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IACM-Bulletin of 04 July 2021

IACM: IACM Journal Cannabis and Cannabinoid Research receives first impact factor of 5.764

Cannabis and Cannabinoid Research announces its first Impact Factor of 5.764. These figures are based on the citations in 2020 to papers published in 2018 and 2019. The impact factor reflects the relative importance of a scientific journal within its field. Journals with higher impact factor values are often deemed to be more important. Cannabis and Cannabinoid Research has rapidly become the voice of the global cannabinoid community, and this high first impact factor solidifies the Journal’s position in the market.

The journal downloads have also increased tremendously and are up 76% January through May, as compared to the same time last year. More than 193,000 journal articles have been downloaded already in 2021. These achievements would not have been possible without the commitment by the publisher Mary Ann Liebert and by Dr Daniele Piomelli, editor-in-chief of the journal and member of the IACM Board of Directors.

Cannabis and Cannabinoid Research

USA: Connecticut becomes the 18th state to legalise the use of cannabis by adults

Connecticut on 22 June joined 17 other U.S. states in legalizing adult use of cannabis as Governor Ned Lamont signed a bill that he said would also help heal economic scars left by the war on drugs. The cannabis measure, which took effect on 1 July, automatically erases many criminal convictions and sets up a regulatory structure that directs opportunities and revenue toward communities hard-hit by its prohibition.

“For decades, the war on cannabis caused injustices and created disparities while doing little to protect public health and safety,” Lamont said in a statement. The legalization movement has gained momentum this year as five state legislatures, including Connecticut's, have approved the drug's recreational use, most recently in Virginia, where the law also takes effect on 1 July. Connecticut, whose law allows for personal cultivation of marijuana plants in 2023, becomes the 18th state to approve legalization. Voters in a 19th state, South Dakota, approved legalization last year, but a legal challenge to the measure is now pending before the state Supreme Court.

Reuters of 22 June 2021

Mexico: Government wants to hold a referendum on the legal status of cannabis after the Supreme Court ruled that it should be legalised

Mexico's President Andres Manuel Lopez Obrador said on 29 June he will respect a ruling of the Supreme Court told the government and lawmakers to legalize the use of cannabis for adults. The court also opened the door to convening a public referendum on the issue.

The Supreme Court ruling on 28 June 2021 brings Mexico closer to creating one of the world's largest legal cannabis markets and pressures the Mexican Senate to approve the sweeping legalization bill that has been stalled there since the Lower House of Congress approved it in March 2021. "Of course we're going to respect what the court has decided and we're going to evaluate. We're going to see what effects it has," Lopez Obrador said at a regular news conference in response to a question about the Supreme Court's decision.

Reuters of 29 June 2021

Science/Human: Cannabis use has no negative effect on male sexual function according to long-term study

According to a cohort study with 7809 males from the andrology clinic of the University of Manitoba in Winnipeg, Canada, cannabis use was not associated with significant negative effects on sexual function. Patients from 2008-2017 were included in the study. Intake questionnaires provided baseline demographic information, as well as data regarding substance use and various sexual function parameters.

A total of 993 patients (12.7%) were cannabis users and 6816 (87.3%) were non-users. Cannabis users had a significantly higher mean Sexual Health Inventory for Men score (21.9 versus 21.2) and higher mean serum total testosterone (13.4 nmol/L versus 12.6) than non-users, although they also had a higher rate of positive Androgen Deficiency in the Aging Male scores (52% versus 46%). Cannabis users also reported higher sexual frequency compared to non-users. The authors concluded that “Cannabis use was not associated with clinically significant deleterious effects on male sexual parameters in this cohort.”

Shiff B, Blankstein U, Hussaen J, Jarvi K, Grober E, Lo K, Lajkosz K, Krakowsky Y. The impact of cannabis use on male sexual function: A 10-year, single-center experience. Can Urol Assoc J. 2021 Jun 22. [in press].

Science/Human: Cannabis may be an effective substitution in patients with alcohol use disorder

In a Managed Alcohol Program (MAP) with 19 patients suffering from alcohol use disorder the use of cannabis was helpful in reducing alcohol intake. Data were collected from MAP organizational leaders (n = 7), program participants (n = 19), staff and managers (n = 17) across 6 Managed Alcohol Programs in Canada. The study was undertaken by investigators of the Canadian Institute for Substance Use Research of the University of Victoria, Canada.

Among MAP participants, 63% (n = 12) were already substituting cannabis for alcohol, for cravings (79%,) and withdrawal (53%), most often on a weekly basis (42%). Participants preferred staff administration of dry, smoked cannabis, followed by edibles and capsules with replacement of some doses of alcohol through a partial substitution model. Participants requested peer, social, and counselling supports. Staff requested education resources and enhanced clinical staffing. Authors concluded that “cannabis substitution was considered feasible by all three groups.”

