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IACM-Bulletin of 04 December 2022

Science/Human: Cannabis may be helpful in the treatment of children with autism

A study with 14 participants conducted at Melbourne's Monash Children's Hospital, Australia, has supported the benefits of using medicinal cannabis as a treatment for children diagnosed with autism spectrum disorder. The phase I trial, which was designed to assess product safety, discovered "significant changes" in the symptoms and behaviours of the 14 participants.

Study lead and head of Paediatric Neurology at Monash Medical Centre, Professor Michael Fahey, said that the results were "pleasing". “We weren't looking for a significant outcome really... but we found significant changes," he said. "[The participants] told us that their socialisation was better, they communicated better, they were able to do things both as a person and as a family that they hadn't been able to do before.”

ABC Radio Melbourne of 17 November 2022

Science/Human: Cannabis legalisation was associated with lower use of opioids in cancer patients

According to a cross-sectional study with 58,195 cancer patients cannabis legalisation “was associated with a lower rate of opioid dispensing and pain-related hospital events among some adults receiving treatment for newly diagnosed cancer”. It used data from 2012 to 2017 and included privately insured patients aged 18 to 64 years who received anticancer treatment during the 6 months after a new diagnosis of one of breast cancer, colorectal cancer or lung cancer. The study was published by investigators of several medical institutions in New York in the Journal of the American Medical Association.

Medical cannabis legalization was associated with a reduction in the rate of 1 or more opioid days from 90% to 84% among patients with breast cancer with recent opioids, from 89% to 84% among patients with colorectal cancer with recent opioids, and from 34% to 27% among patients with lung cancer without recent opioids. Medical marijuana legalization was associated with a reduction in the rate of 1 or more pain-related hospital admissions from 19% to 13% among patients with lung cancer with recent opioids.

Bao Y, Zhang H, Bruera E, Portenoy R, Rosa WE, Reid MC, Wen H. Medical Marijuana Legalization and Opioid- and Pain-Related Outcomes Among Patients Newly Diagnosed With Cancer Receiving Anticancer Treatment. JAMA Oncol. 2022 Dec 1. [in press].

Science/Human: A transdermal CBD gel improved symptoms in fragile X syndrome according to controlled study

In a placebo-control study with 212 patients with fragile X syndrome a subgroup of participants profited from a treatment with a CBD transdermal gel. Patients were randomised to 12 weeks of CBD (250 or 500 mg daily depending of weight) or a placebo. Investigators from 16 institutions in the US and Australia participated in this trial.

A total of 169 (80%) patients presented with  more than 90% methylation of the FMR1 promoter and full mutation of FMR1. “Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1.” In this subgroup there were significant improvements in behavioural problems, including isolation, irritable and disruptive behaviors, and social interactions. The medication was well tolerated.

Berry-Kravis E, Hagerman R, Budimirovic D, Erickson C, Heussler H, Tartaglia N, Cohen J, Tassone F(, Dobbins T, Merikle E, Sebree T, Tich N, Palumbo JM, O'Quinn S. A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX). J Neurodev Disord. 2022;14(1):56.

Science/Human: Palmitoylethanolamide improved diabetic-related neuropathic pain in a placebo-controlled trial

According to a placebo-controlled trial with 70 patients suffering from diabetic-related peripheral neuropathic pain the endocannabinoid palmitoylethanolamide (PEA ) improved pain. They either received 600 mg or placebo daily for eight weeks. 94% of participants completed the whole study, which was conducted by researchers of the Universities of Queensland and Sydney, Australia.

There was a significant reduction in total pain and pain interference in the PEA group. In addition, sleep improved, but not anxiety or stress scores. Signs of inflammation, measured as interleukin-6 and C-reactive protein levels, were significantly reduced. The treatment was well tolerated.

Pickering E, Steels EL, Steadman KJ, Rao A, Vitetta L. A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain. Inflammopharmacology. 2022;30(6):2063-2077.

News in brief

USA: Senate and House of Representatives pass marijuana research bill
On 16 November the Senate passed the Medical Marijuana and Cannabidiol Research Expansion Act, which passed the House of Representatives in July 2022. It’s goal is to facilitate research on marijuana and its potential health benefits. The bill will accomplish this by streamlining the application process for scientific marijuana studies and removing existing barriers for researchers that frequently slow the research process.
Website of Dianne Feinstein of 16 November 2022

Israel: 1.5 % of citizens are allowed to use cannabis for medical purposes
In October 2022 the number of cannabis licence holders has officially crossed the 120,000 mark, which is 1.5 of Israeli citizens.
Cannabis Magazine of 20 November 2022

Science/Animal: THC and CBN reduces tumour volume in cholangiocarcinoma
In a study with mice both THC and CBN (cannabinol) induced programmed cell death (apoptosis) in cholangiocarcinoma cells and reduced tumour growth compared to non-treated animals.
Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani, Thailand.
Leelawat S, et al. Evid Based Complement Alternat Med. 2022;2022:6477132.

Science/Human: Simultaneous alcohol and cannabis use increased following cannabis legalisation in the USA
Comparing data from 2008 and 2019 the prevalence of simultaneous alcohol and cannabis use declined in US citizens aged 12 to 20, but increased in people above the age of 20.
Department of Epidemiology, Columbia University Mailman Sch ja er war auch ool of Public Health, New York, USA.
Gonçalves PD, et al. J Gen Intern Med. 2022 Nov 30. [in press].

Science/Human: Cancer survivors report of cannabis-related stigma
According to an interview with 24 adults, who survived cancer, many cancer patients experience cannabis-related stigma. Authors wrote that “healthcare providers who depend on patient transparency when gathering medical histories and devising care plans may wish to neutralize perceptions of medical cannabis-related stigma.”
Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, USA.
Nayak MM, et al. J Cancer Surviv. 2022 Nov 26. [in press].

