Synthetic cannabinoids nano-micelles for the management of triple negative breast cancer.

 Journal of Controlled Release

“Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with poor prognosis and inadequate therapeutic outcome. This contribution reports the use of a cannabinoid derivative, WIN55,212-2 (WIN) on the growth of TNBC in a 4T1 syngeneic mouse model.

To reduce the well-known psychoactive side effects of cannabinoids, we prepared a nanomicellar formulation of WIN (SMA-WIN). In vivo biodistribution, in silico ADME predictions, anticancer activity, and psychoactive effect of WIN and SMA-WIN studies suggest that SMA-WIN formulation can reduce to greater extent tumor growth with milder psychoactive side effects when compared to free drug.

Finally, the effects of WIN and SMA-WIN in combination with doxorubicin (Doxo), an established chemotherapeutic agent for the treatment of TNBC, were investigated in vitro and in vivo. SMA-WIN in combination with Doxo showed therapeutic efficacy and was able to reduce the tumor volume of TNBC murine model drastically. Moreover, SMA-WIN, while favoring drug tumor accumulation, minimized the adverse psychoactive effects that have impeded the use of this agent in the clinic.

To our knowledge, this is the first report for the assessment of cannabinoid nanoparticles in vivo for the treatment of TNBC and its enhanced anticancer effect at low doses with Doxo. These findings suggest a new therapeutic strategy in the management of TNBC.”

https://www.ncbi.nlm.nih.gov/pubmed/30367922

https://www.sciencedirect.com/science/article/pii/S0168365918306114?via%3Dihub

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Report of Objective Clinical Responses of Cancer Patients to Pharmaceutical-grade Synthetic Cannabidiol.

“Cannabinoids are widely used in the management of pain, nausea and cachexia in cancer patients. However, there has been no objective clinical evidence of any anticancer activity yet.

The aim of this study was to assess the effects of pharmaceutical-grade synthetic cannabidiol on a range of cancer patients.

RESULTS:

Clinical responses were seen in 92% of the 119 cases with solid tumours including a reduction in circulating tumour cells in many cases and in other cases, a reduction in tumour size, as shown by repeat scans. No side-effects of any kind were observed when using pharmaceutical grade synthetic cannabidiol.

CONCLUSION:

Pharmaceutical-grade synthetic cannabidiol is a candidate for treating breast cancer and glioma patients.”

https://www.ncbi.nlm.nih.gov/pubmed/30275207

http://ar.iiarjournals.org/content/38/10/5831

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At 70, Singer Olivia Newton-John​ Using Cannabis To Treat Cancer.

“At 70, Singer Olivia Newton-John​ Using Cannabis To Treat Cancer. Olivia Newton-John says she has been diagnosed with cancer for the third time in three decades. Newton-John says she’s “treating it naturally and doing really well.” The “Grease” star says she is taking cannabis oil, made from marijuana her husband John Easterling grows on their ranch in Santa Barbara. She said, “I believe I will win over it.”” https://sanfrancisco.cbslocal.com/2018/09/10/olivia-newton-john-cannabis-cancer/

“Grease star Olivia Newton-John is battling her breast cancer with cannabis. Grease star Olivia Newton-John is offering an update on her third battle with cancer and revealing how cannabis has become a key component in her treatment plan.”   http://www.digitalspy.com/showbiz/news/a865881/grease-olivia-newton-john-battling-breast-cancer-with-cannabis/

Olivia Newton-John Says She’s Managing Breast Cancer with Cannabis. Newton-John explained that she uses cannabis oil to treat the pain and help her sleep, much of which her husband John Easterling (who runs Amazon Herb Company) grows for her. “I’m very lucky that I live in a state where it’s legal and that I have a husband who is a plant medicine man,” she said. “How lucky is that?” Newton-John also advocated for legalizing cannabis in her home country of Australia, adding, “My dream is that it will be available to all the cancer patients or people going through cancer or any kind of disease that causes pain.” Newton-John turns 70 on September 26.” http://exclaim.ca/music/article/olivia_newton-john_says_shes_managing_breast_cancer_with_cannabis

“Olivia Newton-John diagnosed with cancer for a third time but believes she ‘will win’ health battle with homegrown cannabis treatment. The Grease actress is using homegrown cannabis as part of her treatment to fight the disease. She drinks a cannabis mixture made by her herbalist husband to control the illness.” https://www.mirror.co.uk/3am/celebrity-news/olivia-newton-john-diagnosed-cancer-13220595

“Olivia Newton-John uses medical marijuana to treat cancer”  https://www.buzz.ie/celebs/olivia-newton-john-drinks-cannabis-extract-numb-pain-cancer-253796

