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Sager AR, Desai R, Mylavarapu M, Shastri D, Devaprasad N, Thiagarajan SN, Chandramohan D, Agrawal A, Gada U, Jain A. Cannabis use disorder and severe sepsis outcomes in cancer patients: Insights from a national inpatient sample. World J Crit Care Med 2025; 14:100844. [DOI: 10.5492/wjccm.v14.i2.100844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 01/08/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND The burden of cannabis use disorder (CUD) in the context of its prevalence and subsequent cardiopulmonary outcomes among cancer patients with severe sepsis is unclear.
AIM To address this knowledge gap, especially due to rising patterns of cannabis use and its emerging pharmacological role in cancer.
METHODS By applying relevant International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes to the National Inpatient Sample database between 2016-2020, we identified CUD(+) and CUD(-) arms among adult cancer admissions with severe sepsis. Comparing the two cohorts, we examined baseline demographic characteristics, epidemiological trends, major adverse cardiac and cerebrovascular events, respiratory failure, hospital cost, and length of stay. We used the Pearson χ2 d test for categorical variables and the Mann-Whitney U test for continuous, non-normally distributed variables. Multivariable regression analysis was used to control for potential confounders. A P value ≤ 0.05 was considered for statistical significance.
RESULTS We identified a total of 743520 cancer patients admitted with severe sepsis, of which 4945 had CUD. Demographically, the CUD(+) cohort was more likely to be younger (median age = 58 vs 69, P < 0.001), male (67.9% vs 57.2%, P < 0.001), black (23.7% vs 14.4%, P < 0.001), Medicaid enrollees (35.2% vs 10.7%, P < 0.001), in whom higher rates of substance use and depression were observed. CUD(+) patients also exhibited a higher prevalence of chronic pulmonary disease but lower rates of cardiovascular comorbidities. There was no significant difference in major adverse cardiac and cerebrovascular events between CUD(+) and CUD(-) cohorts on multivariable regression analysis. However, the CUD(+) cohort had lower all-cause mortality (adjusted odds ratio = 0.83, 95% confidence interval: 0.7-0.97, P < 0.001) and respiratory failure (adjusted odds ratio = 0.8, 95% confidence interval: 0.69-0.92, P = 0.002). Both groups had similar median length of stay, though CUD(+) patients were more likely to have higher hospital cost compared to CUD(-) patients (median = 94574 dollars vs 86615 dollars, P < 0.001).
CONCLUSION CUD(+) cancer patients with severe sepsis, who tended to be younger, black, males with higher rates of substance use and depression had paradoxically significantly lower odds of all-cause in-hospital mortality and respiratory failure. Future research should aim to better elucidate the underlying mechanisms for these observations.
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Affiliation(s)
- Avinaash R Sager
- Internal Medicine, St. Elizabeth’s Medical Center, Boston, MA 02135, United States
| | - Rupak Desai
- Outcomes Research, Independent Researcher, Atlanta, GA 30033, United States
| | | | - Dipsa Shastri
- Internal Medicine, East Tennessee State University, Johnson, TN 37614, United States
| | - Nikitha Devaprasad
- Internal Medicine, SRM Medical College Hospital and Research Center, Potheri 603211, India
| | - Shiva N Thiagarajan
- Internal Medicine, SRM Medical College Hospital and Research Center, Potheri 603211, India
| | - Deepak Chandramohan
- Department of Nephrology, University of Alabama at Birmingham, Birmingham, AL 35001, United States
| | | | - Urmi Gada
- Infectious Diseases, Deenanath Hospital, Erandwane 411004, India
| | - Akhil Jain
- Department of Hematology and Medical Oncology, University of Iowa Hospitals and Clinics, Iowa, IA 52242, United States
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Chow R, Basu A, Kaur J, Hui D, Im J, Prsic E, Boldt G, Lock M, Eng L, Ng TL, Zimmermann C, Scotte F. Efficacy of cannabinoids for the prophylaxis of chemotherapy-induced nausea and vomiting-a systematic review and meta-analysis. Support Care Cancer 2025; 33:193. [PMID: 39953210 PMCID: PMC11828838 DOI: 10.1007/s00520-025-09251-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 02/06/2025] [Indexed: 02/17/2025]
Abstract
BACKGROUND Cannabinoids have potential efficacy as prophylaxis for chemotherapy-induced nausea and vomiting (CINV), but no recent meta-analysis has reported on their relative efficacy compared to other antiemetics. The aim of this meta-analysis is to examine the relative efficacy of cannabinoids for prophylaxis of CINV. METHODS A literature search was conducted in OVID Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception up until March 2024. Articles were included if they reported on complete response, no nausea, no vomiting or no use of rescue medications, and were randomized controlled trials with cannabinoids in one arm. Meta-analysis was conducted for each endpoint and for a composite endpoint amalgamating existing endpoints. Subgroup analyses by medication used in control arm and by study design were conducted. Cumulative and leave-one-out analysis was also conducted. Type I error was set at 0.05. RESULTS A total of 26 studies were included in this meta-analysis, of which 23 were published before the 2000s. Nearly half of the included studies had some concern for bias. Cannabinoid had superior overall CINV control compared to placebo (RR 2.65, 95% CI 1.70-4.12, I2 = 0.00%). However, there was no difference between cannabinoid and active treatment alternatives (most using dated single-agent regimens) for any outcomes. A recent phase II/III trial demonstrated superior efficacy of THC:CBD for secondary prevention of CINV when used as adjunctive therapy alongside modern antiemetic regimens, albeit mostly without olanzapine. CONCLUSIONS There is scant evidence for efficacy of cannabinoids for CINV in the era of triple and quadruple antiemetics. Although THC:CBD showed promised in a recent trial, further trials should examine its safety and efficacy in the context of regimens containing olanzapine.
