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IACM-Bulletin of 4 June 2023

USA: Minnesota becomes the 23rd state to legalise the use of cannabis for adults

Minnesota became the 23rd state in the country to legalize recreational cannabis for adults after Gov. Tim Walz signed the measure into law on 30 May. Starting 1 August cannabis use and possession will be decriminalized and home-growing of cannabis plants will become legal for people 21 and older. The state will also begin expunging cannabis convictions from Minnesotans' records in August. But the start of retail sales is likely at least a year away.

The bill signing marked a watershed moment for Minnesota, which legalized medical cannabis nearly a decade ago but had seen efforts to allow recreational cannabis repeatedly stall at the State Capitol. „This has been a long journey," Walz said. "I assure Minnesotans that a lot of thought has gone into this. A lot of the things we've learned in other states are incorporated into how we do this."

StarTribune of 30 May 2023

Science/Human: Cannabis may reduce symptoms and opioid use in multiple sclerosis

Investigators of the Dent Neurologic Institute in Buffalo, USA, conducted a retrospective medical records review of 141 patients with multiple sclerosis receiving cannabis. The drug was well tolerated and eased pain and spasticity.

Patients experienced extensive symptom improvement after initiation of medical cannabis, with alleviation of pain (72% of patients) and spasticity (48% of patients) and improvement in sleep (40% of patients) the most common. There was a significant reduction in concomitant opioid use after initiating cannabis as evidenced by a significant decrease in daily morphine milligram equivalents among patients prescribed opioid analgesics. Decreases in muscle relaxant use and benzodiazepine use did not reach significance.

Rainka MM, Aladeen TS, Mattle AG, Lewandowski E, Vanini D, McCormack K, Mechtler L. Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population.Int J MS Care. 2023:111-117

Science/Human: Cannabis in patients with Parkinson’s disease shows good long-term safety

In a retrospective analysis of data from 76 patients suffering from Parkinson’s disease cannabis use was safe and had no detrimental effects on disease progression. Investigators of the Department of Neurology at Sheba Medical Center in Tel-Hashomer, and Sackler School of Medicine of Tel Aviv University, Israel, included patients who used licensed whole-plant medical cannabis for at least a year. They were compared to a matched group who did not receive cannabis.

The median monthly dose of cannabis was 20 g, with a median THC percentage of 10 and a median CBD percentage of 4. There were no significant differences between the cannabis and the control groups for stage progression. A statistical analysis showed no evidence of relative worsening of psychotic, depressive, or cognitive symptoms reported by patients to their treating physicians over time in the cannabis group.

Goldberg T, Redlich Y, Yogev D, Fay-Karmon T, Hassin-Baer S, Anis S. Long-term safety of medical cannabis in Parkinson's disease: A retrospective case-control study. Parkinsonism Relat Disord. 2023:105406.

Science/Human: CBD shows long-term efficacy in epilepsy

The Cannabidiol Expanded Access Program initiated in 2014, provided the CBD cannabis extract Epidiolex to patients with treatment-resistant epilepsy. In the final pooled analysis of 892 patients treated through January 2019 (median exposure 694 days), by PANDA Neurology in Atlanta, USA, CBD treatment was associated with a 46%-66% reduction in median monthly seizure frequency.

CBD was well tolerated. Approximately 50% of patients had at least 50% reduction in convulsive and nonconvulsive seizure types and epileptic spasms at nearly all intervals. Authors noted that “these results show a favourable effect of long-term CBD use” in patients with treatment resistant epilepsy who may experience various convulsive and nonconvulsive seizure types.

Flamini RJ, Comi AM, Bebin EM, Chez MG, Clark G, Devinsky O, Hussain SA, Lyons PD, Patel AD, Rosengard JL, Sahebkar F, Segal E, Seltzer L, Szaflarski JP, Weinstock A. Efficacy of cannabidiol in convulsive and nonconvulsive seizure types associated with treatment-resistant epilepsies in the expanded access program. . Epilepsia. 2023 May 26. [in press]

Science/Human: CBD may be a helpful adjunct in the treatment of children with cerebral palsy

Investigators of the Paediatric Orthopaedic Surgery Department at Stanford Hospital and Clinics, USA, sought to describe CBD use patterns and perceived efficacy in the paediatric population with cerebral palsy. Of 119 participants, 17% endorsed CBD use and 83% denied it. Before treatment participants in the CBD group had worse functional status and lower health-related quality of life.

