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IACM Monthly Meeting for Professionals July 2024

Brazil: Supreme Court votes to decriminalize personal use of cannabis

On 25 June Brazil's highest court voted to decriminalize the possession of cannabis for personal use after nearly 10 years of deliberating, but more decisions still need to be made.

The 11-person Brazilian Supreme Court, which began its deliberation on cannabis decriminalization in 2015, decriminalized use of the plant for up to 40 grams.

"The position is clear that no user of any drug can be considered a criminal," Justice Dias Toffoli, one of the judges said.

UPI of 26 June 2024

Science/Human: Cannabis may be helpful in autism spectrum disorder

In a retrospective analysis of 30 patients with autism spectrum disorder aged 5 to 18 years a cannabis extract may improve symptoms. Investigators of the University Hospital of Brasilia, Brazil, administered a cannabis extract with a CBD:THC ratio of 33 to 1 for varying durations.

Researchers “found significant improvements in various symptomatic and non-symptomatic aspects of ASD, with minimal untoward effects, as reported by both clinical assessments and parental perceptions. The observed improvements included increased communicative skills, attention, learning, eye contact, diminished aggression and irritability, and an overall increase in both the patient's and family's quality of life.”

Mazza JAS, Ferreira LS, Martins-Vieira AF, Beserra DDL, Rodrigues VA, Malcher-Lopes R, Caixeta FV. Clinical and Family Implications of Cannabidiol (CBD)-Dominant Full-Spectrum Phytocannabinoid Extract in Children and Adolescents with Moderate to Severe Non-Syndromic Autism Spectrum Disorder (ASD): An Observational Study on Neurobehavioral Management. Pharmaceuticals (Basel). 2024;17(6):686.

Science/Human: The medical use of cannabis may be helpful in people with trauma histories

According to an analysis of 100 cannabis users with trauma histories presented by investigators of the Dalhousie University in Halifax, Canada, they profited from the drug. They completed standardised measures of post-traumatic stress, depressive symptoms and hopelessness.

Sexual assault was experienced more often by women than men. The authors concluded from their research that “across many different trauma, women survivors' use of cannabis to cope with negative affect should be a specific therapeutic focus. Moreover, we identified specific emotional and cannabis use outcomes that should be of specific clinical concern among sexual assault survivors regardless of gender.”

Stewart SH , Khoury JMB, Watt MC, Collins P, DeGrace S, Romero-Sanchiz P. Effects of sexual assault vs. other traumatic experiences on emotional and cannabis use outcomes in regular cannabis users with trauma histories: moderation by gender? Front Psychol. 2024;15:1386264.

Science/Human: Oral CBD may be helpful in anxiety disorders according to a clinical study

According to a placebo-controlled clinical study conducted in multiple sites across India CBD was successful in the treatment of mild-to-moderate anxiety disorders. In this 15 week trial 178 participants received either oral nanodispersible CBD or placebo.

Researchers used several established questionnaires and concluded from the results that “nanodispersible CBD was therapeutically safe with no serious adverse events, well tolerated, and effective for the treatment of mild to moderate anxiety disorders, as well as associated depression and sleep quality disturbances. These results pave the way for probable prospective use of nanodispersible CBD formulation for various psychiatry disorders alone or in conjunction with other drugs.“

Gundugurti PR, Banda N, Yadlapalli SSR, Narala A, Thatikonda R, Kocherlakota C, Kothapalli KS. Evaluation of the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol oral solution (150 mg/mL) versus placebo in mild to moderate anxiety subjects: A double blind multicenter randomized clinical trial. Asian J Psychiatr. 2024;97:104073.

Science/Cells: CBD may inhibit the development of atherosclerosis by inhibition of foam cell formation

A basic study with macrophages, certain white blood cells, demonstrated that CBD may reduce foam cell formation, which may have a positive impact on the development of atherosclerosis. Researchers of the Center of Food Safety and Quality Control in Jiangsu Province of Jiangnan University in Wuxi, China, also noted that CBD increased cholesterol efflux within macrophages.

They concluded that their “study confirms that CBD can be an effective therapeutic candidate for atherosclerosis treatment.” They also investigated the mechanism of action, which is among others the activation of a certain receptor called PPAR Gamma and the down-regulation of ceramide, a certain family of lipid molecules.

He M, Shi J, Xu YJ, Liu Y. Cannabidiol (CBD) Inhibits Foam Cell Formation via Regulating Cholesterol Homeostasis and Lipid Metabolism. Mol Nutr Food Res. 2024:e2400154.