Pauly B, Brown M, Chow C, Wettlaufer A; East Side Illicit Drinkers Group for Education (EIDGE), Graham B, Urbanoski K, Callaghan R, Rose C, Jordan M, Stockwell T, Thomas G, Sutherland C. "If I knew I could get that every hour instead of alcohol, I would take the cannabis": need and feasibility of cannabis substitution implementation in Canadian managed alcohol programs. Harm Reduct J. 2021;18(1):65.

Science/Human: Cannabidivarin (CBDV) may normalise brain function in autism

According to a study with 28 men, of whom 13 were diagnosed with autism spectrum disorder, the plant cannabinoid CBDV (Cannabidivarin) may normalise altered brain function in autism. Investigators of the Institute of Psychiatry at King's College London, UK, showed that patients with autism show altered functional connectivity between certain brain regions (ventral striatum and frontal and pericentral regions) and other changes in regions involved in speech and language compared to 15 healthy men. All participants received 600 mg of CBDV or a placebo at two occasions, separated by at least 13 days.

CBDV reduced hyperconnectivity to the normal level. Authors concluded that the study provides “preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function.” They noted that further studies are needed if this normalisation is associated with changes in autism symptoms.

Pretzsch CM, Floris DL, Voinescu B, Elsahib M, Mendez MA, Wichers R, Ajram L, Ivin G, Heasman M, Pretzsch E, Williams S, Murphy DGM, Daly E, McAlonan GM. Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin. Mol Autism. 2021;12(1):49.

News in brief

USA: A member of the Supreme Court says that cannabis prohibition “may no longer be necessary”
U.S. Supreme Court Justice Clarence Thomas on Monday said the federal ban on the cultivation and use of cannabis within states "may no longer be necessary or proper" and that inconsistent enforcement led to "traps" for cannabis businesses. Thomas issued the statement in connection with the court's refusal to hear an appeal by a Colorado cannabis dispensary.
Reuters of 28 June 2021

Science/Human: CBD improved anxiety and depression in an observational study
In a retrospective observational study with 279 adults treatment with CBD rich cannabis improved anxiety and depression over the course of three and six months. Addition of THC to the treatment at the first follow-up appointment had no effect on symptom changes.
Research Department, Santé Cannabis, Montréal, Canada.
Rapin L, et al. J Cannabis Res. 2021;3(1):19.

Science: The bioavailability of CBD depends on food intake
New research shows that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may contribute to an increase in CBD bioaccessibility. Authors wrote that “the increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules.”
Department of Plant and Environmental Sciences, New Mexico State University, Las Cruces, USA.
Mozaffari K, et al. Molecules. 2021;26(12):3573.

Science/Animal: Increased endocannabinoid tone alters anxiety like behaviour in a rat model of autism
In a rat model of autism male and female rats reacted in different ways to an increase of endocannabinoids. Authors concluded “considerations should be paid to the possible sex-specific effects of cannabinoids for the treatment of symptoms associated with autism.”
Physiology, School of Medicine, National University of Ireland Galway, Ireland.
Thornton AM, et al. Molecules. 2021;26(12):3720.

Science/Human: Cannabis use before pregnancy may increase the risk for postpartum depression
In a study with 516 pregnant women the risk of developing depression after giving birth was higher in those, who used cannabis before pregnancy.
Faculty of Medicine, School of Public Health, Centre for Longitudinal and Life Course Research, The University of Queensland, Australia.
Cao S, et al. Drug Alcohol Depend. 2021;226:108860.

Science: Investigation of cannabinoid effects on the metabolism of other medicinal drugs in the liver
Researchers investigated the effects of 12 cannabinoids on the activity of liver enzymes (CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2B6, and CYP2C19) responsible for the degradation of many medicinal drugs. They found that mainly “CYP2C9-mediated metabolism was inhibited by cannabinoids at clinically relevant concentrations.”
Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre, The University of Sydney, Australia.
Doohan PT, et al. AAPS J. 2021;23(4):91.

Science/Animal: CBD may reduce damage to the heart after myocardial infraction CBD was able to reduce the damage to heart cells following reduced blood supply (ischaemia).
Authors concluded that the “use of cannabinoids was shown to have beneficial effects when used as a treatment for myocardial reperfusion damage.”
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico.
Franco-Vadillo A, et al. Pharmacol Res Perspect. 2021;9(4):e00784.

Science/Animal: Mice without CB1 receptors have symptoms, which may be observed in autism
In a study with genetically modified mice without CB1 receptors researchers found behavioural alterations which resemble symptoms in autism. They noted that the endocannabinoid system “is important for brain development and neural function and is therefore likely to be involved in neurodevelopmental disorders such as Autism Spectrum Disorder.”
University of Bordeaux, France.
Fyke W, et al. Autism Res. 2021 Jun 26. [in press].

