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IACM-Bulletin of February 19, 2017


Science/Human — Cannabis improved survival of patients with aggressive brain cancer in controlled clinical study

A cannabis extract with THC and CBD improved survival of patients with recurrent glioblastoma, a particularly aggressive brain tumour, if given together with standard therapy. This is the result of a placebo-controlled study with 21 patients, which was reported by the producer of the cannabis extract Sativex, GW Pharmaceuticals from the UK. 12 patients were randomized to receive Sativex together with temozolomide and 9 patients received placebo together with temozolomide.

The study showed that 83% of patients with documented recurrent glioblastoma treated with THC and CBD had survived the first year compared with 53% of patients in the placebo group (p=0.042). Median survival for the cannabis group was greater than 550 days compared with 369 days in the placebo group. The press release says: “GW conducted substantial pre-clinical oncologic research on several cannabinoids in various forms of cancer including brain, lung, breast, pancreatic, melanoma, ovarian, gastric, renal, prostate and bladder. These studies have resulted in approximately 15 publications and show the multi-modal effects of cannabinoids on a number of the key pathways associated with tumor growth and progression.”

Press release by GW Pharmaceuticals of 7 February 2017

Science/Human — Cannabis may be helpful in the treatment of ADHD according to a small clinical trial

The cannabis extract Sativex improved hyperactivity and impulsivity in patients with ADHD (attention deficit hyperactivity disorder) according to a study by researchers of King’s College London and other medical institutions from London, UK. The data were presented at the 29th ECNP Congress, 17-20 September 2016 in Vienna, Austria, and published in the European Neuropsychopharmacology. 30 patients with ADHD received either Sativex or placebo for four weeks.

There was a significant improvement in hyperactivity/impulsivity (p=0.03) and a trend for improvement in inattention, cognitive performance and emotional lability. Authors wrote that “although individual findings did not reach conventional significance levels, effects across multiple measures showed consistent improvements in cognition and behaviour. ADHD may represent a subgroup of individuals that gain cognitive enhancement and reduction of ADHD symptoms from the use of cannabinoids.”

Cooper RE, Williams E, Seegobin S, Tye C, Kuntsi J, Asherson P. Cannabinoids in attention-deficit/hyperactivity disorder: a randomised-controlled trial. European Neuropsychopharmacology 2016;26:S130.

PowerPoint presentation of the talk

Sweden — First patients get approval to use cannabis for medicinal purposes

Two patients have been granted the right to use cannabis flowers to relieve chronic pain - the first time the drug has been prescribed in Sweden. The decision was made in relation to two patients with back injuries, after doctors applied to the MPA (Medical Products Agency) for a license to prescribe cannabis for their pain. On 27 August 2015 a Swedish court acquitted a pain patient, who used illegal cannabis, because no other medication helped him.

"I am happy that the MPA has taken the pragmatic step of making [cannabis] available for patients with chronic pain which no approved drug can relieve," Fredrik von Kieseritzky, doctor of organic chemistry and medicinal chemistry, who advised the doctors involved with the two patients. Licensing regulations mean that permission to prescribe must be applied for with each individual patient. The two approved patients will be supplied cannabis via the Dutch company Bedrocan.

The Local of 12 February 2017 of 28 August 2015

Ireland — Government report proposes legalization of cannabis for medical use

Ireland is moving forward to legalise the use of cannabis for treating specific medical conditions, after a report commissioned by the government said the drug could be given to some patients with certain illnesses. The Irish health minister, Simon Harris, said he would support the use of medical cannabis "where patients have not responded to other treatments and there is some evidence that cannabis may be effective".

The report said cannabis could be given to patients with a range of illnesses including multiple sclerosis and severe epilepsy, and to offset the effects of chemotherapy. "I believe this report marks a significant milestone in developing policy in this area," Harris said. "This is something I am eager to progress but I am also obligated to proceed on the basis of the best clinical advice." Last November, Harris asked Ireland's Health Products Regulatory Authority (HPRA) to examine the latest evidence on cannabis for medical use and how schemes to facilitate this operate in other countries.

The Guardian of 10 February 2017

Science/Human — THC showed mixed results in the treatment of pain and spasticity in multiple sclerosis

Pain and spasticity was reduced by a THC preparation of Echo Pharmaceuticals in a placebo-controlled study with 24 patients suffering from multiple sclerosis according to research by several scientific institutions in Leiden and Amsterdam, The Netherlands. Patients received either a placebo or oral THC for 4 weeks.

Pain was significantly reduced when measured directly after administration of THC in the clinic but not when measured in a daily diary. A similar pattern was observed in subjective muscle spasticity. Other clinical outcomes were not significantly different between active treatment and placebo.

van Amerongen G, Kanhai K, Baakman AC, Heuberger J, Klaassen E, Beumer TL, Strijers RL, Killestein J, van Gerven J, Cohen A, Groeneveld GJ. Effects on Spasticity and Neuropathic Pain of an Oral Formulation of Δ9-Tetrahydrocannabinol in Patients With Progressive Multiple Sclerosis. Clin Ther. 2017 Feb 9. [in press]

News in brief

Peru — Government proposes to legalise the medical use of cannabis

President Pedro Pablo Kuczynski said that he plans to legalise the medical use of cannabis and that his plans stems from a Lima police raid in a house where a group of parents were found growing cannabis to make oil to treat children's epilepsy. The government says it will present to the opposition-dominated legislature a plan to legalise the medical use of cannabis “for the treatment of serious and terminal illnesses.”

