Involvement of PPARγ in the antitumoral action of cannabinoids on hepatocellular carcinoma.

Logo of cddis “Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. In this study, we examined whether the PPARγ-activated pathway contributed to the antitumor effect of two cannabinoids, Δ9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC cells. Taken together, we demonstrate for the first time that the antiproliferative action of the cannabinoids THC and JWH-015 on HCC, in vitro and in vivo, are modulated by upregulation of PPARγ-dependent pathways.”  http://www.ncbi.nlm.nih.gov/pubmed/23640460

“The antitumor activity of cannabinoids against HCC cells has been related to the ability of these drugs to induce apoptosis and autophagy. In particular, it has been previously described that cannabinoids arrest cell proliferation, reduce cell migration and inhibit angiogenesis, and therefore, cannabinoid-like compounds offer a therapeutic potential for the treatment of many types of cancer.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674350/

“We here illustrate that the cannabinoids THC and JWH-015 exert antitumor effect against the human HCC cell lines HepG2 and HUH-7 in vitro and in vivo through PPARγ.”  https://www.nature.com/articles/cddis2013141

Evaluation of anti-invasion effect of cannabinoids on human hepatocarcinoma cells.

“Cancer is a disease characterized by abnormal growth of cells. One of the most common types of liver cancers is called hepatocellular carcinoma (HCC) which is highly metastatic. As most of cannabinoids have shown anticancer effect against different cell lines in a number of reports, a biological investigation of two cannabinoids, CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist) was carried out in this study.

In an attempt to find natural products as a new solution of cancer, this study was designed to investigate the potential antitumoral and anti-invasive activity of cannabinoids…

The results revealed that both cannabinoids reduce cell viability, cell invasion as well as MMP-2 and MMP-9 expression in higher dose of 20 nM. Furthermore, higher concentrations of examined cannabinoids were more effective.

These data suggest ACEA and CB65 as an option for novel treatment of hepatocellular cancer.

Our findings may contribute to design of new therapeutic strategies for the management of HCC.”

http://www.ncbi.nlm.nih.gov/pubmed/22978792

Antitumor Effects of THC.

“1-Trans-[delta.sup.9]-tetrahydrocannabinol (THC) the main active component of marijuana, has been shown to exhibit anticancer activity.

Galve-Roperh et al. reported that intratumoral administration of THC induces apoptosis of transformed neural cells in culture, and also induces a considerable regression of malignant gliomas in Wistar rats and in mice… These authors suggest that their “results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.”

Thus, in our studies, rats and mice that received THC for 2 years exhibited body weight reductions, enhanced survival rates, and decreased tumor incidences in several sites, mainly organs under hormonal control.

These earlier experimental carcinogenesis results on THC clearly lend further validity to the notion that cannabinoids may indeed be anticarcinogenic.”

http://www.thefreelibrary.com/Antitumor+Effects+of+THC.-a068148345

“Antitumor effects of THC.” http://www.ncbi.nlm.nih.gov/pubmed/11097557

Study: THC Not Cancer-Causing

A federal study completed more than two years ago reportedly found that marijuana’s main ingredient did not cause cancer in laboratory animals. A 126-page report on the $2 million study has not been published, although expert reviewers found in June 1994 that the scientific methods used and the conclusions reached were sound, The Boston Globe reported today.

The findings go against the contention of some federal officials that marijuana is carcinogenic. The study will likely add grist to the debate over using marijuana for medical treatment.

A spokesman for White House drug policy adviser Barry R. McCaffrey said his office was not aware of the study.

The Globe said the National Toxicology Program study was revealed earlier this month in a newsletter called AIDS Treatment News.

According to the probe, high doses of the main active ingredient in marijuana, _ tetrahydrocannabinol, or THC _ were put directly into the stomachs of mice and rats daily for two years.

“We found absolutely no evidence of cancer,” said John Bucher, deputy director of the National Toxicology Program.

Because the animals were not exposed to marijuana smoke, the potential of inhaled marijuana to cause cancer was not looked at.

The study was overseen by the Federal Drug Administration, the National Cancer Institute and other federal agencies.

Bucher said publication of the report was overdue, but his agency had not been pressured to bury it. A personnel shortage caused the delay, he said.

The New England Journal of Medicine has come out in favor of allowing doctors to prescribe marijuana for medical purposes.

Some doctors believe marijuana can relieve internal eye pressure in glaucoma, control nausea in cancer patients on chemotherapy and combat the severe weight loss seen in AIDS patients.

However, Clinton administration officials note that such uses of marijuana have not been proved.”

Associated Press, Jan 30, 1997 BOSTON

http://www.ukcia.org/research/cancer.php

Medical Marijuana For Arthritis: A Natural Cure?

“TruthOnPot.com – Medical marijuana seems to be a gift from nature for anyone who suffers from pain, which is a symptom that most patients with arthritis are all-too-familiar with. Interestingly, the earliest evidence of medical marijuana’s use as a treatment for arthritis dates as far back as 2800 BC, which makes it more of a historical finding than a scientific breakthrough.
 

Today, more than 31 million Americans suffer from arthritis. And while the Arthritis Foundation lists over 100 different medications that are available for this disease, many patients continue to suffer from painful and often debilitating symptoms without adequate relief.

For those patients, medical marijuana seems to provide hope.”

