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IACM-Bulletin of 30 September 2018

South Africa: Constitutional Court allows private use of cannabis

South Africa’s highest court allows the private use of cannabis, upholding a lower court’s ruling that found the criminalization of cannabis was unconstitutional. Activists who include traditional healers greeted the ruling with loud applause.

Several government departments, including the health and justice ministries, oppose its legalization and warn of harmful effects. But in a unanimous judgment read by Deputy Chief Justice Raymond Zondo, the Constitutional Court decriminalized home consumption, saying “the use of cannabis must be for the personal consumption of the adult”. The ruling also approves growing cannabis for personal consumption.

Reuters of 18 September 2018

Science/Human: Drug addicts have higher retention to opioid replacement treatment if they use cannabis

In a large study with 820 people who used illicit drugs and underwent opioid agonist treatment retention to treatment was improved if they also used cannabis at least daily. Scientists of the British Columbia Centre on Substance Use in Vancouver, Canada, published these results in the journal Addiction. Participants initiated treatment with methadone or buprenorphine/naloxone between December 1996 and May 2016. The primary outcome was retention to the treatment, defined as remaining in in the treatment (methadone or buprenorphine/naloxone-based) for two consecutive 6-month follow-up periods.

At least daily cannabis use in addition to methadone or buprenorphine was positively associated with retention to the treatment compared to non-users of cannabis or less than daily users. Authors concluded that among “people who use illicit drugs initiating opioid agonist treatment in Vancouver, at least daily cannabis use was associated with approximately 21% greater odds of retention in treatment compared with less than daily consumption.”

Socías ME, Wood E, Lake S, Nolan S, Fairbairn N, Hayashi K, Shulha HP, Liu S, Kerr T, Milloy MJ. High-intensity cannabis use is associated with retention in opioid agonist treatment: a longitudinal analysis. Addiction. 2018 Sep 20. [in press]

Science/Human: Cannabis extract with high CBD and low THC content effective in childhood epilepsy

In a study with 19 children with Dravet syndrome a cannabis extract produced by the company Tilray containing 100 mg/ml CBD and 2 mg/ml THC reduced the number of seizures and improved quality of life. The 20-week study was conducted at the Hospital for Sick Children in Toronto, Canada. The cannabis extract was given add on to standard treatment.

Mean daily dose achieved was 13.3 mg/kg of CBD (range: 7 to 16 mg/kg bodyweight) and 0.27 mg/kg of THC (range: 0.14 to 0.32 mg/kg bodyweight). Authors wrote that there “was a statistically significant improvement in quality of life, reduction in EEG spike activity, and median motor seizure reduction of 70.6%.”

McCoy B, Wang L, Zak M, Al-Mehmadi S, Kabir N, Alhadid K, McDonald K, Zhang G, Sharma R, Whitney R, Sinopoli K, Snead OC 3rd. A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome. Ann Clin Transl Neurol. 2018;5(9):1077-1088.

Science/Human: Cannabis improves pain in patients with failed back surgery syndrome

In a study with 11 patients suffering from pain after back surgery cannabis in combination with spinal cord stimulation (SCS) was found to be very effective. Researchers of the University of Messina in Italy published their results in the Journal of Pain Research. All patients underwent a treatment with SCS and a combination of THC/CBD for 12 months.

Effective pain management as compared to baseline was achieved in all the cases studied. The positive effect of cannabis on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.2 to 4.7 by the end of the study. Authors wrote that these results indicate “remarkable capabilities” of cannabis for the treatment of chronic refractory pain in this patient group.

Mondello E, Quattrone D, Cardia L, Bova G, Mallamace R, Barbagallo AA, Mondello C, Mannucci C, Di Pietro M, Arcoraci V, Calapai G. Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain. J Pain Res. 2018;11:1761-1767.

Science/Human: No difference on reduced appetite between THC, megestrol and mirtazapine

In a retrospective study of 38 hospitalised patients with reduced appetite there was no difference between THC, megestrol and mirtazapine in change in meal intake or weight. It was conducted by scientists of the University of North Texas System College of Pharmacy, USA.

Mirtazapine was most commonly used (42%). There was no significant difference between groups of appetite-stimulating medications with regard to mean change in meal intake, weight, albumin, or documented improvement in diet. Within groups, each agent showed numerical improvement in percentage meal intake, with a mean change from initiation to discontinuation of 17%. Almost half (48%) of the patients experienced improvements in diet after the start of medications. No serious adverse effects were observed.

Howard ML, Hossaini R, Tolar C, Gaviola ML. Efficacy and Safety of Appetite-Stimulating Medications in the Inpatient Setting. Ann Pharmacother. 2018 Sep 19:1060028018802816.

News in brief

Science/Human: Pain relief by cannabis may be best described as Restored Self
In a study with 19 patients treated with cannabis against pain interviews revealed 3 themes: the Sigh of Relief, the Return to Normality and Side Effects. Authors proposed “the term Restored Self to conceptualize the effect of medical cannabis. Restored Self is the experience of regaining one's sense of self, sense of normality, and sense of control over one's life.”
Siaal Research Center for Family Medicine and Primary Care, Beer-Sheva, Israel.
Lavie-Ajayi M, et al. Pain Med. 2018 Sep 12. [in press]

USA: CBD-extract transferred to lowest classification of narcotics laws
Epidiolex, a CBD extract manufactured by GW Pharmaceuticals, has been transferred to schedule V, the lowest restriction classification, by the US narcotics laws. Epidiolex was approved by the US medical agency FDA on 25 June 2018 for the treatment of certain forms of epilepsy.
Press release by GW Pharmaceuticals of 27 September 2018

