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IACM-Bulletin of 29 July 2012

Science/Human: Cannabis improves symptoms of multiple sclerosis in large clinical study

In a clinical study with 279 patients suffering from multiple sclerosis a cannabis extract improved muscle stiffness, pain, spasms and sleep. The Multiple Sclerosis and Extract of Cannabis (MUSEC) study was headed by Dr. John Zajicek, a professor of the University of Plymouth, and conducted at 22 hospitals in the UK. One capsule of the extract contained 2.5 mg THC and 1.25 mg CBD (cannabidiol). A 2 week dose titration phase, in which participants could increase daily doses from 5 mg to a maximum of 25 mg of THC, was followed by a 10 week maintenance phase.

The rate of relief in patient reported change in muscle stiffness after 12 weeks was almost twice as high with cannabis than with placebo (29.4 per cent vs 15.7 per cent). Similar results were found also for pain, spasms and sleep quality. Authors concluded: “The study met its primary objective to demonstrate the superiority of CE [cannabis extract] over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables.”

Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG; on behalf of the MUSEC Research Group. MUltiple Sclerosis and Extract of Cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012 Jul 12. [in press]

Science/Human: Sativex improves a range of symptoms in multiple sclerosis according to a survey

The use of the cannabis extract Sativex results in improvements across a range of daily functional activities, a reduction in the use of concomitant anti-spasticity medication and in the use of other healthcare resources. This is the result of responses to a survey by patients and their caregivers conducted by Dr. William Notcutt of James Paget University Hospital in Great Yarmouth, UK.

A short questionnaire survey consisting mostly of multiple-choice questions, along with some free-text questions aimed at the patient and primary caregiver. It was distributed to prescribers of Sativex in the United Kingdom, with the request that they in turn forward it to any patients who had received repeat prescriptions for Sativex within the previous 16 weeks. Most patients had MS, and the primary reasons for using Sativex were spasticity and pain. The response rate was 57 per cent, with 124 questionnaires returned.

Notcutt WG. A questionnaire survey of patients and carers of patients prescribed Sativex as an unlicensed medicine. Prim Health Care Res Dev. 2012 Jul 12:1-8. [in press]

Science/Human: THC may improve fear extinction in anxiety disorders according to experimental study

THC prevented the recovery of fear in an experiment of extinction learning. This is the result of a placebo controlled study with 29 healthy subjects at the Department of Psychiatry of the University of Michigan in Ann Arbor, USA. Participants were subjected to a standard fear extinction paradigm. In this experiment of classical conditioning a neutral stimulus, for example a sound, is followed by a second (unpleasant) stimulus, for example pain. If this experiment is repeated the first (neutral) stimulus will provoke a physical reaction, since the subject expects pain (the second stimulus) to follow. In extinction learning this learned response to the first stimulus is eliminated when this stimulus is presented in the absence of the second (unpleasant) stimulus. Extinction learning is a first-line approach to treat anxiety disorders.

In the study 14 participants received oral THC two hours before extinction learning, while 15 received placebo. 24 hours after extinction learning subjects were tested again. Compared to subjects that received placebo, subjects that received THC presented with a better extinction of fear. Thus, THC may be useful to improve treatment of anxiety disorders such as post-traumatic stress disorder. Scientists concluded that “these results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing.”

Rabinak CA, Angstadt M, Sripada CS, Abelson JL, Liberzon I, Milad MR, Phan KL. Cannabinoid facilitation of fear extinction memory recall in humans. Neuropharmacology. 2012 Jul 13. [in press]

Science/Human: Cannabis reduces symptoms in a patient with severe post-traumatic stress disorder

Symptoms of severe post-traumatic stress disorder in a young man were significantly improved following self-treatment with cannabis, according to a case report from the Department of Psychiatry of Hannover Medical School, Germany. From about the age of four, the patient was a victim of long-time sadistic sexual abuse by his father and paternal uncle, which continued until age 15 when he attempted to commit suicide for the second time.

