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IACM-Bulletin of 3 December 2023

IACM: 13th IACM Conference on Cannabinoids in Medicine in 2024 to be held online

The 13th IACM Conference on Cannabinoids in Medicine, which was originally scheduled to take place in Aberdeen from 11 to 13 April 2024, will unfortunately have to be held online for various reasons. Further information on the dates and programme will follow in the coming weeks.

In addition, the IACM will probably hold another conference in 2024 in cooperation with a national organisation, as we did in November 2023 together with WeCann in Brazil.

IACM Conference 2024

Japan: Parliament opens the way for the medical use of pharmaceuticals based on cannabis

Japan recently took a major step towards reform, potentially providing a major boom for the country’s CBD industry and opening the door for the establishment of a medical cannabis and industrial hemp industry in the country. A bill proposed by the government has been passed by the House of Representatives on 14 November 2023.

 The revision of the Japanese cannabis law will mean that pharmaceutical products containing ingredients extracted from cannabis plants can be used domestically. It will open up the possibility of a medical cannabis market in Japan, marking a significant shift in attitudes towards cannabis from the government.

Business of Cannabis of 20 November 2023

South Africa: Parliament legalised the possession and cultivation of cannabis

The Cannabis for Private Purposes Bill was adopted by the National Assembly on 14 November. The decision to adopt the bill has finally stubbed out a five-year-long lull which followed a groundbreaking 2018 judgement of the Constitutional Court, which stated that criminalisation of private cannabis use is unconstitutional.

Member of Parliament Janho Engelbrecht, who spoke on the bill in the National Assembly, stressed that adults will be allowed to use cannabis only in their homes. “People should bear in mind what this bill is about. It is about cannabis for private use by adults. You are not allowed to buy or sell cannabis, because this still remains a criminal activity with severe consequences. If you want to smoke it, you have to grow it, don’t buy it,” he said. The bill does not specify the quantities of cannabis plants and dried cannabis that a person may possess for private use. The bill will now be transferred to the National Council of Provinces for concurrence.

The Citizen of 14 November 2023

Science/Human: People with sleeping problems prefer cannabis over other medicinal drugs

According to a survey by investigators of the School of Medicine at Boston University, USA, with 1216 individuals people with sleeping problems prefer cannabis over other medicinal drugs.

Participants predominantly reported smoking cannabis cigarettes or vaping flower as their methods of administration, and seeking THC, CBD, and the terpene myrcene in the cannabis they use for sleep. Only a small minority reported using cannabis in conjunction with conventional sleep aids. Comparisons of the self-reported effects of cannabis to conventional sleep aids revealed that participants reported feeling more refreshed, focused, better able to function, fewer headaches, and less nausea the morning after using cannabis for sleep than after using more conventional sleep aids or no sleep aids. However, they indicated they were more sleepy, anxious, and irritable in the mornings following the use of cannabis relative to other sleep aids.

Stueber A, Cuttler C. A large-scale survey of cannabis use for sleep: preferred products and perceived effects in comparison to over-the-counter and prescription sleep aids. Explor Med. 2023;4:709–719.

Science/Human: Cannabis may be effective in treatment resistant cancer pain

In a cross-sectional study by investigators of Tel Aviv Sourasky Medical Center, Israel, 252 consecutive refractory cancer-related pain patients filled out detailed self-report questionnaires. Of these, 126 patients (55%) were treated with cannabis and 105 patients (45%) were not.

Cannabis was mainly started for pain relief, sleep difficulties and anorexia. About 70% of patients reported subjective improvement from cannabis , with almost 40% reporting a significant improvement in coping with their illness. Side effects were generally mild, with fatigue and dizziness being the most common (22% and 23%, respectively). Of non-users, 65% had tried cannabis before and stopped due to lack of effectiveness or side effects.

Sharon H, Agbaria Y, Brill S, de Santiago J. Medical cannabis for refractory cancer-related pain in a specialised clinical service: a cross-sectional study. BMJ Journals of 16 November 2023.

