Urgent need for “EBMM” in pediatric oncology: Evidence based medical marijuana.

Publication Cover“Marijuana has been used by many different civilizations for numerous different purposes, including its use for medical indications. Recently, there has been significant media coverage of the efficacy of medical marijuana in the treatment of seizures in children with Dravet syndrome, and this has led many to search for other possible pediatric indications for cannabinoids, including many different indications in pediatric cancer. However, there is very little evidence on safety or efficacy of cannabinoids in children being treated with cancer. This commentary accompanies a recent paper by a group in Israel who have published their experience of medical marijuana in 50 children and adolescents with cancer, showing excellent satisfaction and better symptom control, and without significant adverse drug reactions. This study from Israel is an excellent first step, but prospective well-designed trials of medical marijuana in pediatric oncology are urgently needed.”

Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.

Image result for frontiers oncology“Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%.

One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed.

This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer.

In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy.

Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials.

Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts.

The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.”

https://www.ncbi.nlm.nih.gov/pubmed/31396485

“In this study, a flavonoid derivative of cannabis demonstrates significant therapy potential in the treatment of pancreatic cancer, including radio-sensitizing and cancer metastasis treatment potential. The results justify further studies to optimize therapy outcomes toward clinical translation.”

https://www.frontiersin.org/articles/10.3389/fonc.2019.00660/full

“Flavonoids as anticancer agents: structure-activity relationship study.”  https://www.ncbi.nlm.nih.gov/pubmed/12678721

“The antitumor activities of flavonoids.”  https://www.ncbi.nlm.nih.gov/pubmed/16097445

“Anticancer properties of flavonoids: roles in various stages of carcinogenesis.”  https://www.ncbi.nlm.nih.gov/pubmed/21644918

Attitudes and Beliefs About Medical Usefulness and Legalization of Marijuana among Cancer Patients in a Legalized and a Nonlegalized State.

View details for Journal of Palliative Medicine cover image “There is a growing preference for the use of marijuana for medical purposes, despite limited evidence regarding its benefits and potential safety risks. Legalization status may play a role in the attitudes and preferences toward medical marijuana(MM).

Objectives: The attitudes and beliefs of cancer patients in a legalized (Arizona) versus nonlegalized state (Texas) regarding medical and recreational legalization and medical usefulness of marijuana were compared.

 

Results: The majority of individuals support legalization of marijuana for medical use (Arizona 92% [85-97%] vs. Texas 90% [82-95%]; p = 0.81) and belief in its medical usefulness (Arizona 97% [92-99%] vs. Texas 93% [86-97%]; p = 0.33) in both states. Overall, 181 (91%) patients supported legalization for medical purposes whereas 80 (40%) supported it for recreational purposes (p < 0.0001). Patients preferred marijuana over current standard treatments for anxiety (60% [51-68%]; p = 0.003). Patients found to favor legalizing MM were younger (p = 0.027), had worse fatigue (p = 0.015), appetite (p = 0.004), anxiety (p = 0.017), and were Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs (CAGE-AID) positive for alcohol/drugs (p < 0.0001).

Conclusion: Cancer patients from both legalized and nonlegalized states supported legalization of marijuana for medical purposes and believed in its medical use. The support for legalization for medical use was significantly higher than for recreational use in both states.”

https://www.ncbi.nlm.nih.gov/pubmed/31386595

https://www.liebertpub.com/doi/10.1089/jpm.2019.0218

Olivia Newton John says medicinal cannabis is key to her cancer recovery

“Olivia Newton-John says medicinal marijuana is a key part of her treatment for stage four cancer. In an exclusive interview with 60 Minutes reporter Liz Hayes, Newton-John says that not only has cannabis assisted with her pain management, sleep and anxiety – but it’s having affects on her physical health too. “I’m incredibly pro cannabis,” she told Liz Hayes. “If I don’t take the cannabis, I can feel the pain so I know it’s working.”

