Can Marijuana Cure Cancer? Pharmaceutical Company Developing Cannabis Medicine To Treat Brain Cancer
Cannabidiol: an alternative therapeutic agent for oral mucositis?
“Chemo- and radiotherapy are therapeutic modalities often used in patients with malignant neoplasms. They kill tumour cells but act on healthy tissues as well, resulting in adverse effects.
Oral mucositis is especially of concern, due to the morbidity that it causes.
We reviewed the literature on the etiopathogenesis of oral mucositis and the activity of cannabidiol, to consider the possibility of its use for the prevention and treatment of oral mucositis.
The control of oxidative stress may prevent and alleviate oral mucositis. Studies have demonstrated that cannabidiol is safe to use and possesses antioxidant, anti-inflammatory and analgesic properties.
The literature on the use of cannabidiol in dentistry is still scarce. Studies investigating the use of cannabidiol in oral mucositis and other oxidative stress-mediated side effects of chemotherapy and radiotherapy on the oral mucosa should be encouraged.”
Implication of cannabinoids in neurological diseases.
“1. Preparations from Cannabis sativa (marijuana) have been used for many centuries both medicinally and recreationally. 2. Recent advances in the knowledge of its pharmacological and chemical properties in the organism, mainly due to Delta(9)-tetrahydrocannabinol, and the physiological roles played by the endocannabinoids have opened up new strategies in the treatment of neurological and psychiatric diseases. 3. Potential therapeutic uses of cannabinoid receptor agonists include the management of spasticity and tremor in multiple sclerosis/spinal cord injury, pain, inflammatory disorders, glaucoma, bronchial asthma, cancer, and vasodilation that accompanies advanced cirrhosis. CB(1) receptor antagonists have therapeutic potential in Parkinson’s disease. 4. Dr. Julius Axelrod also contributed in studies on the neuroprotective actions of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/16699878
Concise review of the management of iatrogenic emesis using cannabinoids: emphasis on nabilone for chemotherapy-induced nausea and vomiting.
“Chemotherapy-induced nausea and vomiting (CINV) is a prevalent, distressing, and burdensome side effect of cancer chemotherapy. It is estimated to affect the majority of patients receiving certain anti-cancer drug regimens and can be treatment-limiting, even for life-saving medications. Despite seemingly numerous options, such as antimuscarinic anticholinergics, antihistamines, 5-HT3 receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists, preventative therapies are often inadequately effective, particularly for “delayed CINV”-leaving an important unmet clinical need.
Cannabinoid receptor agonists, by virtue of their unique mechanism of action and efficacy and safety data reported in clinical trials, appear to offer a useful additional option.
The mechanistic value of cannabinoids has been well known for many years, but these agents may have been underutilized in the past because of the notoriety and legal status of marijuana. While botanical marijuana contains nearly 500 components, including the psychoactive tetrahydrocannabinol (THC), nabilone is an established, single-entity synthetic cannabinoid receptor agonist that has become the focus of renewed interest. We review the basic pharmacology and clinical trial data of nabilone for use in prophylaxis and treatment of CINV.”
Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic ApcMin/+ Mice, Correlating with CB1 Receptor Up-Regulation.
“Mediterranean diet components, such as olive oil and ω-3 polyunsaturated fatty acids (ω-3 PUFAs), can arrest cell growth and promote cell apoptosis.
Recently, olive oil has been demonstrated to modulate type-1 cannabinoid (CB1) receptor gene expression in both human colon cancer cells and rat colon. The aim of this study was to investigate a possible link between olive oil and ω-3 PUFAs effects and CB1 receptor expression in both intestinal and adipose tissue of ApcMin/+ mice.
To confirm the role for the CB1 receptor as a negative modulator of cell proliferation in human colon cancer, CB1 receptor gene expression was also detected in tumor tissue and in surrounding normal mucosa of patients with colorectal cancer (CRC).
