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IACM-Bulletin of 27 September 2020

IACM: Prof. Elisaldo Araújo Carlini, cannabinoid research pioneer, passed away at the age of 90

The Brazilian cannabis and cannabinoid researcher Prof Elisaldo Araujo Carlini (1930-2020) passed away on September 16 at the age of 90. He was the pioneer in discovering the anticonvulsant effects of cannabidiol, still in the 70s. Carlini lived a period of his childhood in a small rural district of Pirajá, Săo Paulo. In this village devoid of all resources, including health care, he came into contact with herbal treatments and developed a deep sense of solidarity with human suffering. The Professor used to say to his students that his passion for research with medicinal plants began in that period.

Carlini published his initial papers on cannabis almost simultaneously as that of Raphael Mechoulam's group at Hebrew University, Israel. At that time, Mechoulam and Carlini established an extremely productive partnership and a lifetime friendship. A few years later, with his colleague Isaac Karniol, he observed that Brazilian cannabis samples' THC content did not explain all of its biological activities. This finding highlighted that other cannabinoids might also produce pharmacological effects that, as in the case of cannabidiol (CBD), could be even opposite to those observed with THC. These studies were fundamental to the subsequent discovery of CBD's anxiolytic and antipsychotic properties.

Source: Excerpts from the manuscript “Prof. Elisaldo Araújo Carlini, Cannabis and Cannabinoids Research Pioneer (1930–2020)” for the IACM Journal Cannabis and Cannabinoid Research written by Antonio Zuardi, Francisco Guimaraes, and José Crippa from the University of Săo Paulo, Brazil. [To be published]

Science/Human: Cannabis use may reduce cancer risk according to review

According to a review published online in Cannabis and Cannabinoid Research by scientists of the Department of Biological Sciences at Indiana University South Bend, USA, cannabis use may reduce cancer risk. Authors identified 34 studies and excluded data with high risk of selection bias (defined as those from North Africa and those that failed to adjust for tobacco) and data with high risk of performance bias (defined as those with fewer than 20 cases or controls among Cannabis users).

Of all cancer sites, only testicular cancer showed a relative risk value of above 1, although this was not significant and had a negligible effect size of 12% (RR=1.12). Following removal of testicular cancers the remaining data showed a decrease in risk by 13% (RR=0.87). Cancers of the head and neck showed a negative association with cancer risk (RR=0.83). Relative risks did not reach statistical significance in the remaining cancer site categories (lung, testicular, obesity-associated, other). Authors concluded that these data “are consistent with a negative association between Cannabis use and non-testicular cancer, but there is low confidence in this result due to high heterogeneity and a paucity of data for many cancer types.”

Clark TM. Scoping Review and Meta-analysis Suggests that Cannabis Use May Reduce Cancer Risk in the United States. Cannabis Cannabinoid Res. 2020 Aug 21. [in press]

Science/Human: People living with HIV, who use cannabis, present with better cognitive performance

People living with HIV (PLWH) report higher rates of cannabis use than the general population. In a study with 138 patients those who used cannabis performed better on neuropsychological than non-users. This is the result of scientists of the Department of Psychology at Fordham University in New York, USA.

Patients, who were cannabis users performed significantly better on tests of processing speed, executive functioning, verbal fluency, learning, memory, and motor ability then non-users. Authors wrote that their findings “suggest PLWH with past cannabis use have similar or better neurocognition across domains compared to PLWH without past use.

Crook CL, Savin MJ, Byrd D, Summers AC, Guzman VA, Morris EP, Tureson K, Aghvinian M, Cham H, Mindt MR. The neurocognitive effects of a past cannabis use disorder in a diverse sample of people living with HIV. AIDS Care. 2020:1-10.

Science/Human: A large number of patients with back pain are able to stop opioid use after initiation of cannabis use

In a retrospective cohort study of 61 patients with low back pain about half were able to stop all opioid usage, which usually took several years. This is the result of a study by the Society of Cannabis Clinicians in Sebastopol, USA. Cannabis recommendations were provided to patients as a way to mitigate their low back pain.

Authors found “that 50.8% were able to stop all opioid usage, which took a median of 6.4 years (IQR=1.75-11 years) after excluding two patients who transitioned off opioids by utilizing opioid agonists. For those 29 patients (47.5%) who did not stop opioids, 9 (31%) were able to reduce opioid use, 3 (10%) held the same baseline, and 17 (59%) increased their usage.” They noted that there “were no variables that predicted who stopped opioids, except that those who used higher doses of cannabis were more likely to stop, which suggests that some patients might be able to stop opioids by using cannabis, particularly those who are dosed at higher levels.”

Takakuwa KM, Hergenrather JY, Shofer FS, Schears RM. The Impact of Medical Cannabis on Intermittent and Chronic Opioid Users with Back Pain: How Cannabis Diminished Prescription Opioid Usage. Cannabis Cannabinoid Res. 2020;5(3):263-270.