 “Newton-John is maintaining her health with a combination of conventional and alternative medicines and remedies. But her husband of ten years, John Easterling, says he’s confident medicinal cannabis is contributing significantly to maintaining her health.
Easterling, who spent years cultivating herbs from the Amazon, has long held a strong belief in the medicinal power of plants. In a greenhouse at the Santa Barbara ranch the couple share in California, he grows various strains of cannabis that he uses to help treat his wife. “Cannabis can be used for so many things,” he told Hayes. “I don’t use the word cure…. but I’m confident. We had MRIs showing a lesser number of tumours, and the majority of the other ones are shrinking.”
 “Now a cannabis convert, Newton-John is joining the fight for medicinal cannabis to be legalised. She and Easterling want Australians to have greater access to the plant, like they do in their home state of California – where both medicinal and recreational cannabis is legal.  She’s also hoping to break down the stigma surrounding cannabis use.
“It’s not a drug, it’s a herb and a plant,” she told Hayes. “I think when people use the word drug, it’s a misconception as to what it is and it gets people thinking, ‘oh it’s just another drug’, but it’s not.” Doctors at the Olivia Newton-John Research Institute will conduct a clinical trial to determine the effectiveness of medicinal cannabis later this year.”
 
 “EXCLUSIVE: Olivia Newton-John and Chloe Lattanzi emotional interview | 60 Minutes Australia” https://www.youtube.com/watch?v=rJtPgpedcFo&feature=share

“Olivia Newton-John: ‘Medicinal cannabis enhanced my quality of life’.  For this special 60 Minutes report, Olivia Newton-John tells Liz Hayes that despite her latest diagnosis she was “getting strong again” and that her quality of life had been greatly enhanced by medicinal cannabis, grown for her by her husband John. Olivia and John are strong believers in the power of plants particularly cannabis. “I really believe the cannabis has made a huge difference,” says Olivia. “I’m confident,” John concurs. Olivia, John and Chloe are now cannabis converts, and now want medicinal cannabis legalised as an alternative treatment in Australia.” https://www.9news.com.au/national/olivia-newton-john-60-minutes-medical-cannabis-advocate-after-cancer-treatment-news/da315271-7387-47e0-a14e-c7fbb9a4b18b

“I have to credit again my wonderful husband because he gives me Cannabis oil that he makes for me, grows the plants here. We’re so lucky in California that we can grow our own, and so he’s made me these incredible tinctures that help with my pain and with sleep, and everything.” https://www.today.com/video/watch-olivia-newton-john-s-full-interview-with-natalie-morales-1455610947796

