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IACM-Bulletin of 20 June 2021

Science/Human: The use of cannabis is associated with improved quality of life in pain patients according to a survey

According to self-reported questionnaires with 429 participants suffering from chronic non-cancer pain the medical use of cannabis improved quality of life and resulted in the reduction of other pain medication. Investigators of the Faculty of Biology of Technion-Israel Institute of Technology in Haifa, Israel conducted cross-sectional questionnaire-based study among licensed medical cannabis patients with a diagnosis of chronic non-cancer pain. They were asked to answer questions in one-month intervals for a period of six months.

429, 150, 98, 71, 77 and 82 patients reported fully on their cannabis treatment regimens at six one-month intervals, respectively. Although pain intensities did not change during the study period, analgesic medication consumption rates decreased from 46 to 28% and good Quality of Life rates increased from 49 to 62%.

Aviram J, Lewitus GM, Vysotski Y, Yellin B, Berman P, Shapira A, Meiri D. Prolonged Medical Cannabis Treatment is Associated With Quality of Life Improvement and Reduction of Analgesic Medication Consumption in Chronic Pain Patients. Front Pharmacol. 2021;12:613805.

Science/Human: Cannabis improved quality of life in brain cancer patients according to a clinical study

In a controlled clinical study with 88 patients suffering from high-grade glioma the medical use of cannabis significantly improved sleep and quality of life. The study was conducted at the National Centre for Naturopathic Medicine of Southern Cross University in Lismore, Australia. Patients received two cannabis strains with different ratios of CBD and THC. They were compared with a retrospective control group.

A comparison between the two cannabis strains after 12 weeks found that a 1:1 ratio of CBD and THC scored better than the other strain with regard to physical and functional capacity as well as improved sleep. Analysis of changes from baseline to week 12 also found 11% of 61 participants had a reduction in disease, 34% were stable, 16% had slight enhancement, and 10% had progressive disease. No serious adverse events occurred. Authors concluded that the study “demonstrated that a single nightly dose of THC-containing medicinal cannabis was safe, had no serious adverse effects and was well tolerated in patients. Medicinal cannabis significantly improved sleep, functional wellbeing, and quality of life. “

Schloss J, Lacey J, Sinclair J, Steel A, Sughrue M, Sibbritt D, Teo C. A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas. Front Oncol. 2021 May 21;11:649555.

Science/Human: Low doses of THC may improve the analgesic effects of opioids according to a study with experimental pain

In a laboratory study with 29 healthy adults low doses of oral THC (dronabinol) improved the analgesic effects of the opioid hydromorphone in tests of acute pain (thermal and pressure pain) and chronic pain (cream with capsaicin). The investigation was conducted at the Department of Psychiatry and Behavioral Sciences of Johns Hopkins University School of Medicine in Baltimore, USA. Participants received 4 mg of oral hydromorphone and the placebo or different THC doses.

A consistent dose-effect relationship of dronabinol on hydromorphone across all measures was not observed. Analgesia only improved in the hydromorphone + dronabinol 2.5 mg condition. Higher doses of THC (5 mg and 10 mg) produced adverse effects.

Dunn KE, Bergeria CL, Huhn AS, Speed TJ, Mun CJ, Vandrey R, Campbell CM. Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model. Neuropsychopharmacology. 2021;46(8):1451-1459.

Science/Human: An archaeological finding of cannabis seeds in a cemetery suggests the medical use of cannabis in China 2000 years ago

An archaeological finding of 120,000 cannabis seeds in a cemetery of the Han Dynasty (202 years BC to 220 years AD) in Chengdu, South China, suggests that cannabis was used more than 2000 years ago in China. The investigation was conducted by the National Resource Center for Chinese Materia Medica of the China Academy of Chinese Medical Sciences in Beijing, China, and other institutions from China. Authors noted that this finding “represents the largest amount of cannabis fruit remains that have been statistically analysed from any cemetery in the world thus far.”

The cannabis fruits are suspected to have been used for medical purposes in a secular context and were most likely used to stop severe bleeding of the uterus and treat lumbago and/or arthralgia. Authors concluded from their research that the “cannabis fruit remains reported here likely represent the first physical evidence of medicinal cannabis use for the treatment of metrorrhagia, severe lumbago, and/or arthralgia.”

Bai Y, Jiang M, Xie T, Jiang C, Gu M, Zhou X, Yan X, Yuan Y, Huang L. Archaeobotanical evidence of the use of medicinal cannabis in a secular context unearthed from south China. J Ethnopharmacol. 2021;275:114114.

