Cannabinoid compounds are potential analgesics. Users of medicinal Cannabis report efficacy for pain control, clinical studies show that cannabis can be effective and opioid sparing in chronic pain, and some constituent cannabinoids have been shown to target nociceptive ion channels. Here, we explore and compare a suite of cannabinoids for their impact upon the physiology of TRPV1. The cannabinoids tested evoke differential responses in terms of kinetics of activation and inactivation. Cannabinoid activation of TRPV1 displays significant dependence on internal and external calcium levels. Cannabinoid activation of TRPV1 does not appear to induce the highly permeant, pore-dilated channel state seen with Capsaicin, even at high current amplitudes. Finally, we analyzed cannabinoid responses at nociceptive channels other than TRPV1 (TRPV2, TRPM8, and TRPA1), and report that cannabinoids differentially activate these channels. On the basis of response activation and kinetics, state-selectivity and receptor selectivity, it may be possible to rationally design approaches to pain using single or multiple cannabinoids.

大麻化合物是潜在的止痛药。药用大麻的使用者报道了控制疼痛的功效，临床研究表明，大麻在慢性疼痛中可能有效且阿片类药物保留，并且已表明某些成分的大麻素可靶向伤害性离子通道。在这里，我们探索并比较了一系列大麻素对TRPV1生理的影响。测试的大麻素在激活和失活动力学方面引起了不同的反应。TRPV1的大麻素活化显示出对内部和外部钙水平的显着依赖性。即使在高电流振幅下，TRPV1的大麻素激活似乎也不会诱导辣椒素所见的高度渗透的孔扩张通道状态。最后，我们分析了除TRPV1（TRPV2，TRPM8和TRPA1）以外的其他伤害性通道上的大麻素响应，并报告了大麻素差异激活这些通道。