Innovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Innovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
Biomed Pharmacother. 2023 Feb;158:114163. doi: 10.1016/j.biopha.2022.114163. Epub 2023 Jan 4.
Cannabis has been used for centuries to treat pain. The antinociceptive activity of tetrahydrocannabinol (THC) or cannabidiol (CBD) has been widely studied. However, the antinociceptive effects of other cannabis components, such as cannabichromene (CBC) and cannabigerol (CBG), have rarely been revealed. The antinociceptive mechanism of CBG is not yet clear, so we investigated the antinociceptive effect of CBG on different pain models, and explored the mechanism of action of CBG to exert antinociceptive effects. In the current study, we compared the antinociceptive effects of CBC, CBD, and CBG on the carrageenan-induced inflammatory pain model in mice, and the results showed that CBG had a better antinociceptive effects through intraplantar administration. On this basis, we further investigated the antinociceptive effect of CBG on CIA-induced arthritis pain model and nerve pain model in mice, and found that CBG also relieved on both types of pain. Then, we explored the antinociceptive mechanism of CBG, which revealed that CBG can activate TRPV1 and desensitize it to block the transmission of pain signals. In addition, CBG can further activate CB2R, but not CB1R, to stimulate the release of β-endorphin, which greatly promotes the antinociceptive effect. Finally, the safety test results showed that CBG had no irritating effect on the rabbits' skin, and it did not induce significant biochemical and hematological changes in mice. Transdermal delivery results also indicated that CBG has certain transdermal properties. Overall, this study indicates that CBG is promising for developing a transdermal dosage for pain management.
大麻被用于治疗疼痛已有数百年的历史。四氢大麻酚（THC）或大麻二酚（CBD）的抗伤害活性已得到广泛研究。然而，其他大麻成分（如大麻色烯（CBC）和大麻萜酚（CBG））的抗伤害作用很少被揭示。CBG 的抗伤害作用机制尚不清楚，因此我们研究了 CBG 对不同疼痛模型的抗伤害作用，并探讨了 CBG 发挥抗伤害作用的作用机制。在本研究中，我们比较了 CBC、CBD 和 CBG 对小鼠角叉菜胶诱导的炎症性疼痛模型的抗伤害作用，结果表明 CBG 通过皮内给药具有更好的抗伤害作用。在此基础上，我们进一步研究了 CBG 对 CIA 诱导的关节炎疼痛模型和小鼠神经痛模型的抗伤害作用，发现 CBG 也能缓解这两种类型的疼痛。然后，我们探讨了 CBG 的抗伤害作用机制，揭示了 CBG 可以激活 TRPV1 并使其脱敏以阻断疼痛信号的传递。此外，CBG 可以进一步激活 CB2R，但不激活 CB1R，刺激β-内啡肽的释放，这极大地促进了抗伤害作用。最后，安全性测试结果表明，CBG 对兔皮肤无刺激性，在小鼠中也不会引起明显的生化和血液学变化。经皮给药结果也表明 CBG 具有一定的经皮特性。总的来说，这项研究表明 CBG 有望开发用于疼痛管理的经皮制剂。
