IACM-Bulletin of 13 August 2023

Israel: Major changes of the policy on medical cannabis to ease access

The Health Ministry says that from December 2023, doctors will be able to prescribe cannabis to patients. The ministry publishes its reforms into the medical cannabis system, saying that it will review the system again after a year. Today, many of the about 120,000 Israelis with licenses to use medical cannabis have been facing rising costs, more bureaucracy, and more difficulties in obtaining their supply.

The reform is intended to make it easier for patients to access the drug and remove bureaucratic hurdles. Up until now, those eligible for medical cannabis had to get a special license. The reform also removes CBD products that do not have psychoactive properties, from drug restrictions.

The Times of Israel of 7 August 2023

The Jerusalem Post - Israel News of 23 July 2023

Science/Human: Cannabis halves the risk for the development of diabetes mellitus type 2

A review of previous research was conducted by the Student Research Committee of the Faculty of Medicine at Tabriz University of Medical Sciences, Iran, on the relationship between cannabis use and the development of diabetes mellitus

The meta-analysis of seven studies, containing 11 surveys and 4 cohorts, revealed that the odds of developing diabetes mellitus type 2 in individuals exposed to cannabis was 0.48 times lower than in those without cannabis exposure. Authors concluded, that “a protective effect of cannabis consumption on the odds of diabetes mellitus type 2 development has been suggested.”

Mousavi SE, Tondro Anamag F, Sanaie S. Association between cannabis use and risk of diabetes mellitus type 2: A systematic review and meta-analysis. Phytother Res. 2023 Aug 1. [in press]

Science/human: Cannabis use does not increase the risk for heart attack

Using data of the National Health and Nutrition Examination Survey investigators of the University of California in San Diego, USA, did not find an increased risk for cannabis using middle-aged adults to develop a heart attack. They used five 2-year cycles between 2009 and 2018 representing 9,769 adults aged 35 to 59 years old. Multivariable logistic regression models accounting for sampling weights and adjusting for cardiovascular risk factors were used to assess associations between a history of monthly cannabis use before myocardial infarction and a subsequent myocardial infarction.

A quarter of respondents (n = 2,220) reported a history of monthly use for more than 1 year before a heart attack. A history of new myocardial infraction was reported by 2.1% of all respondents and 3.2% of those who reported a history of monthly use. Compared with never use, a history of monthly cannabis use preceding a myocardial infarction was not associated with a myocardial infarction. However, when stratified by recent use, the odds of heart attack were threefold greater when no use was reported within the past month than when use was reported within the past month. Duration of monthly use was also not significantly associated with myocardial infarction, including monthly use >10 years.

Corroon J, Grant I, Allison MA, Bradley R. Associations Between Monthly Cannabis Use and Myocardial Infarction in Middle-Aged Adults: NHANES 2009 to 2018. Am J Cardiol. 2023;204:226-233

Science/Human: CBD may not attenuate cognitive symptoms of anxiety but slightly reduce physical anxiety symptoms

Within a sample of 63 individuals with elevated trait worry, the current study by investigators of the University of Arkansas in Fayetteville, USA, on open established custom getup aimed to assess the effects of a high dose of 300 mg CBD compared to a dose of 50 mg CBD versus placebo on worry severity and anxiety symptoms after an acute dose and after a 2-week administration period.

Results indicated no effect of acute CBD dosing on worry severity or anxiety symptoms. Repeated CBD administration similarly did not impact worry severity. However, 300mg of CBD reduced anxiety symptoms across the 2-week administration period compared to placebo. Authors concluded that “taken together, these findings suggest 300mg of oral CBD does not attenuate cognitive symptoms of anxiety (i.e., worry), following both acute and repeated administration. Some evidence for repeated administration of 300mg on physical symptoms of anxiety was obtained.”

Gournay LR, Ferretti ML, Bilsky S, Vance E, Nguyen AM, Mann E, Williams P, Leen-Feldner EW. The effects of cannabidiol on worry and anxiety among high trait worriers: a double-blind, randomized placebo controlled trial. Psychopharmacology (Berl). 2023 Aug 8. [in press]

Science/Human: CBD may reduce side effects of tamoxifen in breast cancer treatment

Tamoxifen, which is used in long-term treatment of certain forms of breast cancer, may lead to bothersome side effects contributing to non-compliance and decreased quality of life. Investigators of the Department of Medical Oncology at Erasmus Medical Center Cancer Institute in Rotterdam, The Netherlands conducted an open-label, single-arm study and found out that CBD oil may relieve symptoms. Pharmacokinetic sampling and side effect assessment was done at initiation of CBD-oil and 28 days thereafter.

