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IACM-Bulletin of 13 October 2019

IACM: 10th Conference on Cannabinoids in Medicine in Berlin

At the end of the months the opening of the leading international conference on medical uses of cannabis and cannabinoids begins. Don’t miss this opportunity to meet the leading researchers in the field, learn from their experience, exchange with others and get first-hand and latest information!

Participants from developing countries pay a reduced registration fee of €200.

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We are delighted to announce that Plena Global will be our Diamond Sponsor. It is due to the generous sponsorship of companies like Plena Global that make holding the conference possible. We would also like to highlight the support by our Platinum Sponsors Bedrocan, Storz & Bickel, Tilray Iqanna and Spektrum Therapeutics, the support by our Gold Sponsors Bionorica ethics, Fundacion Canna, CBDepot, Elite Healthcare Distribution, Aphria, Medical Hemp, Cannabics, International Medical Cannabis, MYCB1, ProPharma, and PhytoGro, by our Silver Sponsors Emerald Health Biotechnology España , THC Pharm, Aurora, Leafly, CanPharma, PureGreen, CC Pharma, Deutsches Institut für Medizinalcannabis, PAX, Waters, Medizinalhanf GmbH, Linneo Health, and by our Bronze Sponsors California NORML, Almirall, Symrise, and Cloud 9 Switzerland.

Science/Human: A large proportion of pain patients are able to reduce or stop the use of opioids according to a large survey

An Internet-based survey of a nationally representative sample of 16,280 adults showed that a large number of pain patients are able to reduce their intake of opioids or even stop use. The survey was conducted by scientists of the Department of Medicine and the VA Medical Center in San Francisco, USA. They developed questions designed to assess the extent and reasons for substitution of cannabis for opioids.

There were 9,003 respondents, corresponding to a 55.3% response rate. The mean age was 48 years. Among the 5% (n = 486) who reported ever using cannabis and using opioids in the past year, 43% used opioids daily, and 23% reported current (past 30 day) cannabis use. Forty-one percent reported a decrease or cessation of opioid use due to cannabis; 46% reported no change in opioid use; and 8% reported an increase in opioid use. authors concluded that “a substantial number of US adults reported that they substituted marijuana for opioids.”

Ishida JH, Wong PO, Cohen BE, Vali M, Steigerwald S, Keyhani S. Substitution of marijuana for opioids in a national survey of US adults. PLoS One 2019;14(10):e0222577.

Science/Human: CBD may have a positive effect on survival in glioblastoma according to open study

According to a case series with 9 patients suffering from glioblastoma CBD in a dose of 400 mg may have positive effects on survival. The study was conducted at the Department of Anaesthesiology and Intensive Care, Klinikum Klagenfurt am Wörthersee, Austria.

Grade IV glioblastoma multiforme is a deadly disease, with a median survival of around 14 to 16 months. All patients received CBD concomitantly to the standard therapeutic procedure of maximal resection followed by radiochemotherapy. By the time of the submission of the article to the journal Anticancer Research, all but one patient were still alive with a mean survival time of 22.3 months (range=7-47 months). Authors wrote that this “is longer than what would have been expected.”

Likar R, Koestenberger M, Stultschnig M, Nahler G. Concomitant Treatment of Malignant Brain Tumours With CBD - A Case Series and Review of the Literature. Anticancer Res. 2019;39(10):5797-5801.

Science/Animal: How CBD mitigates psychological effects of THC

Canadian researchers demonstrated that THC induces cognitive and affective abnormalities resembling neuropsychiatric symptoms directly in the hippocampus, a certain brain region. And this effect was induced by the modulation of a certain signalling pathway, the so-called extracellular signal-regulated kinase (ERK) signaling pathway. In contrast, CBD co-administration blocked THC-induced ERK changes, and prevented THC-induced behavioural and neural abnormalities. This research was published in the Journal of Neuroscience by scientists of the University of Western Ontario in London, Canada.

These findings identify a novel molecular mechanism that may account for how CBD functionally mitigates the neuropsychiatric side-effects of THC. Authors wrote that “strains of marijuana with high levels of delta-9-tetrahydrocannabinol (THC) and low levels of cannabidiol (CBD) have been shown to underlie neuropsychiatric risks associated with high potency cannabis use. However, the mechanisms by which CBD mitigates the side effects of THC have not been identified.”

