Category Archives: Multiple Myeloma

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

[The endocannabinoid system as a target for the development of new drugs for cancer therapy].

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“Studies on the main bioactive components of Cannabis sativa, the cannabinoids, and particularly delta 9-tetrahydrocannabinol (THC), led to the discovery of a new endogenous signalling system that controls several physiological and pathological conditions: the endocannabinoid system. This comprises the cannabinoid receptors, their endogenous agonists–the endocannabinoids–and proteins for endocannabinoid biosynthesis and inactivation.

Recently, evidence has accumulated indicating that stimulation of cannabinoid receptors by either THC or the endocannabinoids influence the intracellular events controlling the proliferation and apoptosis of numerous types of cancer cells, thereby leading to anti-tumour effects both in vitro and in vivo.

This evidence is reviewed here and suggests that future anti-cancer therapy might be developed from our knowledge of how the endocannabinoid system controls the growth and metastasis of malignant cells.”

http://www.ncbi.nlm.nih.gov/pubmed/12723496

Endocannabinoid system modulation in cancer biology and therapy.

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“The discovery of the endocannabinoid system and the recognition of its potential impact in a plethora of pathological conditions, led to the development of therapeutic agents related to either the stimulation or antagonism of CB1 and CB2 cannabinoid receptors, the majority of which are actually tested in preclinical studies for the pharmacotherapy of several diseases. Endocannabinoid-related agents have been reported to affect multiple signaling pathways and biological processes involved in the development of cancer, displaying an interesting anti-proliferative, pro-apoptotic, anti-angiogenic and anti-metastatic activity both in vitro and in vivo in several models of cancer. Emerging evidence suggests that agonists of cannabinoid receptors, which share the useful property to discern between tumor cells and their non-transformed counterparts, could represent novel tumor-selective tools to treat cancer in addition to their already exploited use as palliative drugs to treat chemotherapy-induced nausea, pain and anorexia/weight loss in cancer patients. The aim of this review is to evidence and update the recent emerging knowledge about the role of the endocannabinoid system in cancer biology and the potentiality of its modulation in cancer therapy.”  http://www.ncbi.nlm.nih.gov/pubmed/19559362

http://www.sciencedirect.com/science/article/pii/S1043661809000863

Changes in the Endocannabinoid System May Give Insight into new and Effective Treatments for Cancer

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“The endocannabinoid system comprises specific cannabinoid receptors such as Cb1 and Cb2, the endogenous ligands (anandamide and 2-arachidonyl glycerol among others) and the proteins responsible for their synthesis and degradation. This system has become the focus of research in recent years because of its potential therapeutic value several disease states. The following review describes our current knowledge of the changes that occur in the endocannabinoid system during carcinogenesis and then focuses on the effects of anandamide on various aspects of the carcinogenic process such as growth, migration, and angiogenesis in tumors from various origins.

Marijuana and its derivatives have been used in medicine for centuries, however, it was not until the isolation of the psychoactive component of Cannabis sativa (Δ9-tetrahydrocannabinol; Δ9-THC) and the subsequent discovery of the endogenous cannabinoid signaling system that research into the therapeutic value of this system reemerged. Ongoing research is determining that regulation of the endocannabinoid system may be effective in the treatment of pain (Calignano et al., 1998; Manzanares et al., 1999), glaucoma (Voth and Schwartz, 1997), and neurodegenerative disorders such as Parkinson’s disease (Piomelli et al., 2000) and multiple sclerosis (Baker et al., 2000). In addition, cannabinoids might be effective anti-tumoral agents because of their ability to inhibit the growth of various types of cancer cell lines in culture (De Petrocellis et al., 1998; Ruiz et al., 1999; Sanchez et al., 1998, 2001) and in laboratory animals (Galve-Roperh et al., 2000).

In conclusion, the endocannabinoid system exerts a myriad of effects on tumor cell growth, progression, angiogenesis, and migration. With a notable few exceptions, targeting the endocannabinoid system with agents that activate cannabinoid receptors or increase the endogenous levels of AEA may prove to have therapeutic benefit in the treatment of various cancers. Further studies into the downstream consequences of AEA treatment are required and may illuminate other potential therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791688/

The endocannabinoid system and cancer: therapeutic implication

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“The endocannabinoid system is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others).

The main active ingredient of cannabis, Δ(9) -tetrahydrocannabinol (Δ(9) -THC), produces its effects through activation of CB(1) and CB(2) receptors. CB(1) receptors are expressed at high levels in the central nervous system (CNS), whereas CB(2) receptors are concentrated predominantly, although not exclusively, in cells of the immune system.

Endocannabinoids are endogenous lipid-signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized endocannabinoids identified to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Here we review the relationship between the endocannabinoid system and anti-tumour actions (inhibition of cell proliferation and migration, induction of apoptosis, reduction of tumour growth) of the cannabinoids in different types of cancer.

This review will focus on examining how activation of the endocannabinoid system impacts breast, prostate and bone cancers in both in vitro and in vivo systems. The therapeutic potential of cannabinoids for cancer, as identified in clinical trials, is also discussed.

Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients.

Further basic research on anti-cancer properties of cannabinoids as well as clinical trials of cannabinoid therapeutic efficacy in breast, prostate and bone cancer is therefore warranted.” http://www.ncbi.nlm.nih.gov/pubmed/21410463

“The available literature suggests that the endocannabinoid system may be targeted to suppress the evolution and progression of breast, prostate and bone cancer as well as the accompanying pain syndromes. Many in vitro and in vivo studies have shown that cannabinoids are efficacious in reducing cancer progression (i.e. inhibition of tumour growth and metastases as well as induction of apoptosis and other anti-cancer properties) in breast, prostate and bone cancer. Although this review focuses on these three types of cancer, activation of the endocannabinoid signalling system produces anti-cancer effects in other types of cancer.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01327.x/full