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IACM-Bulletin of 01 January 2023

Science/Human: Cannabis had no negative effect in lung cancer patients treated with immunotherapy

According to a study with 201 lung cancer patients by the Oncology Institute of the Tel Aviv Medical Center, and the Sackler School of Medicine, Israel, the use of cannabis had no negative effects on a treatment with pembrolizumab, an immune checkpoint inhibitor, for metastatic disease. 102 (50.7%) patients received licence for cannabis within the first month of treatment. The most common indication for cannabis was pain (71%) followed by loss of appetite (34%).

Time to tumour progression was similar for cannabis-naive and cannabis-treated patients, while survival was numerically higher in the cannabis-naive group (55 versus 24 months but did not reach statistical significance. Authors wrote that in multivariate analyses “we did not identify cannabis use as an independent predictor factor for mortality.” This research was supported by studies with mice. Authors concluded that “preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first-line monotherapy for advanced NSCLC [non-small cell lung cancer]. The differences in overall survival can most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting.”

Waissengrin B, Leshem Y, Taya M, Meiri D, Merimsky O, Shamai S, Wolf I, Rubinek T. The use of medical cannabis concomitantly with immune checkpoint inhibitors in non-small cell lung cancer: A sigh of relief? EUR J Cancer. 2022;180:52-61.

Science/Human: Cannabis improves sleep in patients with insomnia according to a controlled study

According to a placebo-controlled 6 week study with 29 adults with insomnia and oral cannabis preparation improved sleep. Participants in this investigation by the National Institute of Integrative Medicine in Melbourne, Australia, received a cannabis oil containing 10 mg/ml THC and 15 mg/ml CBD for 2 weeks of placebo in a crossover design.

After a 2 weeks of active treatment 60% of participants were no longer classified as insomniacs. Midnight melatonin levels significantly improved in the active group by 30% compared to a 20% decline in the placebo group . Medicinal cannabis oil improved both time and quality of sleep. The quality of sleep improved by 80%.

Ried K, Tamanna T, Matthews S, Sali A. Medicinal cannabis improves sleep in adults with insomnia: a randomised double-blind placebo-controlled crossover study. J Sleep Res. 2022:e13793.

Science/Animal: A cannabis oil was safe and effective for at least 2 years

The outcomes of a large Australian clinical electronic registry cohort of 3961 patients showed sustained safety and efficacy of a cannabis oil for 2 years. The study was conducted by Emyria Pty in Leederville, Australia. Clinical indications were for: chronic pain (72%), psychiatric (15%), neurological (2%), and other diagnoses (11%).

Median total oral daily dose was 10mg for THC and 22.5mg for CBD. Statistically significant improvements across all outcomes were sustained for over two years, including: clinical global impression, pain interference and severity, mental health, insomnia and health status. Authors concluded that there “was significant improvement across all measured clinical outcomes over two years. “

Vickery, Roth, Ernenwein, Kennedy, Washer. A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years. PLoS One. 2022;17(11):e0272241.

Science/Human: A cannabis extract did not pose increased cardiovascular risks in patients after stroke

In a placebo-controlled study from Italy with 34 patients, who had experienced stroke, medical treatment with the cannabis extract Sativex did not cause “significant blood pressure and heart rate variation or cardiovascular complications”. Patients were treated with cannabis or placebo and assessed before and after two phases of 1-month duration each.

From the whole group 31 were taking antihypertensive drugs and, among these, 12 were taking beta-blockers. During the study, no arrhythmic events were recorded, blood pressure and heart rate did not show pathological fluctuations, and no cardiovascular or cerebrovascular events occurred. Authors concluded that these data support the safety of this cannabis extract.

Rosa, Puce, Mori, Currà, Fattapposta, Porto, Bragazzi, Trompetto, Marinelli. Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled study. Front Cardiovasc Med. 2022;9:990188.

Science/Human: Cannabis was effective in reducing seizures in children with epilepsy

Using data from the UK Medical Cannabis Registry investigators of Imperial College London, UK, cannabis reduced seizure frequency in a case series of 35 children with treatment resistant epilepsy. Patients were prescribed during their treatment with either CBD broad-spectrum oils or CBD/THC oils.

Twenty-three (65.7%) patients achieved and at least 50% reduction in seizure frequency. 94% of patients treated with CBD and THC observed at least 50% reduction in seizure frequency compared to 32% and 18% of patients treated with CBD isolates and broad-spectrum CBD products respectively. The extracts were generally well tolerated.

