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IACM-Bulletin of 12 March 2023

IACM: Raphael Mechoulam has passed away at the age of 92

On 9 March 2023, Raphael Mechoulam, professor emeritus of medicinal chemistry at the Hebrew University in Jerusalem, passed away at his home in Jerusalem at the age of 92. He is often referred to as the father or grandfather of cannabinoid research because of his ground-breaking discoveries. He had first determined the exact chemical structure of the cannabis active ingredient delta-9-THC in 1964, together with Yehiel Gaoni, and his research group discovered the first endocannabinoid in 1992, which he named anandamide.

Raphi, as he was called by his friends, enjoyed high international recognition not only because of his great scientific achievements, but also because of his impressive personality, which made him a role model and inspiration for many scientists. He contributed significantly to improving the lives of thousands and thousands of people with severe diseases through cannabis treatment. We were fortunate and honoured to have him as a member of the IACM Board of Directors for many years and as Chairman of the IACM from 2003-2005. Among many other awards given to him during his life, he received the IACM Special Award in 2014 for his contributions to the re-introduction of cannabis and cannabinoids into medicine.

We will miss him. He will live on in our hearts.

Roger Pertwee on Raphael Mechoulam

Raphael Mechoulam on Wikipedia

Science/Human: Cannabis may be effective in patients with severe tics in Tourette syndrome according to controlled study

A placebo-controlled study with 97 patients suffering from Tourette syndrome found no significant effects of treatment with the cannabis extract Sativex on total tic severity. However researchers of the Department of Psychiatry, Social Psychiatry and Psychotherapy at the Hannover Medical School, Germany, observed improvements in subgroups. Two thirds of participants (64 patients) received the cannabis extract and one third (33 patients) placebo for 13 weeks.

Although a much larger number of patients in the cannabis compared to the placebo group (22% versus 9%) showed a reduction in Tic severity of 25% or more superiority of Sativex could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Authors noted that “exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from a treatment with cannabis-based medication.”

Müller-Vahl KR, Pisarenko A, Szejko N, Haas M, Fremer C, Jakubovski E, Musil R, Münchau A, Neuner I, Huys D, van Elst LT, Schröder C, Ringlstetter R, Koch A, Jenz EB, Großhennig A. CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders - Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study. Psychiatry Res. 2023;323:115135

Science/Human: Cannabis use may reduce symptoms of tinnitus according to a survey

Cannabis use is common among patients with tinnitus and is perceived to be effective against symptoms. Investigators of the Faculty of Medicine at the University of Ottawa, Canada, analysed data of a questionnaire filled in by 45 patients with a primary presenting complaint of tinnitus in a tertiary neuro-otology clinic.

Overall, 96% of patients reported that they would consider cannabis as treatment for their tinnitus. Patients considered cannabis use for auditory symptoms (91%), and symptoms related to their tinnitus, such as emotional complaints (60%), sleep disturbances (64%), and functional disturbances (56%). Researchers concluded that “current users of cannabis reported that it helped with their symptoms.”

Mavedatnia D, Levin M, Lee JW, Hamour AF, Dizon K, Le T. Cannabis use amongst tinnitus patients: consumption patterns and attitudes. J Otolaryngol Head Neck Surg. 2023;52(1):19.

Science/Human: CBD may be effective in the treatment of epilepsy due to glycosylphosphatidylinositol-anchored protein deficiencies

In a study with 6 patients suffering from treatment resistant epilepsy due to a rare genetic disorder, called glycosylphosphatidylinositol-anchored protein deficiencies, CBD was shown to be effective in the majority of participants. They received add-on treatment with the CBD extract Epidyolex by investigators of the Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health of the University of Genoa, Italy.

In 5 out of 6 (83%) patients monthly seizure frequency was reduced by more than 50% after 12 months of treatment. No severe adverse events were reported. Mean prescribed CBD dose was 18 mg per kilograms body weight per day.

Riva A, D'Onofrio G, Pisati A, Roberti R, Amadori E, Bosch F, de Souza CFM, Thomas A, Russo E, Striano P, Bayat A. Cannabidiol Add-On in Glycosylphosphatidylinositol-Related Drug-Resistant Epilepsy. Cannabis Cannabinoid Res. 2023 Mar 1 [in press].

