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IACM-Bulletin of 29 April 2018

Science/Human: Cannabis use reduces mortality in patients with burns

In a study on 3299 patients with a burn injury cannabis use was associated with lower mortality and shorter hospital stays compared to non-users and users of other drugs. Researchers of the Jaycee Burn Center of North Carolina in Chapel Hill, USA, analysed data of all patients admitted to the centre in 2015.

All included patients were tested for drugs, including amphetamine, cocaine, cannabis and alcohol, and 56% tested positive for at least one substance. The most prevalent drug was cannabis at 29% of study population, followed by alcohol, cocaine, and then amphetamine. Patients who tested positive for cannabis had shorter lengths of stay in hospital compared to non-users and users of other drugs. Mortality was 4% for patients with positive cocaine and amphetamine screens, as well as those testing negative for drugs and alcohol. Mortality was 8% for those positive for alcohol and 1% for patients with positive cannabis screens.

Williams F, Chrisco L, Nizamani R, Cairns B, Jones S. Marijuana Use is Protective in Burns. J Burn Care & Res. 2018;39(suppl_1):S198–S199.

Science/Human: A cannabis extract with THC and CBD reduced seizures in epilepsy in an open study

A cannabis extract with a CBD/THC ratio of 20 to 1 reduced disease severity in an open study with 57 patients suffering from various epilepsy forms. The investigation was performed by researchers of the Paediatric Neurology Unit at the Tel Aviv Medical Centre, Israel. The patients in the age 1 to 20 years were treated for at least 3 months with a median follow-up of 18 months. Average daily dose of CBD was 11.4 mg/kg bodyweight, corresponding to 0.55 mg THC/kg bodyweight. 46 patients were included in the efficacy analysis.

Twenty-six patients (56%) had at least 50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy aetiologies, and cannabis strain used. Younger age at treatment onset (younger than 10 years) and higher dose were associated with better response to treatment. Authors wrote that their “results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports.” However, effects may be due to THC, at least in part.

Hausman-Kedem M, Menascu S, Kramer U. Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents - An observational, longitudinal study. Brain Dev. 2018 Apr 16. [in press]

Science/Human: Acute use of cannabis may reduce anxiety and depression according to large study

Cannabis reduces symptoms of depression, anxiety and stress according to a study by researchers from the Washington State University in Pullman, USA. Using data from an app they analysed 11,953 cannabis sessions of people suffering from depression (3151 cannabis intakes), anxiety (5085) and stress (3717). The app (StrainprintTM) provides medical cannabis users a means of tracking changes in symptoms as a function of different doses and cannabis strains.

Medical cannabis users perceived a 50% reduction in depression and a 58% reduction in anxiety and stress following cannabis use. Two puffs were sufficient to reduce intensity of depression and anxiety, while 10 puffs or more produced the greatest perceived reductions in stress. Strains with high CBD and low THC was associated with the largest changes in depression ratings, while strains with high CBD and high THC produced the largest perceived changes in stress.

Cuttler C, Spradlin A, McLaughlin RJ. A naturalistic examination of the perceived effects of cannabis on negative affect. J Affect Disord.18;235:198-205.

Science/Human: CBD may be used against anxiety and depression without altering normal sleep

Cannabidiol (CBD), a non-psychedelic compound of the cannabis plant, does not alter normal sleep cycle. This is the result of a clinical study with 27 healthy volunteers, who received either CBD (300 mg) or placebo in a double-blind design by researchers from the University of São Paulo, Brazil. CBD or placebo was administered 30 min before the start of polysomnography recordings that lasted 8 hours. During polysomnography a number of sleeping-related parameters are measured, including leg movements, eye movements and electrical activity of the brain.

The drug did not induce any significant effect. Authors wrote that “different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD does not alter normal sleep architecture.”

Linares IMP, Guimaraes FS, Eckeli A, Crippa ACS, Zuardi AW, Souza JDS, Hallak JE, Crippa JAS. No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study. Front Pharmacol. 2018;9:315.

News in brief

Science/Human: Effect of cannabis on adolescents on cognitive performance overstated
A review of 69 studies on the effects of cannabis on cognitive function in young people came to the conclusion that “associations between cannabis use and cognitive functioning in cross-sectional studies of adolescents and young adults are small and may be of questionable clinical importance for most individuals. Furthermore, abstinence of longer than 72 hours diminishes cognitive deficits associated with cannabis use.”
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, USA.
Cobb Scott J, et al. JAMA Psychiatry. 2018 April 18. [in press]

Science/Human: Cannabis use was associated with a lower risk of artrial fibrillation
In patients with heart failure cannabis users were less likely to have artrial fibrillation compared to non-users (19.1% versus 21.4%). Researchers used a database of 3,950,392 patients admitted to hospital with a diagnosis of heart failure in the United States in 2014. Among these there were 17,755 cannabis users. They wrote, that this reduced risk was not explained by other reasons, for example age.
Department of Internal Medicine, Englewood Hospital and Medical Center, USA.
Adegbala O, et al. Am J Cardiol. 2018 Mar 28. [in press]

Science/Human: High doses of oral THC reduced intake of inhaled THC
In a study with 13 daily cannabis users administration of 120, 180 or 240 mg of oral THC (dronabinol) per day divided in 3 doses (3 times 40, 60 or 80 mg) reduce the intake of inhaled cannabis with high THC/dronabinol concentrations. Authors concluded that “chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users.”
Johns Hopkins University School of Medicine, Baltimore, USA.
Schlienz NJ, et al. Drug Alcohol Depend. 2018;187:254-260.

