Effect of a synthetic cannabinoid agonist on the proliferation and invasion of gastric cancer cells.

“Although cannabinoids are associated with antineoplastic activity in a number of cancer cell types, the effect in gastric cancer cells has not been clarified. In the present study, we investigated the effects of a cannabinoid agonist on gastric cancer cell proliferation and invasion.

The cannabinoid agonist WIN 55,212-2 inhibited the proliferation of human gastric cancer cells in a dose-dependent manner and that this effect was mediated partially by the CB(1) receptor. We also found that WIN 55,212-2 induced apoptosis and down-regulation of the phospho-AKT expression in human gastric cancer cells. Furthermore, WIN 55,212-2 treatment inhibited the invasion of gastric cancer cells, and down-regulated the expression of MMP-2 and VEGF-A through the cannabinoid receptors.

Our results open the possibilities in using cannabinoids as a new gastric cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/20336665

Antiproliferative mechanism of a cannabinoid agonist by cell cycle arrest in human gastric cancer cells.

“For gastric cancers, the antineoplastic activity of cannabinoids has been investigated in only a few reports and knowledge regarding the mechanisms involved is limited. We have reported previously that treatment of gastric cancer cells with a cannabinoid agonist significantly decreased cell proliferation and induced apoptosis.

Here, we evaluated the effects of cannabinoids on various cellular mediators involved in cell cycle arrest in gastric cancer cells. AGS and MKN-1 cell lines were used as human gastric cancer cells and WIN 55,212-2 as a cannabinoid agonist.

 …Cell cycle arrest preceded apoptotic response. Thus, this cannabinoid agonist can reduce gastric cancer cell proliferation via G1 phase cell cycle arrest, which is mediated via activation of the MAPK pathway and inhibition of pAKT.”

http://www.ncbi.nlm.nih.gov/pubmed/21312237

Cannabinoid Receptor Agonist as an Alternative Drug in 5-fluorouracil-resistant Gastric Cancer Cells.

“Fluorouracil is the main chemotherapeutic drug used for gastrointestinal cancers, which suffers the important problem of treatment resistance. There is little information whether cannabinoid agonists can be used as an alternative drug for fluorouracil-resistant gastric cancer cells. In this study, we investigated the effects of a cannabinoid agonist, WIN-55,212-2, on 5-fluorouracil (5-FU)-resistant human gastric cancer cells, to examine whether the cannabinoid agonist may be an alternative therapy.

These results indicate that a cannabinoid agonist may, indeed, be an alternative chemotherapeutic agent for 5-FU-resistant gastric cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/23749906

GW Pharmaceuticals: Giving New Meaning To ‘High Potential’

“GW Pharmaceuticals (GWPH) is an UK-based biopharmaceutical company focused on the discovery and development of cannabinoid-based products for a wide range of indications. GW has established a technology platform based on genetically modified cannabis plants and has become a leader in plant-derived cannabinoid therapeutics.

 GW’s lead program is Sativex, a cannabis extract based oromucosal spray whose main actives are the cannabinoids delta-9- tetrahydrocannabinol (THC), and cannabidiol (CBD). It is approved for the treatment of multiple sclerosis (MS) spasticity in 21 countries outside of the U.S and already marketed in seven countries (eight following Italian launch in Q213).

…While MS spasticity has provided proof-of-concept in the worldwide approvability of Sativex, a more meaningful commercial opportunity is in the treatment of opioid-refractory cancer pain. Sativex has been tested in two Phase II trials in cancer pain. The trials have demonstrated that Sativex is safe and effective when used in addition to opioids in patients whose cancer pain is not sufficiently managed by opioids alone. Based on these results, GW has initiated three Phase III trials. The first two are expected to complete during 2014 and support an FDA filing.”

More: http://seekingalpha.com/article/1490392-gw-pharmaceuticals-giving-new-meaning-to-high-potential

Marijuana Spray Proves Effective as Cancer Pain Treatment

“A mouth spray containing cannabinoids is effective in reducing pain in cancer patients who are still in pain despite using opioid medicines, according to a new study published in The Journal of Pain.”

 
“The oral mucosal spray known as nabixmols, which is marketed under the trade name Sativex, contains a formulation of cannabinoids, marijuana’s most active ingredients.”
 

More: http://americannewsreport.com/nationalpainreport/marijuana-spray-proves-effective-as-cancer-pain-treatment-8814518.html

A Double-Blind, Placebo-Controlled, Crossover Pilot Trial With Extension Using an Oral Mucosal Cannabinoid Extract for Treatment of Chemotherapy-Induced Neuropathic Pain.

