IACM-Bulletin of October 16, 2005

Science — Cannabinoids may promote the development of new brain cells

According to animal research at the University of Saskatchewan, Canada, cannabinoids that bind to the CB1 receptor promote the development of new nerve cells in the hippocampus, a brain region that is very important for memory and behaviour. This cannabinoid effect may decrease anxiety and depression.

Scientists used the synthetic cannabinoid HU210 that acts similar to THC on CB1 receptors in the brain. Chronic, but not acute treatment with this cannabinoid promoted nerve cell proliferation in the hippocampus of adult rats and exerted anxiolytic- and antidepressant-like effects.

Other illegal and legal drugs, including opiates, alcohol, nicotine and cocaine, have been shown to suppress the formation of new brain cells when used chronically, but the effect of cannabis on that process was uncertain. Cannabis appears "to be the only illicit drug whose capacity to produce increased ... neurons is positively correlated with its (anti-anxiety) and anti-depressant-like effects," Dr. Xia Zhang and his colleagues wrote in an article for the November issue of the Journal of Clinical Investigation, which was already posted online on 13 October.

(Sources: Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, Zhang X. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest. 2005 Oct 13 [Electronic publication ahead of print]; United Press International of 13 October 2005)

Science — Mice without CB1 receptors show accelerated cognitive impairment

Researchers of the University of Bonn demonstrated that young mice (6-7 weeks) with a genetic deletion of the cannabinoid-1 receptor performed as well as normal mice, or often better, in a number of learning and memory tasks. In contrast, the performance of older mice (3-5 months) lacking CB1 receptors was much worse than that those of the normal animals with the same age. In most tests, these mice performed at the same level as old animals (14-17 months), suggesting that the age-related decline in cognitive performance is accelerated in the absence of CB1 receptors. This rapid decline in CB1-deficient animals was accompanied by a loss of nerve cells in the hippocampus.

"Our results suggest that the abscence of CB1 receptors results in an accelerated decrease of cognitive functions," lead researcher Dr. Andreas Zimmer said. He noted that these results may have consequences for the medical use of CB1 receptor antagonists if used long-term.

(Sources: Bilkei-Gorzo A, Racz I, Valverde O, Otto M, Michel K, Sarstre M, Zimmer A. Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. Proc Natl Acad Sci U S A 2005 Oct 12; [Electronic publication ahead of print]; www.innovations-report.de of 12 October 2005; www.heise.de of 15 October 2005)

Australia — Survey on cannabis for medical purposes

Researchers of the University of New South Wales conducted a questionnaire survey on the medical use of cannabis. Data were available for 128 participants. Long term and regular medical cannabis use was frequently reported for multiple medical conditions including chronic pain (57 per cent), depression (56 per cent), arthritis (35 per cent), persistent nausea (27 per cent) and weight loss (26 per cent).

Cannabis was perceived to provide "great relief" overall (86 per cent), and substantial relief of specific symptoms such as pain, nausea and insomnia. It was also typically perceived as superior to other medications in terms of undesirable effects, and the extent of relief provided. However, nearly one half (41 per cent) experienced conditions or symptoms that did not improve with the use of cannabis. Issues related to the illegality of the drug caused the most concerns. Participants reported strong support for their use from their physicians and their family.

(Source: Swift W, Gates P, Dillon P. Survey of Australians using cannabis for medical purposes. Harm Reduct J 2005;2(1):18.)

Science France — Largest study ever conducted on cannabis and driving found only low increased accident risk for cannabis

Drivers under the influence of cannabis are far less likely to be culpable in traffic accidents than drunk drivers. According to the newspaper "Libération" the results of an epidemiological study with approximately 8,000 accidents will be published in several weeks in the British Medical Journal.

Researchers at the French National Institute for Research on Transportation and Safety found that alcohol intoxication and speeding were nearly ten times more likely to be an attributing factor in traffic fatalities than the use of cannabis. Overall, researchers estimated that cannabis' psychomotor impairment was similar to that exhibited by drivers with blood alcohol concentrations (BAC) ranging from 0.02 to 0.05 per cent. The relative risk for causing a fatal accident was 1.8-2.2 for cannabis, similar to that for alcohol below a BAC of 0.05. It was about 20 for alcohol above a BAC of 0.05 and speeding.

The study results have been provoking the greatest embarrassment among government officials since they always claimed that "drugs behind the wheel are responsible for more deaths than

speeding." Under French law, drivers who test positive for even trace levels of THC in their blood face up to two years in prison.

(Source: Libération of 3 October 2005)

News in brief

Canada — Nausea in pregnancy

In a survey by several Canadian institutions, including the Vancouver Island Compassion Society and the University of Vancouver 92 per cent of pregnant users who suffered from nausea and vomiting reported relief from cannabis. The survey will be published by the Journal of Complementary Therapies in Clinical Practice, likely in 2006. (Source: The Province of 6 October 2005)

Science — Osteoporosis

Researchers of the University of Bonn demonstrated that the gene that encodes the CB2 receptor is associated with osteoporosis. They analyzed the genes for the CB1 and the CB2 receptor in postmenopausal women with osteoporosis. Compared with a control group the scientists found more often a certain variant of the CB2 receptor gene in patients with osteoporosis. They conclude that these results "demonstrate a role for the peripherally expressed CB2-receptor in the etiology of osteoporosis." (Source: Karsak M, et al. Hum Mol Genet. 2005 Oct 4; [Electronic publication ahead of print])

Science — Amyotrophic lateral sclerosis

In a mouse model of amyotrophic lateral sclerosis (ALS) the application of cannabinol (CBN) significantly delays disease onset while survival was not affected. Genetically modified mice, which develop a disease that resembles ALS, received CBN over a period of up to twelve weeks which delayed disease onset by more than two weeks. (Source: Weydt P, et al. Amyotroph Lateral Scler Other Motor Neuron Disord 2005;6(3):182-4)

Science — Haloperidol and CB1 receptors

In animal studies treatment with haloperidol resulted in elevated binding levels of a synthetic cannabinoid in certain brain regions (striatum and substantia nigra). These increased binding levels were normalized at 1-4 weeks after termination of haloperidol treatment. Authors note that these "results help to elucidate the underlying biochemical mechanism of CB(1) receptor supersensitivity after haloperidol treatment." (Source: Andersson M, et al. J Neurosci Res 2005;82(2):264-72)