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IACM-Bulletin of 03 February 2019

World: The World Health Organisation accepts the medical value of cannabis and cannabinoids

In a letter of 24 January to the Secretary-General of the United Nations, Antonio Guterres, the Director-General of the WHO, Dr Tedros Adhanom Ghebreyesus, informed the UN about suggested changes within the international Drug Conventions. These suggestions followed meetings of the WHO Expert Committee on Drug Dependence (ECDD) in June and November 2018.

WHO acknowledges the therapeutic potential of cannabis and cannabinoids and changes its position from 1954 according to which "there should be efforts towards the abolition of cannabis from all legitimate medical practice." The new international scheduling proposed by the WHO provides an increased possibility for countries to provide legal and safe access to the medical use of cannabis and to research into its medical value. Now 53 UN countries have to approve these WHO recommendations, thus amending the Convention’s schedules if the simple majority vote, that is 27 countries, is positive. Initially planned for March 2019, it is entirely possible that the 2-months delay in the publication of the results postpones the vote until March 2020.

Letter by WHO to the UN of 24 January 2019
Press release by FAAAT of 1 February 2019

Science/Human: The legalisation of medical cannabis in the USA is associated with lower opioid use

According to an analysis of 4.8 million persons in the United States living in a state with legal access to cannabis for medicinal purposes was associated with a significant reduction of opioid use. Scientists of Pharmerit International in Bethesda, USA, published results of their study in the Journal of General Internal Medicine. A 10% sample of a nationally representative database of insured population was used to gather information on opioid use, chronic opioid use, and high-risk opioid use for the years 2006-2014.

Medical cannabis legalization was found to be associated with a lower probability of any opioid use by 5%, regular opioid use by 7% and high-risk opioid use by 4%. Authors concluded that “in states where marijuana is available through medical channels, a modestly lower rate of opioid and high-risk opioid prescribing was observed. Policy makers could consider medical marijuana legalization as a tool that may modestly reduce chronic and high-risk opioid use.”

Shah A, Hayes CJ, Lakkad M, Martin BC. Impact of Medical Marijuana Legalization on Opioid Use, Chronic Opioid Use, and High-risk Opioid Use. J Gen Intern Med. 2019 Jan 25. [in press]

Science/Human: Cannabis may be helpful in autism

In a study with 53 children suffering from autism about two third profited from a treatment with a cannabis extract high in CBD and low in THC. Authors from the Clinical Pharmacology and Toxicology Unit of Assaf Harofeh Medical Center in Tel Aviv, Israel, published their results in Frontiers in Pharmacology. The median age was 11 (range: 4 to 22) years. They received a cannabis extract with a CBD:THC ratio of 1 to 20. The median dose of THC was 7 mg (range: 4 to 11 mg) and of CBD 90 mg (45 to 143 mg). Median duration of therapy was 66 days (3-588 days

Self-injury and rage attacks improved in 68% and worsened in 9%. Hyperactivity symptoms improved in 68%, did not change in 29% and worsened in 3%. In a comment Dr Franjo Grotenhermen, Executive Director of the IACM, noted, that the denomination of the extract as CBD OIL is misleading. “I have seen several patients with autism in my medical practice profiting alone from THC, while I’ve never seen a patient with autism significantly profiting alone from CBD,” he noted. “These children received a normal and effective THC dose in the range of about 5 to 10 mg and only a moderate CBD dose. Thus, I have the impression that study participants may have profited mainly from THC and less from CBD.”

Barchel D, Stolar O, De-Haan T, Ziv-Baran T, Saban N, Fuchs DO, Koren G, Berkovitch M. Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities. Front Pharmacol. 2019;9:1521.

Science/Human: Cannabis may be highly effective in the self-management of endometriosis according to survey

According to a survey with 484 women with endometriosis living in Australia cannabis was highly effective in pain reduction. Results of the study by scientists of NICM Health Research Institute of Western Sydney University, Australia, were published in BMC Complementary and Alternative Medicine. An online survey was distributed via social media. Women were eligible to answer the survey if they were 18-45, lived in Australia, and had a confirmed diagnosis of endometriosis.

The most common forms of self-management strategies used were heat (70%), rest (68%), and meditation or breathing exercises (47%). Cannabis, heat, HEMP/CBD OIL, and dietary changes were the most highly rated in terms of self-reported effectiveness in pain reduction. Physical interventions such as yoga/Pilates, stretching, and exercise were rated as being less effective. Authors wrote that “women using cannabis reported the highest self-rated effectiveness.”

