The Risks and Benefits of Cannabis in the Dermatology Clinic.

SAGE Journals

“Cannabis ( Cannabis sativa/indica), also known as marijuana, has been used for medicinal and recreational purposes for millennia.

There has been a recent trend to legalize the use of cannabis, as illustrated by the recent legalization votes in numerous states in the United States and legislation in Canada to allow recreational cannabis use. With this increasing consumption of cannabis, dermatologists will see increased pressure to prescribe cannabis and will see the side effects of cannabis use with greater frequency.

There are several approved medical indications for cannabis use, including psoriasis, lupus, nail-patella syndrome, and severe pain. In addition, very preliminary studies have suggested cannabis and its derivatives might have use in acne, dermatitis, pruritus, wound healing, and skin cancer.

In this review, we summarize some of the studies and reports regarding the medicinal uses of cannabis in the dermatology clinic and some of the side effects that might present more often to dermatologists as the use of cannabis increases.”

“Cannabinoid system in the skin – a possible target for future therapies in dermatology.” https://www.ncbi.nlm.nih.gov/pubmed/19664006

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A review of methods for the chemical characterization of cannabis natural products.

Journal of Separation Science

“Cannabis has garnered a great deal of new attention in the past couple of years in the United States due to the increasing instances of its legalization for recreational use and indications for medicinal benefit.

Despite a growing number of laboratories focused on cannabis analysis, the separation science literature pertaining to the determination of cannabis natural products is still in its infancy despite the plant having been utilized by humans for nearly 30 000 years and it being now the most widely used drug world-wide. This is largely attributable to the restrictions associated with cannabis as it is characterized as a Schedule 1 drug in the United States.

Presented here are reviewed analytical methods for the determination of cannabinoids (primarily) and terpenes (secondarily), the primary natural products of interest in cannabis plants. Focus is placed foremost on analyses from plant extracts and the various instrumentation and techniques that are used, but some coverage is also given to analysis of cannabinoid metabolites found in biological fluids. The goal of this work is to provide a collection of relevant separation science information, upon which the field of cannabis analysis can continue to grow.”

https://www.ncbi.nlm.nih.gov/pubmed/28986974

http://onlinelibrary.wiley.com/doi/10.1002/jssc.201701003/abstract

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Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome.

Current Issue

“Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV1.1.

The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased. Treatment with lower doses of CBD also improved autistic-like social interaction deficits in DS mice.

Phenotypic rescue was associated with restoration of the excitability of inhibitory interneurons in the hippocampal dentate gyrus, an important area for seizure propagation. Reduced excitability of dentate granule neurons in response to strong depolarizing stimuli was also observed.

The beneficial effects of CBD on inhibitory neurotransmission were mimicked and occluded by an antagonist of GPR55, suggesting that therapeutic effects of CBD are mediated through this lipid-activated G protein-coupled receptor.

Our results provide critical preclinical evidence supporting treatment of epilepsy and autistic-like behaviors linked to DS with CBD. We also introduce antagonism of GPR55 as a potential therapeutic approach by illustrating its beneficial effects in DS mice.

Our study provides essential preclinical evidence needed to build a sound scientific basis for increased medicinal use of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/28973916

http://www.pnas.org/content/early/2017/09/26/1711351114

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Efficacy and Tolerability of Phytomedicines in Multiple Sclerosis Patients: A Review.

 CNS Drugs

“Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world.

The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms.

Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa.

C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms.

Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS.

The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.”

https://www.ncbi.nlm.nih.gov/pubmed/28948486

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Cannabinoid CB1 Discrimination: Effects of Endocannabinoids and Catabolic Enzyme Inhibitors.