Science/Human: Cannabis treatment is associated with an improvement in quality of life in patients with chronic diseases

An analysis of the treatment outcomes of 2833 patients enrolled in the UK Medical Cannabis Registry demonstrated an improvement of quality of life. Results were presented by investigators of the Medical Cannabis Research Group at the Department of Surgery and Cancer of Imperial College London, UK. They participated in standardised questionnaires at baseline, and after1, 3, 6, and 12 months follow-up.

Data revealed an improvement of health-related quality of life, anxiety and sleep. There was no difference in quality of life between former or current illicit cannabis consumers and patients without cannabis experience. Adverse events were reported by 17%. Authors concluded that cannabis-based medicines “are associated with an improvement in health-related quality of life in UK patients with chronic diseases. Treatment was tolerated well by most participants, but adverse events were more common in female and cannabis-naïve patients.”

Olsson F, Erridge S, Tait J, Holvey C, Coomber R, Beri S, Hoare J, Khan S, Weatherall MW, Platt M, Rucker JJ, Sodergren MH. An observational study of safety and clinical outcome measures across patient groups in the United Kingdom Medical Cannabis Registry. Expert Rev Clin Pharmacol. 2023:1-10.

Science/Human: Cannabis use may be associated with reduced clotting propensity in trauma patients

According to a descriptive analysis by investigators of the Department of Surgery Penn Medicine Lancaster General Health, USA, cannabis use may be associated with a reduced number of venous thromboembolism (VTE). This was a retrospective, single institutional study performed from January 2018 through June 2021, utilizing data from patients presenting to a Level 1 Trauma Center.

Authors observed less frequent venous thromboembolism development in the cannabis-positive group compared to the cannabis-negative group. Authors noted that the overall occurrence venous thromboembolism “was too low for definitive conclusions, but a trend toward reduction in VTE frequency among marijuana users compared to nonusers was noted.”

LoPolito A, Mourabet T, Syed H, Brown CT, Saint-Fort L, Horst MA, Perea LL. Clotting Propensity in Trauma Patients According to Marijuana Use: A Descriptive Analysis. Am Surg. 2023:31348231157889.

Science/Human: Pain patients with anxiety benefit more from a treatment with cannabis then those without anxiety

An analysis of data of patients enrolled in the UK Medical Cannabis Registry showed that pain patients with anxiety show a better improvement in quality of life than those without anxiety. Data were presented by investigators of the Imperial College Medical Cannabis Research Group Department of Surgery and Cancer in London, UK. Participants were divided in 2 groups according to results of a questionnaire measuring anxiety scores.

Of 1254 patients 711 were categorised into the anxiety group and 543 in the no anxiety group. Authors wrote that the anxiety cohort reported greater improvements in quality of life scores “but there were no consistent differences in pain outcomes.”

Bapir L, Erridge S, Nicholas M, Pillai M, Dalavaye N, Holvey C, Coomber R, Hoare J, Khan S, Weatherall MW, Rucker JJ, Platt M, Sodergren MH. Comparing the effects of medical cannabis for chronic pain patients with and without co-morbid anxiety: A cohort study. Expert Rev Neurother. 2023:1-15.

Science/Human: Cannabis use was associated with shorter length of hospital stay after total joint arthroplasty

Using data from the National Inpatient Sample of the US from 2006 to 2015 with 8,740,798 patients undergoing total joint arthroplasty cannabis use disorder was associated with shorter length of hospital stay and increased home discharge. Investigators of the Department of Foundational Medical Studies at Oakland University William Beaumont School of Medicine in Rochester, USA, found that cannabis use disorder is increased during this time period.

Patients with cannabis use disorder had a significantly shorter length of hospital stay (3.0 vs. 3.2 days). When compared with the control group, cannabis use disorder was associated with significantly greater odds of home discharge, and significantly lower odds of rehab discharge. There were no differences in overall complication profile or in the vast majority of individual in-hospital complications between groups.

