutic benefits of the Cannabis plant are well known, especially for pain relief. Here, we have assessed ten “minor” cannabinoids for their analgesic effects in an established model of neuronal hypersensitivity, a key mechanism which underlies neuropathic pain.
Methods: Adult rat DRG neurons were cultured in medium containing 100 ng/mL nerve growth factor (NGF) and 50 ng/mL glial cell-line derived neurotrophic factor (GDNF) for 48 hours to sensitize the neurons. Ca2+ imaging was used to measure the responses to pain stimulation using capsaicin, and to determine the modulatory effects of the cannabinoids, in individual neurons.
Results: Control neurons (nociceptors) showed robust responses of Ca2+ influx to capsaicin application, while neurons treated with ten minor cannabinoids tetrahydrocannabiorcol (THCC), cannabitriol (CBT), cannabidivarin (CBDV), cannabinol (CBN), cannabichromene (CBC), cannabichromevarin (CBCV), cannabicitran (CBCT), cannabigerol monomethyl ether (CBGM), tetrahydrocannabutol (THCB) or tetrahydrocannabiphorol (THCP), at concentrations of 0.001-100 μM, showed differential dose-related effects on the responses to capsaicin. Ca2+ influx in response to capsaicin application was completely inhibited for each compound in 35-78% capsaicin-sensitive neurons, while other neurons showed reduced responses. The opioid receptor agonist morphine and α2δ1- Ca2+ channel inhibitor gabapentin were also tested for comparison and showed similar results. All the cannabinoids tested here inhibited calcium influx in response to capsaicin, and two, namely, CBN and THCC elicited calcium influx at higher doses. Inhibition of Ca2+ influx due to cannabichromene (CBC) was reversed by the potassium channel inhibitor Tertiapin Q.
Conclusion: All the cannabinoids tested here inhibited TRPV1 signalling. CBC targeted K+ channels to block TRPV1 mediated Ca2+ influx, demonstrating potential analgesic effects in vitro.”
https://pubmed.ncbi.nlm.nih.gov/41322279
“The therapeutic benefits of the Cannabis plant are well known, especially for pain relief.”
“In conclusion, our results show that the minor cannabinoids potently inhibit TRPV1 signaling in sensitized DRG neurons, and for CBC by blocking Ca2+ influx via K+ channel activation. This conclusion is based on the reversal of CBC-mediated inhibition in the presence of the K+ channel inhibitor Tertiapin Q. Further studies are necessary to confirm the mechanism, pathways and targets involved in the observed inhibitory effects of the other minor cannabinoids. This will facilitate the identification of cannabinoid combinations likely to have the maximum effect in providing analgesia for inhibiting neuronal sensitization that underlies chronic pain.”