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IACM-Bulletin of 12 April 2020

Science/Human: The use of cannabis alone in Multiple Sclerosis may replace several medications

A team of Spanish researchers from different universities and hospitals propose the concept of “Spasticity-Plus Syndrome" in Multiple Sclerosis, since the use of cannabis may not only be helpful in the treatment of spasticity but because improvements in several symptoms/functions including spasms, cramps, pain, gait, sleep, bladder function, fatigue, and possibly tremor.

They concluded that they “can conceptualize and, therefore, hypothesize, through this indirect information, that it could be considered the existence of a broad "Spasticity-Plus Syndrome" that involves, a cluster of symptoms apart from spasticity itself, the rest of the mentioned functions/symptoms, probably because they are interlinked after the increase of muscle tone and mediated, at least in part, in the same or close areas of the brainstem.” Thus, cannabis may replace several medications.

Fernández Ó, Costa-Frossard L, Martínez-Ginés M, Montero P, Prieto JM, Ramió L. The Broad Concept of "Spasticity-Plus Syndrome" in Multiple Sclerosis: A Possible New Concept in the Management of Multiple Sclerosis Symptoms. Front Neurol. 2020;11:152.

Science/Human: Subjective effects of CBD preparations after oral intake and inhalation in a clinical study

In a study with 18 healthy adults (9 men, 9 women), who received different CBD preparations subjective effects of oral CBD did not differ from placebo, but inhalation caused subjective effects. This research was conducted by scientists of Johns Hopkins University School of Medicine in Baltimore, USA. In 4 sessions separated by one week participants self-administered 100 mg oral CBD, 100 mg vaporized CBD, vaporized CBD-dominant cannabis (100 mg CBD; 3.7 mg THC), and placebo. researchers analysed subjective effects, cognitive and psychomotor performance and THC and CBD blood concentrations.

Vaporized CBD and CBD-dominant cannabis increased ratings on several subjective items (e.g., Like Drug Effect) relative to placebo. Subjective effects did not differ between oral CBD and placebo and were generally higher for CBD-dominant cannabis compared to vaporized CBD. CBD did not increase ratings for several items typically associated with acute cannabis/THC exposure. Authors concluded that “vaporised CBD and CBD-dominant cannabis produced discriminable subjective drug effects, which were sometimes stronger in women, but did not produce cognitive/psychomotor impairment. Subjective effects of oral CBD did not differ from placebo.”

Spindle TR, Cone EJ, Goffi E, Weerts EM, Mitchell JM, Winecker RE, Bigelow GE, Flegel RR, Vandrey R. Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. Drug Alcohol Depend. 2020 Mar 12:107937.

News in brief

USA: CBD patient Charlotte Figi dies of cardiac arrest
Charlotte Figi, (13 years), the Colorado child whose seizure relief inspired Charlotte's Web medical cannabis and CBD, died in Colorado Springs of cardiac arrest, her family said. Charlotte had been hospitalized after flu-like symptoms struck the family, her stepfather, Greg Iafeliece, said. The child then was released to go home. On Tuesday, she was found unresponsive and taken back to the hospital, where she died, Iafeliece said. The family believes she suffered cardiac arrest due to her fragile health condition, he said. Family members had been dealing for weeks with symptoms that could have been related to COVID-19.
UPI of 9 April 2020

Australia: Clinical trials with new cannabis capsules
AusCann Group’s hard shell medicinal cannabis products are now available for prescription Australia-wide, with clinical trials also ready to kick-off into evaluating different doses of its THC-CBD formulations. In parallel with the upcoming clinical study, AusCann has made its medicinal cannabis capsules available to Australian patients via the Therapeutic Goods Administration Special Access Scheme.
Smallcaps of 31 March 2020

USA: Researchers study COVID-19 and cannabis use
Researchers are analyzing the effects of the coronavirus on medicinal cannabis users, one of the vulnerable populations that may be disproportionately affected by the disease. Their study includes an electronic survey to obtain epidemiologic data. A large portion of medicinal cannabis users are people with compromised immune systems or chronic medical conditions. These are also many of the same traits that people most vulnerable to COVID-19 share. That is why a University of Miami research team is hoping to document how cannabis users are faring during the height of the coronavirus pandemic in the United States.
News Miami of 2 April 2020

Science/Cells: CBN induces cell death in several cancer cells
According to a doctoral thesis from the University of Lethbridge, Canada, cannabinol (CBN) inhibits proliferation and induces cell cycle arrest and apoptosis in glioblastoma, hepatocellular carcinoma and breast cancer cells.
Doctoral Thesis by N. Zhong

Mexico: Senate asks Supreme Court for more time on cannabis legalisation
Mexican lawmakers were racing to meet an April 30 deadline to legalize cannabis for adult use. But amid the coronavirus outbreak, a draft bill to legalize cannabis for medical, adult, and industrial uses has been stalled in the Senate one month before a Supreme Court deadline requiring that lawmakers pass such a bill.
Cannabis newswire of 2 April 2020

