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IACM-Bulletin of 21 May 2023
According to an analysis of data from 306 fibromyalgia patients in the UK Medical Cannabis Registry the treatment with cannabis was associated with a global health-related improvement of quality of life. The research was conducted by investigators of the Medical Cannabis Research Group from the Department of Surgery and Cancer at Imperial College London, UK.
The medical use of cannabis “was associated with improvements in fibromyalgia-specific symptoms, in addition to sleep, anxiety, and health-related quality of life. Those who reported prior cannabis use appeared to have a greater response.”
Wang C Erridge S, Holvey C, Coomber R, Usmani A, Sajad M, Guru R, Holden W, Rucker JJ, Platt MW, Sodergren MH. Assessment of clinical outcomes in patients with fibromyalgia: Analysis from the UK Medical Cannabis Registry. Brain Behav. 2023:e3072.
According to an observational study with 3148 patients, who were receiving cannabis for any indication, the treatment was associated with an increased health-related quality of life. Investigators from the Centre for Human Psychopharmacology at Swinburne University of Technology in Melbourne, Australia, and other scientific institutions in Australia reported of patients at a network of specialist medical clinics between December 2018 and May 2022.
Cannabis products types and cannabinoid content varied over time in accordance with the treating physician's clinical judgement. Mean Age was 56 years at baseline before treatment. Chronic noncancer pain was the most common indication for treatment (69%), followed by cancer pain (6%), insomnia (5%), and anxiety (4%). After commencing treatment with medical cannabis, patients reported significant improvements relative to baseline on all 8 domains of a questionnaire in health-related quality of life and these improvements were mostly sustained over time.
Using data of the Quebec Cannabis Registry Canadian and Irish investigators found significant improvements in pain of 358 cancer patients. Statistically significant decreases were observed at 3-month, 6-month and 9-month follow-up on the worst and average pain.
THC:CBD balanced strains were associated with better pain relief as compared with THC-dominant and CBD-dominant strains. Researchers concluded that “real-world data from this large, prospective, multicentre registry indicate that MC is a safe and effective complementary treatment for pain relief in patients with cancer.”
Aprikian S, Kasvis P, Vigano M, Hachem Y, Canac-Marquis M, Vigano A. Medical cannabis is effective for cancer-related pain: Quebec Cannabis Registry results. BMJ Support Palliat Care. 2023:spcare-2022-004003.
Science/Human: Pain reduction by the opioid hydromorphone was only slightly improved by a low dose of oral THC in a placebo-controlled study
According to a study with 37 patients diagnosed with knee osteoarthritis a fixed dose of 10 mg of THC in addition to 4 mg of hydromorphone investigators of Johns Hopkins University in Baltimore, USA, noted only “minimal benefit” of oral THC (dronabinol). This was a double-blind, randomized, placebo-controlled study. Participants received (1) placebo-placebo, (2) hydromorphone (4 mg)-placebo; (3) dronabinol (10 mg)-placebo, and (4) hydromorphone (4 mg)-dronabinol (10 mg).
No significant analgesic effects were observed for clinical pain severity or physical functioning across all drug conditions. Authors noted that “little enhancement of hydromorphone analgesia by dronabinol was observed on evoked pain indices.” Side effects of the combination of hydromorphone and dronabinol produced more moderate adverse events than both placebo and hydromorphone alone. Only hydromorphone impaired cognitive performance.
Campbell CM, Mun CJ, Hamilton KR, Bergeria C, Huhn AS, Speed TJ, Vandrey R, Dunn KE. Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain. Neuropsychopharmacology. 2023 May 18 [in press].
Science/Human: CBD may be an effective adjuvant treatment in adults with drug-resistant focal epilepsy
According to an observational, prospective cohort study with 44 adult epilepsy patients CBD treatment showed an additional benefit. Investigators of the National University Arturo Jauretche in Buenos Aires, Argentina, included patients with the drug-resistant focal epilepsy for at least 6 months.
After starting the CBD therapy 5% of patients became seizure-free, 32% of patients reduced their seizures more than 80% and 87% of patients reduced 50% of their monthly seizures. Eleven percent presented a decrease of less than 50% in seizure frequency. The average final daily dose was 335 mg of oral CBD. Authors wrote that “at the end of the study, we found in most patients a significant improvement in the quality of life, in all the items evaluated.”
In a multicentre study from Argentina CBD reduced seizures in children with epilepsy with myoclonic-atonic seizures (EMAtS) (n = 22) and Sturge Weber syndrome (SWS) with myoclonic-atonic seizures (n = 4). CBD was added in doses ranging from 8 to 40 mg per kilogram per day. Efficacy was assessed by comparing seizure frequency before and after initiating CBD therapy.
After a mean follow-up of 19 months, 15 of 26 patients who received add-on CBD had a greater than 50% seizure decrease and three became seizure-free. The remaining 11 patients had a 25-50% seizure reduction. Authors wrote that “drop attacks, including myoclonic-atonic seizures and generalized tonic-clonic seizures, as well as atypical absences and nonconvulsive status epilepticus responded well to CBD.”
