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IACM-Bulletin of June 23, 2019


Science China — Oldest evidence for inhalation of cannabis

Cannabis residue has been found in incense burners apparently used during funerary rites at a mountainous site in western China in about 500 BC, providing what may be the oldest evidence of smoking cannabis for its mind-altering properties.

The evidence found on 10 wooden braziers containing stones with burn marks that were discovered in eight tombs at the Jirzankal Cemetery site in the Pamir Mountains in China’s Xinjiang region, scientists said. The tombs also bore human skeletons and artifacts including a type of angular harp used in ancient funerals and sacrificial ceremonies. “We can start to piece together an image of funerary rites that included flames, rhythmic music and hallucinogen smoke, all intended to guide people into an altered state of mind,” the researchers wrote in the study published in the journal Science Advances.

Ren M, Tang Z, Wu X, Spengler R, Jiang H, Yang Y, Boivin N. The origins of cannabis smoking: Chemical residue evidence from the first millennium BCE in the Pamirs. Sci Adv. 2019;5(6):eaaw1391.

Reuters of 12 June 2019

Science/Human — Nabilone improved agitation in patients with Alzheimer’s disease

The synthetic cannabinoid nabilone improved agitation in 39 patients with Alzheimer’s disease. This placebo-controlled study was conducted by scientists of Sunnybrook Research Institute and the University of Toronto, Canada. The 14-week randomized double-blind crossover trial compared nabilone to placebo (6 weeks each) with a 1-week washout between phases. Target daily doses were 1 to 2 mg of nabilone.

The mean nabilone dose was 1.6 mg. There were significant improvements in agitation and caregiver distress. There was more sedation during nabilone (45%) compared to placebo (16%). Authors concluded that nabilone “may be an effective treatment for agitation. However, sedation and cognition should be closely monitored.”

Herrmann N, Ruthirakuhan M, Gallagher D, Verhoeff NPLG, Kiss A, Black SE, Lanctôt KL. Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer’s Disease. Am J Geriatr Psychiatry. 2019 May 8. [in press]

Science/Human — Cannabis users have lower mortality following pancreatitis

In an analysis of 2.8 million patients with acute pancreatitis cannabis users had a significantly lower risk of death. This is the result of scientists of the Department of Medicine at the Leonard M. Miller School of Medicine of the University of Miami, USA. The National Inpatient Sample database from 2003 to 2013 was queried for all patients with acute pancreatitis and active exposure to cannabis.

More than 2.8 million patients with patients suffering from acute pancreatitis were analyzed. Cannabis-exposed patients’ prevalence was 0.3%. Cannabis users had significantly lower inpatient mortality compared with the noncannabis group (odds ratio: 0.17). Cannabis-exposed patients also had decreased length of stay, inflation-adjusted charges, acute kidney injury, ileus, shock, acute respiratory distress syndrome, and parenteral nutrition requirement.

Simons-Linares CR, Barkin JA, Jang S, Bhatt A, Lopez R, Stevens T, Vargo J, Barkin JS, Chahal P. The Impact of Cannabis Consumption on Mortality, Morbidity, and Cost in Acute Pancreatitis Patients in the United States: A 10-Year Analysis of the National Inpatient Sample. Pancreas. 2019;48:850-855.

Science/Human — A metered dose inhaler for cannabis showed promising results in a pilot study

The use of a new vaporiser, Syqe inhaler, during hospitalisation of cannabis patients yielded high levels of patients and staff satisfaction with no complications. The study was conducted by scientists from the Faculty of Medicine of the Israel Institute of Technology in Haifa, Israel. Patients suffering from different symptoms, including chemotherapy-induced nausea and vomiting, spasticity and pain, received four daily doses of 0.5 mg THC delivered from 16 mg cannabis flowers per inhalation.

Mean daily cannabis dose during hospitalisation was 51 mg (range: 20-96 mg) compared to 1000 mg (range: 660-3300) before hospitalisation. Pain intensity 30-60 minutes following inhalations (pain intensity of 4 on a scale from 0 to 10) was reported to be significantly lower than before inhalation (pain intensity of 7) . Participants ranked their satisfaction with Syqe Inhaler as 6 (range: 5-7).

Vulfsons S, Ognitz M, Bar-Sela G, Raz-Pasteur A, Eisenberg E. Cannabis treatment in hospitalized patients using the SYQE inhaler: Results of a pilot open-label study. Palliat Support Care. 2019 Jun 14:1-6.

Science/Human — Cannabis was effective in the treatment of fibromyalgia in an observational study

In an observational study with 367 fibromyalgia patients the use of cannabis resulted in effective pain reduction in most participants. The study was conducted by researchers at the Ben-Gurion University of the Negev, Be’er-Sheva, Israel. Patients were treated in a specialised medical cannabis clinic between 2015 and 2017 and followed for 6 months.

Twenty eight patients (7.6%) stopped the treatment prior to the six months follow-up. The six months response rate was 70.8%. Pain intensity reduced from a median of 9.0 at baseline to 5.0, and 194 patients (81.1%) achieved treatment response. Authors concluded that “medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms.”

