IACM-Bulletin of March 15, 2009

Science UK — Cannabis extract Sativex effective in reducing spasticity in MS patients in phase III clinical trial; GW Pharmaceuticals will submit a regulatory application in some European countries

According to a press release of the British company GW Pharmaceuticals a phase III clinical study with their cannabis extract in patients with spasticity due to multiple sclerosis was successful. This study was requested by the UK regulator in order to gain approval in this indication and following these results, the company will fill a regulatory submission in the second quarter of this year. In this phase III study 573 patients initially received Sativex for 4 weeks in a single blind manner (Phase A). Then patients who responded to a treatment with Sativex (241 patients) continued to receive Sativex or switched to placebo for a further 12 weeks in a double-blinded manner (Phase B). During the second period, patients were not permitted to change their dose.

The change in spasticity severity was highly statistically significant in favour of Sativex. 74 per cent of Sativex patients achieved an improvement of greater than 30 per cent in their spasticity score over the entire study versus 51 per cent on placebo. In addition, statistically significant improvements were also seen in spasm frequency, sleep disturbance, patient global impression of change, and physician global impression of change. Following these positive results, GW Pharmaceuticals will submit a regulatory application in the UK and, subject to discussion with the company Almirall, which has the marketing rights for the other European countries, other selected European countries. The study was conducted in 52 hospital sites in five countries - UK, Spain, Italy, Czech Republic and Poland.

More at:

http://www.gwpharm.com

(Source: Press release by GW Pharmaceuticals of 11 March 2009)

Science — Oral intake of a cannabinoid together with a meal improved bioavailability by avoiding first-pass metabolism

Researchers of Monash University in Victoria, Australia, investigated the reason why the oral bioavailability of a synthetic cannabinoid receptor agonist (CRA13) was significantly improved if taken together with a meal rich in fat. Oral bioavailability was assessed in human volunteers and in dogs with and without a meal. Food had a substantial positive effect on the oral bioavailability of CRA13 in human volunteers and in dogs. This cannabinoid is highly lipophilic (soluble in fat) as other cannabinoids including THC.

The absolute bioavailability of the cannabinoid was low in fasted dogs (8-20 per cent), in spite of good absorption (72-75 per cent of radio-labelled CRA13 recovered in the systemic circulation). In fed dogs, bioavailability increased to 47.5 per cent and the majority (43.7 per cent) of the dose was absorbed via the lymphatic system of the intestine. Researchers concluded that the positive food effect for CRA13 does not appear to result from increased absorption. Rather the increase in bioavailability was stimulated via almost complete transport into the lymph, in turn resulting in a reduction in first-pass metabolism. In fasted dogs most of the cannabinoid was metabolised, i.e. changed to inactive compounds, at once in the liver before reaching the whole body, while the liver was bypassed in fed animals.

(Source: Trevaskis NL, Shackleford DM, Charman WN, Edwards GA, Gardin A, Appel-Dingemanse S, Kretz O, Galli B, Porter CJ. Intestinal Lymphatic Transport Enhances the Post-Prandial Oral Bioavailability of a Novel Cannabinoid Receptor Agonist Via Avoidance of First-Pass Metabolism. Pharm Res. 2009 Mar 12. [Electronic publication ahead of print])

News in brief

Germany — Bionorica

According to a press release on business development the German company Bionorica intends to start a process for regulatory approval of dronabinol this year. Bionorica develops and distributes herbal pharmaceuticals with a business volume of 130 million Euros in the year 2008. The company already offers dronabinol to pharmacies to prepare medications (liquids, capsules). (Source: Press release by Bionorica of 6 March 2009)

Holland — Coffee shops

All the coffee shops in the border towns of Roosendaal and Bergen op Zoom must close by 16 September 2009, the towns' respective mayors said. The mayors said last year that by closing the coffee shops they hoped to bring to an end the nuisance caused by the 25,000 drug tourists a week. (Source: www.dutchnews.nl of 5 March 2009)

USA — California

Medical cannabis patients in California won't be at risk of losing their driver's licenses unless they drive while under the direct influence of cannabis. The Department of Motor Vehicles sent a revised training manual to its employees last month explaining how to treat drivers who have a doctor's approval to use cannabis. The medical use of cannabis will be treated exactly the same as the use of other prescription drugs. (Source: San Francisco Chronicle of 3 March 2009)

Science — Heart attack

French scientists investigated the effects of CB2 receptor activation in states of reduced blood supply to the heart in mice. Heart attacks were caused in the animals by interrupting blood supply for a certain time. If the animals received a synthetic cannabinoid (JWH131) that activates the CB2 receptor they presented with a decreased infarct size by protecting heart muscle cells. They had an improved heart function after three days and four weeks. (Source: Defer N, et al. FASEB J. 2009 Feb 26. [Electronic publication ahead of print])

Science — Vomiting

The inhibition of the degradation of the endocannabinoid anandamide resulted in reduced vomiting in musk shrews, which was caused by cisplatin, a substance used to treat cancer. If degradation was inhibited and additional anandamide was injected to the animals vomiting was suppressed completely. (Source: Parker LA, et al. Physiol Behav. 2009 Feb 23. [Electronic publication ahead of print])