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IACM-Bulletin of 14 February 2021

USA: Democrats advance cannabis legalisation in Congress

Three Senators (Cory Booker, Ron Wyden, and Chuck Schumer) issued a joint statement saying they would work together to advance comprehensive cannabis reform legislation in the current Congress. “The War on Drugs has been a war on people—particularly people of colour. Ending the federal marijuana prohibition is necessary to right the wrongs of this failed war and end decades of harm inflicted on communities of colour across the country. But that alone is not enough,” they said.

All three senators have previously supported legislation to decriminalize cannabis in some form. “In the early part of this year, we will release a unified discussion draft on comprehensive reform to ensure restorative justice, protect public health and implement responsible taxes and regulations,” the three senators said. “Getting input from stakeholder groups will be an important part of developing this critical legislation.”

The Verge of 1 February 2021

Science/Human: Cannabis improves symptoms in ulcerative colitis in a placebo-controlled trial

In a placebo-controlled trial with 32 patients suffering from ulcerative colitis there was a significant improvement in symptoms, but no improvement in markers of inflammation. The study was conducted by investigators of the Institute of Gastroenterology and Hepatology of Meir Medical Center in Kfar Saba, Israel. Patients received either cigarettes containing 0.5 g of dried cannabis flowers with 80 mg of THC or placebo cigarettes for 8 weeks.

The Lichtiger index, a score of symptom intensity in ulcerative colitis, improved in the cannabis group from 10.9 to 5 and in the placebo group from 11 to 8. Quality of life improved in the cannabis group from 77 to 98 but not in the placebo group, with 78 at week 0 and 78 at week 8. The Mayo endoscopic score of inflammation changed in the cannabis group from 2.1 to 1.3 and in the placebo group from 2.2 to 1.7. Authors concluded that short term treatment with THC rich cannabis induced clinical remission and improved quality of life in patients with mild to moderately active ulcerative colitis. However, these beneficial clinical effects were not associated with significant anti-inflammatory improvement.”

Naftali T, Bar-Lev Schleider L, Scklerovsky Benjaminov F, Konikoff FM, Matalon ST, Ringel Y. Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial. PLoS One. 2021;16(2):e0246871.

Science/Human: Cannabis extracts were effective in reducing symptoms of autism in a controlled clinical trial

Two cannabis extracts reduced symptoms in people with autism Spectrum disorder and were well tolerated in a placebo-controlled trial with 150 participants. Investigators of Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel, tested a whole-plant cannabis extract containing THC and CBD in a ratio of 1 to 20 and purified THC and CBD at the same ratio. The 150 participants received either placebo or cannabinoids for 12-weeks followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability.

Changes in total scores of a standardised questionnaire on autism spectrum disorder did not differ among groups. Disruptive behaviour on another questionnaire was either much or very much improved in 49% on whole-plant extract versus 21% on placebo. On a questionnaire for parents there was an improvement by 14.9 on whole-plant extract versus 3.6 points after placebo. There were no treatment-related serious adverse events.

Aran A, Harel M, Cassuto H, Polyansky L, Schnapp A, Wattad N, Shmueli D, Golan D, Castellanos FX. Cannabinoid treatment for autism: a proof-of-concept randomized trial. Mol Autism. 2021;12(1):6.

Science/Human: Inhalation of cannabis reduces anxiety and stress

A study among 670 people using a software to directly report cannabis effects suggests the majority of patients experienced relief from distress-related symptoms following consumption of cannabis flowers, and that among product characteristics, higher THC levels were the strongest factors of relief. Researchers of the Department of Economics of the University of New Mexico in Albuquerque, USA, used an observational research design to evaluate which types of commonly labelled cannabis flower product characteristics are associated with changes in momentary feelings of distress-related symptoms.

In total, a decrease in symptom intensity levels was reported in about 96% of cannabis usage sessions, an increase in about 2% of sessions, and no change in about 2% of sessions. Fixed effects models showed, on average, respondents recorded a maximum symptom intensity reduction of 4.3 points for agitation/irritability, 3.5 points for anxiety, and 4.0 for stress on an 11-point visual analogue scale. Symptom relief was mainly associated with THC levels, while CBD levels “were generally not associated with changes in symptom intensity levels.” In a minority of cannabis use sessions (less than 13%), cannabis users reported anxiogenic-related negative side effects including feeling anxious, irritable or paranoid.

