Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1.

JNCI: Journal of the National Cancer Institute

“Cannabinoids, in addition to having palliative benefits in cancer therapy, have been associated with anticarcinogenic effects. Although the antiproliferative activities of cannabinoids have been intensively investigated, little is known about their effects on tumor invasion.”

“Increased expression of TIMP-1 mediates an anti-invasive effect of cannabinoids. Cannabinoids may therefore offer a therapeutic option in the treatment of highly invasive cancers.”

“There is considerable evidence to suggest an important role for cannabinoids in conferring anticarcinogenic activities. In this study, we identified TIMP-1 as a mediator of the anti-invasive actions of MA, a hydrolysis-stable analog of the endocannabinoid anandamide, and THC, a plant-derived cannabinoid.”

“In conclusion, our results suggest that there exists a signaling pathway by which the binding of cannabinoids to specific receptors leads via intracellular MAPK activation to induction of TIMP-1 expression and subsequent inhibition of tumor cell invasion. To our knowledge, this is the first report of TIMP-1–dependent anti-invasive effects of cannabinoids.”

http://jnci.oxfordjournals.org/content/100/1/59.long

Media Ignored Expert’s Shocking Findings That Marijuana Helps Prevent Lung Cancer: Now It’s Med-School Material

  “You’d think it would have been very big news in the spring of 2005 when Donald Tashkin, a professor of pulmonology at UCLA’s David Geffin School of Medicine, revealed at a conference that components of marijuana smoke, although they damage cells in respiratory tissue, somehow prevent them from becoming malignant. But headlines announcing “Pot Doesn’t Cause Cancer” did not ensue. ”

“As to the highly promising implication of his own study — that something in marijuana stops damaged cells from becoming malignant — Tashkin noted that an anti-proliferative effect of THC has been observed in cell-culture systems and animal models of brain, breast, prostate, and lung cancer. THC has been shown to promote known apoptosis (damaged cells die instead of reproducing) and to counter angiogenesis (the process by which blood vessels are formed — a requirement of tumor growth). Other antioxidants in cannabis may also be involved in countering malignancy, Tashkin said.”

Read more: http://www.alternet.org/drugs/media-ignored-experts-shocking-findings-marijuana-helps-prevent-lung-cancer-now-its-med-school

Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain.

Image result for The Journal of Supportive Oncology

“Many patients with life-threatening diseases such as cancer experience severe symptoms that compromise their health status and deny them quality of life. Patients with cancer often experience cachexia, pain, and depression,which translate into an unacceptable quality of life. The discovery of the endocannabinoid system has led to a renewed interest in the use of cannabinoids for the management of nausea, vomiting, and weight loss arising either from cancer or the agents used to treat cancer. The endocannabinoid system has been found to be a key modulator of systems involved in pain perception, emesis, and reward pathways. As such, it represents a target for development of new medications for controlling the symptoms associated with cancer. Although the cannabinoid receptor agonist tetrahydrocannabinol and one of its analogs are currently the only agents approved for clinical use, efforts are under way to devise other strategies for activating the endocannabinoid system for therapeutic uses.”

http://www.ncbi.nlm.nih.gov/pubmed/15357514

News about therapeutic use of cannabis and endocannabinoid system.

“Growing basic research in recent years led to the discovery of the endocannabinoid system with a central role in neurobiology. New evidence suggests a therapeutic potential of cannabinoids in cancer chemotherapy-induced nausea and vomiting as well as in pain, spasticity and other symptoms in multiple sclerosis and movement disorders. Results of large randomized clinical trials of oral and sublingual Cannabis extracts will be known soon and there will be definitive answers to whether Cannabis has any therapeutic potential. Although the immediate future may lie in plant-based medicines, new targets for cannabinoid therapy focuses on the development of endocannabinoid degradation inhibitors which may offer site selectivity not afforded by cannabinoid receptor agonists.”  http://www.ncbi.nlm.nih.gov/pubmed/15033046

http://www.elsevier.es/es-revista-medicina-clinica-2-linkresolver-novedades-sobre-las-potencialidades-terapeuticas-13059327

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

Philosophical Transactions of the Royal Society B: Biological Sciences: 367 (1607)

“Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive ‘multi-targeting’.”  https://www.ncbi.nlm.nih.gov/pubmed/23108552

“Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities”  http://rstb.royalsocietypublishing.org/content/367/1607/3353.long

Therapeutic aspects of cannabis and cannabinoids

The British Journal of Psychiatry

“HISTORY OF THERAPEUTIC USE

The first formal report of cannabis as a medicine appeared in China nearly 5000 years ago when it was recommended for malaria, constipation, rheumatic pains and childbirth and, mixed with wine, as a surgical analgesic. There are subsequent records of its use throughout Asia, the Middle East, Southern Africa and South America. Accounts by Pliny, Dioscorides and Galen remained influential in European medicine for 16 centuries.”

“It was not until the 19th century that cannabis became a mainstream medicine in Britain. W. B. O’Shaughnessy, an Irish scientist and physician, observed its use in India as an analgesic, anticonvulsant, anti-spasmodic, anti-emetic and hypnotic. After toxicity experiments on goats and dogs, he gave it to patients and was impressed with its muscle-relaxant, anticonvulsant and analgesic properties, and recorded its use-fulness as an anti-emetic.”

“After these observations were published in 1842, medicinal use of cannabis expanded rapidly. It soon became available ‘over the counter’ in pharmacies and by 1854 it had found its way into the United States Dispensatory. The American market became flooded with dozens of cannabis-containing home remedies.”