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Affiliation(s)
- Ronald Chow
- Princess Margaret Cancer Centre, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
- Centre for Evidence-Based Medicine, University of Oxford, Oxford, UK.
- Verspeeten Family Cancer Centre, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
| | - Anna Basu
- Verspeeten Family Cancer Centre, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada
| | - Jagdeep Kaur
- Verspeeten Family Cancer Centre, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada
| | - David Hui
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - James Im
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Elizabeth Prsic
- Yale School of Medicine, Yale University, New Haven, CT, USA
| | - Gabriel Boldt
- Verspeeten Family Cancer Centre, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada
| | - Michael Lock
- Verspeeten Family Cancer Centre, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada
| | - Lawson Eng
- Princess Margaret Cancer Centre, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Terry L Ng
- Faculty of Medicine, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada
| | - Camilla Zimmermann
- Princess Margaret Cancer Centre, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Florian Scotte
- Gustave Roussy, Université Paris-Saclay Faculté de Médecine, Université Paris-Saclay, Paris, France
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Scott C, Hall S, Zhou J, Lehmann C. Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19-A Scoping Review. J Clin Med 2023; 13:227. [PMID: 38202234 PMCID: PMC10779964 DOI: 10.3390/jcm13010227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/21/2023] [Accepted: 12/27/2023] [Indexed: 01/12/2024] Open
Abstract
Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute "long" COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations. This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.
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Affiliation(s)
- Cassidy Scott
- Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 1X5, Canada; (C.S.); (J.Z.)
| | - Stefan Hall
- Department of Physiology and Biophysics, Dalhousie University, Halifax, NS B3H 1X5, Canada;
| | - Juan Zhou
- Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 1X5, Canada; (C.S.); (J.Z.)
| | - Christian Lehmann
- Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 1X5, Canada; (C.S.); (J.Z.)
- Department of Physiology and Biophysics, Dalhousie University, Halifax, NS B3H 1X5, Canada;
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Tarasiuk A, Mirocha G, Fichna J. Current status of Complementary and Alternative Medicine Interventions in the Management of Pancreatic Cancer - An Overview. Curr Treat Options Oncol 2023; 24:1852-1869. [PMID: 38079061 PMCID: PMC10781793 DOI: 10.1007/s11864-023-01146-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2023] [Indexed: 01/11/2024]
Abstract
OPINION STATEMENT Pancreatic cancer (PC) remains the deadliest cancer worldwide. Most patients are diagnosed at the advanced or metastatic stage, leading to a poor prognosis. Awareness of the limitations of current therapy and accompanying pain, depression, malnutrition, and side effects of chemoradiotherapy may lead patients and physicians towards complementary and alternative medicine (CAM). CAM refers to a diverse set of medical and healthcare practices, products, and systems that are not part of conventional Western medicine. Despite the low-quality evidence supporting the efficacy of these methods, they remain appealing due to patients' beliefs, fear of death, and the slow development of conventional therapy. Hence, the possibility of using natural products for pancreatic cancer is increasing. CAM options such as: medical cannabis, plants, fungi, herbal formulas, and injections, which originate primarily from traditional Chinese or Japanese medicine i.e. Curcuma longa, Panax ginseng, Poria cocos, Hochuekkito, Juzentaihoto, and Rikkunshito, Shi-quan-da-bu-tang/TJ-48, Huang-qin-tang, Shuangbai San, Wen Jing Zhi Tong Fang, Xiang-Sha-Liu-jun-zi-tang, Aidi injection, Brucea javanica oil emulsion/Yadanziyouru injection, Compound Kushen injection, Huachansu injection, Kangai injection and Kanglaite injections are becoming promising candidates for the management of pancreatic cancer. The abovementioned substances/medications are the most popular or potentially effective in PC treatment and consequently CAM-based adjuvant therapy through improving patients' quality of life, might be a useful addition in the treatment of pancreatic cancer patients.
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Affiliation(s)
- Aleksandra Tarasiuk
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland.
| | - Grzegorz Mirocha
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 5, 92-215, Lodz, Poland
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Prateeksha P, Sharma VK, Singh SM, Sharma M, Diwan D, Hesham AEL, Guleria S, Nguyen QD, Gupta VK, Singh BN. Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy. Cancer Metastasis Rev 2023; 42:823-845. [PMID: 36696005 DOI: 10.1007/s10555-023-10078-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 12/31/2022] [Indexed: 01/26/2023]
Abstract
Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality. Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.
