Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

“Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system.

Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms.

However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease.

… we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability.

Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels.

In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans…

… demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo.

Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.”

http://www.ncbi.nlm.nih.gov/pubmed/25537576

http://www.thctotalhealthcare.com/category/experimental-autoimmune-encephalomyelitis/

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

[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

 

 

Cannabinoids in experimental stroke: a systematic review and meta-analysis.

“Cannabinoids (CBs) show promise as neuroprotectants with some agents already licensed in humans for other conditions. We systematically reviewed CBs in preclinical stroke to guide further experimental protocols…

Cannabinoids reduced infarct volume in transient and permanent ischemia and in all subclasses: endocannabinoids, CB1/CB2 ligands, CB2 ligands, cannabidiol, Δ9-tetrahydrocannabinol, and HU-211. Early and late neuroscores significantly improved with CB use…

Overall, CBs significantly reduced infarct volume and improve functional outcome in experimental stroke.”

 http://www.ncbi.nlm.nih.gov/pubmed/25492113

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

The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat.

“Our study addressed the hypothesis that spinal release of endogenous opioids underlies Delta9-tetrahydrocannabinol (Delta9-THC)-induced antinociception in Freund’s adjuvant-induced arthritic and nonarthritic rats…

Our results indicate that morphine or Delta9-THC is equally potent and efficacious in both nonarthritic and arthritic rats.

Delta9-THC-induced antinociception…

We hypothesize that the elevated idyn A level in arthritic rats contributes to hyperalgesia by interaction with N-methyl-D-aspartate receptors, and that Delta9-THC induces antinociception by decreasing idyn A release.”

http://www.ncbi.nlm.nih.gov/pubmed/15189765

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

The antinociceptive effect of Delta9-tetrahydrocannabinol in the arthritic rat involves the CB(2) cannabinoid receptor.

“Cannabinoid CB(2) receptors have been implicated in antinociception in animal models of both acute and chronic pain.

We evaluated the role both cannabinoid CB(1) and CB(2) receptors in mechanonociception in non-arthritic and arthritic rats.

The antinociceptive effect of Delta(9)-tetrahydrocannabinol (Delta(9)THC) was determined…

Our results indicate that the cannabinoid CB(2) receptor plays a critical role in cannabinoid-mediated antinociception, particularly in models of chronic inflammatory pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17588560

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

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

Cannabinoids and muscular pain. Effectiveness of the local administration in rat.

“Pain associated with musculoskeletal disorders can be difficult to control and the incorporation of new approaches for its treatment is an interesting challenge.

Activation of cannabinoid (CB) receptors decreases nociceptive transmission in acute, inflammatory and neuropathic pain states…

Our results provide evidence that both, CB 1 and CB 2 receptors can contribute to muscular antinociception and, interestingly, suggest that the local administration of CB agonists could be a new and useful pharmacological strategy in the treatment of muscular pain, avoiding adverse effects induced by systemic administration.”

http://www.ncbi.nlm.nih.gov/pubmed/22354705

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

Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain.

“Cannabinoid (CB) receptors have emerged as an attractive therapeutic target for pain management in recent years and the interest in the use of cannabinoids is gradually increasing, particularly in patients where conventional treatments fail…

This study suggests that THC could be a future pharmacological option in the treatment of muscle pain.

The local administration of THC could be an interesting option to treat this type of pain avoiding the central adverse effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25446925

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

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/

Cannabinoids inhibit migration of microglial-like cells to the HIV protein Tat.

“Microglia are a population of macrophage-like cells in the central nervous system (CNS) which, upon infection by the human immunodeficiency virus (HIV), secrete a plethora of inflammatory factors, including the virus-specified trans-activating protein Tat.

Tat has been implicated in HIV neuropathogenesis since it elicits chemokines, cytokines, and a chemotactic response from microglia. It also harbors a β-chemokine receptor binding motif, articulating a mode by which it acts as a migration stimulus.

Since select cannabinoids have anti-inflammatory properties, cross the blood-brain barrier, and target specific receptors, they have potential to serve as agents for dampening untoward neuroimmune responses.

The aim of this study was to investigate the effect of select cannabinoids on the migration of microglial-like cells toward Tat.

…it was demonstrated that the exogenous cannabinoids Delta-9-tetrahydrocannabinol (THC) and CP55940 exerted a concentration-related reduction in the migration of BV-2 cells towards Tat.

These results indicate that cannabinoid-mediated inhibition of BV-2 microglial-like cell migration to Tat is linked functionally to the CB2R…”

http://www.ncbi.nlm.nih.gov/pubmed/21735070

Chronic administration of Δ9-tetrahydrocannabinol induces intestinal anti-inflammatory microRNA expression during acute SIV infection of rhesus macaques.

“In SIV-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC), inhibited viral replication, intestinal inflammation and slowed disease progression.

Persistent gastrointestinal disease/inflammation has been proposed to facilitate microbial translocation, systemic immune activation and promote disease progression. Cannabinoids including Δ9-THC attenuated intestinal inflammation in mouse colitis models and SIV-infected rhesus macaques…

Gastrointestinal tract (GI) disease/inflammation is a hallmark of HIV/SIV infection. Previously, we showed that chronic treatment of SIV-infected macaques with Δ9 tetrahydrocannabinol (Δ9-THC) increased survival and decreased viral replication and infection induced gastrointestinal inflammation.

Here, we show that chronic THC administration to SIV-infected macaques induced an anti-inflammatory microRNA expression profile…

Overall, our results show that selective upregulation of anti-inflammatory miRNA expression, contributes to THC-mediated suppression of gastrointestinal inflammation and maintenance of intestinal homeostasis.”