Sagy I, Bar-Lev Schleider L, Abu-Shakra M, Novack V. Safety and Efficacy of Medical Cannabis in Fibromyalgia. J Clin Med. 2019 Jun 5;8(6).

Russia — Parliament passed a law allowing the cultivation of cannabis

Russian parliament has passed a law that would allow the cultivation of psychoactive plants, including cannabis and opium poppies, for pharmaceutical purposes. The move aims to cover the country's needs for painkillers.

According to bitte mittlerweile haben wir ganz Gutsystem für die Rezepte noch ich mittlerweile ziemlich sicheres gutes System für die Rezepte würde er Herr a document from the Russian government attached to the law, there are 13 opium-based drugs registered in Russia that are being produced by state companies from imported ingredients. Nine of these drugs are included in the list of lifesaving and most important medications. Finding replacements for painkillers is important for the country's national security, and that's why it's necessary to set up the entire production cycle of psychotropic and narcotic substances, including growing the plants containing their ingredients, according to the Russian government.

Benzinga of 19 June 2019

France — Medical cannabis experiment will start soon

As a nearly unanimous French Senate gave medical cannabis the green light on May 28, France will start experimenting the use of medical cannabis for “about two years”, pending the approval of the health ministry. Therapeutic cannabis may soon be legally available in France to hundreds of thousands of patients.

“There will be about two years of experimentation with therapeutic cannabis, beginning as soon as the health ministry gives the green light,” Professor Nicolas Authier, the head of pharmacology at Clermont-Ferrand University Hospital Centre’s pain clinic, said. Authier heads the committee of experts charged by the National Agency for the Safety of Health Products of evaluating the practical arrangements for the distribution of medical cannabis . The committee’s report will be released on June 26.

France24 of 2 June 2019

Science/Human — Cannabis is effective as add-on treatment in severe chronic pain according to an analysis of the German Pain Registry

According to an exploratory analysis of anonymized 12-week open-label data provided by the German Pain e-Registry add-on treatment with the cannabis spray Sativex was effective and well-tolerated. Data were analysed by scientists of the Institute of Neurological Sciences in Nuernberg, Germany, and other German institutions.

Among that 30.228 cases documented in the database in 2017, 800 (2.6%) received a treatment with Sativex containing THC and CBD in a ratio of about 1:1. Authors found a significant treatment effect. Improvement was significantly superior in the neuropathic pain subgroup compared with mixed or nociceptive pain. Authors concluded that the cannabis spray “proved to be an effective and well-tolerated add-on treatment for patients with elsewhere refractory chronic pain - especially of neuropathic origin.”

Ueberall MA, Essner U, Mueller-Schwefe GH. Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-Registry. J Pain Res. 2019;12:1577-1604.

Science/Human — CBD was effective in the treatment of epileptic encephalopathy

In an open study with 29 patients suffering from developmental and epileptic encephalopathy (DEE) CBD had beneficial effects. The study was conducted at the Children’s Hospital of the IRCCS in Rome, Italy. Participants were aged 1 to 18 years and suffered from intractable seizures. They did not respond to standard antiepileptic drugs, vagal nerve stimulation and ketogenic diet. They received pure CBD in a solution at a starting dose of 2-5 mg/kg per day in 2 doses, which was titrated until a maximum dose of 25 mg/kg per day.

Mean age at beginning of the study was 9.3 years (range: 2-16 years). Patients received CBD for a mean duration of 11.2 months. Eleven out of 29 patients (37.9%) had an improvement in seizure frequency by 50% or more. One patient became seizure free. None of the patients reported worsening seizure frequency. Adverse effects were reported in seven patients, most commonly somnolence, decreased appetite and diarrhea.

Pietrafusa N, Ferretti A, Trivisano M, de Palma L, Calabrese C, Carfì Pavia G, Tondo I, Cappelletti S, Vigevano F, Specchio N. Purified Cannabidiol for Treatment of Refractory Epilepsies in Pediatric Patients with Developmental and Epileptic Encephalopathy. Paediatr Drugs. 2019 Jun 10. [in press]

News in brief

Colombia — Constitutional Court overrules a ban on consumption of cannabis in public

Colombia’s Constitutional Court overruled a ban on the consumption of drugs and alcohol in public, one of the key elements of the government’s anti-drug policy. According to the court, the police code that came to force in 2017 and became a pillar of President Ivan Duque‘s anti-drug policy last year is in violation of Colombians’ constitutional rights. Citizens will continue to be allowed to use drugs and alcohol in public.

Colombian Reports of 7 June 2019

Cyprus — Government paves the way for granting three licences for the cultivation of cannabis

A committee tasked with evaluating applicants for licences to cultivate medical cannabis is to be set up, the cabinet agreed. Under the law passed in February regulating the cultivation and distribution of medical cannabis, the committee will process the submitted applications and select the three to whom a licence will be granted.