“Cannabis was outlawed in 1928 by ratification of the 1925 Geneva Convention on the manufacture, sale and movement of dangerous drugs. Prescription remained possible until final prohibition under the 1971 Misuse of Drugs Act, against the advice of the Advisory Committee on Drug Dependence.”

“In the USA, medical use was effectively ruled out by the Marijuana Tax Act 1937. This ruling has been under almost constant legal challenge and many special dispensations were made between 1976 and 1992 for individuals to receive ‘compassionate reefers’. Although this loophole has been closed, a 1996 California state law permits cultivation or consumption of cannabis for medical purposes, if a doctor provides a written endorsement. Similar arrangements apply in Italy and Canberra, Australia.”

“Results and Conclusions Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.”

http://bjp.rcpsych.org/content/178/2/107.long

The therapeutic potential of novel cannabinoid receptors.

Cover image

“Cannabinoids produce a plethora of biological effects, including the modulation of neuronal activity through the activation of CB(1) receptors and of immune responses through the activation of CB(2) receptors. The selective targeting of either of these two receptor subtypes has clear therapeutic value. Recent evidence indicates that some of the cannabinomimetic effects previously thought to be produced through CB(1) and/or CB(2) receptors, be they on neuronal activity, on the vasculature tone or immune responses, still persist despite the pharmacological blockade or genetic ablation of CB(1) and/or CB(2) receptors. This suggests that additional cannabinoid and cannabinoid-like receptors exist. Here we will review this evidence in the context of their therapeutic value and discuss their true belonging to the endocannabinoid signaling system.”  http://www.ncbi.nlm.nih.gov/pubmed/19248809

“The therapeutic potential of novel cannabinoid receptors”  http://www.sciencedirect.com/science/article/pii/S0163725809000266

Update on the endocannabinoid system as an anticancer target.

Image result for Expert Opin Ther Targets.

“INTRODUCTION:

Recent studies have shown that the endocannabinoid system (ECS) could offer an attractive antitumor target. Numerous findings suggest the involvement of this system (constituted mainly by cannabinoid receptors, endogenous compounds and the enzymes for their synthesis and degradation) in cancer cell growth in vitro and in vivo.

AREAS COVERED:

This review covers literature from the past decade which highlights the potential of targeting the ECS for cancer treatment. In particular, the levels of endocannabinoids and the expression of their receptors in several types of cancer are discussed, along with the signaling pathways involved in the endocannabinoid antitumor effects. Furthermore, the beneficial and adverse effects of old and novel compounds in clinical use are discussed.

EXPERT OPINION:

One direction that should be pursued in antitumor therapy is to select compounds with reduced psychoactivity. This is known to be connected to the CB1 receptor; thus, targeting the CB2 receptor is a popular objective. CB1 receptors could be maintained as a target to design new compounds, and mixed CB1-CB2 ligands could be effective if they are able to not cross the BBB. Furthermore, targeting the ECS with agents that activate cannabinoid receptors or inhibitors of endogenous degrading systems such as fatty acid amide hydrolase inhibitors may have relevant therapeutic impact on tumor growth. Additional studies into the downstream consequences of endocannabinoid treatment are required and may illuminate other potential therapeutic targets.”  http://www.ncbi.nlm.nih.gov/pubmed/21244344

“Update on the endocannabinoid system as an anticancer target”  http://www.tandfonline.com/doi/abs/10.1517/14728222.2011.553606?journalCode=iett20

Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents.

Image result for Best Pract Res Clin Endocrinol Metab

“Cannabinoids (the active components of Cannabis sativa) and their derivatives have received renewed interest in recent years due to their diverse pharmacological activities. In particular, cannabinoids offer potential applications as anti-tumour drugs, based on the ability of some members of this class of compounds to limit cell proliferation and to induce tumour-selective cell death. Although synthetic cannabinoids may have pro-tumour effects in vivo due to their immunosuppressive properties, predominantly inhibitory effects on tumour growth and migration, angiogenesis, metastasis, and also inflammation have been described. Emerging evidence suggests that agonists of cannabinoid receptors expressed by tumour cells may offer a novel strategy to treat cancer. In this chapter we review the more recent results generating interest in the field of cannabinoids and cancer, and provide novel suggestions for the development, exploration and use of cannabinoid agonists for cancer therapy, not only as palliative but also as curative drugs.” https://www.ncbi.nlm.nih.gov/pubmed/19285265

“Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents” http://www.bprcem.com/article/S1521-690X(09)00005-0/abstract

Cannabis-derived substances in cancer therapy–an emerging anti-inflammatory role for the cannabinoids.

“Cannabinoids, the active components of the cannabis plant, have some clinical merit both as an anti-emetic and appetite stimulant in cachexic patients. Recently, interest in developing cannabinoids as therapies has increased following reports that they possess anti-tumour properties.

 Research into cannabinoids as anti-cancer agents is in its infancy, and has mainly focussed on the pro-apoptotic effects of this class of agent. Impressive anti-cancer activities have been reported; actions that are mediated in large part by disruptions to ubiquitous signalling pathways such as ERK and PI3-K. However, recent developments have highlighted a putative role for cannabinoids as anti-inflammatory agents. Chronic inflammation has been associated with neoplasia for sometime, and as a consequence, reducing inflammation as a way of impacting cancer presents a new role for these compounds.

 This article reviews the ever-changing relationship between cannabinoids and cancer, and updates our understanding of this class of agent. Furthermore, the relationship between chronic inflammation and cancer, and how cannabinoids can impact this relationship will be described.”

http://www.ncbi.nlm.nih.gov/pubmed/20925645