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IACM-Bulletin of October 7, 2012

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Science/Human — Cannabis affects people differently and this can be seen in images of brain activity

In a clinical study with 21 healthy men, who were given 10 mg oral THC, some participants reacted with transient minor psychotic symptoms and the others not. And this difference was associated with differences in brain activity shown by brain imaging. This is the result of a placebo controlled study at the Institute of Psychiatry of King's College London, UK, under the guidance of Professor Philip McGuire, head of the Department of Psychosis Studies of the institute. The sample was subdivided on the basis of a scale used to measure the intensity of so-called “positive” symptoms in schizophrenics following administration of THC. There were 11 participants with transient psychotic symptoms (changes in perception, feelings of grandiosity, etc.) and 10 participants without such symptoms.

Both groups showed differential activation in certain brain regions (left parahippocampal gyrus, left and right middle temporal gyri and in the right cerebellum). In these regions, THC had opposite effects on activation relative to placebo in the two groups. The transient psychotic subjects also showed less activation than the other group in the right middle temporal gyrus and cerebellum, independent of the effects of THC. Authors concluded “that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.”

Atakan Z, Bhattacharyya S, Allen P, Martín-Santos R, Crippa JA, Borgwardt SJ, Fusar-Poli P, Seal M, Sallis H, Stahl D, Zuardi AW, Rubia K, McGuire P. Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol: a functional magnetic resonance imaging study with healthy volunteers. Psychol Med. 2012 Oct 1:1-13. [in press]

Science/Human — The risk for the development of anxiety disorders may depend on certain genetic variants of the cannabinoid-1 receptor

The ability to extinguish fearful experiences depends on the genetic variability of the CB1 receptor. This is the result of research with 150 healthy subjects at the Department of Experimental Psychology & Psychopharmacology of Utrecht University in The Netherlands. Failure to extinguish fear can lead to persevering anxiety and has been postulated as an important mechanism in the development of anxiety disorders, such as posttraumatic stress disorder. Participants underwent a fear conditioning and extinction procedure in a virtual reality environment. Fear conditioning is a form of learning in which an aversive stimulus (e.g. an electrical shock) is associated with a particular neutral stimulus (e.g., a tone), resulting in the expression of fear responses to the originally neutral stimulus.

Acquisition and expression of conditioned fear did not differ between participants with different genetic variants of the cannabinoid-1 receptor. However, extinction of fear was absent in 51 participants with a certain genetic variant. Authors concluded that these results suggest “involvement of the human endocannabinoid system in fear extinction. Implications are that genetic variability in this system may underlie individual differences in anxiety, rendering cannabinoid receptor 1 a potential target for novel pharmacological treatments of anxiety disorders.”

Heitland I, Klumpers F, Oosting RS, Evers DJ, Leon Kenemans J, Baas JM. Failure to extinguish fear and genetic variability in the human cannabinoid receptor 1. Transl Psychiatry. 2012 Sep 25;2:e162.

News in brief

USA — Los Angeles City Council rescinds ban on medical cannabis dispensaries

The Los Angeles City Council voted to rescind a newly enacted ban on medical cannabis shops, allowing the city to avoid a referendum next year that some officials said would likely succeed in reversing the prohibition. The council voted in July to ban cannabis dispensaries. But medical cannabis advocates collected in August the necessary 27,425 valid signatures to put the decision to a March 2013 referendum. Many cannabis dispensaries in California are threatened by repressive measures of the Federal Government since they violate federal law.

Reuters of 2 October 2012

USA — Medicinal cannabis law took effect in Connecticut

Despite a change in the law, which took effect on 1 October, to allow the medicinal use of cannabis by people who suffer from specific debilitating conditions, patients and advocates say it could be months before they have safe, legal access to the drug. The state Legislature voted last spring to create a registration and oversight system within the Department of Consumer Protection for medical cannabis use. However, the state hasn’t yet made available application forms for individual pharmacists to build and maintain secure indoor growing facilities for medical marijuana.

Norwich Bulletin of 23 September 2012

Science/Human — Anandamide levels are increased in high blood pressure in patients with sleep apnoea

Sleep apnoea patients showed positive correlations between blood pressure and blood anandamide concentrations in a clinical study. Authors write that their “data suggest a previously not recognized role of the endocannabinoid system for blood pressure regulation in patients with high risk for hypertension and cardiovascular disease.”

Institute of Clinical Pharmacology, Hannover Medical School, Germany.

Engeli S, et al. J Hypertens. 2012 Oct 1. [in press]

Science/Human — Cosmonauts in the ISS have high blood concentrations of endocannabinoids

Chronic but well-tolerated exposure to weightlessness and emotional and environmental stressors on the ISS (International Space Station) for 6 months resulted in a sustained increase in endocannabinoid blood concentrations, which returned to baseline values after the cosmonauts' return.

Department of Anaesthesiology, Klinikum Großhadern, University of Munich, Germany.

Strewe C, et al. Rev Neurosci 2012;0(0):1-8.

Science/Animal — Cannabinoids increase urine production

In studies with rats THC and other cannabinoids, which activate the CB1 receptor, increased urine production in a dose-dependent manner.

McLean Hospital/Harvard Medical School, Belmont, USA.

Paronis CA, et al. J Pharmacol Exp Ther. 2012 Sep 27. [in press]

Science/Human — Endocannabinoid level associated with the risk of cognitive problems following heart surgery

Patients who developed delirium after heart surgery had significantly lower blood levels of the endocannabinoid 2-AG before surgery. Patients with depression at 6 months after surgery had significantly lower anandamide and 2-AG levels during and shortly after surgery.

Department of Anaesthesiology, Klinikum Großhadern, University of Munich, Germany.

Hauer D, et al. Rev Neurosci. 2012 Sep 24;0(0):1-10. [in press]