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Affiliation(s)
- Prateeksha Prateeksha
- Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, 79410, USA
| | - Vivek K Sharma
- Herbal Nanobiotechnology Lab, Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow, 226001, India
| | - Shiv M Singh
- Department of Botany, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India
| | - Minaxi Sharma
- Haute Ecole Provinciale de Hainaut-Condorcet, Rue de la Sucrerie, 7800, Mons, ATH, Belgium
| | - Deepti Diwan
- Washington University, School of Medicine, Saint Louis, MO 63108, USA
| | - Abd El-Latif Hesham
- Genetics Department, Faculty of Agriculture, Beni-Suef University, Beni-Suef, 62521, Egypt
| | - Sanjay Guleria
- Natural Product-cum-Nano Lab, Division of Biochemistry, Faculty of Basic Sciences, Sher-e-Kashmir University of Agricultural Sciences and Technology of Jammu, Main Campus Chatha, Jammu and Kashmir, 180009, India
| | - Quang D Nguyen
- Department of Bioengineering and Alcoholic Drink Technology, Institute of Food Science and Technology, Hungarian University of Agriculture and Life Sciences, Ménesi út 45, Budapest, H-1118, Hungary
| | - Vijai K Gupta
- Biorefining and Advanced Materials Research Center, SRUC, Kings Buildings, West Mains Road, Edinburgh, EH9 3JG, UK
- Center for Safe and Improved Food, SRUC, Kings Buildings, West Mains Road, Edinburgh, EH9 3JG, UK
| | - Brahma N Singh
- Herbal Nanobiotechnology Lab, Pharmacology Division, CSIR-National Botanical Research Institute, Lucknow, 226001, India.
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Le Bozec A, Guédon M, Brugel M, Laurent M, Carlier C, Hettler D, Perrier M, Aubert L, Slimano F, Mongaret C, Bouché O. Prevalence of cannabidiol (CBD) consumption and cancer patients' expectations in one oncology day-hospital: A cross-sectional study and questionnaire validation. J Oncol Pharm Pract 2023:10781552231187136. [PMID: 37437182 DOI: 10.1177/10781552231187136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
INTRODUCTION The growing interest of cannabidiol (CBD) in medical care prompted French health authorities to explore the potential of CBD in cancer-related severe symptoms. This study aimed to assess the prevalence of CBD use among cancer patients with potential associated factors and to measure the cancer patient's health literacy (HL) on CBD consumption. METHODS In a prospective study in oncology day-care hospital including patients from 29 October to 20 December 2021, we collected demographic, biological, and oncological characteristics. Patient CBD HL was measured by the hetero-questionnaire 8-item-CBD HL scale (HLS-8-CBD) whose conception has been validated by a psychometric analysis. RESULTS Among 363 participants, 20 patients (5.5%) reported CBD use. Factors associated with CBD use were: age <60 years (odd ratio = 7.80[1.36-13.32], p < 10-4 versus ≥60 years), smoking history (OR = 5.53[1.81-16.88], p < 0.01), and no smoking cessation (OR = 5.07[1.66-15.46], p < 0.01). CBD use was also associated with a better CBD total HL score than non-users (p-value = 0.02). CONCLUSION Identification of factors associated with CBD use and a relatively high patient CBD HL in CBD users showed that CBD use in cancer patients care represented a new concern and should enhance health professionals to consider CBD with its associated drug-related problems.
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Affiliation(s)
| | - Marie Guédon
- CHU Reims, Department of Pharmacy, Reims, France
| | - Mathias Brugel
- CHU Reims, Service de Gastroentérologie et Oncologie Digestive, Reims, France
| | | | - Claire Carlier
- CHU Reims, Oncology Day-Hospital, Reims, France
- Institut Jean Godinot, Département d'Oncologie Médicale, Reims, France
| | | | - Marine Perrier
- CHU Reims, Service de Gastroentérologie et Oncologie Digestive, Reims, France
| | - Léa Aubert
- CHU Reims, Oncology Day-Hospital, Reims, France
| | - Florian Slimano
- Université de Reims Champagne-Ardenne, Biospect, CHU Reims, Department of Pharmacy, Reims, France
| | - Céline Mongaret
- Université de Reims Champagne-Ardenne, BIOS, CHU Reims, Department of Pharmacy, Reims, France
| | - Olivier Bouché
- Université de Reims Champagne-Ardenne, Biospect, CHU Reims, Oncology Day-Hospital, Reims, France
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Myint ZW, St. Clair WH, Strup SE, Yan D, Li N, Allison DB, McLouth LE, Ellis CS, Wang P, James AC, Hensley PJ, Otto DE, Arnold SM, DiPaola RS, Kolesar JM. A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer. Cancers (Basel) 2023; 15:2505. [PMID: 37173971 PMCID: PMC10177512 DOI: 10.3390/cancers15092505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/09/2023] [Accepted: 04/19/2023] [Indexed: 05/15/2023] Open
Abstract
PURPOSE Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. EXPERIMENTAL DESIGN This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. RESULTS Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1-2), 25% nausea (grade 1-2), and 20% fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). CONCLUSION Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.