Science/Human: The liberalisation of CBD products resulted in the reduction of other medicinal drugs

Some governments worldwide are concerned about the booming use of CBD (cannabidiol) products. Researchers of the Department of Law, Economics and Sociology at "Magna Graecia" University in Catanzaro, Italy, as well as from Germany studied a case of unintended liberalization of a CBD-based product that occurred in Italy in 2017.

Using unique and high-frequency data on prescription drug sales and by exploiting the staggered local availability of the new product in each Italian province, researchers document a significant substitution effect between CBD products and anxiolytics, sedatives, opioids, anti-depressants and anti-psychotics. Authors concluded that these results “suggest that bans on light cannabis use would disregard the needs of patients to seek effective reliefs of their symptoms.”

Carrieri V, Madio L, Principe F. Do-It-Yourself medicine? The impact of light cannabis liberalization on prescription drugs. J Health Econ. 2020;74:102371.

News in brief

Science/Animal: CBD may reduce the cytokine storm in acute respiratory distress syndrome
In this study, researchers showed that intranasal application of the synthetic analogue of a viral RNA simulated symptoms of severe acute respiratory distress syndrome accompanied by high levels of pro-inflammatory cytokines. The administration of CBD down regulated the level of these cytokines and ameliorated the clinical symptoms. This may be beneficial in the treatment of COVID-19.
Dental College of Georgia, Augusta University, Augusta, Georgia, USA.
Khodadadi H, et al. Cannabis Cannabinoid Res. 2020;5(3):197-201.

Science/Human: CBD may modulate brain function during fear for people at high risk for psychosis
In a double blind placebo controlled study with 33 people at high risk for psychosis and 19 healthy controls a single oral dose of CBD (600 mg) participants were scanned with functional magnetic resonance imaging (fMRI) during a fearful face-processing paradigm. During fear processing, participants with high risk for psychosis receiving placebo (n = 15) showed greater activation than controls (n = 19) in the parahippocampal gyrus but less activation in the striatum. Authors noted that “CBD modulates brain function in regions implicated in psychosis risk and emotion processing.”
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
Davies C, et al. Transl Psychiatry. 2020;10(1):311.

Science/Human: Many MS patients use cannabis for the treatment of spasticity, pain and sleep
According to a survey by the North American Research Committee on Multiple Sclerosis (NARCOMS) with 3249 patients with multiple sclerosis 31 percent (n=1012) indicated they had used cannabis for their MS symptoms at least once; of these respondents, 50.5% had used cannabis to treat spasticity, 43.6% had used cannabis for pain, and 38.4% had used cannabis for sleep. There were 636 (19.6%) respondents who reported current use of cannabis for their MS, while 376 (11.6%) reported past use but not current use.
Salter A, et al. Joint ACTRIMS-ECTRIMS Meeting- MSVirtual2020 P0439.

Spain: Online conference in Spanish of ICEERS
The third CANNABMED by ICEERS will take place from 6 to 7 October 2020. Registration is possible here.

Switzerland: Council of States approves a trial for cannabis use by adults
Switzerland’s Council of States has approved a plan to start cannabis trials for recreational use, but only 'experienced cannabis users' should apply. The study hopes to find out more about the effects that a controlled legalisation of the drug would have in Switzerland. The government is looking "only for adults who already use cannabis to take part in the study". The proposal was previously approved by Switzerland's lower house - the National Council - in June.
The Local of 10 September 2020

UK: Health insurance pays for the cannabis of a severely epileptic boy
The NHS has agreed to pay for the cannabis medicine of a severely epileptic boy nearly two years after his case helped persuade the government to legalise the treatment. The health service announced that it would fund Billy Caldwell’s cannabis medicine, in a move that is likely to allow parents of other epileptic children to obtain financial support for similar treatments.
The Times of 11 September 2020

UK: Police chiefs back calls for medicinal cannabis card
Despite medicinal cannabis being legalised in 2018, and tens of thousands of people using the drug medicinally, only around 100 people have been given an NHS prescription for the drug. Others have gone private to get a prescription, often at a huge cost. Most people who need cannabis to help with conditions such as multiple sclerosis and epilepsy are still buying the Class B drug illegally, and risk arrest and prosecution.
Vice of 9 September 2020

Sweden: Two companies are allowed to supply medical cannabis extracts to patients
Two companies announced that they expect to supply medical cannabis oil products to Swedish patients during 2020. Under an agreement signed in November 2019, Emerald will supply their medical cannabis products to markets serviced by STENOCARE and its partners. Several Swedish patients have applied via their doctor for a special approval for treatment with medical cannabis oil products and have been granted a license for this treatment.
Stenocare of 8 September 2020

USA: Hemp-CBD dietary supplement bill introduced in the House
Two members of the House of Representatives have introduced the Hemp and Hemp-Derived CBD Consumer Protection and Market Stabilization Act of 2020 to allow hemp and hemp derived CBD to be legally marketed in dietary supplements.
Foodnavigator of 4 September 2020