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

According to a prospective case series with 77 patients from the UK Medical Cannabis Registry cannabis-based medicines may be helpful in osteoarthritis. 

Pain and other symptoms were measured at 1-, 3-, 6-, and 12-month follow-ups from baseline. The initiation of cannabis treatment was associated with reduced pain in the Brief Pain Inventory, pain interference and pain according to another established questionnaire. There were also improvements in quality of life and anxiety.

Francis A, Erridge S, Holvey C, Coomber R, Holden W, Rucker J, Platt M, Sodergren M. Assessment of Clinical Outcomes in Patients With Osteoarthritis: Analysis From the UK Medical Cannabis Registry. J Pain Palliat Care Pharmacother. 2024;38(2):103-116.

Science/Human: The endocannabinoid like substance palmitoylethanolamide and polydatin improved irritable bowel syndrome in children

In a placebo-controlled study a combination of the endocannabinoid like substance palmitoylethanolamide and polydatin, which is found in several plants, improved abdominal pain caused by irritable bowel syndrome. It was a multicentre trial conducted at 3 Italian paediatric gastroenterology centres. Participations were aged between 10 and 17 years.

The study involved 70 children with irritable bowel syndrome. Of the participants, 34 received the therapy and 36 received a placebo. As compared with the placebo group, the therapy group had significantly more patients achieving complete remission after 12 weeks, with particular benefit in the diarrhea subtype of the disease. “The treatment group also experienced a significant reduction in abdominal pain intensity and frequency compared with the placebo group.”

Di Nardo G, Bernardo L, Cremon C, Barbara G, Felici E, Evangelisti M, Ferretti A, Furio S, Piccirillo M, Coluzzi F, Parisi P, Mauro A, Di Mari C, D'Angelo F, Mennini M. Palmitoylethanolamide and polydatin in pediatric irritable bowel syndrome: A multicentric randomized controlled trial. Nutrition. 2024;122:112397.

News in brief

American Medical Association delegates vote to decriminalize drug use, possession

On 13 June the American Medical Association's House of Delegates voted 345-171 to decriminalize drug personal use and possession. "We have tried for decades to criminalize our way out of a substance use crisis in this country, and it has not worked," said AMA Connecticut delegate Ryan Englander.

UPI of 13 June 2024

USA: Pardon of more than 175,000 cannabis convictions in Maryland

Maryland Govenor Wes Moore issued a "historic" pardon of more than 175,000 individual cannabis convictions, his first since the state's legalization of recreational cannabis went into effect last year. "We cannot celebrate the benefits of legalization if we do not address the consequences of criminalization," the first-term Democrat governor said on17 June.

UPI of 17 June 2024

Science/Human: CBD had no relevant effect on stress, sleep and overall mood disturbance

In a placebo-controlled study 54 healthy males and females with a mean age of 25 years received either CBD in a dose of 2×50 mg per day or a placebo. There were no differences in immune or inflammatory biomarkers and no relevant effects on perceived stress, sleep quality and overall mood disturbance.

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

Krzyżewska, A. et al. IJMS 2021; 22:10048

Science/Human: Lenabasum has some abuse potential

Lenabasum is a synthetic selective CB2 receptor agonist. In a study with 56 healthy participants 3 doses of lenabasum (20, 60, and 120 mg) were compared to placebo. There was no hint on abuse potential at 20 mg but some at the higher doses.

Columbia University, USA.

Luba R, et al. J Pharmacol Exp Ther. 2024:JPET-AR-2024-002129. PMID: 38932553 

Science/Cells: Cannabinoids may protect against peripheral neuropathy caused by a chemotherapeutic agent

Cannabis extracts and medium dried flowers preserve the viability of nerve cells and other cells exposed to paclitaxel, a chemotherapeutic agent.

Advanced Research and Development Center for Experimental Medicine (CEMEX), Iasi, Romania.

Creanga-Murariu I, et al. Front Pharmacol. 2024;15:1395951.

 

Science/Animal: Antidepressant-like and anti-inflammatory effects of cannabis were confirmed in mice

In studies with mice and cells the anti-inflammatory and antidepressant -like effects of cannabis were confirmed. The effects were due to several bioactive compounds in cannabis.

Institute for Global Rare Disease Network, Professional Graduate School space of Korean Medicine, Wonkwang University, Republic of Korea.

Shin J, et al. Plants (Basel). 2024;13(12):1619.

Science/Animal: CBD may be effective in severe neonatal inflammation of the colon

In studies with rats CBD reduced mortality and damage to the bowel in an experimental model of necrotising enterocolitis of neonates.

