Psychoactive cannabinoids reduce gastrointestinal propulsion and motility in rodents.

“Marijuana has been reported to be an effective antinauseant and antiemetic in patients receiving cancer chemotherapy.

Whether this is due to psychological changes, central antiemetic properties and/or direct effects on gastrointestinal (GI) function is not known. The purpose of these investigations was to determine whether the major constituents of marijuana and the synthetic cannabinoid nabilone have any effects on GI function which can be detected in rodent models of GI transit and motility. Intravenous delta 9-tetrahydrocannabinol (delta 9-THC) slowed the rate of gastric emptying and small intestinal transit in mice and in rats. Delta 9,11-THC, cannabinol and nabilone given i.v. also inhibited small intestinal transit in mice, but were less effective in reducing gastric emptying. Cannabidiol given i.v. had no effect on gastric emptying or intestinal transit. Those cannabinoids which inhibited GI transit did so at doses equal to, or lower, than those reported to produce central nervous system activity. In rats, delta 9-THC produced greater inhibition of gastric emptying and small intestinal transit than large bowel transit, indicating a selectivity for the more proximal sections of the gut. In addition, i.v. delta 9-THC decreased the frequency of both gastric and intestinal contractions without altering intraluminal pressure. Such changes probably reflect a decrease in propulsive activity, without change in basal tone.

These data indicate that delta 9-THC, delta 9,11-THC, cannabinol and nabilone (but not cannabidiol) exert an inhibitory effect on GI transit and motility in rats.”

http://www.ncbi.nlm.nih.gov/pubmed/2542532

Pharmacological synergism between cannabinoids and paclitaxel in gastric cancer cell lines.

“Orally applicable Delta9-tetrahydrocannabinol and its synthetic derivatives have been used as antiemetic drugs during chemotherapy in cancer patients.

 However, it is not well known how cannabinoids influence the effects of chemotherapeutic agents on malignant tumors. In this study, we investigated how the endogenous cannabinoid anandamide (AEA) changes the effect of paclitaxel on gastric cancer cell lines.

 In the human gastric cancer cell line, HGC-27, which express cannabinoid receptor 1 (CB1), AEA stimulated proliferation at concentrations under 1 microM, while it strongly suppressed proliferation through the induction of apoptosis at 10 microM. This bimodal effect was reproduced by a selective CB1 agonist, arachidonyl-2-chloroethylamide, although the effects were less marked. When AEA was used with paclitaxel, AEA at 10 microM synergistically enhanced the cytotoxic effect of paclitaxel, whereas it showed no significant effect at lower concentrations. Flow cytometric analysis revealed that addition of 10 microM AEA synergistically enhanced paclitaxel-induced apoptosis, possibly through the activation of caspase-3, -8, and -9.

Our results suggest that cannabinoids could be a good palliative agent for cancer patients receiving paclitaxel.”

http://www.ncbi.nlm.nih.gov/pubmed/19394652

Even More Science Suggesting That Cannabinoids May Halt Diabetes

“Preclinical study data published online in the scientific journal Nutrition & Diabetes reports that tetrahydrocannabivarin (THCV) — a naturally occurring analogue of THC — possesses positive metabolic effects in animal models of obesity.

British researchers assessed the effects of THCV administration on dietary-induced and genetically modified obese mice. Authors reported that although THCV administration did not significantly affect food intake or body weight gain in any of the models, it did produce several metabolically beneficial effects, including reduced glucose intolerance, improved glucose tolerance, improved liver triglyceride levels, and increased insulin sensitivity.

Researchers concluded: “Based on these data, it can be suggested that THCV may be useful for the treatment of the metabolic syndrome and/or type 2 diabetes (adult onset diabetes), either alone or in combination with existing treatments. Given the reported benefits of another non-THC cannabinoid, CBD in type 1 diabetes, a CBD/THCV combination may be beneficial for different types of diabetes mellitus.””

More: http://beforeitsnews.com/marijuana-debate/2013/06/even-more-science-suggesting-that-cannabinoids-may-halt-diabetes-2444932.html

The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity

“Δ9-Tetra-hydrocannabivarin (THCV) is a naturally occurring analogue of the psychoactive principle of cannabis, Δ9-tetra-hydrocannabinol (THC).

THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists.

In conclusion, THCV produces therapeutic metabolic effects in two different mouse models of obesity. In particular, its strongest effects are exerted on plasma glucose and insulin levels, especially following an OGTT in DIO mice and on liver triglycerides in ob/obmice.

Based on these data, it can be suggested that THCV may be useful for the treatment of the metabolic syndrome and/or type 2 diabetes, either alone or in combination with existing treatments. Given the reported benefits of another non-THC cannabinoid, CBD in type 1 diabetes, a CBD/THCV combination may be beneficial for different types of diabetes mellitus.”

Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671751/

Medicinal marijuana stops seizures, brings hope to a little Black Forest girl

“Six-year-old Charlotte Figi, a picture of precious in her “Gatsby”-style bob and blue toenails, stands patiently as her mother reaches up her dress to change her out of her soiled Pull-Ups. – Charlotte never says a word. She hasn’t in the past hour, and won’t for at least another 30 minutes, when she finally whispers the name of a visitor who is about to leave.

In the Figi household, these are signs of progress: Charlotte saying something. Charlotte eating and drinking. Charlotte standing and walking.

Charlotte breathing.

About 18 months ago, in the winter of 2011, Paige and Matt Figi signed a “do not resuscitate” order telling medical personnel to forgo life-saving measures for their daughter and let fate take its course.

They’d done all they could to control the seemingly endless, violent seizures that hit Charlotte 20, 40, 60 times a day. They put her on an extreme diet. They tried at least a dozen medications, many with harmful side effects. Despite some promising starts, nothing worked. And the rescue medications they were giving her to stop the seizures in fact stopped her breathing. CPR brought her back to life more than once.

After years of watching a cruel, incurable genetic disorder called Dravet Syndome rob their daughter of her basic bodily functions and send her into convulsions that caused head injuries and broken teeth, they had reached the end.

“We really thought, this is a horrible existence; she’s not going to live much longer.” Paige says. “This is not a life for her. This is torture. She is suffering all day. I’m not OK with this. She wasn’t even human anymore. She’d lie in my arms drooling, seizing, screaming and crying.”

Then, in an act of desperation, or inspiration – or maybe both – Matt called Paige from overseas, where he was working, and suggested a radical approach to Charlotte’s treatment.

“We need to try cannabis for Charlotte,” he told Paige. “We live in a compassionate state.”

Fifteen months later, the little girl with the DNR order is standing in the kitchen of their Black Forest home with her mother getting her Pull-Ups changed, cuddling in the arms of a visitor, playing with toys and strategically pushing the buttons on her “talker,” an electronic device that communicates when Charlotte can’t.

Her seizures have dropped from 1,200 a month to three, and the ones she has are shorter in duration and less severe. She’s off all the other medications with their troubling side effects. And, as one of the youngest medical marijuana patients in Colorado, her dramatic turnaround is starting to draw national attention, with a CNN report on the horizon.”

More: http://gazette.com/medicinal-marijuana-stops-seizures-brings-hope-to-a-little-girl/article/1502070

New Study: Cannabinoids Protect the Brain and Heart From Injury

“Cannabis is in the news again for its purported medicinal benefits, with researchers in Israel last week indicating it may help prevent trauma to the brain in certain circumstances and may also help with cardiac problems. A few months ago an English pharmaceutical company that manufactures cannabinoids announced it was developing a new treatment for epilepsy using them.”

Los Angeles City Council Votes To Ban Medical Marijuana Dispensaries

“Prof. Yosef Sarne in the Adelson Center for the Biology of Addictive Diseases in the Department of Physiology and Pharmacology at Tel Aviv University says that cannabis has neuro-protective qualities. He has found that extremely low doses of tetrahydrocannabinol or THC- the psychoactive component of marijuana- can protect the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures, or toxic drugs.”

More: http://jewishbusinessnews.com/2013/06/09/new-study-cannabinoids-protect-the-brain-and-heart-from-injury/

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