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IACM-Bulletin of 28 February 2021

USA: New Jersey legalises adult use of cannabis

Governor Phil Murphy signed a bill on 22 February making New Jersey the latest US state to legalise cannabis for recreational use, but it is expected to take up to a year before dispensaries begin selling cannabis to the public. The Democratic governor signed a package of three bills after voters overwhelmingly approved a ballot measure in November 2020 to legalise adult use of the drug.

The laws allow the possession of up to six ounces (about 170 grans) of cannabis for people 21 and older. Distribution and cultivation of cannabis without a licence remain illegal. New Jersey joins more than a dozen other US states, including the East Coast states of Maine, Vermont and Massachusetts, in legalising cannabis for adults.

Reuters of 22 February 2021

Science/Human: Cannabis use is associated with a reduced risk of developing HPV-negative head and neck cancers

Sexually acquired human papillomavirus (HPV) infection is an established cause of tonsillar and tongue base carcinomas. A new study of 249 newly diagnosed cases of squamous cell carcinoma of the oral cavity and pharynx (OSCC) shows that cannabis users had a lower risk of developing HPV-negative OSCC cancers. The study by the Department of Thoracic/Head and Neck Medical Oncology at the MD Anderson Cancer Center at the University of Texas at Houston, USA, compared 249 cancer patients and 498 controls with no history of cancer. The cancer patients were either HPV-positive or HPV-negative.

The risk of developing HPV-positive cancer decreased with the education level of the patients. Annual income, tobacco smoking, alcohol consumption and poor oral hygiene were not associated with HPV-positive OSCC. In contrast, the risk of HPV-negative OSCC increased with low annual income and decreased with long-term cannabis use. The authors concluded that "long-term marijuana use appears to be protective for HPV-negative cancer."

Shewale JB, Pickard RKL, Xiao W, Jiang B, Gillison ML. Independent association of marijuana use and poor oral hygiene with HPV-negative but not HPV-positive head and neck squamous cell carcinomas. Cancer, 23. Feb 2021. [in press]

Science/Human: Cannabis reduces the development of neuropathy in cancer patients treated with oxaliplatin

In a study of 513 cancer patients treated with oxaliplatin and 5-fluorouracil-based combinations, the use of cannabis reduced the development of severe neuropathy, a known side effect of oxiplatin. Researchers from the Department of Oncology at Tel Aviv Sourasky Medical Center, Israel, conducted an analysis of medical records at their centre from 2015 to 2018. 248 patients were treated with cannabis and 265 did not receive cannabis. Cannabis users were divided into 2 groups, 116 (47%) of whom received cannabis before oxiplatin and 132 (53%) who received oxiplatin first.
Cannabis users had a lower risk of developing neuropathy compared to the control group without cannabis. The study also showed that the "protective effect of cannabis was more pronounced in patients who received cannabis first than in those who received oxaliplatin first (75% and 46.2%, respectively)." The authors concluded that cannabis has a protective effect on this oxiplatin side effect and mentioned that a large prospective study is planned.

Waissengrin B, Mirelman D, Pelles S, Bukstein F, Blumenthal DT, Wolf I, Geva R. Effect of cannabis on oxaliplatin-induced peripheral neuropathy among oncology patients: a retrospective analysis. Ther Adv MedOncol.2021;13:1758835921990203.

Science/Human: Cannabis may be helpful in treating fibromyalgia, according to a case series

Cannabis may be helpful in treating fibromyalgia, according to a case series of 38 patients with fibromyalgia by doctors at a pain clinic in Ponderano, Italy. The patients received cannabis flowers with varying THC and CBD content as an oil extract or for inhalation with a vaporiser. 30, 18 and 12patients continued therapy for 1, 3 and 12 months, respectively. The median daily dose of gflowers administered as THC-dominant medicinal cannabis and hybrid medicinal cannabis (with similar THC/CBD ratio) was 200 mg/day and 400 mg/day, respectively.

Therapy was interrupted by 17 patients (48.6 %) due to non-serious side effects. The most common side effects were mental confusion (37%), dizziness (14%), nausea/vomiting (14%) and agitation/irritation (14%). After a 3-month titration, the median THC content was 46.2 mg when administering THC-dominant medical cannabis strains and 23.6 mg + 38 mg when administering THC + CBD in the form of a hybrid medical cannabis strain. After one, three and twelve months, pain was reduced by at least 30%. The authors concluded that cannabis "may provide an alternative treatment for patients with FMS who do not respond to conventional therapy. However, its use may be limited by the occurrence of non-serious AEs [adverse events]."

Mazza M. Medical cannabis for the treatment of fibromyalgia syndrome: a retrospective, open-label case series. J Cannabis Res 2021;3(1):4.