Read More: http://www.truthonpot.com/2013/04/18/medical-marijuana-for-arthritis-a-natural-cure/

Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4+ T Cells

“Agents that activate cannabinoid receptor pathways have been tested as treatments for cachexia, nausea or neuropathic pain in HIV-1/AIDS patients… Cannabinoid agonists activate the CB1R and CB2R cannabinoid receptors…

Cannabinoid agonists are currently under investigation for the treatment of AIDS-associated cachexia, nausea, and neuropathic pain. One such drug, dronabinol (Δ9-THC; Marinol®), has won Food and Drug Administration (FDA) approval for treatment of HIV-associated anorexia. Additionally, the prescription of smoked or ingested cannabis (marijuana) for treatment of AIDS-related symptoms has been approved…. Despite the use of cannabinoids by HIV/AIDS patients, few studies have investigated the impact of such drugs in regard to viral pathogenesis or immune regulation…

….Indeed, both smoked marijuana and dronabinol were reported to increase total CD4+ T cell number and naïve T cell number over a 21-day period. A decrease in viral load was also observed in these patients. Similarly, in SIV infected rhesus macaques, Δ9-THC exposure reduced viral load and CD4+ T cell depletion, significantly increasing animal survival over an 11 month period.

. Our findings suggest that CB2R activation in CD4+ T cells can inhibit actin reorganization and impair productive infection following cell-free or cell-associated viral acquisition of CXCR4-tropic HIV-1 in resting cells.

Therefore, the clinical use of CB2R agonists in the treatment of AIDS symptoms may also exert beneficial adjunctive antiviral effects against CXCR4-tropic viruses in late stages of HIV-1 infection.

Further study of cannabinoids and other neuroendocrine regulators that selectively modulate immune function may result in the discovery of new anti-viral drugs that can also mitigate AIDS-associated symptoms.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309010/

Cannabinoids may be therapeutic in breast cancer.

“Cannabinoids are a group of compounds synthesized exclusively by the Cannabis sativa plant, commonly known as marijuana. In 1990, the first cannabinoid-specific membrane (CB1) was characterized and cloned (Matsuda, Lolait, Brownstein, Young, & Bonner, 1990), which catapulted biomedical research on these unique compounds.

 Cannabinoids refer to both marijuana-derived compounds with the active ingredient of 9-tetrahydrocannabinol (THC) and also the synthetic molecules that activate the same primary targets as THC.

Therapeutic properties of marijuana have been well established; however, the clinical use of either plant-sourced or pure cannabinoids remains limited.

The anticachexia properties of cannabinoids are found in tetrahydrocannabinol (oral capsules of synthetically generated THC) and are used to manage weight loss, wasting syndrome, and nausea and vomiting associated with cancer treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/23448745

Cannabis for better sleep

“The use of both natural cannabinoids and cannabis extracts are associated with improved sleep in patients with various debilitating illnesses, according to a review of clinical trial data published in the journal Chemistry & Biodiversity.

“Cannabis … has been utilized for [the] treatment of pain and sleep disorders since ancient times,” authors wrote. “Modern clinical trials indicate that patients administered cannabis extracts report experiencing “more restful sleep, [an] increase [in] their daytime level of function, and [a] markedly improve[d] … quality of life.”

According to available data, of the 2,000 subjects that have been administered cannabis extracts in clinical trials, most “demonstrate marked improvement in subjective sleep parameters.”

Trial volunteers have not reported developing tolerance to the drug, even after using it for several years.

Full text of the study, “Cannabis, pain, and sleep: Lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine,” appears in the journal Chemistry & Biodiversity.”

http://azarius.net/news/193/Cannabis_for_better_sleep/

Smoking Cannabis Reduces Pain, Helps Sleep And Improves Mood For Those With Chronic Symptoms

“For patients with chronic (long-term) neuropathic pain, smoking cannabis was found to reduce symptoms of pain, improve mood and help sleep, a report published in CMAJ (Canadian Medical Journal Association) revealed. When damage or dysfunction of the nervous system results in chronic neuropathic pain, patients have few treatment options, such as antidepressants, local anesthetics, anticonvulsants or opioids. However, these medications often have undesirable side effects and do not work for everybody.

The authors inform that oral cannabinoids have been effective in reducing the symptoms of some types of pain. However, they many have different effects and risks compared to smoked cannabis.

Investigators from McGill University Health Centre (MUHC) and McGill University carried out a randomized, controlled trial to determine the analgesic effect of smoked cannabis in 21 patients, aged 18 years or more, all of them with chronic neuropathic pain. THC levels (drug potencies) were divided into 2.5%, 6% and 9.4%. Some participants also received a placebo (0%).

The researchers inform that there was a correlation between increased THC content and better sleep quality. Symptoms of depression and/or anxiety were also reduced at 9.5% THC level.”

More: http://www.medicalnewstoday.com/articles/199376.php

Study: Oral THC Administration Mitigates Sleep Apnea

“The oral administration of synthetic THC reduces symptoms of sleep apnea, according to clinical trial data published online in the scientific journal Frontiers in Psychiatry. Sleep apnea is a medical disorder characterized by frequent interruptions in breathing of up to ten seconds or more during sleep. The condition is associated with numerous physiological disorders, including fatigue, headaches, high blood pressure, irregular heartbeat, heart attack and stroke.

Investigators at the University of Illinois at Chicago, Department of Medicine assessed the safety, tolerability, and efficacy of dronabinol (oral THC in sesame seed oil) in 17 subjects with Obstructive Sleep Apnea.

Oral THC administration was associated with a significant change in Apnea Hypopnea Index over a 21-day period. Authors further determined dronabinol treatment to be safe and well tolerated.

They concluded, “These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy.”

Dronabinol, marketed under the trade name Marinol, is FDA-approved to treat nausea and vomiting caused by chemotherapy.”

http://norml.org/news/2013/02/14/study-oral-thc-administration-mitigates-sleep-apnea