Rahmon D, Zalikha AK, Mazur M, Hajj Hussein I, El-Othmani MM. Cannabis use disorder is associated with shorter length of stay and increased home discharge after primary total joint arthroplasty: a propensity-weighted analysis. Arthroplasty. 2023;5(1):9.

News in Brief

Europe: The European Medicines Agency is calling for scientific data on the medical use of cannabis

The Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency “invites all interested parties such as pharmaceutical industry associations, health care professional groups, learned societies, consumers and patients’ associations, governmental institutions as well as EU and EEA-EFTA Member States to submit selected specific scientific data, which may be used in the assessment of Cannabis sativa L., flos as part of the establishment of European Union herbal monographs and/or European Union list entries.” The deadline for submissions is 14 May 2023.

EMA call for scientific data on medical cannabis

Science/Cells: Cannabis extracts with high CBD contents may be helpful in neuroblastoma

Cannabis extracts with a high CBD concentration induced mortality in cells of neuroblastoma, a childhood cancer of the nervous system.

Research and Development Department, IMG Pharma Biotech S.L., Derio, Spain.

Sánchez-Sánchez L, et al. Int J Mol Sci. 2023;24(4):3837.

Science/Animal: The CB2 receptor plays an important role in the prevention of colon cancer

A study with mice demonstrated that genetically modified mice without the CB2 receptor exhibit a higher incidence of spontaneous colon cancer.

Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Israel.

Iden JA, et al. Int J Mol Sci. 2023;24(4):4060.

Science/Human: CBD may not be effective in reducing post-ureteroscopic stent discomfort

In 90 patients undergoing ureteroscopy a very low dose of CBD (20 mg) was not superior to placebo in reducing discomfort after the procedure.

Department of Urology, University of North Carolina, Chapel Hill, USA.

Narang G, et al. J Urol. 2023;209(4):726-733.

Science/Animal: Electroacupuncture repairs intestinal barrier by increasing CB1 receptors

In a mouse model of colitis researchers demonstrated that electroacupuncture “may protect intestinal barrier functions by increasing the expression of CB1 to enhance autophagy through gut microbiota.”

Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Yang J, et al. Chin Med. 2023;18(1):24.

Science/Animal: Cannabinoids modulate the microbiota-gut-brain axis in HIV infection by reducing neuroinflammation

A study with rhesus monkeys demonstrates the potential of long-term, low-dose THC to positively modulate the microbiota-gut-brain axis “by reducing neuroinflammation, enhancing endocannabinoid levels and promoting the growth of gut bacterial species that produce neuroprotective metabolites, like indole-3-propionate.”

Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.

McDew-White M, et al. J Neuroinflammation. 2023;20(1):62.

Science/Human: Cannabis use may cause arterial stiffness

Cannabis use of 46 219 volunteers of the middle-aged UK Biobank population was assessed by questionnaire and investigates several aspects of cannabis use. Heavy lifetime cannabis use was associated with higher levels of arterial stiffness in men but not in women.

Department of Epidemiology-Data-Biostatistics, Delegation of Clinical Research and Innovation (DRCI), Foch Hospital, Suresnes, France.

Vallée A. J Hypertens. 2023;41(4):658-669.

Science/Human: The incidence of myocardial infarction increased in recent years in young cannabis users

Using a nationwide database of 819,175 hospitalisations researchers found, that the number of young cannabis users with acute myocardial infraction has increased in recent years. The risk is higher among males and African Americans.

Department of Internal Medicine, Louis A Weiss Memorial Hospital, Chicago, USA.

Sandhyavenu H, et al. Int J Cardiol Cardiovasc Risk Prev. 2022;16:200167.

Science/Animal: A treatment with THC may protect from colorectal cancer cachexia through modulation of inflammation

A study with mice demonstrated that a treatment with THC reduces muscle atrophy in colorectal cancer. THC was shown to reduce inflammation.

Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Ng SK, et al. Biomed Pharmacother. 2023;161:114467.

Science/Animal: CBD improves motor dysfunction due to a neuroleptic medication

CBD was shown to improve motor dysfunction after the administration of haloperidol, a well-known neuroleptic, in zebrafish.

