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IACM-Bulletin of 02 September 2018

Europe: The EURopean Parliament is preparing a resolution on the medical use of cannabis

The EURopean Parliament is preparing a resolution on the medical use of cannabis. The draft says among others that “research on medical cannabis has been underfunded and should be properly addressed under the next Framework Programme 9.” It “calls on Member States to encourage increased knowledge among medical professionals regarding the use of such cannabis-based medicine and consider allowing doctors to freely use their professional judgement to prescribe cannabis and cannabisbased medicines to patients with relevant conditions.”

It calls “on the Commission to work with Member States to improve equal access to medicinal cannabis and ensure that medical cannabis, where allowed, is covered by health insurance schemes as is the case for other medicinal products. Asks Member States to provide safe and equal choice for patients between different types of cannabisbased medicine, while ensuring that patients are accompanied by specialised medical professionals during their treatment.”

European Commision of 7 June 2018

Science/Human: Cannabis lozenges reduce pain in an observational study

In an observational study with 49 participants with chronic pain cannabis lozenges (Trokie) produced a significant reduction in pain. The study was conducted by investigators of Palliative Care Corporation in Huntington Beach, USA, and further institutions from the Netherlands and Spain. Trokie lozenges are a standardised formulation containing cannabis extracts to deliver cannabinoids by the oral mucosa. Participants were asked to report pain perception before and after 1 to 12 weeks.

A mean reduction in pain scores on the scale between 0 and 10 of 4.9 was observed. Onset of analgesia typically varied between 5 and 40 min, which seems consistent with, at least partial, absorption through the oral mucosa. Adverse events were reported by 16 subjects, the most common being dizziness/unsteadiness, bad taste, and throat irritation/dry mouth. Despite the adverse events 90% of participants reported being "satisfied" or "very satisfied" with the product.

Crowley K, de Vries ST, Moreno-Sanz G. Self-Reported Effectiveness and Safety of Trokie® Lozenges: A Standardized Formulation for the Buccal Delivery of Cannabis Extracts. Front Neurosci. 2018;12:564.

Science/Cells: A new mechanism involved in anti-cancer effects of CBD

CBD (cannabidiol) was shown to inhibit the release of certain structures from cancer cells, which are associated with the resistance to chemotherapeutic agents and the transfer of factors, which promote cancer. The structures are called exosomes and microvesicles (EMV). They are structures, released by cells and involved in intercellular communication through transfer of proteins and genetic material.

Scientists from the School of Human Sciences of London Metropolitan University, UK, found this novel role for CBD as a potent inhibitor of exosomes and microvesicles release from three cancer cell lines: prostate cancer, hepatocellular carcinoma and breast adenocarcinoma. CBD significantly reduced exosome release in all three cancer cell lines, and also significantly, albeit more variably, inhibited microvesicle release. These effects of CBD were found to be dose dependent and cancer cell type specific. Investigators suggested “that CBD can be used to sensitize cancer cells to chemotherapy” and “that the known anti-cancer effects of CBD may partly be due to the regulatory effects on EMV biogenesis.”

Kosgodage US, Mould R, Henley AB, Nunn AV, Guy GW, Thomas EL, Inal JM, Bell JD, Lange S. Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer. Front Pharmacol. 2018;9:889.

News in brief

Germany: Germany will import up to 1.5 tons of cannabis per year from the Netherlands
Since the demand to medical cannabis increased faster than expected the Dutch Health Minister Hugo de Jonge promised to his German colleague Jens Spahn to increase the yearly amount exported to Germany from the promised 700 kg to up to 1.5 tons.
Spiegel Online of 24 August 2018

New Zealand: Second licence granted for the cultivation of cannabis
An East Coast company has become the second organisation in New Zealand to be granted a licence to cultivate cannabis for research purposes for medicinal cannabis. Hikurangi Enterprises wants to be the centre in the medicinal cannabis industry. A university was the first organisation to be granted a licence.
Radio New Zealand of 26 August 2018

Science/Human: Tobacco smokers have reduced concentrations of brain CB1 receptors
In a study with 18 tobacco smokers and 28 non-smokers of tobacco investigators found that distribution volume of CB1 receptors was about 20% lower in subjects who smoke tobacco compared to non-smokers.
National Institute of Mental Health, National Institutes of Health, Bethesda, USA.
Hirvonen J, et al. Biol Psychiatry. 2018 Jul 21. [in press]

Science/Human: Cannabis use is protective against lower urinary tract symptoms
In a study with 3037 men suffering from LUTS (lower urinary tract symptoms such as increased urgence of urination and incomplete voiding) between 20 and 59 years of age 14.4% reported cannabis use. Regular cannabis users were about half as likely to report LUTS (odds ratio of 0.55). Authors wrote that obesity, diabetes and other diseases were risk factors for LUTS, “regular THC use, however, appears to be protective from LUTS.”
Department of Surgery, University of Chicago Medicine, USA.
Fantus RJ, et al. 2018 Aug 21. [in press]

Science/Human: Many patients with fibromyalgia profit from a treatment with cannabis according to survey
According to a survey among 383 Israeli patients with fibromyalgia 84% use cannabis and 44% had a licence for using cannabis medicinally. Mean monthly use was 31.4 g and 80% smoked it. Pain relief was reported by 94% of cannabis users and 93% reported improved sleep quality. Of licensed cannabis users 55% bought cannabis beyond the medical allowance on the black market. About two thirds (64%) were working full- or part-time, and 74% reported driving “as usual.”
Nazareth Hospital and Faculty of Medicine, Israel.
Habib G, et al. Pain Res Treat. 2018;2018:7829427.

