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IACM-Bulletin of 28 March 2021

Science/Human: Cannabis may be helpful in pain from unstable angina and coronary artery disease according to a case report

Investigators from the Center for Primary Care Medicine in Lawrenceville, USA, described the case of a 63-year-old man who presented to a primary care physician for a medical cannabis consult due to unstable angina (UA) not relieved by morphine or cardiac medications. He had failed all first- and second-line polypharmaceutical therapies. The patient first presented 22 years ago after a suspected myocardial infarction. He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease. He developed pain due to unstable angina over the past 6 years.

In conjunction with his standard cardiac care, the patient had a gradual lessening of pain, including frequency and character, after using an edible form of cannabis. Following continued treatment, he ceased long-term morphine treatment and described the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.

Shaffer BL, Davis GM, Incitti MA, Piper BJ, Entler BV. Application of medical cannabis in unstable angina and coronary artery disease: A case report. Medicine (Baltimore). 2021;100(11):e25172.

Science/Human: Cannabis may be helpful in the treatment of nausea and vomiting during pregnancy according to a case series

Investigators of Adelson Faculty of Medicine of Ariel University, Israel, presented 4 case reports of women with hyperemesis gravidarum (nausea and vomiting during pregnancy), who profited from a treatment with cannabis. They noted, that “Hyperemesis Gravidarum (HG) responds only partially to standard antiemetic medications.”

There was a highly significant improvement in symptoms. The score of the PUQE (Pregnancy Unique Quantification of Emesis) improved from a mean of 14.5 to 7.5 in addition to an improvement in quality of life. Authors wrote that these “results suggest that cannabis may be effective for HG, and should be studied in appropriately powered, controlled studies, fully considering potential fetal risks.”

Koren G, Cohen R. The use of cannabis for Hyperemesis Gravidarum (HG).J Cannabis Res, 2020;2(4).

Science/Human: Cannabis may be effective in the treatment of Hodgkin’s lymphoma according to a case report

Self-treatment with cannabis resulted in a reduction of tumour mass of Hodgkin’s lymphoma in a woman, who refused chemotherapy due to her pregnancy. This case was reported by investigators from the Faculty of Medicine and Pharmacy of the University of Oradea, Romania. The 21-year-old patient was diagnosed with stage IIB Hodgkin’s lymphoma and started first line chemotherapy and radiotherapy, with incomplete remission.

Five years later, she became pregnant for the second time and was proposed termination of pregnancy, that she refused. A MRI scan revealed progression of Hodgkin’s lymphoma and she was admitted in the hospital several times for altered general condition, respiratory infections and increased need of painkillers including opioids. At 26 weeks of pregnancy, the patient began on her own a treatment with pure cannabis. Her pain and general status got better and the tumor tissue decreased. She delivered by cesarean section at 34 weeks a boy. Authors concluded that “cannabis could be part of oncological treatment. No other case like this, as far as we know, has been previously reported.”

Huniadi A, Sorian A, Iuhas C, Bodog A, Sandor MI. The effect of cannabis in the treatment of Hodgkin's lymphoma in a pregnant patient - extensive case report and literature review. J BUON. 2021;26(1):11-16.

News in brief

Israel: About 85,000 patients receive cannabis for medicinal use
The number of cannabis patients has crossed the 85,000 mark in February 2021, including an increase of about 2,000 in the last month alone, slightly lower than the monthly average of about 3,000 new patients a month in recent months.
Cannabis Magazine of 17 March 2021

Zambia: The government wants to legalise the cultivation of cannabis for medicinal use
Zambia’s cabinet has approved the publication and introduction of a bill in parliament to legalise the cultivation of cannabis.
News Agency of Nigeria of 3 March 2021

Science: CBD shows antiviral effects against the new coronavirus
CBD and its metabolite, 7-OH-CBD potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription.
Ben May Department for Cancer Research, University of Chicago, USA.
Nguyen LC, et al. bioRxiv, 2021, Mar 10. [under review].

Science/Human: Cannabis may increase exercise
In a study with 12,043 young adults results “show that, particularly for fixed-effects models, marijuana use is not significantly related to exercise, counter to conventional wisdom that marijuana users are less likely to be active. Indeed, the only significant estimates suggest a positive relationship, even among heavier users during the past 30 days.”
Department of Health Management and Policy, Miami Herbert Business School, University of Miami, Coral Gables, USA.
French MT, et al. Prev Med. 2021 Mar 9:106518.