“Olivia Newton-John reveals marijuana helping her beat cancer”   http://www.9news.com.au/national/2017/09/03/08/58/olivia-newton-john-backs-medicinal-cannabis

“Olivia Newton-John’s cancer battle is going well… Thanks to cannabis oil!”  https://closeronline.co.uk/celebrity/news/olivia-newton-john-daughter-chloe-lattanzi-cannabis-oil-cancer/ 

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Olivia Newton-John ‘Feeling Great’ as Source Denies ‘False’ Report Her Cancer Has Spread Further. “This is just false,” a source close to Newton-John tells PEOPLE. “She’s feeling and looking great. Everything that’s being reported about her diagnosis is the same news she released last year.” https://people.com/music/olivia-newton-john-denies-false-report-cancer-spread/

“Olivia Newton-John Reveals Secret Cancer Battle in 2013: ‘I Just Decided to Keep It to Myself.” Last year, Newton-John announced she’d been diagnosed with stage 4 breast cancer that had metastasized to her back, but the 69-year-old actress has been treating the illness with natural wellness therapies, including medicinal marijuana. A source close to Newton-John tells PEOPLE that she’s been feeling fine and healthy as of late.” https://people.com/music/olivia-newton-john-secret-cancer-battle-decided-keep-myself/

Olivia Newton-John: It’s not just cancer sufferers needing help, carers do too. The mum-of-one discovered she had a tumour in the base of her spine last year. She had previously overcome breast cancer in 1992 after undergoing surgery and chemo, before secretly beating the disease again in 2013. Praising both husband John and her daughter Chloe, Olivia said: “Of course they’ve been a huge support, I think it’s hard for people on the outside – the care takers – because they have to be taken care of too sometimes, because it is hard for them.” John grows cannabis plants for Olivia, as she has chosen natural therapies such as cannabis oil to help ease her pain from the disease, instead of opioids and other drugs such as chemo this time round. He grows the plants in California where the couple live, as it is legal there.” https://startsat60.com/entertainment/tv-movies/olivia-newton-john-cancer-sufferers-carers-husband-john-help

“‘I use cannabis’: Olivia Newton-John talks cancer treatment” https://startsat60.com/health/i-use-cannabis-olivia-newton-john-opens-up-on-cancer-treatment

“Olivia Newton-John using cannabis oil as she battles cancer for the third time”  https://www.hellomagazine.com/healthandbeauty/health-and-fitness/2018091162192/olivia-newton-john-using-cannabis-oil-battles-cancer-third-time/

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“Olivia Newton-John Is Using Cannabis Oil To Treat Her Cancer”  https://www.inverse.com/article/32780-cannabis-oil-cancer-treatment-cannabinoid-chemotherapy

“Olivia Newton John’s cannabis oil for cancer treatment” https://www.msn.com/en-nz/health/medical/olivia-newton-johns-cannabis-oil-for-cancer-treatment/ar-AAoTvE3

“‘I believe I will win’: Olivia Newton-John, 69, reveals the tragic cancer diagnosis she kept secret… as she fights the disease for a third time with the help of her husband” https://www.dailymail.co.uk/tvshowbiz/article-6148177/Olivia-Newton-John-69-reveals-tragic-cancer-diagnosis-kept-secret.html

“Olivia’s husband grows her medical marijuana”  https://au.be.yahoo.com/entertainment/celebrity/a/37038356/john-easterling-home-grows-olivia-newton-johns-medical-marijuana/

“Olivia Newton-John Admits to Using Home-Grown Medical Marijuana to Battle Cancer” http://popculture.com/2017/09/11/olivia-newton-john-medical-marijuana-breast-cancer/

“Olivia Newton-John Reveals She Was Unable to Walk After Cancer Relapse – and She’s Using Marijuana to Ease Pain. The 68-year-old said that the “hardest thing” has been her pain level, admitting that trying to do shows was “really agonizing.” Now, she’s been treating the pain with medical marijuana her husband John Easterling grows. “I’ll be fine,” said Newton-John.” https://people.com/music/olivia-newton-john-cancer-update-couldnt-walk-australian-60-minutes/

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“Olivia Newton-John on Being a Cancer ‘Thriver’ and Using Weed to Cope with Her Relapse: It’s a ‘Healing Plant’. The actress also shared that she’s been treating the pain with medical marijuana her husband John Easterling grows. “People have this vision from the ’60s of people just sitting around and getting stoned,” she said. “It’s not about that. This plant is a healing plant. I think we need to change the vision of what it is because it helped me greatly and it helps with pain and inflammation.”” https://people.com/music/olivia-newton-john-cancer-relapse-weed/

Olivia Newton-John reveals she is on medical cannabis for cancer” https://www.dailymail.co.uk/health/article-6171365/Olivia-Newton-John-reveals-medical-cannabis-breast-cancer.html

