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IACM-Bulletin of 23 May 2021

Japan: Government plans to allow cannabis containing medicines

Japan has very strict drug laws. Cannabis in all its forms is also absolutely forbidden, which is, however, a problem especially for doctors. For this reason, the regulation of drugs is to be relaxed. A few months ago, the Japanese government set up a committee to discuss an adjustment of the cannabis prohibition. In addition to tightening the laws, there was a discussion about whether cannabis should not be allowed as a substance in medicine.

According to initial reports, the Ministry of Health has decided in favour and wants to allow cannabis as a medicinal substance for the first time. If permission for the approval of such drugs is indeed approved, Japan will have to change its drug laws, as so far neither the production nor the import of drugs containing cannabis is legal. How far Japan will relax the laws in the process is not yet certain.

Sumikai of 15 May 2021

USA: The medical use of oral cannabis preparations becomes legal in Alabama

A new law permits state-registered patients to possess up to “70 daily dosages” of medical cannabis at one time. Doses of authorized cannabis products will be capped at a maximum of 50 milligrams for the first 90 days. Doctors may raise this dosage to 75 milligrams after 90 days. Patients are not permitted access to cannabis flower under the law. Rather, medical cannabis formulations need to be in the form of: “tablets, capsules, tinctures, or gel cubes for oral use; gels, oils or creams for topical use, or suppositories, transdermal patches, nebulizers, or liquids or oils for use in an inhaler.” These restrictions are rather unusual for medical cannabis laws in the US.

To qualify to participate in the program, patients must be diagnosed with one of 15 eligible conditions, including chronic pain, epilepsy, depression, nausea due to different causes, multiple sclerosis, autism spectrum disorder, Crohn’s disease, post-traumatic stress disorder, Tourette syndrome and Parkinson’s disease.

NORML of 20 May 2021

Science/Human: The authorisation to use cannabis reduced high opioid use

The authorisation to use cannabis resulted in a reduction of opioid use in a sample of 5373 regular opioid users in the Canadian province of Alberta. This is the result of research at the Li Ka Shing Centre for Health Research Innovation of the University of Alberta in Edmonton, Canada. All adult patients defined as chronic opioid users who were authorized medical cannabis by their health care provider in Alberta, Canada from 2013 to 2018 were compared to non-authorized chronic opioid using controls.

Average age was 52 years and 54% were female. Patients on low dose opioids had an increase in their weekly opioid dose per week, whereas higher dose users, showed a significant decrease over 6 months compared to controls. Authors concluded that “this short-term study found that medical cannabis authorization showed intermediate effects on opioid use, which was dependent on initial opioid use. Greater observations of changes (…) appear to be in those patients who were on a high dosage of opioids.”

Lee C, Lin M, Martins KJB, Dyck JRB, Klarenbach S, Richer L, Jess E, Hanlon JG, Hyshka E, EURich DT. Opioid use in medical cannabis authorization adult patients from 2013 to 2018: Alberta, Canada. BMC Public Health 2021:21;843.

Science/Human: Topical cannabis may be helpful in the treatment of venous leg ulcers

In an open study with 14 patients suffering from treatment resistant leg ulcers the administration of cannabis resulted in significant improvements. Patient suffered from 16 recalcitrant leg ulcers and were treated with Topical Cannabis-Based Medicines in conjunction with compression bandaging, every second day, to both wound bed and peri-wound tissues. The cohort had a mean age of 76 years and was medically complex.

Complete wound closure, defined being fully epithelialized, was achieved among 11 patients (79%) and 13 wounds (81%) within a median of 34 days. All three remaining patients demonstrated progressive healing trends but were lost to follow-up. The treatments were well tolerated, and no significant adverse reactions were experienced. Authors from the Division of Palliative Care of the University of Toronto, Canada, concluded that “the rapid wound closure of previously non-healing venous leg ulcers among elderly and highly complex patients suggests that Topical Cannabis-Based Medicines may become effective adjuvants in conjunction with compression therapy.”

Maida V, Shi RB, Fazzari FGT, Zomparelli L. Topical Cannabis-Based Medicines - A Novel Adjuvant Treatment for Venous Leg Ulcers: An Open-Label Trial. Exp Dermatol. 2021 May 19. [in press].