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Affiliation(s)
- Zin W. Myint
- Department of Medicine, Division of Medical Oncology, University of Kentucky, Lexington, KY 40536, USA
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
| | - William H. St. Clair
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Radiation Medicine, University of Kentucky, Lexington, KY 40536, USA
| | - Stephen E. Strup
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Urology, University of Kentucky, Lexington, KY 40536, USA
| | - Donglin Yan
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY 40536, USA
| | - Ning Li
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY 40536, USA
| | - Derek B. Allison
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY 40536, USA
| | - Laurie E. McLouth
- Department of Behavioral Science, University of Kentucky, Lexington, KY 40536, USA
| | - Carleton S. Ellis
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
| | - Peng Wang
- Department of Medicine, Division of Medical Oncology, University of Kentucky, Lexington, KY 40536, USA
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
| | - Andrew C. James
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Urology, University of Kentucky, Lexington, KY 40536, USA
| | - Patrick J. Hensley
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- Department of Urology, University of Kentucky, Lexington, KY 40536, USA
| | - Danielle E. Otto
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
| | - Susanne M. Arnold
- Department of Medicine, Division of Medical Oncology, University of Kentucky, Lexington, KY 40536, USA
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
| | - Robert S. DiPaola
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
| | - Jill M. Kolesar
- Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA
- College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
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Waissengrin B, Leshem Y, Taya M, Meiri D, Merimsky O, Shamai S, Wolf I, Rubinek T. The use of medical cannabis concomitantly with immune checkpoint inhibitors in non-small cell lung cancer: A sigh of relief? Eur J Cancer 2023; 180:52-61. [PMID: 36535195 DOI: 10.1016/j.ejca.2022.11.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 11/02/2022] [Accepted: 11/20/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND The use of medical cannabis has rapidly increased among cancer patients worldwide. Cannabis is often administered concomitantly with cancer medications, including immune checkpoint inhibitors (ICIs). As the cannabinoid receptors are abundantly expressed and modulate immune cells, it has been hypothesised that cannabis may attenuate the activity of ICIs. We aimed to assess the effect of cannabis on ICIs' efficiency in patients having non-small cell lung cancer (NSCLC). METHOD The murine model of CT26 tumour-bearing mice treated with an anti-PD-1 antibody and Δ9-tetrahydrocannabinol (THC) was used to evaluate the interaction between THC and ICIs in vivo. Correlation between use of medical cannabis and clinical outcome was evaluated in a cohort of 201 consecutive metastatic NSCLC patients treated with monotherapy pembrolizumab as a first-line treatment. RESULTS Median overall survival (OS) of the mice receiving a control vehicle, THC, anti-PD-1 antibody or their combination was 21, 24, 31 and 54 days, respectively (p < 0.05 for the combination treatment compared to a control vehicle), indicating that THC did not reduce the efficacy of anti-PD-1 therapy. Of 201 NSCLC patients treated with first-line monotherapy pembrolizumab for metastatic disease, 102 (50.7%) patients received licence for cannabis within the first month of treatment. Cannabis-treated patients were younger compared to the cannabis naïve patients (median age 68 versus 74, p = 0.003), with female predominance (62, 60.8% versus 34, 34.3%, p = 0.002) and with more prevailing brain metastasis (15.7% versus 5%, p = 0.013). Similar distribution of histology, smoking status, ECOG (Eastern Cooperative Oncology Group) and programmed death-ligand 1 expression was noted between the groups. Liver metastases were marginally significant (19.6% versus 10.1%, p = 0.058). The most common indication for cannabis was pain (71%) followed by loss of appetite (34.3%). Time to tumour progression was similar for cannabis-naive and cannabis-treated patients (6.1 versus 5.6 months, respectively, 95% confidence interval, 0.82 to 1.38, p = 0.386), while OS was numerically higher in the cannabis-naive group (54.9 versus 23.6 months) but did not reach statistical significance (95% confidence interval 0.99 to 2.51, p = 0.08). In multivariate analyses, we did not identify cannabis use as an independent predictor factor for mortality. CONCLUSIONS Preclinical and clinical data suggest no deleterious effect of cannabis on the activity of pembrolizumab as first-line monotherapy for advanced NSCLC. The differences in OS can most likely be attributed to higher disease burden and more symptomatic disease in the cannabis-treated group. These data provide reassurance regarding the absence of a deleterious effect of cannabis in this clinical setting.
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Affiliation(s)
- Barliz Waissengrin
- Oncology Institute, Tel Aviv Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv, Israel
| | - Yasmin Leshem
- Oncology Institute, Tel Aviv Medical Center, Tel Aviv, Israel; Weizmann Institute of Science, Rehovot, Israel
| | - Marwa Taya
- Oncology Institute, Tel Aviv Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv, Israel
| | - David Meiri
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ofer Merimsky
- Oncology Institute, Tel Aviv Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv, Israel
| | - Sivan Shamai
- Oncology Institute, Tel Aviv Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv, Israel
| | - Ido Wolf
- Oncology Institute, Tel Aviv Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv, Israel.
| | - Tami Rubinek
- Oncology Institute, Tel Aviv Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv, Israel
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Naim-Feil E, Elkins AC, Malmberg MM, Ram D, Tran J, Spangenberg GC, Rochfort SJ, Cogan NOI. The Cannabis Plant as a Complex System: Interrelationships between Cannabinoid Compositions, Morphological, Physiological and Phenological Traits. PLANTS (BASEL, SWITZERLAND) 2023; 12:493. [PMID: 36771577 PMCID: PMC9919051 DOI: 10.3390/plants12030493] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 06/18/2023]
Abstract
Maintaining specific and reproducible cannabinoid compositions (type and quantity) is essential for the production of cannabis-based remedies that are therapeutically effective. The current study investigates factors that determine the plant's cannabinoid profile and examines interrelationships between plant features (growth rate, phenology and biomass), inflorescence morphology (size, shape and distribution) and cannabinoid content. An examination of differences in cannabinoid profile within genotypes revealed that across the cultivation facility, cannabinoids' qualitative traits (ratios between cannabinoid quantities) remain fairly stable, while quantitative traits (the absolute amount of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG), Δ9-tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV)) can significantly vary. The calculated broad-sense heritability values imply that cannabinoid composition will have a strong response to selection in comparison to the morphological and phenological traits of the plant and its inflorescences. Moreover, it is proposed that selection in favour of a vigorous growth rate, high-stature plants and wide inflorescences is expected to increase overall cannabinoid production. Finally, a range of physiological and phenological features was utilised for generating a successful model for the prediction of cannabinoid production. The holistic approach presented in the current study provides a better understanding of the interaction between the key features of the cannabis plant and facilitates the production of advanced plant-based medicinal substances.