The endocrine sub-scale of the FACT-ES, a questionnaire on side effects, improved clinically relevant with 6.7 points and health-related quality of life improved with 4.7 points after using CBD. There was no significant change in bioavailability of tamoxifen. The authors concluded “that CBD-oil, if of good quality and with a dosage below 50 mg, does not have to be discouraged in patients using it for tamoxifen-related side effects.

Buijs SM, Braal CL, Buck SAJ, van Maanen NF, van der Meijden-Erkelens LM, Kuijper-Tissot van Patot HA, Hoop EO, Saes L, van den Boogerd SJ, Struik LEM, van Rossum-Schornagel QC, Mathijssen RHJ, Koolen SLW, Jager A. CBD-oil as a potential solution in case of severe tamoxifen-related side effects. NPJ Breast Cancer. 2023;9(1):63.

Science/Human: Cannabis may improve recovery from exercise in trained individuals

According to an anonymous survey by investigators of Exercise Science and Exercise Physiology at Kent State University, USA, with 111 trained individuals cannabis, THC and CBD may improve recovery after exercise. All participants were regularly using cannabis or cannabinoids as well as were currently exercising.

85% of participants reported participating in aerobic training. In addition, 85% of participants also reported regular participation in resistance exercise. 72% of participants participated in both aerobic and resistance exercise. 93% of participants felt that CBD use assisted them with recovery from exercise, while 87% of participants felt the same regarding THC use. Authors concluded “that Individuals who habitually use cannabis, CBD or THC, and regularly engage in exercise do feel that cannabis assists them with exercise recovery.”

Pinzone AG, Erb EK, Humm SM, Kearney SG, Kingsley JD. Cannabis use for exercise recovery in trained individuals: a survey study. J Cannabis Res. 2023;5(1):32.

Science/Human: Cannabis may be helpful in the treatment of post-traumatic stress disorder

investigators of the School of Pharmacy of the Faculty of Medicine and Health at the University of Sydney, Australia, conducted an interim analysis of an observational study. Survey scores of 198 participants with an anxiety disorder were compared at baseline and after treatment with medicinal cannabis.

The median doses taken were 50 mg/day for CBD and 4.4 mg/day for THC. The total participant sample reported significantly improved anxiety, depression, fatigue, and ability to take part in social roles and activities. Those who were diagnosed with posttraumatic stress disorder (n = 57) reported significantly improved anxiety, depression, fatigue, and social abilities. The most common reported side effects across the whole participant cohort were dry mouth (33%), somnolence (31%), and fatigue (19%).

Stack SK, Wheate NJ, Moloney NC, Abelev SV, Barlow JW, Schubert EA. The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study. J Pharm Technol. 2023;39(4):172-182.

 News in brief

Science/Cells: Extracts from cannabis leaves show anticancer effects in several cell lines

Cell experiments with extracts from cannabis leaves “revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.”

Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá, Colombia.

Camargo FDG, et al. Metabolites. 2023;13(7):788.

Science: A combination of CBD and nonsteroidal anti-inflammatory drugs shows efficacy against the new coronavirus

A study on combinations of CBD and nonsteroidal anti-inflammatory drugs such as ibuprofen may have a “potential therapeutic role for these compounds in the treatment of emerging coronavirus infections. (…) Our findings provide a promising new approach to combatting current and future viral emergencies.”

Department of Organic Chemistry, Pharmaceutical Faculty, Poznan University of Medical Sciences, Poland.

Pawełczyk A, et al. Pathogens. 2023;12(7):951

Science: Stilbenes of the cannabis plant may have anti-inflammatory and anti-cancer effects

14 stilbenes have been identified to be present in cannabis. “The stilbenes summarized in this analysis show varying degrees of therapeutic benefits ranging from anti-inflammatory, antiviral, and anti-cancer to antioxidant effects.”

Faculty of Pharmacy and Pharmaceutical Sciences, Katz Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Canada.

O'Croinin C, et al. Pharmaceutics. 2023;15(7):1941.

Science/Animal: How low doses of THC cause anti-ageing effects

 “This study demonstrated the use of hippocampal transcriptome profiling in uncovering the molecular basis of the atypical, anti-aging effects of THC microdose treatment in old mice.”

Faculty of Medicine, Tel Aviv University, Israel.

Shapira G, et al. Front Neurosci. 2023;17:1182932.

Science/Human: cannabis may attenuate cognitive deficits resulting from methamphetamine

A survey with 423 participants, stratified by presence or absence of lifetime methamphetamine and/or cannabis abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. “People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains.”

San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, USA.

Rogers JM, et al. J Int Neuropsychol Soc. 2023:1-10.

Science/Human: Long-term cannabis use may cause cannabis -induced hyperalgesia

Investigators found out that “daily long-term cannabis use may be associated with increased pain sensitivity using the cold pressor test (CPT) to measure pain tolerance.”