Science/Human: THC may improve perfusion in patients with vascular disease of the eye

In a placebo controlled study with 24 healthy subjects, who received 5 mg oral THC or a placebo, THC improved blood flow in the retina. This is the result presented by investigators at the Department of Clinical Pharmacology of the Medical University of Vienna, Austria.

Placebo had no effect on total blood flow in the retina and retinal venous oxygen content. In contrast, THC induced a significant increase in retinal blood flow from a mean of 39 microlitres per minute to 41 microlitres per minute, which was accompanied by a significant increase in retinal venous oxygen content (from mean of 0.129  to 0.132 mL oxygen per millilitre. Authors concluded that the “drug may therefore be a candidate for improving perfusion in patients with ocular vascular disease.”

Hommer N, Schmidl D, Kallab M, Bauer M, Werkmeister RM, Schmetterer L, Abensperg-Traun M, Garhöfer G. The Effect of Orally Administered Low-Dose Dronabinol on Retinal Blood Flow and Oxygen Metabolism in Healthy Subjects. J Ocul Pharmacol Ther. 2021 May 17. [in press].

Science/Human: Many patients believe that CBD may be helpful in reducing pain

In a survey with 253 participants the majority answered that CBD help with their pain (59%) and allow them to reduce their pain medications (67%). Investigation was conducted by Clinical Research of Vitamed Research in Palm Desert, USA. Among participants, 62% reported trying a CBD product [including products containing THC].

They reported believing that CBD was a good treatment option (71%), not harmful (75%), and not addictive (65%). About half of participants (52%) report that they would be more comfortable with their physician prescribing CBD products. The overall attitude and experience of participants regarding CBD is reported as positive, while 92% of people expressed a desire to learn more about it.

Schilling JM, Hughes CG, Wallace MS, Sexton M, Backing M, Moeller-Bertram T. Cannabidiol as a Treatment for Chronic Pain: A Survey of Patients' Perspectives and Attitudes. J Pain Res. 2021;14:1241-1250.

News in brief

IACM: Some new research articles in Cannabis and Cannabinoid Research
Khodadadi H, et al. Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA
Purcell C, et al. Reduction of Benzodiazepine Use in Patients Prescribed Medical Cannabis
Schlienz NJ, et al. A Cross-Sectional and Prospective Comparison of Medicinal Cannabis Users and Controls on Self-Reported Health
Nichols JM, et al. Immune Responses Regulated by Cannabidiol
Wright M, et al. Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence

Science/Human: Cannabis may be helpful in palliative end-of-life care
In a survey among 342 patients, who were terminally ill and received palliative or hospice care, “cannabis use may operate as an alternative to support forms of care like hospice.”
Department of Health Management & Policy, Iowa City, USA.
Croker JA 3rd, Bobitt J, et al. am J Hosp Palliat Care. 2021:10499091211018655.

Economy: Tilray and Aphria merge to the world’s biggest cannabis company
Tilray shareholders approve Aphria merger, creating world's biggest cannabis company by revenue
MarketWatch of 2 May 2021

Morocco: The country wants to export cannabis for medicinal use mainly to EURope
Morocco’s Ministry of Interior developed a study, showing the country’s interest to prioritize the EURopean market in terms of the supply of medical cannabis.
Morocco World News of 5 May 2021

Zimbabwe: Government announces guidelines for the production of medicinal cannabis
The southern African nation's laws only allow for cultivation of cannabis for medicinal and scientific uses. Zimbabweans were allowed to apply for licences to grow cannabis for medicinal and research purposes since April 2018 but the process to put in place laws to regulate the enterprises has been slow.
Bulawayo of 13 May 2021

Science/Cells: CBDV and CBG have protective effects on the blood-brain barrier
New research shows that CBG (cannabigerol) and CBDV (cannabidivarin) were protective against injuries of the blood-brain barrier due to reduced blood supply, which may happen in stroke and according to authors “warrant further investigation into these compounds in ischemic stroke.
Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom.
Stone NL, et al. Cannabis Cannabinoid Res. 2021 Mar 17. [in press].

Science/Cells: CBD protects bowel cells from inflammation
In a cell model of intestinal epithelium CBD was shown to protect cells from inflammation. Authors wrote that their research “show cannabidiol as the most promising compound against intestinal inflammatory condition.”
Department of Pharmaceutical Sciences, University of Padova, Italy.
Cocetta V, et al. Front Pharmacol. 2021;12:641210.