“‘It’s a magical miracle plant:’ Olivia Newton-John reveals husband John Easterling grows marijuana to aid her breast cancer battle” https://www.dailymail.co.uk/tvshowbiz/article-4869940/Olivia-Newton-John-benefits-medical-marijuana.html

“‘It’s really important and should be available’: Olivia Newton-John speaks about how ‘medical cannabis’ is helping her beat breast cancer” https://www.dailymail.co.uk/tvshowbiz/article-4846664/Olivia-Newton-John-talks-cannabis-use-time.html

“Olivia Newton-John voices her support for medical marijuana after revealing her husband grows the plant to aid her breast cancer battle” https://www.dailymail.co.uk/tvshowbiz/article-4891760/Olivia-Newton-John-voices-support-medical-marijuana.html

“‘Medical cannabis has helped me a lot’: Olivia Newton-John speaks candidly about the ‘healing remedies’ that have helped CURE her pain during her agonising cancer battle” https://www.dailymail.co.uk/tvshowbiz/article-5181401/Olivia-Newton-John-speaks-candidly-medical-cannabis.html

“Let’s Get Physical! Olivia Newton-John beams in green as she dazzles Melbourne crowds at charity walk to raise funds for her cancer research centre… after speaking candidly about her attempts to ‘win over’ the disease” https://www.dailymail.co.uk/tvshowbiz/article-6172857/Olivia-Newton-John-beams-green-dazzles-crowds-cancer-research-charity-walk.html

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Olivia Newton-John leads the biggest ever Wellness Walk and Research Run! With participant numbers up by over 50 per cent from last year, the beautiful grounds at La Trobe University were filled with a vibe of family, community, love and hope. Olivia Newton-John was an enthusiastic participant enjoying the sunshine, along with her husband John Easterling, her niece Tottie Goldsmith (herself an ONJ Centre Goodwill Champion) and other family members. She was grateful for the large crowd of people who were there to support her ONJ Centre.“It’s very moving actually, to see so many people turn out,” says Olivia. “It looks like there are more people than last year which is fantastic, people with their dogs and their children and their friends. It’s wonderful.”” https://www.onjcancercentre.org/news/article/2018/09/18/biggest-ever-wellness-walk-and-research-run

“Well over half a million dollars has been raised so far and while the event itself is over for this year, fundraising is still open until the 30 September. You can continue to support family and friends by donating to their page, or you can donate to Olivia’s page here: https://secure.artezpacific.com/registrant/FundraisingPage.aspx?registrationID=1213890&langPref=en-CA

“The Olivia Newton-John Cancer Wellness & Research Centre is at the frontier of cancer medicine, with over 200 ongoing clinical trials.” https://www.onjcancercentre.org/patients-family/clinical-trials

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http://www.thctotalhealthcare.com/olivia-newton-john-champions-the-use-of-magical-miracle-medicinal-cannabis/

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Combined CB2 Receptor Agonist and Photodynamic Therapy Synergistically Inhibit Tumor Growth in Triple Negative Breast Cancer.

Photodiagnosis and Photodynamic Therapy

“Triple negative breast cancer (TNBC) is the deadliest form of breast cancer because compared with other types of breast cancer, it is more aggressive, diagnosed at later stage and more likely to develop recurrence.

Many patients do not experience adequate tumor control after current clinical treatments involving surgical removal, chemotherapy and/or radiotherapy, leading to disease progression and significantly decreased quality of life.

Here we report a new combinatory therapy strategy involving cannabinoid-based medicine and photodynamic therapy (PDT) for the treatment of TNBC.

This combinatory therapy targets two proteins upregulated in TNBC: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the combined CB2R agonist and TSPO-PDT treatment resulted in synergistic inhibition in TNBC cell and tumor growth.

This combinatory therapy approach provides new opportunities to treat TNBC with high efficacy. In addition, this study provides new evidence on the therapeutic potential of CB2R agonists for cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/30240926

https://www.sciencedirect.com/science/article/pii/S1572100018301571?via%3Dihub

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Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer.

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“Exosomes and microvesicles (EMV) are lipid bilayer-enclosed structures, released by cells and involved in intercellular communication through transfer of proteins and genetic material. EMV release is also associated with various pathologies, including cancer, where increased EMV release is amongst other associated with chemo-resistance and active transfer of pro-oncogenic factors.

Recent studies show that EMV-inhibiting agents can sensitize cancer cells to chemotherapeutic agents and reduce cancer growth in vivo.

Cannabidiol (CBD), a phytocannabinoid derived from Cannabis sativa, has anti-inflammatory and anti-oxidant properties, and displays anti-proliferative activity.