 Olivia Newton-John: “The choices of your treatment is a very personal thing. I can’t tell anyone else what they should do. I’d like to tell you all something that I did that people should know about. I’ve mixed traditional medicine and herbal medicine and homoeopathic medicine and a lot of mind-body spiritual focus. Staying positive and believing I can get well is really important. I’m very fortunate that I have a husband who’s a plant medicine man who helps me with herbs and medicinal cannabis, it’s been a huge part of my journey. I weaned myself off morphine with cannabis and I just want people to know that that is possible and it’s not going to kill you. If we can start teaching people that cannabis can help keep the pain away and not kill you, that’s an important message to get out there. I want to see an end to cancer in my lifetime. I’ve had three bouts with cancer. I am living with it well, and I think I’m going to see an end of it. And that’s my dream, that it will be gone.” https://www.image.ie/life/olivia-newton-john-shares-her-advice-for-women-with-cancer-154470
 “”I want to see an end to cancer in my lifetime. And if it could be through cannabis, or helping people with cannabis, the patients, particularly who are in pain, that’s my goal. I want everyone to have access to this amazing plant”” https://www.facebook.com/watch/?v=269501097009373
 ““I truly believe medicinal cannabis will play a huge part in defeating cancer.”“I absolutely believe all patients should have the right to try. It is a matter of common-sense and it is a compassionate thing to do for people,” she said,” https://starinvesting.com.au/medicinal-cannabis-to-play-huge-role-in-beating-cancer-olivia-newton-john/
Olivia Newton-John reveals she’s using marijuana grown by her husband to fight cancer – and says reports she was on death’s door hurt her deeply. Australian singing sensation Olivia Newton-John says she has been using marijuana grown by her husband to help her through her cancer battle. ‘I really believe the cannabis has made a huge difference,'”
“‘It Has Helped Incredibly’. It’s an amazing plant, a maligned plant, but it’s helping so many people.”” https://www.inquisitr.com/5330159/home-grown-cannabis-is-helping-olivia-newton-john-amid-cancer-battle-it-has-helped-incredibly/
“Olivia Newton-John says she uses cannabis to treat her stage 4 breast cancer… and her husband grows it at home” https://www.dailymail.co.uk/tvshowbiz/article-6782847/Olivia-Newton-John-uses-cannabis-treat-stage-4-breast-cancer.html
““I’m Living With Cancer and It’s Going Away!” Olivia Newton John Declares That Her Body is “Winning” Against Stage 4 Cancer” https://www.survivornet.com/articles/im-living-with-cancer-and-its-going-away-olivia-newton-john-declares-that-her-body-is-winning-against-stage-4-cancer/
“Mainstream media has reported that the cannabis tincture she takes helps with pain, but Amazon John Easterling eagerly expounds on its many healing properties, including the potential to cause cancer cell death. “Cannabis initiates a number of healing responses that can result in apoptosis, cancer cell death—while healing and strengthening the body,” he detailed. His focus is on the plant as chemovar, a more scientific approach to looking at the many compounds, via terpene and cannabinoid extraction from the whole plant to treat the cancer and the entire body, building the immune system so it can aid in fighting the disease.“ https://culturemagazine.com/olivia-newton-john-and-john-easterling/
“Medicinal cannabis is a big part of my recovery. I’m living proof that it works. It’s a healing herb.” https://www.facebook.com/watch/?v=1580591005362546

Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells.

 biomolecules-logo“The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties.

The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells.

We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells.

These results indicated that CBD could induce G0-G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/31349651

“These findings may be utilized in the development of CBD as a potential drug for the treatment of gastric cancer.”

https://www.mdpi.com/2218-273X/9/8/302

Cannabinoid Signaling in Cancer.

“The family of chemical structures that interact with a cannabinoid receptor are broadly termed cannabinoids. Traditionally known for their psychotropic effects and their use as palliative medicine in cancer, cannabinoids are very versatile and are known to interact with several orphan receptors besides cannabinoid receptors (CBR) in the body. Recent studies have shown that several key pathways involved in cell growth, differentiation and, even metabolism and apoptosis crosstalk with cannabinoid signaling. Several of these pathways including AKT, EGFR, and mTOR are known to contribute to tumor development and metastasis, and cannabinoids may reverse their effects, thereby by inducing apoptosis, autophagy and modulating the immune system. In this book chapter, we explore how cannabinoids regulate diverse signaling mechanisms in cancer and immune cells within the tumor microenvironment and whether they impart a therapeutic effect. We also provide some important insight into the role of cannabinoids in cellular and whole body metabolism in the context of tumor inhibition. Finally, we highlight recent and ongoing clinical trials that include cannabinoids as a therapeutic strategy and several combinational approaches towards novel therapeutic opportunities in several invasive cancer conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31332734

https://link.springer.com/chapter/10.1007%2F978-3-030-21737-2_4

Strong reasons make strong actions: medical cannabis and cancer—a call for collective action

Logo of curroncol“Call it cannabis, not marijuana or weed.

