Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as Adjunctive Therapy in Advanced Cancer Patients With Chronic Uncontrolled Pain.

Journal of Pain and Symptom Management Home

“Prior phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain.

To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol, in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy.

Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at week 3 and on all three at week 5.

The safety profile of nabiximols was consistent with earlier studies.

Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in US patients.

Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/28923526

http://www.jpsmjournal.com/article/S0885-3924(17)30465-7/fulltext

Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

Image result for frontiers in oncology

“Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. These nanoparticle drones can be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy.

In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

As discussed earlier, nanoparticle drones are particularly attractive because they can also be loaded with drugs payload like cannabinoids. Cannabinoids, which are the bioactive components of Cannabis sativa and their derivatives, may exert palliative effects in cancer patients by preventing nausea, vomiting, and pain and by stimulating appetite .

Furthermore, studies indicate that cannabinoids can inhibit cancer cell growth in in vitro and in vivo. A Nature Reviews Cancer article and other recently published work highlight the potential of cannabinoids for treating cancer, working in synergy with radiotherapy and serving as radiosensitzers to enhance damage to lung tumor cells in particular. Consistent with this, our own experiments have confirmed the potential of cannabinoids in treating lung cancer, with results confirming that cannabinoids can enhance damage to cancer cells.

Overall, the use of nanoparticle drones administered via INH to enhance NRT, as highlighted in this article, may provide a good strategy for maximizing therapeutic efficacy in external beam NRT for lung cancer. Also there is growing evidence that cannabinoids can serve as radiosensitizers, enhance damage to tumor cells, slow tumor growth, and work synergistically with radiotherapy in cancer treatment.”

http://journal.frontiersin.org/article/10.3389/fonc.2017.00208/full

“Cannabis Science Announces Publication of Initial Research Results Using Nanoparticle Drones to Target Lung Cancer With Radiosensitizers and Cannabinoids in the Renowned Journal Frontiers in Oncology” https://ca.finance.yahoo.com/news/cannabis-science-announces-publication-initial-120522920.html

“Cannabis Science “Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids” Full Publication Released Today In Frontiers In Oncology” http://www.marketwired.com/press-release/cannabis-science-nanoparticle-drones-target-lung-cancer-with-radiosensitizers-cannabinoids-2234167.htm

Olivia Newton-John champions the use of ‘magical, miracle’ medicinal cannabis

Cannabis is a "magical miracle plant" says singer Olivia Newton-John.“Let’s get medicinal, says Olivia Newton-John, who has spoken out about the use of medicinal cannabis on a recent visit to Australia. “I will do what I can to encourage it. It’s an important part of treatment and it should be available,” the singer, who announced a second battle with breast cancer in May, told News Corp Australia. The Australian entertainer said the drug – which is legal in her home state of California – had helped her during her second fight against cancer.” https://www.stuff.co.nz/entertainment/celebrities/96702731/olivia-newtonjohn-champions-the-use-of-magical-miracle-medicinal-cannabis

“OLIVIA NEWTON-JOHN TELLS HOW MARIJUANA IS HELPING HER BEAT CANCER”.“I use medicinal cannabis, which is really important for pain and healing,” “It’s a plant that has been maligned for so long, and has so many abilities to heal.”“I will do what I can to encourage it,” “It’s an important part of treatment, and it should be available. I use it for the pain and it’s also a medicinal thing to do — the research shows it’s really helpful.”” http://www.dailytelegraph.com.au/news/nsw/olivia-newtonjohn-tells-how-marijuana-is-helping-her-beat-cancer/news-story/12705dfadc0579a1139472271aa03bf8

 “It’s a magical miracle plant:’ Olivia Newton-John reveals husband John Easterling grows marijuana to aid her breast cancer battle… as star recalls her struggle to tell daughter Chloe about heartbreaking diagnosis. In an emotional interview with Karl Stefanovic on 60 Minutes, Olivia revealed that the controversial plant has helped her immeasurably in her cancer battle. ”It’s been a maligned plant all these years and it really is a magical miracle plant.”” http://www.dailymail.co.uk/tvshowbiz/article-4869940/Olivia-Newton-John-benefits-medical-marijuana.html

“OLIVIA NEWTON-JOHN TELLS ALL ON HER CANCER BATTLE & WHY WEED IS HER ‘HEALING PLANT'” http://okmagazine.com/photos/olivia-newton-john-cancer-weed-today-show/

“Olivia Newton-John on Being a Cancer ‘Thriver’ and Using Weed to Cope with Her Relapse: It’s a ‘Healing Plant’” http://people.com/music/olivia-newton-john-cancer-relapse-weed/

