Category Archives: Hepatocellular Carcinoma (HCC)

Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model.

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“Extensive structure-activity relationship studies have demonstrated that specific requirements within the cannabinoid structure are necessary to produce potent analgesia.

A three-point association between the agonist and the receptor mediating analgesia consists of: 1) the C ring hydroxyl, 2) the phenolic A ring hydroxyl, and 3) the A ring alkyl hydrophobic side chain. Potent tricyclic and bicyclic structures were synthesized as “nonclassical” cannabinoid analgetics that conform to this agonist-receptor three-point interaction model.

At the cellular level, centrally active cannabinoid drugs inhibit adenylate cyclase activity in a neuroblastoma cell line. The structure-activity relationship profile for inhibition of adenylate cyclase in vitro was consistent with this same three-point association of agonists with the receptor.

A correlation exists between the potency of drugs to produce analgesia in vivo and to inhibit adenylate cyclase in vitro.

Based on the parallels in structure-activity relationships and the enantioselective effects, it is postulated that the receptor that is associated with the regulation of adenylate cyclase in vitro may be the same receptor as that mediating analgesia in vivo.

A conceptualization of the cannabinoid analgetic receptor is presented.”

http://www.ncbi.nlm.nih.gov/pubmed/3352594

Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase.

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“A putative endogenous cannabinoid ligand, arachidonylethanolamide (termed “anandamide”), was isolated recently from porcine brain.

Here we demonstrate that this compound is a specific cannabinoid agonist and exerts its action directly via the cannabinoid receptors.

Anandamide specifically binds to membranes from cells transiently (COS) or stably (Chinese hamster ovary) transfected with an expression plasmid carrying the cannabinoid receptor DNA but not to membranes from control nontransfected cells.

Moreover, anandamide inhibited the forskolin-stimulated adenylate cyclase in the transfected cells and in cells that naturally express cannabinoid receptors (N18TG2 neuroblastoma) but not in control nontransfected cells. As with exogenous cannabinoids…

These data indicate that anandamide is an endogenous agonist that may serve as a genuine neurotransmitter for the cannabinoid receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/8515284

Regulation of adenylate cyclase by cannabinoid drugs. Insights based on thermodynamic studies.

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“The abilities of lipophilic cannabinoid drugs to regulate adenylate cyclase activity in neuroblastoma cell membranes were analyzed by thermodynamic studies…

These data suggest that, for the entropy-driven hormone-stimulated adenylate cyclase enzyme, less disorder of the system occurs in the presence of regulators that inhibit the enzyme via Gi.

In summary, thermodynamic data suggest that cannabidiol can influence adenylate cyclase by increasing membrane fluidity, but that the inhibition of adenylate cyclase by delta 9-tetrahydrocannabinol is not related to membrane fluidization.”

http://www.ncbi.nlm.nih.gov/pubmed/2554920

“Regulation of adenylate cyclase in a cultured neuronal cell line by marijuana constituents, metabolites of delta-9-tetrahydrocannabinol, and synthetic analogs having psychoactivity.” http://www.ncbi.nlm.nih.gov/pubmed/2830535

Cannabinoid inhibition of adenylate cyclase: relative activity of constituents and metabolites of marihuana.

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“delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.”

http://www.ncbi.nlm.nih.gov/pubmed/3601007

Therapeutic potential of cannabinoid medicines.

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Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Cannabis Ingredient Can Help Cancer Patients Regain Their Appetites And Sense Of Taste

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“The active ingredient in cannabis can improve the appetites and sense of taste in cancer patients, according to a new study published online in the cancer journal, Annals of Oncology  today.

Loss of appetite is common among cancer patients, either because the cancer itself or its treatment affects the sense of taste and smell, leading to decreased enjoyment of food. This, in turn, can lead to weight loss, anorexia, a worse quality of life and decreased survival; therefore, finding effective ways of helping patients to maintain a good diet and consume enough calories is an important aspect of their treatment.

The majority of THC-treated patients (64%) had increased appetite, three patients (27%) showed no change, and one patient’s data was incomplete. No THC-treated patients showed a decrease in appetite. By contrast, the majority of patients receiving placebo had either decreased appetite (50%) or showed no change (20%).

Although there was no difference in the total number of calories consumed by both groups, the THC-treated patients tended to increase the proportion of protein that they ate, and 55% reported that savoury foods tasted better, whereas no patients in the placebo group reported an increased liking for these foods. (Cancer patients often find that meat smells and tastes unpleasant and, therefore, they eat less of it).

In addition, THC-treated patients reported better quality of sleep and relaxation than in the placebo group.”

More:  http://www.medicalnewstoday.com/articles/217062.php

“Miracle” Cannabis Oil: May Treat Cancer, But Money and the Law Stand in the Way of Finding Out

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“Cannabis oil, which cancer-sufferers credit with saving their lives, and which is supposedly useful in healing other ailments, from diabetes to skin rashes, is made by distilling raw bud down to its essential ingredients.”

 

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“First it was a cough. Then it was bronchitis. Then it was time to say goodbye to Michelle Aldrich.

