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IACM-Bulletin of 05 August 2007

Science/UK: A widely cited new review supports findings from earlier studies that cannabis use may be associated with an increased risk of psychosis

On 28 July the Lancet published a review that a comment called "the most comprehensive meta-analysis to date of a possible causal relation between cannabis use and psychotic and affective illness later in life." A major reason, why this review attracts much attention is the consideration of the new British Government and the new Prime Minister Gordon Brown to reclassify cannabis under British narcotics law from a class C (non-arrestable drug) to a class B drug, so that possession of cannabis again would carry the risk of being arrested. In 2004 cannabis was downgraded from a class B to a class C drug.

In their new review of seven longitudinal studies, Dr. Theresa Moore of the University of Bristol, UK and her colleagues found that individuals who had ever used cannabis had an increased risk of psychosis or psychotic symptoms of 41 per cent compared to individuals who had never used cannabis. Frequent cannabis users had twice the risk of non-users (odds ratio: 2.09), as suggested in earlier reviews. Results for an association between cannabis use and depression, suicidal thoughts, and anxiety were less consistent.

Researchers noted that these studies do not allow positive determination of whether the use of cannabis causes psychosis but they stated: "The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life." In an editorial the Lancet wrote: "In 1995 we began a Lancet editorial with the since much-quoted words: 'The smoking of cannabis, even long-term is not harmful to health.' Research published since 1995 including Moore's systematic review in this issue, leads us now to conclude that cannabis use could increase the risk of psychotic illness."

Recently, several British politicians have outed themselves as previous users of cannabis and demonstrated their contrition. It would be considered an absurd joke if, in analogy, politicians would have committed to alcohol abstinence - to set a good example for adolescents and because of the association between alcohol use and cardiovascular disease, liver disease, malignant tumours and psychiatric conditions such as depression, mania, phobias, generalized anxiety disorder, personality disorders, schizophrenia, and suicide. Such a commitment and the idea of alcohol prohibition would be considered as ignorance with regard to the rules of international drug policy and the impact on sales rates of Scotch whiskey. General prohibition of alcohol is not an option, simply because it would promote the development of criminal structures, reduce tax revenues, deter the police from more important tasks and increase the health implications of alcohol use due to a lack of quality control and contamination. All these undesirable side effects of prohibition are already well established for cannabis.

The entire article, the comment by Nordentoft & Hjorthøj and the editorial are available for download at:

(Source: Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007;370(9584):319-28.)

Europe: Withdrawal of current regulatory application for Sativex

On 20 July the British company GW Pharmaceuticals announced that it has withdrawn its current regulatory application for Sativex in EURope for the treatment of spasticity in patients with multiple sclerosis. It expects to resubmit an application for approval either for spasticity or for neuropathic pain in MS in 2008. This decision followed discussions with regulatory authorities.

In September 2006, GW filed an application for Sativex under the decentralised procedure in four EURopean countries (UK, Spain, Denmark, Netherlands). So far, GW has been able to resolve most of the questions raised by the regulators during this process except one, which requires the conduction of an additional study. The current regulatory application process has confirmed that quality and safety data are already sufficient to support a marketing authorisation of Sativex. The regulators have also confirmed that existing efficacy data provide statistically significant evidence and “could in principle lead to a positive risk benefit conclusion”.

In addition, the regulators wish however to be able to identify patients, which are effectively treated by Sativex ("responders"), in the first 4 weeks of treatment and to confirm that the improvements gained by such responders over a further 12 week period is significantly greater than placebo.

More at: www.gwpharm.com

(Source: Press release by GW Pharmaceuticals of 20 July 2007)

Science: With the use of cannabis tea only a small proportion of THC in the cannabis is ingested

The users of medicinal cannabis in The Netherlands are advised by the Office of Medicinal Cannabis to prepare cannabis tea as follows: "add 1.0 g of cannabis to 1.0 L of bOILing water and let simmer for 15 min. Filter out solid parts by using a common tea-sieve. Tea can be consumed immediately, or stored in a closed bottle in a refrigerator for up to 5 days."

