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IACM-Bulletin of 09 May 2021

IACM: IACM: Two Decades of the International Association for Cannabinoid Medicines

In an article for the IACM journal Cannabis and Cannabinoids Research the current chairwoman and the executive director of the IACM give a historical overview of the development of the Association. During the past 20 years until today, it evolved toward the most important scientific society for clinical research in the field of cannabis-based medicines.

The overarching aim of the IACM is to advance the knowledge on cannabis, cannabinoids, the endocannabinoid system, and related topics especially with regard to their therapeutic potential, which would allow more patients to profit from a treatment with cannabis-based medicines and ease legislators to adopt their policies.

Grotenhermen F, Müller-Vahl KR. Two Decades of the International Association for Cannabinoid Medicines: 20 Years of Supporting Research and Activities Toward the Medicinal Use of Cannabis and Cannabinoids. Cannabis Cannabinoid Res. 2021;6(2):82-87.

Science/Human: About 20% of paediatric oncology patients in Canada use cannabis products

According to a survey conducted among patients and caregivers of children with cancer attending a paediatric oncology clinic with 64 participants 14 (22%) reported the use of cannabis. The study was published by investigators of the Department of Pediatrics and Child Health of the University of Manitoba in Winnipeg, Canada.

Half of cannabis users used it for either cancer treatment or symptom management, or both. Leukaemia was the most frequent diagnosis in children whose caregivers reported using cannabis and the majority of them were still receiving active cancer treatment. All of the respondents using cannabis experienced symptom improvement. Oily solutions were the most commonly used preparations (86%). Authors concluded that their survey “shows that cannabis, mostly oil products, was used by one-fifth of children with cancer during or after the completion of cancer treatment.”

Chapman S, Protudjer J, Bourne C, Kelly LE, Oberoi S, Vanan MI. Medical cannabis in pediatric oncology: a survey of patients and caregivers. Support Care Cancer. 2021 May 1. [in press].

Science/Human: CBD may be effective in many forms of epilepsy in children and young adults

According to a retrospective analysis of 78 patients treated with CBD (cannabidiol) in the years 2016 to 2019 the cannabinoid may be effective in different forms of treatment resistant epilepsy. This research was conducted by investigators of the Department of Paediatrics of the Danish Epilepsy Centre Filadelfia in Dianalund, Denmark.

In 51 patients with seizure frequency registration, about 31% had a 50% or more seizure reduction at three months, 31% at six months, 28% at 12 months and 20% at 24 months. Some degree of seizure reduction was seen after 3 months in 69% of patients. Seizure reduction was higher with clobazam co-medication. Authors concluded that “cannabidiol is a treatment option in children and young adults with severe refractory epilepsy other than Dravet and Lennox-Gastaut syndromes.”

Zilmer M, Olofsson K. Cannabidiol treatment of severe refractory epilepsy in children and young adults. Dan Med J. 2021;68(5):A07200527.

Science/Human: New research does not confirm the gateway theory

Cannabis use has been proposed to serve as a “gateway” that increases the likelihood that users will engage in subsequent use of harder and more harmful substances. In a new study by investigators of Boise State University, USA, extends the literature on this theory by using three waves of data from the National Longitudinal Study of Adolescent to Adult Health (1994–2002), several tests of the cannabis gateway hypothesis were conducted.

Six of the eighteen tests were statistically significant. However, only three were substantively meaningful. These three tests found weak effects of frequent cannabis use on illicit drug use but they were also sensitive to hidden bias. Authors wrote that “results from this study indicate that marijuana use is not a reliable gateway cause of illicit drug use. As such, prohibition policies are unlikely to reduce illicit drug use.”

Jorgensen C, Wells J. Is marijuana really a gateway drug? A nationally representative test of the marijuana gateway hypothesis using a propensity score matching design. Journal of Experimental Criminology. 2021 Apr 05. [in press].

Science/Human: The relationship between cannabis use and schizophrenia may be mediated by common genetic risk factors

According to a large study from the USA liability to cannabis use disorders was significantly associated with schizophrenia. Investigators from the Department of Psychiatry of Washington University School of Medicine in St. Louis used large genome-wide association studies summary statistics, which ranged from 161,405 to 357,806 individuals of EURopean ancestry.

Authors found mixed evidence of a causal relationship, with one analysis (the latent causal variable analysis) finding no evidence of causality, but another analysis (the multivariable Mendelian Randomization analysis) suggesting a significant, risk-increasing effect of cannabis use disorder on liability to schizophrenia. Authors concluded that “liability for cannabis use disorder appears to be robustly associated with schizophrenia, (…) with mixed evidence to support a causal relationship between cannabis use disorder and schizophrenia.”