Dietary ω-3 PUFAs significantly inhibited intestinal polyp growth in mice, correlating with CB1 receptor gene and protein expression induction. CB1 receptor gene up-regulation was also detected in adipose tissue, suggesting a close communication between cancer cells and the surrounding environment. Tissue CB1 receptor induction was associated with a concurrent inactivation of the Wnt/β-catenin pathway.
Moreover, there was a significant reduction in CB1 receptor gene expression levels in cancer tissue compared to normal surrounding mucosa of patients with CRC, confirming that in cancer the “protective” action of the CB1 receptor is lost.”
It’s Colorectal Cancer Awareness Month. Please Be Aware:
“Cannabinoids have become a novel therapeutic approach against colon cancer with protective and anti-tumoral effects on colorectal carcinoma cell lines and in animal models of colon cancer” http://impactjournals.com/oncoscience/index.php?pii=119
“Inhibitors of endocannabinoid inactivation may prove useful anticancer agents.” https://www.ncbi.nlm.nih.gov/pubmed/12949714
“Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755791/
“The endogenous cannabinoid system protects against colonic inflammation” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC385396/
Can Marijuana Cure Cancer? Mom Claims To Have Cured Son’s Leukemia By Secretly Giving Him Weed
“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
“‘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
It’s Oral, Head & Neck Cancer Awareness Month. Please Be Aware.
“Oral, Head & Neck Cancer Awareness Month. While smoking and tobacco use are still major risk factors, the fastest growing segment of oral cancer patients is young, healthy, nonsmoking individuals due to the connection to the HPV virus. We cannot stop this virus from spreading; our only hope to save lives is with professional involvement and public awareness.” http://oralcancerfoundation.org/events/oral-head-neck-cancer-awareness-month/
“Oral Sex Linked to Rise in Oral Cancers” https://www.roswellpark.org/cancertalk/201304/oral-sex-linked-rise-oral-cancers
“Role of human papilloma virus in the oral carcinogenesis” https://www.ncbi.nlm.nih.gov/pubmed/19542661 “A causal role for human papillomavirus in head and neck cancer.” https://www.ncbi.nlm.nih.gov/pubmed/15135592/
“Bogarting that joint might decrease oral hpv among cannabis users. The development of oral cancer is not a result of smoking cannabis per se; rather, it is hypothesized to be a result of contracting hpv through various forms of sharing and passing joints and other smoking apparatuses. Therefore, it is hypothesized that bogarting (and not passing) joints might decrease oral hpv among cannabis smokers.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794675/
“Additive found in toothpaste and food products could cause cancer, say scientists” http://www.independent.co.uk/news/science/toothpaste-additive-e171-titanium-dioxide-food-products-cancer-cause-scientists-a7541956.html
“Mouthwash And Poor Dental Hygiene May Up The Risk Of Oral Cancer” http://www.npr.org/sections/health-shots/2014/04/08/300257396/mouthwash-and-poor-dental-hygiene-may-up-the-risk-of-oral-cancer
“Gum Disease Linked to Risk of Oral Cancer Causing Virus” https://www.bloomberg.com/news/articles/2013-08-21/gum-disease-linked-to-risk-of-oral-cancer-causing-virus
“ROUGH TEETH AND RUBBING DENTURES MAY BE LINKED TO ORAL CANCER” http://www.managedhealthcareconnect.com/content/rough-teeth-and-rubbing-dentures-may-be-linked-oral-cancer
“Unhealthy lifestyles blamed for sharp rise in mouth cancer cases” http://www.itv.com/news/2016-11-25/bad-habits-linked-to-soaring-rates-of-mouth-cancer/
“Type of food and risk of oral cancer. To reduce the risk of oral and pharyngeal cancer, especially squamous cell carcinoma, the most common oral cancer, diet must be optimized, primarily to reduce calorie intake, monounsaturated fat, and red or processed meat. Consumption of fruits, vegetables, and cereals, which are the major source of vitamins and fiber, should be adequate in the daily diet. Optimal levels of daily allowance of micronutrients like vitamin C, E, antioxidants, zinc, beta-carotene, and folate are effective in prevention of oral cancer. Consumption of fried or broiled foods and employment of microwave cooking, because of formation of heterocyclic amines, must be avoided because of increasing risks of oral cancer including the salivary gland tumors.” https://www.ncbi.nlm.nih.gov/pubmed/17367228
