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IACM-Bulletin of 22 December 2019

Science/Human: Cannabis may be helpful in restless legs syndrome

A French scientist, who already presented 6 cases on successful self-medication of restless legs syndrome (RLS) with cannabis in 2017 wrote about 12 additional patients, who reported using cannabis. All patients complained of severe to very severe RLS symptoms and were treated with one or more available standard medication with poor or limited efficacy.

The author wrote that “all but one patient (patient 2) admitted total relief of symptoms following cannabis smoking but none discontinued current RLS treatment mainly because of illicit aspect of marijuana smoking and the concern about a potential risk for abuse and psychoactive effects.” He added that “the potential benefit of cannabis use in patients with refractory RLS should therefore be questioned by robust clinical trials.”

Ghorayeb I.More evidence of cannabis efficacy in restless legs syndrome. Sleep Breath. 2019 Dec 9. [in press]

Science/Human: Cannabis may be helpful in a rare genetic form of neurodegeneration of children

Some children with a rare form of neurodegeneration, associated with dystonia or spasticity profited from treatment with cannabis. Doctors of the Division of Pediatric Neurology of the Oregon Health & Science University in Portland, USA, contacted families of 44 children with so-called pantothenate kinase-associated neurodegeneration and received 18 responses.

Children were a mean of 11 years old. The 15 respondents with dystonia or spasticity were on a median of 2 tone medications. Seven children had ever used cannabis (39%). The most common source of information about cannabis was other parents. Authors wrote that “physicians should be aware that parents may treat their child with severe, painful dystonia with cannabis. Placebo-controlled studies of products containing cannabidiol and 9-tetrahydrocannabinol are needed for pediatric tone disorders.”

Wilson JL, Gregory A, Wakeman K, Freed A, Rai P, Roberts C, Hayflick SJ, Hogarth P. Cannabis Use in Children With Pantothenate Kinase-Associated Neurodegeneration. J Child Neurol. 2019 Dec 11:883073819890516.

Science/Human: People living with HIV, who use cannabis, have better neurocognitive performance

In a study with 679 people living with HIV and 273 people living without HIV the use of cannabis was associated with lower proportion of neurocognitive impairment. The research was conducted by scientists of the University of California in San Diego. Participants completed neurocognitive, neuromedical, and substance use assessments. HIV has adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of decline in cognition.

In people with HIV using cannabis the proportion of neurocognitive impairment was lower than in patients with HIV not using cannabis (odds ratio: 0.53). Authors concluded that their findings “suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV [people living with HIV].”

Watson CW, Paolillo EW, Morgan EE, Umlauf A, Sundermann EE, Ellis RJ, Letendre S, Marcotte TD, Heaton RK, Grant I. Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV. J Acquir Immune Defic Syndr. 2020;83(1):56-64.

Science/Human: Cannabis leaf powder reduces pain in cancer patients

In a study with 24 cancer patients cannabis leaf powder reduced pain, anxiety and depression. The study was conducted by several Ayurvedic institutes across India, including the Gujarat Ayurved University in Jamnagar. Ayurveda recommends use of Shodhita (Processed) Bhanga (Cannabis) for the management of pain but no research has been carried out so far on its clinical effectiveness. Researchers administered waterwash processed Cannabis leaves powder filled in capsule at a dose of 250 mg thrice a day. This was a single arm study without a control group.

Several well-known measures of pain, anxiety and depression were applied in addition to the performance score by Eastern Cooperative Oncology Group and the Karnofsky score, measures of general well-being. Researchers found that the Ayurvedic cannabis powder “relieves cancerinduced pain, anxiety and depression significantly and does not cause any major adverse effect and withdrawal symptoms during trial period.”

Tavhare SD, Acharya R, Reddy RG, Dhiman KS. Management of chronic pain with Jalaprakshalana (water-wash) Shodhita (processed) Bhanga (Cannabis sativa L.) in cancer patients with deprived quality of life: An open-label single arm clinical trial. Ayu. 2019;40(1):34-43.

Science/Human: CBD may be helpful in controlling epilepsy due to a brain tumour according to a case report

Glioma-related epilepsy has a significant impact on patients' quality of life, and can often be difficult to treat. Doctors of the Department of Medical Oncology of Flinders Medical Centre in Adelaide, Australia, reported of a 32 year old woman, who was diagnosed with oligodendroglioma. She developed epilepsy and finally suffered from up to 10 or more seizures per day despite treated with several antiepileptic drugs (including valproate, zonisamide, and levetiracetam).

