The synthetic cannabinoids attenuate allodynia and hyperalgesia in a rat model of trigeminal neuropathic pain.

 

“Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain and continues to be a real therapeutic challenge.

At present there are few effective drugs. Here we have evaluated the effects of the synthetic cannabinoid WIN 55,212-2 on mechanical allodynia and thermal hyperalgesia in a rat model of trigeminal neuropathic pain produced by a chronic constriction injury (CCI) of the infraorbital branch of the trigeminalnerve (ION).

Taken together, these results suggest that cannabinoids may be a useful therapeutic approach for the clinical management of trigeminal neuropathic pain disorders.”

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Refractory trigeminal neuralgia responsive to nabiximols in a patient with multiple sclerosis.

“Nabiximols is a cannabinoid compound approved for the treatment of multiple sclerosis (MS)-related spasticity.

However, additional symptoms, such as pain, urinary urgency and sleep disturbance, may benefit from treatment.

CASE REPORT:

The present report describes a patient with secondary progressive MS and severe lower limbs spasticity who was started on treatment with nabiximols. The patient also suffered from trigeminal neuralgia, which he was not treating due to inefficacy or side effects of all previously tried medications. After nabiximols initiation the patient experienced a marked benefit on trigeminal neuralgia, which completely resolved, while spasticity responded only partially to treatment.

CONCLUSION:

Nabiximols mechanism of action is based on the interaction with CB1 and CB2 receptors, which are expressed by central nervous system neurons and are known to modulate pain among other effects. The present case indicates that nabiximols and other cannabinoids need to be further tested for the treatment of trigeminal neuralgia.”

http://www.ncbi.nlm.nih.gov/pubmed/27456876

“Therapeutic potential of cannabinoids in trigeminal neuralgia. Considering the pronounced antinociceptive effects produced by cannabinoids, they may be a promising therapeutic approach for the clinical management of trigeminal neuralgia.”  http://www.ncbi.nlm.nih.gov/pubmed/15578967

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ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from 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 down in 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 of 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 acts 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.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

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Therapeutic potential of cannabinoids in trigeminal neuralgia.

“Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain and continues to be a real therapeutic challenge to the clinicians. While the exact cause and pathology of this disorder is uncertain, it is thought that trigeminal neuralgia caused by irritation of the trigeminal nerve. This irritation results from damage due to the change in the blood vessels, the presence of a tumor or other lesions that cause the compression of the trigeminal root.

The pain of trigeminal neuralgia is characterized by unilateral pain attacks that start abruptly and last for varying periods of time from minutes to hours. The quality of pain is usually sharp, stabbing, lancinating, and burning. The attacks are initiated by mild stimuli such as light touch of the skin, eating, chewing, washing the face, brushing the teeth, and exposure to wind.

Although antiepileptic drug therapy may be beneficial in the treatment of trigeminal neuralgia, up to one-half of the patients become refractory or intolerant to these medications. At present there are few other effective drugs. In cases of lacking effect after pharmacotherapy, surgical options may be considered.

Currently there is growing amount of evidence to suggest that the psychoactive ingredient in cannabis and individual cannabinoids may be effective in alleviating neuropathic pain and hyperalgesia. Evidence suggests that cannabinoids may prove useful in pain modulation by inhibiting neuronal transmission in pain pathways.

Considering the pronounced antinociceptive effects produced by cannabinoids, they may be a promising therapeutic approach for the clinical management of trigeminal neuralgia.”

http://www.ncbi.nlm.nih.gov/pubmed/15578967

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Neuropathic orofacial pain: cannabinoids as a therapeutic avenue.

“Neuropathic orofacial pain (NOP) exists in several forms including pathologies such as burning mouth syndrome (BMS), persistent idiopathic facial pain (PIFP), trigeminal neuralgia (TN) and postherpetic neuralgia (PHN).

The pathophysiology of some of these conditions is still unclear and hence treatment options tend to vary and include a wide variety of treatments including cognitive behavior therapy, anti-depressants, anti-convulsants and opioids; however such treatments often have limited efficacy with a great amount of inter-patient variability and poorly tolerated side effects.

Analgesia is one the principal therapeutic targets of the cannabinoid system and many studies have demonstrated the efficacy of cannabinoid compounds in the treatment of neuropathic pain.

This review will investigate the potential use of cannabinoids in the treatment of symptoms associated with NOP.”

http://www.ncbi.nlm.nih.gov/pubmed/25150831

http://www.thctotalhealthcare.com/category/neuropathic-pain/

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The endocannabinoid system and its therapeutic exploitation.

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“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

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