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IACM-Bulletin of October 2, 2016


Germany — First patient gets a permission to grow his own cannabis

On 28 September the Federal Institute for Drugs and Medical Devices, an agency of the Federal Health Ministry, issued its first permission to grow cannabis for his own medical needs to a 57-year-old patient suffering from multiple sclerosis. The permission is valid until 30 June 2017. It has to be prolonged, if the health insurance does not cover the costs for cannabis flowers from the pharmacy thereafter.

The Federal Health Ministry was forced by a ruling of the Federal Administrative Court of 6 April to grant such permission. The Federal Government and the German Bundestag are preparing a law, according to which the costs for a treatment with cannabis flowers have to be reimbursed by the health insurances under certain conditions so that the need for self-cultivation would be eliminated. It is intended to make the law come into force in early 2017.

Permission for self-cultivation by the Federal Institute for Drugs and Medical Devices of 28 September 2016

Science/Human — Cannabidiol is effective in febrile infection-related epilepsy syndrome in a case series

Doctors from several paediatric centres in the USA, in Philadelphia, New York, Houston and Chicago, presented the cases of seven children with febrile infection-related epilepsy syndrome (FIRES), who had not responded to antiepileptic drugs or other therapies who were given the cannabidiol extract Epidiolex. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflurane. An average of 4 antiepileptic drugs was weaned. Authors wrote that “while this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.”

FIRES is a severe form of epilepsy affecting normal children after a febrile illness. It presents with an acute phase with a very difficult to treat status epilepticus and all patients develop a chronic phase with persistent refractory epilepsy. The typical outcome is severe brain damage or death.

Gofshteyn JS, Wilfong A, Devinsky O, Bluvstein J, Charuta J, Ciliberto MA, Laux L, Marsh ED. Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases. J Child Neurol. 2016 Sep 21. [In press]

Science/Human — Cannabidiol improves severe form of childhood epilepsy in controlled clinical trial

The manufacturer of the CBD extract Epidiolex, GW Pharmaceuticals, reported of positive results of the second placebo-controlled Phase 3 clinical trial of this preparation for the treatment of seizures associated with Lennox-Gastaut syndrome, a rare and severe form of childhood-onset epilepsy. The trial randomized 225 patients into three arms, where Epidiolex was added to the current treatment in a dose of 20mg/kg body weight per day (n=76) or in a dose of 10mg/kg/day (n=73). The other patients (n=76) received a placebo.

Patients taking Epidiolex in the higher dose achieved a median reduction in monthly drop seizures of 42 percent compared with a reduction of 17 percent in patients taking placebo, and patients taking Epidiolex in the lower dose achieved a median reduction in monthly drop seizures of 37 percent. “The positive outcome in this second trial of Epidiolex in patients with Lennox-Gastaut syndrome demonstrates the effectiveness of this product in this particularly difficult to treat, childhood-onset epilepsy,” stated Dr Orrin Devinsky of New York University Langone Medical Centers and principal investigator in the trial.

Press release by GW Pharmaceuticals of 26 September 2016.

Science/Human — The synthetic cannabinoid Resunab reduces inflammation in healthy subjects

Resunab, formerly known as ajulemic acid, reduced signs of inflammation in 15 healthy subjects, in whom inflammation was induced by the subcutaneous injection of heat-killed bacteria (E. coli). Resunab inhibited infiltration by white blood cells, a key determinant of inflammation severity, by approximately 70%. The data were presented at the 6th European Workshop on Lipid Mediators on 28 September in Frankfurt, Germany.

The first set of data is from 15 subjects (5 on placebo, 5 on 5 mg Resunab twice a day and 5 on 20 mg Resunab twice a day). The top dose of Resunab in this study is the same as the top dose in the Phase 2 clinical trials currently underway with Resunab in cystic fibrosis, systemic sclerosis and dermatomyositis, respectively. Resunab is a synthetic oral cannabinoid that preferentially binds to the CB2 receptor.

Press release by Corbus Pharmaceuticals of 28 September 2016.

News in brief

Science/Animal — The endocannabinoid system may be a target for the treatment of autism

In a rat model of autism researchers observed changes of the CB1 receptor and reduced levels of the endocannabinoid anandamide. Authors concluded that “the endocannabinoid system may represent a therapeutic target for the core and associated symptoms displayed by autistic patients.”