Science/Cells: Hemp seed extracts may be effective against acne vulgaris
In a study with certain skin cells (HaCaT cells) a hemp seed hexane extract showed anti-microbial activity against Propionibacterium acnes and exerted anti-inflammatory and collagen-promoting properties. It also reduced fat production. Authors concluded that this extract “could be utilised to treat acne vulgaris.”
College of Medical Science, SoonChunHyang University, Asan, Korea.
Jin S, et al. PLoS One. 2018;13(8):e0202933.

Science/Animal: Cannabinoids in combination with standard chemotherapy may improve treatment outcome in brain cancer
Researchers found that the combined administration of CBD and THC and the standard treatment temozolomide produces a strong anti-tumoural effect in glioblastoma multiforme, while the combined administration of these cannabinoids together with BCNU, another chemotherapeutic agent used for the treatment of this brain cancer did not show a stronger effect than individual treatments.
School of Biology, Complutense University, Madrid, Spain.
López-Valero I, et al. Biochem Pharmacol. 2018 Aug 17. [in press]

Science/Animal: CBD shows anti-inflammatory properties in an animal model of multiple sclerosis
In a mouse model of multiple sclerosis (EAE) use of cannabidiol (CBD) slowed the progression of the disease, decreased infiltration by certain immune cells (T cells) in the central nervous system and reduced the levels of pro-inflammatory cytokines (interleukin-17, interferon gamma). CBD treatment also led to an increase in so-called MDSCs (myeloid-derived suppressor cells), which inhibit the proliferation of T cells. Authors concluded that “these studies demonstrate for the first time that CBD treatment may ameliorate EAE through induction of immunosuppressive MDSCs.”
University of South Carolina School of Medicine, Columbia, USA.
Elliott DM, et al. Front Immunol. 2018;9:1782.

Science/Human: Cannabis use does not influence gray matter of the brain in schizophrenia
In a study with schizophrenia patients with (n = 92) and without (n = 66) significant cannabis and/or alcohol use cannabis use was found to “not significantly compound the gray matter deficits associated with schizophrenia.”
Vanderbilt University Medical Center, Nashville, USA.
Quinn M, et al. Psychiatry Res Neuroimaging. 2018;280:9-14.

Science/Animal: Activation of the peripheral CB1 receptor may improve symptoms of irritable bowel syndrome
In a mouse model of diarrhoea, hypermotility and abdominal pain a synthetic agonist of the CB1 receptor (AM9405) reduced these symptoms. Some of the effects were mediated by 5-HT3 receptors. Authors concluded that the combination of CB1 agonism together with 5-HT3 agonism may be promising for the future treatment of functional gastrointestinal disorders.
Faculty of Medicine, Medical University of Lodz, Poland.
Salaga M, et al. EUR J Pharmacol. 2018;836:34-43.

Science/Cells: Cannabis extracts are effective against bacteria resistant to antibiotics
Scientists investigated the antimicrobial activities of three plant extracts, including extracts from cannabis, against MRSA (methicillin-resistant Staphylococcus aureus). They found that the “leaf extracts of C. sativa, T. orientalis and P. guajava had potential for the control of both hospital- and community-acquired MRSA.”
Saaii College of Medical Science and Technology, Chaubepur, India.
Chakraborty S, et al. J Integr Med. 2018 Jul 29. [in press]

Science/Animal: How CBD reduces neuropathic pain
In studies with rats CBD reduced pain caused by nerve injury, and this effect was predominantly exerted by activation of the TRPV1 receptor. Anxiety was reduced by activation of the 5-HT1A receptor.
Department of Psychiatry, McGill University, Montreal, Canada.
De Gregorio D, et al. Pain. 2018 Aug 27. [in press]

Science/Animal: The intake of dietary fibres and starch influences the numbers of CB1 receptors
It is known that dietary fibre supplementation can improve cognition. Rats were fed a high-fat diet, which induced increases in the number of CB1 receptors and other receptors in brain regions involved in cognition and appetite. Addition of dietary fibres and starch reduced this effect. Authors wrote that “increased fiber intake may have beneficial effects on improving learning and memory, as well as reducing excessive appetite” during a high-fat diet.
Department of Pathogen Biology and Immunology, Xuzhou Medical University, China.
Yu Y, et al. Mol Nutr Food Res. 2018:e1800422.

Science/Human: Genetic investigation shows positive influence of schizophrenia risk on cannabis use
In the largest genome-wide study for lifetime cannabis use with more than 180,000 participants genes explained 11% of the risk for cannabis use. The “analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use” and not the other way round.
Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
Pasman JA, et al. Nat Neurosci. 2018 Aug 27. [in press]

Science/Human: CBD blood concentrations after smoking CBD cigarettes
In Switzerland cannabis with a THC content less than 1% and high CBD content is increasingly popular. Investigators analysed THC and CBD blood concentrations after single use and one week of daily use of 0.2 grams of cannabis with THC concentrations of 0.94 % and 0.8% and CBD concentrations of 23.5% and 17%. After 4 hours THC blood concentrations reached 2.7 and 4.5 ng/mL after a single and one week use and CBD concentrations of 45.7 and 82.6 ng/mL.
Institute of Forensic Medicine of the University of Basel, Switzerland.
Meier U, et al. Forensic Sci Int. 2018;291:62-67.

Science/Human: Cannabis use was associated with less pain after orthopaedic surgery
In a study with 937 patients undergoing orthopaedic surgery cannabis use was associated with decreased pain intensity at the operative site and better lower extremity activity.
University of Maryland Rehabilitation and Orthopaedic Institute, Baltimore, USA.
Medina SH, et al. Int Orthop. 2018 Aug 22. [in press]

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