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IACM-Bulletin of June 7, 2020

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Science Israel — Ancient Israelites may have used a cannabis high as part of religious ritual 3000 years ago

The ancient Israelites may have used cannabis to get high as part of their religious ritual, according to Israeli researchers who found residue of the drug at a nearly 3,000-year-old shrine. The traces were found on an altar at the Tel Arad temple, in the Negev Desert about 10 km (six miles) from the southern Israeli town of Arad.

The site was discovered more than 50 years ago but new analysis of unidentified organic material on the limestone altar yielded the surprising result. Archaeologist Eran Arie, who led the research project on behalf of the Israel Museum and Israel’s Volcani Institute, said the material contained traces of cannabis and animal dung, likely used to help the plant burn. Arie said there has been no evidence of cannabis having been cultivated locally during the 8th century BC, suggesting someone had gone to the trouble of importing it “for its psychoactive effect”.

Reuters of 1 June 2020

Science/Human — Study finds no evidence for cannabis use to increase risk for stroke

An observational study conducted at hospitals found no evidence that cannabis use increases risk for stroke. "Our observational study looked specifically at recent cannabis use by reviewing drug testing data for people admitted to the hospital. While more research is needed with larger numbers of people, our study lends support to the studies showing that cannabis use does not increase the risk of stroke," said researcher Dr. Carmela San Luis, of the University of Mississippi in Jackson, USA.

Specifically, the researchers found that using cannabis did not affect the risk for ischemic stroke, which is the most common type of stroke and is caused by a blood clot in the brain. For the study, San Luis and her team collected data on more than 9,300 people who had been admitted to a hospital and screened for drug use. Eighteen percent -- 1,643 people -- tested positive for cannabis use. These participants were likely to be young men and current smokers. Among this group, 8 % suffered a stroke, compared with 16 % of people whose drug test showed they didn't use cannabis. After taking into account other factors, such as age, high blood pressure, high cholesterol, sickle cell disease, obesity, diabetes, smoking and heart conditions the researchers could not find any connection between the risk of stroke and cannabis use.

UPI of 4 June 2020

Science/Human — The available scientific data do not support the assumption that cannabis use may increase occupational injury

According to a systematic review by researchers of the University of British Columbia in Prince George, Canada, there was no link between cannabis use and occupational injury. Seven of the 16 reviewed studies showed evidence supporting a positive association between cannabis use and occupational injury. One study showed evidence supporting a negative association and the remaining eight studies showed no evidence of a significant relation. Only three of the reviewed studies showed clear evidence that cannabis use preceded the occupational-injury event.

Authors concluded that the “current body of evidence does not provide sufficient evidence to support the position that cannabis users are at increased risk of occupational injury. Further, the study quality assessment suggests significant biases in the extant literature are present due to potential confounding variables, selection of participants, and measurement of exposures and outcomes.”

Biasutti WR, Leffers KSH, Callaghan RC. Systematic Review of Cannabis Use and Risk of Occupational Injury. Subst Use Misuse. 2020:1-13.

Science/Human — Cannabis use is associated with reduced symptoms in patients with post-traumatic stress disorder

According to data from 404 medical cannabis users in the US, who self-identified as having post-traumatic stress disorder cannabis effectively reduced symptoms by more than 50%. Data were obtained from a medical cannabis app that patients use to track changes in symptoms as a function of different strains and doses of cannabis across time. The participants used the app 11,797 times over 31 months to evaluate the symptoms (intrusive thoughts, flashbacks, irritability, and/or anxiety) immediately before and after inhaling cannabis.

All symptoms were reduced by more than 50% immediately after cannabis intake. Time predicted larger decreases in intrusions and irritability, with later cannabis use sessions predicting greater symptom relief than earlier sessions. Higher doses of cannabis predicted larger reductions in intrusions and anxiety, and dose used to treat anxiety increased over time. Baseline severity of all symptoms remained constant across time. Authors from the Washington State University, who conducted the study, noted limitations, that are self-selection of the sample, self-identification as having post-traumatic stress disorder and no control group using a placebo.

