IACM-Bulletin of April 22, 2012

Science/Human — The cannabis extract Sativex improves cancer pain in large clinical study

Patients with advanced cancer, who already receive opioids for pain treatment, may profit from additional cannabis. This is the result of a clinical study with 360 patients, who either received the cannabis extract Sativex or a placebo for 5 weeks in addition to their current opioid medication. Researchers intended to evaluate the analgesic efficacy and safety of the extract. Patients received either 1-4 sprays, 6-10 sprays or 11-16 sprays of Sativex per day. Each spray contains 2.7 mg THC and 2.5 mg CBD. At baseline patients in the Sativex group rated their pain intensity as 5.8 points and in the placebo group as 5.7 points on a scale from "0 = no pain" to "10 = pain as bad as you can imagine."

263 patients completed the study. The number of patients with a 30 per cent or greater reduction in the mean pain scores for average pain during the last 3 days of the study was not different between the placebo and the Sativex group. However, there was a treatment effect in the two lower dose groups. In the low-dose group (1-4 sprays) the pain scores were reduced by 1.5 points, in the medium-dose group (6-10 sprays) there was a 1.1 point reduction, and in the placebo group there was a difference of 0.75 points compared to the baseline score. There was no difference between the high-dose group and the placebo group. Adverse events were dose-related and only the high-dose group compared unfavourably with placebo. Authors concluded that Sativex "may be a useful add-on analgesic for patients with opioid refractory cancer pain." Authors also noted several limitations due to the design, which allowed no individual dose titration of cannabis and no dose adjustment of the opioids. "A controlled trial that incorporates dose individualisation within a large range for all patients will be needed to expand the current findings," they wrote in their article for the Journal of Pain.

(Source: Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, McQuade R, Wright S, Fallon MT. Nabiximols for Opioid-Treated Cancer Patients With Poorly-Controlled Chronic Pain: A Randomized, Placebo-Controlled, Graded-Dose Trial. J Pain. 2012 Apr 5. [in press])

News in brief

USA — New Jersey and Washington D.C. will get cannabis dispensaries

On 16 April New Jersey granted its first permit for a facility to immediately begin growing medical cannabis. Cannabis could be available to state residents with chronic diseases by midsummer, said Donna Leusner, spokeswoman for the Department of Health. Washington D.C granted licenses to six medical cannabis cultivators on 30 March. With this action, the District is finally moving toward implementing the medical cannabis program that was approved in a 1998 vote. (Sources: Washington Post of 6 April 2012, Wall Street Journal of 17 April 2012)

Science/Animal — Cannabinoids reduce negative effects of amyloid-beta on nerve cells

According to research at a University of Tehran, Iran, the activation of CB1 receptors reduced the effects of amyloid-beta on nerve cells of the hippocampus and prefrontal cortex. The injection of amyloid-beta had several negative effects on the animals including an impairment of recall capability. The treatment with a cannabinoid that binds to the CB1 receptor preserved almost the normal properties of the affected nerve cells. Amyloid-beta is a substance, which is highly increased in the nerve cells of patients suffering from Alzheimer's disease. (Source: Haghani M, et al. Cell Physiol Biochem 2012;29(3-4):391-406.)

Science/Human — Cannabis use increases risk for chronic bronchitis

According to a prospective long-term study with 299 participants at the University of California in Los Angeles, USA, both tobacco and cannabis smoking increase the risk for heaving chronic bronchitis. If participants stopped smoking they were no more likely to have chronic respiratory symptoms than never smokers. Authors concluded that "these findings demonstrate the benefit of marijuana smoking cessation in resolving pre-existing symptoms of chronic bronchitis." (Source: Tashkin DP, et al. COPD. 2012 Apr 12. [in press])

Science/Animal — Cannabinoids block activation of mediator of inflammation

Research at the Pennington Biomedical Research Center in Baton Rouge, USA, shows that cannabinoids, which activate the CB1 receptor, reduce the activation of tumour necrosis factor (TNF) in the brainstem. The pro-inflammatory cytokine TNF is released in significant quantities by the activated immune system in response to infection, leukaemia, autoimmune disorders, and radiation sickness. Nausea, emesis, and anorexia are common features of these disorders. Authors concluded that "these results help to explain the effectiveness of cannabinoids in blocking the malaise generated by TNF-releasing disease processes." (Source: Rogers RC, et al. J Neurosci 2012;32(15):5237-41.)

Science/Animal — Cannabidiol improves symptoms in a model of psychosis

Scientists at Monash University in Melbourne, Australia, investigated the effects of CBD (cannabidiol) and the anti-psychotic drug clozapine in a rat model of psychosis. A treatment with CBD normalized social behaviour. (Source: Gururajan A, et al. J Psychopharmacol. 2012 Apr 9. [in press])

Science/Animal — Ajulemic acid improves systemic sclerosis

Systemic sclerosis is an autoimmune disease, which is characterized by deposition of collagen in the skin and internal organs. Research by Italian scientists shows, that the synthetic cannabinoid ajulemic acid reduces the progression of fibrosis in a mouse model of systemic sclerosis. Experimental fibrosis (sclerosis) was induced in mice by a chemical (bleomycin), which was prevented by pre-treatment with ajulemic acid. If the disease was already present its progression was slowed. Authors concluded that "since therapeutic doses of AjA are well tolerated in humans, it is suggested that AjA is an interesting molecule targeting fibrosis in patients with scleroderma." (Source: Gonzalez EG, et al. Ann Rheum Dis. 2012 Apr 4. [in press])

Science/Human — More gray matter of the brain in schizophrenics with cannabis use

According to research at the Universities of Hamburg and Cologne, Germany, patients with schizophrenia, who use cannabis have a higher density of the brain's gray matter compared to patients with schizophrenia and no cannabis use. 30 first episode schizophrenia patients with cannabis use were compared with 24 patients without cannabis use. Cannabis users presented also with less severe cognitive impairment. Researchers concluded that "results may support the hypothesis of a lower biological vulnerability in at least one subgroup of SCH+CAN patients." (Source: Schnell T, et al. Schizophr Res. 2012 Apr 3. [in press])

Science/Animal — FAAH inhibitor increases endocannabinoid level in the brain

Scientists of an Italian pharmaceutical company (Sigma-tau Industrie Farmaceutiche Riunite S.p.A.) investigated the effects of an inhibitor of fatty acid amide hydrolase (FAAH) on the concentrations of several endocannabinoids in the brain. ST4070 increased the brain levels of anandamide and palmitoylethanolamine, but not that of 2-arachidonoylglycerol in mice. In addition it decreased neuropathic pain. FAAH is an enzyme, which catalyses the degradation of endocannabinoids. (Source: Caprioli A, et al. J Pharmacol Exp Ther. 2012 Apr 18. [in press])