Science/Human: Multiple sclerosis may be associated with lower levels of endocannabinoids
In MS patients researchers found lower levels of the endocannabinoids 2-AG (2-arachidonoylglycerol) and PEA (palmitoylethanolamide) in peripheral blood mononuclear cells compared to healthy controls. 2-AG levels increased within 24 months and reached normal levels.
Neuroimmunology Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain.
Sánchez-Sanz A, et al. Sci Rep. 2022;12(1):20300.

Science/Animal: THC exposure during pregnancy adversely impacts placental function and development
In a study with rhesus macaques THC during pregnancy adversely impacted the function of the placenta and development of the offspring.
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, USA.
Roberts VHJ, et al. Sci Rep. 2022;12(1):20260.

Science/Human: Cannabis may have no influence on hospital admissions of patients with sickle cell disease
Using data of the New York State Prescription Monitoring Program (NYS PMP) investigators did not find an influence of medical cannabis certification on hospital admissions in patients with sickle cell disease.
Columbia University Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, USA.
Aron JA, et al. Cannabis Cannabinoid Res. 2022 Nov 22. [in press].

Science/Animal: The CB1 receptor is involved in inflammation and pruritus of psoriasis
In a mouse model of psoriasis the CB1 receptor in sensory nerve cells was involved in the reduction of inflammation and pruritus.
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Liu X, et al. J Invest Dermatol. 2022:S0022-202X(22)02770-1.

Science/Human: CBD did not reduce symptoms in advanced cancer
In a placebo-controlled study with 144 patients CBD oil “did not add value to the reduction in symptom distress provided by specialist palliative care alone.”
Department Palliative and Supportive Care, Mater Health Services, South Brisbane, Queensland, Australia.
Hardy J, et al. J Clin Oncol. 2022:JCO2201632.

Science/Human: Cannabis had different effects on sleep in the young and other people
Young adults (18-44 years) who reported daily-use of cannabis had an increased risk ratio for either short or long sleep while midlife adults (45-64 years) had an increased prevalence of long sleep and older adults (≥65 years) had an increased prevalence of short sleep.
Oregon Institute of Occupational Health Sciences, Oregon Health and Sciences University, Portland, USA.
Gonzalez JE, et al. Sleep Health. 2022:S2352-7218(22)00189-9.

Science/Animal: Cannabis sativa and cannabis Indica strains may have different effects on rats
Results of a study with rats, which received extracts of different cannabis strains “support the suggestion that products marketed as different cannabis cultivars have dissociable cognitive effects that may not resemble pure THC and emphasize the importance of the route of administration in experimental design.”
Djavad Mowafaghian Centre for Brain Health, Department of Psychology, University of British Columbia, Vancouver, Canada.
Brodie HG, et al. Behav Neurosci. 2022 Nov 17. [in press].

Science/Human: Depressive symptoms are negatively associated with lower levels of endocannabinoids in hair
In a prospective community-based cohort study including 128 individuals, depressive symptoms as well as hair cortisol and endocannabinoids were measured annually over four years. Depressive symptoms after 3 years were associated with lower levels of endocannabinoids after 4 years.
Clinical Psychology and Psychotherapy, University of Zurich, Switzerland.
Walther A, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2023;121:110658.

Science/Animal: Endocannabinoids attenuate global cerebral injury after reduced blood supply
In a study with rats inhibition of the degradation of the endocannabinoid 2-AG was similar effective as hypothermia in reducing global cerebral injury after cardiac arrest.
Department of Emergency, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Xu J, et al. Biomed Pharmacother. 2022;156:113847.

Science/Animal: THC may reduce inflammation in hyperinsulinaemia
In a study with rats with hyperinsulinaemia THC reduced inflammation, measured as cytokine levels. interleukin-6 and tumour-necrosis-factor-alpha levels were reduced by THC.
Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Demiroglu Bilim University, Istanbul, Turkey.
Yazici ZMC, et al. Mol Biol Rep. 2022;49(12):11891-11899.

Science/Animal: Sex-dependent differences of CBD in anxiety
In a rat model of anxiety researchers found “sex differences in the anxiolytic-like effects of CBD in rats that reflect different underlying mechanisms: based on literature data, gonadal hormone status linked to GABAA receptor expression in females, and 5-HT1A receptor activation in males.”
Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Brazil.
Fabris D, et al. J Psychopharmacol. 2022;36(12):1371-1383.

Science/Animal: CBD may improve compulsive-like behaviour
In a study with mice CBD ameliorated “the anxiogenic and compulsive-like behaviors induced by chronic consumption of a high-carbohydrate diet.” Ein
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Marçal AP, et al. Metab Brain Dis. 2022;37(8):2711-2718.

Science/Animal: The anxiolytic effects of CBD depend in part on the CB1 receptor
The reduction of panic in mice caused by snakes “of CBD depends at least in part on the recruitment of CB1 receptors.”
Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Brazil.
de Paula Rodrigues BM, Coimbra NC. J Psychopharmacol. 2022;36(12):1384-1396.

Science/Animal: Cannabinoids may be helpful in the repair of nerves following spinal cord injury
Transplantation of oligodendrocyte progenitor cell (OPC) at the injury site is being developed as a potential therapeutic strategy for promoting remyelination and locomotor function recovery after spinal cord injury. In a study with mice researchers found that “CB1R/CB2R activation results in more efficient generation of OPCs that can mature and efficiently myelinate.”
Sun Yat-Sen University, Shenzhen, China.
Gao H, et al. Stem Cell Rev Rep. 2022;18(8):3033-3049.

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