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IACM-Bulletin of 17 December 2023

Science/Human: Cannabis can improve symptoms in refractory cancer-related pain

According to a cross-sectional study with 252 refractory cancer-related pain patients cannabis was shown to effectively improve symptoms. Investigators of Tel Aviv Sourasky Medical Center, Israel, asked participants to fill out a detailed self-report questionnaire. 126 patients were treated with medical cannabis and 105 were not.

Most patients received pain management from their oncologist, not a pain specialist. Cannabis was mainly started for pain relief, sleep difficulties and anorexia. About 70% of patients reported improvement from cannabis , with almost 40% reporting a significant improvement in coping with their illness. Of non-users, 65% had tried cannabis before and stopped due to lack of effectiveness or side effects (39.7% and 34.6%, respectively).

Sharon H, Agbaria Y, Brill S, de Santiago J, Hochberg U. Medical cannabis for refractory cancer-related pain in a specialised clinical service: a cross-sectional study. BMJ Support Palliat Care. 2023:spcare-2023-004421.

Science/Human: Cannabis use may improve sleep in people with anxiety

A total of 347 individuals with intentions to use cannabis to cope with anxiety reported their cannabis and alcohol use in the previous 24 h and their previous nights' sleep quality for 30 consecutive days. The research by investigators of the School of Public Health at the University of Haifa, Israel, examined whether the within-person daily variation in use of cannabis and alcohol was associated with subjective sleep quality.

Compared to non-use, participants reported better sleep after cannabis-use-only and after co-use, but not after alcohol-use-only. People who more frequently use alcohol and cannabis reported sleeping better after cannabis-use-only days compared to those who use cannabis and alcohol less frequently.

Sznitman SR, Martin-Willett R, Ma W, Karoly HC, Bidwell LC. Daily diary study of associations between alcohol, cannabis, co-use and sleep quality in individuals with intentions to use cannabis to cope with anxiety. Drug Alcohol Rev. 2023 Nov 20. [in press]

Science/Human: Cannabis may improve quality of life in patients suffering from different chronic diseases

In an observational study by investigators of the Imperial College Medical Cannabis Research Group at Imperial College London, UK, 1378 patients with different diseases were prescribed cannabis preparations. They measured changes in patient-reported outcomes. 581 participants were current users of cannabis at baseline.

46.51%, 17.05%, and 36.43% patients were treated with oils, dried flowers, or a combination of the two, respectively. Improvements were found in all patient-reported outcomes in each route of administration at 1, 3, 6, and 12 months from baseline. Those prescribed dried flowers only or both oils and dried flowers experienced greater improvements.

Erridge S, Leung O, Holvey C, Coomber R, Beri S, Khan S, Weatherall MW, Rucker JJ, Platt MW, Sodergren MH. An observational study of clinical outcome measures in patients treated with cannabis-based medicinal products on the UK Medical Cannabis Registry. Neuropsychopharmacol Rep. 2023 Dec 6. [in press]

Science/Human: Cannabis may be helpful in the treatment of ADHD

An analysis of 68 patients with ADHD (attention deficit hyperactivity disorder) from the UK Medical Cannabis Registry by investigators of the Medical Cannabis Research Group at Imperial College London, UK, showed several health improvements.

Improvements were observed in quality of life at 1, 3, and 6 months after initiation of treatment. Improvements were also identified in anxiety and sleep quality scores at 1, 3, 6, and 12 months. Authors noted, that results “must be interpreted with caution as a causative effect cannot be proven. These results, however, do provide additional support for future evaluation within randomized controlled trials.”

Ittiphakorn P, Erridge S, Holvey C, Coomber R, Rucker JJ, Sodergren MH. UK Medical Cannabis Registry: An analysis of clinical outcomes of medicinal cannabis therapy for attention-deficit/hyperactivity disorder. Neuropsychopharmacol Rep. 2023 Dec 6. [in press]

News in brief

Science/Cells: CBD may improve efficacy of remdesevir in the treatment of Covid-19

Remdesevir (RDV) is the first drug to receive FDA approval for the treatment of Covid-19. Researchers found, that remdesevir “was rapidly and completely metabolized by human liver microsomes within 60 min. Coincubation with CBD substantially reduced microsomal metabolism (...).The current study strongly suggests that CBD significantly inhibits human liver microsomal metabolism of RDV and extends its in vitro half-life. Thus, concomitant administration of CBD with RDV intravenous injection could be a promising strategy to prevent premature metabolism in COVID-19 patients.”