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Affiliation(s)
- Erez Naim-Feil
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
- School of Applied Systems Biology, La Trobe University, Melbourne, VIC 3086, Australia
| | - Aaron C. Elkins
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
| | - M. Michelle Malmberg
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
| | - Doris Ram
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
| | - Jonathan Tran
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
- School of Applied Systems Biology, La Trobe University, Melbourne, VIC 3086, Australia
| | - German C. Spangenberg
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
- School of Applied Systems Biology, La Trobe University, Melbourne, VIC 3086, Australia
| | - Simone J. Rochfort
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
- School of Applied Systems Biology, La Trobe University, Melbourne, VIC 3086, Australia
| | - Noel O. I. Cogan
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Melbourne, VIC 3083, Australia
- School of Applied Systems Biology, La Trobe University, Melbourne, VIC 3086, Australia
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10
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Rodriguez-Almaraz JE, Butowski N. Therapeutic and Supportive Effects of Cannabinoids in Patients with Brain Tumors (CBD Oil and Cannabis). Curr Treat Options Oncol 2023; 24:30-44. [PMID: 36633803 PMCID: PMC9867687 DOI: 10.1007/s11864-022-01047-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OPINION STATEMENT The potential medicinal properties of Cannabis continue to garner attention, especially in the brain tumor domain. This attention is centered on quality of life and symptom management; however, it is amplified by a significant lack of therapeutic choices for this specific patient population. While the literature on this matter is young, published and anecdotal evidence imply that cannabis could be useful in treating chemotherapy-induced nausea and vomiting, stimulating appetite, reducing pain, and managing seizures. It may also decrease inflammation and cancer cell proliferation and survival, resulting in a benefit in overall patient survival. Current literature poses the challenge that it does not provide standardized guidance on dosing for the above potential indications and cannabis use is dominated by recreational purposes. Furthermore, integrated and longitudinal studies are needed but these are a challenge due to arcane laws surrounding the legality of such substances. The increasing need for evidence-based arguments about potential harms and benefits of cannabis, not only in cancer patients but for other medical use and recreational purposes, is desperately needed.
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Affiliation(s)
- J. Eduardo Rodriguez-Almaraz
- Neuro Surgery Department Division of Neuro-Oncology, University of California San Francisco, 400 Parnassus Avenue, 8th floor, RM A808, San Francisco, California USA
- Deparment of Epidemiology and Biostatistics, University of California San Francisco, 400 Parnassus Avenue, 8th floor, RM A808, San Francisco, California USA
| | - Nicholas Butowski
- Neuro Surgery Department Division of Neuro-Oncology, University of California San Francisco, 400 Parnassus Avenue, 8th floor, RM A808, San Francisco, California USA
- Deparment of Molecular Science, University of California San Francisco, 400 Parnassus Avenue, 8th floor, RM A808, San Francisco, California USA
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11
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Alderman B, Hui D, Mukhopadhyay S, Bouleuc C, Case AA, Amano K, Crawford GB, de Feo G, Sbrana A, Tanco K, To J, Garsed J, Davis M. Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer. Support Care Cancer 2022; 31:39. [PMID: 36525085 DOI: 10.1007/s00520-022-07480-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 11/24/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Gastrointestinal symptoms are common in patients with cancer, whether related to treatment or a direct effect of the disease itself. Patients may choose to access cannabinoids outside of their formal medical prescriptions to palliate such symptoms. However, clinical guidelines are lacking in relation to the use of such medicines for gastrointestinal symptoms in patients with cancer. METHODS A systematic review of the evidence for the use of cannabinoids for symptom control in patients with cancer was undertaken. Search strategies were developed for Medline, Embase, PsychINFO, and the Cochrane Central Register of Controlled Trials, including all publications from 1975 up to 12 November 2021. Studies were included if they were randomized controlled trials of cannabinoids compared with placebo or active comparator in adult patients with cancer, regardless of type, stage, or treatment status. Articles for inclusion were agreed by all authors, and data extracted and summarized by two authors. Each study was scored according to the Jadad scale. This review was specifically for the purpose of developing guidelines for the use of cannabis for gastrointestinal symptoms, including chemotherapy-induced nausea and vomiting (CINV), chronic nausea, anorexia-cachexia syndrome, and taste disturbance. RESULTS Thirty-six randomized controlled trials were identified that met the inclusion criteria for this review of gastrointestinal symptoms: 31 relating to CINV, one to radiotherapy-induced nausea and vomiting, and the remaining four to anorexia-cachexia and altered chemosensory disturbance. The populations for the randomized controlled trials were heterogeneous, and many studies were of poor quality, lacking clarity regarding method of randomization, blinding, and allocation concealment. For CINV, eleven RCTs showed improvement with cannabis compared to placebo, but out of 21 trials where cannabis was compared to other antiemetics for CINV, only 11 favoured cannabis. CONCLUSION Tetrahydrocannabinol (THC) and nabilone were more effective in preventing CINV when compared to placebo but are not more effective than other antiemetics. For refractory CINV, one study of THC:CBD demonstrated reduced nausea as an add-on treatment to guideline-consistent antiemetic therapy without olanzapine. The MASCC Guideline Committee found insufficient evidence to recommend cannabinoids for the management of CINV, nausea from advanced cancer, cancer-associated anorexia-cachexia, and taste disturbance. High-quality studies are needed to inform practice.