Hudson R, Renard J, Norris C, Rushlow WJ, Laviolette SR. Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus Through Bi-Directional Control of ERK1-2 Phosphorylation. J Neurosci. 2019 [in press]

Science/Human: Clinical improvement of inflammatory bowel disease in observational study

In a study with 127 patients with inflammatory bowel disease conducted at the Meir Medical Center Institute of Gastroenterology and Hepatology in Kfar Saba, Israel, cannabis caused a considerable clinical improvement. Laboratory parameters on inflammation and other variables were assessed before, one month and at least one year after medical cannabis treatment was initiated.

The average dose used was 31 month. The average Harvey-Bradshaw index improved from 14 to 7 during a median follow-up of 44 months. there was a slight, but statistically significant, average weight gain of 2 kg within 1 year of cannabis use. The need for other medications was significantly reduced. Employment among patients increased from 65 to 74%. Authors concluded “that the majority of inflammatory bowel disease patients using cannabis are satisfied with a dose of 30 g/month. We did not observe negative effects of cannabis use on the patients' social or occupational status.”

Naftali T, Bar-Lev Schleider L, Sklerovsky Benjaminov F, Lish I, Konikoff FM, Ringel Y. Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects. EUR J Gastroenterol Hepatol. 2019;31(11):1376-1381.

Science/Human: Cancer -related anoxia was improved by oral cannabis in a small study

In a study with cancer patients, which was completed by 11 participants, capsules containing an oily cannabis preparation caused a significant weight increase. It was conducted by several Israeli centres and the Bethesda Metro Center, USA. The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 9.5 mg THC and 2 x 0.5 mg CBD per 24 hours for six months.

11 patients received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point of weight increase of at least 10%. The remaining three patients had stable weights. Patients reported less appetite loss after the cannabis treatment. According to patients' self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated.

Bar-Sela G, Zalman D, Semenysty V, Ballan E. The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study. Integr Cancer Ther. 2019;18:1534735419881498.

News in brief

Science/USA: Several cases of deaths due to vaping have been observed in the USA
As the number of cases and deaths tied to vaping-linked lung injury continues to rise across the United States, a meticulous examination of 17 such cases suggests a possible culprit. All of the patients examined had severe forms of the illness, and two had died. "Based on what we have seen in our study, we suspect that most cases involve chemical contaminants, toxic byproducts or other noxious agents within vape liquids," said lead researcher Dr. Brandon Larsen. He's a surgical pathologist at the Mayo Clinic Arizona in Scottsdale.
UPI of 3 October 2019

Europe: CBD extract approved for epilepsy
The EU has approved for the first time the use of a CBD extract aimed at patients with two rare, but severe, forms of childhood epilepsy (Lennox-Gastaut syndrome, Dravet syndrome). Doctors can prescribe Epidyolex- an oral solution with cannabidiol.
BBC of 23 September 2019

Czech Republic: Government plans to pay for patients’ medical cannabis
The Czech government announced plans to subsidise the cost of medical Cannabis from public health insurance. Medical Cannabis patients will be reimbursed for up to 90% of the cost of their prescriptions.
CaneX of October 2019

India: A further state intends to legalise the use of cannabis
Cannabis has been already legalised in three states in the country. To legalise cannabis in Manipur, the matter will be discussed in the next cabinet meeting with the objective to increase the state economy Chief minister, N. Biren Singh stated during a press conference held on 2 September at his secretariat office located at Babupara, Imphal.
Imphal Free Press of 2 September 2019

Morocco: Plans for a study on the medical value of cannabis
The Tangier-Tetouan-Al Hoceima Regional Council has decided to finance a feasibility study on the therapeutic and pharmacological exploitation of the properties of cannabis. This study will be carried out in collaboration with the Rabat Scientific Institute attached to Mohammed V University.
Bladi of 21 September 2019

Lebanon: Proposal to legalise cannabis for medical purposes
The legalisation of cannabis production and sales is being discussed in Lebanon as a way to address the country’s worsening economic situation and give a semblance of legality to a practice that dates back to Ottoman times. According to Lebanon’s French daily L'Orient-Le Jour, the idea comes from Nabih Berri, speaker of the Lebanese parliament, who announced that the country "could legalise the cultivation of cannabis and its use for medical purposes."
Asia News of 26 September 2019

Science/Human: Laws on medical cannabis result in a reduction of opiates
A study investigates the effect of Medical Marijuana Laws on opioid use and misuse controlling for a number of relevant factors using data from several years of the National Survey on Drug Use. Results provide evidence that medical cannabis laws may be effective at reducing opioid reliance as survey respondents living in states with medical cannabis legislation are much less apt to report using opioid analgesics than people living in states without such laws.
Florida International University, Miami, USA.
Flexon JL, et al. Int J Drug Policy. 2019;74:152-159.