Health Research Institute of the Hospital Clínico San Carlos (IdISSC). Community of Madrid's Youth Employment Program, Madrid, Spain. 

Huertos Soto N, et al. Lab Anim Res. 2024;40(1):26. 

Science/Cells: Cannabinerol (CBNR) may protect against Alzheimer’s disease

Cannabinerol (CBNR) was shown to be neuroprotective in a cellular model of Alzheimer’s disease. CBNR pretreatment  counteracts the loss of cell viability of  certain nerve cells.

IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, Messina, Italy. 

Chiricosta L, et al. Cells. 2024;13(12):1012. 

Science/Animal: Hemp oil may improve the healing of burned skin

In studies with rats cannabis seed oil improved the healing of burned skin wards.

Laboratory of Biotechnology, Environment, Agri-Food and Health (LBEAS), Faculty of Sciences Dhar El Mehraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Bouarfa M, et al. Front Chem. 2024;12:1381527. 

Science/Animal: Cannabis may reduce the DNA of mitochondria in young adults

According to studies with mice the use of cannabis may transiently reduce mitochondrial DNA in young adults.

Department of Pharmacology & Toxicology, Medical Sciences Building, University of Toronto, Toronto, Canada. 

Powlowski P, et al. Cannabis Cannabinoid Res. 2024 Jun 26.

Science/Animal: CBD during pregnancy may cause postnatal cardiac deficits

In a study with rats authors demonstrated that “gestational exposure to CBD, a constituent perceived as safe, leads to early sex-specific postnatal cardiac deficits and alterations in the cardiac ECS [endocannabinoid system] in offspring.” 

Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. 

Lee K Cannabis Cannabinoid Res. 2024;9(3):781-796. 

Science/Human: CBD may be effective in refractory status epilepticus

According to 2 cases with super-refractory status epilepticus highly purified CBD may be very effective in symptom control.

Epilepsy Centre, Neurology Unit, University Hospital Tor Vergata, Rome, Italy.

Di Mauro G, et al. CNS Neurol Disord Drug Targets. 2024 Jun 21. 

Science/Animal: THC may help to revitalise polycystic ovary syndrome

In a study with female rats THC was shown to revitalise polycystic ovary syndrome through reduction of oxidative stress and modulation of macrophage polarisation.

School of Biology, Damghan University, Damghan, Iran. 

Zavareh S, et al. Iran J Basic Med Sci. 2024;27(8):1040-1049. 

Science/Animal: Hemp oil may have anti-cancer effects

In a study with mice hemp oil was shown both to reduce chemotherapy-induced peripheral neuropathy and antitumour effects.

National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, China. 

Xu Y, et al. Fitoterapia. 2024;177:106092. 

Science/Animal: CBD may be helpful in acne

According to studies with different skin cells CBD may be helpful in the management of acne because of its anti-inflammatory, apoptotic and lipid-inhibitory effects.

Department of Dermatology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea. 

Lee JH, et al. Arch Dermatol Res. 2024;316(7):428. 

Science/Human: CBD may have some pain reducing effects

In a placebo-controlled study with 54 healthy males and females with a mean age of 25 years CBD showed some pain reducing effects but had otherwise little effects.

University of South Carolina, Department of Exercise Science, Columbia, USA.

Mastrofini GF, et al. J Int Soc Sports Nutr. 2024;21(1):2370430.

Science: The plasma binding of CBD may be non-linear

The unbound fraction of CBD to certain materials was more than twofold greater at high concentrations of CBD compared to low concentrations.

Department of Biomedical and Pharmaceutical Sciences, Touro College of Pharmacy, New York, USA.

Babayeva M, Srdanovic I. J Cannabis Res. 2024;6(1):27. 

Science/Animal: CBD may protect nerve cells against amyloid beta

In studies with mice CBD was shown to protect the nerve cells of the hippocampus, a certain brain region, from nerve damage caused by amyloid beta peptides, which play a role in Alzheimer’s disease.

Laboratory of Neurobiology and Biomaterials, Federal University of Ouro Preto, MG, Brazil.

Del Carmen Barboza Salgado K, et al. Toxicol In Vitro. 2024:105880. 

Science/Human: A single dose of THC may reduce cognitive functioning in patients with schizophrenia

A single dose of 15 mg oral THC or smoked cannabis reduced cognitive functioning in a placebo-controlled study with 150 patients with schizophrenia without symptom exacerbation several hours after administration.

Dartmouth College Geisel School of Medicine at Dartmouth, Department of Psychiatry, Lebanon, USA. 

Brunette MF, et al. Schizophr Bull. 2024 Jun 20:sbae097. 