LaFrance EM, Glodosky NC, Bonn-Miller M, Cuttler C. Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder. J Affect Disord. 2020;274:298-304.

Science/Human — Cannabis may be helpful in the treatment of fibromyalgia according to an open study

According to a study with 101 patients suffering from fibromyalgia and followed up at Laniado Hospital in Netanya and at the Nazareth Hospital in Nazareth, Israel, cannabis use was effective in reducing pain and reducing other pain medication. The mean duration of cannabis use was 15 months. The mean monthly consumption amount was 29 g cannabis, which was smoked pure (54%), inhaled by using a vaporiser (18%) or used orally (3 participants), while the rest used the variety of combinations.

Mean improvement in sleep and pain was slightly more than 77% with less improvement in other parameters; 36% of the patients reported weight gain, while 16% reported weight loss; 51% reported having more leisure time outdoors. Nearly one quarter of the patients reported mild adverse effects and one patient developed a psychotic attack. He was consuming 70 gram of cannabis monthly. Authors concluded that medical cannabis “is an effective treatment for fibromyalgia, with nearly zero % withdrawal from this treatment.”

Habib G, Levinger U.

[Characteristics of medical cannabis usage among patients with fibromyalgia]. [Article in Hebrew] Harefuah. 2020;159(5):343-348.

Science/Human — Cannabis in addition to standard medication further improves motor performance in patients with multiple sclerosis

In a controlled study patients with multiple sclerosis found significant improvement with an add-on treatment with a cannabis spray (Sativex®) compared to standard treatment. The study conducted by the IRCCS Centro Neurolesi Bonino Pulejo in Messina, Italy, compared 20 patients with multiple sclerosis, who received the cannabis spray in addition to the ongoing oral antispastic therapy (group A), and 20 patients only receiving the ongoing antispastic therapy (group B).

The Functional Independence Measure improved in group A more than in group B. Moreover, 10 metres walking test decreased in group A more than in group B. authors noted that these and other findings show that this “approach could be useful in improving gait performance in patients with MS.”

Calabrò RS, Russo M, Naro A, Ciurleo R, D'Aleo G, Rifici C, Balletta T, La Via C, Destro M, Bramanti P, Sessa E. Nabiximols plus robotic assisted gait training in improving motor performances in people with Multiple Sclerosis. Mult Scler Relat Disord. 2020;43:102177.

News in brief

Science/Human — A small controlled study showed that CBD may be effective in children with severe behavioural problems

A placebo-controlled study with 8 participants showed that CBD may be helpful in treating children with severe behavioural problems. Children aged 8 to 16 years were randomised to either receive CBD oil or placebo for 8 weeks, which was uptitrated to 20 mg per kilogram per day in 2 divided doses with a maximum dose of 500 mg. All parents reported they would recommend the study to other families with children with similar problems. There was an efficacy signal in favour of active drug.

Murdoch Children's Research Institute, Parkville, Canada.

Efron D, et al. Br J Clin Pharmacol. 2020 Jun 1. [in press]

Switzerland — National Council has approved trial on cannabis use for adults

Switzerland’s National Council has approved a plan to start cannabis trials for recreational use. If it is to be legalised however, the government says it must be organic and grown locally. The study, which was approved on 2 June, hopes to find out more about the effects that a controlled legalisation of the drug for adults use would have in Switzerland. The experiments are to be carried out in Switzerland’s larger cities. Basel, Bern, Biel, Geneva and Zurich have all expressed interest in conducting the trials.

The Local of 3 June 2020

Science/Human — Legalisation of cannabis for adult use had a positive effect on tourism in the USA

Researchers from Berry College used monthly hotel occupancy data to examine the effect of cannabis legalization on tourism in Colorado and Washington. The results indicate a large increase in hotel rooms rented in Colorado, with a considerably smaller effect for Washington. The effects are larger in both states once commercial sale was permitted above and beyond legalizing possession and individual cultivation.

Department of Economics, Berry College, Rome, USA.

Meehan B, et al. J Reg Analysis Policy 2020;50(1):46–53.