College of Pharmacy and Health Sciences, St. John's University, Queens, USA.

Saraswat A, et al. Cannabis Cannabinoid Res. 2023;8(6):1008-1018.

Science/Animal: Several cannabinoids may reduce nausea

In a study with rats “THC, CBD, CBDA, and OlAla dose dependently reduced conditioned gaping in both male and female rats in a similar manner. Conclusions: These results suggest that cannabinoids may be equally effective in treating nausea in both males and females.”

Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Canada.

Rock EM, et al. Cannabis Cannabinoid Res. 2023;8(6):1060-1068.

Science/Animal: CBD and CBG may be effective in the treatment of arthritis

Results of a study with mice with osteoarthritis “show evidence for the therapeutic efficacy of CBD oil and CBG oil, where both oils ameliorate pain and inflammation, and improve gait and locomotor activity.”

Center for Orthopedic Research and Translational Science (CORTS), Penn State College of Medicine, Hershey, USA.

Karuppagounder V, et al. Cannabis Cannabinoid Res. 2023;8(6):1030-1044.

Science/Cells: THC may be helpful against flavivirus infections

From their research with cells investigators propose THC “be further investigated in-vitro as a cure against dengue and zika virus infections.”

Department of Biochemistry, Assam Royal Global University, Guwahati, India.

Patar AK, et al. J Biomol Struct Dyn. 2023;41(20):11219-11230.

Science/Human: Contrary to alcohol and tobacco cannabis does not have effects on DNA methylation

Researchers “evaluated the effects of tobacco, alcohol, and marijuana on DNA methylation in the same cohort (N = 3,424).” They “found that tobacco and alcohol have large effects on genome wide DNA methylation while marijuana consumption has nonsignificant effects.”

Epidemiology, Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.

Carreras-Gallo N, et al. Epigenetics. 2023;18(1):2214392.

Science/Human: Interaction between CBD and anti-seizure medications may not be of clinical significance

“In 169 participants (80 adults), with increasing weight-based CBD dose, there were associated increases in serum levels of clobazam and N-desmethylclobazam, free valproate, felbamate, and topiramate in the adult and pediatric arms combined, levetiracetam in the pediatric arm only, and permapanel in the adult arm only. (...) This study confirms some previously identified interactions with CBD and identifies other potential pharmacokinetic interactions; however, the clinical significance of these observations is likely minor, and there is no effect of time on these findings.”

Department of Neurology, Division of Epilepsy, University of Alabama, Birmingham, USA.

Gaston TE, et al. Epilepsia Open. 2023;8(4):1405-1412

Science/Cells: CBD may may cause adverse effects on human Leydig cells

“In this study, we examined the effects of CBD and its main metabolites, 7-carboxy-CBD and 7-hydroxy-CBD, on primary human Leydig cells, which play a crucial role in male reproductive health. Our results showed that CBD (...) inhibited the growth of human Leydig cells.”

Division of Biochemical Toxicology, U.S. Food and Drug Administration, National Center for Toxicological Research, Jefferson, USA.

Li Y, et al. Arch Toxicol. 2023;97(12):3227-3241.

Science/Animal: Inhibition of endocannabinoid degradation may reduce infarction area in the brain

In a study with rats exposed to reduced blood supply to the brain a novel FAAH inhibitor (MCH1) limited “damage from ischemic stroke, although it is not reflected in neurological or sensorimotor behavior and spatial learning and memory.”

Laboratorio de Investigación en Neurociencia, Instituto Científico, Universidad Andina del Cusco, Peru.

Taboada-Rosell K, et al. Brain Res. 2024;1822:148636.

