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IACM-Bulletin of 24 August 2014

Science/Human: Vaporized cannabis safe and effective in the treatment of neuropathic pain

A significant reduction in pain intensity was achieved after cannabis inhalation with a vaporizer in 8 patients suffering from chronic neuropathic pain. This is the result of an open study by Israeli researchers published in the Journal of Pain and Palliative Care Pharmacotherapy. The objective of the study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of the Syqe Inhaler, a novel portable thermal-metered-dose inhaler for cannabis. The patients were on a stable analgesic regimen including medicinal cannabis. They received one dose of 15 mg THC in cannabis.

Mean maximum THC plasma concentration was 38 ng/mL, which was achieved on average after 3 minutes. Mean reduction in pain intensity was 45% and noted 20 minutes after inhalation, turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event.

Eisenberg E, Ogintz M, Almog S. The Pharmacokinetics, Efficacy, Safety, and Ease of Use of a Novel Portable Metered-Dose Cannabis Inhaler in Patients With Chronic Neuropathic Pain: A Phase 1a Study. J Pain Palliat Care Pharmacother. 2014 Aug 13. [in press]

Canada: Several medical cannabis companies prepare their stock market launch

Four Canadian medical cannabis producers are working on transactions that will allow them to realise a stock market launch in the next few weeks. Mettrum Ltd, OrganiGram Inc, Bedrocan Canada Inc and PharmaCan Capita will join Tweed Marijuana Inc, now the only listed producer, on the TSX Venture Exchange, a stock exchange in Canada. Once these companies become public, investors will be able to directly or indirectly own shares in seven, including the three associated with PharmaCan, of the 13 medical cannabis producers licensed by Health Canada.

Tweed went public in April and has a market value of 101 million Canadian Dollars (about 70 million EURos). Several medical cannabis firms are listed on the less actively regulated over-the-counter market in the United States. But the nationwide regulations governing medical cannabis in Canada distinguish it from the U.S. market, where cannabis is illegal at the federal level, and are making the Canadian market attractive to both Canadian and foreign investors. The partner of Dutch medical cannabis producer Bedrocan BV is currently valued at about 57 million Canadian Dollars (about 40 million EURos). Its rival, Toronto-based Mettrum, is expected to be valued at about 80 million Canadian Dollars (55 million EURos). OrganiGram is valued at about 35 million Canadian Dollars (24 million EURos). PharmaCan was most recently valued at about 50 million Canadian Dollars (34 million EURos).

Reuters of 6 August 2014

Science/Human: THC may be detectable in blood up to 16 days after last cannabis use

16 days after last cannabis use, the THC-levels of 28 % of patients, who were treated in several hospitals in Germany, were still above 1 nanogram per millilitre (ng/ml) in blood serum. This is the result of research published in the journal Drug and Alcohol Dependence by researchers of the Department of Psychiatry, Psychotherapy and Psychosomatics of the Evangelisches Krankenhaus Castrop-Rauxel and the Department of Addictive Behavior and Addiction Medicine, LVR-Klinikum Essen.

Scientists included 39 treatment-seeking chronic cannabis dependents in the study. They were studied on admission and on abstinent days 2, 4, 8 and 16. Withdrawal symptoms peaked on day 4. Women had significantly stronger symptoms than men. The serum levels of THC-OH declined most rapidly below detection limit, on median at day 4. At abstinence day 16, the THC-levels of 28 % of the patients were still above 1ng/ml (range: 1.3 to 6.4ng/ml). Researchers concluded that “residual THC was found in the serum of almost one-third of the patients at abstinence day 16.”

Bonnet U, Specka M, Stratmann U, Ochwadt R, Scherbaum N. Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification: Cannabis withdrawal syndrome and its correlation with delta-9-tetrahydrocannabinol and -metabolites in serum. Drug Alcohol Depend. 2014 Aug 1. [in press]

News in brief

Germany: Petition to the German Bundestag on cannabis as medicine
Since 13 August 2014 a petition by Dr Franjo Grotenhermen, Chairman of the German Association for Cannabis as Medicine, to the petition committee of the German Bundestag can be signed. The signing period ends on 10 September 2014. Online or offline 50.000 signatures have to be collected in order to achieve a discussion of the petition by the petition committee. Citizens of all nationalities and countries are allowed and invited to sign the petition. The petition has two aims. The costs for cannabis-based medicines shall be paid. Patients with a certificate by their doctor confirming that they need a treatment with cannabis shall no longer be prosecuted due to illegal cannabis possession.
Grotenhermen’s website on the petition
Signing of the petition on the website of the German Bundestag