Cyprus Mail of 5 June 2019

Science/Human — Long-term use of CBD does not alter cognitive performance

In an open long-term study with 27 adults, who received high doses of CBD (mean dose: 36.5 mg/kg per day) due to epilepsy, there was no effect on cognitive performance.

University of Alabama at Birmingham, Department of Neurology, Birmingham, USA.

Martin RC, et al. Epilepsy Behav. 2019;97:105-110.

Science/Human — Dramatic improvement by a combination of laetrile and CBD in ovarian cancer

A 81-year-old woman with metastatic ovarian cancer responded well to a treatment with high doses of Laetrile tablets and low doses of cannabidiol. She started treatment in May 2017 and continued to show improvements in December 2018. Authors wrote: “She is clinically asymptomatic with a performance status of 0, which is unchanged from her performance status at time of diagnosis.”

University of California San Diego Moores Cancer Center, La Jolla, USA.

Barrie AM, et al. Gynecol Oncol Rep 2019;29:10-12.

Science/Animal — Activation by the CB2 receptor improves memory in aged mice

In a study with mice aged 3, 12, and 18 months treatment with beta-caryophyllene, which activates the CB2 receptor, reduced blood levels of pro-inflammatory substances (cytokines) and improved working memory.

Mercer University College of Pharmacy, Mercer University Health Sciences Center, Atlanta, USA.

Lindsey LP, et al. Behav Brain Res. 2019;372:112012.

Science/Animal — CBD shows anti-depressant effects in mice

in a mouse model of depression infusion of 10 mg CBD per kilogram bodyweight showed significant antidepressant effects.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Xu C, et al. Environ Toxicol Pharmacol. 2019;70:103202.

Science/Animal — CBD inhibits sugar self-administration

In a study with rats CBD reduced self-administration of sucrose and this effect was mediated likely by antagonism at the CB1 receptor and activation of the CB2 receptor.

National Institute on Drug Abuse, Baltimore, USA.

Bi GH, et al. Addict Biol. 2019 Jun 19:e12783.

Science/Animal — Cannabis extracts were effective in an animal model of multiple sclerosis

In an animal model of multiple sclerosis cannabis extracts with different ratios of THC and CBD improved neurological disability and reduced the concentration of a pro-inflammatory cytokine (tumour necrosis factor alpha).

College of Medicine, University of Manitoba, Winnipeg, Canada.

Zhou T, et al. Biochem Biophys Res Commun. 2019 Jun 15. [in press]

Science/Human — Cannabis may be helpful in children undergoing chemotherapy

In a cancer centre 103 children and young adults with cancer received cannabis for the management of symptoms, mostly against chemotherapy-related nausea, pain and cachexia. Authors wrote, that “pediatric and young adult oncology patients are interested in medical cannabis to help manage treatment-related symptoms.”

Division of Pediatric Hematology-Oncology, Children’s Minnesota, USA.

Skrypek MM, et al. Children (Basel). 2019;6(6).

Science/Human — CBD may increase the blood level of brivaracetam

In a case series of 5 patients with epilepsy receiving CBD in addition to brivaracetam, the cannabinoid increased the level of brivaracetam by 95% to 280%, which needed a reduction of brivaracetam dose.

Faculty of Medicine, University of Freiburg, Germany.

Klotz KA, et al. Epilepsia. 2019 Jun 18. [in press]

Science/Animal — Cannabinoids induce reduction of CB1 receptors in the retina

Endogenous and synthetic cannabinoids reduced the number of CB1 receptors in the retina of rats.

School of Medicine, University of Crete and Foundation for Research and Technology, Heraklion, Crete, Greece.

Papadogkonaki S, et al. Exp Eye Res. 2019 Jun 11:107694.

Science/Cells — CBD reduces development of resistance to a chemotherapeutic agent

CBD reduces the development of resistance to the chemotherapeutic agent oxaliplatin, which is used for the treatment of colorectal cancer. Scientists investigated the reason for this action, which makes oxaliplatin more effective.

Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.

Jeong S, et al. Cancers (Basel). 2019 Jun 5;11(6).

Science/Cells — Activation of the CB2 receptor may reduce survival of non-small-cell lung cancer cells

In a study with non-small-cell lung cancer cells researchers found an increased level of CB2 receptors. Activation of these cannabinoid receptors decreased proliferation, migration and invasion abilities and induced apoptosis (programmed cell death).

The Second Hospital of Shandong University, Jinan, China.

Xu S, et al. Biomed Pharmacother. 2019;117:109080.

Science/Human — War veterans substitute alcohol and medicinal drugs by cannabis

In a survey with 93 US military veterans with access to legal cannabis most of them reported using cannabis as a substitute for alcohol, tobacco, prescription medication or illicit substances usually in a dose of 5 to 8 g per week.

VA San Diego Healthcare System, San Diego, USA.

Loflin MJE, et al. Am J Drug Alcohol Abuse. 2019 May 28:1-8.