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

https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4044

https://www.ncbi.nlm.nih.gov/pubmed/28457057

Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells

“Preparations derived from Cannabis sativa (marijuana and hashish) have become widespread since ancient times, both as therapeutic agents and in recreational smoking.

Among the more than 60 phytocannabinoids identified in Cannabis extracts, the two most abundant are Δ9-tetrahydrocannabinol (THC), the major psychotropic constituent, and cannabidiol (CBD), the major non-psychoactive component.

Cannabinoids were shown to exert a wide range of therapeutic effects, and many of the cannabinoids, especially CBD, were shown to possess potent anti-inflammatory and immunomodulatory activities. In addition, it was shown that several cannabinoids have pro-apoptotic, neuroprotective, and antitumor properties

Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells.

The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD. DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury. In addition, DMH-CBD decreases the proliferation of pathogenic activated TMOG cells.

Several CBD derivatives were also shown to have anti-inflammatory and anti-proliferative properties.

The results show that DMH-CBD induces similar anti-inflammatory, anti-proliferative, and stress response effects to those previously observed for CBD.”

https://www.degruyter.com/view/j/jbcpp.2016.27.issue-3/jbcpp-2015-0071/jbcpp-2015-0071.xml

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

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“Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids.

In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death. These observations indicate that cannabinoids may play an important role in the regulation of cellular homeostasis and, thus, may contribute to tissue remodelling and cancer treatment.

For a long time, the study of cannabinoid receptor signalling has been focused on the classical adenylyl cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not totally explain the wide array of biological responses to cannabinoids. In addition, the diversity of receptors and signalling pathways that endocannabinoids modulate offers an interesting opportunity for the development of specific molecules to disturb selectively the endogenous system.

Moreover, emerging evidences suggest that cannabinoids ability to limit cell proliferation and to induce tumour-selective cell death may offer a novel strategy in cancer treatment.

This review describes the main properties of cannabinoids in cell death and attempts to clarify the different pathways triggered by these compounds that may help to understand the complexity of respective molecular mechanisms and explore the potential clinical benefit of cannabinoids use in cancer therapies.”

https://www.ncbi.nlm.nih.gov/pubmed/28425013

Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus.

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“Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood.

Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations.

Our immunohistochemical and ultrastructural study demonstrates the morphological substrate for cannabinoid-conducted feeding behavior via retrograde dis-inhibition of hunger-promoting AgRP/NPY neurons.”

https://www.ncbi.nlm.nih.gov/pubmed/28377876

(-)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis.

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“(-)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain.

Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination.

Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor.

Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.” https://www.ncbi.nlm.nih.gov/pubmed/28368293

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

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

deryn

“Boy’s miracle recovery from rare cancer after mum gave him cannabis”  http://metro.co.uk/2017/03/26/boys-miracle-recovery-from-rare-cancer-after-mum-gave-him-cannabis-6534160/

“A mother in England reports that she secretly gave her son marijuana, and credits it with curing his leukemia, and saving the teen’s life. Callie Blackwell chose to secretly give her dying son illegally bought marijuana to help him deal with the pain and anxiety from his aggressive leukemia, because she felt he had “nothing else to lose,” The Independent reported. The drug did far more than the mother could have hoped; it not only relieved Deryn’s pain, it reportedly cured his cancer. Now, Blackwell hopes to share her family’s story in an effort to raise awareness about the healing potential of marijuana.

Deryn was first diagnosed with his severe and aggressive form of leukemia, a type of cancer that originates in the blood cells, at age 10. At 14, doctors informed him that there was nothing more they could do, and the young teen went to live out the rest of his short life in a hospice facility. However, that was three years ago, and now at 17, Deryn has fully recovered from his disease and plans to start a career in the food industry. Callie teamed up with author Karen Hockney to write The Boy in 7 Million, a book detailing the family’s experience and highlighting the potential of marijuana in cancer treatment.