Researchers of the University of Leiden investigated the cannabinoid composition of this tea. They found that tea prepared with different batches of cannabis with an overall THC concentration (phenolic THC + THC acid) of 19.7 per cent showed only a moderate variation in THC concentrations of 15 per cent. The mean concentration of THC was 10 mg per litre and of THC acid (THCA) 43 mg/L. In the plant THC is mainly present as THCA and is converted into the psychotropic THC upon heating (baking, smoking, bOILing). Since with cooking of water only a relatively low temperature of 100 degrees Celsius is reached only a small part of THCA was transformed into THC, resulting in an availability of only about 5 per cent phenolic THC of the whole THC (10 mg of 197 mg THC acid + THC). The authors also found, that the THC concentration rapidly declined during storage, which was largely prevented by the addition of coffee creamer powder.

(Source: Hazekamp A, Bastola K, Rashidi H, Bender J, Verpoorte R. Cannabis tea revisited: A systematic evaluation of the cannabinoid composition of cannabis tea. J Ethnopharmacol 2007 May 24; [Electronic publication ahead of print])

News in brief

Science: THC and Kaposi's sarcoma
In cell experiments scientists of the Harvard University in Boston, USA, found that the presence of THC in low concentrations, which are found in medical users of THC and cannabis, increased the infection with Kaposi's sarcoma-associated herpesvirus (KSHV) in endothelial cells. THC, in a dose-dependent manner, also promoted other steps that lead to the development of Kaposi's sarcoma, a type of cancer mainly found in AIDS patients. Researchers concluded that "use of cannabinoids may place individuals at greater risk for the development and progression of Kaposi's sarcoma." They point out that further epidemiological studies and clinical research are needed to clarify the importance and safety of THC. (Source: Zhang X, et al. Cancer Res 2007;67:7230-7.)

Science: Withdrawal
In a study with 12 participants, who used both cannabis and tobacco, withdrawal symptoms were investigated. Researchers found that "overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude" in 5-day periods of abstinence from either cannabis or tobacco. Withdrawal after abstinence from both drugs was more severe than for each substance alone. Substantial differences were noted between the 12 subjects. (Source: Vandrey RG, et al. Drug Alcohol Depend 2007 Jul 21; [Electronic publication ahead of print])

Science: Multiple sclerosis
The endocannabinoid system was found to be dysregulated in multiple sclerosis. The concentration of anandamide was increased in the cerebrospinal fluid and lymphocytes (a kind of white blood cells) of MS patients. The higher concentrations in lymphocytes were associated with an increased synthesis and reduced degradation of anandamide. These alterations may be regarded as an attempt of the body to counteract the disease. (Source: Centonze D, et al. Brain 2007 Jul 11; [Electronic publication ahead of print])

Holland: Coffee-shops
In the recent past the number of articles increases, according to which there are efforts to end the liberal cannabis policy in the Netherlands. For example, minimum distances between coffee-shops and schools are increased in some cities, so that many coffee-shops have to close. The conservative Prime Minister Jan Peter Balkenende has made it clear already several years ago, that he does not want to tolerate the sales of the soft drug any longer and wants to end it. Since he governs the number of coffee-shops decreased by one third to currently about 750. (Source: Die Presse of 4 June 2007)

Science: Bladder over-activity
Bladder over-activity is often observed in patients with spinal cord injury and multiple sclerosis. In an animal study with rats the synthetic cannabinoid ajulemic acid (IP-751) reduced this over-activity. This effect was blocked by a CB1 receptor antagonist, which indicates that it was at least in part mediated by the CB1 receptor. (Source: Hiragata S, et al. Urology 2007;70(1):202-8.)

Science: Smoking
Scientists from New Zealand reported that one cannabis cigarette was as harmful as between 2.5 and 6 tobacco cigarettes in reducing the function of the large airways. In contrast, cannabis smoking was rarely associated with emphysema. (Source: Aldington S, et al. Thorax 2007 Jul 31; [Electronic publication ahead of print])

Switzerland: Bern
In May 2006 the city council of the Swiss capital Bern decided to start a pilot project on the controlled sale of cannabis. This project was withdrawn now, after the canton spoke out against such a project. (Source: 20min.ch of 14 June 2007, www.20min.ch/news/bern/story/26021725)

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