CBG: Pain Killer + Endorphin Factory

CBG has been shown to have stronger antinociceptive activity [pain relief] than CBC and CBD, and CBG has been reported to have a stronger antinociceptive effect than THC.

Accordingly, we finally selected the compound CBG for follow-up experimental studies combined with our preliminary screening results. Using the same model, we explored the onset time of action, effective dose, and comparison of CBG antinociceptive with multiple antinociceptive agents.

CBG begins to work at 60 min and gradually weakens over time, and its antinociceptive effect were not dose-dependent, which works best at 2 mg/kg [150 mg for a 165-pound person], and there is no significant difference in antinociceptive effects compared with antinociceptive effects such as indometacin [arthritis NSAID], aspirin and ibuprofen.

For neuropathic pain, CBG can exert antinociceptive effect; for arthritis pain CBG has no effect but CBG may be more effective in local administration and can be developed as an external preparation.

TRPV1 is a temperature receptor and key nociceptor [pain receptor]. The literature reports that cannabinoids can activate the TRPV1 channel. Our results indicated that CBG can bind and interact with the TRPV1 protein, and we demonstrated that CBG may be antinociceptive by activating the TRPV1 channel and desensitizing it. [Could this have implications in treating CHS, thought to be a disorder of TRPV1?]

Cannabinoid receptors include CB1R and CB2R, and CB2R agonists have been reported to promote the release of β-endorphin, which then act on the ends of nociceptors and analgesia.

Based on experiments on the efficacy of CBG, the results showed that CBG local administration is more effective than injection. As a result, we speculated that CBG may exert antinociceptive effects by activating CB2R on HaCaT cells to promote the secretion of β-endorphin.

It was shown that activating CB2R increased the release of β-endorphin, which is consistent with previously reported results. Correspondingly, we demonstrated that CBG promoted the release of β-endorphin, and PCR experiments also showed that CBG upregulated the mRNA levels of POMC, which is the precursor of β-endorphin.

Therefore, all of the above results show that CBG may exert antinociceptive effects by activating TRPV1 to desensitize it and activating CB2R to promote β-endorphin release (Fig. 8):

Conclusions
In this study, we demonstrated the antinociceptive activity of CBG in different pain models and elucidated the mechanism by which CBG targets two receptors, TRPV1 and CB2R, to produce antinociceptive effects. CBG may activate the TRPV1 receptor to desensitize it and block the transmission of pain signals; antinociception of CBG may be mediated by stimulation of β-endorphin release from HaCaT cells. In addition, CBG is safe and nontoxic and is promising for development as a topical formulation for pain management.

Read the study at: https://www.sciencedirect.com/science/article/pii/S0753332222015529?via%3Dihub

[Edited for brevity and clarity but not content by RR, other than bracketed comments]