Erridge, Holvey, Coomber, Hoare, Khan, Platt, Rucker, Weatherall, Beri, Sodergren. Clinical Outcome Data of Children Treated with Cannabis Based Medicinal Products for Treatment Resistant Epilepsy - Analysis from the UK Medical Cannabis Registry. Neuropediatrics. 2022 Dec 20. [in press].

Science/Human: Topical CBD may be effective in the treatment of digital ulcers in patients with systemic sclerosi

In total, 45 patients with systemic sclerosis who had digital ulcers were consecutively enrolled between January 2019 and December 2019 by investigators of several Italian institutions. Of the participants, 25 were treated with CBD during surgical debridement and 20 were treated with standard local therapy.

Local treatment with CBD was significantly associated with lower pain scores, higher health assessment scores, and an increase in participants' total hours of sleep. Patients in the control group more frequently required additional analgesic therapy. Authors concluded that “topical CBD may be a valuable tool to treat pain related to digital ulcers“ in patients with systemic sclerosis.

Spinella, de Pinto, Baraldi, Galluzzo, Testoni , Lumetti, Parenti, Guerzoni, Salvarani, Giuggioli. Topical Cannabidiol in the Treatment of Digital Ulcers in Patients with Scleroderma: Comparative Analysis and Literature Review. Adv Skin Wound Care. 2023;36(1):18-23.

Science/Human: Cannabis could be helpful in the treatment of depression

An analysis of a case series of 129 patients with depression is from the UK Medical Cannabis Registry by investigators of Imperial College in London, UK, therapy with cannabis may improve depression.

There were reductions in PHQ-9 (Patient Health Questionnaire-9) at 1-month, 3 months and 6 months. Improvements were also observed in a questionnaire of generalised anxiety disorder, sleep quality and general health. Authors concluded that cannabis treatment “was associated with reductions in depression severity at 1, 3, and 6 months.”

Mangoo, Erridge, Holvey, Coomber, Barros, Bhoskar, Mwimba, Praveen, Symeon, Sachdeva-Mohan, Rucker, Sodergren. Assessment of clinical outcomes of medicinal cannabis therapy for depression: Analysis from the UK Medical Cannabis Registry. Expert Rev Neurother. 2022 Dec 26.[in press].

Science/Human: Cannabinoids are safe and well tolerated in people living with HIV

Investigators conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. Ten People living with HIV were randomized to oral THC, a CBD/THC combination, and pure CBD. Individuals titrated doses as tolerated to a maximum daily dose THC 15 mg/CBD 15 mg or 800 mg CBD, respectively, for 12 weeks.

Out of 10 individuals, 8 completed the study. Cannabinoids did not alter hematology/biochemistry profiles. CD4 count, CD4/CD8 ratio, and HIV suppression remained stable. In patients with HIV, “cannabinoids seem generally safe and well-tolerated, though larger studies are needed.”

Mboumba, Needham, Nohynek, Singer, Lee, Bobeuf, Samarani, Del Balso, Paisible, Vertzagias, Sebastiani, Margolese, Mandarino, Klein, Lebouché, Cox, Brouillette, Routy, Szabo, Thomas, Huchet E, Vigano, Jenabian, Costiniuk. Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial Biomedicines. 2022;10(12):3168.

Science/Human: Cannabis may be effective in the treatment of inflammatory bowel disease

An analysis of a case series of 76 patients with Crohn’s disease and ulcerative colitis from the UK Medical Cannabis Registry by investigators from Imperial College in London, UK, demonstrated benefits of cannabis medicines.

The median baseline score of the Short Inflammatory Bowel Disease Questionnaire improved at 1 and 3 months. General health, anxiety and sleep quality also improved after 3 months according to standardised questionnaires. Sixteen (21%) patients reported adverse events with the majority being classified as mild to moderate in severity.

Dalavaye, Erridge, Nicholas, Pillai, Bapir, Holvey, Coomber, Rucker, Hoare, Sodergren. The effect of medical cannabis in inflammatory bowel disease: analysis from the UK Medical Cannabis Registry. Expert Rev Gastroenterol Hepatol. 2022:1-14.