Science/Human: No significant changes of cognition by medical cannabis in chronic health conditions

40 patients with various health conditions attended a single laboratory session in which they self-administered a standard dose of prescribed medical cannabis as per instructions on the pharmacy label. Investigators of the School of Health Sciences at Swinburne University of Technology in Melbourne, Australia, assessed cognitive performance and subjective drug effects prior to and following (1, 2 and 4 h) medical cannabis self-administration. Participants were prescribed a range of products including orally administered oils (n = 23) and flower for vaporization (n = 17).

Participants had a mean age of 41 years and had been using medical cannabis for a mean of 10 months. Participants' performance improved over time on a multitasking test and rapid visual information processing test. All other changes in cognitive performance measures over time were non-significant. Authors concluded that these “findings suggest that prescribed medical cannabis may have minimal acute impact on cognitive function among patients with chronic health conditions.”

Arkell TR, Manning B, Downey LA, Hayley AC. A Semi-Naturalistic, Open-Label Trial Examining the Effect of Prescribed Medical Cannabis on Neurocognitive Performance. CNS Drugs. 2023;37(11):981-992.

Science/Human: Children and young adults with treatment resistant epilepsy may profit from CBD

A retrospective analysis of medical records of 139 children and young adults (median age 12 years) with treatment resistant epilepsy treated with purified CBD from 2018 to 2022 at five medical centers in Israel showed that the cannabinoid may be an effective treatment option. The most common diagnosis was Lennox-Gastaut syndrome (37.4%) followed by Dravet syndrome (16.5%) and tuberous sclerosis complex (16.5%). Median purified CBD dose was 12.5 mg/kg, and median treatment duration was 9 months .

Most patients (92.2%) had a reduced seizure frequency following treatment initiation; 41.1% had more than 50% reduction. Fifty-three patients (38.1%) had further positive effects: improved alertness (31.7%), improved speech (10.1%), and achievement of new developmental milestones (2.2%). Concomitant treatment with clobazam, valproic acid, or everolimus did not affect seizure reduction by purified CBD. The most common adverse events were irritability (20.9%) and drowsiness (12.9%). Authors concluded that “CBD is well-tolerated and effective in reducing seizure frequency in children and young adults” with treatment resistant epilepsy.

Tzadok M, Gur-Pollack R, Florh H, Michaeli Y, Gilboa T, Lezinger M, Heyman E, Chernuha V, Gudis I, Nissenkorn A, Lerman-Sagie T, Ben Zeev B, Uliel-Sibony S. Real-Life Experience With Purified Cannabidiol Treatment for Refractory Epilepsy: A Multicenter Retrospective Study. Pediatr Neurol. 2023;150:91-96.

Science/Human: Cannabidiol (CBD) and cannabigerol (CBG) may have a moderate effect on recovery from muscle soreness

A placebo-controlled pilot study tested the safety, tolerability, and preliminary effects on recovery of a formulation containing CBD (35 mg), CBG (50 mg), beta caryophyllene (25 mg), branched-chain amino acids (3.8 g), and magnesium citrate (420 mg). Exercise-trained individuals (N = 40) underwent an experimental induction of delayed onset muscle soreness and completed follow-up visits 24-, 48-, and 72-hours after initiation of muscle soreness. Participants were randomized to active or placebo formulation, and consumed the formulation twice per day for 3.5 days. The study was conducted by investigators of Canopy Growth Corporation in Smiths Falls, Canada, and of Nova Southeastern University, Exercise and Sport Science, in Davie, USA.

For the primary outcome of interest, the estimate of effect for ratings of average soreness/discomfort 72 hours after the initiation of muscle soreness between active and placebo groups there was moderate evidence of a treatment difference. The estimate of effect for the outcome of ratings of interference of soreness, discomfort, or stiffness on daily activities at work or home 48 hours after initiation of muscle soreness indicated a treatment difference of potential clinical importance. There was no significant effect between active and placebo groups on objective measures of recovery, sleep quality, or mood disturbance.

Peters EN, Yardley H, Harrison A, Eglit GML, Antonio J, Turcotte C, Bonn-Miller MO. A randomized, double-blind, placebo-controlled, repeated-dose pilot study of the safety, tolerability, and preliminary effects of a cannabidiol (CBD)- and cannabigerol (CBG)-based beverage powder to support recovery from delayed onset muscle soreness (DOMS). J Int Soc Sports Nutr. 2023;20(1):2280113.