Science/Human: Running stimulates the endocannabinoid system and reduces anxiety

Endocannabinoids are better candidates than endorphins to explain the "runner's high" in humans. This is the finding of researchers from the Human Behaviour Laboratory, Institute for Sexual Research, Sexual Medicine and Forensic Psychiatry, Centre for Psychosocial Medicine at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany. The "runner's high" describes a feeling of well-being during endurance exercise, characterised by euphoria and anxiolysis. It is a widely held belief that the release of endogenous opioids, such as endorphins, underlies the "runner's high".

In a new study, 63 participants showed increased euphoria and decreased anxiety after 45 minutes of running on a treadmill at a moderate intensity level. Running led to higher plasma levels of the endocannabinoids anandamide and 2-arachidonoglycerol. Opioid blockade did not prevent the development of euphoria. The authors concluded that their "study indicates that the development of a runner's high in humans is not dependent on opioid signalling, but eCBs are strong candidates in humans, as previously shown in mice."

Siebers M, Biedermann SV, Bindila L, Lutz B, Fuss J. Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans. Psychoneuroendocrinology 2021;126:105173.

Science/Human: Cannabis may reduce inflammation in multiple sclerosis

In a study of 150 patients with multiple sclerosis, 28 of whom used cannabis, cannabis use was associated with reduced signs of inflammation and a reduction in relapses. The study was conducted by researchers from the faculties of medicine at Mansoura University and Delta University for Science and Technology, Egypt. In addition to the 150 patients, the study also included 150 healthy controls. All were asked about their cannabis use, which was confirmed by urine tests.

Blood concentrations of pro-inflammatory cytokines, a sign of inflammatory intensity, were higher in the MS patients who did not use cannabis than in the cannabis users and healthy controls. Pro-inflammatory mediators measured included interleukin-1, interleukin-2, interleukin-12, interleukin-17, interleukin-22, interferon-gamma (IF-gamma) and tumour necrosis factor alpha (TNF-alpha). 15 cannabis users (54 %) reported that their symptoms were improved by cannabis. The authors concluded that "cannabis may have a positive impact on cytokine and clinical profiles in multiple sclerosis cases."

Mustafa W, Elgendy N, Salama S, Jawad M, Eltoukhy K. The Effect of Cannabis on the Clinical and Cytokine Profiles in Patients with Multiple Sclerosis. Mult Scler Int 2021;2021:6611897.

News in brief

Malta: Government to legalise cannabis
Cannabis users will not be sent to prison and will be able to grow a limited amount of plants as part of the government's reform, Prime Minister Robert Abela said. The proposals were fleshed out by the Prime Minister on 18 February when he spoke to journalists on the sidelines of a business breakfast on employment.Malta Today of 18 February 2021

USA: Massachusetts has more than 100,000 medical cannabis patients
The number of medical cannabis card holders in Massachusetts has increased by more than 30,000 in the past year to a total of 100,000. This represents about 1.5% of the total population of 6.9 million.
Boston Business Journal of 13 February 2021

Science/Human: Workers' compensation benefits decreased in states with recreational cannabis laws
A study examined the effect of cannabis legalisation on the receipt of workers' compensation benefits among adults aged 40 to 62. Workers' compensation benefits decreased in response to these laws, both in terms of the propensity to receive benefits and the amount of benefits received. The research provided evidence that the primary driver of these reductions was an improvement in work ability, likely through access to an additional form of pain management.
National Bureau of Economic Research, Cambridge, USA.
Abouk R, Ghimire KM, Maclean JC, Powell D. Does Marijuana Legalization Affect Work Capacity? Evidence from Workers’ Compensation Benefits. Working Paper 28471, National Bureau of Economic Research, Cambridge, 2021.

Science/Spain: Exploring the origins of the cannabis plant
The Barcelona Botanical Institute is working on several continents to research the chemical and genetic variants of the purest cannabis, the one that grows wild in its natural habitat. This research, funded by the Ministry of Science and Innovation, aims to discover the origin of this plant and the bibliographic record of its traditional uses in human history.
El Publico of 8 February 2021

France: Parliamentarians propose lighter regulation for CBD products
Current laws should be changed to improve safety for consumers of the cannabis-based product and allow the French market to grow, according to a new parliamentary report. While CBD shops have flourished in France in recent years - there are now nearly 400 - the parliamentary report describes the market around CBD products as "downright grotesque". The authors of the report described CBD as a "collateral victim of a heavy-handed approach to cannabis" in France.
Connexion France of 11 February 2021

Science/Europe: EIHA sponsors study on health effects of THC traces
The largest ever clinical trial on the toxicological effects of ingesting trace amounts of THC in food will begin in the next few weeks. The EURopean Industrial Hemp Association (EIHA) is spending over €1.6 million on the study. The EIHA believes the study, which is taking place in EURope, will help provide an evidence base for regulators to adjust allowable THC levels in food.
Business CANN of 11 February 2021

Israel: List of cannabis patients not handed over to police
About four months ago, it was reported that the Health Ministry had complied with police demands to obtain the list of all medical cannabis patients in Israel, ostensibly to be able to verify whether a person caught with cannabis is a licensed patient. A petition filed with the Supreme Court was rejected this week after a promise that the data would not be provided until further notice.
Cannabis Magazine of 9 February 2021