“Neuropathic pain caused by chemotherapy limits dosing and duration of potentially life-saving anti-cancer treatment and impairs quality of life. Chemotherapeutic neuropathy responds poorly to conventional treatments, and there is an urgent medical need for new treatments. Recent preclinical studies demonstrate that cannabinoid agonists suppress established chemotherapy-evoked neuropathy.

This was a pilot trial to begin to investigate a currently available cannabinoid agent, nabiximols (oral mucosal spray containing cannabinoids), in the treatment of chemotherapy-induced neuropathic pain.

CONCLUSION:

Chemotherapy-induced neuropathic pain is particularly resistant to currently available treatments. This pilot trial found a number needed to treat of five and an average decrease of 2.6 on an 11-point NRS-PI in five “responders” (as compared with a decrease of 0.6 with placebo) and supports that it is worthwhile to study nabiximols in a full randomized, placebo-controlled trial of chemotherapy-induced neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/23742737

Delta–9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer – Harvard University

“Lung cancer is the major cause of cancer-related mortality worldwide.Many of these over-express epidermal growth factor receptor(EGFR), and are usually highly aggressive and resistant to chemotherapy.

Recent studies have shown that {Delta}-9 Tetrahydrocannabinol (THC),the major component of Cannabis sativa, possess anti-tumor propertiesagainst various types of cancers.

 However, not much is knownabout its effect on lung cancer. In this study, we sought tocharacterize the effect of THC on EGF-induced growth and metastasisof human non small lung cancer cell (NSCLC) lines A549 and SW-1573.

We demonstrate that these cell lines and primary tumor samplesderived from lung cancer patients express cannabinoids receptorsCB1 and CB2, the known targets for THC action. We further showthat THC inhibits EGF-induced growth in these cell lines. Inaddition THC attenuated EGF-stimulated chemotaxis and chemoinvasion.Next we characterized the effect of THC on in vivo lung cancergrowth and metastasis in a murine model. A549 cells were implantedin SCID mice (n=6 per group) through subcutaneous and intravenousinjections to generate subcutaneous and lung metastatic cancer,respectively. THC (5mg/kg body wt.) was administered once dailythrough intraperitoneal injections for 21 days. The mice wereanalyzed for tumor growth and lung metastasis.

 A significantreduction (~50%) in tumor weight and volume were observed inTHC treated animals compared to the vehicle treated animals.THC treated animals also showed a significant (~60%) reductionin macroscopic lesions on the lung surface in comparison tovehicle treated control. Immunohistochemical analysis of thetumor samples from THC treated animals revealed anti-proliferativeand anti-angiogenic effects of THC with significant reductionin staining for Ki67, a proliferative marker and CD31, an endothelialmarker indicative of vascularization. Investigation into thesignaling events associated with reduced EGF-induced functionaleffects revealed that THC also inhibits EGF-induced Akt phosphorylation.Akt is a central signaling molecule of EGFR-mediated signalingpathways and it regulates a diverse array of cellular functions,including proliferation, angiogenesis, invasion and apoptosis.

Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.”

http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/4749%20?maxtoshow&hits=80&RESULTFORMAT&fulltext=cannabinoid&searchid=1&FIRSTINDEX=1760&resourcetype=HWCIT

Cannabidiol (CBD): Fighting Inflammation & Aggressive Forms of Cancer

“Marijuana contains at least 60 known chemicals called cannabinoids, which activate cannabinoid receptors in your body. Tetrahydrocannabinol, or THC, is the main component responsible for the psychoactive effects, or “high,” marijuana is known for. While THC is known to have some medicinal value, there has been recent investigation into a new cannabinoid that is rumored to have more medicinal benefits than any single pharmaceutical drug on the market.”

“What is Cannabidiol (CBD)?

This cannabinoid is known as Cannabidiol (CBD), and is the second most abundant cannabinoid in cannabis. Research done by G.W. Pharmaceuticals suggests that CBD could be used for treating symptoms of rheumatoid arthritis and other autoimmune diseases, diabetes, nausea, bowel disorders, and many other hard-to-control side effects. According to an article from Projectcbd.com, CBD has even demonstrated neuroprotective effects, and its anti-cancer potential is currently being explored.

