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IACM-Bulletin of 16 August 2020

Thailand: Patients may cultivate their own cannabis for medical use

Thailand’s cabinet approved amendments on 4 August to its narcotics act to allow private production and sale of cannabis for medical use, officials said. With a tradition of using the drug to relieve pain, Thailand became the first Southeast Asian nation to legalise cannabis in 2017 for medical use and research, but only the government was allowed to grow plants.

Deputy government spokeswoman Traisuree Taisaranakul told reporters after a cabinet meeting that the proposed amendments would also allow patients, businesses and medical professionals to produce, export, import and sell cannabis. “The law will promote the pharmaceutical industry and increase competitiveness, which will be important for Thailand in becoming a leader in medical cannabis,” Public Health Minister Anutin Charnvirakul also told reporters.

Reuters of 4 August 2020

Science/Human: THC may be helpful in the treatment of post-traumatic stress disorder

According to a placebo-controlled study with 71 participants, THC lowered amygdala reactivity. The amygdala is a brain structure which plays an important role in the processing in emotional responses, including fear, anxiety and and aggression. The study was conducted by researchers from Wayne State University in Detroit, USA, and recently published in in the journal Psychopharmacology. They formed 3 groups of adults (1) 25 non-trauma-exposed healthy controls (2) 27 trauma-exposed adults without post-traumatic stress disorder (PTSD) , and (3) 19 trauma-exposed adults with PTSD. They received either THC or placebo and completed a well-established threat processing paradigm during functional magnetic resonance imaging.

In adults with PTSD, THC lowered threat-related amygdala reactivity and showed further functional signs of resistance to threat in brain activity. Authors concluded that these “preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.”

Rabinak CA, Blanchette A, Zabik NL, Peters C, Marusak HA, Iadipaolo A, Elrahal F. Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study. Psychopharmacology (Berl). 2020;237(6):1813-1826.

Science/Human: Cannabis use is associated with reduced viral load in people with HIV who use cocaine

An analysis of interview data from 119 people living with HIV and using cocaine and cannabis, the use of cannabis was associated with reduced viral load. The study was conducted by scientists of Albert Einstein College of Medicine/Montefiore Medical Center in New York, USA. Participants were adult people living with HIV and prescribed antiretrovirals for at least 16 weeks and used cocaine in the past 30-days.

Participants with viral load suppression used cocaine less frequently than those with no viral load suppression. Cannabis use was not significantly different. Compared with no use, daily/near-daily cannabis use was associated with significant viral load suppression. Less-frequent cannabis use was not associated with viral load suppression.

Slawek DE, Arnsten J, Sohler N, Zhang C, Grossberg R, Stein M, Cunningham CO. Daily and near-daily cannabis use is associated with HIV viral load suppression in people living with HIV who use cocaine. AIDS Care. 2020:1-8.

Science/Human: CBD was effective in the treatment of cannabis use disorders in clinical study

In a placebo-controlled study with 84 patients with cannabis use disorders 400 mg and 800 mg of CBD were effective in reducing cannabis intake. The trial was conducted by researchers from the University College London and King's College London, UK, among others. Results were published in Lancet Psychiatry. In the first stage of the trial there was a 4-week treatment with three different doses of oral CBD (200 mg, 400 mg, or 800 mg) or placebo including 48 patients. For the second stage of the trial, additional 34 participants were randomly assigned to placebo or 400 mg or 800 mg, doses deemed efficacious in the interim analysis,

For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was very high for 400 mg CBD and 800 mg CBD. In both groups the concentration of the THC metabolite THC-COOH significantly decreased in the urine compared to placebo. Authors concluded that “cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use.”

Freeman TP, Hindocha C, Baio G, Shaban NDC, Thomas EM, Astbury D, Freeman AM, Lees R, Craft S, Morrison PD, Bloomfield MAP, O'Ryan D, Kinghorn J, Morgan CJA, Mofeez A, Curran HV. Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. Lancet Psychiatry. 2020:S2215-0366(20)30290-X.

Science/Human: Cannabis use associated with reduced hospital deaths due to heart failure

Scientists from Brookdale University Hospital Medical Center in New York, USA, demonstrated that cannabis use disorders were associated with reduced hospital deaths in patients suffering from congestive heart failure (CHF). They used the Nationwide Inpatient Sample database of the USA from 2010 to 2014 including 4,596,024 CHF patients, of whom 23,358 were diagnosed with cannabis use disorders.

Inpatient deaths (1.1% versus 3.1%) were lower , and mean length of stay was shorter among cannabis users compared to non-users. Alcohol abuse and depression were more prevalent among cannabis users compared to non-users. Authors concluded that cannabis use disorders were “associated with reduced inpatient deaths.” But they also noted that the prevalence of cannabis use disorder was on the rise in patients with congestive heart failure.

Ajibawo T, Ajibawo-Aganbi U, Jean-Louis F, Patel RS. Congestive Heart Failure Hospitalizations and Cannabis Use Disorder (2010-2014): National Trends and Outcomes. Cureus. 2020;12(7):e8958.