The year 2011 was supposed to be a good one for the 66-year-old. That June, she and her husband, Michael, were feted with a lifetime achievement award by High Times magazine for their four decades of work on marijuana legalization. Yet something was off. She was smoking a lot, maybe more than ever.

And she couldn’t get high.

In the fall of that year — a bad time for the local marijuana movement, as the federal Justice Department began shutting down hundreds of California medical cannabis dispensaries — Aldrich went in to see a series of doctors for what she thought was a flu that just refused to go away.

After six weeks of progressively worse diagnoses — flu became bronchitis, which became pneumonia — a CT scan revealed the cause behind the “heat” she felt in the middle of her chest. A tumor, “poorly-differentiated non-small cell adenocarcinoma.” In other words, stage 3 lung cancer.

Lung cancer is a killer, with nearly 70 percent of new cases resulting in deaths, according to statistics published by the National Cancer Institute. “I thought I was going to die,” Aldrich says from her Marina District apartment. But she didn’t. And now, she is busy telling anyone who will listen that, along with diet and chemotherapy, a concoction of highly concentrated cannabis oil eliminated her cancer in less than four months.”

More: http://www.sfweekly.com/2013-04-24/news/key-words-cannabis-oil-cure-cancer-constance-finley/full/

Fighting Cancer: Another Study Reveals the Cannabis and Cancer Prevention Link

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“Does marijuana cause cancer? Revealing the link between cannabis and cancer yet again, researchers with the California Pacific Medical Center in San Francisco have released findings that further bolster cannabis as an anti-cancer solution.
The researchers have found a compound in the much-talked-about plant could “halt the spread” of many types of aggressive cancers, including breast cancer.

The Cannabis and Cancer Link

Cannabidiol is the compound, and while it fights cancer cells, it does not produce the high feelings commonly associated with cannabis. Instead, it seems to “switch off” the gene responsible for metastasizing breast cancer.

They reportedly found the compound doesn’t only stop the breast cancer cells from growing, but even causes them to return back to normal cells, cancer-free.”

More: http://naturalsociety.com/study-positive-cannabis-and-cancer-link/

Smoking Marijuana Does Not Cause Lung Cancer

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“New research shows here seems to be something in pot that actually undermines cancer, instead of causing it. — and the media are doing their best to ignore it.
 
There is a groundswell of attention in the news to marijuana’s role in causing and preventing various types of cancers. Last week, AlterNet published an article from the Marijuana Policy Project about a new study finding that pot smokers have a lower risk of head and neck cancers than people who don’t smoke pot…
 
Smoking pot doesn’t cause lung cancer. In fact, the study found that cigarette smokers who also smoked marijuana were at a lower risk of contracting lung cancer than tobacco-only smokers…
 

You’d think it would have been very big news in June 2005 when UCLA medical school professor Donald Tashkin reported that components of marijuana smoke somehow prevent them from becoming malignant.

 In other words, something in marijuana exerts an anti-cancer effect!”

More:http://www.alternet.org/story/142271/smoking_marijuana_does_not_cause_lung_cancer

Marijuana Unlikely to Cause Head, Neck, or Lung Cancer – WebMD

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“Marijuana, unlike tobacco and alcohol, does not appear to cause head, neck, or lung cancer, says a researcher from Johns Hopkins Medical School in Baltimore who presented findings from a study here recently at a meeting of internal medicine physicians.

There has been an ongoing debate about whether marijuana is as dangerous as tobacco in terms of cancer development. Daniel E. Ford, MD, tried to sort out the evidence by the lifestyles — including marijuana, tobacco, and alcohol use — of 164 persons who were newly diagnosed with head, neck, or lung cancer compared to a group of 526 healthy persons living in the same area. The average age of patients was 49, while the average age of the healthy volunteers was 44. The cancer patients were all treated at four Baltimore-area hospitals, and the “controls” (healthy comparison group) were selected from a large group of people living in the Baltimore area who had been participating in an ongoing study. Ford tells WebMD that he wanted to find out whether the cancer patients were more likely to smoke marijuana or tobacco or to drink than were the healthy volunteers.

According to Ford, he thought he would find an association between marijuana use and cancer, but “that the association would fall away when we corrected for tobacco use. That was not the case. The association was never there.” And that surprised him because of the way marijuana is smoked: deep inhalations, with the smoke held in for effect. “It seemed natural that there would be some connection,” he tells WebMD.

Based on these findings, Ford says that cancer prevention efforts should “remain focused on tobacco and alcohol, two known carcinogens.””

More: http://www.webmd.com/smoking-cessation/news/20000508/marijuana-unlikely-to-cause-cancer

Update from WebMD:

“Pot Smoking Not Linked to Lung Cancer

Study Shows No Increased Risk for Even the Heaviest Marijuana Smokers.
 
People who smoke marijuana do not appear to be at increased risk for developing lung cancer, new research suggests.While a clear increase in cancercancer risk was seen among cigarette smokers in the study, no such association was seen for regular cannabis users.Even very heavy, long-term marijuana users who had smoked more than 22,000 joints over a lifetime seemed to have no greater risk than infrequent marijuana users or nonusers.”

More: http://www.webmd.com/lung-cancer/news/20060523/pot-smoking-not-linked-to-lung-cancer