“Coffee consumption associated with reduced risk of oral cancer: a meta-analysis” http://www.sciencedirect.com/science/article/pii/S2212440315013656
“Tobacco and alcohol use are among the strongest risk factors for oral cavity and oropharyngeal cancers.” https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/causes-risks-prevention/risk-factors.html
“Marijuana use on its own does not merit definitive oral cancer development, according to research. In fact, cannabis also contains cannabinoids, such as THC, which contain anticancer properties. Some of these anticancer properties include the slowing of the inflammatory arm of the immune system designed to slow free-radical growths. Some researchers link medicinal marijuana to these anticancer properties.” http://www.dentistryiq.com/articles/2014/04/should-marijuana-users-be-worried-that-smoking-causes-oral-cancer.html
“Marijuana has been used in herbal remedies for centuries. More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells.” http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/chemotherapyeffects/marijuana-and-cancer
“Cannabis has been shown to kill cancer cells in the laboratory. Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all
“Marijuana Kills Cancer Cells, Admits The U.S. National Cancer Institute” http://naturalsociety.com/marijuana-kills-cancer-cells-admits-the-u-s-national-cancer-institute/
“US government says cannabis kills cancer cells” http://www.telegraph.co.uk/news/worldnews/northamerica/usa/11820620/US-government-says-cannabis-kills-cancer-cells.html
“US government finally admits that cannabis kills cancer cells” http://www.mirror.co.uk/news/world-news/government-finally-admits-cannabis-kills-6303176
“Review of Various Herbal Supplements as Complementary Treatments for Oral Cancer. Diet changes, supplementation with antioxidants, high-dose vitamin C therapy, and cannabinoid use have been suggested to decrease cancer cell replication and increase chance of remission.” https://www.ncbi.nlm.nih.gov/pubmed/26863913
“Cannabinoids Offer Some Hope for Oral Cancer Pain” https://www.practicalpainmanagement.com/meeting-summary/cannabinoids-offer-some-hope-oral-cancer-pain
“Cannabinoids Attenuate Cancer Pain and Proliferation in a Mouse Model. Our results suggest that systemic administration of cannabinoids decease oral cancer pain. Our findings suggest a direct role for cannabinoid mechanisms in oral cancer pain and proliferation. The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer. The present findings suggest that cannabinoid treatment may be a promising alternative therapy for oral cancer pain management.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099480/
“Cannabinoids Inhibit Cellular Respiration of Human Oral Cancer Cells. The primary cannabinoids, Δ9-tetrahydrocannabinol (Δ9-THC) and Δ8-tetrahydrocannabinol (Δ8-THC) are known to disturb the mitochondrial function and possess antitumor activities. These observations prompted us to investigate their effects on the mitochondrial O2 consumption in human oral cancer cells (Tu183). This epithelial cell line overexpresses bcl-2 and is highly resistant to anticancer drugs. A rapid decline in the rate of respiration was observed when Δ9-THC or Δ8-THC was added to the cells. These results show the cannabinoids are potent inhibitors of Tu183 cellular respiration and are toxic to this highly malignant tumor.” https://www.karger.com/Article/Abstract/312686
“CANNABINOIDS INHIBIT ORAL CANCER CELLS” https://pharmotech.ch/cannabinoids-inhibit-oral-cancer-cells/
“Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival. The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue squamous cell carcinoma (SCC) and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.” https://www.ncbi.nlm.nih.gov/pubmed/26459312
“Review: cannabidiol may be beneficial for oral mucositis. The researchers found evidence that oxidative stress control could prevent and relieve oral mucositis. Cannabidiol was found to be safe to use and demonstrated antioxidant, anti-inflammatory, and analgesic properties,” https://medicalxpress.com/news/2017-02-cannabidiol-beneficial-oral-mucositis.html
“Salivary bacteria linked to oral cancers” http://middleeast.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70266-7/abstract
“Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study” http://pubs.acs.org/doi/abs/10.1021/np8002673