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Affiliation(s)
- Bryony Alderman
- Department of Palliative Care, Frimley Park Hospital, Frimley, UK
- Phyllis Tuckwell Hospice Care, Farnham, UK
| | - David Hui
- Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sandip Mukhopadhyay
- Indian Council of Medical Research - National Institute of Cholera and Enteric Disease, Kolkata, India
| | - Carole Bouleuc
- Department of Supportive and Palliative Care, PSL University, Institut Curie, Paris, France
| | - Amy A Case
- Department of Palliative and Supportive Care, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
- Division of Geriatrics and Palliative Medicine University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, USA
| | - Koji Amano
- Department of Palliative Medicine, National Cancer Center Hospital, Tokyo, Japan
| | - Gregory B Crawford
- Northern Adelaide Palliative Service, Adelaide, Australia
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
| | - Giulia de Feo
- Supportive Care in Cancer Unit, Fondazione IRCCS, Istituto Nazionale Dei Tumori, Onco-Haematology, Milan, Italy
| | - Andrea Sbrana
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Kimberson Tanco
- Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Josephine To
- Division of Aged Care, Rehabilitation and Palliative Care, Northern Adelaide Local Health Network, Adelaide, Australia
| | | | - Mellar Davis
- Palliative Care Department, Geisinger Medical System, Danville, USA.
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12
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Birenboim M, Kengisbuch D, Chalupowicz D, Maurer D, Barel S, Chen Y, Fallik E, Paz-Kagan T, Shimshoni JA. Use of near-infrared spectroscopy for the classification of medicinal cannabis cultivars and the prediction of their cannabinoid and terpene contents. PHYTOCHEMISTRY 2022; 204:113445. [PMID: 36165867 DOI: 10.1016/j.phytochem.2022.113445] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 06/16/2023]
Abstract
Cannabis sativa L. is used to treat a wide variety of medical conditions, in light of its beneficial pharmacological properties of its cannabinoids and terpenes. At present, the quantitative chemical analysis of these active compounds is achieved through the use of laborious, expensive, and time-consuming technologies, such as high-pressure liquid-chromatography- photodiode arrays, mass spectrometer detectors (HPLC-PDA or MS), or gas chromatography-mass spectroscopy (GC-MS). Hence, we aimed to develop a simple, accurate, fast, and cheap technique for the quantification of major cannabinoids and terpenes using Fourier transform near infra-red spectroscopy (FT-NIRS). FT-NIRS was coupled with multivariate classification and regression models, namely partial least square-discriminant analysis (PLS-DA) and partial least squares regression (PLS-R) models. The PLS-DA model yielded an absolute major class separation (high-THC, high-CBD, hybrid, and high-CBG) and perfect class prediction. Using only three latent variables (LVs), the cross-validation and prediction model errors indicated a low probability of over-fitting the data. In addition, the PLS-DA model enabled the classification of chemovars with genetic-chemical similarities. The classification of high-THCA chemovars was more sensitive and more specific than the classifications of the remaining chemovars. The prediction of cannabinoid and terpene concentrations by PLS-R yielded 11 robust models with high predictive capabilities (R2CV and R2pred > 0.8, RPD >2.5 and RPIQ >3, RMSECV/RMSEC ratio <1.2) and additional 15 models whose performance was acceptable for initial screening purposes (R2CV > 0.7 and R2pred < 0.8, RPD >2 and RPIQ <3, 1.2 < RMSECV/RMSEC ratio <2). Our results confirm that there is sufficient information in the FT-NIRS to develop cannabinoid and terpene prediction models and major-cultivar classification models.
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Affiliation(s)
- Matan Birenboim
- Department of Food Safety, Institute for Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel; Department of Plant Science, The Robert H Smith Faculty of Agriculture, Food and Environment, Rehovot, 7610001, Israel
| | - David Kengisbuch
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel
| | - Daniel Chalupowicz
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel
| | - Dalia Maurer
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel
| | - Shimon Barel
- Kimron Veterinary Institute, Department of Toxicology, Bet Dagan, 50250, Israel
| | - Yaira Chen
- Department of Food Safety, Institute for Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel
| | - Elazar Fallik
- Department of Food Safety, Institute for Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel
| | - Tarin Paz-Kagan
- French Associates Institute for Agriculture and Biotechnology of Dryland, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, 8499000, Israel
| | - Jakob A Shimshoni
- Department of Food Safety, Institute for Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel.