News in brief

Spain: Health Minister drafts medical cannabis law
In Spain, the Ministry of Health is drafting the law that will regulate medical cannabis in the country. The Spanish government announced that the Spanish Agency of Medicines and Health Products (AEMPS) is working on the issue, after a deputy from the political party Ciudadanos asked a parliamentary question.
El Planto of 23 November 2022

USA: More young people use cannabis than tobacco
A new study shows the use of cannabis and hallucinogens among young adults is at all-time highs. This comes as, for the first time ever, more people say they use cannabis more than tobacco cigarettes.
CNN of 22 August 2022

Costa Rica: Congress has passed a bill to legalise the use of cannabis for medicinal purposes
Costa Rica's Congress has passed a bill which will legalise the use of cannabis for medical purposes and allow its cultivation for industrial use.The cultivation and sale of cannabis for recreational purposes, however, will remain banned. President Carlos Alvarado is expected to sign it within days.
BBC of 2 March 2022

Mexico: Supreme Court ruled that cannabis possession for personal use is legal
Drawing limits on the amount of cannabis a person can have for personal use are unconstitutional, Mexico's Supreme Court ruled . It is the latest in a series of rulings invalidating the cannabis ban, dating back to 2015 and coming after the court ruled last year that personal consumption and home cultivation bans were unconstitutional.
Newsweed of 13 May 2022

Science/Cells: THC and CBD may be a potential therapy for cutaneous leishmaniasis
THC, CBD and caryophyllene showed a good inhibition of Leishmania and human arginases. “These components may serve as therapeutic agents or in co-administrated therapy for leishmaniasis.”
Ain Chock Faculty of Sciences, Hassan II University of Casablanca, Morocco.
Assouab, et al. Trop Med Infect Dis. 2022;7(12):400.

Science/Cells: Cannabis extracts show anti-cancer affects against colon cancer cells
“Phytocannabinoid extracts from plants of the THCA-dominant chemotype interacted synergistically and showed selective cytotoxicity against” a colon cancer cell line.
Department of Agroenvironmental Chemistry and Plant Nutrition, Faculty of Agrobiology, Czech University of Life Sciences Prague.
Malík M, et al. Cannabis Cannabinoid Res. 2022 Dec 1. [in press].

Science/Animal: Cannabis alleviates loperamide induced constipation
A water extract of cannabis animated low pyramid induced constipation in mice.
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Li R. et al. Front Pharmacol. 2022;13:1033069.

Science/Animal: The CB1 receptor may influence disuse induced bone loss
In a study with mice CB1 deficiency in males exacerbated bone loss, while in females CB1 deficiency appeared to protect against disuse-induced bone loss. “These results suggest that CB1 receptors may represent a potential therapeutic target for mitigation of disuse-induced bone loss.”
Department of Biomedical Engineering, Virginia Commonwealth University, Engineering Research Building, Richmond, USA.
DeNapoli RC. et al. J Biomech. 2022;146:111414.

Science/Human: CBD is effective in the treatment of epilepsy for 4 years
In an observational study with 892 patients suffering from epilepsy “add-on CBD was associated with sustained seizure reduction up to 192 weeks with an acceptable safety profile.”
University of Alabama at Birmingham, USA.
Szaflarski JP. et al. Epilepsia. 2022 Dec 20. [in press].

Science/Cells: CBD and THCV contract the development of resistance to doxorubicin in breast cancer
In a study with triple negative breast cancer cells the natural cannabinoids CBD (cannabidiol) and THCV (tetrahydrocannabivarin) counteracted the development of resistance to the chemotherapeutic agent doxorubicin.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, USA.
Kalvala AK. et al. Biochimie. 2022:S0300-9084(22)00332-7.

Science/Animal: A combination of endocannabinoids and activation of the melatonin receptor is effective against brain inflammation
In a study with rats a combination of an inhibitor of endocannabinoid degradation and an activator of the melatonin receptor showed neuroprotective effects and stimulated inflammation resolution.
Division of Pharmacology, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, Federico II University of Naples, Italy.
Cammarota M. et al. Br J Pharmacol. 2022 Dec 16. [in press].

Science/Animal: A combination of celecoxib and CBD exert antidepressant effects
In a study with mice a combination of the anti-inflammatory drug celecoxib and CBD exerted antidepressant and anxiolytic effects.
Department of Psychology, The Hebrew University of Jerusalem, Israel.
Dinur E. et al. Cannabis Cannabinoid Res.2022 Dec 14. [in press].

Science/Animal: A combination of celecoxib and CBD exert antidepressant effects
In a study with mice a combination of the anti-inflammatory drug celecoxib and CBD exerted antidepressant and anxiolytic effects.
Department of Psychology, The Hebrew University of Jerusalem, Israel.
Dinur E. et al. Cannabis Cannabinoid Res.2022 Dec 14. [in press].

Science/Animal: CBD acts synergistically with antibiotics against Salmonella typhimurium
Researchers demonstrated synergy between CBD and 3 broad-spectrum antibiotics (ampicillin, kanamycin, and polymyxin B) in the treatment of salmonella typhimurium. “This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating S. typhimurium.”
The Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering, and Mathematics (C-STEM), Alabama State University, Montgomery, USA.
Gildea L. et al. Microorganisms. 2022;10(12):2360.

