Hippocampal Cb2 receptors: an untold story

The field of cannabinoid research has been receiving ever-growing interest. Ongoing debates worldwide about the legislation of medical cannabis further motivates research into cannabinoid function within the central nervous system (CNS). To date, two well-characterized cannabinoid receptors exist. While most research has investigated Cb-1 receptors (Cb(1)Rs), Cb-2 receptors (Cb(2)Rs) in the brain have started to attract considerable interest in recent years. With indisputable evidence showing the wide-distribution of Cb(2)Rs in the brain of different species, they are no longer considered just peripheral receptors. However, in contrast to Cb(1)Rs, the functionality of central Cb(2)Rs remains largely unexplored. Here we review recent studies on hippocampal Cb(2)Rs. While conflicting results about their function have been reported, we have made significant progress in understanding the involvement of Cb(2)Rs in modulating cellular properties and network excitability. Moreover, Cb(2)Rs have been shown to be expressed in different subregions of the hippocampus, challenging our prior understanding of the endocannabinoid system. Although more insight into their functional roles is necessary, we propose that targeting hippocampal Cb(2)Rs may offer novel therapies for diseases related to memory and adult neurogenesis deficits.

Automated summary

The field of cannabinoid research is gaining increasing interest, with a focus on the function of cannabinoids within the CNS. While Cb-1 receptors have been extensively studied, recent attention has shifted towards Cb-2 receptors in the brain, which remain largely unexplored. Through studies on hippocampal Cb(2)Rs, significant progress has been made in understanding their role in modulating cellular properties and network excitability, challenging prior notions of the endocannabinoid system. Targeting hippocampal Cb(2)Rs may offer novel therapies for memory and adult neurogenesis deficits.