Science/Animal: Activation of the CB2 receptor may reduce damage to the heart from sepsis

Researchers caused sepsis in mice and found that “CB2 receptor activation has a protective effect on the myocardium of mice with sepsis by inhibiting pyroptosis.”

Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Zhang J, et al. Immunol Lett. 2023;264:17-24.

Science/Cells: Activation of the CB2 receptor may prevent from muscle degeneration in cancer

Researchers found that “cancer-cachexia induced human skeletal muscle myotube degeneration is prevented via cannabinoid receptor 2 agonism in vitro.”

School of Biochemistry & Immunology, Trinity College Dublin, Ireland.

Noone J, et al. Pharmaceuticals (Basel). 2023;16(11):1580.

Science/Animal: THC can protect against schizophrenia later in life when maternal immune activation occurs during pregnancy

Maternal immune activation (MIA) during pregnancy is hypothesised to disrupt offspring neurodevelopment and predispose offspring to neurodevelopmental disorders such as schizophrenia. THC and/or CBD were administered to MIA rodents during periadolescence. “At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. (...) In conclusion, contrary to expectations, THC exhibited greater behavioural and morphometric benefits, despite promoting a pro-inflammatory state that CBD partially reverted.”

Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

Lamanna-Rama N, et al. Psychiatry Res. 2023;331:115643.

Science/Animal: CBD may prevent Alzheimer’s disease

CBD mitigated amyloid beta-induced "cognitive deficits by modulating microglial activity, promoting neurotrophic factor release, and regulating inflammatory genes. The administration of CBD demonstrated a protective effect against Aβ toxicity both in vitro and in vivo, along with an amelioration of cognitive impairment in mice. These findings support the potential inclusion of CBD in future nutritional guidelines for Alzheimer's disease prevention.”

Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.

Chen L, et al. Cells. 2023;12(23):2672.

Science/Animal: CBD may alleviate pain

In a study with rats CBD reduced pain following thermal stimulation and mechanical pain.

Institute of Neurosciences and Behavior and Laboratory of Neuropsychopharmacology of Faculty of Philosophy, Sciences and Letters of University of São Paulo, Ribeirao Preto, Brazil.

Arantes ALF, et al. Behav Brain Res. 2023;459:114793.

Science/Animal: CBD improves heart regeneration after heart attack

In a study with mice CBD promotes heart cell proliferation  and heart regeneration after myocardial infarct,  which according to authors “provides a new strategy for cardiac repair in adult myocardium.”

College of Pharmacy, Harbin Medical University, China.

Ren Z, et al. Eur J Pharmacol. 2023:176245.

Science/Human: Cannabis reduced pain in a patient with Fabry disease

“We  report the case of a 32 years old man with classic FD and severe neuropathic  pain who, after the failure of several standard pharmaceutical approaches, was  treated with medical cannabis with relief of nocturnal pain and sleep  improvement.”

Regional Coordinating Center for Rare Diseases, University Hospital of Udine, Italy.

 

Bon M, et al. Mol Genet Metab Rep. 2023;37:101010.

Science/Animal: CBD may inhibit allergic reactions

In studies with mice the “intraperitoneal administration of CBD suppressed passive  cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and  decrease in the number of degranulated mast cells.”

School of Pharmacy, Jeonbuk National University, Jeonju, Republic of Korea.

Yang X, et al. Mol Nutr Food Res. 2023:e2300136.

Science/Cells: CBD induces programmed cell death in cancer cells

In a breast cancer cell line and a prostate cancer cell line CBD decreased the viability of cells in a concentration-dependent fashion. This was caused by apoptosis, a form of programmed cell death.

Department of RNA Structure and Function, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.

Śledziński P, et al. Molecules. 2023;28(23):7887.

Science/Human: Genetic analysis suggests that cannabis may not cause atherosclerosis

“Using a genetic approach approximating a clinical trial does not  provide evidence consistent with a causal effect of genetic predisposition to  cannabis use” on coronary artery disease or ischaemic stroke.

Department of Medicine, Division of Internal Medicine, University Hospital of Lausanne, Switzerland. 

de La Harpe R, et al. BMC Cardiovasc Disord. 2023;23(1):611.