There have been a number of instances where marijuana was suspected of significantly improving, and in some cases even curing cancer, but the science remains inconclusive. Research suggests that cannabinoids—chemicals found in the marijuana plants—can target and kill cancer cells in ways that drugs cannot.” http://www.medicaldaily.com/can-marijuana-cure-cancer-mom-claims-have-cured-sons-leukemia-secretly-giving-414375

“Teenager dying of cancer ‘recovers after mother gives him marijuana'” http://www.independent.co.uk/life-style/health-and-families/health-news/teenager-deryn-boy-dying-cancer-mother-callie-blackwell-recover-medical-marijuana-cannabis-weed-a7652106.html

‘I GAVE MY BOY CANNABIS’. Mum reveals she gave her cancer-stricken son CANNABIS in bid to ease his pain… and now he’s made a miracle recovery. Deryn Blackwell, who was expected to die, has defied doctors by surviving two deadly cancers”  https://www.thesun.co.uk/news/3181956/mum-callie-blackwell-cancer-stricken-son-deryn-cannabis/

“I gave my little boy CANNABIS to help cure his cancer: Mother reveals how her teenage son who was given days to live made a miracle recovery when she gave him the drug behind his doctors’ backs” http://www.dailymail.co.uk/femail/article-4349232/Mother-gave-young-son-cannabis-help-cure-cancer.html

One in 7 Billion: Deryn Blackwell begins his hospital ordeal aged 10

“‘I gave my dying son cannabis to ease his cancer symptoms and he made a miracle recovery’ reveals mum” http://www.mirror.co.uk/news/uk-news/i-gave-dying-son-cannabis-10103387

“I Secretly Gave My Son Cannabis to Save His Life | This Morning”  https://www.youtube.com/watch?v=qqvJOAV7oAc&t=4s

“This Morning fans praise mum who risks prosecution after giving son cannabis cancer drug” http://www.express.co.uk/showbiz/tv-radio/784387/This-Morning-Phillip-Schofield-Holly-Willoughby-cannabis-based-drug-cancer

“Mum claims cannabis cured son’s cancer after he was given days to live. A MUM has claimed that cannabis cured her son’s terminal cancer.”  http://www.dailystar.co.uk/showbiz-tv/hot-tv/600294/cannabis-cures-cancer-this-morning-holly-willoughby

“As teenage boy ‘beats’ cancer with cannabis oil here are nine illnesses the drug could ‘cure’. Deryn Blackwell’s parents secretly gave him the class B drug to ease his pain and anxiety as he underwent gruelling treatment in hospital for leukaemia and cancer.” http://www.mirror.co.uk/lifestyle/health/after-cannabis-oil-miracle-recovery-10111458

I gave my cancer-stricken son weed and it saved his life” http://nypost.com/2017/03/26/i-gave-my-cancer-stricken-son-weed-and-it-saved-his-life/

“London mother claims cannabis helped her dying son recover from rare cancer” http://www.nydailynews.com/news/world/u-mother-claims-cannabis-helped-dying-son-recover-cancer-article-1.3010404

“Mother gives marijuana to cancer-struck son and he makes full recovery”  http://topexaminer.com/2017/03/28/mother-gives-marijuana-cancer-struck-son-makes-full-recovery/

“CALLIE BLACKWELL SAYS CANNABIS OIL HELPED SON’S CANCER: ‘THE BOY IN 7 BILLION’” http://www.inquisitr.com/4095508/callie-blackwell-says-cannabis-oil-helped-sons-cancer-the-boy-in-7-billion/

“Teenager Dying Of Cancer Survives After His Mother Gives Him A Dose Of Marijuana” http://www.indiatimes.com/health/buzz/teenager-dying-of-cancer-survives-after-his-mother-gives-him-a-dose-of-marijuana-274499.html

“Mother risked 14 years in prison to smuggle cannabis into hospital for dying son – and she claims it saved his life.‘” http://metro.co.uk/2017/10/23/mother-risked-14-years-in-prison-to-smuggle-cannabis-into-hospital-for-dying-son-and-she-claims-it-saved-his-life-7021003/
“Teen boy ‘saved by cannabis’ reveals how his mum’s illegal drug-buying stopped him from dying. Deryn Blackwell, from Norfolk, was sent to a hospice shortly after his 14th birthday to live out his final few days. He was frail and in extraordinary pain after a relentless battle with a one in a billion form of cancer, Langerhans cell sarcoma. But after his parents secretly gave him cannabis oil to ease his pain and anxiety, he made a miracle recovery. Today, Deryn – who had also battled leukaemia – is a happy and healthy 17-year-old student, with friends and a girlfriend.” http://www.mirror.co.uk/tv/tv-news/teen-boy-saved-cannabis-reveals-11393969

http://www.thctotalhealthcare.com/category/leukemia/

Cannabinoid CB2 receptors are involved in the protection of RAW264.7 macrophages against the oxidative stress: an in vitro study.