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13
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Birenboim M, Chalupowicz D, Maurer D, Barel S, Chen Y, Fallik E, Paz-Kagan T, Rapaport T, Sadeh A, Kengisbuch D, Shimshoni JA. Multivariate classification of cannabis chemovars based on their terpene and cannabinoid profiles. PHYTOCHEMISTRY 2022; 200:113215. [PMID: 35483556 DOI: 10.1016/j.phytochem.2022.113215] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/18/2022] [Accepted: 04/19/2022] [Indexed: 06/14/2023]
Abstract
Cannabis is used to treat various medical conditions, and lines are commonly classified according to their total concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Based on their ratio of total THC to total CBD, cannabis cultivars are commonly classified into high-THC, high-CBD, and hybrid classes. While cultivars from the same class have similar compositions of major cannabinoids, their levels of other cannabinoids and their terpene compositions may differ substantially. Therefore, a more comprehensive and accurate classification of medicinal cannabis cultivars, based on a large number of cannabinoids and terpenes is needed. For this purpose, three different chemometric-based classification models were constructed using three sets of chemical profiles. We examined those models to determine which provides the most accurate "chemovar" classification. This was done by analyzing profiles of cannabinoids, terpenes, and the combination of these substances using the partial least square-discriminant analysis multivariate (PLS-DA) technique. The chemical profiles were selected from the three major classes of medicinal cannabis that are most commonly prescribed to patients in Israel: high-THC, high-cannabigerol (CBG), and hybrid. We studied the correlations between cannabinoids and terpenes to identify major bio-indicators representing the plant's terpene and cannabinoid content. All three PLS-DA models provided highly accurate classifications, utilizing six to nine latent variables with an overall accuracy ranging from 2 to 11% CV. The PLS-DA model applied to the combined cannabinoid-and-terpene profile did the best job of differentiating between the chemovars in terms of misclassification error, sensitivity, specificity, and accuracy. The combined cannabinoid-and-terpene PLS-DA profile had cross-validation and prediction misclassification errors of 4% and 0%, respectively. This is the first study to demonstrate the highly accurate classification of samples of medicinal cannabis based on their cannabinoid and terpene profiles, as compared to cannabinoid profiles alone. Furthermore, our correlation analysis indicated that 11 cannabinoids and terpenes might serve as bio-indicators for 32 different active compounds. These findings suggest that the use of multivariate statistics could assist in breeding studies and serve as a tool for minimizing the mislabeling of cannabis inflorescences.
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Affiliation(s)
- Matan Birenboim
- Department of Food Safety, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel & Department of Plant Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot, 7610001, Israel
| | - Daniel Chalupowicz
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel
| | - Dalia Maurer
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel
| | - Shimon Barel
- Kimron Veterinary Institute, Department of Toxicology, Bet Dagan, 50250, Israel
| | - Yaira Chen
- Department of Food Safety, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel & Department of Plant Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot, 7610001, Israel
| | - Elazar Fallik
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel
| | - Tarin Paz-Kagan
- Department of Sensing, Information and Mechanization Systems, Institute of Agricultural Engineering, Agricultural Research Organization (ARO), Volcani Center, Israel
| | - Tal Rapaport
- Department of Sensing, Information and Mechanization Systems, Institute of Agricultural Engineering, Agricultural Research Organization (ARO), Volcani Center, Israel
| | - Alona Sadeh
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel
| | - David Kengisbuch
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel.
| | - Jakob A Shimshoni
- Department of Food Quality, Institute for Postharvest and Food Sciences, Agricultural Research Organization, Volcani Center, Rishon LeZion, 7505101, Israel.
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14
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Vinette B, Côté J, El-Akhras A, Mrad H, Chicoine G, Bilodeau K. Routes of administration, reasons for use, and approved indications of medical cannabis in oncology: a scoping review. BMC Cancer 2022; 22:319. [PMID: 35331185 PMCID: PMC8953058 DOI: 10.1186/s12885-022-09378-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 03/07/2022] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Some patients diagnosed with cancer use medical cannabis to self-manage undesirable symptoms, including nausea and pain. To improve patient safety and oncological care quality, the routes of administration for use of medical cannabis, patients' reasons, and prescribed indications must be better understood. METHODS Based on the Joanna Briggs Institute guidelines, a scoping review was conducted to map the current evidence regarding the use of medical cannabis in oncological settings based on the experiences of patients diagnosed with cancer and their healthcare providers. A search strategy was developed with a scientific librarian which included five databases (CINAHL, Web of Science, Medline, Embase, and PsycINFO) and two grey literature sources (Google Scholar and ProQuest). The inclusion criteria were: 1) population: adults aged 18 and over diagnosed with cancer; 2) phenomena of interest: reasons for cannabis use and/or the prescribed indications for medical cannabis; 3) context: oncological setting. French- or English-language primary empirical studies, knowledge syntheses, and grey literature published between 2000 and 2021 were included. Data were extracted by two independent reviewers and subjected to a thematic analysis. A narrative description approach was used to synthesize and present the findings. RESULTS We identified 5,283 publications, of which 163 met the eligibility criteria. Two main reasons for medical cannabis use emerged from the thematic analysis: limiting the impacts of cancer and its side effects; and staying connected to others. Our results also indicated that medical cannabis is mostly used for three approved indications: to manage refractory nausea and vomiting, to complement pain management, and to improve appetite and food intake. We highlighted 11 routes of administration for medical cannabis, with oils and oral solutions the most frequently reported. CONCLUSION Future studies should consider the multiple routes of administration for medical cannabis, such as inhalation and edibles. Our review highlights that learning opportunities would support the development of healthcare providers' knowledge and skills in assessing the needs and preferences of patients diagnosed with cancer who use medical cannabis.
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Affiliation(s)
- Billy Vinette
- Faculty of Nursing, University of Montreal, Montreal, QC, Canada.
- Research Chair in Innovative Nursing Practices, Montreal, QC, Canada.
- Quebec Network On Nursing Intervention Research, Montreal, QC, Canada.
