INSIGHT ON THE IMPACT OF ENDOCANNABINOID SYSTEM IN CANCER: A REVIEW.

Posted on April 18, 2018 by David

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“In the last decades, the endocannabinoid system has attracted a great interest in medicine and cancer disease is probably one of its most promising therapeutic areas.

On the one hand, endocannabinoid system expression has been found altered in numerous types of tumours compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type.

On the other hand, it has been reported that cannabinoids exert an anticancer activity by inhibiting the proliferation, migration and/or invasion of cancer cells; and also tumour angiogenesis.

The endocannabinoid system may be considered as a new therapeutic target, although further studies to fully establish the effect of cannabinoids on tumour progression remain necessary.”

https://www.ncbi.nlm.nih.gov/pubmed/29663308

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14331

Study shows non-hallucinogenic cannabinoids are effective anti-cancer drugs

Posted on June 5, 2017 by David

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“New research has shown that the non-hallucinogenic components of cannabis could act as effective anti-cancer agents. The anti-cancer properties of tetrahydrocannabinol (THC), the primary hallucinogenic component of cannabis, has been recognised for many years, but research into similar cannabis-derived compounds, known as cannabinoids, has been limited.

The study was carried out by a team at St George’s, University of London. It has been published in the journal Anticancer Research. The team, led by Dr Wai Liu and colleagues carried out laboratory investigations using a number of cannabinoids, either alone or in combination with each other, to measure their anti-cancer actions in relation to leukaemia.

Of six cannabinoids studied, each demonstrated anti-cancer properties as effective as those seen in THC. Importantly, they had an increased effect on cancer cells when combined with each other.

Dr Liu said: “This study is a critical step in unpicking the mysteries of cannabis as a source of medicine. The cannabinoids examined have minimal, if any, hallucinogenic side effects, and their properties as anti-cancer agents are promising.

“These agents are able to interfere with the development of cancerous cells, stopping them in their tracks and preventing them from growing. In some cases, by using specific dosage patterns, they can destroy cancer cells on their own.

“Used in combination with existing treatment, we could discover some highly effective strategies for tackling cancer. Significantly, these compounds are inexpensive to produce and making better use of their unique properties could result in much more cost effective anti-cancer drugs in future.”

The study examined two forms of cannabidiol (CBD), two forms of cannabigerol (CBG) and two forms of cannabigevarin (CBGV). These represent the most common cannabinoids found in the cannabis plant apart from THC.” https://www.sgul.ac.uk/alumni/magazine/study-shows-non-hallucinogenic-cannabinoids-are-effective-anti-cancer-drugs

“Enhancing the Activity of Cannabidiol and Other Cannabinoids In Vitro Through Modifications to Drug Combinations and Treatment Schedules” http://ar.iiarjournals.org/content/33/10/4373.abstract

“Non-hallucinogenic cannabinoids are effective anti-cancer drugs” https://www.sciencedaily.com/releases/2013/10/131014094105.htm

“Cannabinoids used in sequence with chemotherapy are a more effective treatment for cancer. New research has confirmed that cannabinoids – the active chemicals in cannabis – are effective in killing leukaemia cells, particularly when used in combination with chemotherapy treatments.” https://www.sgul.ac.uk/news/news-archive/cannabinoids-used-in-sequence-with-chemotherapy-are-a-more-effective-treatment-for-cancer

“Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.” https://www.ncbi.nlm.nih.gov/pubmed/28560402

Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.

Posted on June 1, 2017 by David

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“Phytocannabinoids possess anticancer activity when used alone, and a number have also been shown to combine favourably with each other in vitro in leukaemia cells to generate improved activity.

We have investigated the effect of pairing cannabinoids and assessed their anticancer activity in cell line models. Those most effective were then used with the common anti-leukaemia drugs cytarabine and vincristine, and the effects of this combination therapy on cell death studied in vitro.

Results show a number of cannabinoids could be paired together to generate an effect superior to that achieved if the components were used individually.

For example, in HL60 cells, the IC50 values at 48 h for cannabidiol (CBD) and tetrahydrocannabinol (THC) when used alone were 8 and 13 µM, respectively; however, if used together, it was 4 µM. Median-effect analysis confirmed the benefit of using cannabinoids in pairs, with calculated combination indices being <1 in a number of cases.

The most efficacious cannabinoid-pairs subsequently synergised further when combined with the chemotherapy agents, and were also able to sensitise leukaemia cells to their cytotoxic effects.

The sequence of administration of these drugs was important though; using cannabinoids after chemotherapy resulted in greater induction of apoptosis, whilst this was the opposite when the schedule of administration was reversed.

Our results suggest that when certain cannabinoids are paired together, the resulting product can be combined synergistically with common anti-leukaemia drugs allowing the dose of the cytotoxic agents to be dramatically reduced yet still remain efficacious. Nevertheless, the sequence of drug administration is crucial to the success of these triple combinations and should be considered when planning such treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/28560402

https://www.spandidos-publications.com/10.3892/ijo.2017.4022

Cannabinoids as Modulators of Cell Death: Clinical Applications and Future Directions.

Posted on April 21, 2017 by David

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“Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids.