At this time CBD was added to her medication and within 2 weeks seizure frequency was “dramatically reduced to one or less episodes per day with subjective improvement on her overall quality of life.” She tolerated 750 mg twice daily “with mild fatigue as the only toxicity.” Doses of “other anti-epileptics were reduced with maintained seizure control.”

Hsu K, Whitham E, Kichenadasse G. Potential role of cannabidiol for seizure control in a patient with recurrent glioma. J Clin Neurosci. 2019 Dec 14.[in press]

Science/Human: Cannabinoids may be helpful in people in palliative care

In an open study with 21 patients in palliative care escalating doses of either CBD or THC showed promising results in improving health and well-being. Participants had advanced cancer and cancer -related symptoms in a palliative and supportive care service in the Department of Palliative and Supportive Care of Mater Misericordiae in Brisbane, Australia.

Of the 21 participants enrolled (CBD group  = 16; THC group  = 5), 18 completed the primary outcome measure at day 14 and 8 completed at day 28. The median maximum tolerated doses were 300 mg CBD per day (range 100-600 mg) and 10 mg THC daily (range 5-30 mg). 9 of the 21 patients showed a treatment response. Drowsiness was the most common adverse effect.

Good PD, Greer RM, Huggett GE, Hardy JR. An Open-Label Pilot Study Testing the Feasibility of Assessing Total Symptom Burden in Trials of Cannabinoid Medications in Palliative Care. J Palliat Med. 2019 Dec 3. [in press]

News in brief

Canada: Three Canadian provinces will not allow sale of cannabis vapes
The Canadian provinces of Quebec and Newfoundland and Labrador said on Wednesday they would not allow the sale of cannabis vapes, just weeks before the start of marijuana derivatives sales, as concerns linger about a possible connection between the vaping products and severe lung disease.
Reuters of 4 December 2019

Italy: Parliament and Senate disagree on legal status of cannabis with a low THC content
Parliament voted to allow tobacconists and specialized shops to stock cannabis products, which must not contain more than 0.5 percent of the psychoactive compound THC. However, this move was blocked by the Italian Senate.
The Local of 16 December 2019
The Local of 17 December 2019

Trinidad/Tobago: The country wants to decriminalise cannabis use
In Trinidad and Tobago’s House of Representatives two bills were proposed that could transform the landscape of cannabis regulation across the various islands that make up the Caribbean country. The Dangerous Drugs Amendment Bill would permit people to possess up to 30 grams of cannabis or 5 grams of cannabis resin without suffering legal trials.
WIC News of 29 November 2019

USA: People in states where cannabis is legal are more likely to believe in its benefits
If you live in a state where recreational cannabis is legal, you're more likely to think that it offers health benefits, a new study finds. People think those benefits include relieving pain, anxiety and depression, researchers say. The study was conducted by researchers of the University of California in San Francisco. For the study, the research team asked roughly 9,000 adults about their beliefs and opinions of cannabis.
UPI of 17 C December 2019

Australia: Medical cannabis pioneers receive Honorary Fellowships by the University of Sydney
Philanthropists Barry and Joy Lambert have been recognised with Honorary Fellowships by the University of Sydney for their pioneering collaboration on the establishment of the Lambert Initiative for Cannabinoid Therapeutics. Barry and Joy Lambert were conferred with Honorary Fellowships at the University of Sydney’s Great Hall on 12 December in recognition of their support for medicinal cannabis research.
The University of Sydney of 12 December 2019

UK: Government wants to ban edibles containing cannabis extracts with CBD
Beer, sweets and chocolate containing cannabis extracts could be banned in Britain after health officials in America warned last week they may not be safe.
The Times of 1 December 2019

Science/Animal: Changes of endocannabinoid signalling due to stress delayed strengthening of nerve cell connection in a certain brain region
According to a study with rats stress causes changes of endocannabinoid signalling in the amygdala, a certain brain region. This resulted in danger of low nerve cell connectivity. These negative effects on the amygdala could be prevented by an inhibitor of endocannabinoid degradation. Authors wrote that modulation of the endocannabinoid system could be used “to prevent the gradual development of emotional symptoms and underlying amygdala dysfunction triggered by traumatic stress.”
Department of Neurobiology, National Centre for Biological Sciences, Bangalore, India.
Yasmin F, et al. Proc Natl Acad Sci U S A. 2019 Dec 16. [in press]

Science/Animal: Beta-caryophyllene improves wound healing
Researchers demonstrated, that beta-caryophyllene, an essential oil found in cannabis, pepper and other plants, improves wound healing in mice and this effect was “generated by synergetic impacts of multiple pathways.”
Medical Sciences, School of Medicine, Indiana University, Bloomington, USA.
Koyama S, et al. PLoS One. 2019;14(12):e0216104