Science/Cells: CBD may protect against dental caries
Dental caries is caused by biofilm-forming acidogenic bacteria, especially Streptococcus mutans. Researchers demonstrated that CBD “as a strong inhibitory effect” against these bacteria “suggesting that it is a potential drug adjuvant for reducing oral pathogenic bacterial load as well as protecting against dental caries.”
Biofilm Research Laboratory, The Institute of Biomedical and Oral Research (IBOR), Faculty of Dental Medicine, The Hebrew University of Jerusalem, Israel.
Barak T. et al. Int J Mol Sci. 2022;23(24):15878.

Science/Cells: CBD shows anti-cancer effects against vulvar squamous cell carcinoma
CBD and its combination with anti-inflammatory drugs (diclofenac, ibuprofen) are toxic against vulvar squamous cell carcinoma cells and “are promising candidates for the adjuvant treatment of high-risk” patients with this rare cancer.
Poznan University of Medical Sciences, Poland.
Krajka-Kuźniak V. et al. . Molecules. 2022;27(24):8779.

Science/Cells: Cannabinoids exhibit synergistic anti-inflammatory effects with other drugs
Cannabinoids (CBD, CBG and THCV) and other anti-inflammatory drugs (dexamethasone, budesonide, diclofenac, ibuprofen) “exhibit synergistic anti-inflammatory effects on macrophages and lung epithelial cells.”
Institute of Plant Science, Agriculture Research Organization, Volcani Institute, Israel.
Vinayaka AC. et al. Pharmaceuticals (Basel). 2022;15(12):1559.

Science/Animal: Beta-caryophyllene reduced seeking behaviour for sweetened food
In a study with mice the CB2 receptor agonist bete-caryophyllene (BCP) reduced the seeking behaviour of mice for sweetened food. “Altogether, these preclinical data demonstrate the potential role of BCP in treating disorders associated with food addiction-like behaviour.”
Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Dos Santos Barbosa LA. et al. Addict Biol. 2023;28(1):e13249.

Science/Human: There may be negative effects on learning by adolescents, who use alcohol or cannabis
According to a study with 135 adolescents without or with significant alcohol or cannabis use these drug may reduce learning abilities. “Findings suggest that adolescent cannabis use is related to slowed instrumental learning (…), whereas adolescent alcohol use may be more closely linked to broader impairments in instrumental learning.”
Department of Psychology, University of Nebraska-Lincoln, Nebraska, USA.
Hubbard NA. et al. Addict Biol. 2023;28(1):e13258.

Science/Cells: THC may combat dengue and zika virus infections
Experimental investigations suggest that THC may be used as a treatment against flavivirus infections, including infections with the dengue and zika viruses. Thus, offers suggested THC to be “further investigated in-vitro as a cure against dengue and zika virus infections.”
Department of Biochemistry, Assam Royal Global University, Guwahati, Assam, India.
Patar AK. et al. J Biomol Struct Dyn. 2022:1-12.

Science/Cells: Beta-caryophyllene ameliorates experimental colitis inflammation
Beta-caryophyllene (BCP) potentially ameliorates “experimental colitis inflammation by inhibiting macrophage ferroptosis.” Ferroptosis is a form of programmed cell death.
Department of Cell Biology, College of Life Science and Technology, Jinan University, China.
Wu YT. et al. Int J Mol Sci. 2022;23(24):16055.

Science/Animal: Activation of the CB2 receptor may reduce acute lung injury due to inflammation
Activation of the selective CB2 receptor agonist HU-308 reduced systemic and pulmonary inflammation in a most model of pneumonia.
Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
Hall S. et al. Int J Mol Sci. 2022;23(24):15857.

Science/Cells: CBD may be a therapeutic drug for oral cancer
CBD showed a cytotoxic effect on oral cancer cells. “CBD also increases cytotoxicity on cell survival and the migration of oral cancer cells, so it may be a therapeutic drug for oral cancer.”
Department of Obstetrics and Gynecology, China Medical University Hospital, Taiwan.
Huang CC. et al. Int J Mol Sci. 2022;23(24):15842.

Science/Human: Cannabis use does not predispose to hypertension
According to a survey with 4565 respondents findings “indicate that neither past nor current cannabis use is associated with clinical hypertension.”
Northwestern University Feinberg School of Medicine, Chicago, USA.
Shah RM. et al. J Clin Hypertens (Greenwich). 2022 Dec 22. [in press].

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