Canada — Despite the lockdown due to the corona crisis the cannabis sector is still hiring people

Unlike many industries, the cannabis sector is still hiring during the pandemic. Yet the number of open positions has dwindled as layoffs become more common and many of the jobs that do exist are temporary. The cannabis sector employed 243,700 people at the beginning of 2020, up 15 per cent from the prior year and nearly doubled the number of jobs in 2017.

Bloomberg of 3 May 2020

Science/Human — A small controlled study showed that CBD may be effective in children with severe behavioural problems

A placebo-controlled study with 8 participants showed that CBD may be helpful in treating children with severe behavioural problems. Children aged 8 to 16 years were randomised to either receive CBD oil or placebo for 8 weeks, which was uptitrated to 20 mg per kilogram per day in 2 divided doses with a maximum dose of 500 mg. All parents reported they would recommend the study to other families with children with similar problems. There was an efficacy signal in favour of active drug.

Murdoch Children's Research Institute, Parkville, Canada.

Efron D, et al. Br J Clin Pharmacol. 2020 Jun 1. [in press]

Science/Human — No increase in number of adolescents, who need treatment for cannabis use following legalisation in Colorado and Washington

Annual data on 2008-2017 treatment admissions for cannabis use from the SAMHSA TEDS-A dataset for adolescents age 12-17 were used to model state treatment admissions trends. Over all states in the analysis, the rate of adolescent treatment admissions for cannabis use declined significantly over the study period, with the mean rate falling nearly in half. The decline in admissions rate was greater in Colorado and Washington compared to states that did not legalise cannabis use for adults. However, the difference was not statistically significant. Authors concluded that “adolescent treatment admissions for marijuana use did not increase in Colorado and Washington following RML [recreational marijuana legalisation].”

Department of Geography and Urban Studies, Temple University, USA.

Mennis J, et al. Drug Alcohol Depend. 2020;210:107960.

Science/Human — Many cancer patients use cannabis

According to a survey with 188 cancer patients 46 (25%) used cannabis. Symptoms at the beginning of treatment were higher in cannabis users. Pain was the symptom with the highest frequency of improvement (81%), followed by appetite (77%), and anxiety (73%).

Department of Hematology Oncology, Beaumont Health, Royal Oak, USA.

Macari DM, et al. Am J Clin Oncol. 2020 Jun 2. [in press]

Science/Animal — CBD and CBDA reduce nausea in rats and shrews

Both acute and repeated administration of CBD and CBDA reduced symptoms in animal models of nausea (rats, shrews). They maintained the effectiveness during a four-week study. Effects were mediated by the 5-HT1A receptor. Authors noted “that these cannabinoids may be useful anti-nausea and anti-emetic treatments for chronic conditions, without the development of tolerance.”

Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Canada.

Rock EM, et al. Psychopharmacology (Berl). 2020 Jun 2. [in press]

Science/Human — How many cannabis users develop cannabis use disorders?

According to a meta-analysis, which included 21 studies, 22% (18-26%) of cannabis users have a cannabis use disorder and 13% (10-15%) have cannabis dependence. Cannabis dependence increased to 33% in regular users (weekly or daily).

The University of Queensland, Australia.

Leung J, et al. Addict Behav. 2020;109:106479.

Science/Animal — Blockade of CB1 receptors in a certain brain region increases pain

In a study with rats blockade of the CB1 receptor in a certain brain region, which is involved in pain perception (ventrolateral periaqueductal grey matter), increases pain of the gums and reduces associated learning and memory performance. Researchers concluded that the endocannabinoid system in this brain region is involved in the modulation of pain signals.

Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Iran.

Sofiabadi M, et al. Behav Pharmacol. 2020 May 29. [in press]

Science/Animal — CBDA reduces trauma-induced anxiety-related behaviour

In studies with mice researchers found that CBD and CBDA had different effects in anxiety due to trauma. While CBD but not CBDA disrupted cued fear memory expression, CBDA but not CBD normalized trauma-induced generalized anxiety-related behaviour.