Armour M, Sinclair J, Chalmers KJ, Smith CA. Self-management strategies amongst Australian women with endometriosis: a national online survey. BMC Complement Altern Med. 2019;19(1):17.

Science/Human: Medical cannabis users reduce their intake of benzodiazepines

According to an analysis of 146 medical cannabis patients, who used benzodiazepines, 30% discontinued the use of these drugs within 2 months. Researchers of Dalhousie University Faculty of Medicine, Canada, published their research in the IACM partner journal Cannabis and Cannabinoid Research.

Average age was 47 years, 61% female, and 54% reported prior use of cannabis. After completing an average 2-month prescription course of medical cannabis, 30.1% of patients had discontinued benzodiazepines. At a follow-up after two prescriptions, 65 total patients (44.5%) had discontinued benzodiazepines. At the final follow-up period after three medical cannabis prescription courses, 66 total patients (45.2%) had discontinued benzodiazepine use, showing a stable cessation rate over an average of 6 months.

Purcell C, Davis A, Moolman N, Taylor SM. Reduction of Benzodiazepine Use in Patients Prescribed Medical Cannabis.
Cannabis Cannabinoid Res. 2019 Jan 24. [in press]

Science/Human: Low doses of CBD increased psychedelic effects of THC and high CBD doses reduced these effects

In a placebo-controlled study with 36 healthy cannabis users concomitant inhalation of low CBD doses together with THC increased psychedelic effects of THC, while high doses of CBD reduced these effects. Researchers at the School of Psychology and Illawarra Health and Medical Research Institute of the University of Wollongong, Australia, published their data in the EURopean Archives of Psychiatry and Clinical Neuroscience. Participants inhaled placebo versus CBD alone (400 mg), THC alone (8 mg) versus THC combined with low (4 mg) or high (400 mg) doses of CBD.

Objective (blind observer ratings) and subjective (self-rated) measures of intoxication differed. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users.

Solowij N, Broyd S, Greenwood LM, van Hell H, Martelozzo D, Rueb K, Todd J, Liu Z, Galettis P, Martin J, Murray R, Jones A, Michie PT, Croft R. A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects. EUR Arch Psychiatry Clin Neurosci. 2019 Jan 19. [in press]

News in brief

Germany: The government will select producers for medical cannabis
The government has accepted bids for supply contracts from 79 prospective cannabis growers as the country seeks to develop its own medicinal cannabis industry and reduce reliance on imports from Canada and the Netherlands. The country’s drugs regulator BfArM said on 28 January it aimed to select growers between April and June, for a total cannabis procurement volume of 10,400 kg over four years.
Reuters of 28 January 2019

Thailand: The country revoked foreign patents requests for the use of cannabis
On 28 January Thailand effectively revoked all foreign patent requests for the use of cannabis after fears foreign firms would dominate a market thrown open in December 2018 when the government approved the drug for medical use and research. Civil society groups and researchers feared domination by foreign firms could make it harder for Thai patients to get access to medicines and for Thai researchers to get cannabis extracts.
Reuters of 28 January 2019

Israel: Government allows export of medical cannabis
On 27 January Israel’s government approved a law to allow exports of medical cannabis in a move expected to boost state revenues and the agriculture sector. Israeli companies - benefiting from a favourable climate and expertise in medical and agricultural technologies - are among the world’s biggest producers of medical cannabis. Eight companies cultivate cannabis in Israel, many of which have opened farms abroad to get into the international market.
Reuters of 27 January 2019

Philippines: The House of Representatives approves a bill in favour of medical cannabis
The House of Representatives has achieved a historical milestone after the chamber voted in favour of the proposed legalization of medical cannabis in the country. During the plenary proceedings of 29 January, a total of 163 lawmakers voted for the approval of the “Philippine Compassionate Medical Cannabis Act” and 5 voted against.
Politiko of 29 January 2019

Science/Human: Cannabis patients reduce the use of other medicinal drugs and alcohol
In a survey with 2032 medical cannabis patients from Canada 69% reported a substitution for prescription drugs, followed by alcohol (45%), tobacco (31%) and illicit substances (27%). Opiate medications accounted for 35% of all prescription drugs, followed by antidepressants (22%).
Social Dimensions of Health, University of Victoria, Canada.
Lucas P, et al. Harm Reduct J. 2019;16(1):9.

