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IACM-Bulletin of 01 February 2009

Science: New synthetic cannabinoid tested in phase I clinical study

A new cannabinoid receptor agonist (CRA13) developed by the pharmaceutical company Novartis was tested for safety, tolerability and pharmacokinetics in a phase I clinical study with 69 healthy subjects. CRA13, as THC, binds both to CB1 and CB2 receptors. Participants were divided into seven groups of nine subjects, each one to receive one dose of increasing doses of the cannabinoid (1 to 80 mg) or placebo orally in fasted condition in the morning without later breakfast. To investigate the effect of food 6 additional subjects received 40 mg of CRA13 in fasted condition and two weeks later again after a high-fat and high-caloric breakfast.

Side effects of CRA13 were similar to those observed after the use of THC or cannabis and were dose-dependent. Maximum blood concentrations were observed about two hours after administration, also similar to results from studies with oral THC. Administration of the cannabinoid together with the meal doubled bioavailability. Authors noted that the absorption of many lipophilic compounds is enhanced by high-fat food, which was attributed to several factors including improved solubilization of the drug.

(Source: Gardin A, Kucher K, Kiese B, Appel-Dingemanse S. CRA13, a novel cannabinoid agonist: first in human pharmacokinetics and safety. Drug Metab Dispos. 2009 Jan 14. [Electronic publication ahead of print])

World: Synthetic cannabinoids find their way to the illegal drug market

Several mixtures herbs known under the brand name Spice and sold in EURope, Canada and New Zealand since around 2002 contain synthetic cannabinoids, that activate the CB1 receptor causing similar effects as THC. Even though the manufacturer officially warns against human ingestion of the "fumigation mixture" Spice, it is usually smoked. Since December 2008 three synthetic cannabinoids have been detected in these mixtures and some have been prohibited recently in several countries, including Germany. In Canada they are prohibited since they are "similar synthetic preparations" to cannabis.

On 15 December 2008, it was announced by German pharmaceutical company THC Pharm, that JWH-018 had been found as one of the active components in at least three versions of Spice. On 19 January 2009, it was announced by the University of Freiburg, Germany, that the other main active substance in Spice is an undisclosed analogue of the synthetic cannabinoid CP 47,497. Another potent synthetic cannabinoid, HU-210, has been reported to have been found in Spice seized by the US Customs & Border Protection. Since many cannabinoids can be synthesized easily it is expected that the detected substances can easily be replaced by similar substances.

More at:
en.wikipedia.org/wiki/Spice_(drug)
www.cbp.gov/xp/cgov/newsroom/news_releases/01142009_3.xml
hosted.ap.org/dynamic/stories/E/EU_GERMANY_SPICE_BAN?SITE=FLTAM&SECTION=HOME&TEMPLATE=news_generic.htm

(Sources: CBP of 14 January 2009, Associated Press of 21 January 2009, others)

News in brief

USA: California
The San Francisco Chronicle reported on 26 January that although the city approved regulations requiring medical cannabis clubs to get city permits in late 2005, few permits have been issued. The newspaper said the city has issued 10 permits to cannabis clubs, with 13 more in progress. Officials said there are currently 23 cannabis clubs in the city, compared with more than 40 when the regulatory process began in 2005. (Source: Associated Press of 26 January 2009)

USA: New Mexico
The New Mexico Department of Health has finalized regulations for issuing identification cards and for a production/distribution system for its medical cannabis program. The new guidelines specify that qualified patients may possess up to six ounces (about 170 grams) of medical cannabis (or more if authorized by their physician) and/or 16 plants (four mature, 12 immature). More at: www.health.state.nm.us/marijuana.html (Source: New Mexico Department of Health)

Science: Pruritus
In animal research scientists investigated the effect of modulation of the endocannabinoid system on scratching due to pruritus induced in mice. Inhibition of the enzyme that degradates the endocannabinoid anandamide (FAAH) resulting in an increase of anandamide concentration reduced scratching. Authors noted that "these are the first preclinical data suggesting that FAAH represents a novel target to treat pruritus without eliciting overt side effects." (Source: Schlosburg JE, et al. J Pharmacol Exp Ther. 2009 Jan 23. [Electronic publication ahead of print])

Science: Bipolar disorder
In a large study with 3459 patients suffering from bipolar disorder the effects of cannabis use on the course of disease was investigated. Over 12 months of treatment, cannabis users exhibited less compliance and higher levels of overall illness severity, mania, and psychosis compared with nonusers. (Source: van Rossum I, et al. J Nerv Ment Dis 2009;197(1):35-40)

Science: Stress
A research group from Brazil investigated the way how cannabidiol (CBD) exerts its effects. Treatment of rats with CBD reduced heart rate and anxiety in tests that caused stress. A blocker of a serotonin receptor (5-HT(1A) receptor) abolished these effects. Authors concluded "that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT(1A) receptor-mediated neurotransmission." (Source: Resstel LB, et al. Br J Pharmacol 2009;156(1):181-8)

Science: Psychosis
Swiss researchers investigated the development of psychiatric disorders in adolescents presenting subclinical hallucinations. Full remission of subclinical hallucinations occurred in over half and at least partial remission in two thirds of these patients at one-year follow-up. No effect of cannabis use was observed. Researchers concluded that "subclinical hallucinations occur across a wide range of mental states in adolescents and show high rates of remission." (Source: Simon AE, et al. Schizophr Res. 2009 Jan 21. [Electronic publication ahead of print])

Science: Heart attack
In a mouse model of decreased blood supply (ischaemia) the effect of a cannabinoid that binds to CB2 receptors was investigated. In the animals a coronary artery was ligated for 30 minutes and then perfused again with blood. Five minutes before reperfusion animals received the cannabinoid (JWH-133) by injection. It significantly reduced infarct size of the heart, which was attributed to a direct protective activity on heart cells. (Source: Montecucco F, et al. J Mol Cell Cardiol. 2009 Jan 7. [Electronic publication ahead of print])

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