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Olivia Newton-John credits weed for helping cancer battle http://pagesix.com/2017/09/21/olivia-newton-john-credits-weed-for-helping-cancer-battle/

“Olivia Newton-John’s cancer battle is going well… Thanks to cannabis oil!” http://lifestyle.one/closer/celebrity/news/olivia-newton-john-daughter-chloe-lattanzi-cannabis-oil-cancer/

“Olivia Newton-John is Using Cannabis Oil for her Breast Cancer—Here’s How It Could Help” http://www.health.com/breast-cancer/cannabis-cancer-treatment-olivia-newton-john

“Cannabis Oil Will Help Olivia Newton-John Battle Breast Cancer”  https://thefreshtoast.com/celebrity/olivia-newton-john-will-use-cannabis-oil-in-battling-second-breast-cancer-diagnosis/

“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 USES MEDICINAL CANNABIS IN CANCER FIGHT”  http://www.wsfm.com.au/entertainment/the-feed/olivia-newton-john-uses-medicinal-cannabis-in-cancer-fight

Olivia Newton-John is using medical marijuana during her battle with breast cancer” http://www.kansascity.com/entertainment/article171116417.html
“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
“Newton-John backs medicinal cannabis”

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

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 “”I use medicinal cannabis, which is really important for pain and healing. It’s a plant that has been maligned for so long and has so many abilities to heal,” Newton-John told the Daily Telegraph in a recent interview. Newton-John does not have a problem with her supplies of cannabis oil as her daughter, Chloe Lattanzi, owns a cannabis farm in Oregon, and can be easily obtained in her home state of California, where the use of medical marijuana is legal. However, as many parts of the world are still pessimistic about the medical use of marijuana, Newton-John has declared that she will advocate for its use, including in her home country Australia, where obtaining permits to use it still requires a long process even after it was legalized earlier this year. “I will do what I can to encourage it. It’s an important part of treatment, and it should be available. I use it for the pain and it’s also a medicinal thing to do — the research shows it’s really helpful,” Newton John said.” http://www.christianpost.com/news/olivia-newton-john-news-70s-icon-reveals-advocates-use-of-cannabis-oil-to-deal-with-cancer-pain-197915/
 “Olivia Newton-John champions use of medicinal cannabis in breast cancer battle” http://www.ibtimes.co.uk/olivia-newton-john-champions-use-medicinal-cannabis-breast-cancer-battle-1637729
“Newton-John champions medicinal cannabis use after it helped her cancer battle” https://thewest.com.au/news/health/newton-john-champions-medicinal-cannabis-use-after-it-helped-her-cancer-battle-ng-b88588000z
‘It’s really important and should be available’: Olivia Newton-John speaks for the first time about how ‘medical cannabis’ is helping her beat breast cancer” http://www.dailymail.co.uk/tvshowbiz/article-4846664/Olivia-Newton-John-talks-cannabis-use-time.html
“Grammy-winning singer/songwriter and actor Olivia Newton-John has opened up about her use of marijuana. “I use medicinal cannabis, which is really important for pain and healing,”“I will do what I can to encourage it. It’s an important part of treatment, and it should be available.”” https://www.civilized.life/articles/medicinal-cannabis-olivia-newton-john/
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“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/

 “Grassed Lightning: Olivia Newton-John is using cannabis instead of popping pills for breast cancer pain relief” http://www.mirror.co.uk/3am/celebrity-news/grassed-lightning-olivia-newton-john-11158137

“WEED ALL ABOUT IT.  Olivia Newton-John reveals she is drinking cannabis extract to ease her back pain as she battles cancer”  https://www.thesun.co.uk/fabulous/4454398/olivia-newton-john-reveals-she-is-drinking-cannabis-extract-to-ease-her-back-pain-as-she-battles-cancer/

“Olivia Newton-John Reveals She Was Unable to Walk After Cancer Relapse – and She’s Using Marijuana to Ease Pain” http://people.com/music/olivia-newton-john-cancer-update-couldnt-walk-australian-60-minutes/

“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 Talks Using Medical Marijuana In Cancer Treatment. “I use medical cannabis, which is really important to pain and healing. It’s an important part of treatment, and it should be available.”” https://www.thefix.com/olivia-newton-john-talks-using-medical-marijuana-cancer-treatment