Science/Human: Tourette syndrome is associated with increased endocannabinoid levels
In a study with 20 patients with Tourette syndrome and 19 healthy controls the levels of the endocannabinoids anandamide (arachidonoylethanolamide) and 2-AG (2-arachidonoylglycerol) as well as arachidonic acid were increased in cerebrospinal fluid in patients. Authors wrote that “elevated endocannabinoid levels either represent secondary changes in order to compensate for alterations in other neurotransmitter systems (…) or, alternatively, represent the primary cause of TS.”
Clinic of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Germany.
Müller-Vahl KR, et al. Neuropsychopharmacology. 2020 Apr 9. [in press]

Science/Human: Possible serious side effects of CBD if combined with antiepileptic drugs
According to a review CBD administration may be associated with elevated liver enzymes if combined with valproate and with sedation and upper respiratory tract infection if combined with clobazam.
Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Brazil.
Dos Santos RG, et al. Expert Opin Drug Metab Toxicol. 2020 Apr 9. [in press]

Science/Human: The Association of cannabis use with withdrawal symptoms
According to an analysis of 47 studies representing 23 518 participants the prevalence of withdrawal symptoms was 17% in population-based samples, 54% in outpatient samples and 87% in inpatient samples. Authors concluded that their findings “suggest that cannabis withdrawal syndrome appears to be prevalent among regular users of cannabis.”
Department of Public Health Sciences, Queen's University, Kingston, Canada.
Bahji A, et al. JAMA Netw Open. 2020;3(4):e202370.

Science: Terpenes usually do not exert their entourage effect by the activation of cannabinoid receptors
Researchers investigated the mode of action of 5 terpenes present in cannabis products: myrcene, alpha- and beta-pinene, beta-caryophyllene, and limonen. They concluded that with “possible exception of a weak interaction of beta-caryophyllene with CB2, no data were produced to support the hypothesis that any of the five terpenes tested (either alone or in mixtures) have direct interactions with CB1 or CB2.”
Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
Finlay DB, et al. Front Pharmacol. 2020;11:359.

Science/Human: CBD has few serious adverse effects in clinical studies
According to a review of clinical studies with CBD authors found that the cannabinoid “is well tolerated and has relatively few serious adverse effects, however interactions with other medications should be monitored carefully.”
King's College London, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, London, UK.Chesney E, et al. Neuropsychopharmacology. 2020 Apr 8. [in press]

Science/Animal: CBD may prevent the development of severe movement disorders following the intake of neuroleptics
In a study with rats the administration of CBD together with the neuroleptic medication haloperidol authors found that “CBD can be combined with haloperidol to prevent the emergent of extrapyramidal side effects and long-term movement disorders, such as acute dystonic disorder and tardive dyskinesia.”
Consultant Psychiatrist, Federal Neuropsychiatric Hospital, Yaba, Lagos.
Kajero JA, et al. World J Biol Psychiatry. 2020:1-35.

Science/Cells: CBD may block the development of breast cancer
CBD was shown to block progression of an interleukin-1 beta-induced signaling pathway, which is called epithelial-mesenchymal transition, in breast cancer cells. This program is used to execute a multi-step process leading to cancer development and metastasis. Cannabidiol reestablished the epithelial organization.
Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
García-Morales L, et al. Int J Mol Sci. 2020;21(7).

Science/Human: Chronic exercise changes in the endocannabinoid system and other systems
In a study with 52 young adults, who underwent an 80-day aerobic and strength exercise program there were several changes in clinical parameters. Authors wrote that there “were highly significant changes across many classes of metabolic substrates including lipids, ketone bodies, arginine metabolites, endocannabinoids, nucleotides, markers of proteolysis, products of fatty acid oxidation, microbiome-derived metabolites, markers of redox stress, and substrates of coagulation.”
Heart Research Institute, Sydney, Australia.
Koay YC, et al. Cardiovasc Res. 2020 Apr 1. [in press]

Science: Labelled CBD content may differ from real CBD content in Swiss CBD products
In an analysis of 20 samples of CBD products the total CBD content ranged from 0.182 to 3.346% and differed in ten samples from the CBD content presented by the manufacturer by more than 10% relative CBD. Furthermore, two of the analysed samples contained only 0.348% and 0.182% total CBD despite being labelled as "CBD rich". Seven of the 20 samples contained the correct CBD content (in the range of the labelled CBD content ± 10%).
Institute of Forensic Medicine, University of Bern, Switzerland.
Grafinger KE, et al. Forensic Sci Int. 2020;310:110261.

Science/Human: THC may be associated with higher risk of embolic complications in trauma patients without affecting mortality
In an analysis of 593,818 trauma patients the presence of THC was associated with an increased risk of thromboembolic complications, no increased risk of stroke and no influence on mortality.
Department of Surgery, College of Medicine, University of Arizona, Tucson, USA.
Stupinski J, et al. J Trauma Acute Care Surg. 2020 Mar 23. [in press]

Science/Animal: Cannabinoids block cocaine induced seizures by restoring dysfunction of glycine receptors
Researchers showed that cannabinoids significantly suppress cocaine-exaggerated nerve excitability in 2 brain regions (the prefrontal cortex and hippocampus) by rehabilitating dysfunction of glycine receptors.
University of Science and Technology of China, Hefei , China.
Zou G, et al. Cell Rep. 2020;30(12):4209-4219.e7.

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