The Expression Level of CB1 and CB2 Receptors Determines Their Efficacy at Inducing Apoptosis in Astrocytomas

“Cannabinoids represent unique compounds for treating tumors, including astrocytomas.

One of the most promising therapeutic uses of cannabinoids is linked to their ability to induce apoptosis in tumors, including in astrocytoma…

Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB1, CB2…

…the treatment of tumors with high concentrations of cannabinoids should not be overlooked. In fact, stereotaxic injection of high concentrations of cannabinoids will eradicate a significant portion of C6 astrocytomas…”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806825/

 

Cannabinoid and cannabinoid-like receptors in microglia, astrocytes and astrocytomas

“…compounds targeting cannabinoid-like receptors constitute promising therapeutics to manage neuroinflammation and eradicate malignant astrocytomas.

Importantly, the selective targeting of cannabinoid-like receptors should provide therapeutic relieve without inducing the typical psychotropic effects and possible addictive properties…

 Taken together, the studies outlined in this review suggest that stereotactic injection of high concentrations of CBD could constitute a useful regimen for neurosurgeons to use in the treatment of malignant astrocytomas and of excessive/chronic neuroinflammation.

Such a treatment could provide therapeutic effects both directly, by killing the astrocytoma and limiting its propagation, and indirectly, by reducing the accumulation of activated microglia or invading peripheral immune cells.

The fact that non-psychotropic cannabinoids acting through CB-like receptors affect such fundamental processes involved in microglial cell activation and astrocytoma propagation constitutes, in my opinion, one of the most exciting areas of research in our search for new chemotherapeutic agents to treat malignant brain tumors and new anti-inflammatory agents to temper the damage linked to chronic neuroinflammation.

Furthermore, the curative properties of cannabinoids do not overlap with currently available medicines, and therefore cannabinoid-based treatments constitute a new therapeutic platform.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919281/

Cannabinoid receptors in human astroglial tumors.

“…cannabinoids are reported to inhibit the growth of tumors, including gliomas. These effects have been claimed to be mediated via cannabinoid receptors 1 and 2 (CB1, CB2).

We conclude that cannabinoid therapy of human gliomas targets not only receptors on tumor, but also on other cell types…”

http://www.ncbi.nlm.nih.gov/pubmed/16893424

Cannabinoid system and neuroinflammation: implications for multiple sclerosis.

“There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in central nervous system inflammatory conditions.

Advances in the understanding of the physiology and pharmacology of the cannabinoid system have potentiated the interest in cannabinoids as potential therapeutic targets.

…The effects of cannabinoids on cytokine brain work and on the regulation of neuroinflammatory processes may affect chronic inflammatory demyelinating diseases such as multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/18073512

Use of Dronabinol for Cannabis Dependence: Two Case Reports and Review

“Based on recent laboratory studies, dronabinol (delta-9-tetrahydrocannabinol) has been shown to reduce cannabis withdrawal symptoms and the subjective effects of marijuana.

Given that agonist agents have been found to be effective for opiate and nicotine dependence, the clinical utility of dronabinol for cannabis dependence is a reasonable approach…

It is clear from the two cases that both patients found the induction onto dronabinol helpful.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733248/

Dronabinol for the Treatment of Cannabis Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

“… there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence.

This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms…

In conclusion, agonist substitution pharmacotherapy with dronabinol, a synthetic form of THC, showed promise for treatment of cannabis dependence, reducing withdrawal symptoms and improving retention in treatment…

The trial showed that among adult cannabis-dependent patients, dronabinol was well accepted, with good adherence and few adverse events.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154755/

 

5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid.

“It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation.

…the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system…”

http://www.ncbi.nlm.nih.gov/pubmed/18028339

Cannabinoids induce glioma stem-like cell differentiation and inhibit gliomagenesis.

“Glioma stem-like cells constitute one of the potential origins of gliomas, and therefore, their elimination is an essential factor for the development of efficient therapeutic strategies.

Cannabinoids are known to exert an antitumoral action on gliomas that relies on at least two mechanisms: induction of apoptosis of transformed cells and inhibition of tumor angiogenesis…

The discovery of an endogenous cannabinoid system, together with the great improvement in our understanding of the signaling mechanisms responsible for cannabinoid actions, has fostered the interest in the potential therapeutic applications of cannabinoids.

Several studies have demonstrated a significant antitumoral action of cannabinoid ligands in animal models. Thus, cannabinoid administration to nude mice curbs the growth of different tumors, including gliomas…

Cannabinoids are known to exert an antitumoral action against gliomas…

Overall, our results demonstrate that cannabinoids target glioma stem-like cells, promote their differentiation, and inhibit gliomagenesis, thus giving further support to their potential use in the management of malignant gliomas.

In conclusion, our results demonstrate the action of cannabinoids on glioma stem-like cells and thus may open new avenues for cannabinoid-based antitumoral strategies.”

http://www.jbc.org/content/282/9/6854.long

Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells.

“Nuclear factor (NF)-κB is the key transcription factor involved in the inflammatory responses, and its activation aggravates tumors. Peptidoglycan (PGN), a main cell wall component of Gram-positive bacteria, stimulates Toll-like receptor 2 (TLR-2) and activates a number of inflammatory pathways, including NF-κB…

Cannabinoids have been reported to exert anti-inflammatory and antitumor effects…

Our finding that cannabinoids suppress the NF-κB inflammatory pathway and cell growth via CB1 receptors in glioma cells provides evidence for the therapeutic potential of targeting cannabinoid receptors for the treatment of inflammation-dependent tumor progression.”

http://www.ncbi.nlm.nih.gov/pubmed/22842590

Medical marijuana as protection against the H1N1 swine flu virus?

“When the immune system attacks a flu virus, it causes widespread inflammation throughout the body. This inflammation presents itself in runny noses, soar throats, and body aches that accompany influenza. Runaway inflammation can cause the immune system to destroy the body it was meant to protect and lead to death.

 “When inflammation goes off the handle, the body releases endocannabinoids, which are natural chemicals that suppress the immune system, taking down the inflammation before it does more harm than good. This endocannabinoid system, as it’s called, is one of the many systems responsible for maintaining balance and health in the body,” ABC News reported.

If the endocannabinoid system cannot keep up – which often happens in very severe influenza infections – organ failure, particularly lung failure, may result.

 “They die not from the virus itself but from their own immune response,” Melamede told ABC News.
Cannabis Science intends to solve this threat. Marijuana contains natural, plant-based cannabinoids, called phytocannabinoids. A medical marijuana lozenge provides the body with a boost of endocannabinoids and helps to relieve the dangerous inflammation.
While viruses like the H1N1 swine flu bug are clever in their ability to mutate and outsmart even the latest vaccines, the human body’s response – with regard to inflammation management – does not change. Cannabis Science may be on to something here.”

http://digitaljournal.com/article/276928