Tag Archives: cancer

Local Delivery of Cannabinoid-Loaded Microparticles Inhibits Tumor Growth in a Murine Xenograft Model of Glioblastoma Multiforme

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“Treatment with cannabinoid-loaded microparticles activates apoptosis and inhibits tumor angiogensis. The aim of the present study was therefore to evaluate the antitumor efficacy of biodegradable polymeric microparticles allowing the controlled release of the phytocannabinoids THC and CBD. Our findings show that administration of cannabinoid-loaded microparticles reduces the growth of glioma xenografts supporting that this method of administration could be exploited for the design of cannabinoid-based anticancer treatments.

Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) – the two major ingredients of marijuana – have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1:1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.

Δ9-Tetrahydrocannabinol (THC), the main active component of the hemp plant Cannabis sativa, exerts a wide variety of biological effects by mimicking endogenous substances – the endocannabinoids – that bind to and activate specific cannabinoid receptors. So far, two G protein–coupled cannabinoid-specific receptors have been cloned and characterized from mammalian tissues: CB1, abundantly expressed in the brain and at many peripheral sites, and CB2, expressed in the immune system and also present in some neuron subpopulations and glioma cells. One of the most active areas of research in the cannabinoid field is the study of the potential application of cannabinoids in the treatment of different pathologies. Among these therapeutic applications, cannabinoids are being investigated as anti-tumoral agents. Thus, cannabinoid administration curbs the growth of several types of tumor xenografts in rats and mice including gliomas. Based on this preclinical evidence, a pilot clinical trial has been recently run to investigate the anti-tumor action of THC on recurrent gliomas. The mechanism of THC anti-tumoral action relies on the ability of this compound to: (i) promote the apoptotic death of cancer cells (ii) to inhibit tumour angiogenesis and (iii) to reduce the migration of cancer cells.

Conclusions

Data presented in this manuscript show for the first time that in vivo administration of microencapsulated cannabinoids efficiently reduces tumor growth thus providing a proof of concept for the utilization of this formulation in cannabinoid-based anti-cancer therapies.”

Full text: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054795. 

Cannabinoids for Cancer Treatment: Progress and Promise

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Cancer Research: 68 (2)

“Cannabinoid refers to a group of chemicals naturally found in the marijuana plant Cannabis sativa L. and includes compounds that are either structurally or pharmacologically similar to Δ(9)-tetrahydrocannabinol or those that bind to the cannabinoid receptors. Although anticancer effects of cannabinoids were shown as early as 1975 in Lewis lung carcinoma, renewed interest was generated little after the discovery of the cannabinoid system and cloning of the specific cannabinoid receptors.

Cannabinoids are a class of pharmacologic compounds that offer potential applications as antitumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival. In particular, emerging evidence suggests that agonists of cannabinoid receptors expressed by tumor cells may offer a novel strategy to treat cancer. Here, we review recent work that raises interest in the development and exploration of potent, nontoxic, and nonhabit forming cannabinoids for cancer therapy.”

Full Text: http://cancerres.aacrjournals.org/content/68/2/339.long

US Investigators Praise Cannabinoids As Chemo Treatment

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“Cannabinoids inhibit cancer cell proliferation and should be clinically tested as chemotherapeutic agents, according to a review published in the January issue of the journal Cancer Research.

Investigators at the University of Wisconsin School of Medicine and Public Health reported that the administration of cannabinoids halts the spread of a wide range of cancers, including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, and lymphoma.

Researchers suggested that cannabinoids may offer significant advantages over standard chemotherapy treatments because the compounds are both non-toxic and can uniquely target malignant cells while ignoring healthy ones.

“Cannabinoids … offer potential applications as anti-tumor drugs, based on the ability of some members of this class to limit inflammation, cell proliferation, and cell survival,” authors concluded. “[T]here is overwhelming evidence to suggest that cannabinoids can be explored as chemotherapeutic agents for the treatment of cancer.””