Science/Human: Legalisation in Canada did not have an effect on cannabis use in adolescents
In a large study results show that “it appears that cannabis legalization has not yet been followed by pronounced changes on youth cannabis use. High prevalence of youth cannabis use in this sample remains a concern. These data suggest that the Cannabis Act has not yet led to the reduction in youth cannabis use envisioned in its public health approach.”
University of Waterloo, School of Public Health and Health Systems, Waterloo, Canada.
Zuckermann AME, et al. Science Direct, 2021, Jun 12:.101351

Science/Human: Alcohol but not cannabis use reduced thickness of the brain cortex
According to a study with 436 twins aged 24 years greater alcohol, but not cannabis use was associated with reduced thickness of the cortex in several brain regions.
Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, USA.
Harper J, et al. Biol Psychiatry. 2021 Jan 20:S0006-3223(21)00048-

Science/Human: Medical cannabis laws in the US are not associated with higher cannabis use by adolescents
According to an analysis with 1,091,723 participants in the years 1991 to 2015 “adolescents reporting any past 30-day marijuana use was lower in states that enacted MMLs any time during the study period.” Authors also “found no effects on heavy marijuana use.”
Cannabis Control Commission, Commonwealth of Massachusetts, Worcester, USA.
Johnson JK, et al. Subst Abus. 2021 Mar 22:1-5.

Science/Human: "When they say weed causes depression, but it's your favourite antidepressant"
An article entitled “When they say weed causes depression, but it's your fav antidepressant" analyses the relationship between cannabis and depression.
Wright State University, Dayton, Ohio, USA.
Yadav S, et al. PLoS One. 2021;16(3):e0248299.

Science/Human: CBD may reduce alcohol consumption according to an observational study
According to an observational study with 120 cannabis and alcohol users, which compared 3 groups, a group using cannabis with high THC, a group using cannabis strains high in THC and CBD and a group using high CBD strains, the CBD group drank fewer drinks per drinking day and had fewer alcohol use days. There was no difference between the THC and the THC/CBD groups.
Department of Psychology, Colorado State University, Fort Collins, CO, USA.
Karoly HC, et al. Psychol Addict Behav. 2021 Mar 25. [in press].

Science/Animal: Both CBD and THC reduce neuropathic pain
In studies with mice both THC and CBD provided analgesic effects against neuropathic pain. Authors wrote that this “suggests that CBD provides a safer, albeit lower efficacy, oral treatment for nerve injury induced neuropathic pain than THC-containing preparations.”
Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, University of Sydney at Royal North Shore Hospital, NSW, Australia.
Mitchell VA, et al. Neuropharmacology. 2021 Mar 16:108529.

Science/Human: Dysregulation of the immune system influences the cannabis-psychosis association
According to an analysis of the immune status of 153 first-episode psychotic patients and 256 healthy controls “immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis-psychosis association, in line with a two-hit hypothesis.”
Department of Neuroscience and Behaviour, Division of Psychiatry, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Corsi-Zuelli F, et al. Psychol Med. 2021 Mar 19:1-11.

Science/Human: Many illicit drug users use cannabis for harm reduction
In a study with people use drugs based in Vancouver, Canada, “approximately 1 in 4 participants reported using cannabis for harm reduction at least once during the study period.”
British Columbia Centre on Substance Use, Vancouver, BC, Canada.
Mok J, et al. Am J Public Health. 2021 Mar 18:e1-e4.

Science/Human: People with bipolar disorder use cannabis more often
An analysis of data on bipolar disorder and cannabis use show that “genetic liability to bipolar disorder was significantly associated with an increased risk of lifetime cannabis use; however, genetic liability to lifetime cannabis use showed no association with the risk of bipolar disorder.”
Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Denmark.
Jefsen OH, et al. Addict Biol. 2021 Mar 17:e13030.

Science/Human: The legalisation of cannabis in the USA was associated with an increased risk for fatal traffic accidents
A study shows that “recreational cannabis legalization in the US was associated with a relative increased risk of fatal motor vehicle collisions of 15% and a relative increase in associated deaths of 16%, with no conclusive difference between the first and subsequent years after legalization.”
McGill University, Montréal, Canada.
Windle SB, et al. CMAJ Open. 2021;9(1):E233-E241.

Science/Cells: How cannabinoids exert their anti-cancer effects in ER(+) breast cancer
Research with cannabinoids in ER(+) breast cancer cells shows that the anti-cancer effects involve aromatase and steroid receptors.
Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal.
Amaral C, et al. J Steroid Biochem Mol Biol. 2021 Mar 17;210:105876.