Johnson EC, Hatoum AS, Deak JD, Polimanti R, Murray RM, Edenberg HJ, Gelernter J, Di Forti M, Agrawal A. The relationship between cannabis and schizophrenia: a genetically informed perspective. Addiction. 2021 May 5. [in press].

Science/Human: Many people with Parkinson’s disease profit from a treatment with cannabis

To understand the experience of cannabis for people with Parkinson’s, The Michael J. Fox Foundation (MJFF) launched a survey through its online Fox Insight study in January 2020. It asked about types of cannabis used and methods of use, as well as how cannabis affected Parkinson’s disease symptoms. Over four months, nearly 1,900 people with Parkinson’s participated.

Study leader Dr Maureen Leehey of the University of Colorado Denver, recently presented study results at the 2021 American Academy of Neurology Virtual Annual Meeting. More than half of respondents reported mild benefits on sleep, mood and pain. On average, respondents said they used a once daily, oral dose of cannabis. Side effects were common but usually mild. Over 30 percent of respondents did not discuss cannabis use with their physician.

The Michael J. Fox Foundation of 26 April 2021

News in brief

USA: Fourteenth National Clinical Conference on Cannabis Therapeutics
Patients Out of Time is pleased to present The Fourteenth National Clinical Conference on Cannabis Therapeutics, an online conference, from Thursday May 20th through Saturday, May 22nd. The theme of the conference is "The State of the Science.”
Conference website

Switzerland: Cannabis legalisation moves closer
The Health Committee of the National Council wants to adapt the regulations on using cannabis to social reality. A regulated market should also provide better protection and prevention. The Committee for Social Security and Health of the National Council (SGK-N) approved a proposal for the legalisation of cannabis for adults by 13 votes to 11, with one abstention.
Zuerichsee-Zeitung of 30 April 2021

Italy: A cannabis patient, who grew his own cannabis, was acquitted
A judgement in Italy rekindles the debate on the adoption of an ad hoc law. The Court of Arezzo acquitted Walter De Benedetto - patient rendered disabled by rheumatoid arthritis - from the charge of cultivation of cannabis. Judge Lombardo considered the production of cannabis found by the carabinieri in the house of Ripa di Olmo, on the outskirts of Arezzo, as necessary for the personal therapeutic use of the 49-year-old.
adnkronos of 27 April 2021

Science/Human: After legalisation of cannabis many fibromyalgia patients in Canada use the drug medicinally
In a group of 1000 rheumatology participants in a survey 117 were diagnosed with fibromyalgia. The medical use of cannabis was reported by 28 (24%). Reported symptom relief was substantial.
Division of Rheumatology, McGill University Health Centre, Montreal, and Alan Edwards Pain Management Unit, McGill University Health Centre, Canada.
Fitzcharles MA, et al. Clin Exp Rheumatol. 2021 Apr 29. [in press].

Science/Animal: The endocannabinoid system involves sleep patterns
A study with rats shows that the activation of the CB1 receptor in a certain brain region, the septal nucleus, increases rapid eye movement sleep (REM). REM sleep is associated with dreaming.
All India Institute of Medical Sciences, New Delhi, India.
Puskar P, et al. Physiol Behav. 2021:113448.

Science/Animal: The endocannabinoid system may be altered after regular opioid administration
According to research with rats the endocannabinoid system may be changed after the administration of opiates. Authors noted “that the endogenous cannabinoid system may participate in the opioid-induced reward.”
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, United States.
Zhang H, et al. Front Pharmacol. 2021;12:632757.

Science/Human: CBD may be an inhibitor of the liver enzyme CYP1A2
In a study with healthy adults, who received different doses of CBD from 250 mg once daily to 750 mg twice daily and caffeine results show, that CBD may be an inhibitor of CYP1A2, a liver enzyme, which is involved in the degradation of several medicinal drugs.
GW Research Ltd, Cambridge, UK.
Thai C, et al. Clin Pharmacol Drug Dev. 2021 May 5. [in press].

Science/Human: CBD may be helpful in the management of bruxism according to a case report
Researchers presented a case report of a man with severe bruxism, whose symptoms were nearly completely relieved by treatment with CBD (cannabidiol).
Global Brain Health Institute, University of California, San Francisco, USA.
Pina-Escudero SD, et al. Neurocase. 2021:1-3.