Science/Human: A cannabis extract improved sleep in patients suffering from chronic insomnia in a control study

In a placebo-controlled cross-over study with 23 patients suffering from chronic insomnia (20 females and 3 males) a cannabis extract called ZTL-101 was superior to placebo. It was conducted by investigators of the Centre for Sleep Science, School of Human Sciences of the University of Western Australia in Crawley, Australia.

Compared to placebo, the cannabis extract decreased the Insomnia Severity Index, self-reported sleep and sleep onset latency, wake after sleep onset, total sleep time, sleep efficiency and self-reported assessments of sleep quality. Authors concluded that “two weeks of nightly sublingual administration of a cannabinoid extract (ZTL-101) is well tolerated and improves insomnia symptoms and sleep quality in individuals with chronic insomnia symptoms.”

Walsh JH, Maddison KJ, Rankin T, Murray K, McArdle N, Ree MJ, Hillman DR, Eastwood PR. Treating Insomnia Symptoms with Medicinal Cannabis: A Randomized, Cross-Over Trial of the Efficacy of a Cannabinoid Medicine Compared with Placebo. Sleep. 2021:zsab149.

Science/Human: Cannabis improved pain in patients with advanced cancer in a controlled study

In a randomised clinical study with 30 patients suffering from advanced cancer cannabis was well tolerated and improved pain control. The study was conducted by scientists of the Cancer Research of CenterHealthPartners/Park Nicollet in Minneapolis, USA. Participants were divided into groups, 15 receiving early start cannabis and 15 receiving delayed start cannabis. The early group obtained three months of medical cannabis, while the delayed group received standard oncology treatment without cannabis for the first three months. The mean doses of THC and CBD at three months were 34 mg and 17 mg, respectively.

A higher proportion of early cannabis patients achieved a reduction in opiate use and improved pain control. Patients reported higher satisfaction. Authors concluded that the “addition of MC (medical cannabis) to standard oncology care was well-tolerated and may lead to improved pain control and lower opioid requirements.”

Zylla DM, Eklund J, Gilmore G, Gavenda A, Guggisberg J, VazquezBenitez G, Pawloski PA, Arneson T, Richter S, Birnbaum AK, Dahmer S, Tracy M, Dudek A. A randomized trial of medical cannabis in patients with stage IV cancers to assess feasibility, dose requirements, impact on pain and opioid use, safety, and overall patient satisfaction. Support Care Cancer. 2021 Jun 4. [in press].

News in brief

Brasil: A committee of the House of Representatives approves a bill on the medical use of cannabis
On 8 June a special commission of the House of Representatives approved the basic text of a proposal favorable to the legalization of cultivation in Brazil, exclusively for medicinal, veterinary, scientific and industrial purposes of cannabis.
Camara of 8 June 2021

Czech Republic: Parliament advances bill to liberalise the medical use of cannabis
On 2 June the lower house of the Czech Parliament approved a bill of
amendments to the country's laws governing the production and prescription of medical cannabis and hemp. According to this law medical cannabis may be cultivated by multiple licensed private groups who may also manufacture medical cannabis products and the export of medical cannabis will now be legal point. In addition, the marketing of extracts such as isolates and tinctures will be permissible and the system of electronic prescriptions for cannabis will be updated to ease the process for doctors and patients.
Prohibition Partners of 4 June 2021

Germany: More than 80% of citizens support legal access to
About 82 % of Germans are in favour of the use of cannabis for medical purposes being exempt from punishment. This is the result of a survey conducted by the opinion research institute Civey on behalf of the editorial staff of web.de. According to the survey, about 45% of the respondents were in favour of legalising cannabis for medical purposes only. 29% advocated that cannabis should be completely legal, like tobacco. A further 8% stated that cannabis should be illegal but exempt from punishment. Only 12.7% explicitly argued that cannabis should be completely illegal, even for medical purposes. 5.6% had no opinion.
Arbeitsgemeinschaft Cannabis als Medizin of 29 May 2021

Science/Human: In contrast to tobacco use cannabis use is not associated atherosclerosis
According to data from a large study, the CARDIA study, with 5115 people cannabis use does not have an impact on the thickness of the intima-media of large arteries, while tobacco use had. Authors concluded that their study “adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.”
Institute of Primary Health Care (BIHAM), University of Bern, Switzerland; Department of Paediatrics, University Hospital Bern, Switzerland.
Jakob J, et al. Am J Med. 2021;134(6):777-787.e9.

