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.