Anti-tumoural actions of cannabinoids.

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“The endocannabinoid system has emerged as a considerable target for the treatment of diverse diseases.

In addition to the well-established palliative effects of cannabinoids in cancer therapy, phytocannabinoids, synthetic cannabinoid compounds as well as inhibitors of endocannabinoid degradation have attracted attention as possible systemic anticancer drugs.

As a matter of fact, accumulating data from preclinical studies suggest cannabinoids elicit effects on different levels of cancer progression, comprising inhibition of proliferation, neovascularisation, invasion and chemoresistance, induction of apoptosis and autophagy as well as enhancement of tumour immune surveillance.

Although the clinical use of cannabinoid receptor ligands is limited by their psychoactivity, nonpsychoactive compounds, such as cannabidiol, have gained attention due to preclinically established anticancer properties and a favourable risk-to-benefit profile.

Thus, cannabinoids may complement the currently used collection of chemotherapeutics, as a broadly diversified option for cancer treatment, while counteracting some of their severe side effects.” https://www.ncbi.nlm.nih.gov/pubmed/30019449

“During the last few decades, a large body of evidence has accumulated to suggest endocannabinoids, phytocannabinoids and synthetic cannabinoids exert an inhibitory effect on cancer growth via blockade of cell proliferation and induction of apoptosis. Some studies support the hypothesis that cannabinoids may enhance immune responses against the progressive growth and spread of tumours.”  https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14426#bph14426-fig-0001
“Previous research has shown that cannabinoids can help lessen side effects of anti-cancer therapies. Now a new British Journal of Pharmacology review has examined their potential for the direct treatment of cancer. Studies have shown that cannabinoids may stop cancer cells from dividing and invading normal tissue, and they may block the blood supply to tumors. Some studies also indicate that cannabinoids may enhance the body’s immune response against the growth and spread of tumors.” https://www.eurasiareview.com/19072018-cannabinoids-may-have-a-vast-array-of-anti-cancer-effects/
“Cannabinoids may have a vast array of anti-cancer effects” https://www.sciencedaily.com/releases/2018/07/180718082143.htm

“Cannabinoids may have a vast array of anti-cancer effects”  https://www.eurekalert.org/pub_releases/2018-07/w-cmh071718.php

Marijuana may help fight cancer” https://nypost.com/2018/07/18/marijuana-may-help-fight-cancer/

“Cannabis stops cancer spreading and boosts immune system, say scientists. Studies show cannabinoids can stop cancer cells from dividing and spreading, and blocks blood supply to tumours” https://www.plymouthherald.co.uk/news/health/cannabis-can-cure-cancer-proof-1803485
“Cannabis stops cancer spreading and boosts immune system, say scientists. Cannabis can act as a treatment for cancer and boost the immune system, claims a new study.” https://www.devonlive.com/news/health/cannabis-can-cure-cancer-proof-1803485
“Cannabis stops cancer spreading and boosts immune system, say scientists. Cannabis can act as a treatment for cancer and boost the immune system, claims a new study.” https://www.cornwalllive.com/news/uk-world-news/cannabis-can-cure-cancer-proof-1803485
Cannabis ‘can act as a treatment for cancer’. Cannabis can enhance the immune system and act as a treatment for cancer, claims a new study. Scientists at Rostock University Medical Centre in Germany claimed the benefits following a review of more than 100 studies.” https://www.thelondoneconomic.com/news/cannabis-can-act-as-a-treatment-for-cancer/19/07/
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Anti-Proliferative Properties and Proapoptotic Function of New CB2 Selective Cannabinoid Receptor Agonist in Jurkat Leukemia Cells.

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“Several studies demonstrated that cannabinoids reduce tumor growth, inhibit angiogenesis, and decrease cancer cell migration. As these molecules are well tolerated, it would be interesting to investigate the potential benefit of newly synthesized compounds, binding cannabinoid receptors (CBRs).

In this study, we describe the synthesis and biological effect of 2-oxo-1,8-naphthyridine-3-carboxamide derivative LV50, a new compound with high CB2 receptor (CB2R) affinity. We demonstrated that it decreases viability of Jurkat leukemia cells, evaluated by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), but mainly induces a proapoptotic effect. We observed an increase of a hypodiploid peak by propidium iodide staining and changes in nuclear morphology by Hoechst 33258. These data were confirmed by a significant increase of Annexin V staining, cleavage of the nuclear enzyme poly(ADP-ribose)-polymerase (PARP), and caspases activation. In addition, in order to exclude that LV50 non-specifically triggers death of all normal leukocytes, we tested the new compound on normal peripheral blood lymphocytes, excluding the idea of general cytotoxicity. To characterize the involvement of CB2R in the anti-proliferative and proapoptotic effect of LV50, cells were pretreated with a specific CB2R antagonist and the obtained data showed reverse results.

Thus, we suggest a link between inhibition of cell survival and proapoptotic activity of the new compound that elicits this effect as selective CB2R agonist.”

https://www.ncbi.nlm.nih.gov/pubmed/29973514

http://www.mdpi.com/1422-0067/19/7/1958

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Effects of CB2 and TRPV1 receptors’ stimulation in pediatric acute T-lymphoblastic leukemia

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“T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy.

The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1.

We treated T-ALL lymphoblasts derived from 4 patients and Jurkat cells with a selective agonist at CB2 receptor: JWH-133 [100 nM] and an agonist at TRPV1 calcium channel: RTX [5 uM] at 6, 12 and 24 hours. We analyzed the effect on apoptosis and Cell Cycle Progression by a cytofluorimetric assays and evaluated the expression level of several target genes (Caspase 3, Bax, Bcl-2, AKT, ERK, PTEN, Notch-1, CDK2, p53) involved in cell survival and apoptosis, by Real-Time PCR and Western Blotting.

We observed a pro-apoptotic, anti-proliferative effect of these compounds in both primary lymphoblasts obtained from patients with T-ALL and in Jurkat cell line. Our results show that both CB2 stimulation and TRPV1 activation, can increase the apoptosis in vitro, interfere with cell cycle progression and reduce cell proliferation, indicating that a new therapeutic approach to T-cell ALL might be possible by modulating CB2 and TRPV1 receptors.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=25052

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

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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

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

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

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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.”

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

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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

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

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“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/

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A Science Based Evaluation of Cannabis and Cancer

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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

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

“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

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