News in brief

WHO/UN: Some WHO cannabis recommendations draw opposition from the UN
Two of the World Health Organization’s (WHO) cannabis recommendations might face an opposition getting adopted later this year by the United Nations’ Commission on Narcotic Drugs (CND). If the two recommendations discussed at the CND meeting in June are approved, international trade in certain CBD preparations is expected to become more free. The following recommendations were discussed: (1) delete cannabis “extracts and tinctures” from Schedule 1 of the 1961 Single Convention on Narcotics Drugs, (2) add a footnote to the cannabis entry in Schedule 1 of the 1961 Single Convention to clarify that preparations containing predominantly CBD and up to 0.2% THC are not under international control.
Marijuana Business Daily of 30 July 2020

Science: Cannabis and Cancer Survey
Researchers from the Cancer Research Center at HealthPartners/Park Nicollet in Minneapolis, USA, would like to better understand the opinions of patients and/or their loved ones about the use of medical cannabis and cannabis-related products like cannabidiol (CBD). For this reason they are conducting a survey to better understand how patients use or do not use medical cannabis as a treatment option.
Survey on cannabis in cancer

Science/UK: Project Twenty21 monitoring health outcomes of 20,000 cannabis patients will start
Project Twenty21 is a registry aiming to monitor the health outcomes of 20,000 patients using cannabis based medicinal products, creating the largest body of evidence in EURope for the safety and their efficacy. Drug Science hope that the findings of Project Twenty21 will provide evidence for funding by the British Health Service where the benefits of treatment with medicinal cannabis is proven to outweigh the potential risks. This real-world registry aims to target the following indications: Anxiety Disorder, Chronic Pain, Multiple Sclerosis, Post-Traumatic Stress Disorder (PTSD), Substance Use Disorder (as a harm reduction strategy, Tourette’s Syndrome. In June 2020, the Project Twenty21 team commenced beta testing of the patient pathway and opened up access to one clinic (Medical Cannabis Clinics) for 100 patients.
Drug Science of 4 August 2020

UK: First patient in Scotland legally prescribed cannabis
A young woman has become the first person in Scotland to be prescribed cannabis legally as part of a new EURopean study - and says it allows her to play with her kids and take a shower after years of chronic pain. Kayleigh Compston, 26, first got into smoking cannabis as a teenager, but stopped - until four years ago when she began to self-medicate illegally.
Daily Record of 28 July 2020

Cyprus: Medical cannabis will become legal
Parliament has passed a bill to regulate the prescription, distribution, and availability of medical cannabis. The bill was voted into law 42 votes in favour and seven against. According to the report submitted by the house health committee, the regulations set the standards for prescription of medical cannabis based on the scientific use of the drug. Introducing an amendment, the head of the Green Party Giorgos Perdikis said the minister would have too much control in deciding how much medical cannabis will be available and which specialists will be allowed to prescribe it.
Cyprus Mail of 1 August 2020

World: The World Anti-Doping Agency reduces punishment for drug users
The World Anti-Doping Agency (WADA) is making some changes, where they won't issue long suspensions for athletes testing positive for recreational drugs out of competition. Instead of being banned for two years, the athletes will now be banned for one to three months. "If the athlete can establish that any ingestion or use occurred out of competition and was unrelated to sport performance, then the period of ineligibility shall be three months," WADA's new code says.
BoxingScene of 6 August 2020

Science: Cannabis use during pregnancy maybe linked to increased autism risks for children
Using data on every birth in Ontario, Canada, between April 2007 and March 2012, the University of Ottawa researchers found that pregnant women who used cannabis were 1.5 times more likely to have a child with autism than women who didn't.
UPI of 11 August 2020

USA: CBD extract gets approval for the treatment of additional form of epilepsy
Cannabidiol oral solution (Epidiolex) won approval for a new indication and can be used to treat seizures in patients with tuberous sclerosis complex age 1 year and older, the FDA announced on 31 July. Epidiolex is a pharmaceutical formulation of a highly purified oral solution form of cannabidiol (CBD) produced by the UK company GW Pharmaceuticals.
Medpage Today of 3 August 2020

Science/Animal: A high-fat diet increases endocannabinoid levels
In a study with rainbow trouts a high-fat diet increased the levels of 2-arachidonoylglycerol (2-AG) and AEA (anandamide) in blood and certain brain areas.
Facultade de Bioloxía and Centro de Investigación Mariña, Universidade de Vigo, Spain.
Díaz-Rúa A, et al. Horm Behav. 2020:104825.

Science/Human: Oral intake of cannabis reduced cannabis intake by inhalation
In a placebo -controlled study with 128 cannabis users, of whom 64 received the cannabis extract Sativex and 64 a placebo, conducted to investigate the possibility to treat people with cannabis dependence by using the cannabis extract, Sativex reduced the number of days without inhaled cannabis. Authors wrote that the treatment effect “appears to persist for up to 3 months after the cessation of treatment.”
Drug and Alcohol Services, South East Sydney Local Health District, Australia.
Lintzeris N, et al. Drug Alcohol Depend. 2020;215:108220

Science/Human: Cannabis use is not associated with an increased risk of pneumonia in people with HIV
In a study with 2784 HIV-infected men and 2665 HIV-uninfected men followed from 1984-2013 weekly or daily cannabis use was not significantly associated with increased risk of pneumonia in both groups.
Department of Epidemiology, UCLA School of Public Health, Los Angeles, USA.
Quint JJ, et al. Ann Epidemiol. 2020:S1047-2797(20)30278-7.

