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IACM-Bulletin of 05 May 2013

Science/Human: THC reduces agitation and aggressive behaviour in patients with severe dementia in an open clinical study

In 40 patients with severe Alzheimer’s disease and other forms of dementia a treatment with oral THC was associated with significant decreases in agitation, as well as improvements in sleep duration and appetite. This is the result of a study at the McLean Hospital Geriatric Neuropsychiatry Inpatient Unit at Harvard Medical School in Belmont, USA. Using a retrospective systematic chart review, 40 patients diagnosed with dementia and treated with oral THC (dronabinol) for behavioural or appetite disturbances were analysed. A group of geriatric psychiatrists consulted medical records to rate the patients' behaviours prior to initiation of THC treatment and following up to seven days of treatment.

The addition of THC to patients' treatment regimens was associated with significant decreases in all domains of the Pittsburgh Agitation Scale. There were also significant improvements in Clinical Global Impression scores, sleep duration and percentage of meals consumed. 26 adverse events were recorded during THC treatment, none of which led to medication discontinuation. Authors concluded that this report “represents the largest studied cohort of dementia patients treated with dronabinol to date and confirms earlier reports that dronabinol can serve as an adjunctive treatment for neuropsychiatric symptoms in dementia.” Behavioural disturbances occur frequently in demented individuals and greatly increase the burden of their care. The efficacy of medical treatment options is modest so far.

Woodward MR, Harper DG, Stolyar A, Forester BP, Ellison JM. Dronabinol for the Treatment of Agitation and Aggressive Behavior in Acutely Hospitalized Severely Demented Patients with Noncognitive Behavioral Symptoms. Am J Geriatr Psychiatry. 2013 Apr 15. [in press]

Science/Human: In healthy cannabis users the analgesic effects of oral THC are similar to smoked cannabis

In healthy regular cannabis users oral THC (dronabinol) and smoked cannabis (marijuana) caused similar effects on pain sensitivity and pain tolerance. This is the result of a study conducted at New York State Psychiatric Institute and Department of Psychiatry at the College of Physicians and Surgeons of Columbia University in New York, USA. 15 healthy male and 15 female daily cannabis smokers participated in this study comparing the analgesic, subjective, and physiological effects of cannabis (0.0, 1.98, or 3.56% THC) to oral THC (0, 10, or 20 mg). Pain response was assessed using the Cold-Pressor Test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded.

Compared to placebo, cannabis and oral THC decreased pain sensitivity (3.56%; 20 mg), increased pain tolerance (1.98%; 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56%; 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between cannabis and oral THC, although oral THC produced analgesia that was of a longer duration. Authors concluded that “these data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana.”

Cooper ZD, Comer SD, Haney M. Comparison of the Analgesic Effects of Dronabinol and Smoked Marijuana In Daily Marijuana Smokers. Neuropsychopharmacology. 2013 Apr 22. [in press]

News in brief

USA: Illinois House votes to legalize the medical use of cannabis
The Illinois House of Representatives voted narrowly on 17 April to legalize the use of cannabis for medical purposes. The chamber voted 61 to 57 in favour of a measure to allow patients with a doctor's permission to use cannabis. The measure will now go to the state senate. Democratic Governor Pat Quinn has said he is open minded on the proposal.
Reuters of 17 April 2013

Science/Human: No differences in brain structure between psychotic patients with or without cannabis use
In a study with patients with first episode psychosis, of whom 33 were cannabis users (15 with heavy and 18 with light use) and 17 were non-users no differences were found of grey and white matter of the brain with advanced brain-imaging techniques. This was also the case when only heavy users were compared to non-users. Authors wrote that they cannot “formally exclude subtle morphometric changes associated with cannabis consumption. However, even if present, such potential alterations would be of low magnitude.”
Service neuro-diagnostique et neuro-interventionnel DISIM, University Hospitals of Geneva, Switzerland.
Haller S, et al. Brain Topogr. 2013 Apr 19. [in press]

Science/Cells: The anti-cancer effects of evavirenz were increased by cannabinoids
Evavirenz shows anti-cancer effects in several tumour cells and this effect was increased by cannabinoids. Authors concluded that “the observed synergistic effect with cannabinoid agonists implicates an involvement of the cannabinoid system.”
Department of Radiation Oncology, University Hospital, University of Erlangen-Nuremberg, Germany.
Hecht M, et al. AIDS. 2013 Apr 26. [in press]

Science/Animal: Concentrations of anandamide are decreased in old mice, which increases the risk for neuropathic pain
Aged mice developed stronger pain after sciatic nerve injury than young mice. This was associated with low levels of the endocannabinoid anandamide in several parts of the nervous system including spinal cord and cortex, which further decreased after nerve injury. Authors noted that these changes may “contribute to the heightened risk for neuropathic pain at old age.”
Institute of Clinical Pharmacology, Goethe-University Frankfurt am Main, Germany.
Bishay P, et al. Neuropharmacology. 2013 Apr 15. [in press]

Science/Animal: Involvement of the endocannabinoid system in the action of sesamol
Sesamol is a natural compound of sesame OIL. Following chronic treatment of rats with sesamol, similar to the anti-depressant amitriptyline, resulted in a sustained elevation of endocannabinoid content in a dose-dependent and brain region-specific manner. The CB1 receptor was involved in the action of sesamol.
Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hassanzadeh P & Hassanzadeh A. Psychopharmacology (Berl). 2013 Apr 27. [in press]

Science/Human: The number of cannabinoid receptors is altered in celiac disease
The number of CB1 and CB2 receptors was increased in the mucosa of the duodenum during active celiac disease. Authors noted that this “points to the therapeutic potential of targeting CBR in patients with celiac disease.”
Department of Biomedical Sciences, University of Teramo, Italy.
Battista N, et al. PLoS One. 2013;8(4):e62078.

Science/Human: Endocannabinoids in obese women
In a study with 30 obese postmenopausal women higher circulating levels of the endocannabinoid 2-AG were found in insulin resistant compared to insulin sensitive postmenopausal women, and weight loss was associated with an increase in the endocannabinoid PEA.
Faculty of Health Science, University of Ottawa, Canada.
Abdulnour J, et al. Obesity (Silver Spring). 2013 Apr 24. [in press]

Science/Animal: Cannabinoids may worsen gastric dysmotility induced by cisplatin
The anti-cancer agent cisplatin may be associated with side effects on motility of the stomach delaying gastric emptying. This effect was increased by administration of the synthetic cannabinoid WIN55,212-2. Authors concluded that “cannabinoids should be handled with caution if chronically administered during chemotherapy.”
Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.
Abalo R, et al. Neurogastroenterol Motil 2013;25(5):373-e292.

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