Science/Animal: No effect of terpenes on cannabis -related pain reduction
In a study with rats THC alone produced robust analgesia equivalent to the full cannabis extract, whereas terpenes alone did not produce analgesia. Authors concluded “that data suggest the analgesic activity of cannabis is largely mediated by THC, whereas terpenes alone do not cause alterations in cannabis-mediated analgesia.”
National Center for Natural Products Research, University of Mississippi, USA.
Harris HM, et al. Cannabis Cannabinoid Res. 2019;4(3):177-182.

Science/Cells: Major terpenes in cannabis do not exert their effects by activation of cannabis receptors
Research with cells showed, that none of the 6 most common terpenes in cannabis investigated in this study (alpha-Pinene, beta-pinene, beta-caryophyllene, linalool, limonene, and beta-myrcene) directly activated cannabis receptors (CB1 or CB2). Authors wrote that “it seems more likely that they may act at different molecular target(s) in the neuronal circuits important for the behavioral effect of Cannabis.”
Department of Biomedical Sciences, Macquarie University, Sydney, Australia.
Santiago M, et al Cannabis Cannabinoid Res. 2019;4(3):165-176.

Science/Animal: A combination of cannabinoids and opiates may reduce chemotherapy-induced neuropathy
A study with mice showed, that the chemotherapeutic agent paclitaxel induced chemotherapy-induced peripheral neuropathy and that this symptom may be treated by targeting heteromers of the CB1 receptor and the delta opioid receptor. A combination of very low doses of a cannabinoid (HU-210) and an opioid (SNC80) were very effective in releasing mechanical allodynia (pain following non-painful stimulation) caused by this peripheral neuropathy.
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
Sierra S, et al. ACS Pharmacol Transl Sci 2019;2(4):219-229.

Science/Cells: Dysregulation of the an endcannabinoid system in squamous cell carcinoma
Researchers demonstrated that the endlcannabinoid system may be dysfunctional in squamous cell carcinoma of the oral tongue.
Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden.
Alhouayek M, et al. Cancer Invest 2019;37(8):327-338.

Science/Cells: The endocannabinoid system is altered in hepatocellular carcinoma
Research shows that the endocannabinoid system is altered in human hepatocellular carcinoma. For example, the endlcannabinoid anandamide was reduced in hepatocellular carcinoma tissues compared with normal tissue.
Department of Pharmacy, The Fifth Hospital of Xiamen, Fujian, China.
Yang J, et al. Oncol Lett 2019;18(2):1530-1538.

Science/Human: Endocannabinoid levels are increased in people with high risk for psychosis
In a study with 33 people with a high risk for psychosis, who were compared with 58 healthy controls, those with a high risk for psychosis presented with elevated endocannabinoid levels in peripheral blood. Endocannabinoids were also increased in patients, who had undergone childhood trauma or maltreatment.
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience, UK.
Appiah-Kusi E, et al. Psychol Med 2019:1-10.

Science: Nutmeg compounds may inhibit the degradation of endlcannabinoids
Some nutmeg compounds may inhibit the degradation of endocannabinoids by reducing the activity of certain enzymes (FAAH, MAGL). One compound was shown to be most active, selective to FAAH and showing anxiolytic activity.
School of Pharmacy, Medical College of Wisconsin, Milwaukee, USA.
El-Alfy AT, et al. J Pharm Pharmacol. 2019 Oct 8. [in press]

Science/Human: E-cigarettes may cause lung injuries
The use of E-cigarettes has been shown to be associated with a range of lung injury patterns that have only recently been recognised.
Department of Radiology and Biomedical Imaging, University of California San Francisco, USA.
Henry TS, et al. AJR Am J Roentgenol 2019:1-8.

Science/Animal: A hydrophilic prodrug of THC reduces intraocular pressure
THC-valine-hemisuccinate, a hydrophilic prodrug of THC was shown to reduce intraocular pressure in normotensive rabbits. It was directly applicated to the eyes. Authors wrote that in addition improved permeation to the back of the eye, may possibly provide neuroprotective benefits in glaucoma management.”
Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, USA.
Taskar PS, et al. Transl Vis Sci Technol 2019;8(5):15.

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