Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.

内源性大麻素信号传导研究的进展极大地增进了我们对其如何控制健康和疾病中神经回路兴奋性的理解。一般来说，兴奋性突触的内源性大麻素信号传导通过抑制谷氨酸释放来抑制癫痫发作。相比之下，内源性大麻素信号传导通过抑制抑制性突触处的 GABA 释放来促进癫痫发作。在内侧颞叶癫痫患者和实验诱发癫痫的动物模型中，随着癫痫病灶的发展，内源性大麻素信号分子的生理分布被破坏。内源性大麻素信号传导的增强可以促进初始阶段癫痫病灶的发展。然而，在后期，内源性大麻素信号传导的增加会延迟并抑制自发性癫痫发作。因此，在疾病发展的特定阶段引起过度兴奋的特定突触内源性大麻素信号传导的调节可能对治疗癫痫和癫痫发生有效。