While it was originally believed that THC is a breakdown product of CBD, it is now known that both THC and CBD are actually metabolites of their decarboxylated acidic forms, THCa and CBDa. These acidic precursors are decarboxylated (essentially dried) by heat or extraction to produce THC and CBD; only then do they become psychoactive. The compound has medicinal benefits without the “high” that some patients do not desire. This makes CBD appealing to patients who are looking for an alternative to their current meds, which often have opiate-like effects.”

More: http://www.medicaljane.com/2012/12/20/cannabidiol-cbd-medicine-of-the-future/

Marijuana habit not linked to lung cancer – Clinical Psychiatry News

“Regular cannabis smokers are no more likely to develop lung cancer than are people who indulge occasionally.”

“The finding of no significant increased risk held true whether the smokers imbibed once or twice – or more – each day, and regardless of how many years they had smoked, Dr. Li Rita Zhang reported at the annual meeting of the American Association of Cancer Research.”More: http://www.clinicalpsychiatrynews.com/news/across-specialties/single-article/marijuana-habit-not-linked-to-lung-cancer/73840afd2cca226b9e6a9ddc7cb0d039.html

http://www.oncologypractice.com/single-view/marijuana-habit-not-linked-to-lung-cancer/73840afd2cca226b9e6a9ddc7cb0d039.html

Medicinal Use of Marijuana — Polling Results – The New England Journal of Medicine

“Readers recently joined in a lively debate about the use of medicinal marijuana. In Clinical Decisions,1 an interactive feature in which experts discuss a controversial topic and readers vote and post comments, we presented the case of Marilyn, a 68-year-old woman with metastatic breast cancer. We asked whether she should be prescribed marijuana to help alleviate her symptoms. To frame this issue, we invited experts to present opposing viewpoints about the medicinal use of marijuana. J. Michael Bostwick, M.D., a professor of psychiatry at Mayo Clinic, proposed the use of marijuana “only when conservative options have failed for fully informed patients treated in ongoing therapeutic relationships.” Gary M. Reisfield, M.D., from the University of Florida, certified in anesthesiology and pain medicine, and Robert L. DuPont, M.D., a clinical professor of psychiatry at Georgetown Medical School, provide a counterpoint, concluding that “there is little scientific basis” for physicians to endorse smoked marijuana as a medical therapy.

We were surprised by the outcome of polling and comments, with 76% of all votes in favor of the use of marijuana for medicinal purposes — even though marijuana use is illegal in most countries. A total of 1446 votes were cast from 72 countries and 56 states and provinces in North America, and 118 comments were posted. However, despite the global participation, the vast majority of votes (1063) came from the United States, Canada, and Mexico. Given that North America represents only a minority of the general online readership of the Journal, this skew in voting suggests that the subject of this particular Clinical Decisions stirs more passion among readers from North America than among those residing elsewhere. Analysis of voting across all regions of North America showed that 76% of voters supported medicinal marijuana. Each state and province with at least 10 participants casting votes had more than 50% support for medicinal marijuana except Utah. In Utah, only 1% of 76 voters supported medicinal marijuana. Pennsylvania represented the opposite extreme, with 96% of 107 votes in support of medicinal marijuana.

Outside North America, we received the greatest participation from countries in Latin America and Europe, and overall results were similar to those of North America, with 78% of voters supporting the use of medicinal marijuana. All countries with 10 or more voters worldwide were at or above 50% in favor. There were only 43 votes from Asia and 7 votes from Africa, suggesting that in those continents, this topic does not resonate as much as other issues.

Where does this strong support for medicinal marijuana come from? Your comments show that individual perspectives were as polarized as the experts’ opinions. Physicians in favor of medicinal marijuana often focused on our responsibility as caregivers to alleviate suffering. Many pointed out the known dangers of prescription narcotics, supported patient choice, or described personal experience with patients who benefited from the use of marijuana. Those who opposed the use of medicinal marijuana targeted the lack of evidence, the lack of provenance, inconsistency of dosage, and concern about side effects, including psychosis. Common in this debate was the question of whether marijuana even belongs within the purview of physicians or whether the substance should be legalized and patients allowed to decide for themselves whether to make use of it.

In sum, the majority of clinicians would recommend the use of medicinal marijuana in certain circumstances. Large numbers of voices from all camps called for more research to move the discussion toward a stronger basis of evidence.”

http://www.nejm.org/doi/full/10.1056/NEJMclde1305159

“New England Journal of Medicine Endorses Medical Marijuana; San Francisco Medical Society Releases Study; New York Times Editorial Welcomes Debate” http://ndsn.org/feb97/nejm.html