Science/Human: Cannabis was not effective in the treatment of post-traumatic stress disorder in a controlled study
In a cross-over study on cannabis in post-traumatic stress disorder 80 participants received 1 of 3 strains of smoked cannabis (12% THC and very low CBD, 11% CBD and very low THC, about 8% THC and 8% CBD) or a placebo for 3 weeks separated by 2 weeks without treatment. There were no differences in treatment effects between the active cannabis strains and placebo. Authors wrote that “all treatment groups, including placebo, showed good tolerability and significant improvements in PTSD symptoms during three weeks of treatment, but no active treatment statistically outperformed placebo in this brief, preliminary trial.”
Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Bonn-Miller MO, et al. PLoS One. 2021;16(3):e0246990.

Science/Human: Very mild effects of CBD on white matter structure in patients with epilepsy
Researchers found only very mild effects of high CBD doses in patients with treatment resistant epilepsy on white matter structural integrity of the brain.
Department of Neurology and UAB Epilepsy Center, University of Alabama at Birmingham, USA.
Houston JT, et al. Epilepsy Res. 2021 Mar 8;172:106603.

Science: THC may be helpful in Alzheimer’s disease
In a study using atom molecular dynamics simulation researchers show that THC disrupts the structure of the amyloid-beta fibrils. Researchers wrote that the “destabilization of the protofibrils by the THC molecules leads to the conclusion that THC molecules may be considered for the therapy in treating Alzheimer's disease.”
Department of Chemical Engineering, Indian Institute of Technology Guwahati, Assam, India.
Kanchi PK, et al. J Mol Graph Model. 2021 Mar 9;105:107889.

Science/Animal: CBD influences molecules relevant for inflammation, a study with horses shows
In a study with horses, which received 0.5, 1 and 2 mg CBD per kilogram bodyweight researchers found changes in levels of so-called eicosanoids, in a way that is indicative of anti-inflammatory effects. Eicosanoids such as prostaglandins are signalling molecules, which among others are relevant for inflammation.
K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
Ryan D, et al. Drug Test Anal. 2021 Mar 15. [in press]

Science/Cells: Low THC concentrations protect nerve cells during overexcitation
A study found that CB1 receptors play a role in the growth of nerve cells and the low concentration of THC protects nerve cells during overexcitation.
The Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Savchenko VL, et al. Cell Mol Neurobiol. 2021 Mar 16. [in press]

Science/Animal: Activation of the CB1 receptor protects the organism from social stress
A study with mice shows “that CB1 signalling protects the organism from the physical and emotional harm of social stress and implicate endocannabinoid-mediated modulation of microglia in the development of stress-related pathologies.”
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Germany.
Beins EC, et al. Transl Psychiatry. 2021;11(1):164.

Science/Human: Anandamide (AEA) plays a role in fear extinction
In a study with 51 healthy humans results “indicate a putative role for AEA in fear extinction learning. Pre-treatment with AEA-enhancing drugs could promote extinction learning during psychotherapeutic interventions.”
Clinic for Child and Adolescent Psychiatry/Psychotherapy, Ulm University, Germany.
Spohrs J, et al. Transl Psychiatry. 2021;11(1):161.

Science/Animal: Hemp oil may reduce pain
In an animal study different doses of hemp oil reduced acute and chronic pain. It was also effective if combined with different doses of palmitoylethanolamine.
Department of Anatomy and Neurobiology, University of California, USA.
Tagne AM, et al. Pharmacol Res. 2021 Mar 12:105545.

Science/Animal: Chronic inflammatory pain causes changes of CB1 receptors in a certain brain region
Animal studies show that inflammatory pain induces changes in localisation of CB1 receptors in the so-called PAG (periaqueductal gray), a major pain centre in the brain. Authors wrote that these “findings complement a growing body of evidence which demonstrate pain-induced changes in brain regions that are responsible for both the analgesic and rewarding properties of analgesic pharmacotherapies.”
Department of Neurobiology, Legacy Research Institute, Portland, USA.
Wilson-Poe AR, et al. Pain Rep. 2021;6(1):e897.

Science/Human: Stable blood concentrations of CBD were reached after 7 days of dosing
In a study 43 healthy people were divided in 5 dose groups: 120 mg CBD and 5.4 mg THC daily, 240 mg CBD and 10.8 mg THC daily, 360 mg CBD and 16.2 mg THC daily, 480 mg CBD and 21.6 mg THC daily, or placebo. Steady-state blood CBD concentrations were reached by Day 7. Across Days 1 and 7, there were no consistent differences in subjective effects between placebo and active study medication.
Canopy Growth Corporation, Smiths Falls, Ontario, Canada.
Peters EN, et al. J Anal Toxicol. 2021 Mar 12:bkab026.

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