University "Roma Tre", Italy.

Servadio M, et al. Transl Psychiatry. 2016;6(9):e902.

Science/Animal — Cannabinoids increase the effects of standard anti-epileptic drugs

Cannabinoids, which activate the CB1 receptor (WIN 55,212-2, ACEA), potentiated the anti-epileptic effects of carbamazepine, diazepam, felbamate, gabapentin, phenobarbital, topiramate and valproate in a mouse model of epilepsy.

Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Italy.

Citraro R, et al. Eur J Pharmacol. 2016;791:523-534.

Science/Human — Cannabis use during pregnancy is not associated with adverse birth outcome

According to a review of studies on effects of cannabis use on pregnancy outcome there was no increased risk for low birth weight and preterm birth. Authors concluded that “maternal marijuana use during pregnancy is not an independent risk factor for adverse neonatal outcomes after adjusting for confounding factors.”

Department of Obstetrics and Gynecology, Washington University in St. Louis, USA.

Conner SN, et al. Obstet Gynecol. 2016;128(4):713-23.

Science/Human — The legalization of cannabis in the USA had minimal adverse effects on health

According to a report by the CATO Institute in Washington DC legalization of cannabis in Alaska, Colorado, Oregon and Washington had only “minimal” adverse health and safety effects, including drug use, suicide rates, crime rates, and road safety.

Dose of Reality: The Effect of State Marijuana Legalizations

Science/Animal — Activation of the new cannabinoid receptor GPR18 has beneficial effects on the heart

The activation of the endocannabinoid receptor GPR18 by abnormal cannabidiol (abn-CBD) caused hypotension, suppressed the cardiac sympathetic dominance, and improved left ventricular function and reduced left ventricular end diastolic pressure in rats. Authors wrote that “the current findings present new evidence for a salutary cardiovascular role for GPR18.”

Brody School of Medicine, East Carolina University, North Carolina, USA.

Matouk AI, et al. J Cardiovasc Pharmacol. 2016 Sep 20. [In press]

Science/Human — CB1 receptor blockade increases inflammation

In 20 obese patients with polycystic ovary syndrome blockade of the CB1 receptor by rimonabant increased signs of inflammation, namely the concentrations of VEGF (vascular endothelial growth factor) and interleukin 8, pro-inflammatory cytokine.

Department of Academic Endocrinology, Diabetes and Metabolism, University of Hull, UK.

Sathyapalan T, et al. Clin Endocrinol (Oxf). 2016 Sep 21. [In press]

Science/Cells — THC reduces permeability of airway epithelial cells

In a study with bronchial epithelial cells THC reduced permeability after exposure to pro-inflammatory cytokines by activation of the CB2 receptor. Authors wrote, that THC “beneficial in the prevention of inflammation-induced changes in airway epithelial cell permeability, an important feature of airways diseases.”

School of Life Sciences, University of Nottingham, UK.

Shang VC, et al. Biochem Pharmacol. 2016 Sep 15. [In press]

Science/Cells — Cannabinoids reduce viability of stomach cancer cells

In a study with adenocarcinoma cells of the stomach of humans several cannabinoids (CP 55,940, anandamide and methanandamide) reduced their viability. Authors wrote that their results “support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells.”

Instituto Nacional de Cancerología, Mexico City, Mexico.

Ortega A, et al. Life Sci. 2016 Sep 15. [In press]

Science/Cells — THC causes death in cancer cells by inducing changes in the endoplasmatic reticulum

THC increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum, a cell compound, of certain brain cancer cells (glioma cells), and this alteration finally leads to apoptosis, a form of programmed cell death.

School of Biology, Complutense University, Madrid, Spain.

Hernández-Tiedra S, et al. Autophagy. 2016 Sep 16:1-17. [In press]

Science/Cells — Anandamide causes relaxation of human arteries

In mesenteric arteries from 31 patients, who had undergone bowel resection, the endocannabinoid anandamide caused moderate endothelium-dependent vasorelaxation via activation of CB1 receptors.

School of Medicine, University of Nottingham, Royal Derby Hospital, UK.

Stanley CP, et al. Pharmacol Res. 2016;113(Pt A):356-363.