It has been more than 17 years since the Canadian prohibitory regulations on the use of medical cannabis began to ease and more than 17 weeks (more than 6 months by the time of publication) since the Cannabis Act (Bill C-45) became law. Cannabis use for medical purposes has been part of the historical record and medical writings for millennia. However, it is only in the last 30 years that the workings of the human endocannabinoid system have been described and its receptors discovered. Amazing as all of those developments have been, the challenge of reintegrating cannabis into the science of modern medicine—and particularly care for patients with cancer—is a need whose time has come.

Surveys inform us that patients with cancer are using cannabis to manage symptoms related to cancer and cancer treatment. More concerning is that their use is for a medical need occurring outside the confines of modern cancer care, with patients accessing their cannabis from friends and family, and often from casual or unlicensed suppliers. Beliefs in the benefits of cannabis—for its yet unfounded therapeutic potential—are commonly held or supported by poor-quality evidence. Patients and their caregivers are inundated with media stories about a budding industry and its mergers and acquisitions while it grows to meet a need for what is regarded by some as overlooked and undertreated ailments. How should oncologists and the oncology team, trusted as the informed and compassionate advocates for their patients, reconcile the overwhelming public attention being given to this product—growing more, creating new routes of administration, and reaching for new uses—with the work needed to further the science of cannabis as it pertains to cancer care?

The onus is on us, the community of cancer care providers, to act.

Therapeutic and clinical developments in oncology are resulting in improvements in the survival of many patients. Costly immunologic therapies are promising and are being implemented for a variety of cancers. New science about the microbiome, about cancer detection, and about targeted therapies are being researched. And yet, contrasted against those celebrations of scientific ingenuity are the glaring gaps in the work pertaining to cannabis to settle unsubstantiated claims and anecdotal observations of this elixir for the ages. As clinicians and scientists, we must work to generate the needed evidence-based outcomes and to document or dispel the potential interactions and sequelae between cannabis and prescribed cancer treatments. “There are in fact two things, science and opinion, the former begets knowledge, the latter ignorance”.

The frameworks to lead this charge are ours to create. The current legal framework is focused on issues of access and control to regulate production, distribution, and sale. The medical framework for cannabis research is more tenuous, concentrated in silos of expertise as a result of the previous prohibitory environment. The study of cannabis is ripe for development, but even intra-institutional endeavors require help. The machinery of science requires some assembly and repurposing to address the new challenges.

If the current and future oncology landscape is a challenge for those working in cancer care, we must remember that patients deserve our compassion as they attempt to navigate this emotional journey with or without cannabis. More importantly, they need our support and deserve to see us take leadership in cannabis research. Oncologists who have expertise in both the clinical and scientific worlds must inform the necessary work. We must be the architects of its design, building bridges to industry and patients, while engaging our academic institutions.

“Coming together is a beginning, staying together is progress, and working together is success”.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588059/

Isolation, Synthesis And Structure Determination Of Cannabidiol Derivatives And Their Cytotoxic Activities.

Publication Cover

“In a continuing effort to explore the structural diversity and pharmacological activities of natural products based scaffolds, herein, we report the isolation, synthesis, and structure determination of cannabidiol and its derivatives along with their cytotoxic activities. Treatment of cannabidiol (1) with acid catalyst POCl3 afforded a new derivative 6 along with six known molecules 2  57 and, 8. The structure of 6 was elucidated by extensive spectroscopic analyses and DFT calculations of the NMR and ECD data. All the compounds (2  8) were evaluated for their cytotoxic potential against a panel of eight cancer cell lines. Compounds 457, and 8showed pronounced in vitro cytotoxic activity with IC50 values ranging from 5.6 to 60 μM. Out of the active molecules, compounds 4, and 7 were found to be comparable to that of the parent molecule 1 on the inhibition of almost all the tested cancer cell lines.”

https://www.ncbi.nlm.nih.gov/pubmed/31282748

https://www.tandfonline.com/doi/abs/10.1080/14786419.2019.1638381?journalCode=gnpl20

The heterogeneity and complexity of Cannabis extracts as antitumor agents

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“The Cannabis plant contains over 100 phytocannabinoids and hundreds of other components. The biological effects and interplay of these Cannabis compounds are not fully understood and yet influence the plant’s therapeutic effects.