“Targeting Id1 reduces proliferation and invasion in aggressive human salivary gland cancer cells. Id1 suppression could represent a novel and effective approach for the treatment of salivary gland cancer.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639030/
“Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.” https://www.ncbi.nlm.nih.gov/pubmed/27087608
“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells. Moreover, reducing Id-1 expression with cannabinoids could also provide a therapeutic strategy for the treatment of additional aggressive cancers because Id-1 expression was found to be up-regulated during the progression of almost all types” http://mct.aacrjournals.org/content/6/11/2921.long
“Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species.” https://www.ncbi.nlm.nih.gov/pubmed/24797795
“The endocannabinoid system and cancer: therapeutic implication. Many in vitro and in vivo studies have shown that cannabinoids are efficacious in reducing cancer progression (i.e. inhibition of tumour growth and metastases as well as induction of apoptosis and other anti-cancer properties) in breast, prostate and bone cancer. Although this review focuses on these three types of cancer, activation of the endocannabinoid signalling system produces anti-cancer effects in other types of cancer.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01327.x/full
“Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy. The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM). HNC patients report MM use to help with long-term side effects of radiotherapy.” http://www.ncbi.nlm.nih.gov/pubmed/27005465
“Head and neck cancer among marijuana users: A meta-analysis of matched case–control studies. No association between lifetime marijuana use and the development of head and neck cancer was found.” http://www.aobjournal.com/article/S0003-9969(15)30041-8/abstract
“A Population-based Case-Control Study of Marijuana Use and Head and Neck Squamous Cell Carcinoma. Our study suggests that moderate marijuana use is associated with reduced risk of head and neck cancer (HNSCC). In fact, many of these studies reported non-significant protective estimates of effect, consistent with a possible anticarcinogenic action of cannabinoids.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812803/
“Smoking Marijuana Regularly May Reduce Risk of Some Neck, Head Cancers” http://www.foxnews.com/story/2009/08/26/smoking-marijuana-regularly-may-reduce-risk-some-neck-head-cancers.html
http://www.thctotalhealthcare.com/category/oral-cancer/
http://www.thctotalhealthcare.com/category/head-and-neck-squamous-cell-carcinoma-hnscc/
Cannabinoids as Modulators of Cell Death: Clinical Applications and Future Directions.
“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.”
Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications.
“A flowering plant of variegated ingredients and psychoactive qualities, cannabis has long been used for medicinal and recreational purposes. Currently, cannabis is approved in several countries for indications of symptomatic alleviation. However, limited knowledge on the benefits and risks precludes inclusion of cannabis in standard treatment guidelines. This review provides a summary of the available literature on the use of cannabis and cannabinoid-based medicines in palliative oncology. Favorable outcomes are demonstrated for chemotherapy-induced nausea and vomiting and cancer-related pain, with evidence of advantageous neurological interactions. Benefit in the treatment of anorexia, insomnia and anxiety is also suggested. Short- and long-term side effects appear to be manageable and to subside after discontinuation of the drug. Finally, cannabinoids have shown anti-neoplastic effects in preclinical studies in a wide range of cancer cells and some animal models. Further research is needed before cannabis can become a part of evidence-based oncology practice.”
The Role of Cannabinoids in the Treatment of Cancer in Pediatric Patients.
“Cannabis has been used in folk medicine to alleviate pain, depression, amenorrhea, inflammation and numerous other medical conditions. In cancer patients specifically, cannabinoids are well known to exert palliative effects; their best-established use is the inhibition of chemotherapy-induced nausea and vomiting, but they are applied also to alleviate pain, stimulate appetite, and attenuate wasting. More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death.