Department of Psychiatry and Behavioral Sciences, State University of New York Upstate Medical University, Syracuse, USA.

Zhang-James Y, et al. Am J Addict. 2023 Aug 7. [in press)

Science/Animal: CB1 receptors on microglia may be responsible for social memory deficits caused by THC

Studies with mice suggest “that adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC),” which may cause deficits in social memory in adulthood.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA..

Hasegawa Y, et al. bioRxiv. 2023:2023.07.24.550212.

Science/Cells: Mechanisms of CBD-induced effects against colorectal cancer

Studies with cells “demonstrate an intricate interplay between apoptosis and macroautophagy in CBD-treated colorectal cancer cells, which is regulated by the complex interactions of p53wt and Hsp70.”

TranslaTUM-Central Institute for Translational Cancer Research, Klinikum rechts der Isar, Technische Universität München, Germany.

Wang F, et al. Cell Death Discov. 2023;9(1):286

Science/Animal: CBD may protect from obesity induced heart disease

According to a study with rats “CBD appears to be relatively safe for the treatment of obesity-induced heart disease, as it has anti-inflammatory and partially antioxidative properties.”

Department of Physiology, Medical University of Bialystok, Poland.

Sztolsztener K, et al. Prostaglandins Other Lipid Mediat. 2023;169:106767.

Science/Human: Dramatic improvement of pain in adolescent with sickle cell disease by CBD

“Here, we report a dramatic efficacy of cannabidiol in an adolescent with SCD suffering from chronic pain refractory to other analgesics, with complete regression of chronic pain and rapid plasma histamine level normalization after treatment.”

Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Imagine Institute, Inserm, Université Paris Cité, France.

Mayrand L, et al. Am J Hematol. 2023 Aug 4. [in press]

Science/Animal: Anandamide may protect from graft-versus-host disease

The endocannabinoid “anandamide reduces the migration of lymphocytes to the intestine by CB2 activation and reduces TNF-α in the target organs, protecting mice from graft-versus-host disease”, a severe complication after organ transplantation.

Graduate Program in Biological Sciences: Physiology and Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Berg BB, et al. Eur J Pharmacol. 2023;956:175932.

Science/Animal: CBD reduces alcohol intake in adolescent rats

CBD “tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats.”

Pharmacology Section, Department of Health Care Surveillance and Bioethics, Università Cattolica del Sacro Cuore, Rome, Italy.

Tringali G, et al. Phytother Res. 2023 Jul 31. [in press]

Science/Human: Cannabis use is not associated with workplace injury if used outside the workplace

In a survey with 2745 Canadian workers “compared to no past-year cannabis use, there was no difference in workplace injury risk for non-workplace cannabis use (…). However, workplace use was associated with an almost two-fold increased risk of experiencing a workplace injury (…). Findings were similar for workers in safety-sensitive and non-safety-sensitive work.”

Institute for Work & Health, Toronto, Ontario, Canada.

Carnide N, et al. Can J Public Health. 2023 Jul 31. [in press]

Science/Human: The legalisation of cannabis in Canada had no effect on adult crimes

Researchers used the “National police-reported adult cannabis-related offenses (n = 247,249), property crimes (n = 2,299,777), and violent crimes (n = 1,903,762)” to analyse the effects of cannabis legalisation on crimes. “Implementation of the Cannabis Act was associated with decreases in adult police-reported cannabis-related offenses.” Authors noted “that Canada's cannabis legalization was successful in reducing cannabis-related criminalization among adults.” there was also no effect on property or violent crimes.

University of Northern British Columbia, Northern Medical Program, Prince George, Canada.

Callaghan RC, et al. Addict Behav. 2023;146:107813.

Science/Human: No effect of cannabis use on survival after liver transplantation

“Current observational data do not support a link between cannabis use and poor patient survival post-transplantation” in patients receiving liver transplants.

Faculty of Medicine, University of Ottawa, Canada.

Yau MTK, Hussaini T, Yoshida EM. Can Liver J. 2023;6(2):269-277.

Science/Cells: The endocannabinoid anandamide may play a role in early pregnancy

Several experiments “provide novel evidence about an active role of anandamide on endometrial fibroblast behavior as a mechanism regulating uterine vascular adaptations in early gestation.”

Laboratorio de Fisiología y Farmacología de la Reproducción, Centro de Estudios Farmacológicos y Botánicos, Paraguay.

Cañumil VA, et al. Placenta. 2023;139:99-111.

Science/Human: CBD may be helpful in Lennox-Gastaut syndrome and Dravet syndrome.           

A retrospective chart review of 114 patients “support favorable effectiveness and retention of CBD without concomitant clobazam for up to 12 months in clinical practice” in Lennox-Gastaut syndrome and Dravet syndrome.

