IACM-Bulletin of December 11, 2005

Science — Cream with endocannabinoids effective in the treatment of pruritus due to kidney disease

Researchers of the University of Wroclaw, Poland, investigated the effects of an ointment with structured physiological lipids and endocannabinoids in 21 patients with pruritus due to end-stage failure of kidney function. So-called uremic pruritus is still a common symptom in patients with end-stage renal failure. However, there is no effective treatment for this condition. All patients applied the tested cream twice daily for a period of three weeks. Global pruritus and dry skin were examined before the trial, on study visits at weekly intervals, and two weeks after completion of the study.

After 3-week therapy pruritus was completely eliminated in 8 patients. Dry skin was significantly improved. Researchers noted that "it is very probable that the observed decrease of pruritus with the test product therapy was not only the result of dry skin improvement but that the addition of endocannabinoids may have also played a role."

(Source: Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat 2005;13(2):97-103.)

Science — Drivers with THC in their blood have only a small increased risk to cause an accident

Researchers of the French National Institute for Transport and Safety Research (INRETS) and other French research institutions presented results of the largest ever conducted study on cannabis and driving in the British Medical Journal. The government funded study confirms results of earlier investigations that found no or only a small increase in the risk of causing an accident following the use of cannabis. The risk increased with increased THC blood concentrations as already observed in an Australian study published in 2004.

The case-control study included 10,748 drivers of different motor vehicles who were involved in fatal accidents in France between October 2001 to September 2003. Researchers compared the 6,766 drivers considered at fault in their crash (cases) with 3,006 drivers selected from the 3,982 other drivers (controls). 681 drivers had a THC blood concentration of above 1 ng/ml, of whom 42 per cent had also a blood alcohol concentration of above 0.05 per cent. 60.5 per cent of THC positive drivers were under the age of 25 compared to 24.5 per cent in the whole analyzed group of 9,772 drivers.

Detection of THC at any dose was associated with an increases risk of responsibility of 3.3. A THC blood concentration of below 1 ng/ml was associated with a responsibility rate of 2.2, which increased to 4.7 above a THC blood concentration of 5 ng/ml. If the additional presence of alcohol above 0.05 per cent was taken into account the risk for THC positive drivers decreased from 3.3 to 2.4 and if age of the drivers and other confounders were taken into account the risk further decreased to 1.8 for the THC positive group. After adjustment for all confounders a THC blood concentration below 1 ng/ml was associated with an increased risk of 1.6, which increased to 2.1 with a THC blood concentration above 5 ng/ml. Age below 25 was associated with an increased risk of 1.9. The adjusted risk for alcohol above 0.05 per cent in blood was 8.5. From their data researchers attributed 2.5 per cent of all fatal accidents to cannabis and 29 per cent to alcohol.

In a letter to the British Medical Journal Dr. Franjo Grotenhermen of the German nova-Institut wrote. "The presentation of the results in the abstract is somewhat misleading. The figures for the unadjusted odds ratios suggest a more than threefold risk increase for all THC positive drivers and a more than twofold increase even for drivers with a THC blood concentration of less than 1 ng/ml. However, closer review of the results shows that two other factors contributed to the higher accident risk, i.e., alcohol consumption and the younger age of the THC positive drivers, compared to the whole cohort. About 42 per cent of THC positive drivers also tested positive for alcohol, with a blood alcohol concentration (BAC) of 0.05 percent. Even an BAC below 0.05 per cent was reported to be associated with an odds ratio of 2.7 in the study, but no data were given on the percentage of THC positive drivers with an additional BAC < 0.05 per cent. Thus, no information is available on drivers who had only THC in their blood and on their risk of causing an accident, which has been used as a standard way of reporting in previous studies."

