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IACM-Bulletin of 28 October 2007

Science: Cannabis extract effective without development of tolerance in 2-year trial


According to a British study on patients with multiple sclerosis, who suffered from neuropathic pain, a cannabis spray (Sativex) maintained its efficacy in reducing pain over the whole period of two years. Following a five-week controlled study, which was completed by 64 patients, who either received the cannabis extract Sativex or a placebo, 63 patients entered an open-label extension study. The mean duration of the open-label treatment was 463 days. 34 patients completed more than one year and 28 completed the whole study (range: 701-917 days). 17 patients withdrew due to adverse effects of the study medication.

The mean pain score for all patients at entry into the initial short term controlled trial was 6.5. Mean pain scores in the final week of the acute study was 3.8 in the group receiving cannabis and 5.0 in the placebo group. In the 28 patients who completed the 2-year follow up the mean pain score in the final week of treatment was 2.9. 92 per cent of patients experienced at least one adverse effect, which were usually mild to moderate. There were two serious adverse effects, one cardiac arrhythmia and one collapse, which occured in the same patient and needed hospitalisation. Researchers concluded that the cannabis extract was effective without development of tolerance to the pain-relieving effects of the drug over an extended period of time without the necessity to increase the dose of the drug.

The whole study is available online at: www.clinicaltherapeutics.com/articles/2068_rog.pdf

(Source: Rog DJ, Nurmikko TJ, Young CA. Oromucosal delta-9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther 2007;29(9):2068-79.)

Science: Pain-reducing effects of smoked cannabis were dose-dependent in experimental pain in healthy subjects

According to a study at the University of California in San Diego with 15 healthy volunteers the effect of smoked cannabis on experimental pain was strongest at a moderate dose, while a low dose had no relevant effect and high dose increased pain. Pain was caused by injection of capsaicin into opposite forearms 5 and 45 min after drug exposure. Capsaicin is a compound of hot chili peppers that is an irritant to the skin. On four different occasions participants smoked either a placebo cannabis cigarette (0 per cent THC) or a cannabis cigarette with 2 per cent, 4 per cent or 8 per cent THC.

Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose. Researchers concluded that their study suggests that "there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain."

Several earlier studies had shown that cannabis often did not reduce experimental pain of healthy subjects or even increased pain, while pain-reducing effects were observed more constantly in patients suffering from neuropathic pain with the best pain reduction following the highest doses. Experimental studies in animals had also shown that the endocannabinoid system reacts to chronic pain, which may be the reason for these differences between the effects in healthy persons and pain patients. However, in a study from Switzerland of 2006 on the efficacy of THC against spasticity in spinal cord injury some patients withdrew from a study due to an increase of pain following THC.

The article is available online on the website of the journal Anesthesiology:
www.anesthesiology.org

(Source: Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, Gouaux B, Abramson I. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology 2007;107(5):785-796.)

News in brief

UK: Symposium
A joint symposium of the Academy of Pharmaceutical Sciences and the Royal Pharmaceutical Society of Great Britain entitled "Cannabinoid Medicines" will be held on 10 March 2008 in London. More information at: www.rpsgb.org/worldofpharmacy/events. (Source: Personal communication)

Belgium: Conference on cannabis culture
The Institute for Social Drugs Research (ISD) at the University of Gent, Belgium, will organize a two day conference on 3-4 December. Between 2005 and 2007 the ISD carried out a big scale study and interviewed some 750 cannabis growers about their motifs. Belgian and Dutch experts will discuss the different aspects of the production and the economical consequences. Among the speakers are Prof. Tom Decorte, Prof. Adriaan Jansen, Joep Oomen, Prof. Frank Bovenkerk, Prof. Peter Cohen, the mayors Gerd Leers (Maastricht-NL), Marcel Hendrickx (Turnhout-B) and Jan Lonink (Terneuzen-NL). More at: www.law.ugent.be/crim/ISD. (Source: Press release of the ISD on 18 September 2007)

Science: Depression
In an animal model for depression a synthetic cannabinoid (WIN55,212-2) showed anti-depressant effects. This effect was CB1-receptor dependent and mediated by the serotonin receptor (5-HT-receptor). (Source: Bambico FR, et al. J Neurosci 2007;27(43):11700-11711.)

Science: Pneumothorax
Doctors at the Division of General Thoracic Surgery of the University Hospital Berne, Switzerland, observed a remarkable increase in the number of young patients who presented with lung emphysema and spontaneous pneumothorax in recent years. Most of them have a common history of heavy combined cannabis and tobacco use. (Source: Beshay M, et al. EUR J Cardiothorac Surg, 9 Oct 2007; [Electronic publication ahead of print])

Science: Protection of the heart
In experimental studies it was observed that cannabinoids protect the heart during decreased blood and oxygen supply. CB1-receptors are present mainly on endothelial cells in the heart, and exert their protective effects through production of nitric oxide. In contrast, CB2-receptors present on heart cells exert a protective effect independent of this endothelial factor. (Source: Lepicier P, et al. Life Sci, 24 Sep 2007; [Electronic publication ahead of print])

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