Science/Human: The diet may have an effect on endocannabinoids in the bowel
Results of a study with 35 participants aged 18 to 70 years suggests that “fat and energy intake may influence plasma and intestinal concentrations” of endocannabinoids and related substances.
Department of Agricultural Sciences, University of Naples "Federico II", Portici, Italy.
Tagliamonte S, et al. EUR J Nutr. 2021;60(4):2203-2215.

Science: The potency of cannabis in the US increased in the past decade
An analysis of a total of 14,234 samples of herbal cannabis confiscated in the USA between 2009 and 2019 showed that the mean THC concentration increased from 9.8% to 14.9%. Researchers also observed an increase in CBD concentration. Authors concluded that there “appears to be a recent trend of the inclusion of higher CBD levels containing chemovars in illicit cannabis.”
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, USA.
ElSohly MA, et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6(6):603-606.

Science/Human: Cannabis use was associated with increased exercise among young adults
According to an analysis of data from a study with 12,043 participants in the USA “marijuana use is not significantly related to exercise, counter to conventional wisdom that marijuana users are less likely to be active. Indeed, the only significant estimates suggest a positive relationship, even among heavier users during the past 30 days.”
Department of Health Management and Policy, Miami Herbert Business School, University of Miami, United States of America.
French MT, et al. Prev Med. 2021;147:106518.

Science/Animal: Endocannabinoids protect from tardive dyskinesia induced by antipsychotic medication
Tardive dyskinesia, a severe movement disorder, is a side effect associated with the long-term use of certain antipsychotics. Research with rats shows that increasing endocannabinoid concentration by inhibiting their degradation protects from tardive dyskinesia induced by the antipsychotic drug haloperidol.
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Röpke J, et al. Pharmacol Biochem Behav. 2021 Jul;206:173193.

Science/Human: Cannabis intoxication in children increased after legalisation of cannabis in Canada
According to an analysis of data from a division of emergency medicine in Toronto there was a significant increase of children younger than 12 years with overdose symptoms of cannabis use. Particularly, the increase was large with regard to edibles. Authors wrote that the “recreational cannabis legalization in Canada is associated with increased rates of severe intoxications in children.”
Division of Emergency Medicine, The Hospital for Sick Children, Toronto, Canada.
Cohen N, et al. Clin Toxicol (Phila). 2021:1-6.

Science/Human: Cannabis use is associated with altered development of the nervous system
According to a study with 799 participants from eight EURopean sites “cannabis use during adolescence is associated with altered neurodevelopment, particularly in cortices rich in cannabinoid 1 receptors and undergoing the greatest age-related thickness change in middle to late adolescence.”
Department of Psychiatry, University of Vermont Larner College of Medicine, Burlington, USA.
Albaugh MD(, et al. JAMA Psychiatry. 2021 Jun 16. [in press].

Science/Human: Cannabis smokers inhale less toxicants compared to tobacco smokers
According to a comparison between 18 exclusive cigarette smokers and 16 exclusive cannabis smokers cannabis smokers “demonstrated lower levels of toxicant exposure for most biomarkers.” Investigators measured combustion-related biomarkers in urine of participants.
Department of Psychology, University of Wisconsin - Stevens Point, USA.
Meier E, et al. Nicotine Tob Res. 2021:ntab125.

Science/Human: Cannabis use does not have a negative effect on ADHD according to review
According to a systematic review of the scientific literature on cannabis effects on adolescents and young adults the result “does not support the hypothesis that cannabis use has a deleterious impact on neuropsychological tasks in transitional age youth with ADHD.”
Department of Psychiatry and Behavioral Sciences, Stanford University, USA.
Cawkwell PB, et al. Harv Rev Psychiatry. 2021 Jun 16. [in press].

Science: Elucidating the mechanisms of cannabinoid effects on breast cancer cells
A new study investigated the molecular mechanisms of the anti-cancer properties of THC and CBD on estrogen receptor positive breast cancer cells. They disrupt cell cycle progression. While THC induced programmed cell death (apoptosis) CBD triggered autophagy to promote apoptosis. Authors wrote that “all cannabinoids, albeit by different actions, target aromatase and ERs, impairing, in that way, the growth of ER+ breast cancer cells, which is dependent on estrogen signalling.”
Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal.
Amaral C, et al. J Steroid Biochem Mol Biol. 2021;210:105876.

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