Science/Human: Legalisation of cannabis for adult use is associated with reduced opioid use in the USA
The number of prescriptions and total doses of opioids were reduced in states, which legalised the use of cannabis by adults. In models comparing eight states and Washington DC, legalization was not associated with the prescription of Schedule II opioids (e.g. oxycodone), but with the reduction of prescriptions and total dosing of Schedule III opioids (e.g. codeine) by about 30%.
Department of Family Medicine and Public Health, University of California in San Diego, USA.
Shi Y, et al. Drug Alcohol Depend. 2019;194:13-19.

Science/Human: Cannabis may be an effective pain reliever and substitute for opioids according to a survey
According to a survey from the USA with 1321 participants, who suffered from chronic pain, 53% substituted cannabis for opioids and 22% for benzodiazepines.
Anesthesiology Department, University of Michigan Medical School, USA.
Boehnke KF, et al. J Pain. 2019 Jan 25. [in press]

Science/Animal: CBD may induce programmed cell death in malignant melanoma cells
In a study with mice with malignant melanoma a significant decrease in tumour size was detected in animals treated with CBD. Cisplatin, a standard medication against cancer, was more effective, but quality of life of animals treated with CBD was better.
Augusta University Medical Center, USA.
Simmerman E, et al. J Surg Res. 2019;235:210-215.

Science/Animal: How CBD causes death of cancer cells
In a study with cancer cells of the colon CBD caused apoptosis (programmed cell death) by regulating many proteins relevant for apoptosis. The so-called Noxa protein showed high expression after administration of CBD and reactive oxygen species (ROS) increased. Authors concluded that “CBD induced apoptosis in a Noxa-and-ROS-dependent manner.”
Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea
Jeong S, et al. Cancer Letters. 2019;447:12-23.

Science/Human: Cannabis may have negative effects on cancer therapy if given together with immunotherapy
In an analysis of 140 patients in Israel, of whom 89 received only the immunotherapeutic agent involumab and 51 involumab and cannabis, cannabis reduced the response rate to immunotherapy without affecting overall survival. Authors concluded that “although the data are retrospective and a relation to cannabis composition was not detected, this information can be critical for cannabis users and indicates that caution is required when starting immunotherapy.”
Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
Taha T, et al. Oncologist. 2019 Jan 22. [in press]

Science: Considerable increase of THC concentration in cannabis in the USA and EURope within the past 10 years
Mean THC concentrations in cannabis nearly doubled within 10 years in the USA, and increased from 9% in 2008 to 17% in 2017. There were also considerable increases of THC concentrations in hashish OIL. Other potency monitoring programs in several EURopean countries documented increases in THC concentrations in cannabis products.
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, USA.
Chandra S, et al. EUR Arch Psychiatry Clin Neurosci. 2019 Jan 22. [in press]

Science/Human: In driving simulator tests 3 hours after cannabis consumption there were no longer significant faults
In a driving simulator study with 15 regular cannabis users, who received cannabis cigarettes containing 0.3 mg THC per kg bodyweight, equivalent to 21 mg for a person with 70 kg, THC concentrations of more than 15 ng/mL in blood serum increased the number of faults. Three hours after consumption no significant increases of faults were seen.
Institute of Legal Medicine, University Hospital Düsseldorf, Germany.
Tank A, et al. Int J Legal Med. 2019 Jan 30. [in press]

Science/Animal: Lacking of cannabinoid receptors protects mice from obesity
In a study with genetically modified mice without cannabinoid receptors the animals were protected from diet-induced obesity despite no differences in food intake compared to wild-type mice.
Department of Family Medicine, Michigan State University, USA.
Alshaarawy O, et al. Obesity (Silver Spring). 2019 Jan 30. [in press]

Science/Human: Many young children are admitted to hospitals due to accidental cannabis ingestion
Particularly oral products with high THC concentrations (edibles, resins, vaping fluids), which are ingested by young children may lead to sedation, respiratory depression and other adverse effects.
Department of Emergency Medicine, University of Massachusetts Medical School, USA.
Blohm E, et al. Curr Opin Pediatr. 2019 Jan 28. [in press]

Science/Animal: Cannabis use during adolescence may be harmful to the brain
Ingestion of THC by adolescent rats had negative effects on cognition in adulthood. Some detrimental effects disappeared over time.
Centre for Addiction and Mental Health, Toronto, Canada.
Abela AR, et al. Psychopharmacology (Berl). 2019 Jan 29. [in press]

Science/Cells: A compound of HEMP seeds may reduce inflammation
In a study with microglia cells cannabisin F, a lignanamide of HEMP seed, suppressed the production of pro-inflammatory mediators, including interleukin 6 and tumour necrosis factor alpha. Researchers concluded that the substance has neuroprotective properties.
School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Wang S, et al. Int J Mol Sci. 2019;20(3).

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