Science/Animal: THC attenuates colitis and prevents the development of colitis-associated colon cancer
New research shows that THC attenuates colitis-associated colon cancer and colitis induced by anti-CD40. Working through cannabinoid receptor 2, THC increased so-called T regulatory cells. These cells are necessary to reduce systemic the concentration of the pro-inflammatory mediators interferon gamma and tumour necrosis factor alpha. Authors wrote that “using models of colitis and systemic inflammation we show that THC, through CB2, is a potent suppressor of aberrant immune responses (…).”
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, USA
Becker W, et al. iSciene. 2020;23(9):101504

Science: Extracts of the hemp variety Futura 75 was effective against the development of microbes in meat
Researchers present data on the antimicrobial effect of hemp variety Futura 75 against food-borne pathogens as well as against naturally occurring microbial populations on minced meat during storage. They wrote that “in particular, extract corresponding to CBD concentration of 0.017 and 0.3 mg/mL were effective against L. monocytogenes and Staphylococcus spp. respectively. After 8 days of storage at 4°C, treated minced meat showed a bright red colour in comparison to a brownish control meat.”
Department of Agricultural and Food Sciences, University of Bologna, Italy.
Pasquali F, et al. Ital J Food Saf. 2020;9(2):8581.

Science/Human: Add-on therapy with CBD was effective in 3 patients with a rare form of epilepsy
Mutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder. In 3 patients seizures were resistant to at least 5 antiepileptic drugs. After CBD introduction, two patients were responders and achieved a seizure reduction of 90% and 80%, respectively after 2 months, the third showed a late response after 7 months treatment with an 80% decrease in seizure frequency.
Department of Pediatric Neurology Reference Centre for Rare Epilepsies Hôpital Necker-Enfants Malades Paris France.
Kuchenbuch M, et al. Epilepsia Open. 2020;5(3):496-500.

Science/Cells: THC and CBD may suppress the cytokine storm in sepsis
In a model of sepsis with whole blood cells with increased levels of pro—inflammatory cytokines
(interleukin 1 beta, interleukin 6, tumour necrosis factor alpha) exposure to both CBD and a combination of CBD and THC extracts significantly reduced cytokine production in a dose -dependent manner. Authors wrote that these “findings highlight the role that natural cannabinoids may play in suppressing inflammation.”
Sackler Faculty of Medicine, Tel Aviv University, Israel.
Szekely Y, et al. EUR Cytokine Netw. 2020;31(2):50-58.

Science/Animal: THC may have positive effects on repetitive mild traumatic brain injury
In a study with rats, who experienced repeated mild brain injuries researchers observed a number of positive effects of THC administered after these injuries. Authors noted that there were no benefits of THC if it was given before so that it should be “administered post-injury, but not pre-injury.”
Hotchkiss Brain Institute, The University of Calgary, Canada.
Bhatt D, et al. Brain Commun. 2020;2(1):fcaa042.

Science/Human: CBD extract showed positive effects in a patient with autism
The case report of a 15-year-old boy with autism spectrum disorder, anxiety and controlled epilepsy showed that he profited from a CBD-based cannabis extract. Authors noted that this case report “provides evidence that a lower than previously reported dose of a phytocannabinoid in the form of a cannabidiol-based extract may be capable of aiding in autism spectrum disorder-related behavioral symptoms, core social communication abilities, and comorbid anxiety, sleep difficulties, and weight control.”
Caleo Health, Calgary, Canada.
Ponton JA, et al. J Med Case Rep. 2020;14(1):162.

Science/Cells: CBD may be helpful in psoriasis and other autoimmune diseases
A study investigated the antioxidant properties of CBD evaluating the effects of the cannabinoid on so-called neutrophil extracellular trap (NET) formation. Researchers noted, that CBD reduced this formation “mainly in psoriatic neutrophils, possibly due to its antioxidant properties. The anti-NET properties of CBD suggest the positive effect of CBD in the treatment of autoimmune diseases.”
Department of Analytical Chemistry, Medical University of Bialystok, Poland.
Wójcik P, et al. Int J Mol Sci. 2020;21(18):E6795.

Science/Animal: THC was able to improve symptoms of non-alcoholic fatty liver disease (NAFLD)
In a study where mice were fed a high-fat diet “the administration of cannabis containing elevated levels of THC may help ameliorate symptoms of NAFLD, whereas administration of CBD-rich cannabis extracts may cause a proinflammatory effect in the liver, linked with an unfavorable change in the microbiota profile.”
The Hebrew University of Jerusalem, Rehovot, Israel.
Assa-Glazer T, et al. Cannabis Cannabinoid Res. 2020;5(3):202-214.

Science/Cells: CBD has potential therapeutic value in the treatment of psoriasis
UVB phototherapy is a treatment for psoriasis, which increases phospholipid oxidative modifications in the cell membrane of the skin. The treatment of psoriatic skin cells with CBD improved this treatment effect. Authors noted that “CBD has potential therapeutic value in the treatment of psoriasis.”
Department of Analytical Chemistry, Medical University of Bialystok, Poland.
Łuczaj W, et al. Int J Mol Sci. 2020;21(18):E6592.

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