Read more: http://norml.org/news/2008/01/31/us-investigators-praise-cannabinoids-as-chemo-treatment

Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells

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 “Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines …

 Cannabinoids… reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue… results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress–related genes ATF-4 and TRB3.

 These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer.

In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells in vitro and in vivo…

 These findings may help to set the basis for a new therapeutic approach for the treatment of this deadly disease.”

http://www.420magazine.com/forums/pancreatic-cancer/145013-cannabinoids-induce-apoptosis-pancreatic-tumor-cells.html

 

“Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes“

 

Full text: http://cancerres.aacrjournals.org/content/66/13/6748.long

Nabilone for the treatment of paraneoplastic night sweats: a report of four cases.

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“Night sweats are one of many symptoms experienced by patients with advanced cancer. Persistent night sweats tend to decrease quality of life through interference with sleep… night sweats represent one of the symptoms that displays a tendency not to improve as patients with advanced cancer approach end of life…

This paper serves to report on the successful management of four patients suffering from persistent paraneoplastic night sweats using the synthetic orally administered cannabinoid nabilone…”

http://www.ncbi.nlm.nih.gov/pubmed/18715188

Cannabinoids and gliomas.

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Abstract

“Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances–the endocannabinoids–that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Delta(9)-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/17952650

Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells.

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“The active components of Cannabis sativa L., Cannabinoids, traditionally used in the field of cancer for alleviation of pain, nausea, wasting and improvement of well-being have received renewed interest in recent years due to their diverse pharmacologic activities such as cell growth inhibition, anti-inflammatory activity and induction of tumor regression. Here we used several experimental approaches, which identified delta-9-tetrahydrocannabinol (Delta(9)-THC) as an essential mediator of cannabinoid antitumoral action.”

“CONCLUSIONS:

Delta(9)-THC is shown to significantly affect viability of GBM cells via a mechanism that appears to elicit G(1) arrest due to downregulation of E2F1 and Cyclin A. Hence, it is suggested that Delta(9)-THC and other cannabinoids be implemented in future clinical evaluation as a therapeutic modality for brain tumors.”

http://www.ncbi.nlm.nih.gov/pubmed/17934890

Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines

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“Marijuana and its derivatives have been used in medicine for many centuries, and currently there is a renewed interest in the study of the therapeutic effects of cannabinoids…”

“Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines…”

“…the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.”

“In conclusion, a cannabinoid-based therapeutic strategy for neural diseases devoid of undesired psychotropic side effects could find in CBD a valuable compound in cancer therapies along with the perspective of evaluating a synergistic effect with other cannabinoid molecules and/or with other chemotherapeutic agents as well as with radiotherapy. Whatever the precise mechanism underlying the CBD effects, the present results suggest a possible application of CBD as a promising, nonpsychoactive, antineoplastic agent.”

http://jpet.aspetjournals.org/content/308/3/838.full

A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

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“One of the most devastating forms of cancer is glioblastoma multiforme (grade IV astrocytoma), the most frequent class of malignant primary brain tumours. Current standard therapeutic strategies for the treatment of glioblastoma multiforme (surgical resection and focal radiotherapy) are only palliative…”

“The hemp plant Cannabis sativa L. produces approximately 60 unique compounds known as cannabinoids, of which Δ9-tetrahydrocannabinol (THC) is the most important owing to its high potency and abundance in cannabis. Δ9-Tetrahydrocannabinol exerts a wide variety of biological effects by mimicking endogenous substances – the so-called endocannabinoids – that bind to and activate specific cell surface receptors. cannabinoids have been proposed as potential antitumoral agents owing to their ability to inhibit the growth and angiogenesis of various types of tumour xenografts in animal models.”

“Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration… Cannabinoid delivery was safe and could be achieved without overt psychoactive effects…. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360617/

Cannabinoids As Cancer Hope

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NORML - Working to reform marijuana laws

by Paul Armentano
Senior Policy Analyst
NORML | NORML Foundation

““Cannabinoids possess … anticancer activity [and may] possibly represent a new class of anti-cancer drugs that retard cancer growth, inhibit angiogenesis (the formation of new blood vessels) and the metastatic spreading of cancer cells.” So concludes a comprehensive review published in the October 2005 issue of the scientific journal Mini-Reviews in Medicinal Chemistry.

Not familiar with the emerging body of research touting cannabis’ ability to stave the spread of certain types of cancers? You’re not alone.

For over 30 years, US politicians and bureaucrats have systematically turned a blind eye to scientific research indicating that marijuana may play a role in cancer prevention — a finding that was first documented in 1974. That year, a research team at the Medical College of Virginia (acting at the behest of the federal government) discovered that cannabis inhibited malignant tumor cell growth in culture and in mice. According to the study’s results, reported nationally in an Aug. 18, 1974, Washington Post newspaper feature, administration of marijuana’s primary cannabinoid THC, “slowed the growth of lung cancers, breast cancers and a virus-induced leukemia in laboratory mice, and prolonged their lives by as much as 36 percent.”

Despite these favorable preclinical findings, US government officials dismissed the study (which was eventually published in the Journal of the National Cancer Institute in 1975), and refused to fund any follow-up research until conducting a similar — though secret — clinical trial in the mid-1990s. That study, conducted by the US National Toxicology Program to the tune of $2 million concluded that mice and rats administered high doses of THC over long periods experienced greater protection against malignant tumors than untreated controls.

Rather than publicize their findings, government researchers once again shelved the results, which only came to light after a draft copy of its findings were leaked in 1997 to a medical journal, which in turn forwarded the story to the national media.

Nevertheless, in the decade since the completion of the National Toxicology trial, the U.S. government has yet to encourage or fund additional, follow up studies examining the cannabinoids’ potential to protect against the spread cancerous tumors.

Fortunately, scientists overseas have generously picked up where US researchers so abruptly left off. In 1998, a research team at Madrid’s Complutense University discovered that THC can selectively induce apoptosis (program cell death) in brain tumor cells without negatively impacting the surrounding healthy cells. Then in 2000, they reported in the journal Nature Medicine that injections of synthetic THC eradicated malignant gliomas (brain tumors) in one-third of treated rats, and prolonged life in another third by six weeks.

In 2003, researchers at the University of Milan in Naples, Italy, reported that non-psychoactive compounds in marijuana inhibited the growth of glioma cells in a dose dependent manner and selectively targeted and killed malignant cancer cells.

The following year, researchers reported in the journal of the American Association for Cancer Research that marijuana’s constituents inhibited the spread of brain cancer in human tumor biopsies. In a related development, a research team from the University of South Florida further noted that THC can also selectively inhibit the activation and replication of gamma herpes viruses. The viruses, which can lie dormant for years within white blood cells before becoming active and spreading to other cells, are thought to increase one’s chances of developing cancers such as Karposis Sarcoma, Burkitts lymphoma, and Hodgkins disease.

More recently, investigators published pre-clinical findings demonstrating that cannabinoids may play a role in inhibiting cell growth of colectoral cancer, skin carcinoma, breast cancer, and prostate cancer, among other conditions. When investigators compared the efficacy of natural cannabinoids to that of a synthetic agonist, THC proved far more beneficial – selectively decreasing the proliferation of malignant cells and inducing apoptosis more rapidly than its synthetic alternative while simultaneously leaving healthy cells unscathed.

Nevertheless, US politicians have been little swayed by these results, and remain steadfastly opposed to the notion of sponsoring – or even acknowledging – this growing body clinical research, preferring instead to promote the unfounded notion that cannabis use causes cancer. Until this bias changes, expect the bulk of research investigating the use of cannabinoids as anticancer agents to remain overseas and, regrettably, overlooked in the public discourse.”

http://norml.org/component/zoo/category/cannabinoids-as-cancer-hope