Caraballo RH, Reyes Valenzuela G, Fortini S, Espeche A, Gamboni B, Silva W, Semprino M, Fasulo L, Chacón S, Gallo A, Galicchio S, Cachia P. Cannabidiol in children with treatment-resistant epilepsy with myoclonic-atonic seizures. Epilepsy Behav. 2023;143:109245.
Retrospective data were collected for up to 9 years on cannabis use evaluating disease characteristics and cannabis influence from patients with Tourette syndrome being treated in the Movement Disorders Unit of the Tel-Aviv Medical Center, Israel.
Twenty-five patients participated in the study. The mean duration of medical cannabis use was 4 years (range 0.5-10). The majority of patients (96%) consumed cannabis primarily, but not exclusively, through inhalation methods such as smoking or vaporizing dried inflorescence. Cannabis led to a subjectively reported reduction in tics (75% average reduction) and symptoms associated with common comorbidities of the disease.
Anis S, Zalomek C, Korczyn AD, Lassman S, Rosenberg A, Gurevich T. Licensed Medical Cannabis Use in Gilles de la Tourette Syndrome: A Retrospective Long-term Follow-Up. Cannabis Cannabinoid Res. 2023 May 12 [in press].
In an open-label, crossover design with 20 e-cigarette users oral administration of 320 mg CBD reduced withdrawal severity. The study was presented by investigators of the Department of Psychological Sciences at the University of Arkansas in Fayetteville, USA, of the University of Texas, the University of Mississippi and of Canopy Growth from Canada. Participants self-reported symptoms following a 4-h e-cigarette abstinence period compared to abstinence in the absence of CBD.
After controlling for participants' positive CBD expectancies, results were consistent with hypotheses, suggesting CBD reduced both nicotine withdrawal symptom severity and state anxiety during e-cigarette abstinence.
Gournay LR, Petry J, Bilsky S, Hill MA, Feldner M, Peters E, Bonn-Miller M, Leen-Feldner E. Cannabidiol Reduces Nicotine Withdrawal Severity and State Anxiety During an Acute E-cigarette Abstinence Period: A Novel, Open-Label Study. Cannabis Cannabinoid Res. 2023 May 11 [in press].
In a study from the US with 1793 adults experiencing symptoms of sleep disturbance 15 mg of oral CBD were as effective as 5 mg melatonin in improving sleep. Investigators from California, Pennsylvania and Maryland in the US assigned participants to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15 mg CBD or 5 mg melatonin, alone or in combination with CBN (cannabinol) or CBC (cannabichromene).
All formulations exhibited a favourable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance. Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15 mg CBD isolate and formulations containing 15 mg CBD and 15 mg CBN, alone or in combination with 5 mg CBC. There were also no significant differences in effect between 15 mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15 mg CBD and 15 mg CBN.
Saleska JL, Bryant C, Kolobaric A, D'Adamo CR, Colwell CS, Loewy D, Chen J, Pauli EK. The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial. J Am Nutr Assoc. 2023:1-11.
In a study with 20 patients with dementia and severe behavioural and psychological symptoms low doses of CBD improved symptoms. A study conducted by investigators of the Faculty of Health Sciences at Aristotle University of Thessaloniki, Greece. Ten of them were assigned to usual medical treatment, while ten were assigned to a six-month treatment with CBD.
The follow-up assessment showed significant improvement of the symptoms in all patients who received CBD, and no or limited improvement in the control group, regardless of the underlying neuropathology of dementia.
Investigators of the University of British Columbia in Vancouver, Canada, conducted a cross-sectional study of questionnaire responses from female patients with myofascial pelvic pain from two tertiary pelvic pain centres. Of the 135 participants 57% were cannabis users and 43% were non-users.
Most users consumed cannabis daily, (48%) orally (66%) or by smoking (61%), and rated cannabis as effective at relieving pelvic pain. 64% of non-cannabis users responded that they would be willing to use cannabis for pelvic pain. Lack of information and potential adverse effects were the most common reasons for unwillingness to use. Approximately 3 of 4 respondents were willing to try vaginal or vulvar application of cannabis products for pelvic pain.
Yang EC, Koenig NA, Gong M, Brotto LA, Barr AM, Lee T, Yong PJ, Geoffrion R. Cannabis use preferences in women with myofascial pelvic pain: A cross-sectional study. Eur J Obstet Gynecol Reprod Biol X. 2023;18:100192.
Since 2014 when sales began in Colorado and Washington, legalization policies have provided states a new revenue stream. Through the end of 2022, states have reported a combined total of more than 15 billion dollars in tax revenue from legal, adult-use cannabis sales. In 2022, legalization states generated more than 3.5 billion dollars in cannabis tax revenue from adult-use sales. In addition to revenue generated for state-wide budgets, cities and towns have also generated hundreds of thousands of dollars in new revenue from local adult-use cannabis taxes.
According to studies with mice CBD may be an “antidepressant with faster action and efficiency than” sertraline.
Instituto de Neurociencias, Universidad Miguel Hernández, Alicante, Spain.
Nerve cells from the cerebellum were treated with a neurotoxic agent. And CBD protected from this damage.
Laboratorio de Mecanismos de Neurodegeneración y Neuroprotección and Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
In a phase 1 study the cannabis extract Epidyolex in daily doses of 600 and 800 mg were safe and tolerable in patients with prostate cancer.
Department of Medicine, Division of Medical Oncology, University of Kentucky, Lexington, USA.
Experiments with human metastatic melanoma samples showed that activation of the CB1 receptor may suppress its growth.
Department of Biochemistry and Molecular Biology, Instituto Universitario de Investigación Neuroquímica, Complutense University of Madrid, Spain.
Science/Cells: CBD may be a promising adjuvant therapy for estrogen receptor -positive breast tumours
Studies with oestrogen receptor positive breast cancer cells showed that CBD when combined with anastrozole and letrozole caused no beneficial effect in comparison to the isolated aromatase inhibitors. In contrast, when combined with the aromatise inhibitor exemestane; CBD potentiated its pro-cell death effects.
UCIBIO/REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal.
By using: cancer cells investigators found therapeutic synergism of a triple combination of CBD/CBG, curcumin, and piperine.
Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey.
Studies with cells show that CBD alleviates neuroinflammation and attenuates neuropathic pain via targeting the protein FKBP5.
Department of Anesthesiology, Lequn Branch, The First Hospital of Jilin University, Changchun, China
Science/Human: Cannabis use does not increase cardiovascular events according to a review and meta-analysis
According to a review the risk of adverse cardiovascular events including acute myocardial infarction and stroke “does not exhibit a significant increase with cannabis exposure. However, caution should be exercised when interpreting the findings due to the heterogeneity of the studies.”
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Theerasuwipakorn N, et al. Toxicol Rep. 2023;10:537-543.
According to a study with 36 patients suffering from cancer cachexia circulating and current levels of endocannabinoids were significantly higher than those in control patients with other diseases. Authors wrote that in patients with cancer cachexia, “circulating AEA may play a role in anorexia, whereas 2-AG may play a role in serum triglyceride levels.”
Division of Physiology, Department of Nutrition, Graduate School of Humanity and Life Science, Tokyo-Kasei University, Tokyo, Japan.
In a nationally representative sample of 2622 participants, current cannabis use was inversely associated with steatosis (fatty liver). “The pathophysiology is unclear and needs further study. No significant association was established between marijuana use and liver fibrosis, irrespective of past or current use.”
Department of Ultrasound, General Hospital of Central Theater Command, Wuchangqu, Wuhan, Hubei, China.
According to a large study called SPIROMICS “participants with or without COPD (chronic obstructive pulmonary disease), neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development.”
Medicine, University of California at Los Angeles, California, USA.
Study results with rats suggest that CBD may alleviate right ventricular fibrosis and “may act as an adjuvant therapy” for pulmonary hypertension.
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Poland.
Average prices for cannabis flowers are about €6 for 1 g of flowers and about €8-€9 for 1 g of resin in Spanish cannabis social clubs.
Center for Interdisciplinary Addiction Research, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Germany.
In a study that followed adults with HIV for up to 10 years “rates of cognitive decline and functional problems did not vary by average cannabis use.” Recent cannabis use was linked to worse cognition.
Department of Psychiatry, University of California San Diego, USA.
According to a study with mice inhibition of endocannabinoid degradation by FAAH inhibition showed neuroprotective effects in frontotemporal dementia.
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain.
A study with rats shows that CBD attenuated periodontitis and inflammation.
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Science/Human: The risk for schizophrenia in cannabis users may be higher in young men than in young women
Researchers examined about 6.9 million individuals with about 45,000 cases of schizophrenia. The risk for development of schizophrenia was 2.5 in males compared to 2.0 in females. In 16 to 20 year old males the risk was 3.8 compared to 1.8 in young women.
Copenhagen Research Center for Mental Health - CORE, Mental Health Center Copenhagen, Copenhagen University Hospital, Denmark.
According to a placebo controlled study 20 mg of CBD for 3 days after uteroscopy was not superior to placebo in reducing pain.
Department of Urology, University of North Carolina, USA.
Science/Animal: A combination of CBD and hypothermia may increase neuroprotective effects in new-borns with hypoxic encephalopathy
The effects of treating new-born rats following hypoxic-ischaemic injury with CBD in hypothermic conditions were investigated. When used together, CBD and hypothermia ameliorated brain excitotoxicity, oxidative stress, and inflammation, reduced brain infarct volume and lessened the extent of histologic damage.
Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
Peripherally injected cannabidiol reduces neuropathic pain in mice and this effect partially involved the 5-HTA1 and TRPV1 receptors.
Department of Pharmacology, Institute of Biological Sciences, Belo Horizonte, Brazil.