Stith SS., Li X, Diviant JP., Brockelman FC., Keeling KS., Hall B, Vigil JM. The effectiveness of inhaled Cannabis flower for the treatment of agitation/irritability, anxiety, and common stress. J Cannabis Res. 2020;2:47.

Science/Human: Cannabis use is associated with reduced risk of fatty liver in people with HIV/HCV

In a study with about 1000 patients co-infected with HIV (human immunodeficiency virus) and HCV (hepatitis C virus) those using cannabis had a reduced risk for the development of fatty liver. Investigators from several research institutions in France including Aix Marseille University and INSERM, used five-year follow-up data from 997 HIV-HCV co-infected patients.

At the last follow-up visit, 27% of patients reported regular or daily cannabis use and 28% had elevated fatty liver index. After multivariable adjustment, regular or daily cannabis use was associated with a 55% lower risk of elevated fatty liver index and lower mean values of this index.

Barre T, Rojas Rojas T, Lacombe K, Protopopescu C, Poizot-Martin I, Nishimwe M, Zucman D, Esterle L, Billaud E, Aumaitre H, Bouchaud O, Rey D, Piroth L, Salmon-Ceron D, Wittkop L, Sogni P, Carrieri MP, Serfaty L, Marcellin F. Cannabis use and reduced risk of elevated fatty liver index in HIV-HCV co-infected patients: a longitudinal analysis (ANRS CO13 HEPAVIH). Expert Rev Anti Infect Ther. 2021 Feb 4. [in press]

News in brief

Europe: Members of the EURopean Parliament found EURopean Medicinal Cannabis Alliance
The EURopean Medicinal Cannabis Alliance was announced by Alex Agius Saliba from Malta, with a number of others like Poland’s Robert Biedroń, Italy’s Brando Benifel and Belgium’s Maria Arena already on board. In a letter inviting all MEPs to join the alliance, the group noted that though medicinal cannabis is “increasingly being used more frequently to treat patients with various conditions”, any progress is being “slowed” due to different regulations over use of the plant across the EU’s 27 Member States.
Lovin Malta of 4 February 2021

Economy: Jazz Pharmaceuticals acquires GW Pharmaceuticals
Jazz Pharmaceuticals and GW Pharmaceuticals announced the companies have entered into a definitive agreement for Jazz to acquire GW for a total consideration of 7.2 billion US dollars. The transaction, which has been unanimously approved by the Boards of Directors of both companies, is expected to close in the second quarter of 2021.
Jazz Pharma of 3 February 2021

USA: 61% support legalisation of cannabis
A new Emerson College/7 News national poll among 1429 adults shows that legalisation of cannabis is popular in the USA, as 61% state such a policy would be a good idea, compared to 39% who think recreational cannabis legalization would be a bad idea. Seventy-four percent (74%) of Democrats would support this policy, compared to 60% of Independents and 46% of Republicans.
Emerson College Polling of February 2021

Science/Human: The legalisation of cannabis in the USA had no effect on the use of hard drugs by adolescents
According to annual data from Washington and Colorado of the years 2008 to 2017 legalisation of cannabis was not associated with an increase in adolescent or young adult hospital admissions for opioid, cocaine or methamphetamine use disorders.
Department of Geography and Urban Studies, Temple University, Philadelphia, United States of America.
Mennis J, et al. J Subst Abuse Treat. 2021;122:108228.

Poland: Cannabis will be produced for medicinal uses
CanPoland from Łódź intends to launch a production line for cannabis as early as March this year. Until now, it is imported from Canada or Germany.
Cannabis News of 27 January 2021

Science/Human: Pain and psychiatric disorders are the main reasons for medical cannabis use in the USA
According to an analysis of 61,000 patient data from 33 cannabis clinics in the US the top three mutually exclusive primary medical conditions reported were unspecified chronic pain (39%), anxiety (14%) and post-traumatic stress disorder (8%). The average number of comorbid conditions reported was 2.7, of which anxiety was the most common (28%).
CB2 Insights, Mississauga, Canada.
Mahabir VK, et al. J Cannabis Res. 2020;2:32.

Science/Animal: CBD may be helpful in the treatment of methamphetamine use disorder
In a study with methamphetamine dependent rats CBD injections inhibited the liking of methamphetamine.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Islamic Azad University, Tehran, Iran.
Anooshe M, et al. Behav Brain Res. 2021:113158.