Anti-cancer efficacy of cannabinoids:
The ability of cannabinoids to reduce tumor growth was reported for the first time by Munson et al. in 1975. They showed by in vitro and in vivo experiments that several phytocannabinoids, including THC, decreased Lewis lung adenocarcinoma proliferation in a dose-dependent manner. Nevertheless, it was not until the 2000s that the interest in these compounds as anti-cancer agents was renewed, predominantly due to the work of Guzman in gliomas, and the demonstration of cannabinoids’ anti-cancer effects on various types of tumors. The anti-tumorigenic effect of the endo- and phytocannabinoids was demonstrated in several in vitro and in vivo models of a wide variety of adult tumors including glioma, prostate, breast, leukemia, lymphoma, pancreas, melanoma, thyroid, colorectal and hepatocellular carcinoma tumors.
Given our positive results, we suggest that non-THC cannabinoids such as CBD might provide a basis for the development of novel therapeutic strategies without the typical psychotropic effects of THC that limit its use in pediatric patients.
Overall, the cannabinoids, and specifically the non-psychoactive CBD, may show future promise in the treatment of cancer”
https://www.ima.org.il/FilesUpload/IMAJ/0/228/114216.pdf
Synthesis and antitumor activity of cannabigerol
“Cannabigerol was synthesized and evaluated for its inhibitory activity against mouse skin melanoma cells.
Cannabigerol displayed significant antitumor activity.”
Compound found in cannabis helps ‘shrink’ four-year-old’s brain tumour
“The family of a four-year-old boy from Nottinghamshire are backing new research into whether a non-psychoactive compound found in cannabis can reduce paediatric brain cancer cells.
Experts from Nottingham’s Children’s Brain Tumour Research Centre, at The University of Nottingham, will test Cannabidiol (CBD) for its effects on paediatric brain tumours in youngsters. This research will form part of the pre-clinical phase of the evaluation of the potential use of cannabidiol in paediatric brain tumours” http://www.nottinghampost.com/compound-found-in-cannabis-helps-shrink-four-year-old-s-brain-tumour/story-30307458-detail/story.html
“Little boy’s aggressive brain tumour shrinks thanks to CANNABIS compound, his parents claim” https://www.thesun.co.uk/living/3472080/little-boys-aggressive-brain-tumour-shrinks-thanks-to-cannabis-his-parents-claimed/
“Little boy battling golf ball-sized brain tumour given new lease of life after being given a special OIL” http://www.mirror.co.uk/news/uk-news/little-boy-battling-golf-ball-10347423
Systematic review of the potential role of cannabinoids as antiproliferative agents for urological cancers.
“The palliative effects of cannabis sativa (marijuana), which include appetite stimulation, attenuation of nausea and emesis, and pain relief, are well known.
The active components of cannabis sativa (cannabinoids) and their derivatives have received growing interest due to their diverse pharmacological activities, such as cell growth inhibition and tumour regression.
The aim of this review is to look at the current evidence on the antiproliferative effects of cannabinoids in urological malignancies, including renal, prostate, bladder, and testicular cancers.
The search yielded a total of 93 studies from Medline and PubMed, of which 23 studies were included in the final analysis. To date, there are various in vitro studies elucidating the potential mechanism of action of cannabinoids for urological cancers, along with population-based studies specifically for testicular malignancies. To date, no clinical trials have been conducted for urological cancer patients.
These results demonstrate that the role of endocannabinoids for urological malignancies is an area of active research. Further research is required not only to evaluate the crosstalk between cancer signaling pathways and cannabinoids, but also large randomized clinical studies with urological patients need to be conducted before cannabinoids can be introduced as potential therapeutic options for urological neoplasms.”
Single and combined effects of delta9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.
“It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity.
KEY RESULTS:
Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity.
CONCLUSIONS AND IMPLICATIONS:
CBD may be potent and effective at preventing the development of CIPN, and its clinical utility may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of Cannabis-based pharmacotherapies.”
https://www.ncbi.nlm.nih.gov/pubmed/28548225
http://onlinelibrary.wiley.com/doi/10.1111/bph.13887/abstract
Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration.
“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.”