“I’m really hoping that you will have it accessible to people. Particularly for people who are in pain. It’s not just cancer, it’s many, many illnesses. In children with epilepsy, parents are going to jail for trying to help their children, by giving them medicinal cannabis. That has to change, and I think it will. I think people are realizing this has been a maligned plant but it’s a healing plant with lots of wonderful properties. It can help alot of people. And they’re doing alot of research into the healing properties of cannabis, it’s not just for pain but to cure things. So it’s a very exciting time in the research as well.” –Olivia Newton-John http://www.dailymail.co.uk/video/tvshowbiz/video-1537789/Olivia-Newton-John-wants-medical-cannabis-legal-Australia.html

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 “Actress and singer Olivia Newton-John believes in the ‘healing properties’ of medical cannabis and hopes it will become legal, including for children.” http://www.dailymail.co.uk/video/tvshowbiz/video-1537789/Olivia-Newton-John-wants-medical-cannabis-legal-Australia.html

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

“A picture of health! Olivia Newton-John beams at the ONJ Wellness Walk and Research Run in Melbourne as she battles cancer for the second time”   http://www.dailymail.co.uk/tvshowbiz/article-4892342/Olivia-Newton-John-cancer-fun-run.html

Cannabidiol, a novel inverse agonist for GPR12.

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“GPR12 is a constitutively active, Gs protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay.

Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12. Thus, GPR12 is a novel molecular target for CBD.

CBD is a promising novel therapeutic agent for cancer, and GPR12 has been shown to alter viscoelasticity of metastatic cancer cells.

Since we have demonstrated that CBD is an inverse agonist for GPR12, this provides novel mechanism of action for CBD, and an initial chemical scaffold upon which highly potent and efficacious agents acting on GPR12 may be developed with the ultimate goal of blocking cancer metastasis.”

https://www.ncbi.nlm.nih.gov/pubmed/28888984

http://www.sciencedirect.com/science/article/pii/S0006291X1731759X

A selective review of medical cannabis in cancer pain management.

“Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions.

Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population.

This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised.

Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting.

There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients.

However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/28866904

http://apm.amegroups.com/article/view/16199

 

Cannabinoids as Anticancer Drugs.

Advances in Pharmacology

“The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics’ effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression.”

https://www.ncbi.nlm.nih.gov/pubmed/28826542

http://www.sciencedirect.com/science/article/pii/S105435891730039X?via%3Dihub

Use of medical cannabis to reduce pain and improve quality of life in cancer patients.

Journal of Clinical Oncology

“Early attention to pain and symptoms in those with cancer improves both quality of life and survival. Opioid medications are the mainstay treatment of cancer-related pain.

Cannabinoids are increasingly used as adjunctive treatments for cancer pain, but clinical evidence supporting their use as an “opioid sparing agent” or to improve quality of life is as yet unknown.

Our study sought to determine if the addition of cannabinoids (medical cannabis) resulted in the reduction of the average opioid dose required for pain control, and improve self-reported quality of life indices.

Patients with cancer pain benefited from the addition of cannabinoids.

The average opioid dose decreased following access to medical cannabis.

Self-reported ratings of several quality of life indicators showed statistically significant improvement.

Our study shows a signal that cannabinoids may reduce cancer patients’ reliance on opioids to control pain.

Further prospective controlled studies are needed to further elucidate the role of cannabinoids in the treatment of cancer pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28148191

A Review of the Therapeutic Antitumor Potential of Cannabinoids.

:Image result for J Altern Complement Med.

“The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment.

RESULTS:

Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of “cannabinoid sensitizers.” Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness.

CONCLUSIONS:

A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.”

Identification of Terpenoid Chemotypes Among High (−)-trans-Δ9- Tetrahydrocannabinol-Producing Cannabis sativa L. Cultivars

Cover for Cannabis and Cannabinoid Research

Cannabis sativa L. (cannabis) is an annual diecious member of the Cannabaceae family. Since ancient times cannabis has been used by humans for its fiber, seed, as well as its psychoactive and medicinal resin. Despite a long history of use, the legal status of cannabis in modern times often depends on its intended use. Cannabis grown for its fiber or seed, commonly known as hemp, is legally cultivated in many nations. Cannabis used for its psychoactive properties, in North American commonly known as “marijuana,” has been illegal in most nations worldwide since the 1961 United Nations Single Convention on Narcotic Drugs. Recently however, laws concerning the legal status of cannabis are changing around the world. In the United States of America, many states have legalized cannabis for medical use, whereas some have even legalized cannabis for adult consumption. Uruguay recently legalized cannabis and laws in various countries within the European Union (EU) are also changing regarding cannabis. Due to its many and controversial uses, the taxonomic classification of cannabis has been the subject of both legal and scientific debate.