CBD was perceived to be most effective for improving emotional health, spasticity, and pain. Fifty percent of the patients in the CBD group underwent surgery in the previous 2 years and most endorsed a general benefit in the postoperative setting. The most common side effects noted were fatigue and increased appetite. Most participants endorsed no side effects (60%).

Seltzer RA, Langner JL, Javier NM, Kaur J, Shafau AL, Ezeonu T, Bryson X, Hastings K, Tileston K, Vorhies JS. Cannabidiol Use Patterns and Efficacy for Children Who Have Cerebral Palsy. Orthopedics:1-5.

Science/Human: Cannabis use is associated with a lower risk for the development of fatty liver

In a cohort with 2622 participants past and current cannabis users had a lower prevalence of liver steatosis (fatty liver). This cross-sectional study was performed with data from the 2017-2018 cycle of NHANES (National Health and Nutrition Examination Study) by investigators of the Department of Ultrasound at the General Hospital of Central Theater Command in Wuchangqu, Wuhan, China.

The proportions of never cannabis users, past users, and current users were 46%, 35%, and 19%, respectively. Compared to never cannabis users, past and current users had a lower prevalence of liver steatosis (P = 0.2 and P = 0.05, respectively). In the alcohol intake-adjusted model, current cannabis use was an independent predictor of a low prevalence of liver steatosis in people with non-heavy alcohol intake. The association between cannabis use and liver fibrosis was not significant in statistical analyses.

Du R, Tang XY, Yang C, Gao WH, Gao SJ, Xiang HJ, Yang L. Marijuana use is inversely associated with liver steatosis detected by transient elastography in the general United States population in NHANES 2017-2018: A cross-sectional study. PLoS One. 2023;18(5):e0284859.

Science/Human: Pain patients profit from cannabis use according to a survey

A study with 969 participants in a cross-sectional, web-based survey of individuals with self-reported chronic pain showed benefits of cannabis in a large variety of pain disorders. Investigators of the Department of Anesthesiology and Perioperative Medicine at the University of Rochester School of Medicine and Dentistry, USA, invited them to participate through an email that was distributed to the listservs of patient advocacy groups and foundations that engage individuals with chronic pain.

Of the 969 respondents, 46% respondents reported currently taking, 22% previously taken, and 32% never taken cannabinoids for pain. Participants reported using cannabinoids to treat a wide variety of chronic pain conditions. Those currently taking cannabinoids (vs previously) more frequently reported: (1) large improvements from cannabinoids in all pain types, including particularly difficult-to-treat chronic overlapping pain conditions (eg, pelvic pain), (2) improvements in comorbid symptoms (eg, sleep), and (3) lower interference from side effects.

Gewandter JS, Edwards RR, Hill KP, Wasan AD, Hooker JE, Lape EC, Besharat S, Cowan P, Le Foll B, Ditre JW, Freeman R. Cannabinoid Therapy: Attitudes and Experiences of People With Chronic Pain. . Clin J Pain. 2023;39(6):249-258.

Science/Human: Cannabis may be helpful in Parkinson’s disease

In a retrospective chart review of data from 69 patients with Parkinson’s disease treated with cannabis in the normal course of clinical practice most patients showed some treatment effect. The study was conducted by researchers at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, USA. Most patients were initially certified for a 1:1 (THC/CBD) tincture.

87 percent of patients (n = 60) were noted to exhibit an improvement in any symptom after starting cannabis treatment. Symptoms with the highest incidence of improvement included cramping/dystonia, pain, spasticity, lack of appetite, dyskinesia, and tremor. After starting cannabis, 56% of opioid users (n = 14) were able to decrease or discontinue opioid use with an average daily morphine milligram equivalent change from 31 at baseline to 22 at the last follow-up visit.

Aladeen TS, Mattle AG, Zelen K, Mesha M, Rainka MM, Geist T, Myers B, Mechtler L. Medical Cannabis in the Treatment of Parkinson's Disease. Clin Neuropharmacol. 2023 May-Jun 01;46(3):98-104.

