Miscellaneous endocannabinoid-like targets

Miscellaneous endocannabinoid-like targets refers to a heterogeneous group of proteins that interact with endocannabinoids and related lipid signaling molecules but are distinct from the classical CB1 and CB2 cannabinoid receptors (PMID: 20550906). This group includes orphan G protein-coupled receptors such as GPR55, GPR18, and GPR119, which are involved in blood pressure regulation, immune cell migration, and metabolic homeostasis (PMID: 21238501). It also encompasses the transient receptor potential vanilloid 1 (TRPV1) ion channel, which mediates pain and heat sensation, and nuclear receptors like peroxisome proliferator-activated receptors (PPAR-alpha and PPAR-gamma) (PMID: 15313881). These targets are of significant interest in pharmacology because they mediate many of the non-psychoactive effects of cannabinoids like cannabidiol (CBD) and endogenous lipids like palmitoylethanolamide (PEA) (PMID: 12520015). Drugs targeting these pathways are being explored for the treatment of chronic pain, epilepsy, obesity, and inflammatory diseases. However, the broad distribution and diverse functions of these targets present challenges in achieving high therapeutic selectivity and avoiding off-target effects.

Other names

Non-CB1/CB2 cannabinoid targetsEndocannabinoid-related receptorsPutative cannabinoid receptorsGPR55GPR18GPR119Transient receptor potential vanilloid 1 (TRPV1)Peroxisome proliferator-activated receptor alpha (PPAR-alpha)

Modulation of non-canonical cannabinoid receptors and lipid-sensitive signaling pathways including GPCR activation, ion channel gating, and transcriptional regulation via nuclear receptors.