Are Cannabinoids Effective for Orofacial Pain States?

“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).

These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…

This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…

The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.

These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.

They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”

http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw

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

Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity

“In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death.

In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation…

The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.

The effect of THC was in part mediated by the cannabinoid receptor CB1.

These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma.

THC and CBD, are similarly potent antioxidants that protect neuron cultures from glutamate-induced cell death or oxidative stress…

In addition to possessing neuroprotective or retinal neuroprotective activity… cannabinoids, such as THC, have been demonstrated to induce dose-related reductions in intraocular pressure in human and in animal models. 

This suggests that cannabinoids may offer a multifaceted therapy for glaucoma.

In conclusion, our results indicate that lipid peroxidation and ONOO− formation play an important role in NMDA-induced retinal neurotoxicity and cell loss in the retina, and that THC and CBD, by reducing the formation of these compounds, are effective neuroprotectants.

The present studies could form the basis for the development of new topical therapies for the treatment of glaucoma.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892413/

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

Protective effects of Delta(9)-tetrahydrocannabinol against N-methyl-d-aspartate-induced AF5 cell death.

Image result for delta-9-tetrahydrocannabinol

“One of the most promising potential medical applications of cannabinoids involves their ability to protect cells from a variety of toxic events.

Cannabinoids have been reported to protect neurons from death…

Cannabinoids, such as the pharmacologically active component of marijuana (-)Δ9-tetrahydrocannabinol (THC)…

The neuroprotective effects of Δ9-tetrahydrocannabinol (THC) were examined…

Protective effects of Delta(9)-tetrahydrocannabinol… THC may function as an antioxidant to increase cell survival… 

THC can produce receptor-independent neuroprotective or cellular protective effects at micromolar concentrations as a result of its antioxidant properties…

In conclusion, THC produces a potent neuroprotective effect…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1824211/

Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT1A receptors and stressful experiences.

“The infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex are involved in behavioral responses observed during defensive reactions.

Intra-PL or IL injections of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, result in opposite behavioral effects in the contextual fear conditioning (CFC) paradigm…

Together these results indicate that CBD effects in the IL depend on the nature of the animal model, being influenced by previous stressful experiences and mediated by facilitation of 5HT1A receptors-mediated neurotransmission.”

http://www.ncbi.nlm.nih.gov/pubmed/25701682

Evaluation of Phytocannabinoids from High Potency Cannabis sativa using In Vitro Bioassays to Determine Structure-Activity Relationships for Cannabinoid Receptor 1 and Cannabinoid Receptor 2.

“Cannabis has been around for thousands of years and has been used recreationally, medicinally, and for fiber.

Over 500 compounds have been isolated from Cannabis sativa with approximately 105 being cannabinoids. Of those 105 compounds, Δ9-tetrahydrocannabinol has been determined as the primary constituent, which is also responsible for the psychoactivity associated with Cannabis.

Cannabinoid receptors belong to the large superfamily of G protein-coupled receptors.

Targeting the cannabinoid receptors has the potential to treat a variety of conditions such as pain, neurodegeneration, appetite, immune function, anxiety, cancer, and others.

Developing in vitro bioassays to determine binding and functional activity of compounds has the ability to lead researchers to develop a safe and effective drug that may target the cannabinoid receptors…”

http://www.ncbi.nlm.nih.gov/pubmed/25419092

Fatty Acid Binding Proteins (FABPs) are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).

Image result for fatty acid binding proteins

“Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex.

Recent reports suggest that CBD and THC elevates the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance.

Fatty acid binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH).

By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and we demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs.

Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption.

Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD.

Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids.

These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy towards epilepsy and other neurological disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25666611

Cannabidiol protects against doxorubicin-induced cardiomyopathy by modulating mitochondrial function and biogenesis.

“Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX’s cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells, and cell death.

Cannabidiol is a non-psychotropic constituent of marijuana, which is well-tolerated in humans, with antioxidant, anti-inflammatory, and recently discovered antitumor properties.

We aimed to explore the effects of cannabidiol in a well-established mouse model of DOX-induced cardiomyopathy…

Treatment with cannabidiol markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. Cannabidiol also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis.

These data suggest that cannabidiol may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above described effects on mitochondrial function and biogenesis may contribute to its beneficial properties described in numerous other models of tissue injury.”

http://www.ncbi.nlm.nih.gov/pubmed/25569804

Association Between Marijuana Exposure and Pulmonary Function over 20 Years

TU Dublin Kevin St Library: New: American Medical Association journals (JAMA)  collection now available via IReL“Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.

Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms.

Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840897/

https://jamanetwork.com/journals/jama/fullarticle/1104848

“A common misconception about medical marijuana is that if inhaled, it will have detrimental effects on the patient’s lungs. However, according to a 2012 study published in the Journal of the American Medical Association (JAMA), this notion is simply untrue; in fact, this study points to an idea quite the opposite: that medical marijuana just might improve lung health under certain conditions.” HTTPS://AGRIMEDINDUSTRIES.COM/2018/06/08/STUDY-SHOWS-MARIJUANA-HAS-A-POSITIVE-IMPACT-ON-LUNG-HEALTH-UNDER-CERTAIN-CONDITIONS/

[Potential applications of marijuana and cannabinoids in medicine]

“Cannabinoids, psychoactive substances present in cannabis, have been known to mankind for hundreds of years.

Apart from 9-tetrahydrocannabinol (THC) substances found in the cannabis herb with the highest toxicological value are cannabidiol (CBD) and cannabinol (CBN).

The discovery of CB1 and CB2 receptors, located in various tissues (ranging from the brain to peripheral tissues), has defined the potential objective of these new chemical substances’ effects.

Many studies on the application of cannabinoids in the treatment of various diseases such as diabetes, neoplasms, inflammatory diseases, neurological conditions, pain and vomitting were conducted.

Drugs containing e.g. THC appear on the pharmaceutical market.

Substances affecting cannabinoid receptors may show beneficial effects…”

http://www.ncbi.nlm.nih.gov/pubmed/25518584

 

 

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model.

“High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful.

Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis.

In an attempt to improve treatment outcome, we have investigated the effect of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261).

Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS).

Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS.

…increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis.

These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation.

Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities.”

http://www.ncbi.nlm.nih.gov/pubmed/25398831

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