title: Synthetic Cannabinoid Receptor Agonists and Antagonists: Implication in CNS Disorders.
abstract: BACKGROUND
  Since the discovery of the cannabinoid receptors, numerous studies associate the endocannabinoid system with several physiological and pathological processes including cancer, appetite, fertility, memory, neuropathic and inflammatory pain, obesity, and neurodegenerative diseases. Over the last two decades, several researches have been dedicated extensively on the cannabinoid receptors ligands since the direct activation of cannabinoid receptors results in several beneficial effects, in the brain and in the periphery. The cannabinoid CB1 and CB2 receptor synthetic ligands reported in this review have been collected by a wide research of scientific literature in particular in public database for patents and clinical trials. The references for patent numbers, clinical trial registry numbers, websites and scientific articles are reported in the reference section.
  
  
  RESULTS
  During past years, cannabinoid CB1 and CB2 receptor ligands from plants or lab were rapidly developed and then various new structures were reported to be cannabinoids. However the CB1 receptor ligands have had a limited usefulness due to their psychotropic effects, dependence, and cognitive impairment. On the contrary the development of CB2 receptor ligands has been more productive. Furthermore peripherally restricted agonists as well as CB1 receptor positive or negative allosteric modulators were studied with the aim of eliminating the undesirable CB1 receptor central effects.
  
  
  CONCLUSIONS
  The CB1 and CB2 receptor ligands offer several therapeutic opportunities for several CNS-related diseases. Based on the scientific literature, this review provides an overview of CB1 and CB2 receptor synthetic ligands obtained from drug research and in particular those synthesized for therapeutic purposes and potential clinical applications for central nervous system disorders.
authors.affiliation: Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy. clementina.manera@farm.unipi.it.
authors.forename: Clementina
authors.initials: C
authors.lastname: Manera
authors.forename: Chiara
authors.initials: C
authors.lastname: Arena
authors.forename: Andrea
authors.initials: A
authors.lastname: Chicca
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D006801:Humans
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators