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IACM-Bulletin of 17 February 2019

Europe: EURopean Parliament supports a resolution on the medical use of cannabis-based medicines

Following reports about the World Health Organization (WHO) recommending a rescheduling of cannabis and several of its key components under international drug treaties, on 13 February the EURopean Parliament adopted a resolution that would help advance the use of cannabis-based medicines in the countries of the EURopean Union.

While non-binding, the resolution seeks to incentivize EURopean nations to increase access to medical cannabis, prioritizing scientific research and clinical studies. The resolution focuses on standardised cannabis-based medicines but “forgetting” cannabis flowers. Same as the WHO’s recommendation, the EURopean Parliament’s resolution does not change any actual laws on the international or local levels.

European Parliament on medical cannabis
Forbes of 13 February 2019

IACM: Statement on Medical Cannabis to Members of the EURopean Parliament

Before the vote on a resolution on the medical use of cannabis and cannabinoids in the EURopean Parliament EURopean members of the IACM Board of Directors delivered a statement to MEPs. Among others the statement says: “For many years scientists and doctors thought that cannabis is more or less a plant, which exerts its effects by THC and a little bit by CBD. That is what many scientists and doctors still think today. But this is an error, an incorrect simplification of the reality. (…) Cannabis is a rich source of treatment possibilities. As clinicians we do not want to miss all the possibilities that this plant is offering to us and our colleagues to bring this whole richness to our patients. (…)

We understand that the EURopean Parliament would like to ease the access to cannabis and cannabinoids for medicinal purposes. And we heartily welcome these efforts. We think that EURopeans should have access to the best medical treatments. Please allow doctors and patients to profit from the broad spectrum of the therapeutic effects of the cannabis plant. Please do not limit these treatment options to a few.”

The statement was signed by Franjo Grotenhermen (Germany), Manuel Guzmán (Spain), Kirsten R. Müller-Vahl (Germany), Roger G. Pertwee (UK), Ethan Russo (Czech Republic).

Statement by the IACM Board

Science/Human: Chronic pain is the main reason for the medical use of cannabis in the USA

More than 60 percent of people in the US who use medical cannabis want to relieve chronic pain, according to a study published February in Health Affairs. "We did this study because we wanted to understand the reasons why people are using cannabis medically and whether those reasons for use are evidence-based," Kevin Boehnke, a research investigator in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center at University of Michigan in Ann Arbor, USA, said in a news release.

The study included data on medical cannabis license holders in 20 states. More than 60 percent of them said they were seeking relief for "an evidence-based" chronic condition. Those include chronic pain, nausea and vomiting brought on by chemotherapy.

Boehnke KF, Gangopadhyay S, Clauw DJ, Haffajee RL. Qualifying Conditions Of Medical Cannabis License Holders In The United States. Health Aff (Millwood). 2019;38(2):295-302.
UPI of 5 February 2019

Science/Human: Cannabis may be helpful in anxiety disorders according to large survey

In a survey completed by 2032 patients, of whom 888 reported authorisation of cannabis for medicinal purposes nearly half reported replacing a standard medication by cannabis. Scientists of Neuroscience Graduate Program at McMaster University in Hamilton, Canada, wrote that the “vast majority perceived symptom improvement” by cannabis.

Rates of probable disorders were high (Generalized Anxiety Disorder: 46%, Social Anxiety Disorder: 42%, Major Depressive Disorder: 26%, Panic Disorder/Agoraphobia: 26%). 63% met screening criteria for more than one disorder. Most (92%) reported that cannabis improved their symptoms, despite continuing to endorse moderate-level severity. Nearly half (49%) reported replacing a non-psychiatric (53.7%) or psychiatric medication (46.3%) prescribed to them by their physician with cannabis.

Turna J, Simpson W, Patterson B, Lucas P, Van Ameringen M. Cannabis use behaviors and prevalence of anxiety and depressive symptoms in a cohort of Canadian medicinal cannabis users. J Psychiatr Res. 2019;111:134-139.

Science/Animal: Cannabis extracts were more effective than THC or CBD alone in reducing severe side effect of bone marrow transplantation

In an animal model of graft-versus-host disease (GVHD) pure THC and pure CBD reduced this possible severe side effect of bone marrow transplantation. However, “THC-high and CBD-high cannabis extracts treatment reduced the severity of GVHD and improved survival significantly better than the pure cannabinoids.” This is the result of research at Hadassah Medical Center of Hebrew University of Jerusalem, Israel.

Authors concluded that our “results highlights the complexity of using cannabinoids-based treatments and the need for additional comparative scientific results.”

Khuja I, Yekhtin Z, Or R, Almogi-Hazan O. Cannabinoids Reduce Inflammation but Inhibit Lymphocyte Recovery in Murine Models of Bone Marrow Transplantation. Int J Mol Sci. 2019;20(3).

News in brief

World: World Health Organisation publishes report on cannabis
The WHO makes available the report by its Expert Committee on Drug Dependence (ECDD) of 2018.
WHO report on cannabis

Science/Human: Cannabis use was associated with higher sperm concentration
According to an analysis of 662 men, those who had ever used cannabis (365 participants) had higher sperm concentrations (63 million/ml) than 297 participants, who had never used cannabis (45 million/ml). There was no difference between past and current cannabis users. Cannabis users also had higher total sperm count.
Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, USA.
Nassan FL, et al. Hum Reprod. 2019 Feb 6. [in press]

Science/Human: THC may reduce night sweats in cancer patients
According to five case reports oral THC reduced night sweats in cancer patients. Researchers analysed data of cancer patients treated between 2013 and 2016. They found that treatment with oral THC “resulted in the successful management of persistent symptomatic paraneoplastic night sweats.”
School of Nursing, San Francisco State University, San Francisco, California, USA.
Carr C, et al. J Palliat Med. 2019 Feb 13. [in press]

Science/Human: Many families use cannabis oil for their children in British hospices
According to a survey in children’s hospices in the United Kingdom 87.5 % of hospices knew of children, who use cannabis oil. Authors concluded, that cannabis oil “is used extensively by children who use children's hospices. Despite recognizing the use of CO, many hospices are unable to support it.”
Martin House Children's Hospice, Wetherby, UK.
Tatterton MJ, et al. J Palliat Med. 2019 Feb 4. [in press]

Science/Human: CBD showed long-term efficacy in the treatment of epilepsy due to Lenox-Gastaut syndrome
Long-term follow-up of 366 patients with Lenox-Gastaut syndrome treated with CBD with a treatment duration of 38 weeks and a mean dose of 23 mg/kg bodyweight showed persistent efficacy of the treatment. Median reduction in monthly total seizure frequency ranged from 48% to 57%. Most patients experienced adverse events, which were mild or moderate. The most common were diarrhoea (27%), somnolence (24%) and convulsion (21%).
Massachusetts General Hospital, Boston, USA.
Thiele E, et al. Epilepsia. 2019 Feb 11. [in press]

Science/Human: Cannabis use may produce a protective effect against weight gain in psychosis
In a group of patients with first-episode psychosis cannabis users at baseline presented with lower weight, body mass index and cholesterol compared to non-users. This difference persisted over a period of 3 years.
Department of Psychiatry, University Hospital Marqués de Valdecilla-Instituto Investigación Sanitaria Valdecilla, Santander, Spain.
Vázquez-Bourgon J, et al. J Psychopharmacol. 2019 Jan 31:269881118822173.

Science/Human: CBD may increase the effects of chemotherapy and radiation in glioblastoma according to case reports
Researchers presented two cases, where CBD may have improved the effect of chemotherapy and radiotherapy in glioblastoma, a very aggressive brain tumour.
Department of Neuro-Oncology, Sirio Libanes Hospital, São Paulo, Brazil.
Dall'Stella PB, et al. Front Oncol. 2019;8:643.

South Africa: Less than 60 people have legal access to cannabis
There are 56 individuals in South Africa who are legally using cannabis-containing medicine they import, the health-products regulator says. 20 companies are in the process of being licensed for cannabis products.
Business Insider of 6 February 2019

Ukraine: Health Minister endorses access to cannabis for medicinal purposes
Ulyana Suprun, Health Minister of Ukraine urges for the legalization of medical cannabis in Ukraine. She claims that access to certain medications based on this plant would help implement right of patients for medical assistance.
112 UA of 31 January 2019

Science/Human: Children with autism have lower blood levels of endocannabinoids
An analysis of blood concentrations of endocannabinoids in 93 children with autism spectrum disorder (mean age: 13 years) showed that they had lower levels of the endocannabinoids anandamide, palmitoylethanolamine and oleamide compared to healthy children.
Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
Aran A, et al. Mol Autism. 2019;10:2.

Science/Cells: CBD may induce programmed cell death in neuroblastoma
New research shows that CBD may induce apoptosis (programmed cell death) through activation of serotonin and vanilloid receptors. CBD also significantly reduced migration of these cancer cells. Neuroblastoma is one of the most common childhood cancers.
University of South Carolina School of Medicine, Columbia, USA.
Alharris E, et al. Oncotarget. 2019;10(1):45-59.

Science/Animal: Analgesic effects of ketamine involves the activation of the CB1 receptor
Animal studies with mice show, that central pain relieving effects of ketamine involves the activation of the cannabinoid-1 receptor and increase of the concentration of the endocannabinoid anandamide potentiated the effects of ketamine.
Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil.
Pacheco DDF, et al. Neurosci Lett. 2019;699:140-144.