The authors of the report first saw the patient several years later when he was admitted to the psychiatric department for safety and stabilization during a crisis with severe, uncontrolled flashbacks, panic attacks, and impulses for self-mutilation. These had resulted in severe self-injury in the past (mainly lacerations from cutting with knives). After a few days of treatment and stabilization he was referred back to the inpatient psychotherapy treatment centre. In the following weeks his condition improved dramatically. When he was asked what his idea was about the improvement of his condition, he confessed that he had learned to smoke cannabis resin from some other inpatients. He had discovered that he could prevent dissociative states by smoking cannabis when he first felt reactivation and intensification of traumatic memories experienced as flashbacks. Although he still experienced flashback phenomena after the use of cannabis, it alters their course and intensity. Authors conducted a review on the issue and concluded: “Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects.”

Passie T, Emrich HM, Karst M, Brandt SD, Halpern JH. Mitigation of post-traumatic stress symptoms by Cannabis resin: A review of the clinical and neurobiological evidence. Drug Test Anal. 2012 Jun 26.[in press]

News in brief

France: Conference on the medical use of cannabis
A conference on the medical use of cannabinoids and cannabis will be held at the EURopean Parliament in Strasbourg on 19 October 2012, organized by Icare (Strasbourg) and Action Sida Ville (ASV-Strasbourg).
Avancées pharmacologiques et utilisations thérapeutiques des cannabinoïdes

Science/Human: Cannabis improves cognition in bipolar disorder
Compared to non-cannabis using subjects with bipolar disorder those, who used cannabis demonstrated better performance on measures of attention, processing speed and working memory. In the study 50 patients with bipolar disorder and cannabis use (CUD) were compared with 150 patients without cannabis use. Scientists wrote: “Interestingly, bipolar patients with history of CUD had better neurocognitive performance as compared to patients with no history of CUD.”
The Zucker Hillside Hospital, Glen Oaks, New York, USA.
Braga RJ, et al. Psychiatry Res. 2012 Jul 17. [in press]

Science/Human: Cannabis use does not alter thyroid function
Blood levels of thyroid hormones were normal in 24 regular cannabis users. Scientists concluded: “These results argue against a relevant influence of chronic cannabis intake on thyroid function in humans.”
Department of Psychiatry, Psychotherapy and Psychosomatics, Evangelisches Krankenhaus Castrop-Rauxel, Germany.
Bonnet U. Pharmacopsychiatry. 2012 Jul 20. [in press]

Science/Human: Cannabis use associated with increased risk of preterm birth
In a large clinical study with 3234 healthy pregnant women the use of cannabis increased the risk for preterm birth. There were 4.9 per cent of preterm births. Scientists reported several risk factors including cannabis use, but the increase in risks were low.
Lyell McEwin Hospital, Adelaide, Australia.
Dekker GA, et al. PLoS One, 2012;7(7):e39154.

Science/Cells: Endocannabinoids alleviate proinflammatory conditions
The application of endocannabinoids to certain immune cells of the retina helps retinal cells to survive under inflammatory conditions by creating an anti-inflammatory milieu. Scientists concluded that cannabinoids may cause a “molecular switch to bias the innate immune system such that the balance of pro- and anti-inflammatory cytokine generation creates a prosurvival milieu.” The retina is a light-sensitive tissue lining the inner surface of the eye.
Department of Ocular Pathology, Vision Research Foundation, Chennai, India.
Krishnan G, Chatterjee N. Glia. 2012 Jul 17. [in press]

Science/Animal: Activation of the CB2 receptor reverses memory deficiency caused by amyloid
Injection of amyloid into the brains of rats caused some changes that are typical for Alzheimer’s disease. Treatment with a cannabinoid that binds to the CB2 receptor reversed these effects and restored cognition and memory.
Institute of Anesthesiology, Cleveland Clinic, USA.
Wu J, et al. Neurobiol Aging. 2012 Jul 12. [in press]

Science/Animal: Angiotensin II induces the release of endocannabinoids
Angiotensin II increases blood pressure. Now it was demonstrated that this hormone also induces the release of the endocannabinoid 2-AG from the wall of blood vessels, which attenuates the vasoconstrictor effect of angiotensin II by activating CB1 receptors.
Semmelweis University, Budapest, Hungary.
Szekeres M, et al. J Biol Chem. 2012 Jul 11. [in press]

Science/Animal: High anandamide concentrations during lactation induce overweight in adults
New born mice, who received oral anandamide during the whole lactation period, were overweight and showed an increased food intake during adulthood. They were also at high risk for development of diabetes.
Aguirre CA, et al. Diabetol Metab Syndr, 2012;4(1):35.

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