Science/Cells: CBD rescues nerve cells from toxicity 

CBD was able to rescue nerve cells from the hippocampus, a certain brain region, through its antioxidant properties and modulation of the endocannabinoid system.

Laboratory of Neurobiology and Biomaterials, Federal University of Ouro Preto, Brazil.

Salgado KDCB Toxicol In Vitro. 2024 Jun 18;99:105880. 

Science/Cells: CBD and CBG may protect skin cells from ultraviolet radiation

In experiments with human skin cells (fibroblasts and keratinocytes) cannabidiol and cannabigerol protected and regenerated cells when exposed to UVA radiation.

Dermatological Specialized Center "DERMAL" NZOZ in Białystok, Poland. 

Wroński A Cells. 2024 Jun 3;13(11):965. 

Science/Human: Cannabis use during pregnancy may increase the risk of fetal death

In a study with 894 pregnant women, of whom 30% used cannabis, there was a 7 fold increased risk for fetal death in cannabis users. 

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, US. 

Habersham LL J Perinatol. 2024 Jun 18. 

Science/Cells: Cannabigerol and cannabicyclol were active against the new coronavirus

Both cannabigerol and cannabicyclol inhibited the SARS -coronavirus-2 spike protein mediated membrane fusion.

Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Germany.

Classen N Planta Med. 2024 Jun 17. 

Science/Animal: CBD protects against the development of liver cirrhosis

In a study with rats CBD extracts demonstrated protective effects in the development of experimental liver cirrhosis.

Pharmacology Laboratory, Faculty of Human Medicine, Universidad Nacional Mayor de San Marcos-UNMSM, Lima, Peru.

Flores-Cortez D Cannabis Cannabinoid Res. 2024 Jun 17. 

Science/Animal: The metabolite 11-hydroxy-THC may display equal or greater activity than THC

After oral intake of THC in mice its first metabolite 11-OH-THC displayed equal or greater activity than the mother compound THC itself. “Thus, the THC metabolite 11-OH-THC likely plays a critical role in the bioactivity of cannabis,” authors noted.

College of Pharmacy and Nutrition, University of Saskatchewan, Canada.

Zagzoog A J Pharmacol Exp Ther. 2024 Jun 10:JPET-AR-2023-001998. 

Science/Cells: CBD may protect aged astrocytes from cholesterol

Researchers found that endocannabinoids and CBD reduce a buildup of cholesterol in astrocytes. Authors wrote: “Given that reduced neuronal cholesterol affects synaptic plasticity, the ability of cannabinoids to restore cholesterol transport from aged astrocytes to neurons holds significant implications in aging and inflammation.“

Departamento de Neurobiología Molecular y celular, Instituto Ferreyra, INIMEC-CONICET-UNC, Universidad Nacional de Córdoba, Córdoba, Argentina. 

Allende LG Glia. 2024 Jun 10. 

Science/Animal: CBD may be helpful in diseases with vascularisation of the eye cornea

In a study with mice researchers demonstrated that CBD may have the potential to treat illnesses with corneal neovascularization and lymphangiogenesis. 

Eye Hospital, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. 

Wei C Int Immunopharmacol. 2024;137:112429. 

Science/Cells: Cannabispirenone A from cannabis may protect nerve cells

Researchers found that Cannabispirenone A protected nerve cells from toxicity caused by NMDA.

Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu India. 

Thapa S Oxid Med Cell Longev. 2024;2024:3530499. 

Science/Human: Heavy cannabis use increases mortality by cardiovascular disease in females

This study used large data from the UK biobank study with about 120 000 participants followed by a median of 12 years. Heavy cannabis use was associated with an increased mortality by cardiovascular diseases in females, but not in males.

Department of Epidemiology and Public Health, Foch Hospital, Suresnes, France. 

Vallée A JAMA Netw Open. 2024;7(6):e2415227. 

Science/Animal: Delta-8-THC blocks the development of arthritis

In a study with mice delta-8-THC blocked the development of experimentally induced arthritis.

University of Connecticut, USA.

Vanegas SO J Pharmacol Exp Ther. 2024:JPET-AR-2024-002189. 

Science/Cells: CBD reduces growth and metastasis in liver cancer

CBD was tested on hepatocellular carcinoma cells (liver cancer cells) and it was shown to suppress the growth and metastasis of these cells.

Institute of International Rivers and Eco-Security, Yunnan University, Kunming, Yunnan China.

Tan S Biochim Biophys Acta Gen Subj. 2024 Aug;1868(8):130651. 