In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death. These observations indicate that cannabinoids may play an important role in the regulation of cellular homeostasis and, thus, may contribute to tissue remodelling and cancer treatment.

For a long time, the study of cannabinoid receptor signalling has been focused on the classical adenylyl cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not totally explain the wide array of biological responses to cannabinoids. In addition, the diversity of receptors and signalling pathways that endocannabinoids modulate offers an interesting opportunity for the development of specific molecules to disturb selectively the endogenous system.

Moreover, emerging evidences suggest that cannabinoids ability to limit cell proliferation and to induce tumour-selective cell death may offer a novel strategy in cancer treatment.

This review describes the main properties of cannabinoids in cell death and attempts to clarify the different pathways triggered by these compounds that may help to understand the complexity of respective molecular mechanisms and explore the potential clinical benefit of cannabinoids use in cancer therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/28425013

Can Marijuana Cure Cancer? Mom Claims To Have Cured Son’s Leukemia By Secretly Giving Him Weed

Posted on March 30, 2017 by David

deryn

“Boy’s miracle recovery from rare cancer after mum gave him cannabis” http://metro.co.uk/2017/03/26/boys-miracle-recovery-from-rare-cancer-after-mum-gave-him-cannabis-6534160/

“A mother in England reports that she secretly gave her son marijuana, and credits it with curing his leukemia, and saving the teen’s life. Callie Blackwell chose to secretly give her dying son illegally bought marijuana to help him deal with the pain and anxiety from his aggressive leukemia, because she felt he had “nothing else to lose,” The Independent reported. The drug did far more than the mother could have hoped; it not only relieved Deryn’s pain, it reportedly cured his cancer. Now, Blackwell hopes to share her family’s story in an effort to raise awareness about the healing potential of marijuana.

Deryn was first diagnosed with his severe and aggressive form of leukemia, a type of cancer that originates in the blood cells, at age 10. At 14, doctors informed him that there was nothing more they could do, and the young teen went to live out the rest of his short life in a hospice facility. However, that was three years ago, and now at 17, Deryn has fully recovered from his disease and plans to start a career in the food industry. Callie teamed up with author Karen Hockney to write The Boy in 7 Million, a book detailing the family’s experience and highlighting the potential of marijuana in cancer treatment.

There have been a number of instances where marijuana was suspected of significantly improving, and in some cases even curing cancer, but the science remains inconclusive. Research suggests that cannabinoids—chemicals found in the marijuana plants—can target and kill cancer cells in ways that drugs cannot.” http://www.medicaldaily.com/can-marijuana-cure-cancer-mom-claims-have-cured-sons-leukemia-secretly-giving-414375

“Teenager dying of cancer ‘recovers after mother gives him marijuana'” http://www.independent.co.uk/life-style/health-and-families/health-news/teenager-deryn-boy-dying-cancer-mother-callie-blackwell-recover-medical-marijuana-cannabis-weed-a7652106.html

‘I GAVE MY BOY CANNABIS’. Mum reveals she gave her cancer-stricken son CANNABIS in bid to ease his pain… and now he’s made a miracle recovery. Deryn Blackwell, who was expected to die, has defied doctors by surviving two deadly cancers” https://www.thesun.co.uk/news/3181956/mum-callie-blackwell-cancer-stricken-son-deryn-cannabis/

“I gave my little boy CANNABIS to help cure his cancer: Mother reveals how her teenage son who was given days to live made a miracle recovery when she gave him the drug behind his doctors’ backs” http://www.dailymail.co.uk/femail/article-4349232/Mother-gave-young-son-cannabis-help-cure-cancer.html

One in 7 Billion: Deryn Blackwell begins his hospital ordeal aged 10

“‘I gave my dying son cannabis to ease his cancer symptoms and he made a miracle recovery’ reveals mum” http://www.mirror.co.uk/news/uk-news/i-gave-dying-son-cannabis-10103387

“I Secretly Gave My Son Cannabis to Save His Life | This Morning” https://www.youtube.com/watch?v=qqvJOAV7oAc&t=4s

“This Morning fans praise mum who risks prosecution after giving son cannabis cancer drug” http://www.express.co.uk/showbiz/tv-radio/784387/This-Morning-Phillip-Schofield-Holly-Willoughby-cannabis-based-drug-cancer

“Mum claims cannabis cured son’s cancer after he was given days to live. A MUM has claimed that cannabis cured her son’s terminal cancer.” http://www.dailystar.co.uk/showbiz-tv/hot-tv/600294/cannabis-cures-cancer-this-morning-holly-willoughby

“As teenage boy ‘beats’ cancer with cannabis oil here are nine illnesses the drug could ‘cure’. Deryn Blackwell’s parents secretly gave him the class B drug to ease his pain and anxiety as he underwent gruelling treatment in hospital for leukaemia and cancer.” http://www.mirror.co.uk/lifestyle/health/after-cannabis-oil-miracle-recovery-10111458

“I gave my cancer-stricken son weed and it saved his life” http://nypost.com/2017/03/26/i-gave-my-cancer-stricken-son-weed-and-it-saved-his-life/

