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IACM-Bulletin of 03 November 2013

Science/Cells: Basic research shows that non-psychotropic cannabinoids such as cannabidiol are effective anti-cancer drugs in leukaemia

New research has shown that the non-psychotropic cannabinoids of cannabis could act as effective anti-cancer agents. The anti-cancer properties of THC, the primary psychotropic component of cannabis, have been recognised for many years. The study was carried out by a team at St George’s, University of London with leukaemia cells. The team, led by Dr Wai Liu and colleagues carried out laboratory investigations using a number of cannabinoids, either alone or in combination with each other. Of the cannabinoids studied, each demonstrated anti-cancer properties as effective as those seen in THC. Importantly, they had an increased effect on cancer cells when combined with each other.

Dr Liu said: “These agents are able to interfere with the development of cancerous cells, stopping them in their tracks and preventing them from growing. In some cases, by using specific dosage patterns, they can destroy cancer cells on their own. Used in combination with existing treatment, we could discover some highly effective strategies for tackling cancer.” The study examined cannabidiol (CBD), cannabigerol (CBG) and cannabigevarin (CBGV).

Press release by St George's University of London of 14 October 2013

Scott KA, Shah S, Dalgleish AG, Liu WM. Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules. Anticancer Res 2013;33(10):4373-80.

Science/Animal: How the plant cannabinoid CBD may be helpful in cannabis dependence

Basic research of two groups of researchers in the United Arab Emirates and the USA point to a possible mechanism, by which cannabidiol (CBD) has potential as a treatment for cannabis dependence as suggested by previous research with cannabis users. Scientists of the National Institute on Drug Abuse in Baltimore, USA, demonstrated that kynurenic acid, which inhibits the alpha-7-nicotinic acetylcholine receptors (α7-nACh receptor), reduced the rewarding effects of THC in rats and monkeys, who were dependent on THC. Kynurenic acid is a product of the normal metabolism of the amino acid L-tryptophan. Researchers wrote that the modulation of kynurenic acid “offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.”

A group from the College of Medicine and Health Sciences of the University of Abu Dhabi in Al Ain, United Arab Emirates, showed that CBD inhibits acetylcholine-induced currents at the alpha-7-nicotinic acetylcholine receptors. They concluded that their results “indicate that CBD inhibits the function of the α7-nACh receptor.” Other mechanisms may be involved in these effects of CBD.

Mahgoub M, Keun-Hang SY, Sydorenko V, Ashoor A, Kabbani N, Al Kury L, Sadek B, Howarth CF, Isaev D, Galadari S, Oz M. Effects of cannabidiol on the function of α7-nicotinic acetylcholine receptors. EUR J Pharmacol. 2013 Oct 18. [in press]

Justinova Z, Mascia P, Wu HQ, Secci ME, Redhi GH, Panlilio LV, Scherma M, Barnes C, Parashos A, Zara T, Fratta W, Solinas M, Pistis M, Bergman J, Kangas BD, Ferré S, Tanda G, Schwarcz R, Goldberg SR. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. Nat Neurosci 2013;16(11):1652-61.

News in brief

USA: For the first time majority supports legalizing cannabis
A majority of US citizens for the first time favours legalizing cannabis, a poll released on 22 October indicated. Gallup said a clear majority of Americans -- 58 per cent -- say cannabis should be legalized, a 10-point jump over the past year. In 1969 -- the first time Gallup asked the question -- only 12 per cent favoured legalization. By the 1970s the figure was 28 per cent, and it reached 50 per cent in 2011. The poll included 1,028 adults ages 18 and older.
UPI of 22 October 2013

Science/USA: Authorities approve clinical trials with CBD in children with epilepsy
The US authorities have approved two clinical trials to assess the efficacy of cannabidiol (CBD), a nonpsychoactive plant cannabinoid, in the treatment of intractable paediatric epilepsy. The two approved trials will take place at New York Medical School and at the University of California at San Francisco, according to an online report in the journal O'Shaughnessy's. The cannabidiol formulations in the trials will be provided by the British company GW Pharmaceuticals, which produces organic cannabinoid extract medicines, including Sativex.

