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IACM-Bulletin of 22 October 2023

Science/Human: Cannabis users had better outcomes and mortality due to COVID-19 compared to non-users

Investigators of the American College of Chest Physicians in Glenview, USA, analysed data of 322,214 patients with COVID-19 infection admitted to hospitals in the United States, of whom 2,603 were cannabis users.

Cannabis users had lower rates of intubation (OR: 0.64), acute respiratory distress syndrome (OR: 0.39), acute respiratory failure (OR: 0.53), severe sepsis with multiorgan failure (OR: 0.68) and mortality was significantly reduced by about 50% (OR: 0.48). Authors concluded: “Marijuana smokers had better outcomes and mortality compared to non-users. The beneficial effect of marijuana use may be attributed to its potential to inhibit viral entry into cells and prevent the release of proinflammatory cytokines, thus mitigating cytokine release syndrome.”

Siddiqui FS, Sattar SBA, Wei C, Mustafa N, Grovu R, Mustafa A. Exploring the relationship between marijuana smoking and covid-19 outcomes. Chest Journal of 11 October 2023.

Science/Human: CBD may improve sleep quality

According to an 8 week placebo-controlled study CBD (cannabidiol) may improve the quality and enhance the immunosurveillance by natural killer cells. Investigators of the Department of Kinesiology, Nutrition, and Dietetics of the University of Northern Colorado in Greeley, USA, included 28 healthy subjects in the study and administered a daily dose of 50 mg of oral CBD or a placebo.

After completing the 8-week intervention, there were no significant changes in body weight or body fat. There were also no significant differences between the CBD and the placebo groups with respect to mental health measures, sleep quantity, or circulating immunophenotype as a result of the intervention. However, the CBD group experienced significant improvements in sleep quality measured objectively using a sleep questionnaire and enhanced Natural Killer (NK) immune cell function.

Kisiolek JN, Flores VA, Ramani A, Butler B, Haughian JM, Stewart LK. Eight Weeks of Daily Cannabidiol Supplementation Improves Sleep Quality and Immune Cell Cytotoxicity. Nutrients. 2023;15(19):4173.

Science/Human: CBD may reduce increased higher blood flow in the hippocampus in people with high risk for psychosis

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Investigators of the Department of Psychosis Studies at the Institute of Psychiatry, Psychology & Neuroscience of King's College London, UK, investigated the effects of a single dose of 600 mg CBD or a placebo on blood flow of 33 patients with a high risk for psychosis. The results of both groups were compared to 19 healthy controls.

Placebo-treated patients had significantly higher hippocampal cerebral blood flow bilaterally compared to healthy controls. However, investigators found a significant linear relationship in the right hippocampus such that cerebral blood flow was highest in the placebo group, lowest in controls and intermediate in the CBD group. Authors concluded that these “findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.”

Davies C, Bossong MG, Martins D, Wilson R, Appiah-Kusi E, Blest-Hopley G, Zelaya F, Allen P, Brammer M, Perez J, McGuire P, Bhattacharyya S. Increased hippocampal blood flow in people at clinical high risk for psychosis and effects of cannabidiol. Psychol Med. 2023:1-11.

Science/Human: Many cancer survivors use cannabis as sleep aid

According to a survey by investigators of the Department of Psychology at the Faculty of Science of Memorial University, St. John's, Canada, many use cannabis as sleep aid. On average participants received their cancer diagnosis 12.5 years prior.

Of participants, 23.5% currently used cannabis as a sleep aid, with reported benefits including relaxation, reduced time to fall asleep, fewer nocturnal awakenings and improved sleep quality. Two thirds (68.3%,) only began using cannabis for sleep after their cancer diagnosis. Over a third of participants (36.3%) used cannabis as a sleep aid every day.

Lee RM, Donnan J, Harris N, Garland SN. A cross-sectional survey of the prevalence and patterns of using cannabis as a sleep aid in Canadian cancer survivors. J Cancer Surviv. 2023 Oct 14. [in press]

Science/Human: Patients with severe fibromyalgia pain use cannabis more often than those with lesser pain but may have little effect from cannabis

In a cross-sectional study with 1,213 patients suffering from chronic nociplastic pain (NPP) investigators of the Chronic Pain and Fatigue Research Center of the Department of Anesthesiology at the University of Michigan in Ann Arbor, USA, investigated the effects of cannabis.

Higher fibromyalgia scores were associated with less self-reported improvement in pain and health since initiating medical cannabis use, as well as more cannabis-related side effects. Paradoxically, higher fibromyalgia scores were also associated with higher usage of concomitant medication use but also with substituting cannabis for significantly more medication classes, including opioids and benzodiazepines. Authors noted that these “seemingly contradictory findings may reflect higher symptom burden, polypharmacy at baseline, or that NPP may be challenging to treat with cannabis.”