Lambert Initiative for Cannabinoid Therapeutics.

Assareh N, et al. Behav Pharmacol. 2020 May 29. [in press]

Science/Human — THC was beneficial in severe Alzheimer’s dementia in a case report

Austrian researchers presented the case of a female patient, who was diagnosed with Alzheimer’s disease with continuous cognitive decline between 2008 and 2019. In 2018, the patient progressed to severe AD stage and presented with progressive anxiety, suspected delusions, agitation, aggressive behaviour, and suspected pain due to long immobility. Consequently, off-label treatment with low-dose THC was initiated, which facilitated a reduction of psychopharmacological treatment from six to three psychotropics.

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical University of Innsbruck, Austria.

Defrancesco M, et al. Front Psychiatry. 2020;11:413.

Science — The cannabinoid-2 receptor may be a possible target for coronavirus-19 infection

Since COVID-19 patients manifest exacerbated inflammatory and immune responses, cytokine storm, prevalence of pro-inflammatory M1 macrophages and increased levels of resident and circulating immune cells Italian researchers hypothesised the possibility that activation of the CB2 receptor may be beneficial. They state that the “stimulation of CB2 receptors is known to limit the release of pro-inflammatory cytokines, shift the macrophage phenotype towards the anti-inflammatory M2 type and enhance the immune-modulating properties of mesenchymal stromal cells.”

University of Campania "Luigi Vanvitelli", Naples, Italy.

Rossi F, et al. Int J Mol Sci. 2020;21(11).

Science/Cells — CBD may reduce the viability of multiple myeloma cells

Researchers found that “the CB2 receptor is highly expressed on CIK (cytokine-induced killer) cells as well as on MM (multiple myeloma) cells. CBD was able to decrease the viability of tumour cells and can have a protective role for CIK cells.” They also found that very high concentrations of CBD were detrimental to killer cells, so that doses below 1 µmol were appropriate.

Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital Bonn, Germany.

Garofano F, et al. Int J Mol Sci. 2020;21(11).

Science — CBD may be a potential anti-inflammatory treatment for Covid-19

Canadian researchers discuss the hypothesis that CBD may be a potential anti-inflammatory treatment for Covid-19, which is associated with a cytokine storm.

Research Institute of McGill University Health Centre, Montreal, Canada.

Costiniuk CT, et al. Cytokine Growth Factor Rev. 2020 May 20. [in press]

Science/Animal — CBD causes a prohedonic state in stressed rats

In rats who underwent chronic mild stress “CBD exerted a prohedonic effect.” Further investigations also pointed “toward an anxiolytic or antidepressant-like effect of CBD, but this needs further confirmation.”

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania.

Gáll Z, et al. Biomolecules 2020;10(5).

Science/Cells — Both CBD and CBG show antioxidant and neuroprotective effects in brain cells

Cell studies with astrocytes, immune cells in the brain, show that CBD and CBG may have antioxidant effects, while they may also have protective effects in nerve cells.

Department of Pharmacy, Università degli Studi "Gabriele d'Annunzio", Chieti, Italy.

Giacomo VD, et al. Int J Mol Sci. 2020;21(10).

Science/Animal — CBD was able to protect mice from developing multiple sclerosis

In a mouse model of multiple sclerosis (EAE) “early, oral administration of CBD protected mice from disease, but the modest effects on neuroinflammation suggest other mechanisms participate in CBD's neuroprotective effect in EAE.”

Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, USA.

Nichols JM, et al. J Neuroimmune Pharmacol. 2020 May 21. [in press]

Science/Human — Cannabis use in pregnant women increased after legalisation in US states

A retrospective cohort study was conducted from July 2016 to December 2018 of pregnant women who had drug screening of cannabis use before and after legalization of recreational marijuana in California. Authors wrote that “rates of marijuana usage in pregnant women who underwent universal drug screening increased after legalization. There were no differences in neonatal outcomes between users and non-users.”

Department of Obstetrics and Gynecology, University of California, Los Angeles, USA.

Lee E, et al. J Matern Fetal Neonatal Med. 2020:1-8.