Journal of Pharmacology and Experimental Therapeutics

“An improved understanding of the endocannabinoid system has provided new avenues of drug discovery and development toward the management of pain and other behavioral maladies. Exogenous cannabinoid type-1 (CB1) receptor agonists such as Δ9-tetrahydrocannabinol are increasingly utilized for their medicinal actions; however, their utility is constrained by concern regarding abuse-related subjective effects. This has led to growing interest in the clinical benefit of indirectly enhancing the activity of the highly labile endocannabinoids N-arachidonoylethanolamine (anandamide; AEA) and/or 2-arachidonoylglycerol (2-AG) via catabolic enzyme inhibition. The present studies were conducted to determine whether such actions can lead to CB1 agonist-like subjective effects, as reflected in the presence or absence of CB1-related discriminative-stimulus effects in laboratory subjects. Squirrel monkeys (n=8) that discriminated the CB1 full agonist AM4054 (0.01 mg/kg) from vehicle were used to study, first, inhibitors of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MGL) alone or in combination [FAAH (URB597, AM4303); MGL (AM4301); FAAH/MGL (AM4302)] and, second, the ability of the endocannabinoids AEA and 2-AG to produce CB1 agonist-like effects when administered alone or after enzyme inhibition. Results indicate that CB1-related discriminative-stimulus effects were produced by combined, but not selective, inhibition of FAAH and MGL, and that these effects were non-surmountably antagonized by low doses of rimonabant. Additionally, FAAH- or MGL-inhibition revealed CB1-like subjective effects produced by AEA, but not 2-AG. Taken together, the present data suggest that therapeutic effects of combined, but not selective, enhancement of AEA or 2-AG activity via enzyme inhibition may be accompanied by CB1 receptor-mediated subjective effects.”

https://www.ncbi.nlm.nih.gov/pubmed/28947487

http://jpet.aspetjournals.org/content/early/2017/09/25/jpet.117.244392

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Targeting the Endocannabinoid System to Treat Sepsis

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“Sepsis is a complex immune disorder that can affect the function of almost all organ systems in the body. This disorder is characterised by a malfunctioning immune response to an infection that involves both pro-inflammatory and immunosuppressive mediators. This leads to severe damage and failure of vital organs, resulting in patient death. Sepsis, septic shock, and systemic inflammatory response syndrome are the leading causes of mortality in surgical intensive care unit patients internationally.

The current lack of viable therapeutic treatment options for sepsis underscores our insufficient understanding of this complex disease. The endocannabinoid system, a key regulator of essential physiological functions including the immune system, has recently emerged as a potential therapeutic target for sepsis treatment. The endocannabinoid system acquires its name from the plant Cannabis Sativa, which has been used medically to treat a variety of ailments, as well as recreationally for centuries. Cannabis Sativa contains more than 60 active phytocannabinoids with the primary phytocannabinoid Δ9-tetrahydrocannabinol (THC), (6) activating both endogenous endocannabinoid receptors.

The endocannabinoid system represents a potential therapeutic target in sepsis due to the presence of cannabinoid receptors (CB2) on immune cells. In this review we discuss how various targets within the endocannabinoid system can be manipulated to treat the immune consequences of sepsis. One of the targets outlined are the endocannabinoid receptors and modulation of their activity through pharmacological agonists and antagonists. Another therapeutic target covered in this review is the modulation of the endocannabinoid degradative enzyme’s activity. Modulation of degradative enzyme activity can change the levels of endogenous cannabinoids thereby altering immune activity. Overall, activation of the CB2 receptors causes immunosuppression and can be beneficial during the hyperactivated immune state of sepsis, while suppression of the CB2 receptors may be beneficial during a hypoimmune septic state.

The endocannabinoid system modulates the immune response in experimental sepsis. Manipulating the endocannabinoid system may have potential therapeutic benefit in clinical sepsis where immune and inflammatory dysfunction can be detrimental. Multiple targets exist within the endocannabinoid system, e.g. the system can be targeted at the level of receptors by administration of synthetic compounds, similar to the endocannabinoids, which either increase or inhibit receptor activation to provide the desired therapeutic effect. Alternatively, the endogenous enzymes that degrade endocannabinoids or cannabinoid-like lipids can also be targeted in order to manipulate the levels of endocannabinoids. Proper identification of the septic stage is crucial to determine the adequate therapeutic response that will be most beneficial. Due to the biphasic nature of sepsis immunopathology, immune suppression through endocannabinoid modulation can help mitigate the hyper-immune response during the early septic state, while immune activation may be beneficial in later stages.” http://www.signavitae.com/2013/05/targeting-the-endocannabinoid-system-to-treat-sepsis/

Targeting the Endocannabinoid System to Treat Sepsis

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Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use.

