Therapeutic Potential of Nonpsychoactive Cannabinoids by Targeting at Glycine Receptors

Abstract

The glycine receptors GlyRs have been identified as major inhibitory neurotransmission receptors in the brain since the mid of last century. Unfortunately, no therapeutic agent has been developed from targeting these receptors. Accumulating evidence has suggested that GlyRs are one primary target for exogenous and endogenous cannabinoids in the central nervous system. Cannabinoids enhance the function of GlyRs in various neurons in the brain. However, this line of research has been largely ignored since little is known about the molecular mechanism and behavioral implication of cannabinoid modulation of GlyRs. Recent studies using various experimental approaches have explored molecular insights into cannabinoid-GlyR interaction and shed light on the molecular basis of nonpsychoactive cannabinoid modulation of GlyRs. Emerging evidence has suggested that cannabinoid modulation of GlyRs can contribute to some of the cannabis-induced therapeutic effects. In this chapter, I discuss recent development in studies of mechanism and therapeutic potential of cannabinoid modulation of GlyR subunits. This research direction shows considerable promise toward the development of novel therapeutic agents acting at defined modulatory sites of GlyRs in the treatment of various chronic pain, neuromotor disorders, and other GlyR deficiency diseases.

Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System

“…This is also the case for the transient receptor potential (TRP) channels TRPV1-TRPV4, TRPA1, and TRPM8 that have been termed the ionotropic cannabinoid receptors [27]. The ionotropic glycine receptors (GlyRs) are also involved in the ECS [28]. For instance, they have been shown to contribute to cannabinoid-induced analgesia [29].…”