IACM-Bulletin of May 28, 2006

Science — A combination of THC and prochlorperazine effective in reducing nausea and vomiting in women following breast surgery

Researchers of the University of Arkansas and the Central Arkansas Veterans Hospital System investigated the effects of 5 mg oral THC and 25 mg rectal prochlorperazine on the rate of nausea and vomiting in women following breast surgery under general anaesthesia. The rate of nausea decreased from 59 per cent to 15 per cent and the rate of vomiting from 29 per cent to 3 per cent compared to non-treated patients.

A retrospective review of 242 eligible patients, who underwent surgery between July 2001 and March 2003 was performed. 127 patients received surgery before September 2002 and did not receive a prophylaxis. 115 patients received surgery after September 2002 and were treated before surgery with oral THC (dronabinol) and rectal prochlorperazine. Data were collected from hospital records. Researchers concluded that post-operative nausea and vomiting (PONV) is a "significant problem in breast surgical patients. Preoperative treatment with dronabinol and prochlorperazine significantly reduced the number and severity of episodes of PONV."

(Source: Layeeque R, Siegel E, Kass R, Henry-Tillman RS, Colvert M, Mancino A, Klimberg VS. Prevention of nausea and vomiting following breast surgery. Am J Surg 2006;191(6):767-72)

Science — No association between lung cancer and cannabis smoking in large study

A large study on the association between cannabis smoking and lung cancer already presented at the 2005 Meeting of the International Cannabinoid Research Society was now also presented at The American Thoracic Society Conference in San Diego and received much media interest. The study with 611 lung cancer patients and 1,040 healthy controls as well as 601 patients with cancer in the head or neck region found no increased risk for lung cancer even after heavy long-term use of cannabis.

"We expected that we would find that a history of heavy marijuana use - more than 500 to 1,000 uses - would increase the risk of cancer from several years to decades after exposure to marijuana," lead researcher Dr. Donald Tashkin of the University of California, Los Angeles, said in the Scientific American. But the scientists found that even those who smoked more than 20,000 cannabis cigarettes in their life did not have an increased risk of lung cancer.

(Sources: Scientific American of 24 May 2006; Morgenstern H, et al. Marijuana use and cancers of the lung and upper aerodigestive tract: results of a case-control study. Presentation at the ICRS Conference on Cannabinoids, 24-27 June 2005, Clearwater, USA)

Science — Cannabidiol reduces the development of diabetes in an animal study

Researchers of the Hadassah University Hospital of Jerusalem investigated the effects of the plant cannabinoid cannabidiol (CBD) on the development of diabetes in mice, which develop diabetes due to genetic causes. So-called NOD mice develop insulitis within 4 to 5 weeks of age followed by diabetes within a median of 14 weeks. Insulitis is an inflammation of the cells in the pancreas that produce insulin, and diabetes is a result of a destruction of these cells.

NOD mice aged 6 to 12 weeks that were treated with 10 to 20 injections of CBD (5 mg per kilogram body weight) presented with a significantly reduced incidence of diabetes of 30 per cent compared to 86 per cent in untreated control mice. In addition, in the mice that developed diabetes in the treated group disease onset was a significantly delayed. Blood levels of two cytokines that promote inflammation, IFN-gamma and TFN-alpha, are usually increased in NOD mice. A treatment with CBD caused a significant reduction (more than 70 per cent) in levels of both cytokines. In another experiment CBD-treated mice were observed for 26 weeks. While the 5 control mice all developed diabetes, 3 of 5 of the CBD-treated mice remained diabetes-free at 26 weeks.

Researchers concluded that confirmation of the observed immunomodulatory effects of CBD "may lead to the clinical application of this agent in the prevention of type 1 diabetes" and possibly other autoimmune diseases. They note that many patients diagnosed with type 1 diabetes have sufficient residual cells that produce insulin at the time of diagnosis, and may be candidates for immunomodulation therapy.

(Source: Weiss L, Zeira M, Reich S, Har-Noy M, Mechoulam R, Slavin S, Gallily R. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 2006;39(2):143-51)

Economy — Nabilone again available in the USA

Seventeen years after it was withdrawn from U.S. markets nabilone, a synthetic derivative of THC, is going back on sale as a prescription treatment for nausea and vomiting associated with chemotherapy, its manufacturer said on 16 May. Nabilone is marketed under the trade name Cesamet by Valeant Pharmaceuticals International, a company based in Costa Mesa, California. Valeant bought the drug from Eli Lilly in 2004 and currently sells it in Canada.

Eli Lilly originally received approval from the American medicines control agency FDA (Food and Drug Administration) for nabilone in 1985 but withdrew it from the market in 1989, Valeant said. The drug will compete with dronabinol (THC), the main active compound of cannabis, which is marketed under the trade name of Marinol, by Belgium-based Solvay Pharmaceuticals. Dronabinol, which is the international non-proprietary name (INN) of this cannabis compound, is erroneously often called synthetic THC because dronabinol in Marinol is produced synthetically, and Marinol was the first dronabinol product available in pharmacies. Side effects of nabilone are similar to those of dronabinol.

(Sources: Press release of Valeant Pharmaceuticals International of 16 May 2006, Associated Press of 16 May 2006)

News in brief

Switzerland — Bern

The city council of the Swiss capital Bern decided to start a pilot project on the controlled sale of cannabis, although the federal government and the canton oppose it. It is intended that in the project cannabis will be allowed to be sold if certain rules are followed, such as prohibition of advertisement, no sale to minors and maximum amount of sale per day. A measure in support of a controlled sale of cannabis failed last year in the Swiss Parliament. (Source: 20min.ch of 23 May 2006)

Italy — Law changes

On 9 May a law introduced by the old government that increased sanctions for the possession of small amounts of drugs went into effect. However, four new bills proposed after the election of the new government in May would depenalize the possession of cannabis and improve the possibilities of therapeutic uses. (Sources: dire of 5 and 8 May 2006)

Science — Liver fibrosis

French researchers reported that treatment with a CB1 receptor antagonist decreased the wound-healing response to acute liver injury in mice and inhibited progression of fibrosis in three models of chronic liver injury. They concluded that "our study shows that CB1 receptor antagonists hold promise for the treatment of liver fibrosis." (Source: Teixeira-Clerc F, et al. Nat Med. 2006 May 21; [Electronic publication ahead of print])

Science — Depression

Canadian researchers found that the cannabinoid system is involved in the ability of long-term tricyclic antidepressant treatment to suppress stress-induced increase of corticosterone levels in mice. Three-week administration of the tricyclic antidepressant desipramine resulted in a significant increase in the density of CB1 receptors in certain brain areas (hippocampus and hypothalamus) without significantly altering endocannabinoid levels. The reduction of stress-induced corticosterone secretion by the antidepressant was blocked by a CB1 receptor antagonist. (Source: Hill MN, et al. Neuropsychopharmacology. 2006 May 10; [Electronic Publication ahead of print])