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IACM-Bulletin of 18 August 2019

Luxembourg: Luxembourg will become the first country in EURope to legalise cannabis for adults

Luxembourg has called on its EU neighbours to relax their drug laws as its health minister confirmed plans to become the first EURopean country to legalise cannabis production and consumption. “This drug policy we had over the last 50 years did not work,” Etienne Schneider told Politico. “Forbidding everything made it just more interesting to young people … I’m hoping all of us will get a more open-minded attitude toward drugs.”

Residents over the age of 18 are expected to be able to buy the drug for recreational use legally within two years. The state will regulate production and distribution through a cannabis agency. Draft legislation is expected to be unveiled later this year providing further detail on the types of cannabis that will be on sale and the level of tax that will be imposed. Schneider said the legislation was likely to include a ban on non-residents buying cannabis in order to dissuade drug-tourism. Home-growing is also likely to remain prohibited.

The Guardian of 7 August 2019

Mexico: Supreme Court demands regulation on medical cannabis

Mexico’s Supreme Court ordered the health ministry to issue regulation within six months on medical cannabis use, saying its failure to do so after legalization in 2017 had put rights at risk for patients, including children.

The court made the decision as part of its ruling in favour of a child who needed medication derived from the cannabis substance THC to treat epilepsy. “Due to the absence of rules regulating the therapeutic use of cannabis, it was impossible for the plaintiff to access treatment based on this substance or any of its derivatives,” the court said in a statement.

Reuters of 15 August 2019

Science/Human: CBD may be helpful in fragile X syndrome according to a clinical study

In a study with 20 children and adolescents with a diagnosis of fragile X syndrome transdermal CBD caused disease improvement. The study was conducted by several Australian institutions including the Centre for Clinical Trials in Rare Neurodevelopmental Disorders in Brisbane and the University of Queensland in Brisbane. Among the symptoms of the syndrome are intellectual disabilities, attention deficit and hyperactivity, anxiety and unstable mood as well as autistic behaviour. CBD was applied twice daily in a gel to the skin titrated from 50 mg daily to a maximum dose of 250 mg. Treatment duration was 12 weeks.

The primary efficacy endpoint was change in the so-called Anxiety, Depression, and Mood Scale (ADAMS), which improved significantly during the study. Authors wrote that the transdermal CBD preparation called ZYN002 “was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS.“

Heussler H, Cohen J, Silove N, Tich N, Bonn-Miller MO, Du W, O'Neill C, Sebree T.A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome. J Neurodev Disord. 2019;11(1):16.

Science/Human: A CBD preparation was effective in reducing seizures in children with epilepsy

In a study with 16 patients suffering from epilepsy with a mean age of 9 years a highly purified CBD preparation reduced seizure frequency. The study was conducted at the Dana-Dwek Children's Hospital in Tel Aviv, Israel. This phase II, prospective study was open to paediatric patients with treatment resistant epilepsy on stable antiepileptic drugs' doses, who experienced at least 4 seizures within 4 weeks. Following a 4-week observation period, patients began a 2-week dose-titration phase (up to 25mg/kg or 450mg, the lower of the two), followed by a 10-week maintenance treatment period.

Of the 16 participants 11 completed the full treatment program. The average maintenance dose was 14 mg CBD per kilogram bodyweight. By the end of the treatment period there was an average reduction of monthly seizure frequency of 73% compared to baseline. Two patients became fully seizure-free. 73% of caregivers reported an improved or very much improved condition. Most commonly reported treatment-related adverse effects were sleep disturbance/insomnia (25% of patients), followed by somnolence, increased seizure frequency, and restlessness (3 patients each, 19%). No side effect was serious or severe, and all resolved.

Mitelpunkt A, Kramer U, Hausman Kedem M, Zilbershot Fink E, Orbach R, Chernuha V, Fattal-Valevski A, Deutsch L, Heffetz D, Sacks H. The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study. Epilepsy Behav. 2019;98(Pt A):233-237.

News in brief

Thailand: The country delivers first bottles of cannabis oil to hospitals
Thailand delivered 4,500 bottles of cannabis oil to treat hospital patients, its first official use of cannabis for medical purposes since a measure legalizing such use took effect this year. Thailand, which has a tradition of using cannabis to relieve pain and fatigue, legalized cannabis for medical use and research last year to help boost agricultural income.
Reuters of 7 August 2019

USA: Nearly two thirds of US citizens support the legalisation of cannabis
In a new survey 63% of Americans said cannabis should be legalized. Support for cannabis legalization was highest in the West, at 72%, and lowest in the Northeast but still with a majority at 55%.
Investors of 5 August 2019