Department of Forensic Medicine, Tokyo Medical University, Shinjuku, Tokyo, Japan.

Hasumi A, Maeda H. J Cannabis Res. 2023;5(1):6.

Science/Cells: CBD and THC may increase the anticancer effects of gemcitabine and cisplatin in bladder cancer

Cell studies indicate that cannabinoids can reduce the viability of human bladder cancer cells “that they can potentially exert synergistic effects when combined with other agents” including gemcitabine and cisplatin.

Faculty of Medicine, Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.

Whynot EG, et al. J Cannabis Res. 2023;5(1):7.

Science/Animal: CBD may protect from kidney injury induced by Gentamycin

The antibiotic medication Gentamycin may cause kidney damage and this may be prevented by CBD according to a study with rats.

Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.

Hokmabadi V, et al. Iran J Basic Med Sci. 2023;26(3):343-350.

Science/Animal: Low THC doses reduce pain in female but not male rats

Researchers found out, that inflammatory pain responded to low doses of THC in female rats but not in male rats.

Department of Psychology, Washington State University Vancouver, Washington, USA.

Morgan MM, et al. Cannabis Cannabinoid Res. 2023 Mar 1. [ in press].

Science/Human: Cannabis use may be associated with an increased risk of atherosclerosis

Among 104,092 volunteers of the UK Biobank population heavy cannabis use was associated with an increased risk of atherosclerosis.

Department of Epidemiology-Data-Biostatistics, Delegation of Clinical Research and Innovation (DRCI), Foch hospital, Suresnes, France.

Vallée A. Eur J Intern Med. 2023:S0953-6205(23)00060-2.

Science/Cells: Cannabis extracts may induce programmed cell death in melanoma cells

A cannabis extract with equal amounts of THC and CBD induced apoptosis, a form of programmed cell death, in melanoma cells. Researchers suggest THC and CBD “as a potential treatment of melanoma.”

School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, Chiang Rai, Thailand.

Poommarapan K, et al. Anticancer Res. 2023;43(3):1221-1237.

Science/Animal : CBD may be used in the treatment of prostate cancer

Researchers tested the effects of CBD and a cannabis extract on prostate cancer. They found that the “growth of tumours in the mouse models were reduced following treatment with cisplatin and cannabidiol.”

Department of Biochemistry, University of Johannesburg, Auckland Park Campus, Johannesburg, South Africa.

Motadi LR, et al. Mol Biol Rep. 2023 Feb 28. [in press].

Science/Animal: CBD increased the efficacy of doxorubicin bone cancer

In a mouse model of osteosarcoma (bone cancer) CBD and doxorubicin showed synergistic effects in reducing tumour size.

Department of Orthopedics, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Li J, et al. Clin Transl Oncol. 2023 Feb 27. [in press].

Science/Human: CBD may slightly impair driving performance

In a study with 40 people, who either received 300 mg CBD or a placebo there was no significant change in driving performance following CBD in a driving simulator, but those “receiving CBD experienced slightly more collisions.”

Department of Epidemiology and Biostatistics, School of Public Health, West Virginia University, Morgantown, West Virginia, USA.

Rudisill TM, et al. AJPM Focus. 2023;2(1):100053.

Science/Animal: Anxiety associated with palatable food withdrawal may be reversed by blockade of endocannabinoid degradation

In a study with rats abstinence from palatable food increased anxiety pharmacological inhibition of endocannabinoid degradation by FAAH (fatty acid amide hydrolase) blockade exerted anxiolytic -like effects.

UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, Spain.

de Ceglia M, et al. Int J Eat Disord. 2023 Feb 25. [in press].

Science/Animal: CBD may reduce stereotypic behaviour in horses

A 22-year-old mare suffering from chronic crib-biting and wind-sucking was successfully treated with 4 weeks of CBD administration.

Department of Veterinary Medical Sciences, University of Bologna, Italy.

Cunha RZ, et al. Vet Anim Sci. 2023 Feb 7;19:100289.

Science/Human: Cannabis use in female athletes is associated with a reduction in early anaerobic power production

According to a study with 12 female regular cannabis users and 12 non-users “cannabis users produced significantly less power in the first 2 stages of the Wingate assessment, but CU [cannabis users] experienced significantly less anaerobic fatigue.”