The Independent of 9 February 2017

Israel — Israel takes step toward allowing export of medical cannabis

An Israeli government committee gave an initial agreement for the export of medical cannabis. A government statement announcing the vote said it could take months for the legislation to make its way through parliament.

Reuters of 5 February 2017

Science/Human — A treatment with palmithoylethanolamide and polydatin improved pain in irritable bowel syndrome

In a 12-week placebo-controlled study with 54 patients with irritable bowel syndrome administration of twice daily 200mg palmithoylethanolamide and 20mg polydatin significantly improved pain. Authors wrote that “the marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition.”

University of Bologna, Italy.

Cremon C, et al. Aliment Pharmacol Ther. 2017 Feb 6. [in press]

Science/Human — Nabilone was not effective in reducing postoperative nausea and vomiting

In a study with 340 patients, who underwent surgery under general anaesthesia and had an increased risk for postoperative nausea and vomiting, nabilone in a dose of 0.5mg was not superior to placebo in symptom reduction.

Department of Anesthesia, University of Toronto, Canada.

Levin DN, et al. Can J Anaesth. 2017 Feb 3. [in press]

Science/Animal — CBD reduces the intake of alcohol in alcohol dependent mice

CBD given to mice in doses between 30 and 120mg/kg body weight reduced several signs of alcohol dependency, including alcohol consumption and alcohol-induced relapse. Authors wrote that “these findings strongly suggest that CBD may result useful for the treatment of alcohol use disorders.”

Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Spain.

Viudez-Martínez A, et al. Addict Biol. 2017 Feb 13. [in press]

Science/Animal — Increase of endocannabinoids reduced colon cancer

In mice models of colon cancer an inhibitor of the degradation of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) reduced tumour development. Endocannabinoid levels were increased by inhibition of monoacylglycerol lipase (MAGL), which is responsible for the degradation of 2-AG.

Department of Pharmacy, University of Naples Federico II, Italy.

Pagano E, et al. Pharmacol Res. 2017 Feb 10. [in press]

Science/Cells — Activation of the CB2-receptor induces cell death in bladder cancer cells

Activation of the CB2-receptor led to ceramide-mediated bladder cancer cell apoptosis, a form of programmed cell death. Ceramides are a family of lipid molecules, which play a role in cell proliferation and apoptosis.

IRCCS Ospedale San Raffaele, Milan, Italy.

Bettiga A, et al. Sci Rep. 2017;7:42157.

Science/Human — Cannabis use had no relevant influence on outcome of behavioural therapies for co-occurring PTSD and substance use disorders

In 136 individuals who received cognitive-behavioural therapies for co-occurring posttraumatic stress disorder and substance use disorders, the use of cannabis was not associated with adverse outcomes in the treatment.

Department of Psychology, The City College of New York, USA.

Ruglass LM, et al. J Clin Med. 2017;6(2).

Science/Human — Cannabis use alters immune cells in a way, which supports beneficial effects in inflammatory diseases and cancer

Researchers investigated peripheral blood mononuclear cells of cannabis users and found reduction of signalling pathways, which are relevant for inflammation and for cell division. However, long term cannabis exposure in two patients resulted in reversal of this effect. Authors wrote that “while these data provide a powerful mechanistic rationale for the clinical use of medical marijuana in inflammatory and oncological disease, caution may be advised with sustained use of such preparations.”

Department of Gastroenterology and Hepatology, Erasmus University of Rotterdam, Netherlands.

Utomo WK, et al. Front Mol Neurosci. 2017;10:14.

Science/Human — Cannabis and alcohol use were associated with increased risk of schizophrenia

A longitudinal, nationwide Danish study with 3,133,968 individuals found that a diagnosis of substance abuse increased the overall risk of developing schizophrenia. Cannabis use (hazard ratio 5.20) and alcohol (hazard ratio 3.38) presented the strongest associations.

Copenhagen University Hospital, Denmark.

Nielsen SM, et al. Psychol Med. 2017:1-10.

Science/Animal — Cannabinoids mitigate depression caused by social isolation stress

In a mouse model of depression caused by social isolation stress the activation of the CB1 and the CB2 receptor by a synthetic cannabinoid mitigated the symptoms.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Iran.

Haj-Mirzaian A, et al. Brain Res Bull. 2017 Feb 1. [in press]

Science/Animal — Beta-caryophyllene reduced cognitive decline in rats

A complex of beta-caryophyllene-and hydroxypropyl-beta-cyclodextrin was given to rats to investigate its effects on cognitive deficits in vascular dementia rats. Researchers demonstrated that this complex can increase the expression levels of CB2 in brain tissues, particularly the hippocampus and white matter tissues. The study showed protective effects of the complex against cognitive deficits induced by chronic cerebral ischemia.

School of Pharmacy, Chongqing Medical University, China.

Lou J, et al. Front Pharmacol. 2017;8:2.