Science/Animal: CBD reduces motivation to consume methamphetamine
In a study with rats, which were dependent from methamphetamine, the administration of CBD reduced the motivation to self-administer methamphetamine and attenuated relapse to methamphetamine-seeking behaviour. Authors wrote that “cannabidiol might be worth trialing as a novel pharmacotherapy for methamphetamine dependence”.
Department of Psychology, Macquarie University, North Ryde, Australia.
Hay GL, et al. J Psychopharmacol. 2018 Sep 27 [in press]

Science: Treatment of breast cancer may be improved by activation of the CB2 receptor
A combined treatment of triple negative breast cancer, which is the deadliest form of breast cancer, a combination of photodynamic therapy and a cannabinoid, which activates the CB2 receptor, resulted in synergistic inhibition of these cancer cells and tumour growth. Authors wrote that “this study provides new evidence on the therapeutic potential of CB2R agonists for cancer.”
Department of Radiology, Henan, China.
Zhang J, et al. Photodiagnosis Photodyn Ther. 2018 Sep 18. [in press]

Science/Human: Medical cannabis laws in the USA not associated with crime
Researchers found no influence of the legalisation of cannabis for medicinal purposes in the USA on violent or property crime at the national level. There were also no strong effects within individual states except a reduction of both violent and property crime by 20% in California.
Victoria University of Wellington, New Zealand.
Luke Chu Y-W, Townsend W. J Econ Behav Org. 2018 Jul 29 [in press]

Science/Animal: CBDA has pain reducing effects in neuropathic pain
In a study with rats CBDA (cannabidiolic acid) and THC showed anti-hyperalgesia effects and both cannabinoids acted synergistically. Authors wrote that “CBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.” Hyperalgesia means increased sensitivity to pain.
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Canada.
Rock EM, et al. Psychopharmacology (Berl). 2018 Sep 17. [in press]

Science/Animal: New mechanism of action of CBD
In several animal studies researchers found that CBD may block the sigma 1 receptor. This blockade may have a positive effect on chronic neurodegenerative diseases, including stroke and epilepsy, neuropsychiatric disorders, neuropathic pain and certain types of cancer.
Department of Translational Neuroscience, Cajal Institute, Madrid, Spain.
Rodríguez-Muñoz M, et al. Mol Brain. 2018;11(1):51.

Science/Cells: Another new mechanism of action of CBD
Researchers investigated possible mechanisms of action of CBD in certain renal cells and nerve cells. They found that “CBD's mode of action likely involves (1) compound partitioning in lipid membranes, which alters membrane fluidity affecting gating, and (2) undetermined direct interactions with sodium and potassium channels, whose combined effects are loss of channel excitability.”
Xenon Pharmaceuticals Inc, Canada.
Ghovanloo MR, et al. J Biol Chem. 2018 Sep 14. [in press]

Science/Animal: Cannabinoids may be effective in the treatment of prostate cancer
A synthetic cannabinoid showed anti-cancer effects in mice by reducing cancer growth and inducing apoptosis (programmed cell death). This effect was mediated by the CB2 receptor.
Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Canada.
Roberto D, et al. Prostate. 2018 Sep 21. [in press]

Science/Human: Students with ADHD are more likely to use cannabis
In a study with 1748 students aged 18 to 25 years those with a diagnosis of ADHD (attention deficit hyperactivity disorder) were more likely to have used alcohol frequently, to be regular cannabis users and to have used other drugs in the last year.
Department of Psychology, East Carolina University, USA.
Mochrie KD, et al. J Am Coll Health. 2018:1-5.

Science/Animal: Endocannabinoids may be useful against reduced blood supply during birth
The endocannabinoids oleylethanolamide (OEA) and palmitoylethanolamide (PEA) reduced the negative consequences of reduced blood supply during birth in newborn rats. This was caused by neuroprotective effects on nerve cells of the brain.
Department of Experimental Psychology, Faculty of Psychology, Seville, Spain.
Portavella M, et al. Cannabis Cannabinoid Res. 2018;3(1):171-178.

Science/Animal: Endocannabinoids may be helpful in post-traumatic stress disorder
Increase of endocannabinoid levels by reducing their degradation in stressed rats caused anxiolytic-like effects. Authors wrote that “anandamide-mediated signaling at CB1 receptors serves an important regulatory function in the stress response“ and inhibition of endocannabinoid degradation “may offer a potential therapeutic strategy for post-traumatic stress disorder.”
University of California, Irvine, USA.
Danandeh A, et al. Psychopharmacology (Berl). 2018 Sep 24. [in press]

Science/Human: Endocannabinoid levels in obese patients were reduced after surgery against obesity
In a study with 65 obese patients, who underwent surgery to remove a part of their stomach, the levels of circulating endocannabinoids (2-AG, anandamide) were reduced. This was associated with reduced fat mass and improvements of glucose and lipid profiles.
The Hebrew University of Jerusalem, Israel.
Azar S, et al. Obes Surg. 2018 Sep 22. [in press]

Science/Animal: CBD may inhibit the pain reducing effects of THC
In a study with rats, which received either a cannabis extract with THC and CBD or THC alone, repeated administration resulted in a reduced pain relieving effect of THC by CBD. Authors wrote that this effect “may be due to CBD-induced inhibition of THC metabolism, and/or antagonism of THC effects that emerges with repeated CBD treatment.”
Department of Psychology, Washington State University, Pullman, USA.
Greene NZ, et al. Psychopharmacology (Berl). 2018 Sep 20. [in press]

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