USA: Clinical study with cannabis in sickle cell disease may start
A clinical trial of medical cannabis could provide new hope for people suffering from sickle cell anaemia. Lead researcher Dr Donald Abrams of San Francisco General Hospital had demonstrated that mice with sickle cell disease treated with cannabis high in CBD showed less pain and less inflammation. He now has the green light for a human study with federal funding and federal cannabis.
ABC News of 14 August 2014

USA: Citizens of the District of Columbia will vote on cannabis legalisation
An initiative to legalize cannabis possession in Washington DC was cleared for a vote in November 2014. The DC Cannabis Campaign had submitted 57,000 petition signatures last month, more than twice the number needed for the measure to qualify for the vote.
Reuters of 6 August 2014

Science/Animal: THC and CBD may be beneficial in Alzheimer’s disease
THC or CBD extracts, as well as the combination of both cannabinoids preserved memory in a mouse model of Alzheimer’s disease. The study shows that the combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone.
University of Barcelona, Spain.
Aso E, et al. J Alzheimers Dis. 2014 Aug 14. [in press]

Science/Canada: Canadian rheumatologists lack confidence in their knowledge on cannabis
An online survey revealed that rheumatologists lack confidence in their knowledge of cannabinoids in general and in their competence to prescribe any cannabinoid for rheumatic complaints. In line with this uncertainty, there is reticence to prescribe cannabinoid preparations for rheumatology patients.
Division of Rheumatology, Montreal General Hospital, Canada.
Fitzcharles MA, et al. BMC Musculoskelet Disord 2014;15(1):258.

Science/Human: Cannabis use influences blood concentrations of cytokines in MS patients
Cannabis use reduces the movements of certain immune cells (monocytes) and reduces the plasma levels of certain cytokines (CCL2 and IL17), which have effects on inflammation in patients with multiple sclerosis and healthy people. Researches also detected a significant increase in the endocannabinoid anandamide (AEA) in the blood of MS patients.
Center for the Study of Cannabis and Social Policy, Seattle, USA.
Sexton M, et al. Inflammopharmacology. 2014 Aug 19. [in press]

Science/Animal: 2-AG has antidepressant- and anxiolytic-like effects in rats
Blockade of the degradation of the endocannabinoid 2-AG (2-arachidonoylglycerol) produces antidepressant- and anxiolytic-like effects and enhances nerve cell formation in a certain brain region (hippocampus).
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, USA.
Zhang Z, et al. Hippocampus. 2014 Aug 12. [in press]

Science/Animal: THC had no effect in a HIV model of female monkeys
Chronic THC administration did not protect SIV-infected female rhesus monkeys from early mortality. The SI-virus is the equivalence to the HI-virus in humans. In 2010 the same research group had reported that disease progression was slowed by THC in male rhesus monkeys. Authors wrote that “the contrasting effects of chronic delta-9-THC in males versus females remain to be explained.”
Louisiana State University Health Sciences Center, New Orleans, USA
Amedee AM, et al. AIDS Res Hum Retroviruses. 2014 Aug 11. [in press]

Science/Human: Endocannabinoid concentrations differed in obese females compared to controls
In a study with 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls) obese participants differed with regard to the concentrations of the endocannabinoids 2-AG and anandamide in blood.
Department of Psychiatry, University Hospital of Bellvitge-IDIBELL, Barcelona, Spain.
Fernández-Aranda F, et al. PLoS One 2014;9(8):e104534.

Science: Cannabinoids of Radula marginata and Cannabis sativa L.
Radula marginata and Cannabis sativa L. are the only two plant species, which contain cannabinoids, but have no evolutionary relationships. Researchers found similar endophytes (bacteria and fungi) in both plants. An endophyte is an endosymbiont, often a bacterium or fungus that lives within a plant for at least part of its life without causing apparent disease. Radula marginata belongs to the genus radula (liverworts) and grows in New Zealand and Tasmania.
Department of Biochemical and Chemical Engineering, TU Dortmund, Germany.
Kusari P, et al. Antonie Van Leeuwenhoek. 2014 Aug 7. [in press]

Science/Cells: THC and CBD increase susceptibility to destruction of lung cancer cells by immune cells
New research demonstrates that cannabinoids increase the concentration of ICAM-1, a protein on the surface of lung cancer cells, and this was responsible for increased cancer cell susceptibility to destruction of these cells by so-called activated killer cells, a form of immune cells. Authors concluded that “these findings provide proof for a novel antitumorigenic mechanism of cannabinoids.”
Institute of Toxicology and Pharmacology, University of Rostock, Germany.
Haustein M, et al. Biochem Pharmacol. 2014 Jul 25. [in press]

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