“London mother claims cannabis helped her dying son recover from rare cancer” http://www.nydailynews.com/news/world/u-mother-claims-cannabis-helped-dying-son-recover-cancer-article-1.3010404

“Mother gives marijuana to cancer-struck son and he makes full recovery” http://topexaminer.com/2017/03/28/mother-gives-marijuana-cancer-struck-son-makes-full-recovery/

“CALLIE BLACKWELL SAYS CANNABIS OIL HELPED SON’S CANCER: ‘THE BOY IN 7 BILLION’” http://www.inquisitr.com/4095508/callie-blackwell-says-cannabis-oil-helped-sons-cancer-the-boy-in-7-billion/

“Teenager Dying Of Cancer Survives After His Mother Gives Him A Dose Of Marijuana” http://www.indiatimes.com/health/buzz/teenager-dying-of-cancer-survives-after-his-mother-gives-him-a-dose-of-marijuana-274499.html

“Mother risked 14 years in prison to smuggle cannabis into hospital for dying son – and she claims it saved his life.‘” http://metro.co.uk/2017/10/23/mother-risked-14-years-in-prison-to-smuggle-cannabis-into-hospital-for-dying-son-and-she-claims-it-saved-his-life-7021003/

“Teen boy ‘saved by cannabis’ reveals how his mum’s illegal drug-buying stopped him from dying. Deryn Blackwell, from Norfolk, was sent to a hospice shortly after his 14th birthday to live out his final few days. He was frail and in extraordinary pain after a relentless battle with a one in a billion form of cancer, Langerhans cell sarcoma. But after his parents secretly gave him cannabis oil to ease his pain and anxiety, he made a miracle recovery. Today, Deryn – who had also battled leukaemia – is a happy and healthy 17-year-old student, with friends and a girlfriend.” http://www.mirror.co.uk/tv/tv-news/teen-boy-saved-cannabis-reveals-11393969

http://www.thctotalhealthcare.com/category/leukemia/

A Science Based Evaluation of Cannabis and Cancer

Posted on November 18, 2016 by David

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“The irritant properties of all smoke will naturally tend to promote a pro-inflammatory immune response with the corresponding production of potentially carcinogenic free radicals. However, cannabis promotes immune deviation to an anti-inflammatory Th2 response via immune-system specific CB2 receptors. Thus, the natural pharmacological properties of marijuana’s cannabinoids, that are not present in tobacco smoke, would minimize potential irritant initiated carcinogenesis. In contrast, the pharmacological activities of tobacco smoke would tend to amplify its carcinogenic potential by inhibiting the death of genetically damaged cells. Together these observations support the epidemiological study of the Kaiser Foundation that did not find cannabis smoking to be associated with cancer incidence. Additionally, the demonstrated cancer killing activities of cannabinoids has been ignored. Cannabinoids have been shown to kill some leukemia and lymphoma, breast and prostate, pheochromocytoma, glioma and skin cancer cells in cell culture and in animals.” http://www.bmj.com/rapid-response/2011/10/29/science-based-evaluation-cannabis-and-cancer

Cannabinoid Receptors Are Overexpressed in CLL but of Limited Potential for Therapeutic Exploitation.

Posted on June 2, 2016 by David

“The cannabinoid receptors 1 and 2 (CNR1&2) are overexpressed in a variety of malignant diseases and cannabinoids can have noteworthy impact on tumor cell viability and tumor growth.

Patients diagnosed with chronic lymphocytic leukemia (CLL) present with very heterogeneous disease characteristics translating into highly differential risk properties.

To meet the urgent need for refinement in risk stratification at diagnosis and the search for novel therapies we studied CNR expression and response to cannabinoid treatment in CLL.

Expression levels of CNR1&2 were determined in 107 CLL patients by real-time PCR and analyzed with regard to prognostic markers and survival.

In contrast to other tumor entities, our data suggest a limited usability of cannabinoids for CLL therapy. Nonetheless, we could define CNR1 mRNA expression as novel prognostic marker.”

http://www.ncbi.nlm.nih.gov/pubmed/27248492

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Posted on April 19, 2016 by David

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“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Cannabinoid pharmacology in cancer research: A new hope for cancer patients?

Posted on February 9, 2016 by David

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“Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis.

Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies.

Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects.

The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer.

Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address.”

http://www.ncbi.nlm.nih.gov/pubmed/26852955

http://www.thctotalhealthcare.com/category/cancer/

Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns

Posted on January 19, 2016 by David

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“It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia.

To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo.

We here reveal a novel aspect of dronabinol, a cannabinoid derivative, which displays remarkable antiproliferative as well as proapoptotic efficacy in a distinct leukemia patient cohort – in vitro and in ex vivo native leukemia blasts. It has been previously reported that cannabinoids display anticancer properties. However, due to legal issues the use and exploration of such agents is highly limited in many countries.

Importantly, we demonstrate that antileukemic concentrations are achievable in vivo.

Our study provides rigorous data to support clinical evaluation of THC as a low-toxic therapy option in a well defined subset of acute leukemia patients.”

http://www.ncbi.nlm.nih.gov/pubmed/26775260

http://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-2029-8