News in brief

Science/Human: Problematic cannabis use did not increase after cannabis legalisation in Canada

According to a large survey “the risk of problematic cannabis use does not appear to have increased in the 2 years following cannabis legalisation in Canada. Disparities in problematic use persisted, with some racial minority and marginalised groups experiencing higher risk.”

School of Public Health Sciences, University of Waterloo, Canada.

Fataar F, et al. Drug Alcohol Rev. 2023 May 3. [in press]

Science/Human: Cannabis smoking does not have an influence on COPD progression

According to a large prospective study, where most participants were followed for at least 4 years “neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development.”

Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, USA.

Barjaktarevic I, et al. Chronic Obstr Pulm Dis. 2023 May 16. [in press]

Science/Cells: Several natural cannabinoids show antimelanoma effects

“By evaluating for the first time the preliminary anti-melanoma, anti-melanogenic, and anti-tyrosinase properties of CBN and CBC and confirming similar effects for CBD and CBG, this study can expand the utilization of CBD and, in particular, of minor phytocannabinoids to novel cosmeceutical products for skin care.”

Department of Cosmetology, University of Information Technology and Management in Rzeszów, Poland.

Gaweł-Bęben K, et al. Pharmaceuticals (Basel). 2023;16(5):648.

Science/Animal: Cannabinoids may be useful in the treatment of melanoma

In a study with mice investigators “could demonstrate that cannabinoids reduce cell viability in several melanoma cell lines, initiate apoptosis via the intrinsic apoptotic pathway by cytochrome c release and caspase activation and do not interfere with commonly used targeted therapy.” Apoptosis is a form of programmed cell death.

Otto-Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Austria.

Richtig G, et al. . Biology (Basel). 2023;12(5):706.

Science/Cells: Cannabis leaves infusion may be useful in breast cancer

In a study with human breast cancer cells investigators showed antiproliferative potentials of cannabis leaves infusion “as an alternative therapy for the treatment and management of breast cancer as depicted by its modulation of glucose, lipid, amino acid, vitamin, and nucleotide metabolisms, while concomitantly inducing cell death” in breast cancer cells.

Department of Pharmacology, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, South Africa

Erukainure OL, et al. . Heliyon. 2023;9(5):e16156.

Science: Hemp seed proteins may cause allergies with cross-relativity to hazelnut

“Our study thus identifies vicilins and edestins as potential hemp seed allergens and highlights a possible cross-reactivity with hazelnut. The clinical relevance of this cross-reactivity between hemp seed and hazelnut needs to be further investigated in hazelnut-allergic individuals.”

Nantes, unité d'allergologie, Angers, France.

Beriziky P, et al. Food Res Int. 2023;169:112932.

Science/Human: Tinnitus prevalence may be higher in cannabis users than non-users

According to an analysis of data from the National Health and Nutrition Examination Survey “bothersome tinnitus prevalence was significantly higher among cannabis users relative to nonusers.”

Keck School of Medicine of the University of Southern California, Los Angeles.

Reyes Orozco F, et al. Otol Neurotol. 2023 May 31. [in press]

Science/Animal: Cannabis may be helpful in dogs with compulsive disorder

“Combining cannabis and melatonin treatment with a rehabilitation program improved symptoms in a dog with compulsive disorder.”

Department of Veterinary Medicine and Animal Production, University of Federico II, Naples, Italy.

Sacchettino L, et al. Res Vet Sci. 2023;160:26-29.

Science/Animal: CBD may reduce mechanical allodynia caused by a chemotherapeutic agent

In a study with mice researchers found that CBD may attenuate mechanical allodynia caused by the chemotherapeutic agent paclitaxel.

Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, USA.

Ortiz YT, et al. Pharmacol Rep. 2023 May 27. [in press]

Science/Animal: Beta-caryophyllene may be useful in the treatment of urinary tract infections

According to a study with mice the cannabinoid compound beta-caryophyllene may reduce inflammation in the bladder and urinary tract infections.

Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.

Dickson K, et al. Molecules. 2023;28(10):4144.