School of Sport and Exercise Science, University of Northern Colorado, Greeley, USA.

Lisano JK, et al. J Strength Cond Res. 2023;37(3):616-622.

Science/Animal: Hemp oil may induce programmed cell death in tumours

In a study with mice injected with viable Ehrlich ascites carcinoma cells then administered with hemp oil (20 mg/kg) daily for 10 consecutive days pre and post exposure to 6Gy whole body gamma radiation. Hemp oil induced a significant increase in cell death. Authors propose hemp oil “as an adjuvant in cancer treatment.”

National Centre for Radiation Research and Technology, Cairo, Egypt.

Hassan AA, et al. Can J Physiol Pharmacol. 2023 Feb 22. [in press].

Science/Cells: CBD may suppress ovarian cancer

Researchers confirmed “that CBD inhibits ovarian cancer cell growth by disrupting the LAIR-1-mediated interference with mitochondrial bioenergy metabolism.”

School of Basic Medical Sciences, Binzhou Medical University, Shandong Province, China.

Ma L, et al. Environ Toxicol. 2023 Feb 22. [in press].

Science/Cells: A CB1 receptor inverse agonist promotes insulin secretion

“A peripherally restricted CB1R inverse agonist, MRI-1891, augments glucose stimulated insulin secretion in isolated human pancreatic islets and mouse islets.”

Departments of Nutrition, Biochemistry and Molecular Medicine, Université de Montréal, Montreal Diabetes Research Center, Montréal, QC, Canada.

Ghosh A, et al. Eur J Pharmacol. 2023;944:175589.

Science/Human: Legalisation of cannabis was associated with an increase in motor vehicle accident deaths and a decrease in opioid overdose fatalities

Using data from US death certificates from 2009 to 2019 researchers found that “recreational markets were associated with a 10% increase in motor vehicle accident deaths, on average. This study found no evidence that recreational markets impacted suicides. Most states saw a relative reduction in opioid overdose death that ranged between 3 and 28%. On average, recreational markets were associated with an 11% reduction in opioid overdose fatalities.”

Division of Health Policy and Administration, School of Public Health, University of Illinois Chicago, USA.

Marinello S, Powell LM. Soc Sci Med. 2023;320:115680.

Science/Human: Exercise influences endocannabinoid levels and CB1 receptor expression

Investigations “suggest that resistance and endurance exercise regulate the levels of the endocannabinoid ligands and CB1 expression in opposite ways. The physiological impact of the changes observed in the endocannabinoid ligands in human skeletal muscle after exercise needs further investigation.”

Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, Belgium.

van Doorslaer de Ten Ryen S, et al. J Appl Physiol (1985). 2023;134(3):569-580.

Science: It is possible to produce CBD tablets

Researchers found out a way to produce CBD tablets despite it is the lipid material.

Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liège, Belgium.

Koch N, et al. Int J Pharm. 2023;633:122639

Science/Human: Legalisation of cannabis in Canada increased cannabis use

“Cannabis legalization was associated with an increased likelihood of cannabis use, daily cannabis use and cannabis-related problems.”

Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Imtiaz S, et al. Drug Alcohol Depend. 2023;244:109765.

Science/Animal: Altered endocannabinoid metabolism affects the blood-brain barrier

Research findings using a mouse model "suggest endocannabinoids and their metabolizing enzymes play an important role in the brain" including the integrity of the blood-brain barrier.

Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.

Ahluwalia M, et al. Exp Neurol. 2023;361:114320.

Science/Human: Genetic liability to cannabis use may lead to lower educational attainment

A large study showed that “genetic liability to cannabis use disorder may lead to lower educational attainment. Genetic liability to higher educational attainment may also lead to higher life-time cannabis use risk and lower cannabis use disorder risk. However, the bidirectional effect between cannabis use disorder and educational attainment may be due to shared risk factors (e.g. attention-deficit hyperactivity disorder).”

Department of Biostatistics, School of Public Health, Peking University, Beijing, China.

Chen D, et al. Addiction. 2023;118(4):698-710.