Scott JR, Williams DA, Harte SE, Harris RE, Litinas E, Sisley S, Clauw DJ, Boehnke KF. Relationship between Nociplastic Pain Involvement and Medication use, Symptom Relief, and Adverse effects Among People using Medical Cannabis for Chronic Pain. Clin J Pain. 2023 Oct 12. [in press]

Science/Human: CBD may be useful in all types of drug-resistant epilepsy

Investigators of Aix-Marseille University, France, treated 73 patients with purified CBD as add-on treatment for their drug-resistant epilepsy, 51 of them with epileptic encephalopathies (group A) and 22 with focal or multifocal epilepsy (group B).

Respectively, 15 patients (29.4%) and five patients (22.7%) were responders during the follow-up period. The most frequent side effect was somnolence. At the end of follow-up, 15 patients in group A (29.4%) and nine patients in group B (40.1%) had stopped the high-purified-CBD treatment due to aggravation of seizure, absence of positive effects, or adverse events. Authors wrote that their “study showed no significant difference regarding the type of drug-resistant epilepsy and suggests that this treatment may be of interest for all types of drug-resistant epilepsy.”

Perriguey M, Succar ME, Clément A, Lagarde S, Ribes O, Dode X, Rheims S, Bartolomei F. High-purified cannabidiol efficacy and safety in a cohort of adult patients with various types of drug-resistant epilepsies. Rev Neurol (Paris). 2023:S0035-3787(23)01044-5.

Science/Human: Mixed effects on the society following cannabis legalisation in Canada

Writing in the Journal of the Canadian Medical Association investigators of the Centre for Applied Research in Mental Health and Addiction in Vancouver, Canada, had a look at the evidence on the outcome of 5 years of cannabis legalisation in Canada. They noted that there is evidence that “outcomes related to health — such as the prevalence of cannabis use, cannabis-related emergency department visits and admissions to hospital and cannabis-impaired driving — have mostly increased or remained steady.”

On the other hand “substantial reductions in criminal arrests and charges related to cannabis use — and related stigma and other personal burdens — among both adults and youth should be noted as related positive social justice and possibly indirect public health outcomes.”

Fischer B, Jutras-Aswad D, Hall W. Outcomes associated with nonmedical cannabis legalization policy in Canada: taking stock at the 5-year mark. CMAJ of 10 October 2023.

News in brief

France: the country’s medical cannabis experiment will continue

France’s Minister for Health, Aurélien Rousseau, has confirmed that the country’s medical cannabis experiment will continue, providing some solace for its 2,540 patients. Despite pressure from cross-party parliamentarians, elected officials, scientists and doctors, Mr Rousseau refused to commit to rolling medical cannabis out generally across France this year.

Business of Cannabis of 16 October 2023.

UK: The first UK grown cannabis is expected by the end of 2023

The first UK-grown cannabis-based medicines are expected to be available to patients by the end of 2023, in what could be a significant milestone for the sector. Midlands-based medical cannabis producer Dalgety has announced a new contract agreement with Grow Pharma and its licensed JV partner IPS Pharma, enabling the commercial supply of pharmaceutical-grade, THC-rich prescription medicines to the UK market.

CannabisHealth of 19 October 2023.

Science/Human: The medical use of cannabis does not decrease activities of daily living in older adults

According to a prospective observational study of patients aged 65 years or older that initiated cannabis treatment for different indications, mostly chronic non-cancer pain, during 2018–2020 in a specialized geriatric clinic there was no decrease in activities of daily living.

Clinical Research Center, Soroka University Medical Center, Be’er-Sheva, Israel.

Abuhasira R, et al. MDPI Journals of 3 October 2023.

Science/Cells: CBD shows anti-cancer effects in triple-negative breast cancer cells

In triple -negative breast cancer cells “CBD exerts a highly cytotoxic effect inducing bubbling cell death.”

Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.

D'Aloia A, et al. Int J Mol Sci. 2022;23(13):7145.

Science/Cells: CBN inhibits cell growth and triggers cell cycle arrest and apoptosis in cancer cells

Cannabinol (CBN) is a weak-psychoactive cannabinoid and has been shown to exert several bio-logical activities. Researchers showed that CBN inhibits cell growth in several cancer cells, including liver cancer, glioma and breast cancer cell lines.

Department of Biological Sciences, University of Lethbridge, Canada.

Zhong N, et al. ScienceDirect of March 2023.

Science/Cells: Endocannabinoids reverse chemoresistance in ovarian cancer cells

The endocannabinoids anandamide and 2-AG reversed resistance to several chemotherapeutic agents in ovarian cancer cells. “Our findings suggest that drugs targeting ECS may have the potential to be adjuvants for chemotherapy by increasing the efficacy of chemotherapeutic drugs and decreasing their side effects.”

Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University Tainan, Taiwan.

Lin YS, et al. Am J Cancer Res. 2023;13(9):4163-4178.

Science/Cells: CBD and THCV may reduce inflammation in coronary artery muscle cells and endothelial cells

In studies with coronary artery muscle cells and endothelial cells the cannabinoids CBD (cannabidiol) and THCV (tetrahydrocannabivarin) reduced inflammation. “Considering their effect on both cell types studied, further preclinical studies could address the use of CBD and THCV in drug-eluting stents for coronary interventions.”

Institute of Pharmacology and Toxicology, Rostock University Medical Center, Rostock, Germany.

