[Cannabis use in Epilepsy. Current situation in Argentina and abroad].

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“Although at present we have over 20 different types of drugs for epilepsy, 30 to 40% of patients continue to have seizures.

Preliminary data from human studies suggest that cannabis, cannabidiol in particular, is effective in the treatment of some patients with epilepsy.

However, the available data are limited and do not allow defnitive conclusions. Only randomized clinical trials with controlled double-blind, placebo-controlled utilizing secure preparations and one or more cannabinoids, will provide comprehensive information on the effcacy and safety of use.

In order to perform these trials it is necessary to have legislation authorizing the use of cannabis on epilepsy.”

Activation of dorsal horn cannabinoid CB2 receptor suppresses the expression of P2Y12 and P2Y13 receptors in neuropathic pain rats.

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“More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain.

In CCI- and ADPbetaS-treated rats, AM1241 pretreatment could efficiently activate CB2 receptor, while inhibiting p38MAPK and NF-kappaB activation in the dorsal spinal cord. CB2 receptor stimulation decreased P2Y13 receptor expression via p38MAPK/NF-kappaB signaling. On the other hand, CB2 receptor activation decreased P2Y12 receptor expression via p38MAPK-independent NF-kappaB signaling pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/28899427

Effects of coadministration of low dose cannabinoid type 2 receptor agonist and morphine on vanilloid receptor 1 expression in a rat model of cancer pain.

“Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy. Our previous research has showed that nonanalgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons. Whether coadministration of a CB2 receptor agonist and morphine could reduce TRPV1 expression in morphine‑induced antinociception and tolerance in cancer pain is unclear. Therefore, we investigated the effects of coadministration of a CB2 receptor agonist AM1241 and morphine on TRPV1 expression and tolerance in cancer pain. Coadministration of AM1241 and morphine for 8 days significantly reduced morphine tolerance, as assessed by measuring paw withdrawal latency to a radiant heat stimulation, in Walker 256 tumor‑bearing rats. Repeated morphine treatment for a period of 8 days induced upregulation of the TRPV1 protein expression levels in the DRG in the tumor‑bearing rats, although no change in mRNA expression. Pretreatment with AM1241 reduced this morphine‑induced upregulation of TRPV1 and the effect was reversed by the CB2 receptor antagonist AM630. Our findings suggest that coadministration of a CB2 receptor agonist AM1241 and morphine reduced morphine tolerance possibly through regulation of TRPV1 protein expression in the DRG in cancer pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28901432

https://www.spandidos-publications.com/10.3892/mmr.2017.7479

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

Challenges towards Revitalizing Hemp: A Multifaceted Crop.

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“Hemp has been an important crop throughout human history for food, fiber, and medicine. Despite significant progress made by the international research community, the basic biology of hemp plants remains insufficiently understood. Clear objectives are needed to guide future research. As a semi-domesticated plant, hemp has many desirable traits that require improvement, including eliminating seed shattering, enhancing the quantity and quality of stem fiber, and increasing the accumulation of phytocannabinoids. Methods to manipulate the sex of hemp plants will also be important for optimizing yields of seed, fiber, and cannabinoids. Currently, research into trait improvement is hindered by the lack of molecular techniques adapted to hemp. Here we review how addressing these limitations will help advance our knowledge of plant biology and enable us to fully domesticate and maximize the agronomic potential of this promising crop.”

https://www.ncbi.nlm.nih.gov/pubmed/28886910

http://www.cell.com/trends/plant-science/fulltext/S1360-1385(17)30177-2?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1360138517301772%3Fshowall%3Dtrue

Physicians-in-training are not prepared to prescribe medical marijuana.

Drug and Alcohol Dependence Home

“While medical marijuana use is legal in more than half of U.S. states, evidence is limited about the preparation of physicians-in-training to prescribe medical marijuana. We asked whether current medical school and graduate medical educational training prepare physicians to prescribe medical marijuana.

Our study highlights a fundamental mismatch between the state-level legalization of medical marijuana and the lack of preparation of physicians-in-training to prescribe it. With even more states on the cusp of legalizing medical marijuana, physician training should adapt to encompass this new reality of medical practice.”

https://www.ncbi.nlm.nih.gov/pubmed/28892720

http://www.drugandalcoholdependence.com/article/S0376-8716(17)30441-6/fulltext

 

Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

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“Nowadays, therapeutic indications for cannabinoids, specifically Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is its composition of materials approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (1:1, 10mg) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has in serving as a standardized oral cannabinoid formulation. Moreover, the concept of improving oral bioavailability described here, can pave the way for other potential lipophilic active compounds requiring enhancement of their oral bioavailability.”

https://www.ncbi.nlm.nih.gov/pubmed/28890215

http://www.sciencedirect.com/science/article/pii/S016836591730843X

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

Distinct roles of neuronal and microglial CB2 cannabinoid receptors in the mouse hippocampus.

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“The effects of cannabinoids are primarily mediated by type-1 cannabinoid receptors in the brain and type-2 cannabinoid receptors (CB2Rs) in the peripheral immune system. However, recent evidence demonstrates that CB2Rs are also expressed in the brain and implicated in neuropsychiatric effects. Diverse types of cells in various regions in the brain express CB2Rs but the cellular loci of CB2Rs that induce specific behavioral effects have not been determined. To manipulate CB2R expression in specific types of cells in the dorsal hippocampus of adult mice, we used Cre-dependent overexpression and CRISPR-Cas9 genome editing techniques in combination with adeno-associated viruses and transgenic mice. Elevation and disruption of CB2R expression in microglia in the CA1 area increased and decreased, respectively, contextual fear memory. In CA1 pyramidal neurons, disruption of CB2R expression enhanced spatial working memory, whereas their overexpression reduced anxiety levels assessed as an increase in the exploration time in the central area of open field. Interneuronal CB2Rs were not involved in the modulation of cognitive or emotional behaviors tested in this study. The targeted manipulation of CB2R expression in pyramidal neurons and microglia suggests that CB2Rs in different types of cells in the mature hippocampus play distinct roles in the regulation of memory and anxiety.”

https://www.ncbi.nlm.nih.gov/pubmed/28888955

http://www.sciencedirect.com/science/article/pii/S0306452217306292

Medical Marijuana Helps Kids With Cerebral Palsy, Israeli Study Finds

Medical marijuana plants (illustrative)

“Medical marijuana significantly improved the condition of children suffering from cerebral palsy, a study by Wolfson Medical Center near Tel Aviv has found. According to the interim findings, treatment with cannabis oil reduced the disorder’s symptoms and improved the children’s motor skills. It also improved the kids’ sleep quality, bowel movements and general mood.

“The THC’s effect is especially relevant to motor function, whether it’s Parkinson’s disease or other motor symptoms,” says Bar-Lev Schleider. “But the THC is also responsible for the psycho-active effect, so we picked a variety that also has a lot of CBD, which moderates the euphoric effect.”
One group of children was treated with oil with a 1:6 ratio of THC to CBD, while for another group the ratio was 1:20.
“According to the interim findings both oils are effective,” says Bar-Lev Schleider.”
http://www.haaretz.com/israel-news/.premium-1.811010