Title:Endocannabinoid System: A Multi-Facet Therapeutic Target
Volume: 11
Issue: 2
Author(s): Rimplejeet Kaur, Sneha R. Ambwani and Surjit Singh
Affiliation:
Keywords:
Endocannabinoids, CB1 and CB2 receptors, endocannabinoid targets.
Abstract: Cannabis sativa is also popularly known as marijuana. It has been cultivated
and used by man for recreational and medicinal purposes since many centuries. Study of
cannabinoids was at bay for very long time and its therapeutic value could not be
adequately harnessed due to its legal status as proscribed drug in most of the countries.
The research of drugs acting on endocannabinoid system has seen many ups and downs
in the recent past. Presently, it is known that endocannabinoids has role in pathology
of many disorders and they also serve “protective role” in many medical conditions.
Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy,
glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome
related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and
Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid
system. Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the
chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK,
Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer
pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures.
Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but
it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug
Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.
Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse
events in the participating subjects could be discouraging for the research fraternity. Despite some
mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being
carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and
antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue
and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain
barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum
adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group
of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.
In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to
further characterize the endocannabinoid system in terms of identification of the exact cellular location of
cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent
changes in the expression of cannabinoid receptors.