Here we report a novel role for CBD as a potent inhibitor of EMV release from three cancer cell lines: prostate cancer (PC3), hepatocellular carcinoma (HEPG2) and breast adenocarcinoma (MDA-MB-231).

CBD significantly reduced exosome release in all three cancer cell lines, and also significantly, albeit more variably, inhibited microvesicle release.

The EMV modulating effects of CBD were found to be dose dependent (1 and 5 μM) and cancer cell type specific. Moreover, we provide evidence that this may be associated with changes in mitochondrial function, including modulation of STAT3 and prohibitin expression, and that CBD can be used to sensitize cancer cells to chemotherapy.

We suggest that the known anti-cancer effects of CBD may partly be due to the regulatory effects on EMV biogenesis, and thus CBD poses as a novel and safe modulator of EMV-mediated pathological events.”

https://www.ncbi.nlm.nih.gov/pubmed/30150937

https://www.frontiersin.org/articles/10.3389/fphar.2018.00889/full

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Anti-tumoural actions of cannabinoids.

British Journal of Pharmacology banner

“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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Novel mechanism of cannabidiol-induced apoptosis in breast cancer cell lines.

The Breast Home

“Studies have emphasized an antineoplastic effect of the non-psychoactive, phyto-cannabinoid, Cannabidiol (CBD). However, the molecular mechanism underlying its antitumor activity is not fully elucidated.

Herein, we have examined the effect of CBD on two different human breast cancer cell lines: the ER-positive, well differentiated, T-47D and the triple negative, poor differentiated, MDA-MB-231 cells.

In both cell lines, CBD inhibited cell survival and induced apoptosis in a dose dependent manner as observed by MTT assay, morphological changes, DNA fragmentation and ELISA apoptosis assay. CBD-induced apoptosis was accompanied by down-regulation of mTOR, cyclin D1 and up-regulation and localization of PPARγ protein expression in the nuclei and cytoplasmic of the tested cells.

The results suggest that CBD treatment induces an interplay among PPARγ, mTOR and cyclin D1 in favor of apoptosis induction in both ER-positive and triple negative breast cancer cells, proposing CBD as a useful treatment for different breast cancer subtypes.”

“Programmed Cell Death (Apoptosis)” http://www.ncbi.nlm.nih.gov/books/NBK26873/
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Appraising the “entourage effect”: antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer.

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“Breast cancer is the second leading cause of death among women. Although early diagnosis and development of new treatments have improved their prognosis, many patients present innate or acquired resistance to current therapies. New therapeutic approaches are therefore warranted for the management of this disease.

Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer. Most of these studies have been conducted with pure compounds, mainly Δ9-tetrahydrocannabinol (THC).

The cannabis plant, however, produces hundreds of other compounds with their own therapeutic potential and the capability to induce synergic responses when combined, the so-called “entourage effect”.

Here, we compared the antitumor efficacy of pure THC with that of a botanical drug preparation (BDP). The BDP was more potent than pure THC in producing antitumor responses in cell culture and animal models of ER+/PR+, HER2+ and triple-negative breast cancer. This increased potency was not due to the presence of the 5 most abundant terpenes in the preparation.

While pure THC acted by activating cannabinoid CB2 receptors and generating reactive oxygen species, the BDP modulated different targets and mechanisms of action. The combination of cannabinoids with estrogen receptor- or HER2-targeted therapies (tamoxifen and lapatinib, respectively) or with cisplatin, produced additive antiproliferative responses in cell cultures. Combinations of these treatments in vivo showed no interactions, either positive or negative.

Together, our results suggest that standardized cannabis drug preparations, rather than pure cannabinoids, could be considered as part of the therapeutic armamentarium to manage breast cancer.”

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A peripherally restricted cannabinoid 1 receptor agonist as a novel analgesic in cancer-induced bone pain.

 

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“Many malignant cancers, including breast cancer, have a propensity to invade bones, leading to excruciating bone pain.

Opioids are the primary analgesics used to alleviate this cancer-induced bone pain (CIBP) but are associated with numerous severe side effects, including enhanced bone degradation, which significantly impairs patients’ quality of life.

In contrast, agonists activating only peripheral CB1 receptors (CB1Rs) have been shown to effectively alleviate multiple chronic pain conditions with limited side effects, yet no studies have evaluated their role(s) in CIBP.

Here, we demonstrate for the first time that a peripherally selective CB1R agonist can effectively suppress CIBP.

Overall, our studies demonstrate that CIBP can be effectively managed by using a peripherally restricted CB1R agonist, PrNMI, without inducing dose-limiting central side effects.

Thus, targeting peripheral CB1Rs could be an alternative therapeutic strategy for the treatment of CIBP.”

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

British Journal of Pharmacology banner

“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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