Impact of efficacy at the mu opioid receptor on antinociceptive effects of combinations of mu opioid receptor agonists and cannabinoid receptor agonists.

“Cannabinoid receptor agonists, such as delta-9-tetrahydrocannabinol (Δ9-THC),  have antinociceptive effects and, are increasingly used to treat pain, and medications including cannabinoid receptor agonists are approved for use in humans.

Cannabinoid receptor agonists [e.g. Δ9-tetrahydrocannabinol (Δ9-THC)] enhance the antinociceptive effects of mu opioid receptor agonists, suggesting that combining cannabinoids with opioids would improve pain treatment.

…these results provide additional support for combining opioids with cannabinoids to treat pain.”

http://jpet.aspetjournals.org/content/early/2014/09/05/jpet.114.216648.long

http://www.thctotalhealthcare.com/category/pain-2/

Treatment with a Heme Oxygenase 1 Inducer Enhances the Antinociceptive Effects of µ-Opioid, δ-Opioid, and Cannabinoid 2 Receptors during Inflammatory Pain.

“The administration of µ-opioid receptor (MOR), δ-opioid receptor (DOR), and cannabinoid 2 receptor (CB2R) agonists attenuates inflammatory pain.

We investigated whether treatment with the heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), could modulate the local effects and expression of MOR, DOR, or CB2R during chronic inflammatory pain…

This study shows that the HO-1 inducer (CoPP) increased the local antinociceptive effects of MOR, DOR, and CB2R agonists during inflammatory pain by altering the peripheral expression of MOR and DOR.

Therefore, the coadministration of CoPP with local morphine, DPDPE, or JWH-015 may be a good strategy for the management of chronic inflammatory pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25204546

The endocannabinoid system as a potential therapeutic target for pain modulation.

“Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms.

Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the enzymes playing a role in endocannabinoid metabolism.

Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme.

In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/25207181

http://www.thctotalhealthcare.com/category/pain-2/

Oxidative stress and cannabinoid receptor expression in type-2 diabetic rat pancreas following treatment with Δ9 -THC.

“We can suggest that Δ9 -THC may be an important agent for the treatment of oxidative damages induced by diabetes…

Furthermore, the present study for the first time emphasizes that Δ9 -THC may improve pancreatic cells via cannabinoid receptors in diabetes.

The aim of present study was to elucidate the effects of Δ9 -THC, a natural cannabinoid receptor agonist, on the expression and localization of cannabinoid receptors, and oxidative stress statue in type-2 diabetic rat pancreas.

Results demonstrate that the cannabinoid receptors are presented in both Langerhans islets and duct regions.

The curative effects of Δ9 -THC can be occurred via activation of cannabinoid receptors in diabetic rat pancreas.

Moreover, it may provide a protective effect against oxidative damage induced by diabetes.

Thus, it is suggested that Δ9 -THC can be a candidate for therapeutic alternatives of diabetes symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/25187240

http://www.thctotalhealthcare.com/category/diabetes/

Cannabinoid mouth spray brought help to a severely spastic young man.

“Cannabinoid was licensed in 2012 for the treatment of spasticity associated with multiple sclerosis in Finland. Spasticity is one of the main symptoms in cerebral palsies and a risk factor of multiple painful anomalies of the skeletal network. We describe a 28-year-old man with severe cerebral palsy, whose quality of life improved and the need for help decreased by using two daily mouth sprays of cannabinoid.”

http://www.ncbi.nlm.nih.gov/pubmed/25158585

Cannabinoids for Neuropathic Pain.

“Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects.

The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis.

Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions.

This article reviews the history, pharmacologic development, clinical trials results, and the future potential of nonsmoked, orally bioavailable, nonpsychoactive cannabinoids in the management of neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25160710

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

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/

The Role of Endocannabinoid Signaling in the Molecular Mechanisms of Neurodegeneration in Alzheimer’s Disease.

“Alzheimer’s disease (AD) is the most common form of progressive neurodegenerative disease characterized by cognitive impairment and mental disorders… AD is multifaceted in nature and is linked to different multiple mechanisms in the brain…

The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.

Recently, the endocannabinoid system emerged as novel potential therapeutic target to treat AD.

In fact, exogenous and endogenous cannabinoids seem to be able to modulate multiple processes in AD, although the mechanisms that are involved are not fully elucidated.

This review provides an update of this area. In this review, we recapitulate the role of endocannabinoid signaling in AD and the probable mechanisms through which modulators of the endocannabinoid system provide their effects, thus highlighting how this target might provide more advantages over other therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pubmed/25147120

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Cannabinoids: a novel treatment for glaucoma

Acta Ophthalmologica

“…cannabinoids are emerging novel agents for the treatment of glaucoma.

Although increased intraocular pressure (IOP) is a risk factor, associated retinal damage is of prime concern. This study determines the ability of cannabinoids to decrease IOP and confer neuroprotection…

Conclusion: Topically applied cannabinoids are effective agents that reduce IOP and confer neuroprotection and are prime candidates for potential glaucoma treatment.”

http://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2014.T022.x/abstract

http://www.thctotalhealthcare.com/category/glaucoma-2/

Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity.

Brain

“Cannabinoid-derived drugs are promising agents for the development of novel neuroprotective strategies.

…in Huntington’s disease there is a very early downregulation of CB1 receptors in striatal neurons that, together with the undesirable psychoactive effects triggered by CB1 receptor activation, foster the search for alternative pharmacological treatments.

These findings support a pivotal role for CB2 receptors in attenuating microglial activation and preventing neurodegeneration that may pave the way to new therapeutic strategies for neuroprotection in Huntington’s disease as well as in other neurodegenerative disorders with a significant excitotoxic component.

Overall, the reduction of neuronal CB1 receptors and the upregulation of microglial CB2 receptors support a crucial role for the ECB system in the pathogenesis of Huntington’s disease.

The use of drugs targeting the ECB system via CB1 receptors aimed at restoring neurochemical alterations and palliating symptoms might constitute an interesting strategy for the management of Huntington’s disease and other neurodegenerative disorders with a significant excitotoxicity component.”

 http://brain.oxfordjournals.org/content/132/11/3152.long

http://www.thctotalhealthcare.com/category/huntingtons/