From a morphological perspective, three main types of cannabis have been described sativa, indica, and ruderalis. Generally sativa plants are described as taller and loosely branched, whereas indica is typically shorter, more densely branched, and conical in shape. Ruderalis is described as short (≤2 feet) at maturity and sparsely if at all branched.7Whether the genus Cannabis is monotypic and composed of just a single species (C. sativa) or polytypic and composed of multiple species is an old taxonomic debate. A more recent taxonomic classification dividing cannabis into seven putative taxa based on morphological, geographical, and genetic traits has been proposed.

Cannabinoids are a group of terpenophenolic compounds found in cannabis. Today over 100 cannabinoids from cannabis have been characterized. (−)-Trans-Δ9-tetrahydrocannabinol (THC) is considered the primary active ingredient responsible for the intoxicating and medical effects attributed to cannabis. THC has antiemetic, neuroprotectant, and anti-inflammatory properties as well as the ability to reduce certain forms of neuropathic and chronic pain. Another important cannabinoid, cannabidiol (CBD), has neuroprotective, anti-inflammatory, antipsychotic, and antiseizure properties without the intoxicating effects of THC. Other minor cannabinoids, such as cannabigerol (CBG), cannabichromene (CBC), and tetrahydrocannabivarin (THCV), also exhibit interesting pharmacological properties.

Since cannabinoids are the major active ingredients found in cannabis, it makes sense to classify cannabis from a chemotaxonomic perspective according to cannabinoid levels for both medical and legal purposes. Early studies noted that cannabis used for fiber tended to have higher levels of CBD, whereas cannabis used for drug purposes had higher levels of THC

Terpenoids represent another interesting group of biologically active compounds found in cannabis. Due to their volatile nature, the mono- and sesquiterpenoids found in cannabis contribute to the plants’ aroma and flavor. About 100 terpenoids have been identified in cannabis, many of which are found in other plants. Both cannabinoids and terpenoids are produced in the trichomes of cannabis, which are found at highest density on female flower buds.Terpenoids are usually present in cannabis flower buds in the 0.5–3.5% range and are found at significant levels in cannabis smoke and vapor. As biologically active compounds, terpenoids may play a role in the overall effects of herbal cannabis.

The popularly understood distinctions between indica and sativa may have more to do with aroma and subjective effects than plant morphology. Recent studies have shown that terpenoids are useful in distinguishing cannabis cultivars that have similar cannabinoid content. A study of cannabinoid and terpenoid profiles among medical cannabis samples analyzed by a cannabis testing laboratory in California found a continuum of terpenoid profiles among the wide variety of sample names.Another study found that cannabis samples described as indica contained more myrcene and hydroxylated terpenoids, whereas those described as sativa tended to contain more terpinolene, 3-carene, and a few specified sesquiterpenes.” http://online.liebertpub.com/doi/full/10.1089/can.2016.0040

“Due to its astonishing efficacy, nowadays cannabis is prescribed by physicians for the treatment of neurological, psychiatric, immunological, cardiovascular, gastrointestinal, and oncological conditions. The active principles inside plants have been exploited by humans for centuries, with Cannabis sativa being one of the oldest ever used for medicinal purposes. Surprisingly, contrary to whole plant extracts, medicinal products containing exclusively THC have been found to lack efficacy and lead to unbearable side effects. These results arise from the fact that these products lack other important co-factors typically found in the Phyto-complex, such as terpenoids and other cannabinoids that contribute to the synergistic effects seen with whole plant extracts.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482328/

“In silico discovery of terpenoid metabolism in Cannabis sativa. Due to their efficacy, cannabis based therapies are currently being prescribed for the treatment of many different medical conditions. Interestingly, treatments based on the use of cannabis flowers or their derivatives have been shown to be very effective, while therapies based on drugs containing THC alone lack therapeutic value and lead to increased side effects, likely resulting from the absence of other pivotal entourage compounds found in the Phyto-complex. Among these compounds are terpenoids,” https://www.ncbi.nlm.nih.gov/pubmed/28690830

 

“Terpenoids: natural products for cancer therapy.”  https://www.ncbi.nlm.nih.gov/pubmed/23092199

“Inhibition of tumor progression by naturally occurring terpenoids.”  https://www.ncbi.nlm.nih.gov/pubmed/21936626

“Terpenoids as anti-colon cancer agents – A comprehensive review on its mechanistic perspectives.” https://www.ncbi.nlm.nih.gov/pubmed/27940056

 

Regulation of human glioblastoma cell death by combined treatment of cannabidiol, γ-radiation and small molecule inhibitors of cell signaling pathways.

Image result for oncotarget

“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.”