IACM-Bulletin of March 13, 2011

Science — Cannabis extract improved symptoms in patients with refractory spasticity caused by multiple sclerosis

The effects of the cannabis extract Sativex was investigated in a large Phase III study conducted in several European countries in patients with refractory spasticity due to multiple sclerosis. The study consisted of two phases. In the first 4 weeks participants were treated with the cannabis extract in a single-blinded manner, after which those achieving an improvement in spasticity of 20 per cent or more progressed to a 12-week randomized, double-blind, placebo-controlled phase. Results had already been published previously on 11 March 2009 by the manufacturer of Sativex, the British company GW Pharmaceuticals, and thereafter in the IACM-Bulletin.

Of the 572 subjects enrolled, 272 achieved at least a 20 per cent improvement after 4 weeks and 241 were randomized. There was a highly significant difference in favour of Sativex in the reduction of spasticity. In addition spasm frequency, sleep, the global impression of change by patients and physicians were all significant in favour of Sativex. Researchers concluded that the used study design provides a method of determining the efficacy and safety of cannabinoids "in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it."

(Source: Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, Gasperini C, Pozzilli C, Cefaro L, Comi G, Rossi P, Ambler Z, Stelmasiak Z, Erdmann A, Montalban X, Klimek A, Davies P; the Sativex Spasticity Study Group. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol. 2011 Mar 1. [in press])

A Norwegian citizen suffering from post traumatic stress disorder (PTSD) and attention deficit hyperactivity disorder (ADHD) tried to import cannabis of the Dutch company Bedrocan from a Dutch pharmacy to Norway, which was however confisciated by the border police. Mr Berg wanted to try a treatment with cannabis, which is supported by his doctor.

According to an e-mail to the IACM Mr. Berg. received a letter from a juridical adviser under the Health & Social Services (Ombudsman) telling him that the Norwegian Drug Agency has confirmed to them that he did not break the law by bringing cannabis from a Dutch pharmacy to Norway, according to article 75 of the Schengen agreement between European countries. Mr. Berg is now expecting that he will get his cannabis back from the police.

(Source: Personal communication by Mr Berg of 2 March 2011)

Science — THC beneficial in the treatment of children with spasticity, pain and cancer in case reports from a university

According to case reports of the Centre for Palliative Medicine and Paediatric Pain Therapy of the University of the Saarland (Germany) THC (dronabinol) is an effective and well-tolerated medicinal drug in the treatment of different severe illnesses in children. A scientist of a university reported of experiences from the treatment of 13 children with severe disabilities and spasticity aged 7 months to 17 years as well as of about 50 cancer patients aged three months and older.

All children received a slowly increased dose. Mean dronabinol dose was 0.2 mg/kg bodyweight in children with spasticity and pain after finishing dose finding. In all children a reduction in pain, which was considerable in some of them, was observed within 48 hours after start of treatment. Efficacy with regard to spasticity set in within one to two weeks. In some patients opioid treatment could be reduced. Most cancer patients profited from an increase in appetite and weight, reduction of nausea and vomiting, as well as improved sleep and reduced anxiety. Even with long-term treatment no relevant side-effects were noted.

(Source: Gottschling S. [Cannabinoids in children] [Article in German] Cannabinoide bei Kindern. Angewandte Schmerztherapie und Palliativmedizin 2011;(1):55-57.)

News in brief

USA — Synthetic cannabinoids

The Drug Enforcement Administration (DEA) said on 1 March it was using its emergency scheduling authority to control five synthetic cannabinoids (JWH-018, JWH-073, JWH-200, CP-47,497 and cannabicyclohexanol) used in making products such as Spice. The temporary scheduling action will remain in effect for at least one year while the DEA and the United States Department of Health and Human Services further study whether these chemicals should be permanently prohibited. (Source: UPI of 1 March 2011)

Holland — Cannabis clubs

The city of Utrecht wants cannabis users to grow their own cannabis in a cooperative. However, it would be illegal, the government said. The use of cannabis is legal but the mass cultivation of cannabis plants is illegal and controlled by criminal groups. "We want to tackle this in the experiment. If you have some users grow the cannabis you remove it from the criminal and illegal scene," a representative of the city said. (Source: Reuters of 11 March 2011)

USA — Legalization

A poll by the Pew Research Center for the People and the Press shows that support for the legalization of cannabis has again increased compared to the last year. According to the poll published on 3 March voters are divided over whether the use of cannabis should be legal or not. Half (50 per cent) oppose legalization while nearly as many (45 per cent) favour legalizing cannabis. Support for legalizing cannabis is up 4 per cent since March 2010, and continuously increased over the past 40 years. Support for legalizing cannabis has never been higher. (Source: Pew Research Center for the People and the Press of 3 March 2011)