Science/Animal: CBD in combination with bioflavonoids has anti-inflammatory properties
In studies with rats CBD alone produced dose-correlated, statistically significant pain inhibition in several pain models. Authors noted that “enhanced performance in pain and inflammation reduction was observed when CBD was orally administered in complex with the bioflavonoid compositions.”
Unigen, Tacoma, Washington, USA.
Yimam M, et al. J Med Food. 2021 Feb 10. [in press]

Science/Human: High THC doses associated with thinking disorder in people above the age of 50
According to a review of clinical trials high THC doses were associated with a higher incidence of thinking or perception disorder and dizziness or light-headedness, but no other neuropsychiatric adverse events in randomised clinical trials using THC.
Department of Old Age Psychiatry, King's College London, UK.
Velayudhan L, et al. JAMA Netw Open. 2021;4(2):e2035913.

Science/Human: Many migraine patients use cannabis
Among 372 migraine patients participating in a survey recruited from the Move Against Migraine Facebook group 335 reported use of cannabis. Between 114 and 139 (34-42%) found cannabis modalities to be at least mildly effective. 39% reported that cannabis was not effective for them.
Yale School of Medicine, New Haven, USA.
Kuruvilla DE, et al. BMC Complement Med Ther. 2021;21(1):58.

Science/Human: Pain most frequent symptom treated with cannabinoids in report of the German Health Ministry
According to a preliminary report by the German Federal Institute for Drugs and Medical Devices on medical cannabis reimbursed by German health insurers the most frequently treated symptoms were pain (73%), followed by spasticity (10%), and anorexia/wasting (6%). Dronabinol was most frequently (65%) prescribed, followed by cannabis flowers (18%), Sativex (13%), cannabis extract (4%), and nabilone (0.3%).
Explanation by the author of the IACM-Bulletin: German health insurers usually deny reimbursement in most symptoms besides pain, spasticity and anorexia, which means that patients with other conditions usually have to pay the medication from their own pocket and do not appear in this report. The use of cannabis flowers is discouraged by health insurers.
Federal Institute for Drugs and Medical Devices, Federal Opium Agency, Bonn, Germany.
Schmidt-Wolf G, et al. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2021 Feb 9. [in press]

Science/Cells: CBG shows anti-cancer effects against glioblastoma
CBG inhibited glioblastoma invasion in a similar manner to CBD and the chemotherapeutic temozolomide. THC demonstrated little added value in combined cannabinoid glioblastoma treatment with CBD, CBG and THC. Authors suggest replacing THC by CBG.
Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia.
Lah TT, et al. Cells. 2021;10(2):340.

Science/Human: 2-AG levels are reduced in patients with severe depression
In a study with 12 depressed patients and 12 healthy controls there was a significant inverse correlation between the concentration of the endocannabinoid 2-AG and blood plasma and the severity of depression. Authors noted that their results “suggest that 2-arachidonylglycerol, the most abundant endocannabinoid in the central nervous system, might act to mitigate depressive symptoms.”
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy.
Bersani G, et al. Hum Psychopharmacol. 2021:e2779.

Science/Cells: Cannabinoids may reduce oxidative stress in skin cells
In studies with skin cells (keratinocytes) and fibroblasts “obtained results indicate that HEMP extracts can be a valuable source of biologically active substances that reduce oxidative stress, inhibit skin aging processes and positively affect the viability of skin cells. The analysis also showed that hydrogels based on cannabis extracts have a positive effect on skin hydration.”
Department of Technology of Cosmetic and Pharmaceutical Products, Medical College, University of Information Technology and Management in Rzeszow, Tyczyn, Poland.
Zagórska-Dziok M, et al. Molecules. 2021;26(4):802.

Science/Animal: CBD reduces seizures in an epilepsy model with hamsters
In an epilepsy model with hamsters “Acute CBD administration showed subtle attenuation of seizure behaviors, increasing seizure latency and decreasing the duration of the convulsion phase, but without entirely seizure abolition.”
Institute of Neuroscience of Castilla y León (INCYL), University of Salamanca, Spain.
Cabral-Pereira G, et al. Front Behav Neurosci. 2021;14:612624.

