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IACM-Bulletin of 03 January 2021

Science/Human: Cannabis may be helpful in post-traumatic stress disorder

According to a study with 150 patients suffering from post-traumatic stress disorder (PTSD) cannabis use was associated with reduced symptoms after one year compared to non-users. The study was conducted by investigators of the Perelman School of Medicine of the University of Pennsylvania in Philadelphia, USA, and published online ahead of print in Cannabis and Cannabinoid Research. This prospective study assessed PTSD symptoms and functioning in two samples of participants diagnosed with PTSD: (1) those with PTSD using dispensary-obtained cannabis and (2) those with PTSD, who do not use cannabis.

Over the course of 1 year, the cannabis users reported a greater decrease in PTSD symptom severity over time compared to controls. Participants who used cannabis were 2.6 times more likely to no longer meet disease criteria according to DSM 5 for PTSD at the end of the study observation period compared to participants who did not use cannabis. Authors concluded that their “study provides evidence that the types of cannabis available in recreational and medical cannabis dispensaries might hold promise as an alternative treatment for PTSD.”

Bonn-Miller MO, Brunstetter M, Simonian A, Loflin MJ, Vandrey R, Babson KA, Wortzel H. The Long-Term, Prospective, Therapeutic Impact of Cannabis on Post-Traumatic Stress Disorder. Cannabis Cannabinoid Res 2020 Dec 9. [in press]

Science/Human: Cannabis use is associated with reduced risk of fentanyl use

Researchers of the British Columbia Centre on Substance Use and University of British Columbia in Vancouver, Canada, investigated the effect of cannabis use to the exposure to illicitly-manufactured fentanyl, the main driver of the overdose opioid crisis. Data were drawn from two community-recruited prospective cohorts of people who use drugs in Vancouver.

Among the 819 participants on opioid agonist treatment (OAT) who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 versus 56 %). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl. Authors concluded that their findings “reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.”

Socías ME, Choi J, Lake S, Wood E, Valleriani J, Hayashi K, Kerr T, Milloy MJ. Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis. Drug Alcohol Depend 2020:108420.

Australia: Restrictions to the sale of CBD rich cannabis will be removed in Tasmania

Tasmanians will be able to access cannabis rich in CBD without a prescription as soon as February 2021, after a change to the substance's legal status. The Therapeutic Goods Administration (TGA) has said it will remove restrictions on the use and sale of cannabidiol (CBD) in Australia so that pharmacists can sell cannabis with low THC concentrations without prescription to those aged 18 or over.

A prescription is currently needed for CBD under the current TGA's Poison Standard but under the amendments approved CBD products could be sold with professional advice from pharmacists, at a dose of up to 150 mg a day. A government spokesman said no legislative amendment in Tasmania is required for this change. Cannabis Awareness Tasmania founder Lyn Cleaver said it was a shame that children are excluded from the changes to access but added that low doses of CBD would not assist young epilepsy sufferers nor would they help adults such as her son. Such low doses of CBD might instead benefit those with anxiety, post-traumatic stress disorder, insomnia and chronic pain.

Examiner of 17 December 2020

Science/Human: CBD may improve symptoms of Parkinson’s disease

Patients with Parkinson’s disease may propagate from high CBD doses, but these may be associated with liver damage. A CBD extract (Epidiolex) was titrated from 5 to 20-25 mg per kilogram bodyweight and maintained for 10 to 15 days. The study was conducted at the Department of Neurology of the University of Colorado School of Medicine in Aurora, USA.

All 13 participants with a mean age of 68 years reported side effects, including diarrhoea (85%), somnolence (69%), fatigue (62%), weight gain (31%), dizziness (23%), abdominal pain (23%), and headache, weight loss, nausea, anorexia, and increased appetite (each 5%). Adverse events were mostly mild; none serious. Elevated liver enzymes occurred in five only. Three dropped out due to intolerance. Ten that completed the study had improvement in total and motor scores on the Movement Disorder Society Unified Parkinson Disease Rating Scale. Night-time sleep and emotional/behavioural dyscontrol scores also improved significantly. Authors wrote that “CBD, in the form of Epidiolex, may be efficacious in PD, but the relatively high dose used in this study was associated with liver enzyme elevations.”

Leehey MA, Liu Y, Hart F, Epstein C, Cook M, Sillau S, Klawitter J, Newman H, Sempio C, Forman L, Seeberger L, Klepitskaya O, Baud Z, Bainbridge J. Safety and Tolerability of Cannabidiol in Parkinson Disease: An Open Label, Dose-Escalation Study. Cannabis Cannabinoid Res 2020;5(4):326-336.

Science/Human: Cannabis reduces the use of prescription opioids

Cannabis use was associated with a reduction of opioids within 6 months after initiation of cannabis use. The Tilray Observational Patient Study took place at 21 medical clinics throughout Canada. This analysis includes 1,145 patients who had at least one post baseline visit, with follow-up at 1, 3, and 6 months. The study was led by investigators of the University of Victoria, Canada.

Baseline opioid use was reported by 28% of participants, dropping to 11% at 6 months. Mean daily opioid use went down from 152 mg morphine milligram equivalent at baseline to 32 mg MME at 6 months. Similar reductions were also seen in the other four primary prescription drug classes identified by participants, and statistically significant improvements were reported in a questionnaire on quality of life. Authors concluded that “the subsequent reductions in opioid use suggest that cannabis may play a harm reduction role in the opioid overdose crisis, potentially improving the quality of life of patients and overall public health.”