Science/Animal: A derivative of cannabidiol increased wakefulness
Cannabidiolic acid methyl ester (HU-580) was shown to increase wakefulness in rats. Authors wrote, that this synthetic derivative of cannabidiolic acid “seems to possess wake-promoting pharmacological properties and enhances the levels of wake-related neurochemicals.”
División Ciencias de la Salud Universidad Anáhuac Mayab Mérida, México.
Murillo-Rodríguez E, et al. Brain Res Bull. 2019 Dec 12. [in press]

Science/Cells: CBD influences the metabolism of heroin
In a study with human liver tissue researchers demonstrated, that CBD influences the metabolism of heroin, “which may be of potential clinical relevance.”
Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, USA.
Qian Y, et al.Chem Biol Interact. 2019;316:108914

Science/Animal: CBD improves cognitive impairment induced by ketamine
In an animal model of schizophrenia-like cognitive deficits induced by repeated ketamine administration CBD reversed these cognitive deficits.
The Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Kozela E, et al. Mol Neurobiol. 2019 Dec 11. [in press]

Science: Online survey is gathering information about the relationship between cannabis, medical condition and DNA
EndoCannaHealth.com and Ethan Russo conducting a study on cannabis use and different medical conditions. They are mainly interested in cannabis hyperemesis syndrome.
Personal communication by Ethan Russo

Science/Human: Some cannabis users may reduce their use of alcohol
In a study scientists investigated differences between 47 people, who reduce their alcohol use after initiating cannabis use (alcohol abaters), and 65 people, who did not reduce their alcohol intake (non-abaters). A greater percentage of abaters (60%) used medical cannabis two or more times per day than non-abaters (41%). Abaters were more likely to be employed (68%) than non-abaters (51%). Abaters also reported having more health conditions and diseases than non-abaters.
Department of Medical Education, Geisinger Commonwealth School of Medicine, Scranton, USA.
Hayat A, et al. J Psychoactive Drugs. 2019 Dec 7:1-8.

Science/Cells: CBD acts synergistically with the chemotherapeutic agents paclitaxel and doxorubicin
In breast cancer cells coadministration of CBD and paclitaxel or CBD and doxorubicin showed a synergistic effect. Authors wrote that their data “evidences the promising inclusion of CBD in conventional breast cancer chemotherapy.”
Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
Fraguas-Sánchez AI, et al. Int J Pharm. 2019;574:118916.

Science/Animal: A new mechanism of anti-inflammatory effects by the activation of CB2 receptors
High mobility group box 1 (HMGB1) is a late phase inflammatory mediator in many inflammatory diseases. New research shows that the activation of the CB2 receptor “could promote the intracellular degradation of HMGB1 via the autophagy-lysosome pathway in macrophages.”
Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
Zhou H, et al. Brellenthin AG, et al. Int Immunopharmacol. 2019 Dec 2:106007.

Science/Animal: CBD influences motility of the inflamed colon
CBD improved inflammatory conditions in colitis of rats and influenced signs of inflammation, such as lowering of interleukin-6 levels. It also reduced the number of the GPR55 receptor and motility of the colon.
Translational Medicine Center, Huaihe Hospital Affiliated to Henan University, Kaifeng, China.
Wei D, et al. Neurogastroenterol Motil. 2019 Dec 4:e13756.

Science/Human: Moderate impairment of the kidneys has no effect on metabolism of CBD
A placebo-controlled study was conducted with patients with mild, moderate or severe impairment of the kidneys (8 patients each) and 8 subjects with normal renal function. “Renal impairment had no effect on the metabolism of CBD after a single oral 200 mg dose. CBD was generally well tolerated in subjects with varying degrees of renal function.”
GW Research Ltd, Sovereign House, Vision Park, Histon, Cambridge, UK.
Tayo B, et al. Brellenthin AG, et al. Clin Pharmacokinet. 2019 Dec 5. [in press]

Science/Animal: CBD causes vasodilation in arteries of the lung and the bowel and this effect was reduced by high blood pressure and obesity
Researchers observed CBD-induced relaxation in human pulmonary arteries, and this effect was reduced in hypertensive, obese and hypercholesteremic patients. “The CBD effect in rats was CB1-sensitive and dependent on the hypertension model. Thus, modification of CBD-mediated responses in disease should be considered when CBD is used for therapeutic purposes.”
Department of Experimental Physiology and Pathophysiology.
Baranowska-Kuczko M, et al. J Hypertens. 2019 Dec 2. [in press]

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