Science: CBG shows antibacterial properties against Streptococcus mutans
Streptococcus mutans (S. mutans) is a gram-positive facultatively anaerobic bacterium and the most common pathogen associated with tooth caries. In a new study CBG (cannabigerol) showed antibacterial effects against this bacterium.
Institute of Dental Sciences, The Hebrew University of Jerusalem, Israel.
Aqawi M, et al. Front Microbiol. 2021;12:656471.

Science/Human: Medical cannabis use may not increase the risk for stroke or heart attack
A meta-analysis of available studies shows that cannabis use “was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users.
Department of Pharmacotherapy, School of Pharmacy, University of Utah, Salt Lake City, USA.
Watanabe AH, et al. J Am Pharm Assoc (2003). 2021:S1544-3191(21)00111-4.

Science: CBD induces anti-psychotic effects in mice
In mice acute administration of CBD “induces acute antipsychotic-like effects that last for 24-h.”
Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Pedrazzi JFC, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2021:110352.

Science: The endocannabinoid system may mediate the effect of gut bacteria on mood
New research “suggests that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.”
Department of Psychiatry, University of Oxford, UK.
Minichino A, et al. Mol Psychiatry. 2021 May 17. [in press].

Science/Human: Cannabis use may not have an effect on hospitalisation in youth
An analysis of data of 1216 young people showed “that daily cannabis use was not associated with hospitalization among (…) youth.”
BC Centre on Substance Use, University of British Columbia, Vancouver, Canada.
Reddon H, et al. Harm Reduct J. 2021;18(1):53.

Science/Human: Adverse effects of cannabis may not only be attributed to THC and CBD
In an analysis of cannabis patients, who received different cannabis strains for pain treatment, the number of short-term and long-term adverse effects was not only related to THC and CBD, but other cannabis compounds may be of relevance.
Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Aviram J, et al. Pharmacol Res. 2021:105651.

Science/Animal: CBD may have an effect on anaesthesia with isoflurane
In a study with rats CBD had a dose depending effect on the course of isoflurane anaesthesia and it can reduce induction time.
Veterinary Faculty, Institute of Preclinical Sciences, University of Ljubljana, Slovenia.
Uric M, et al. Cannabis Cannabinoid Res. 2021 May 11. [in press].

Science/Human: Different cannabis strains were well tolerated in pain patients
In an analysis of 585 pain patients, who were followed for 12 months, a symptom improvement over time “was observed for pain, tiredness, drowsiness, anxiety, and well-being. Patients authorized THC-dominant products exhibited less symptom improvement for anxiety and well-being relative to those authorized CBD-dominant or balanced (THC:CBD) products. Medical cannabis was well tolerated across all product profiles.”
Canopy Growth Corporation, Smiths Falls, Canada.
Kalaba M, et al. Cannabis Cannabinoid Res. 2021 May 10. [in press].

Science/Human: No relevant effect of cannabis use on outcomes after surgery
In a study, which included 606 cannabis users and 606 controls, who all underwent surgery “results do not demonstrate a convincing association between self-reported cannabis use and major surgical outcomes or pain management.“
Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Zhang BH, et al. Reg Anesth Pain Med. 2021:rapm-2021-102479.

Science/Animal: Inactivation of the CB2 receptor accelerates a mouse model of amyotrophic lateral sclerosis
New research with a mouse model of amyotrophic lateral sclerosis suggests that activation of the CB2 receptor may be neuroprotective in amyotrophic lateral sclerosis.
Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain.
Rodríguez-Cueto C, et al. Brain Pathol. 2021:e12972.

Science/Human: Patients suffering from psychosis with a history of cannabis use have better neurocognitive performance
A study with 30 patients with first-episode schizophrenia, who had a history of cannabis use, had better neurocognitive performance than 53 non-cannabis-users with first-episode schizophrenia.
Institut of Neuropsychiatric Care, Prague, Czech Republic.
Hájková M, et al. Cogn Neuropsychiatry. 2021:1-16.

Science: Cannabinoids are antioxidant agents
CBG, CBD, THC, CBN, CBGA, CBDA and THCA were tested with regard to their antioxidant activity. Authors wrote that their results “prove that all the examined cannabinoids exhibit antioxidant activity manifested in their ability to scavenge free radicals, to prevent the oxidation process and to reduce metal ions.”
Department of Chromatography, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University in Lublin, Poland.
Dawidowicz AL, et al. Fitoterapia. 2021;152:104915.

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