Assistance Publique-Hôpitaux de Paris (APHP), Hospital, Université Paris Cité, France.

Nabbout R, et al. Seizure. 2023;110:78-85.

Science/Cells: Endocannabinoids may show anti-cancer effects in lymphoma of dogs

In several lymphoma cells of dogs the concentrations of CB1 and CB2 receptors were higher than in healthy cells. The 2 endocannabinoids anandamide and 2-AG “dose and time-dependently exhibited significant but differential anti-lymphoma effects on canine and human NHL cells.”

Department of Anatomy, Physiology, & Pharmacology, College of Veterinary Medicine, Auburn University, USA.

Omer S, et al. Life Sci. 2023 Aug 15;327:121862.

Science/Human: The legalisation of cannabis in the US was associated with reduced binge drinking in adolescents

By using “restricted National Survey on Drug Use and Health data (2008-2019)” researchers found that the implementation of cannabis legalisation “was associated with increased past-month binge drinking in adults aged 31+ and decreased past-month binge drinking in those aged < 21.“

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, USA.

Gonçalves PD, et al. Int J Drug Policy. 2023;118:104085.

Science/Animal: Regular THC use reduces the concentration of the CB1 receptor in the brain

Studies with rats demonstrate “that chronic delta-9-THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field.”

Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, USA.

Freeman-Striegel L, et al. Life Sci. 2023 Aug;327:121825.

Science/Human: Many Canadians suffering from epilepsy use cannabis

A survey with 211 respondents “reveals a high prevalence of marijuana use among patients with epilepsy living in Canada particularly when seizures are drug resistant. A significant proportion of patients reported improvement of seizures with marijuana use, consistent with previous studies.”

Schulich School of Medicine and Dentistry, Western University, London, Canada.

Esmonde-White C, et al. Neurol Clin Pract. 2023;13(4):e200174.

Science/Animal: CBD is increasingly used to treat pets according to a national survey in the USA

According to a survey with 1238 participants 356 had administered CBD to their pets before. Dogs were the most prevalent pet (76%), followed by cats (22%). Authors wrote: “We found heterogeneity regarding cannabidiol dosage and dosing frequency. Cannabidiol was mostly perceived as safe and effective, but there is a need to conduct further research on cannabidiol long-term tolerability and therapeutic efficacy for treating various conditions.”

Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, USA.

Corsato Alvarenga I, et al. J Small Anim Pract. 2023;64(8):513-521.

Science/Human: Attenuation of pain severity in people with HIV

From a survey with 134 people with HIV researchers concluded “that attenuating the impact of pain severity on pain-related functional impairment is a potential mechanism for a beneficial role of cannabis for PWH.”

Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine and Boston Medical Center, USA.

Klepp TD, et al. AIDS Care. 2023;35(8):1235-1242.

Science/Animal: CBD may be helpful in pulmonary hypertension

In a study with rats CBD “alleviated right ventricular fibrosis by inhibiting the transforming growth factor β pathway in monocrotaline-induced pulmonary hypertension in rats.” Authors suggest that CBD may be an “adjuvant therapy” for pulmonary hypertension.

Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.

Krzyżewska, et al. Biochim Biophys Acta Mol Basis Dis. 2023;1869(6):166753.

Science/Animal: CBD may reduce periodontal inflammation

According to a study with rats CBD may attenuate periodontal inflammation through inhibiting TLR4/NF-κB pathway. Authors concluded that their research “indicates that topical CBD application is effective in treating periodontitis.”

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Chen H, et al. J Periodontal Res. 2023;58(4):697-707.

Science/Human: The dose is usually quite stable during the first year of treatment with cannabis

According to a 9-month longitudinal cohort study following a 12-week randomized, waitlist-controlled trial in 149 adults who used cannabis to alleviate insomnia, pain, depressed mood, or anxiety “most individuals using cannabis for medical symptoms have a stable pattern of use over the first year.”

Massachusetts General Hospital (MGH) Department of Psychiatry, Center for Addiction Medicine, Boston, USA.

Gilman JM, et al. Addict Behav. 2023;144:107719.

Science/Animal: Activation of the CB2 receptor may alleviate psoriasis

In a study with mice activation of the CB2 receptor by a synthetic cannabinoid (GW842166X) ameliorated “psoriasis-like skin lesions by inhibiting inflammation and oxidative stress.”

Department of Dermatology, Daping Hospital, Army Medical University, Hongqing, China.

He Y, et al. Inflammation. 2023;46(4):1255-1271.

Science/Animal: The endocannabinoid 2-AG reduces fibrosis of the heart

In a study with diabetic mice the endocannabinoid 2-AG (2-arachidonoylglycerol) attenuated myocardial fibrosis.

Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Chen Z, Zheng L, Chen G. Cardiovasc Drugs Ther. 2023;37(4):647-654.