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IACM-Bulletin of 05 July 2020

Switzerland: Government wants to make cannabis available for medical use

The Swiss government wants to empower doctors to prescribe cannabis for medical purposes without authorisation. On 24 June, the Federal Council submitted a revised version of the narcotics law to parliament for deliberation. Cannabis, whether for recreational or medical purposes, has been banned in Switzerland since 1951. However, doctors may prescribe a medicine based on this substance if they get an exceptional green light from the Federal Office of Public Health.

But the government believes this process complicates access to treatment, delays the start of therapies and is no longer adequate in view of the growing number of requests. In 2019, around 3,000 authorisations were issued for patients suffering from cancer, neurological diseases or multiple sclerosis. The government wants to tweak the narcotics law so that the decision to prescribe cannabis-based drugs would be taken directly by doctor and patient. Swissmedic, the national medical oversight body, would be responsible for authorising and supervising the cultivation, manufacture and marketing of cannabis for medical use. The government also wants to allow the commercial export of such medicinal cannabis.

Swiss Info of 24 June 2020

Science/Human: Inhalation cannabis with a new metered-dose inhaler caused immediate pain relief

In placebo-controlled, cross-over trial by Israeli researchers from several institutions, 27 pain patients received a single inhalation of 0.5 mg THC, 1.0 mg THC or a placebo at 3 sessions. Both doses of THC, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150 minutes. Maximum blood plasma levels were 14 ng/mL after inhalation of 0.5 mg of THC and 34 ng/mL after inhalation of 1 mg of THC.

The 1-mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance. Authors concluded that their trial “demonstrated that a metered-dose cannabis inhaler delivered precise and low THC doses, produced a dose-dependent and safe analgesic effect in patients with neuropathic pain/ complex-regional pain syndrome (CRPS).”

Almog S, Aharon-Peretz J, Vulfsons S, Ogintz M, Abalia H, Lupo T, Hayon Y, Eisenberg E. The pharmacokinetics, efficacy, and safety of a novel selective-dose cannabis inhaler in patients with chronic pain: A randomized, double-blinded, placebo-controlled trial. EUR J Pain. 2020 May 23 [in press]

Science/Human: Cannabis use is associated with lower biomarkers for inflammation in patients with HIV

In a study with 56 people with HIV conducted at the University of California in San Diego, USA, recent cannabis use was associated with reduced inflammation. Researchers measured a number of proinflammatory cytokines, including C-reactive protein, interleukin-16 and to soluble tumour necrosis factor receptor type II in cerebral spinal fluid and blood plasma. There were 41 cannabis ever users and 15 never users.

A factor analysis using biomarkers yielded a factor loading on CRP, interleukin-16, and soluble tumour necrosis factor receptor type II significantly associated with recent cannabis use. In particular, more recent cannabis use was related to lower interleukin-16 levels. Authors concluded that “recent cannabis use was associated with lower levels of inflammatory biomarkers, both in CSF and blood, but in different patterns (…). Thus, our findings are consistent with specific anti-neuroinflammatory effects that may benefit HIV neurologic dysfunction.”

Ellis RJ, Peterson SN, Li Y, Schrier R, Iudicello J, Letendre S, Morgan E, Tang B, Grant I, Cherner M. Recent cannabis use in HIV is associated with reduced inflammatory markers in CSF and blood. Neurol Neuroimmunol Neuroinflamm. 2020;7(5).

Science/Human: Cannabis may be helpful in migraine according to small study

Medical cannabis may have promise for managing headache pain, according to results from a small study conducted at the Jefferson Headache Center at Thomas Jefferson University. The researchers found general satisfaction with medical marijuana, more frequent use as an acute medication rather than a preventative, and more than two-thirds using the inhaled form rather than oral. The study was part of the virtual annual meeting of the American Headache Society.

The study included 48 patients with migraine or other types of chronic headache who received medical cannabis treatment between January and September 2019. A total of 28 subjects completed a follow-up questionnaire over the phone. Out of the 28 participants, 3 had stopped using cannabis. Before starting on cannabis, 46.4% of the subjects used abortive medications at least 10 days per month. After starting cannabis treatment, the rate dropped to 25.0%. Cannabis use was associated with improvements in anxiety: 57.1% who had anxiety reported improvement with cannabis use, as did 78.6% with insomnia. On a scale of 10, the average rating of cannabis' usefulness was 5.9, and 17.9% rated it as 10.

Medscape of 25 June 2020

Science/Human: Cannabis may be cause immediate relief in depression and this effect was mainly due to THC

According to a survey with 1819 people, who completed 5876 cannabis self-administration sessions using an app between 2016 and 2019 cannabis may cause immediate relief in depression. The study was conducted by researchers of the University of New Mexico in Albuquerque, USA.