Science/Cells: Anandamide prevents the adhesion of Candida albicans to cervical cells
In a study with cervical epithelial cells researchers demonstrated that the endocannabinoid anandamide prevented the adhesion of the fungus Candida albicans. They concluded that this endocannabinoid has “potential anti-fungal activities by inhibiting hyphal growth and preventing hyphal adherence to epithelial cells.”
The Faculty of Dental Medicine, The Hebrew University of Jerusalem, Israel.
Sionov RV, et al. Ann Epidemiol. Sci Rep. 2020;10(1):13728.

Science/Cells: Cannabinoids showed anti-toxic effects in nerve cells, which may be beneficial against Alzheimer’s disease
In a study with nerve cells from the hippocampus, a certain brain region, several cannabinoids prevented toxic effects against the combination of reduced oxygen supply and amyloid beta peptide, which is highly present in the brain of patients with Alzheimer’s disease (AD). Authors noted that “all agents tested preserved cell viability and stimulated mitochondrial membrane potential, (…).” And they concluded that this affords “new potential modalities for the design of AD therapies.”
Faculty of Medicine, Department of Medical Pharmacology, Gazi University, Beşevler, Ankara, Turkey.
Elmazoglu Z, et al. Neurochem Int. 2020:104817.

Science/Human: Cannabis use is associated with suicide ideas and behaviour in adolescents at rates similar to tobacco and alcohol
Using data from the US National Youth Risk Behavior Survey scientists found that the association between cannabis use by adolescents and suicidal ideation and attempts was similar to tobacco and alcohol. And they wrote that “frequent alcohol use had a significantly stronger association than other substances.”
Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
Kahn GD, et al. Arch Suicide Res. 2020:1-14.

Science/Human: No effect of long-term use of CBD on cognition in children with epilepsy
In a study with 38 children with epilepsy between the age of 3 and 19 years, who were treated with CBD, the cannabinoid did “not appear to cause adverse effects (AEs) involving cognition or adaptive function over one year of treatment.”
Children's of Alabama, Birmingham, USA.
Thompson MD, et al. Epilepsy Behav. 2020;111:107299.

Science/Animal: About the mechanism, by which THC reduces severity of acute respiratory distress syndrome
In a study with mice scientists found protective effects of THC against enterotoxin-induced acute respiratory distress syndrome and this effect was mediated by modulation of microbiota of the lungs.
University of South Carolina, Columbia, USA.
Mohammed A, et al. Br J Pharmacol. 2020 Aug 4. [in press]

Science/Cells: Different mechanisms of cytotoxic effects of CBD and THC against colon cancer cells
The analysis of cytotoxic effects of cannabinoids “proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms.” While THC effects were mediated by cannabinoid receptors.
Department of Medical and Surgical Sciences and Neurosciences, University of Siena, Italy.
Cerretani D, et al. Int J Mol Sci. 2020;21(15):E5533.

Science/Cells: CBD improves efficacy of chemotherapy endometrial cancer cells
Results of a cell study show that the presence of the vanilloid receptor 2 (TRPV 2) increased malignancy of endometrial cancer tissue. Authors found that “CBD improved chemotherapeutic drugs cytotoxic effects, enhanced by TRPV2 over-expression. “
School of Pharmacy, University of Camerino, Italy.
Marinelli O, et al. Int J Mol Sci. 2020;21(15):E5409.

Science/Human: CBD normalises functional connectivity of nerve cells in epilepsy
In a study with 22 patients with treatment-resistant epilepsy a CBD extract (Epidiolex)
modulated and potentially normalised functional connectivity as seen in magnetic resonance imaging in the epileptic brain. Authors concluded that “this effect may underlie its efficacy.”
University of Alabama at Birmingham, USA.
Nenert R, et al. Epilepsy Behav. 2020;112:107297.

Science/Animal: Activation of CB1 receptors in a certain brain region induces pain relief
In a study with mice researchers demonstrated that activation of the CB1 receptor on GABAergic interneurons in the ventrolateral orbital cortex, a certain brain region, by a synthetic cannabinoid (HU210) produced pain reduction. Before researchers had induced neuropathic pain in these animals. THC is also known to activate the CB1 receptor.
MOE Key Laboratory of Modern Teaching Technology, Center for Teacher Professional Ability Development, Shaanxi Normal University, China.
Yuwei W, et al. Neurosci Lett. 2020:135286.

Science/Animal: CBD and CBDA may be given by dermal application
In a study with 6 dogs, who were treated with a cannabis extract rich in CBD and CBDA (CBD acid) twice-daily, about 10 ng/mL of CBD and 21-32 ng/mL of CBDA were present in blood serum after week 1 and 2 of treatment. Only trace amounts of THC and THCA were found.
Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, USA.
Hannon MB, et al. J Vet Pharmacol Ther. 2020 Jul 31. [in press]

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