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IACM-Bulletin of 01 September 2019

Science/Human: CBD attenuates dysfunction of a certain brain region in subjects at high risk for psychosis

Cannabidiol (CBD) in an oral dose of 600 mg “attenuated the increased activation in the left insula/parietal operculum and was associated with overall slowing of reaction time, suggesting a possible mechanism for its putative antipsychotic effect by normalising motivational salience and moderating motor response.” The study was conducted by researchers of King’s College in London, UK. It included 33 subjects at clinical high risk for psychosis and 19 healthy controls. Participants received either CBD or a placebo

Researchers observed abnormal activation in a certain brain region, the left insula/parietal operculum” in participants with high risk for psychosis given placebo compared to healthy controls. “Insular activation correlated with both positive psychotic symptoms and salience perception, as indexed by difference in reaction time between salient and neutral stimuli conditions.”

Wilson R, Bossong MG, Appiah-Kusi E, Petros N, Brammer M, Perez J, Allen P, McGuire P, Bhattacharyya S. Cannabidiol attenuates insular dysfunction during motivational salience processing in subjects at clinical high risk for psychosis. Transl Psychiatry. 2019;9(1):203.

Science/Human: CBD may be helpful in graft-versus-host disease, which may occur after bone marrow transplantation

Kalytera Therapeutics has concluded the second phase of a study examining the possibility of using CBD as a treatment for Graft versus Host Disease. It has been shown that CBD may significantly reduce the chance of developing the condition. Graft versus Host Disease (GvHD) is a condition that is often developed by patients who have received a blood marrow or stem cell transplant. The disease occurs when white blood cells from the donated bone marrow or stem cells (the graft) begin to attack the patient’s own (the host’s) cells.

Kalytera has assessed the results for the second phase of their clinical trial. The study followed 48 transplant patients for 16 months following the procedure. The results showed that only 8% patients receiving a low dose of CBD developed grade 2-4 acute GvHD. The historic norm for patients developing grade 2-4 acute GvHD is 60%-70%. The results were even more positive in patients given a medium dose of CBD, with no patients developing the disease. Phase 3 of the study will be a double-blind placebo-controlled clinical trial. In the trial, 50 patients will be given either a 150mg dose of CBD or placebo, twice daily. Patients will be carried out across clinical sites in Australia and Israel, and the duration will be approximately 12 months.

Cannabis exchange in August 2019

News in brief

USA: About 14% of US citizens use CBD products
One in seven Americans say they personally use cannabidiol- (CBD-) based products, which have proliferated since last year's passage of a federal law legalizing this hemp form of cannabis. Younger Americans and those in the Western U.S. are most likely to report using these products, which are widely touted for their therapeutic benefits without any psychoactive effects because these products contain only a low level of THC. This Is the result of a survey conducted by Gallup between 19 June and 12 July.
Gallup of 17 August 2019

USA: The Drug Enforcement Administration will ease production of cannabis for scientific purposes
The U.S. Drug Enforcement Administration said on 26 August that it will set new guidelines that will allow more cannabis growers to produce the drug for scientific or medical purposes. The DEA also said producers of hemp, an industrial form of the cannabis plant that has little psychoactive effect, will no longer have to register with the U.S. government.
Reuters of 26 August 2019

Science/Human: Cannabis may undermine fertility treatment success in women
Women undergoing fertility treatment who use cannabis may have more success if they quit, recent research suggests. Among more than 400 women undergoing treatment with assisted-reproduction technology (ART), the small fraction who reported using cannabis at the time were more than twice as likely to lose a pregnancy than those who had never smoked marijuana, or who had only used it in the past, Dr. Jorge E. Chavarro of Harvard T.H. Chan School of Public Health in Boston and his colleagues found.
Reuters of 21 August 2019

Canada: Government is overloaded with a large number of requests to study cannabis
The Canadian government is scrambling to respond to a glut of license applications for cannabis research prompted by the drug’s legalization in October 2018. The queue of applicants—there were 251 in line as of late July—and the attendant monthslong waiting times are frustrating scientists interested in the basic biology and therapeutic possibilities of cannabis. The delays are also prompting criticism of Health Canada, the Ottawa-based agency charged with issuing the permits.
Science Magazine of 19 August 2019