Science/Animal: Activation of the endocannabinoid system may be protective against tardive dyskinesia
Tardive dyskinesia is a side effect of treatment with neuroleptics. Research with rats shows, that activation of the CB1 receptor may protect against the development of tardive dyskinesia.
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Röpke J, et al. Pharmacol Biochem Behav. 2021:173193.

Science/Human: Investigation into the willingness to utilise the new prescription medicinal cannabis system in New Zealand
Different predictors were identified with regard to the willingness of the citizens of New Zealand to participate in a new medicinal cannabis program. One major positive predictor was higher income and a major negative predictor was growing of cannabis.
Senior Researcher, SHORE & Whāriki Research Centre, Massey University, New Zealand.
Rychert M, et al. N Z Med J. 2021 Apr 30;134(1534):66-75.

Science/Animal: The CB2 receptor was protective in melanoma
In a study with mice researchers found a protective role of the CB2 receptor in melanoma, which was mediated by certain immune cells, so-called B cells.
Institute of Pathology, University of Bern, Switzerland.
Gruber T, et al. Cancers (Basel). 2021;13(8):1934.

Science/Animal: Palmitoylethanolamide reduces proliferation of colon cancer cells
The endocannabinoid palmitoylethanolamide was shown to reduce proliferation of colon cancer cells as well as their migration in mice.
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Pagano E, et al. Cancers (Basel). 2021;13(8):1923.

Science/Human: Many elder people with multiple sclerosis, rheumatic arthritis and cancer use cannabis
In an analysis of data on people 60 years or older with multiple sclerosis (N = 135), arthritis (N = 582) or cancer (N = 622) from the Medical Cannabis Program in Illinois researchers found that “cannabis may be a viable alternative to opioids for those with these conditions and experiencing pain” among others.
College of Public Health, University of Iowa, USA.
Kaskie B, et al. Brain Sci. 2021;11(5):532.

Science/Cells: How CBD exerts its anti-cancer effects
Researchers found several mechanisms by which CBD exerts anti-cancer effects. For example, CBD is inhibiting an enzyme called FOXM1 involved in cell proliferation. Authors concluded that “CBD could represent a promising nontoxic therapeutic for treating tumors of various origins.”
California Pacific Medical Center, Research Institute, USA.
Desprez PY, et al. Cannabis Cannabinoid Res. 2021;6(2):148-155.

Science/Animal: Morphine induces an increase of CB2 receptors in the spinal cord
In a study with rats administration of morphine resulted in increased expression of CB2 receptors in the dorsal horn of the spinal cord. Authors concluded that “synergistic effects of morphine-cannabinoid treatments, therefore, may involve CB2-mu opioid receptor interactions, pointing to novel therapeutic treatments for a variety of medical conditions.”
Department of Psychology, Queen's University, Kingston, Canada.
Grenier P, et al. Cannabis Cannabinoid Res. 2021;6(2):137-147.

Science/Animal: CBD reduces withdrawal symptoms in nicotine dependence
In a study with nicotine-dependent rats injections of CBD in a dose of 7.5 mg per kilogram per day reduced withdrawal symptoms.
Department of Neuroscience, The Scripps Research Institute, La Jolla, USA.
Smith LC, et al. Psychopharmacology (Berl). 2021 Apr 28. [in press].

Science/Animal: Pharmacokinetics of CBD in dogs
In a placebo-controlled test with 20 healthy adult dogs, who received different doses of CBD ((1, 2, 4, or 12 mg/kg in a cannabis extract) or a placebo for 28 days blood concentrations increased in a dose-dependent manner. Only the higher dose was associated worse adverse events, mainly gastrointestinal.
Canopy Animal Health, Canopy Growth Corporation, Toronto, Canada.
Vaughn DM, et al. Am J Vet Res. 2021;82(5):405-416.

Science: CBD may be transformed to THC in e-cigarettes
In e-cigarettes operating at temperatures between 250 and 500 °C CBD was partly transformed. Depending on temperature 25 to 52% of CBD was transformed mainly to THC, CBN (cannabinol) and CBC (cannabichromene).
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Budapest, Hungary.
Czégény Z, et al. Sci Rep. 2021;11(1):8951.

Science/Animal: CBD induces anticonvulsant effects in genetic models of epilepsy
In a study with genetically modified rats CBD showed antiepileptic effects. Authors noted that anticonvulsant effects of CBD were “associated with reduced chronic neuronal activity and modulation of CB1R expression.”
Neuroscience and Behavioral Sciences Department, Ribeirăo Preto School of Medicine, University of Săo Paulo, Ribeirăo Preto, Brazil.
Lazarini-Lopes W, et al. Epilepsy Behav. 2021;119:107962.

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