Science/Animal: Activation of the CB1 receptor reduces the tonus of arteries in the brain

According to a study with pigs activation of the CB1 receptor may reduce cerebral vascular tone independent of changes in brain metabolism.

Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, The University of Saskatchewan, Saskatoon, Canada.

Morse CJ, et al. Microvasc Res. 2023:104550.

Science/Cells: CBD may protect nerve cells against damage by chemicals independent of cannabinoid receptors

Dopamine-like nerve cells intoxicated with paraquat were used as a model to investigate the protection of nerve cells by CBD. Investigators suggest that this may be of relevance for the treatment of Parkinson’s disease: “Because of its powerful antioxidant and antiapoptotic effects, CBD offers potential therapeutic utility in the treatment of PD (Parkinson’s disease).”

Neuroscience Research Team, Institute of Medical Investigations, Faculty of Medicine, University of Antioquia (UdeA), Colombia.

Mendivil-Perez M, et al. ACS Chem Neurosci. 2023 May 23. [in press]

Science/Human: The expression of the CB2 receptor in breast cancer may be of prognostic relevance

Overexpression of the CB2 receptor in breast cancer (BC) tissue is associated with disease prognosis. Authors noted that “CB2 could be a novel target for the diagnosis and treatment of BC.”

Department of Central Laboratory, Chongqing University Three Gorges Hospital, Chongqing University, Wanzhou, China.

Song Q, et al. Cancer Med. 2023 May 23. [in press]

Science/Animal: Antagonism at the CB1 receptor may be helpful in benign prostatic hyperplasia

According to a study with rats antagonism at the CB1 receptor may be helpful in benign prostatic hyperplasia “through their anti-proliferative, antioxidant, and anti-inflammatory effects.”

Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

Eid BG, et al. Biomol Biomed. 2023 May 19. [in press]

Science/Human: Concomitant CBD does not impact effectiveness of diazepam nasal spray for seizures

Results of a study with patients suffering from seizure clusters “suggest that CBD does not alter the safety and effectiveness of diazepam nasal spray and supports concomitant use in appropriate patients.”

Harvard Medical School and Boston Children's Hospital, Boston, USA.

Peters JM, et al. Epilepsy Behav. 2023;144:109248.

Science/Animal: CBD may attenuate morphine withdrawal

According to a study with mice CBD “attenuates the expression of conditioned place aversion induced by naloxone-precipitated morphine withdrawal through the activation of 5-HT1A receptors.” Authors concluded that “CBD may be a therapeutic alternative for preventing relapse to opioid addiction by decreasing withdrawal-induced negative affective changes.”

Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.

Souza AJ, et al. Behav Brain Res. 2023;450:114504.

Science/Human: Some people may have a genetic risk to develop both schizophrenia and use cannabis

According to genetic analyses “a subgroup of individuals might have a high genetic risk of developing a psychotic disorder and using cannabis.”

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, University of Oslo, Norway.

Cheng W, et al. Lancet Psychiatry. 2023;10(6):441-451.

Science/Animal: CBD and tramadol may act additive on neuropathic pain

In a study with rats investigators found additive pharmacological interaction between CBD and the opioid tramadol over the neuropathic pain associated with experimental diabetes.

Laboratory of Pharmacology of Pain, Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.

Evans AA, et al. Cannabis Cannabinoid Res. 2023 May 19. [in press]

Science/Animal: High doses of CBD were well tolerated

In a study with rats that received up to 150 mg of CBD per kilogram bodyweight were “well tolerated at these dose levels.”

ToxStrategies, Inc, Wilmington, USA.

Henderson RG, et al. Food Chem Toxicol. 2023;176:113778.

Science/Animal: A Chinese herbal medicine inhibits levels of FAAH

According to a study with rats the Chinese medicine Xiaoyao Pills ameliorated depression by inhibiting fatty acid amide hydrolase levels in brain thus increasing endocannabinoid levels.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.

Zhang ZW, et al. J Ethnopharmacol.2023;313:116555.

Science/Animal: The combination of a cannabinoid with tramadol increased pain reduction

In a study with rats the combination of a synthetic cannabinoid (WIN55212) together with tramadol increased analgesic effects.

Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.

Haddad M, et al. Neuroreport. 2023;34(8):441-448.