On average, 95.8% of users experienced symptom relief following consumption with an average symptom intensity reduction of -3.76 points on a 0-10 visual analogue scale. Symptom relief did not differ by labelled plant phenotypes ("C. indica," "C. sativa," or "hybrid") or combustion method. Across cannabinoid levels, THC levels were the strongest independent predictors of symptom relief, while CBD levels, instead, were generally unrelated to real-time changes in symptom intensity levels. Authors concluded that their findings “suggest that, at least in the short term, the vast majority of patients that use cannabis experience antidepressant effects.”

Li X, Diviant JP, Stith SS, Brockelman F, Keeling K, Hall B, Vigil JM. The Effectiveness of Cannabis Flower for Immediate Relief from Symptoms of Depression. Yale J Biol Med. 2020;93(2):251-264.

Science/Human: Cannabis improves pain and quality of life in chronic pain patients according to large observational study

In a prospective observational study by Canadian scientists from Toronto, Canada, a total of 751 chronic pain patients initiating medical cannabis treatment completed a brief survey at baseline and again until 12 months.

Medical cannabis treatment was associated with improvements in pain severity observed at one month and maintained over the 12-month observation period. Significant improvements were also observed in physical and mental health starting at three months. Significant decreases in headaches, fatigue, anxiety, and nausea were observed after initiation of treatment. In patients who reported opioid medication use at baseline, there were significant reductions in oral morphine equivalent doses.

Safakish R, Ko G, Salimpour V, Hendin B, Sohanpal I, Loheswaran G, Yoon SYR. Medical Cannabis for the Management of Pain and Quality of Life in Chronic Pain Patients: A Prospective Observational Study. Pain Med. 2020 Jun 18 [in press].

News in brief

IACM: The IACM remembers Dr Lester Grinspoon
Dr Lester Grinspoon, a Harvard professor, psychiatrist, and author of ground-breaking books on cannabis passed away on 25 June, one day after celebrating his 92nd birthday. Around the world he was mainly known due to his book Marihuana: The Forbidden Medicine, co-written with James B. Bakalar and published in 1993, which was translated into several languages, for example in 1994 into German. Thus, it not only opened the eyes on the medical potential of the cannabis plant to a broad public in the US, but also in EURope. This book was an important inspiration the foundation of the German ACM (Association for Cannabis as Medicine), of which he was an honorary member.

Israel: Parliament votes to advance the legalisation of cannabis for use by adult
The Knesset plenum voted on 24 June to advance in a preliminary reading two bills that would legalize cannabis, but they still have to go through several months of legislation before they become law.
Jerusalem Post of 24 June 2020

Science/Human: Many patients with multiple sclerosis use cannabis
Despite the existence of conventional medications to manage multiple sclerosis symptoms, a majority of patients also rely on alternative therapies, including vitamins, exercise and cannabis, a new survey suggests. For the study, researchers at Oregon Health and Science University in Portland asked MS patients if they used "complementary and alternative therapies" -- medicines and practices outside of standard medical care.
UPI of 2 July 2020

Science/Human: An increasing number of US citizens use cannabis for insomnia, pain and stress
More and more U.S. states are allowing cannabis to be taken as medicine, and a new study suggests that users do indeed feel better. In a survey of nearly 1,300 people with chronic health conditions, researchers found that those using "medicinal cannabis" reported less pain, better sleep and reduced anxiety.
UPI of 26 June 2020

Science/Cells: A synthetic cannabinoid induces apoptosis in acute leukaemia cells
A synthetic cannabinoid (CP55940) selectively induced programmed cell death (apoptosis) in Jurkat cells, a cell line of acute lymphoblastic leukaemia, without affecting healthy blood cells. Authors concluded that their “findings support the use of cannabinoids as a potential treatment for T-ALL cells.”
Medical Research Institute, Faculty of Medicine, University of Antioquia, Medellin, Colombia.
Soto-Mercado V, et al. Leuk Res. 2020;95:106389.

Science/Human: A combination of CBD and valproic acid in children with epilepsy may cause reduced platelets in blood
Doctors of a hospital in the US observed a reduction in the number of platelets (thrombocytopenia) in 9 out of 87 patients treated with CBD. Platelet counts fell below 108,000 per microliter blood. All these children were simultaneously treated with valproic acid. Authors wrote that they report “a novel and clinically important side effect of thrombocytopenia in one-third of patients treated concurrently with cannabidiol and valproic acid.”
Division of Pediatric Neurology, Department of Pediatrics, Ann Arbor, Michigan, USA.
McNamara NA, et al. Epilepsia. 2020 Jul 2 [in press].

Science/Animal: The administration of THC following exposure certain toxins from bacteria protected mice from their toxicity
The administration of THC after exposure with enterotoxin from the bacterium Staphylococcus (SEB) aureus protected mice from respiratory distress syndrome and toxicity of the toxin. Authors assume that this effect is among others mediated by the “suppression of cytokine storm leading to attenuation of SEB-mediated lung injury.”
School of Medicine, University of South Carolina, Columbia, USA.
Mohammed A, et al. Front Pharmacol. 2020;11:893.

Science/Animal: Interaction of CBD and THC in seizure susceptibility in mice
Researchers investigated the interaction of THC and CBD in a mouse model of Dravet syndrome, a genetic disorder associated with epilepsy. They found that low doses of THC are anticonvulsant against seizures in these mice, effects that are enhanced by a sub-anticonvulsant dose of CBD. However, proconvulsant effects and increased premature mortality were observed when CBD and THC are subchronically dosed in combination.
Brain and Mind Centre, The University of Sydney, Australia.
Anderson LL, et al. Br J Pharmacol. 2020 Jul 1 [in press].

Science/Human: Prenatal cannabis exposure may affect sleep in children 9 to 10 years of age
In a study with 11,875 children in the age of 9 to 10, who were investigated with regard to sleep disorders exposure to cannabis during pregnancy of their mother showed symptoms of disorders of initiating and maintaining sleep as well as excessive somnolence. However, authors noted that “causality is not established” between cannabis use during pregnancy and these symptoms.
Institute for Behavioral Genetics, University of Colorado Boulder, United States.
Winiger EA, Hewitt JK. Sleep Health. 2020 Jun 27 [in press].

Science/Animal: The endocannabinoid 2-AG reduced neuropathic pain caused by a chemotherapeutic agent
Researchers observed that during paclitaxel-induced neuropathic pain in mice there is a deficiency of the endocannabinoid 2-AG in the periphery but not in the central nervous system and that is of 2-AG may reduce this pain in a manner, which is dependent on the CB 1 and the CB2 receptor.
Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Kuwait.
Thomas A, et al. Biomed Pharmacother. 2020;129:110456.

Science/Human: Both cannabis use and tobacco use are independently associated with shorter pregnancy
In a study with 8261 mothers, of whom 27.5% had preterm births, cigarette smoking and cannabis use during pregnancy was associated with reduced pregnancy time. Both drugs reduced pregnancy by half a week (0.5 weeks for cannabis and 0.5 weeks for tobacco).
Johns Hopkins University Bloomberg School of Public Health, Baltimore, USA.
Nawa N, et al. Paediatr Perinat Epidemiol. 2020 Jun 30 [in press].

Science/Animal: THC shows antiemetic effects in monkeys
Antiemetic effects THC and methanandamide were observed in squirrel monkeys and this effect was mediated by the CB1 receptor.
McLean Hospital, Harvard Medical School, Boston, USA.
Wooldridge LM, et al. J Pharmacol Exp Ther. 2020 Jun 19 [in press].

Science/Human: Cannabis was effective in reducing tonic spasms in a patient with neuromyelitis optica
Researchers from Thailand presented the case report of a patient suffering from neuromyelitis optica spectrum disorder, who presented with painful tonic spasm. Cannabis was very effective in reducing the spasms. This is an autoimmune disease with severe inflammation of the optic nerve.
Faculty of Medicine Siriraj Hospital Mahidol University, Bangkok, Thailand.
Tisavipat N, et al. Mult Scler Relat Disord. 2020;44:102278.

Science/Human: Patients prefer natural CBD extracts over synthetic CBD
In a survey of 104 patients with different forms of epilepsy 73% responding to treatment wished to receive plant-derived CBD, while 5% preferred synthetic CBD. Reasons for this choice were botanic origin, lack of chemistry, and the assumption of fewer and less dangerous side effects.
Department of Epileptology, University Hospital Bonn, Germany.
von Wrede R, et al. Seizure. 2020;80:92-95.

Science/Cells: CBD showed stronger antimicrobial efficacy than CBDA
CBD showed a significant antimicrobial effect on Gramm -positive Staphylococcus aureus and no effect on Gramm -negative bacteria. CBDA presented 2-fold lower antimicrobial activity than CBD. Authors wrote that “CBD exhibited a strong antimicrobial effect against Gram-positive strains and could serve as an alternative drug for tackling MRSA.” MRSA are bacteria resistant to conventional antibiotics.
Department of Science and Environment, Roskilde University, Denmark.
Martinenghi LD, et al. Biomolecules. 2020;10(6).

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