Science/Human: Most Germans with inflammatory bowel disease still use cannabis from the black market
According to a survey with 417 patients from Germany suffering from inflammatory bowel disease (55% with Crohn’s disease and 43% with ulcerative colitis) 4.3% reported current use of cannabis to treat symptoms. Authors noted that “Cannabis is mainly procured from the black market, with unknown quality.”
Department for Internal and Integrative Medicine, Sozialstiftung Bamberg, Germany.
Neufeld T, et al. Z Gastroenterol. 2021 Jun 22. [in press].

Science/Animal: A combination of CBD and ketamine has antidepressant effects
In a study with mice CBD induced antidepressant effects. Ketamine also produced antidepressant effects. A combination of CBD and ketamine produced antidepressant effects without relevant side-effects of ketamine.
Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
Sartim AG, et al. Neuropharmacology. 2021:108679.

Science/Animal: CBD prevents some behavioural alterations related to cocaine addiction
In a study with mice CBD abolished cocaine-induced hyperactivity without altering spontaneous locomotion of the animals. In addition, CBD reduced the memory deficits by cocaine withdrawal.
Department of Psychiatry and Behavioral Sciences, Stanford University, USA.
Cawkwell PB, et al. Harv Rev Psychiatry. 2021 Jun 16. [in press].

Science/Cells: THC has anti-cancer effects in oral cancer cells
THC decreases cancer cell growth “through various mechanisms, including apoptosis, autophagy, and oxidative stress.”
Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval, Québec, Canada.
Semlali A, et al. Arch Oral Biol. 2021;129:105200.

Science/Animal: The bioavailability of encapsulated CBD is increased when administered with deoxycholic acid
In a study with mice, which either received CBD capsules or capsules filled with CBD and the permeation enhancer deoxycholic acid (DCA) the combination with DCA resulted in 300% increased bioavailability and a considerably higher brain concentration in CBD.
Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
Majimbi M, et al. PLoS One. 2021;16(6):e0243858.

Science/Cells: Anandamide causes apoptosis in granulosa cells
Granulosa cells play an important role in female reproduction. Increased anandamide levels induced cell death in granulosa cells. Authors concluded that the endocannabinoid system is crucial for female reproduction.
Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Portugal.
Costa L, et al. Prostaglandins Leukot Essent Fatty Acids. 2021;171:102311.

Science/Animal: CBD attenuates cognitive deficits induced by early alcohol exposure
In a study with young mice CBD was shown to “counteract cognitive impairments and neuroinflammation caused by early alcohol exposure.”
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
García-Baos A, et al. Biomed Pharmacother. 2021;141:111813.

Science/Cells: CBD interacts with antidepressant medication
CBD (cannabidiol) is metabolised in the liver using similar enzymes as commonly used antidepressant drugs. CBD minimally affected the metabolism of sertraline, fluoxetine, and mirtazapine in cells. However, CBD significantly inhibited the metabolism of citalopram and escitalopram by the enzymes CYP3A4 and CYP2C19. This may be of clinical relevance.
School of Psychology, Faculty of Science, The University of Sydney, Sydney, Australia.
Anderson LL, et al. J Clin Psychopharmacol. 2021 Jun 11. [in press].

Science/Human: A MAGL inhibitor was not effective in the treatment of Tourette syndrome in clinical study
In a 12 week randomised placebo-controlled study with 49 adults with Tourette syndrome a synthetic inhibitor of MAGL called Lu AG06466 had no significant effects on symptom severity. MAGL (monoacylglycerol lipase) is an enzyme, which is mainly responsible for the degradation of the endocannabinoid 2-AG (2-arachidonoylglycerol). MAGL inhibitors thus increase 2-AG concentrations.
Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Germany.
Müller-Vahl KR, et al. Mov Disord. 2021 Jun 12. [in press].

Science: Investigation on CBD and THC degradation in cannabis resin at various temperatures
The transformation rate of CBD and THC increases with increasing temperature in dried cannabis resin. The optimum pH was between pH 4 and 6.
Cosmetics and Natural Products Research Center, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
Jaidee W, et al. Cannabis Cannabinoid Res. 2021 Jun 4. [in press]

Science/Human: 15 years of experience with the medical use of Sativex
An analysis of 38 trials with Sativex in different illnesses (multiple sclerosis, neuropathic pain, chronic pain, rheumatoid arthritis pain) revealed that the drug has an “overall acceptable safety profile.”
Jefe del Servicio de Neurología/Neurology Service Head, Hospital Clínico Universitario, Santiago de Compostela, Spain.
Prieto González JM, et al. Expert Rev Neurother. 2021 Jun 7. [in press].

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