Australia/USA: CBD company receives 40 million US dollars for research into antimicrobial purposes of the cannabinoid
A Perth- and Philadelphia-based medical cannabis company working with CBD is receiving 40 million US dollars in funding from US institutional investors following studies suggesting its cannabis-derived compound could be used as a powerful new antimicrobial including against so-called "superbugs".
The West Australian of 1 August 2019

Science/Human: Obese cannabis users have lower insulin resistance than non-users
According to a study with 129,509 adults aged 18 to 59 years cannabis use is associated with better metabolic status, including lower insulin resistance and lower fasting insulin in obese adults. Former cannabis users with lifetime cannabis use had persistent lower fasting insulin levels.
Faculty of Pharmacy, Laval University, Quebec, Canada.
Ngueta G, et al. J Diabetes. 2019 Jun 1. [in press]

Science/Human: Cannabis use in addition to opioid use was associated increased depression and anxiety
According to an analysis of 150 adults prescribed an opioid medicine additional cannabis use was associated with increased risk of depression and anxiety. It is unclear, whether use increased the risk for anxiety and depression or whether opioid users with anxiety and depression were more likely to use cannabis.
Multicare Neuroscience Institute, Spokane, Washington, USA.
Wildes M, et al. Pain Manag Nurs. 2019 Aug 9. [in press]

Science/Human: Cancer patients support the medical use of cannabis in the US independent of legal status in their state
According to a survey conducted in cancer centres in Arizona (100 patients) and Texas (100 patients) the majority of individuals support legalisation of cannabis for medical use (Arizona 97% versus Texas 90%) and believe in its medical usefulness (Arizona 97%, Texas 93%).
MD Anderson Cancer Center, Houston, USA.
Tanco K, et al. J Palliat Med. 2019 Aug 6. [in press]

Science/Cells: THC reduces inflammation of the brain
In a study with THC and a synthetic cannabinoid, which only binds to the CB2 receptor (JWH-015) researchers demonstrated that both suppressed “specific monocyte-mediated astrocyte inflammatory responses. In the context of viral-induced chronic neuroinflammation, the findings presented here suggest that cannabinoids via CB2 ligation may have beneficial anti-inflammatory effects.”
Michigan State University, USA.
Rizzo MD, et al. J Pharmacol Exp Ther. 2019 Aug 5. [in press]

Science/Cells: CBD may have protective effects for the skin
According to new research CBD significantly enhances the activity of antioxidant enzymes in certain skin cells (keratinocytes), if they are stressed by harmful factors including ultraviolet radiation. Authors concluded that “the antioxidant activity of CBD through Nrf2 activation as well as its anti-inflammatory properties as an inhibitor of NFκB should be considered during design of new protective treatments for the skin.”
Department of Analytical Chemistry, Medical University of Bialystok, Poland.
Jastrząb A, et al. Cells. 2019;8(8).

Science/Human: No relevant effect of another antiepileptic drug on the effect of CBD on seizure frequency
In a study with 132 adults and children with treatment resistant epilepsy receiving CBD, the additional treatment with clobazam, a well-known antiepileptic drug, had no influence on seizure frequency. Researchers compared 2 groups of CBD patients (one with and the other without additional clobazam) for a duration of 48 weeks.
Department of Neurology, Division of Epilepsy, University of Alabama at Birmingham, USA.
Gaston TE, et al. Epilepsy Behav. 2019;98(Pt A):201-206.

Science/Human: Differences in the endocannabinoid system of combat veterans with our without suicide attempts
The levels of anandamide were negatively correlated with suicidal ideation scores among combat veterans, who have not attempted to commit suicide, while it was not correlated with the score among attempters. Also levels of cortisol and the endocannabinoid 2-AG showed differences. Authors concluded that “there are psychological and biological differences between combat veterans with or without a history of suicidal attempt.“
James J. Peters Veterans' Administration Medical Center, Bronx, USA.
Sher L, et al. Psychiatry Res. 2019 Jul 25:112495.

Science/Animal: Beta-caryophyllene ameliorates arthritis
The CB2 receptor agonist and cannabinoid terpene beta-caryophyllene was investigated in an animal model of arthritis. Results show that beta-caryophyllene “ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.” PPAR-gamma is a receptor found within cells and not on the cell surface.
Department of Clinical and Experimental Medicine, University of Messina, Italy.
Irrera N, et al. Biomolecules. 2019 Jul 31;9(8).

Science/Animal: Activation of the CB2 receptor protected the bowel from damage due to reduced perfusion
Administration of a CB2 receptor agonist before reduction of blood supply to the intestine reduced damage “associated with anti-inflammatory mechanisms such as the inhibiting of migration of inflammatory polymorphonuclear cells that origin of acute and initial responses of inflammation, the inhibiting of production of provocative and pro-inflammatory cytokines like TNF-alpha and IL-1beta, …”
Duzce University, Turkey.
Bayram S, et al. Fundam Clin Pharmacol. 2019 Aug 1. [in press]

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