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Targeting the endogenous cannabinoid system to treat neuropathic pain
Cannabinoids are found in the marijuana plant (cannabis sativa) and are said to be effective in pain management from pain symptoms such as multiple sclerosis, diabetic neuropathy, peripheral neuropathy and nausea and vomiting. A cannabinoid is one of a great collection of complex chemical compounds that naturally occur in the body and operates on major cannabinoid receptors in cells that mediates neurotransmitter release in the brain. Cannabinoids for these receptors include the endocannabinoid system, that are produced in the body by animals, the phytocannabinoids in cannabis and some other plants, and synthetic cannabinoids. The main cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC), the primary psychoactive chemical in cannabis. Cannabidiol (CBD) is another main constituent of the plant and produces a non psychotic effect. This paper will look at how the endocannabinoid system can be utilised to treat problems arising from neuropathic pain such as peripheral nerve pain and vitamin deficiencies.
Cannabinoids have the potential to treat neuropathic pain
Chronic neuropathic pain is a disabling disorder that remains badly resolved by current pain medications. Preclinical research has suggested that cannabinoid receptor agonists have therapeutic effectiveness in neuropathic pain experiments, but this is in cahoots with the unwanted adverse events. In recent years, novel plans targeting the endogenous cannabinoid network in nerve fibers in the spinal cord have surfaced, which are being deemed as safer modulatory substances. A recent clinical trial, however, has shown that a new endocannabinoid modulator is not a good therapeutic against osteoarthritic pain, despite showing effectiveness during the preclinical stage. More basic and clinical work is required to treat this disparity.
Cannabinoids have an anti inflammatory role
In a recent clinical experiment, the FAAH inhibitor, PF-04457845 was discovered not efficient in patients with osteoarthritis pain. This happened even after a clear abolition of FAAH activity and increasing in plasma AEA rates in nearly all people tested. This discovery directly goes against those looked at by the same group in an animal experiment of inflammatory and non-inflammatory pain, in which PF-04457845, a synthetic cannabinoid, gave off a strong antinociceptive impact. While the reason for this differing effectiveness between humans and animals is not transparent, it should be said that the former research was likely confounded by numerous human factors. Furthermore, the research evaluated only an osteoarthritic experiment of chronic pain. Thus, the application of FAAH inducers in the healing of neuropathic chronic pain is still yet to be found.
While the lack of effectiveness of a FAAH inducer in a recent clinical experiment is unsatisfactory, there are different methods citing the endocannabinoid network which may still have potential. These need to be first looked at in animal studies prior to going ahead with future clinical experiments. Specifically, the effectiveness of the greatly selective, individual MAGL inducers and the newly produced, dual FAAH/MAGL inducers need to be looked at in more depth in neuropathic chronic pain experiments. More so, the application of these degradation inducers in mixture with these substances that act on associated targets should be evaluated. Both drug effectiveness and adverse event profiles need to be looked at systematically. This may soon lead to an efficient pharmacotherapy to cure the issue ridden disorder of neuropathic pain.Lau_et_al-2014-Frontiers_in_Pharmacology