Science/Human: Women with endometriosis present with high levels of anandamide
An analysis of endocannabinoids in follicular fluid showed high concentrations of the endocannabinoid anandamide in patients with endometriosis. Authors note that this may be one reason for the decreased reproductive potential of woman with this disease.
Faculdade de Farmácia, Universidade do Porto, Portugal.
Fonseca BM, et al. Reprod Fertil Dev. 2021 Feb 8. [in press]

Science/Human: Cannabis use may be associated with higher accident risk in elder people
An analysis of accidents using data National Highway Traffic Safety Administration's Drug and Alcohol Crash Risk Study from the USA showed “no overall association between cannabis use and risk of crash involvement. (…) But THC was associated with increased risk of crash involvement for older drivers. Difference between THC-positive and sober drivers emerged as significant at age 64.”
Pacific Institute for Research and Evaluation (PIRE), Calverton, USA.
Johnson MB, et al. Accid Anal Prev. 2021;152:105987.

Science/Human: No major correlation between impairment and THC blood concentration in driving simulator study
In a driving simulator study there was “a poor and inconsistent relationship between magnitude of impairment and THC concentrations in biological samples, meaning that per se limits cannot reliably discriminate between impaired from unimpaired drivers. There is a pressing need to develop improved methods of detecting cannabis intoxication and impairment.”
Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, New South Wales, Australia.
Arkell TR, et al. Traffic Inj Prev. 2021:1-6.

Science/Cells: CBD is protecting skin cells against damage caused by sunlight
In a study investigating the protective effects of CBD skin cells “CBD-through its antioxidant/anti-inflammatory activity and regulation of protein biosynthesis and degradation-protects skin cells against UVA/B-induced changes.”
Department of Analytical Chemistry, Medical University of Bialystok, Poland.
Gęgotek A, et al. Int J Mol Sci. 2021;22(3):1501.

Science/Human: Cannabis use is not associated with increased balance problems in HIV infected people
In a study with HIV positive individuals cannabis use had no effect on balance. Authors noted that this “suggests that cannabis use in HIV is safe with respect to balance disturbances.”
Interdisciplinary Research Fellowship, University of California San Diego, USA.
Kiendrebeogo P, et al. J Cannabis Res. 2021;3(1):3.

Science/Animal: CBD may reduce aggression towards humans in dogs
In a study with 24 shelter dogs, of whom 12 received CBD, the cannabinoid reduced aggressive behaviour towards humans.
School of Agriculture and Environment, The University of Western Australia, Crawley, Australia.
Corsetti S, et al. Sci Rep. 2021;11(1):2773.

Science/Animal: Beta-caryophyllene protects against cognitive impairment caused by inflammation of the brain
In a study with rats beta-caryophyllene, which activates the CB2 receptor, protects against dementia induced by nerve inflammation with no effect on reduced cognitive function by normal brain ageing induced by dysfunction of the mitochondria.
Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, India.
Kanojia U, et al. CNS Neurol Disord Drug Targets. 2021 Feb 2. [in press]

Science/Animal: Increase of endocannabinoid concentration may be helpful in autism
In a rat model of autism increase of the concentration of the endocannabinoid 2-arachidonoylglycrol by inhibition of its degradation improved autism -like behaviour, including repetitive and stereotypical behaviours, hyperactivity, sociability and cognitive functioning.
Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, China.
Zou M, et al. Open Biol. 2021;11(2):200306.

Science/Human: Patients often don’t tell their physician about their medical cannabis use
According to an anonymous survey with 275 patients 44% didn’t tell their primary physician that they were using medical cannabis, despite 86% had substituted cannabis for pharmaceutical medications. Only 18% rated their physician’s knowledge about medical cannabis is a very good or excellent.
Anesthesiology Department, University of Michigan Medical School, USA.
Boehnke KF, et al. J Cannabis Res. 2021;3(1):2.

Science/Human: Cannabis use before the age of 15 causes memory deficits in adulthood
In a study with 524 young adults, who were followed since birth, results of tests on cognitive function indicate that initiating cannabis use before age 15 placed young adults at greater risk of memory deficits.
Department of Psychology, Slippery Rock University, USA.
Willford JA, et al. Neurotoxicol Teratol. 2021;84:106958.

Science/Animal: CBD shows antidepressant properties in depression caused by inflammation of the brain
CBD caused antidepressant effects in a mouse model of brain inflammation by reducing interleukin-6 levels and other proinflammatory mechanisms. Authors wrote that “more research is needed to completely understand its mechanisms of action in depression linked to inflammation.”
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Florensa-Zanuy E, et al. Biochem Pharmacol. 2021:114433.

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