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“Research in the last decades has widely investigated the anti-oxidant properties of natural products as a therapeutic approach for the prevention and the treatment of oxidative-stress related disorders.

In this context, several studies were aimed to evaluate the therapeutic potential of phytocannabinoids, the bioactive compounds of Cannabis sativa.

Here, we examined the anti-oxidant ability of Cannabigerol (CBG), a non-psychotropic cannabinoid, still little known, into counteracting the hydrogen peroxide (H2O2)-induced oxidative stress in murine RAW264.7 macrophages. In addition, we tested selective receptor antagonists for cannabinoid receptors and specifically CB1R (SR141716A) and CB2R (AM630) in order to investigate through which CBG may exert its action.

Taken together, our in vitro results showed that CBG is able to counteract oxidative stress by activation of CB2 receptors.

Based on its antioxidant activities, CBG may hold great promise as an anti-oxidant agent and therefore used in clinical practice as a new approach in oxidative-stress related disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/28348416

Effects of a Sativex-Like Combination of Phytocannabinoids on Disease Progression in R6/2 Mice, an Experimental Model of Huntington’s Disease.

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“Several cannabinoids afforded in experimental models of Huntington’s disease (HD).

We investigated whether a 1:1 combination of botanical extracts enriched in either ∆⁸-tetrahydrocannabinol (∆⁸-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex®, is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD.

A Sativex-like combination of phytocannabinoids administered to R6/2 mice at the onset of motor symptoms produced certain benefits on the progression of striatal deterioration in these mice, which supports the interest of this cannabinoid-based medicine for the treatment of disease progression in HD patients.”

https://www.ncbi.nlm.nih.gov/pubmed/28333097

A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol

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“Cannabidiol (CBD) is the second most abundant phytocannabinoid, after Δ9-tetrahydrocannabinol (THC) and was first isolated from the cannabis extract in 1940.

Given the increasing clinical use of CBD, and the numerous effects of CBD in the cardiovascular system, the aim of the present study was to systematically review and analyse in vivo studies evaluating the effects of CBD on alterations in haemodynamics.

From the limited data available, we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral blood flow (CBF) in mouse models of stroke.

This meta-analysis and systematic review has highlighted the haemodynamic effects of CBD administration in vivo.

The positive effects induced by CBD include maintaining the fall in BP after global hypoxia, reducing the increase in MBP and HR post-stress, and increasing BF in ischaemia-reperfusion models.

It is possible that beneficial effects of CBD on haemodynamics occurs when the cardiovascular system is abnormally altered, suggesting that CBD may be used as a treatment for various cardiovascular disorders, such as hypertension, myocardial infarction and stroke.”

http://journal.frontiersin.org/article/10.3389/fphar.2017.00081/full

Cannabis for Pain and Headaches: Primer.

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“Marijuana has been used both medicinally and recreationally since ancient times and interest in its compounds for pain relief has increased in recent years. The identification of our own intrinsic, endocannabinoid system has laid the foundation for further research.

Synthetic cannabinoids are being developed and synthesized from the marijuana plant such as dronabinol and nabilone. The US Food and Drug Administration approved the use of dronabinol and nabilone for chemotherapy-associated nausea and vomiting and HIV (Human Immunodeficiency Virus) wasting. Nabiximols is a cannabis extract that is approved for the treatment of spasticity and intractable pain in Canada and the UK. Further clinical trials are studying the effect of marijuana extracts for seizure disorders.

Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects.  Other compounds found in cannabis such as flavonoids and terpenes are also being investigated as to their individual or synergistic effects.

This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches.”

https://www.ncbi.nlm.nih.gov/pubmed/28281107