Science/Animal: THC enhances the analgesic effect of heroin
In a study with monkeys (rhesus macaques) THC increased the analgesic effect of heroin. This effect was mediated by the CB1 receptor.
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, USA ,
Nilges MR, et al. Exp Clin Psychopharmacol. 2019 Aug 29. [in press]

Science/Animal: The endocannabinoid system may be disturbed in the brains of patients with anorexia nervosa
In a rat model of anorexia nervosa the level of the endocannabinoid 2-AG (2-arachidonoylglycerol) was significantly decreased in different brain areas. There was no change in the level of anandamide. The level of the CB1 receptor was reduced only in 2 areas (dentate gyrus of the hippocampus and lateral hypothalamus).
Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
Collu R, et al. Int J Eat Disord. 2019 Aug 27. [in press]

Science/Cells: Anandamide influences aromatase, which may have negative effects on fertility
In a study with human cells the endocannabinoid anandamide reduced the expression of the gene which encodes aromatase, an enzyme which is responsible for a key step in the production of estrogens. Authors wrote that anandamide “may be implicated in endometrial dysfunction and in fertility/infertility disorders.”
Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
Almada M, et al. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Aug 24. [in press]

Science/Animal: Delta-8-tetrahydrocannabivarin may be useful in the treatment of nicotine dependence
In 7 models of nicotine dependence in rats and mice delta-8 THCV (delta-8-tetrahydrocannabivarin) reduced craving for nicotine and relapse to dependence. Authors suggest that this cannabis plant cannabinoid “should be tested for possible anti-addiction efficacy in a broader range of preclinical animal models, against other addictive drugs, and eventually in humans.”
National Institute on Drug Abuse, Baltimore, USA.
Xi ZX, et al. .Br J Pharmacol. 2019 Aug 27. [in press]

Science/Animal: The intake of linoleic acid increases endocannabinoid levels in bowel and liver
In a study with mice bodyweight was influenced by the source of calorie intake. In addition, diets with high levels of linoleic acid resulted in elevated levels of endocannabinoids in blood, liver and small bowel.
National Institute on Aging, Laboratory of Clinical Investigation National Institutes of Health, Baltimore, USA.
Ghosh S, et al. Obes Sci Pract. 2019;5(4):383-394.

Science/Human: Increasing number of adolescents are using concentrates in Arizona where cannabis is legal for adults
A survey with 47,142 adolescents recruited from 245 schools across Arizona shows, that 24% had used cannabis concentrates at least once. They were more likely to experiment with other illegal drugs.
Department of Psychology, Arizona State University, Tempe, USA.
Meier MH, et al. Pediatrics. 2019 Aug 26. [in press]

Science/Human: : In 15-year-old adolescents romantic attraction was associated with a high risk of using drugs
A survey with 14,545 adolescents aged 15 years from 8 EURopean countries showed that those who have not been in love had significantly lower risks for substance use, including cigarettes, alcohol and cannabis.
Health Promotion Research Centre, School of Health Sciences, National University of Ireland Galway, Ireland.
Költő Aet al. Int J Environ Res Public Health. 2019;16(17)

Science/Animal: Cannabidivarin ameliorates autism -like behaviours in animals
The plant cannabinoid cannabidivarin (CBDV) ameliorated autism -like behaviours in rats. Authors wrote that “these data provide preclinical evidence in support of the ability of CBDV to ameliorate behavioral abnormalities resembling core and associated symptoms of ASD “ (autism spectrum disorder) .
Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
, Zamberletti E, et al. Front Cell Neurosci. 2019 Aug 9;13:367.