News in brief

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

In a cell model of cancer-induced human skeletal muscle cachexia the activation of the CB2 receptor reduced the degeneration of muscle cells.

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

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

Science/Human: The legalisation of cannabis in Canada was not associated with cannabis initiation but with cannabis dependence in adolescents

An analysis of a survey of students in Ontario with 89,238 participants showed that cannabis “legalisation was not associated with cannabis initiation, but it was associated with an increased likelihood of any cannabis use, daily cannabis use and cannabis dependence.”

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

Imtiaz S, et al. Drug Alcohol Rev. 2023 Nov 28. [in press]

Science/Animal: The aerosol produced by a cannabis vaporiser may impair endothelial function

In a study with rats “acute direct exposure and modeled secondhand exposure to marijuana leaf vaporizer aerosol, regardless of cannabinoid concentration or aerosol generation temperature, impair endothelial function in rats comparably to marijuana smoke.”

Cardiovascular Research Institute, University of California, San Francisco, USA.

Liu J, et al. J Am Heart Assoc. 2023:e032969.

Science/Animal: High CBD doses may cause some changes in liver function

“Chronic administration of CBD in healthy dogs at 5 mg/kg was better tolerated than 10 mg/kg, and both dosages caused an increase in ALP activity. Although our data does not indicate hepatic damage, it is recommended to monitor liver function in dogs receiving CBD chronically.”

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

Corsato Alvarenga, et al. J Vet Intern Med. 2023 Nov 27. [in press]

Science/Animal: Inhibition of of anandamide degradation may prevent the development of allodynia in trigeminal neuralgia

According to a a study with rats a synthetic inhibitor of FAAH, which is responsible for the degradation of the endocannabinoid anandamide, “may counteract, but not reverse, the development of allodynia in trigeminal neuralgia.”

Department of Brain and Behavioral Sciences, University of Pavia, Italy.

Demartini C, et al. Pharmaceuticals (Basel). 2023;16(11):1626.

Science/Animal: CBD may protect the liver from the toxicity of fly amanita

In a study with mice CBD “protects the liver from α-Amanitin-induced apoptosis and oxidative stress through the regulation of Nrf2.”

NHC Key Laboratory of Drug Addiction Medicine, Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China.

Wang H, et al. Food Chem Toxicol. 2023;182:114196.

Science/Human: The endocannabinoid concentrations in blood is altered in patients with depression

In a study with 161 patients with a depressive disorder and 161 healthy participants researchers observed higher anandamide and decreased 2-AG concentrations in patients with depression.

LWL University Hospital, Department of Psychiatry, Psychotherapy and Preventive Medicine, Ruhr University Bochum, Germany.

Obermanns J, et al. Brain Behav. 2023:e3323

Science/Human: CBD was not effective in typical absence seizures

In a study with 14 patients aged 6 years and older diagnosed with typical absence seizures CBD was not effective.

Comprehensive Epilepsy Center, University of South Florida, Tampa, USA.

Azevedo M, Benbadis SR. Epilepsy Behav. 2023;149:109512.

Science/Animal: CBD may mediate its anticonvulsant effects via modulation of nerve inflammation

In a study with rats with status epilepticus CBD reverted seizures “with probable involvement of CB1 receptors and anti-inflammatory effects by reducing IL-1β and TNF-α markers independent of CB2 and GABAA receptors.”

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Masoumi M, et al. Cannabis Cannabinoid Res. 2023 Nov 17. [in press]

Science/Animal: CBD may mitigate abnormalities in kidney function caused by a chemotherapeutic agent

In a study with rats CBD oil mitigated abnormalities in kidney function, inflammation and renal tissue changes caused by a doxorubicin, a chemotherapeutic agent.

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

Soliman NA, et al. Naunyn Schmiedebergs Arch Pharmacol. 2023 Nov 16. [in press]

Science/Human: High endocannabinoid levels in blood correlate with a worse metabolic profile

High endocannabinoid levels in blood were “related to higher levels of adiposity and worse cardiometabolic profile.”

Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.

Di X, et al. J Clin Endocrinol Metab. 2023:dgad668.