Study shows non-hallucinogenic cannabinoids are effective anti-cancer drugs
“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
Analysis of Natural Product Regulation of Cannabinoid Receptors in the treatment of Human Disease.
“The organized tightly regulated signaling relays engaged by the cannabinoid receptors (CBs) and their ligands, G proteins and other effectors, together constitute the endocannabinoid system (ECS). This system governs many biological functions including cell proliferation, regulation of ion transport and neuronal messaging. This review will firstly examine the physiology of the ECS, briefly discussing some anomalies in the relay of the ECS signaling as these are consequently linked to maladies of global concern including neurological disorders, cardiovascular disease and cancer.
While endogenous ligands are crucial for dispatching messages through the ECS, there are also commonalities in binding affinities with copious exogenous ligands, both natural and synthetic. Therefore, this review provides a comparative analysis of both types of exogenous ligands with emphasis on natural products given their putative safer efficacy and the role of Δ9-tetrahydrocannabinol (Δ9-THC) in uncovering the ECS.
Efficacy is congruent to both types of compounds but noteworthy is the effect of a combination therapy to achieve efficacy without the unideal side-effects. An example is Sativex that displayed promise in treating Huntington’s disease (HD) in preclinical models allowing for its transition to current clinical investigation. Despite the in vitro and preclinical efficacy of Δ9-THC to treat neurodegenerative ailments, its psychotropic effects limit its clinical applicability to treating feeding disorders.
We therefore propose further investigation of other compounds and their combinations such as the triterpene, α,β-amyrin that exhibited greater binding affinity to CB1 than CB2 and was more potent than Δ9-THC and the N-alkylamides that exhibited CB2 selective affinity, the latter can be explored towards peripherally exclusive ECS modulation. The synthetic CB1 antagonist, Rimonabant was pulled from market for the treatment of diabetes, however its analogue SR144528 maybe an ideal lead molecule towards this end and HU-210 and Org27569 are also promising synthetic small molecules.”
https://www.ncbi.nlm.nih.gov/pubmed/28583800
http://www.sciencedirect.com/science/article/pii/S0163725817301511
Medicinal Uses of Marijuana and Cannabinoids
“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”
http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20
“Review Identifies 140 Controlled Clinical Trials Related to Cannabis” http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/
Regulation of human glioblastoma cell death by combined treatment of cannabidiol, γ-radiation and small molecule inhibitors of cell signaling pathways.
“Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The challenging problem in cancer treatment is to find a way to upregulate radiosensitivity of GBM while protecting neurons and neural stem/progenitor cells in the brain. The goal of the present study was upregulation of the cytotoxic effect of γ-irradiation in GBM by non-psychotropic and non-toxic cannabinoid, cannabidiol (CBD).
We emphasized three main aspects of signaling mechanisms induced by CBD treatment (alone or in combination with γ-irradiation) in human GBM that govern cell death: 1) CBD significantly upregulated the active (phosphorylated) JNK1/2 and MAPK p38 levels with the subsequent downregulation of the active phospho-ERK1/2 and phospho-AKT1 levels. MAPK p38 was one of the main drivers of CBD-induced cell death, while death levels after combined treatment of CBD and radiation were dependent on both MAPK p38 and JNK. Both MAPK p38 and JNK regulate the endogenous TRAIL expression. 2) NF-κB p65-P(Ser536) was not the main target of CBD treatment and this transcription factor was found at high levels in CBD-treated GBM cells. Additional suppression of p65-P(Ser536) levels using specific small molecule inhibitors significantly increased CBD-induced apoptosis. 3) CBD treatment substantially upregulated TNF/TNFR1 and TRAIL/TRAIL-R2 signaling by modulation of both ligand and receptor levels followed by apoptosis.
Our results demonstrate that radiation-induced death in GBM could be enhanced by CBD-mediated signaling in concert with its marginal effects for neural stem/progenitor cells and astrocytes. It will allow selecting efficient targets for sensitization of GBM and overcoming cancer therapy-induced severe adverse sequelae.”