France: Sativex has been recommended for approval
GW Pharmaceuticals' cannabis extract Sativex has been recommended for approval in France for the treatment of spasticity due to multiple sclerosis. Sativex will be sold in France by GW's EURopean partner Almirall following completion of national pricing and reimbursement procedures. The drug - which is sprayed under the tongue - is currently available in Britain, Spain, Germany, Canada, Denmark, Norway, Israel, Austria, Poland, Sweden, Italy and Finland.
Reuters of 21 October 2013

Uruguay: Government intends to make cannabis available for 1 Dollar per gram
The Government of Uruguay says the country plans to sell legal cannabis for 1 Dollar per gram to combat drug-trafficking. The plan to create a government-run legal cannabis industry has passed the lower house of Congress, and President Jose Mujica expects to push it through the Senate soon as part of his effort to explore alternatives in the war on drugs.
Associated Press of 21 October 2013

Science/Animal: Cannabinoid increases anti-epileptic effects of other medicinal drugs
Data gained by studies with rats suggest that the combination of the synthetic cannabinoid WIN55,212-2 and standard anti-epileptic medication (lamotrigine, pregabalin and topiramate) is associated with beneficial anticonvulsant interactions in epilepsy.
Department of Pathophysiology, Medical University, Lublin, Poland.
Luszczki JJ, et al. EUR J Pharmacol. 2013 Oct 23. [in press]

Science/Animal: THC and resiniferatoxin act synergistically in reducing nausea
Animal research with shrews shows that THC and resiniferatoxin, which binds to the vanilloid receptor (TRPV1 receptor), act synergistically in reducing nausea and vomiting. Authors wrote “that combination of CB1/2 and TRPV1 agonists have the capacity to completely abolish cisplatin-induced emesis at doses that are ineffective when used individually.”
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, USA.
Darmani NA, et al. EUR J Pharmacol. 2013 Oct 21. [in press]

Science/Animal: The endocannabinoid system is activated in physical exercise and this reduces pain
Studies with rats indicate that exercise could activate the endocannabinoid system, producing pain reduction. Authors wrote that their results “suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels.”
Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Souza GG, et al. Neuropharmacology. 2013 Oct 19. [in press]

Science/Cells: The anti-breast cancer effects of tamoxifen may partly be mediated by cannabinoid receptors
Tamoxifen is classified as a selective oestrogen receptor modulator and is used for treatment of patients with oestrogen receptor-positive breast cancer. A new study shows that tamoxifen also binds to the CB1 and the CB2 receptor. Researchers concluded that these results may be used “for development of novel, efficacious, non-toxic cancer drugs acting via CB1 and/or CB2Rs.”
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.
Prather PL, et al. Biochem Biophys Res Commun. 2013 Oct 19. [in press]

Science/Animal: Angiotensin protects the stomach by activation of CB1 receptors
In studies with rats, stimulation of central angiotensin receptors via activation of cannabinoid CB1 receptors induced protection of the mucosa of the stomach. Angiotensin is a peptide hormone that causes vasoconstriction and a subsequent increase in blood pressure.
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Gyires K, et al. Mol Cell Endocrinol. 2013 Oct 18. [in press]

Science/Animal: The endocannabinoid oleoylethanolamide reduces dyskinesia in Parkinson´s disease
The long-term use of levodopa (L-DOPA) in Parkinson's disease results in the development of abnormal involuntary movements called L-DOPA-induced dyskinesias. In studies with mice these side effects were reduced by the endocannabinoid oleoylethanolamide (OEA). Researchers wrote that “this study supports the hypothesis that the endocannabinoid system plays an important role in the development and expression of dyskinesias and might be an effective target for the treatment of L-DOPA-induced dyskinesias.”
Instituto Cajal, CSIC, Madrid, Spain.
González-Aparicio R, et al. Neurobiol Dis. 2013 Oct 17. [in press]

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