Cancer

“Cannabis is purported to alleviate symptoms related to cancer treatment, although the patterns of use among cancer patients are not well known. This study was designed to determine the prevalence and methods of use among cancer patients, the perceived benefits, and the sources of information in a state with legalized cannabis.

METHODS:

A cross-sectional, anonymous survey of adult cancer patients was performed at a National Cancer Institute-designated cancer center in Washington State. Random urine samples for tetrahydrocannabinol provided survey validation.

RESULTS:

Nine hundred twenty-six of 2737 eligible patients (34%) completed the survey, and the median age was 58 years (interquartile range [IQR], 46-66 years). Most had a strong interest in learning about cannabis during treatment (6 on a 1-10 scale; IQR, 3-10) and wanted information from cancer providers (677 of 911 [74%]). Previous use was common (607 of 926 [66%]); 24% (222 of 926) used cannabis in the last year, and 21% (192 of 926) used cannabis in the last month. Random urine samples found similar percentages of users who reported weekly use (27 of 193 [14%] vs 164 of 926 [18%]). Active users inhaled (153 of 220 [70%]) or consumed edibles (154 of 220 [70%]); 89 (40%) used both modalities. Cannabis was used primarily for physical (165 of 219 [75%]) and neuropsychiatric symptoms (139 of 219 [63%]). Legalization significantly increased the likelihood of use in more than half of the respondents.

CONCLUSIONS:

This study of cancer patients in a state with legalized cannabis found high rates of active use across broad subgroups, and legalization was reported to be important in patients’ decision to use. Cancer patients desire but are not receiving information about cannabis use during their treatment from oncology providers.”

https://www.ncbi.nlm.nih.gov/pubmed/28944449

http://onlinelibrary.wiley.com/doi/10.1002/cncr.30879/abstract;jsessionid=793E288AAC342234D14BA7C96AEEDB74.f02t04?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+7th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+08.00+EDT+%2F+13.00+BST+%2F+17%3A30+IST+%2F+20.00+SGT+and+Sunday+8th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+06.00+EDT+%2F+11.00+BST+%2F+15%3A30+IST+%2F+18.00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience+caused+.

“Study finds up to one-quarter of cancer patients use marijuana”  https://medicalxpress.com/news/2017-09-one-quarter-cancer-patients-marijuana.html

“Up to one-quarter of cancer patients use marijuana”  https://www.sciencedaily.com/releases/2017/09/170925095431.htm

“Cancer Patients Want to Use Marijuana, and with Good Reason”  https://www.inverse.com/article/36751-cancer-patients-want-to-use-marijuana-study-fred-hutchinson-cancer-research-center

“The use of Cannabis for medicinal purposes dates back to ancient times. Cannabis has been shown to kill cancer cells in the laboratory.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all

“Marijuana has been used in herbal remedies for centuries. More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells.” http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/chemotherapyeffects/marijuana-and-cancer

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

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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/

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

“‘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

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“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

 “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

 “‘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
 “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
Bright: Dressed in a lime-coloured ONJ Cancer wellness and Research Centre track suit top over a matching T-shirt in a lighter shade of green, she seemed fit and happy
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The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain.

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“A great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (ie, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics.

Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models.

Emerging clinical studies show that ‘medicinal’ cannabis or cannabinoid-based medications relieve pain in human diseases, such as cancer, multiple sclerosis, and fibromyalgia.

Here, we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/28857069

https://www.nature.com/npp/journal/vaop/naam/abs/npp2017204a.html

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The orphan receptor GPR55 is a novel cannabinoid receptor

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“Preparations of Cannabis sativa have been used for medicinal and recreational purposes for at least 4000 years and extracts of C. sativa contain over 60 different pharmacologically active components the most prominent being Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol

Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB1or CB2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55.

These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB1and CB2 described here will permit delineation of its physiological function(s).”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/

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