Science/Animal: Synergistic action of cannabinoid receptors and serotonin receptors in epilepsy
In rats treated with a convulsant agent (pilocarpine) resulting in status epilepticus activation of both the CB1 receptor and the serotonin receptor increased their antiepileptic efficacy.
Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
Colangeli R, et al. Neurobiol Dis. 2019;125:135-145.

Science/Cells: Cannabinoids may reduce cell viability in cancer of the bowel
Researchers screened 370 cannabinoid-like compounds with regard to their anti-cancer effects against colorectal cancer. They found 10 compounds, which were able to reduce viability of these cancer cells. THC and CBD were much more less effective.
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, USA.
Raup-Konsavage WM, et al. Cannabis Cannabinoid Res. 2018;3(1):272-281.

Science/Cells: Activation of the vanilloid receptor 1 reduced inflammation in microglial cells
Activation of the vanilloid type 1 receptor reduced the release of pro-inflammatory cytokines (tumour necrosis factor alpha and interleukin-6) from microglial cells. Authors wrote that their “results indicate that TRPV1 influences central inflammation in MS by regulating cytokine release by activated microglial cells.”
Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Pozzilli, Italy.
Stampanoni Bassi M, et al. Front Neurol. 2019;10:30.

Science/Human: No hint of efficacy of CBD in autism
Researchers investigated the effects of one single oral dose of 600 mg CBD or placebo on brain physiology of 34 men, of whom 17 suffered from autism spectrum disorder. They concluded that their “results do not speak to the efficacy of CBD.”
King's College London, London, UK.
Pretzsch CM, et al. Neuropsychopharmacology. 2019 Feb 6. [in press]

Science/Cells: The HER2 receptor in breast cancer interacts with the CB2 receptor
HER2-positive breast cancers are often difficult to treat. Researchers show that the HER2 receptor interacts physically with the cannabinoid-2 receptor in breast cancer cells. They suggest that their findings define these receptors as potential targets for anti-cancer therapies.
Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain.
Blasco-Benito S, et al. Proc Natl Acad Sci U S A. 2019 Feb 7. [in press]

Science/Cells: The cannabinoid-2 receptor plays a role in systemic lupus erythematosus
Researchers found a possible new role of the cannabinoid receptor 2 in systemic lupus erythematosus, a systemic autoimmune disease, by using the endocannabinoid 2-AG (2-arachidonoylglycerol).
Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, Kolkata, West Bengal, India.
Rahaman O, et al. J Immunol. 2019 Feb 6. [in press]

Science/Cells: CBD influences the blood-brain barrier
In studies with human brain microvessel endothelial cells, which form the blood-brain barrier (BBB), researchers found that CBD induces proliferation and migration of these cells “suggesting CBD might be a potent target for modulating the human BBB.”
Université Paris Descartes, Paris, France.
Luo H, et al. Mol Pharm. 2019 Feb 5. [in press]

Science/Animal: Depression in an animal model is associated with decreased endocannabinoid levels
In a rat model of depression, the so-called Flinders Sensitive Line, researchers found a lower content of the endocannabinoid 2-AG in the left side of the hippocampus and prefrontal cortex compared to a control group of rats. In blood the concentration of the endocannabinoid anandamide was increased and of 2-AG decreased. There were also other changes of the endocannabinoid system in these rats. Researchers suggest that these changes “could contribute to the depressive -like behavior.”
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Denmark.
Kirkedal C, et al. Neurochem Int. 2019 Feb 1;125:7-15.

Science/Cells: Cannabinoids may influence glioblastoma cell invasion
In a study with glioblastoma cells and slice cultures of the hippocampus cannabinoids reduced invasion of cancer cells and this effect was mediated by cannabis receptors (CB1 and CB2).
Medical Faculty of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Hohmann T, et al. Cancers (Basel). 2019;11(2).

Science/Animal: Cannabinoids may prevent damage to the heart induced by clozapine
The antipsychotic drug clozapine may cause damage to the heart. Research shows that activation of the CB2 receptor and blockade of the CB1 receptor “might confer protective effects against clozapine.”
School of Basic Medical Sciences, Fudan University, Shanghai, China.
Li L, et al. Br J Pharmacol. 2019 Feb 1. [in press]

Science/Animal: Cannabinoids may help to treat damage to the kidneys
In a study with mice a synthetic cannabinoid (SMM-295), which activates the CB2 receptor, increased blood flow in the kidneys. Researchers wrote that these results “provide a new therapeutic target to treat renal injuries that impact renal blood flow dynamics.”
Pharmaceutical Sciences, University of Tennessee Health Science Center, USA.
Pressly JD, et al. Physiol Genomics. 2019 Feb 1. [in press]

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