Science/Human: Cannabis use has no effect on brain structure
In a study with 622 young Australian adults with a mean age of 25.9 years cannabis use was unrelated to brain structure. Investigators studied the volume of 7 brain regions, including thalamus, hippocampus and amygdala by magnetic resonance imaging (MRI). However, high cigarette use was associated with significantly smaller thalamus volume.
Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, USA.
Gillespie NA, et al. Addiction. 2018 Apr 24. [in press]

Science/Human: CBD repaired negative effects of regular cannabis use on a certain brain region
In an open study with 18 regular cannabis users, who took 200 mg of CBD daily for about 10 weeks, the volume of certain areas in the hippocampus of the brain, was increased. Heavy cannabis use may have a negative effect on these areas.
Illawarra Health and Medical Research Institute, University of Wollongong, Australia.
Beale C, et al. Cannabis Cannabinoid Res. 2018;3(1):94-107.

Science/Human: Systemic lupus erythematosus was associated with an altered endocannabinoid system
Compared to healthy subjects blood concentrations of the endocannabinoid 2-AG (2-arachidonoylglycerol) was increased in patients with systemic lupus erythematosus. The highest levels of 2-AG was associated with a lower disease activity.
Department of Medicine, Campus Bio-Medico University of Rome, Italy.
Navarini L, et al. Int J Biochem Cell Biol. 2018;99:161-168.

Science/Human: The number of cannabinoid 1 receptors is increased in brown fat
Activation of brown adipose tissue by cold increased the density of CB1 receptors. In contrast, overweight men with reduced activity of brown fat exhibited decreased numbers of CB1 receptors in the brown adipose tissue.
University of Turku, Finland.
Lahesmaa M, et al. Diabetes. 2018 Apr 12. [in press]

Science/Human: Acute pain is reduced by THC
In a study with 24 healthy volunteers, who received either paracetamol (1000 mg), THC (10 mg) promethazine (50 mg) or placebo, THC and promethazine reduced the pain sensation. The researchers used different tasks, which elicited electrical, pressure, heat, cold and inflammatory pain. They showed that “pain thresholds determined using this pain test battery are not driven by sedation.”
Centre for Human Drug Research, Leiden, The Netherlands.
van Amerongen G, et al. EUR J Pain. 2018 Apr 10. [in press]

Science/Cells: CBD has anti-inflammatory properties in a model of allergic contact dermatitis
In a model of allergic contact dermatitis with human skin cells (keratinocytes) CBD exerted anti-inflammatory effects. CBD elevated the levels of the endocannabinoid anandamide and inhibited the release of several cytokines, which are associated with inflammation, including tumour necrosis factor alpha (TNF-alpha) and interleukin-6.
National Research Council, Italy.
Petrosino S, et al. J Pharmacol Exp Ther. 2018 Apr 9. [in press]

Science/Human: Cannabis use is associated with normal grey matter density of the brain in patients with schizophrenia
Adolescent cannabis use was associated with attenuated reductions of grey matter density, compared to non-users, in patients with schizophrenia. Total and regional grey matter density in individuals with psychosis and adolescent cannabis use were not different from healthy subjects.
Department of Psychiatry, UT Southwestern Medical Center, USA.
Abush H, et al. Psychiatry Res. 2018 Mar 28.[in press]

Science/Animal: Endocannabinoids reduce anxiety
Increase of the concentration of the endocannabinoids anandamide and 2-AG (2-arachidonoylglycerol) by inhibition of degradation through inhibition of the activity of the enzymes FAAH and MAGL produced anti-anxiety effects in stressed mice.
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, USA.
Bedse G, et al. Transl Psychiatry. 2018;8(1):92.

Science/Cells: Hemp shows potential for treating ovarian cancer
Researchers used ovarian cancer cells to investigate the effects of hemp on their growth. They demonstrated in two studies that an extract from hemp of Kentucky slowed cell migration and therefore inhibited metastasis, and that the extract reduced secretion of interleukin-1 beta. This cytokine stimulates cancer growth. The authors concluded that “KY hemp slows ovarian cancer comparable to or even better than the current ovarian cancer drug Cisplatin.”
Sullivan University College of Pharmacy, Kentucky, USA.
Presentation, 2018 Experimental Biology meeting, April 21-25, San Diego

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