Lucas P, Boyd S, Milloy MJ, Walsh Z. Cannabis Significantly Reduces the Use of Prescription Opioids and Improves Quality of Life in Authorized Patients: Results of a Large Prospective Study. Pain Med 2020:pnaa396.

News in brief

Science/Human: Cannabis use was not associated in the development of a second cancer
In 513 patients diagnosed with head and neck cancer, who were followed between 2011 and 2015 cannabis use in 59 of them was not associated with an increased risk to develop a secondary primary cancer. Authors concluded that this study “suggests that cannabis use behaves differently than tobacco smoking.”
Otolaryngology - Head and Neck Surgery, McMaster University, Hamilton, Canada.
Kim J et al. Cureus 2020;12(11):e11483.

Science/Cells: Cannabis extracts reduce viability of melanoma cells
Administration of a cannabis extract alone or together with radiation substantially inhibited melanoma cell viability and proliferation in the extract dose response-dependent manner. The inhibition of melanoma cell viability was paralleled by an increase in necrosis but not apoptosis when melanoma cells were treated with the extract alone.
Isfahan University of Medical Sciences, Iran.
Naderi J, et al. J Cancer Res Ther 2020;16(6):1495-1499.

Science: CBD acts at the 5-HT1A receptor in human brain
Investigators found that “at high concentrations, CBD acts as an inverse agonist of 5-HT1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients” with drug-resistant epilepsy.
Department of Pharmacobiology, Center for Research and Advanced Studies, Mexico City, Mexico.
Martínez-Aguirre C, et al. Front Behav Neurosci 2020;14:611278.

Science/Animal: Inhibition of CYP3A may considerably increase CBD concentration
Pre-treatment of rats with 50 mg ketoconazole per milligram bodyweight, which strongly inhibits CYP3A, an enzyme which participates in the degradation of CBD and the liver, before oral administration of high doses of CBD (10 to 50 mg per kilogram bodyweight) resulted in an increased CBD blood plasma concentration of approximately 3 times. Authors wrote that “it is proposed that caution for dose-dependent drug interactions should be considered for CBD.”
School of Pharmacy, Showa University, Tokyo, Japan.
Nagao M, et al. Cannabis Cannabinoid Res 2020;5(4):318-325.

Science/Cells: CBD causes mitochondrial dysfunction in leukaemia cells
Research shows that CBD, curcumin and quercetin were cytotoxic against leukaemia cells and this effect was shown to be mediated by effects on the mitochondria, the powerhouses of the cells.
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Mexico.
Olivas-Aguirre M, et al. Int J Mol Sci 2020;22(1):E204.

Science/Animal: A lack of CB1 receptors leads to an enhanced age-related loss of certain nerve cells
It is known that a disruption of CB1 receptor activity accelerates brain ageing. Researchers demonstrated that mice without CB1 receptors have fewer nerve cells with receptors for noradrenaline.
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Germany.
Gargano A, et al. Int J Mol Sci 2020;22(1):E5.

Science/Human: No association between cannabis use and atherosclerosis
An analysis of 5115 US citizens from the so-called CARDIA Study found no association between cannabis use and thickness of the carotid, the main artery of the neck. Authors concluded that their “study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.”
Institute of Primary Health Care (BIHAM), University of Bern, Switzerland.
Jakob J, et al. Am J Med 2020:S0002-9343(20)31128-1.

Science: Cannabinoids may be helpful in autism due to their anti-inflammatory effects
A review discusses the current evidence supporting a key role of the endocannabinoid system in the neuroinflammatory state that characterizes autism spectrum disorder, “providing hints to identify new biomarkers in ASD and promising therapies for the future.”
Department of Science, Section of Biomedical Sciences and Technologies, Rome, Italy.
Carbone E, et al. Neurosci Biobehav Rev 2020;121:128-143.

Science/Cells: CBD and THC improved regeneration of stem cells
A study demonstrates that CBD and THC “can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. (…) Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds.”
Department of Surgery, Cooper University Hospital, New Jersey, USA.
Miller H, et al. Cell Biochem Funct. 2020 Dec 21. [in press]

Science/Animal: High doses of CBD may have negative effects on the heart
In a study with rats CBD in a dose of 10 mg per kilogram bodyweight impaired relaxing effects of other medications and in healthy “hearts CBD led to untoward structural and functional effects.” Authors concluded that “due to its modest beneficial effect in hypertension and its adverse effects in normotensive hearts, caution should be taken when using CBD as a drug in therapy.”
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Poland.
Pędzińska-Betiuk A, et al. Toxicol Appl Pharmacol 2020;411:115368.

Science/Human: Cannabis use alone in adolescents was not associated with suicide risk
In a study with 71 adolescents, who were hospitalised for a suicide risk, cannabis use alone wasn’t associated with suicide risk, but a combination of cannabis and alcohol use was.
Department of Psychiatry, Boston Children's Hospital, USA.
Sellers CM, et al. Addict Behav 2020;114:106759.

Science/Human: Cannabis use was associated with suicidal ideation among patients with opioid use disorder
In a study with 2335 participants with opioid use disorder cannabis use was associated with a 41% increased risk for suicidal ideation (Odds ratio: 1.41).
Department of Family Medicine, McMaster University, Ontario, Canada.
Naji L, et al. J Addict Med. 2020 Dec 17. [in press]

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