(Source: Laumon B, Gadegbeku B, Martin JL, Biecheler MB. Cannabis intoxication and fatal road crashes in France: population based case-control study. BMJ 2005 Dec 2 [electronic publication ahead of print])

News in brief

Italy — Clinical study with Sativex in MS

A clinical study with the cannabis extract Sativex in patients with multiple sclerosis has started at the University of Rome. It is a 10-week placebo-controlled trial that investigates the patterns of brain activation associated with movement in 20 MS patients suffering from lower limb spasticity. The study will also investigate levels of spasticity and changes of excitability in certain brain areas including areas responsible for movements. Investigations of brain activations are conducted by Functional Magnetic Resonance Imaging. FMRI is a technique for determining which parts of the brain are activated by different types of physical sensation or activity, such as sight, sound or the movement of a subject's fingers. (Source: http://www.clinicaltrials.gov/ct/show/nct00202423)

Italy — Clinical study with THC in pain

80 patients with cancer will participate in a clinical trial with THC (Marinol) for the treatment of pain. This was announced by Dr. Rosanna Cerbo, professor of neurology at the University of Rome. She presented the study protocol at the meeting "Cannabinoids and pain", held on 28 October in Milan. Half of the patients will receive THC and the other half THC and morphine. The study protocol is available in the Proceedings of the meeting "Cannabinoidi e dolore: attualità e prospettive" at http://medicalcannabis.it. (Source: Press release by ACT of 9 November 2005)

Spain — SEIC Meeting

The Spanish Association for the Investigation of Cannabinoids (SEIC, Sociedad Española de Investigación Sobre Cannabinoides) held its 6th annual meeting on 25 to 27 November in Barcelona. Besides a presentation of basic research there was a round table on the therapeutic use of cannabinoids including a presentation of Sativex, a cannabis extract produced by the British company GW Pharmaceuticals, which will be provided to a limited number of patients in Spain. The abstract book of the meeting is available on the website at http://www.ucm.es/info/seic-web/libro2005.pdf. (Source: Personal communication by Ricardo Navarrete-Varo)

Holland — Legalisation

A broad majority in the Dutch Parliament has presented a measure that would legalized the cultivation of cannabis. The measure is intended to reduce criminal actions surrounding cannabis production. In addition taxes could be taken in. The measure says that in a pilot programme the plants shall be cultivated under public control near the town of Maastricht. Coffee-shops that sell the drug legally would have to inform their customers about the origin of the drug, its chemical composition and the dangers of cannabis use. (Source: Der Spiegel of 2 December 2005)

USA — Time Magazine

In an article entitled "The year in medicine from A to Z" the Time Magazine noted: "Marijuana: Research into the analgesic and anti-inflammatory effects of cannabis continued to bolster the case for the medicinal use of marijuana, making the "patient pot laws" that have passed in 11 states seem less like a social movement than a legitimate medical trend." (Source: Time Magazine of 5 December 2005)

USA — Seattle

In 2003 the citizens of Seattle passed a measure that made arrests of adult cannabis users the lowest priority for law enforcement agencies in the city. An evaluation of the law found that arrests for cannabis use decreased but the use of cannabis did not increase. Similar measures followed in Oakland, Denver, and Columbia, Missouri. (Source: The Stranger of 7 December 2005)

Elías Miguel Moreno Brizuela, president of the Senate’s Health and Social Security Commission, announced that the Commission will discuss the legalisation of cannabis for therapeutic use. (Source: Milenio of 4 November 2005)

Science — Cannabis use by adolescents

Researchers of the Albert Einstein College of Medicine in New York said on 30 November that heavy use of cannabis by adolescents may damage a key brain pathway associated with language development. Brain scans revealed microscopic abnormalities in a region of the brain that governs higher aspects of language and listening functions in adolescents who are heavy marijuana smokers. Similar damage was found in the brains of cannabis smokers and schizophrenics studied. "These findings suggest that in addition to interfering with normal brain development, heavy marijuana use in adolescents may also lead to an earlier onset of schizophrenia in individuals who are genetically predisposed to the disorder," said psychiatry professor Sanjiv Kumra. (Source: Reuters of 30 November 2005)

Science — Pharmacokinetics of THC and CBD

German researchers investigated the pharmacokinetic interactions of THC and CBD in healthy subjects. 24 volunteers received 10 mg THC, a cannabis extract with 10 mg THC and 5.4 mg CBD, and placebo in weekly intervals. The blood concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and of CBD were analysed up to 24 hours after the intake. Researchers observed some evidence of an inhibition of hydroxylation of THC to 11-OH-THC by CBD. However, the effect of CBD on THC was small in comparison to the variability caused by other factors. (Source: Nadulski T, et al. Ther Drug Monit 2005;27(6):799-810.)