Teichmann E, Blessing E, Hinz B. Cells. 2023;12(19):2389.

Science/Cells: Natural cannabinoids reduce inflammation in macrophages

Intestinal inflammation is mediated by a subset of cells populating the intestine, such as enteric glial cells and macrophages. In studies with several cannabinoids of the cannabis plant they reduced inflammation in these cells, the most effective being THC.

Department of Biochemistry Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.

Cohen G, Gover O, Schwartz B. Int J Mol Sci. 2023;24(19):14628

Science/Human: Cannabis use may not increase atherosclerosis related diseases

According to a cross-sectional study with 13,965 participants researchers found no association between self-reported cannabis use and increased burden of atherosclerotic cardiovascular disease.

Department of Medicine, University of Pittsburgh Medical Center, USA.

Alhassan HA, et al. Circ Cardiovasc Qual Outcomes. 2023:e009609.

Science: Delivery of pharmaceutical ingredients from the cannabis plant through smoking is not uniform

The delivery of active pharmaceutical ingredients of cannabis through smoking it is not uniform. The amount per puff increases as smoking progresses and terpenes are inhaled before the cannabinoids.

Bazelet Medical Cannabis Group, Or Akiva, Israel.

Eyal AM, et al. Cannabis Cannabinoid Res. 2023 Oct 17. [in press]

Science/Human: Cannabis had no effect on disability after an injury

Among 1650 workers, disability benefit expenditures obtained from administrative records were combined with self-reported measures of pain symptoms and cannabis use. After 18 months there was “no substantial relationship between cannabis use and disability benefit expenditures, suggesting that neither harm nor significant benefit is associated with cannabis use. “

Institute for Work & Health, Toronto, Canada.

Mustard CA, et al. Can J Public Health. 2023 Oct 16. [in press]

Science/Cells: THC causes cell death in colon cancer cells

According to a new study with colorectal cancer cells, THC “regulated two functional mechanisms, intracellular vesicle formation and cell death. These findings can help to determine how cannabinoids can be used most effectively to improve the efficacy of cancer treatment.”

Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Republic of Korea.

Hwang YN, et al. Genes Genomics. 2023 Oct 14. [in press]

Science/Animal: CBD may improve leukaemia in animals

In a study with male rats with leukaemia, which was induced by a chemical, CBD improved several parameters, including biochemical and antioxidant status as well as morphological and molecular measures.

Department of Zoology, Faculty of Science, Zagazig University, Zagazig, Egypt.

Soliman NA, et al. Naunyn Schmiedebergs Arch Pharmacol. 2023 Oct 14. [in press]


Science: Some novel CBD derivatives showed augmented antibacterial activity against bacteria

Researchers discovered “novel cannabidiol derivatives with augmented antibacterial agents against methicillin-resistant Staphylococcus aureus.”

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, PR China.

Zhang Z, et al. Bioorg Chem. 2023;141:106911.

Science/Human: CBD did not attenuate THC-induced attentional bias toward cannabis

Across four sessions, participants inhaled vaporised cannabis containing 10 mg of THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1) or 30 mg (3:1) of CBD, administered in a randomised order and counter-balanced across participants. The study found “that inhaled delta-9-tetrahydrocannabinol increased attentional bias toward cannabis in the absence of explicit liking, a marker of liability toward cannabis use disorder. At the concentrations normally found in legal and illegal cannabis, cannabidiol had no influence on this effect.

Department of Psychiatry, University of Oxford, UK.

Oliver D, et al. Addiction. 2023 Oct 11. [in press]

Science/Animal: CBD may reduced systemic immune activation in lung injury

According to a study with mice CBD reduced systemic immune activation in experimental acute lung injury.

Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.

Hall S, et al. Cannabis Cannabinoid Res. 2023 Oct 9. [in press]

Science/Animal: CBD may ameliorate topiramate-induced memory loss

In a study with rats “findings revealed that cannabidiol has ameliorative effects on topiramate-induced memory loss, partially via hippocampal and prefrontal cortical NMDA receptors and CREB/BDNF signaling pathways.”

Department of Pharmacology, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Aghamiri H, Jafari-Sabet M, Hoormand M. Neurochem Res. 2023 Oct 9. [in press]

Science/Human: Cannabis prohibition produces harms to people who need cannabis medicine

Semistructured interviews with 24 citizens of the UK revealed that the “government's lack of implementation of medical cannabis legalisation, combined with their ongoing prohibition position, is producing multiple harms to people who need cannabis medicine. The policy context is perpetuating stigmatising attitudes to cannabis which, as we demonstrate, contribute to social harms.”

Liverpool John Moores University, United Kingdom.

Beckett Wilson H, Metcalf McGrath L. Int J Drug Policy. 2023;122:104220.

Science/Cells: THC may adversely affect sickle red blood cells

“THC triggers a pronounced entry of Ca2+ , which may be deleterious, into sickle cell red blood cells via activation of the TRPV2 channel.”

Sorbonne Université, CNRS, UMR8227 LBI2M, Station Biologique de Roscoff, France.

Hatem A, et al. Am J Hematol. 2023 Oct 6. [in press]