Science/Animal: A diet rich in sugar increased CB1 receptor binding in certain brain structures

In a study, minipigs received 2 litres of 25% sucrose solution daily for 12 days. Researchers found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may have negative effects on appetite regulation and feeding.

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Bærentzen SL Neuropharmacology. 2024 Sep 15;256:110018. 

Science/Human: Cannabis use during pregnancy may be associated with autism spectrum disorder

In a study with about 220,000 mothers cannabis use was associated with an increased risk of autism spectrum disorder in offspring compared to nonexposed children.

School of Population Health, Curtin University, Kent Street, Bentley, WA, 6102, Australia

Tadesse AW Psychiatry Res. 2024;337:115971. 

Science/Animal: CBD may be helpful in the treatment of post-traumatic stress disorder

In a mouse model of post-traumatic stress disorder researchers demonstrated that the utilisation of CBD may be helpful in post-traumatic stress disorder from the perspective of its regulation of neuroinflammation.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China. 

Xie G Brain Behav Immun. 2024;119:945-964. 

Science: Analysis of the best forms of storage for cannabis

Storage of cannabis in glass bottles may be most beneficial for the retention of volatile organic compounds compared to a closed high-density polyethylene box. However the glass bottle storage condition caused formation of neutral cannabinoids from acid precursors.

Department of Chemical, Pharmaceutical, and Agricultural Sciences, University of Ferrara, Ferrara, Italy. 

Spadafora ND Anal Bioanal Chem. 2024;416(16):3797-3809. 

Science: Hemp may decontaminate soil from metals such as cadmium and lead

Several hemp varieties were compared with regard to their ability to decontaminate soil from heavy metals, mainly copper, cadmium and lead. The authors noted that “hemp is a viable alternative for phytoattenuation in soils contaminated with heavy metals.”

School of Materials and Environmental Engineering, Changsha University, Changsha, China. 

Guo Y. Chemosphere. 2024;358:142199. 

Science/Cells: CBD may disrupt the homeostasis of pathways in the placenta

In studies with parts of the human placenta researchers demonstrated that “CBD modulates TRP catabolism in the human placenta, potentially disrupting the tightly regulated homeostasis of the serotonin and KYN pathways.”

Department of Pharmacology and Toxicology, Charles University, Faculty of Pharmacy in Hradec Kralove, Czech Republic. 

Portillo R Toxicology. 2024;505:153813. 

Science/Animal: CBD may limit cocaine abuse

Studies with mice suggest “that CBD may act via the gut to reduce the memory of cocaine reward. Our data suggest that improving gut health and using CBD could limit cocaine abuse.” 

School of Medicine, Western Sydney University, Campbelltown, NSW, Australia. 

Chesworth R Prog Neuropsychopharmacol Biol Psychiatry. 2024;133:111014. 

Science/Animal: CBD may be beneficial to counteract cognitive impairment in Alzheimer’s disease

According to studies with mice “CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.” 

Basic Medical and Forensic Medicine, Baotou Medical College, Inner Mongolia, China. 

Ma BQ J Toxicol Environ Health A. 2024;87(11):471-479. 

Science/Animal: The inhibition of endocannabinoid degradation may mitigate MS -related inflammation

According to studies with mice inhibition of the degradation of the endocannabinoid 2-AG by MAGL inhibitors “highlight the therapeutic potential of MAGLi-based drugs in mitigating MS-related inflammatory and neurodegenerative brain damage.”

Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. 

Guadalupi L Neuropharmacology. 2024;252:109940. 

Science/Animal: High doses of CBD may have negative effects on the liver

In studies with rats high doses of CBD induced degenerative changes and genotoxicity in the liver.

Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, Brazil.

Pinto TG Arch Toxicol. 2024;98(6):1877-1890. 

Science/Animal: THC may be beneficial in hyperinsulinaemia

In studies with rats with hyperinsulinaemia THC “exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.” 

Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Demiroglu Bilim University, Istanbul, Turkey.

Coskun Yazici ZM J Pharm Pharmacol. 2024;76(6):701-709. 

Science/Human: Genetic variation in liver enzymes may have an influence on cannabis-related outcomes

In a study with 54 cannabis users and non-users “initial findings suggest that genetic variation in CYP2C9 and CYP3A4 may have sex-specific associations with cannabis-related outcomes. Slow metabolizer genes may serve as a risk factor for CUD [cannabis use disorder] for females independent of subjective effects. Male slow metabolizers may instead be particularly susceptible to the negative subjective effects of cannabis.” 

Ralph H. Johnson VA Medical Center, Charleston, USA

Davis CN Addict Behav. 2024;153:107996.