Science/Animal: Regular exercise may increase the number of CB1 receptors on certain white blood cells

In a study with rats chronic exercise decreased “the proportion of T helper and Tγδ cells but increases the expression of cannabinoids (CBR1) on T helper and natural killer cells, and the production of interleukins, including IL-1β, interferon-gamma, tumor necrosis factor-alpha, IL-10, and IL-4, suggesting higher reactivity and efficiency from the immune system conferred by exercise.”

Department of Integrative Physiology, University of Colorado Boulder, USA.

Valencia-Sánchez S, et al. J Interferon Cytokine Res. 2023 Nov 14. [in press]

Science/Human: Some rare adverse events by high doses of CBD

An investigation of data between 2018 and 2023 following the medical use of Epidyolex, a CBD extract, found some new possible adverse effects, namely “seizure cluster, blood ketone body decrease, cortical visual impairment, hyperactive pharyngeal reflex, and poverty of speech.”

Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu, China.

Zhou Q, et al. Asian J Psychiatr. 2023;90:103828.

Science/Cells: Cannabidivarin (CBDV) may promote neurogenesis

A study with normal stem cells or progenitor cells revealed the “neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target.”

Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal.

Lourenço DM, et al. Eur J Pharmacol. 2023;959:176079.

Science/Cells: CBD may reduce the toxicity caused by inflammation in astrocytes

In a primary cell culture model of lipopolysaccharide (LPS)-induced neurotoxicity in astrocytes CBD “enhances mitochondrial bioenergetic profile, attenuates proinflammatory cytokines release, and ROS overproduction of astrocytes stimulated by LPS. These effects are not mediated directly by CB1 receptors, while these receptors seem to have a key role in the anti-inflammatory response of the endocannabinoid system on astrocytes.”

Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research Centre, Mohammed V University in Rabat, Morocco.

Ibork H, et al. Neurotox Res. 2023;41(6):615-626.

Science/Cells: CBD attenuates inflammatory impairment of intestinal cells

In a new study with intestinal cells “findings demonstrate the potential of CBD as a component of Cannabis-based biomaterials used in the development of novel therapeutic approaches against inflammatory pathogenesis.”

Institute of Veterinary Physiology, School of Veterinary Medicine, Freie Universität Berlin, Germany.

Boehm E, Droessler L, Amasheh S. Mater Today Bio. 2023;23:100808.

Science/Animal: Increased numbers of CB1 receptors in the hippocampus protect from severe seizures

In pregnant mice increased numbers of CB1 receptors in the hippocampus, a certain brain region, protects from seizures.

Program in Neuroscience, University of Mississippi Medical School, Jackson, USA.

Jones-Muhammad M, et al. J Neurosci Res. 2023;101(12):1884-1899.

Science/Human: Cannabis use may be associated with an increased number of incomplete healing after spine surgery

In an analysis of 40,989 patients that underwent lumbar spine fusion “pseudarthrosis rate was greater in cannabis users (2.4%) than in controls (1.1%).” Pseudarthrosis is a permanent failure of healing of broken bones.

Department of Orthopedic Surgery, University of Connecticut Medical School, Farmington, USA.

Barkay G, et al. N Am Spine Soc J. 2023;16:100265.

Science/Human: Cannabis use is not associated with hypertension in middle aged adults

Data of 9,783 middle-aged adults (35-59 years) showed that a history of monthly cannabis use for more than 1 year was not independently associated with either increased blood pressure or prevalent hypertension in a nationally representative sample of middle-aged US adults.

Department of Family Medicine, University of California San Diego, La Jolla, USA.

Corroon J, et al. Am J Hypertens. 2023;36(12):651-659.

Science/Animal: Cannabis roots may reduce dysmenorrhoea symptoms

In a study with female mice an aqueous extract of cannabis sativa roots, which contain cannabisativine, anhydrocannabisativine, feruloyltyramine, and p-coumaroyltyramine, “exhibits an antidysmenorrheic effect both alone and in association with drugs, reducing abdominal contortions in female mice without generating organ enlargement in the animals.”

Central for Analysis of Drugs, Medicines and Food (CAFMA), Federal University of Vale do São Francisco, Pernambuco, Brazil.

Araújo TCL, et al. J Ethnopharmacol. 2024;318(Pt A):116891.