Nepalese authorities have banned the sale of cannabis during a popular Hindu festival at which holy men traditionally smoke the drug and share it with others. About 500,000 devotees attended the festival 2 March in Kathmandu at the most revered Hindu shrine in Nepal. Thousands of holy men travel to Nepal from neighbouring India every year for the festival, which generally marks the end of winter. The highlight is a bonfire at night at which devotees smoke cannabis. (Source: Associated Press of 3 March 2011)

Science — Cannabis and driving

The presence of drugs was investigated in 1714 injured drivers taken to hospital by researchers of Monash University, Victoria, Australia. Alcohol above 0.01 per cent was present in 29 per cent of drivers. The prevalence of THC was 9.8 per cent, of which 70 per cent had a blood concentration of 10 ng/ml or higher. Antidepressants were present in 9.3 per cent, benzodiazepines in 8.9 per cent. (Source: Drummer OH, et al. Forensic Sci Int. 2011 Mar 4. [in press])

Holland — Coffee shops

Researchers at Utrecht University, The Netherlands, investigated the effects of the coffee shop system in the Netherlands. Dutch coffee shop policy has become more restrictive in recent years and the number of coffee shops has decreased. Cannabis prevalence rates in the adult population are somewhat below the European average; the rate is relatively high among adolescents; and age of first use appears to be low. Compared to other European countries the use of hard drugs in both the Dutch adult and adolescent population is average to low. (Source: Monshouwer K, et al. Drug Alcohol Rev 2011;30(2):148-56.)

Science — Psychosis

A prospective population based cohort study was conducted in Germany, which included 1923 individuals from the general population, aged 14-24 years baseline. They were followed for 10 years. In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline, later cannabis use increased the risk of later incident psychotic symptoms. This risk doubled (adjusted odds ratio 1.9). Furthermore, continued use of cannabis increased the risk of persistent psychotic symptoms. Researchers concluded that "cannabis use is a risk factor for the development of incident psychotic symptoms." (Source: Kuepper R, et al. BMJ. 2011;342:d738.)

Science — Injury of the liver

According to research at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, USA, cannabidiol (CBD) reduced the consequences of reduced blood supply to the liver in a mouse model of hepatic ischemia injury. Blood supply to the liver was interrupted for this reason and then restored. CBD significantly reduced the extent of liver inflammation and cell death. This effect was not mediated by cannabinoid receptors. (Source: Mukhopadhyay P, et al. Free Radic Biol Med. 2011 Feb 26. [in press])

Science — Increased blood pressure

According to a study at Johns Hopkins University in Baltimore, USA, abrupt cessation of cannabis use resulted in a significant increase of blood pressure. Participants were 13 regular cannabis users. In 6 of them increase of blood pressure after cessation of use was substantial with mean increases of up to 23 mmHg systolic blood pressure observed. Heart rate also increased during abstinence, but this effect was not clinically significant. (Source: Vandrey R, et al. J Addict Med 2011;5(1):16-20.)

Science — Heart attack

Scientists of Hasselt University in Diepenbeek, Belgium, reviewed the literature on triggers of heart attack (myocardial infarction). The most often observed factors were traffic exposure (7.4 per cent), physical exertion (6.2 per cent), alcohol (5.0 per cent), coffee (5.0 per cent), air pollution (4.8 per cent), negative emotions (3.9 per cent), anger (3.1 per cent), heavy meal (2.7 per cent), positive emotions (2.4 per cent), sexual activity (2.2 per cent), cocaine use (0.9 per cent), use of cannabis (0.8 per cent) and respiratory infections (0.6 per cent). (Source: Nawrot TS, et al. Lancet 2011;377(9767):732-40.)

Science — Alzheimer's' disease

According to the research at the Cajal Institute in Madrid, Spain, cannabidiol (CBD) was able to modulate the function of microglia, immune cells in the brain, in a mouse model of Alzheimer's' disease. Scientists noted that "given that CBD lacks psychoactivity it may represent a novel therapeutic approach for this neurologic disease." (Source: Martin-Moreno AM, et al. Mol Pharmacol. 2011 Feb 24. [in press])

Science — Exercise

US-scientists investigated the hypothesis that exercise of moderate intensity increases the motivation to reduce cannabis use in 146 young adult current cannabis users. Exercise was associated with coping-oriented use motives. They concluded that "these findings extend previous work and offer support for the potential utility of moderate-intensity aerobic exercise for the treatment of marijuana use problems." (Source: Smits JA, et al. Am J Addict 2011;20(2):113-9.)