Czech Republic: Centre for medical cannabis research established at university hospital
St Anne's University Hospital in Brno is setting up its own cannabis research facility to serve as infrastructure for the Cannabis Research Centre. The facility will be used by researchers from the International Centre for Clinical Research to conduct studies on medicinal cannabis. This research will cover a wide range of areas, including the study of genetics, ingredients and new applications for the treatment of diseases.
Brno Daily of 12 February 2021

Science/Human: Tobacco use and cannabis use in adolescence associated with poorer cognitive function
Using data from a large cohort in the UK, the authors of the so-called "Avon Longitudinal Study of Parents and Children" found an association between early regular tobacco use, late regular tobacco use and early regular cannabis useon the one hand and cognition on the other hand. They wrote that their data "suggest that adolescent tobacco and cannabis use was associated with deficits in working memory, response inhibition and emotion recognition."
University of Bristol, Großbritannien.
Mahedy L, et al. Drug Alcohol Depend 2021;221:108591.

Science/Human: Anxiety, stress and sleep disorders are the main reasons for CBD use
In a survey of 387 CBD users, the main reasons for use were self-perceived anxiety, stress, sleep disturbances and general health and well-being
Horsted Clinic, Chronic Pain Clinic, Copenhagen, Denmark.
Moltke J, et al. J Cannabis Res 2021;3(1):5.

Science/Human: The bioavailability of CBD is significantly higher when taken after food intake than in a sober state.
The bioavailability of CBD (cannabidiol) and thus its treatment efficacy is influenced by food intake. This is the result of an analysis of data from 44 clinical trials. CBD showed significantly higher bioavailability in fed patients. In addition, administration in the fed state resulted in smaller differences in bioavailability between different patients.
Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, Ann Arbor, Michigan, United States.
Silmore LH, et al. Pharmacotherapy, 14. Feb 2021. [in press]

Science/Cells: CBD causes breakdown of mitochondria in brain tumour cells
CBD has been shown to cause dysfunction and breakdown of mitochondria in glioma cells, a serious brain tumour. The authors suggest that "CBD should be clinically tested in gliomas, both alone and in combination with temozolomide", a standard chemotherapeutic drug used to treat gliomas.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China.
Huang T, et al. Autophagy 2021:1-15.

Science/Cells: CBD reduces viability of breast cancer cells
CBD has been shown to reduce the viability of breast cancer cells by inducing oxidative stress and stress in certain cellular junctions (endoplasmic reticulum) and disrupting protein folding.
Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth, South Africa.
de la Harpe A, et al. Biotechnol Appl Biochem, 19. Feb 2021.[in press]

Science/Cells: THC impairs cells relevant for a successful pregnancy
THC damages certain cells, called trophoblast cells, which are important for the implantation of the egg in the placenta, thus interfering with a successful pregnancy in the first days after fertilisation.
Graduate Program in Medical Sciences, Department of Pediatrics, McMaster University, Hamilton, Canada.
Walker OS, et al. Sci Rep 2021;11(1):4029.

Science/Human: Legalisation of cannabis in the USA was not associated with an increase in THC detection in injured patients
An analysis of data from trauma centres in six states (Arizona, California, Ohio, Oregon, New Jersey and Texas) between 2006 and 2018 showed that there was no association between legalisation and detection of THC in patients. The largest increase in THC detection was observed in Texas, where cannabis remains illegal. The authors concluded that there was "no apparent increase in the incidence of driving under the influence of marijuana after legalisation."
Hackensack University Medical Center, USA.
Kruse M, et al. Am Surg.2021:3134821995053.

Science/Human: Cannabis use is associated with depression in cancer survivors
In a large sample of 10,799 cancer survivors, those with depression had a higher prevalence of daily or non-daily cannabis use.
School of Nursing, Bouvé College of Health Sciences, Northeastern University, Boston, USA.
Poghosyan H, et al. Nurs Outlook 2021:S0029-6554(21)00016-6.

Science/Human: Cannabis legalisation is associated with more positive health perceptions of cannabis
According to a survey of 429 Californians, legalisation of cannabis use for adults led to increased self-reported use of cannabis within the past 30 days and more positive health perceptions of cannabis use.
Department of Medicine, Stanford Prevention Research Center, Stanford University, Medical School Office Building, USA.
Gali K, et al. Subst Abuse Treat Prev Policy 2021;16(1):16.

Science/Human: No reduced opioid use after cannabis legalisation among pain patients
There was no reduction in opioid use, either for recreational or medical use, in states with cannabis legalisation, according to an analysis of around 142,000 pain patients from different US states.
UPMC Centers for High Value Health Care and Value-Based Pharmacy Initiatives, UPMC Health Plan, Pittsburgh, USA.
Neilson LM, et al. J Gen Intern Med, 11. Feb 2021. [in press]

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