Here we assessed the antitumor effects of whole Cannabis extracts, which contained significant amounts of differing phytocannabinoids, on different cancer lines from various tumor origins.

Our results show that specific Cannabis extracts impaired the survival and proliferation of cancer cell lines as well as induced apoptosis.

Our findings showed that pure (-)-Δ9trans-tetrahydrocannabinol (Δ9-THC) did not produce the same effects on these cell lines as the whole Cannabis extracts. Furthermore, Cannabis extracts with similar amounts of Δ9-THC produced significantly different effects on the survival of specific cancer cells.

In addition, we demonstrated that specific Cannabis extracts may selectively and differentially affect cancer cells and differing cancer cell lines from the same organ origin. We also found that cannabimimetic receptors were differentially expressed among various cancer cell lines and suggest that this receptor diversity may contribute to the heterogeneous effects produced by the differing Cannabis extracts on each cell line.

Our overall findings indicate that the effect of a Cannabis extract on a specific cancer cell line relies on the extract’s composition as well as on certain characteristics of the targeted cells.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26983

“Many previous reports highlight and demonstrate the anti-tumor effects of cannabinoids. In the last decade, accumulating evidence has indicated that phytocannabinoids might have antitumor properties. A number of in vitro and in vivo studies have demonstrated the effects of phytocannabinoids on tumor progression by interrupting several characteristic features of cancer. These studies suggest that specific cannabinoids such as Δ9-THC and CBD induce apoptosis and inhibit proliferation in various cancer cell lines.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=26983&path%5B%5D=85698

https://pubmed.ncbi.nlm.nih.gov/31289609/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609248/

Antitumor Cannabinoid Chemotypes: Structural Insights.

Image result for frontiers in pharmacology“Cannabis has long been known to limit or prevent nausea and vomiting, lack of appetite, and pain. For this reason, cannabinoids have been successfully used in the treatment of some of the unwanted side effects caused by cancer chemotherapy.

Besides their palliative effects, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of tumors.

Cannabinoids of endogenous, phytogenic, and synthetic nature have been shown to impact the proliferation of cancer through the modulation of different proteins involved in the endocannabinoid system such as the G protein-coupled receptors CB1, CB2, and GRP55, the ionotropic receptor TRPV1, or the fatty acid amide hydrolase (FAAH).

In this article, we aim to structurally classify the antitumor cannabinoid chemotypes described so far according to their targets and types of cancer. In a drug discovery approach, their in silico pharmacokinetic profile has been evaluated in order to identify appropriate drug-like profiles, which should be taken into account for further progress toward the clinic.

This analysis may provide structural insights into the selection of specific cannabinoid scaffolds for the development of antitumor drugs for the treatment of particular types of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/31214034

“The first report on the antitumor activity of phytocannabinoids was published over four decades ago. During these last years, significant research has been focused on the therapeutic potential of cannabinoids to manage palliative effects in cancer patients. Besides such palliative applications, some cannabinoids have shown anticancer properties. Since inflammation is a common risk factor for cancer, and some cannabinoids have shown anti-inflammatory properties, they could play a role in chemoprevention.” https://www.frontiersin.org/articles/10.3389/fphar.2019.00621/full
“Antitumor effects of THC.” http://www.ncbi.nlm.nih.gov/pubmed/11097557
“Antitumor effects of cannabidiol” http://www.ncbi.nlm.nih.gov/pubmed/14617682
“Anti-tumour actions of cannabinoids.” https://www.ncbi.nlm.nih.gov/pubmed/30019449
“Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer.” https://www.ncbi.nlm.nih.gov/pubmed/29940172