Science/Human: Cannabis use may decrease or increase sexual experience
In a survey with 216 men and women with cannabis experience opposing effects were found on sexuality: “Many participants in our study found that cannabis helped them relax, heightened their sensitivity to touch, and increased intensity of feelings, thus enhancing their sexual experience, while others found that cannabis interfered by making them sleepy and less focused or had no effect on their sexual experience.”
Department of Family Practice, University of British Columbia, Vancouver, Canada.
Wiebe E, et al. J Sex Med. 2019 Aug 22 [in press]

Science/Animal: A topical inhibitor of endocannabinoid membrane transport reduced symptoms of atopic dermatitis
19 Beagles allergic to dust mites participated in a double-blind crossover study. They received either a gel containing endocannabinoid membrane transporter inhibitor or a placebo. The active substance significantly “minimized allergic flares and pruritus.”
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, USA.
Marsella R, et al. Arch Dermatol Res. 2019 Aug 24. [in press]

Science/Human: Limited knowledge of German pain therapists on the treatment with cannabis-based medicines
A survey with 120 German pain therapists showed, that most of them had good knowledge about treatment with dronabinol but very limited knowledge about other cannabis-based medicines, which may be used medicinally in Germany.
Praxis Gastmeier, Potsdam, Germany.
Gastmeier K. Schmerz. 2019 Aug 23. [in press]

Science/Cells: CBD shows anti-inflammatory effects, but reduces the effects of cortisone
In a study with several kinds of cells, including macrophages and lung fibroblasts CBD reduced inflammation similar to dexamethasone but was acting as an antagonist to steroids, when used in combination.
Department of Environmental Medicine, School of Medicine & Dentistry, University of Rochester Medical Center, USA.
Muthumalage T, et al. Toxicol Appl Pharmacol. 2019 Aug 19. [in press]

Science/Cells: Cannflavin A shows neuroprotective effects against neurotoxicity
The cannabis flavonoid cannflavin A shows neuroprotective effects against neurotoxicity caused by amyloid beta in so-called PC12 cells. Neurotoxicity caused by amyloid beta may be of relevance in Alzheimer’s disease.
Discipline of Pharmacology, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Australia.
Eggers C, et al. Biochem Pharmacol. 2019 Aug 19. [in press]

Science/Animal: CBD attenuates the rewarding effects of cocaine
In a study with rats cocaine attenuated the rewarding effects of cocaine. And this effect was mediated by the CB2 receptor, the 5-HT1A as well as the(TRPV1 receptor. Authors wrote that there “findings suggest that CBD may have certain therapeutic utility by blunting the acute rewarding effects of cocaine.”
National Institute on Drug Abuse, Baltimore, USA.
Galaj E, et al. Neuropharmacology. 2019 Aug 19:107740.

Science/Human: Young adults with cancer often use cannabis for symptom relief
According to an analysis of 1243 cancer patients between the ages of 18 and 31 years 30% tested positive for THC. Authors noted that many young cancer patients “may be managing their cancer-related symptoms with cannabis.”
Department of Supportive Care Medicine, Moffitt Cancer Center, Tampa, USA.
Donovan KA, et al. J Adolesc Young Adult Oncol. 2019 Aug 22 [in press]

Science/Animal: Electroacupuncture reduces allergic contact dermatitis by activation of the CB2 receptor
In a study with rats Chinese researchers demonstrated that electroacupuncture elevated allergic contact dermatitis by reducing mast cell infiltration and degranulation, and this effect was mediated by the CB2 receptor. Authors wrote that electroacupuncture “may be an effective candidate therapy for treating inflammatory skin diseases.”
Medicine, Hubei University of Chinese Medicine, Wuhan, China.
Wang Z, et al. Acupunct Med. 2019 Aug 20. [in press]

Science/Animal: An antagonist at the A2A receptor may enhance neuroprotective effects of endocannabinoids
In a mouse model of Alzheimer’s disease an antagonist of the adenosine A2A receptor increased signalling of endocannabinoids at the cannabinoid-2 receptor. Authors concluded that such an antagonist “would potentiate, via microglia, the neuroprotective action of endocannabinoids with implications for AD therapy.”
Molecular Neurobiology Laboratory, Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, Spain.
Franco R, et al. Glia. 2019 Aug 19. [in press]

Science/Cells: Cortisone reduces the cancer inhibiting effects of cannabinoids in glioma cells
In a study with glioblastoma cells corticosterone modified the endocannabinoid system through downregulation of the CB1 receptor, which may reduce the anti-cancer effects of cannabinoids, which activate the CB1 receptor, in glioblastoma.
Department of Physiology, Graduate School of Medical Sciences, Kanazawa University, Japan.
Sugimoto N, et al. Oncol Lett. 2019;18(2):1557-1563.

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