- Center for Innovation in Nursing Education, Montreal, QC, Canada.
| | - José Côté
- Faculty of Nursing, University of Montreal, Montreal, QC, Canada
- Research Chair in Innovative Nursing Practices, Montreal, QC, Canada
- Quebec Network On Nursing Intervention Research, Montreal, QC, Canada
- Research center of the Montreal University Hospital Center, Montreal, QC, Canada
| | - Ali El-Akhras
- Faculty of Nursing, University of Montreal, Montreal, QC, Canada
| | - Hazar Mrad
- Faculty of Nursing, University of Montreal, Montreal, QC, Canada
| | - Gabrielle Chicoine
- Faculty of Nursing, University of Montreal, Montreal, QC, Canada
- Research Chair in Innovative Nursing Practices, Montreal, QC, Canada
- Quebec Network On Nursing Intervention Research, Montreal, QC, Canada
- Center for Innovation in Nursing Education, Montreal, QC, Canada
- Research center of the Montreal University Hospital Center, Montreal, QC, Canada
| | - Karine Bilodeau
- Faculty of Nursing, University of Montreal, Montreal, QC, Canada
- Quebec Network On Nursing Intervention Research, Montreal, QC, Canada
- Center for Innovation in Nursing Education, Montreal, QC, Canada
- Research center of the Montreal University Hospital Center, Montreal, QC, Canada
- Research Center of the Centre Intégré Universitaire de Santé Et de Services Sociaux de L'Est-de-L'Île-de-Montréal, Montreal, QC, Canada
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15
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The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Pharmaceuticals (Basel) 2022; 15:ph15010100. [PMID: 35056154 PMCID: PMC8778752 DOI: 10.3390/ph15010100] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/07/2022] [Accepted: 01/11/2022] [Indexed: 11/16/2022] Open
Abstract
Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64–31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92–152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33–68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19–9.78), dizziness (OR: 4.60 95% CI: 2.39–8.83) and headache (OR: 2.90; 95% CI: 1.07–7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.
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16
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Lalsare S. Cannabinoids: Legal aspects, pharmacology, phytochemistry, probable targets from biological system, and therapeutic potential. ASIAN JOURNAL OF PHARMACEUTICAL RESEARCH AND HEALTH CARE 2022. [DOI: 10.4103/ajprhc.ajprhc_9_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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17
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Matchett-Oates L, Spangenberg GC, Cogan NOI. Manipulation of Cannabinoid Biosynthesis via Transient RNAi Expression. FRONTIERS IN PLANT SCIENCE 2021; 12:773474. [PMID: 35035388 PMCID: PMC8757041 DOI: 10.3389/fpls.2021.773474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/08/2021] [Indexed: 05/04/2023]
Abstract
Cannabis sativa L. produces unique phytocannabinoids, which are used for their pharmaceutical benefits. To date, there are no reports of in vivo engineering targeting the cannabinoid biosynthesis genes to greater elucidate the role each of these genes play in synthesis of these medically important compounds. Reported here is the first modulation of cannabinoid biosynthesis genes using RNAi via agroinfiltration. Vacuum infiltrated leaf segments of the Cannbio-2 C. sativa strain, transfected with different RNAi constructs corresponding to THCAS, CBDAS, and CBCAS gene sequences, showed significant downregulation of all cannabinoid biosynthesis genes using real-time quantitative PCR. Using RNAi, significant off-targeting occurs resulting in the downregulation of highly homologous transcripts. Significant (p < 0.05) downregulation was observed for THCAS (92%), CBDAS (97%), and CBCAS (70%) using pRNAi-GG-CBDAS-UNIVERSAL. Significant (p < 0.05) upregulation of CBCAS (76%) and non-significant upregulation of THCAS (13%) were observed when transfected with pRNAi-GG-CBCAS, suggesting the related gene's ability to synthesize multiple cannabinoids. Using this approach, increased understanding of the relationship between cannabinoid biosynthesis genes can be further elucidated. This RNAi approach enables functional genomics screens for further reverse genetic studies as well as the development of designer cannabis strains with over-expression and/or downregulation of targeted cannabinoid biosynthesis genes. Functional genomics screens, such as these, will further provide insights into gene regulation of cannabinoid biosynthesis in Cannabis.
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Affiliation(s)
- Lennon Matchett-Oates
- Agriculture Victoria, AgriBio, The Centre for AgriBioscience, Bundoora, VIC, Australia
- School of Applied Systems Biology, La Trobe University, Bundoora, VIC, Australia
| | - German C. Spangenberg
- Agriculture Victoria, AgriBio, The Centre for AgriBioscience, Bundoora, VIC, Australia
- School of Applied Systems Biology, La Trobe University, Bundoora, VIC, Australia
| | - Noel O. I. Cogan
- Agriculture Victoria, AgriBio, The Centre for AgriBioscience, Bundoora, VIC, Australia
- School of Applied Systems Biology, La Trobe University, Bundoora, VIC, Australia
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18
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Riera R, Pacheco RL, Bagattini ÂM, Martimbianco ALC. Efficacy and safety of therapeutic use of cannabis derivatives and their synthetic analogs: Overview of systematic reviews. Phytother Res 2021; 36:5-21. [PMID: 34841610 DOI: 10.1002/ptr.7263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 08/05/2021] [Accepted: 08/14/2021] [Indexed: 01/08/2023]
Abstract
The debate on the use of cannabinoids for therapeutic purposes is constantly on the rise. This overview aimed to map the evidence on the therapeutic effects of cannabis derivatives and their synthetic analogs. Systematic reviews (SRs) of randomized trials were identified through a comprehensive search in several databases, and their methodological quality were evaluated with AMSTAR-2. The results for main outcomes are presented, prioritizing those from updated and better quality SRs. Finally, 68 SRs, addressing 37 different health conditions, were included. The methodological quality was high for eight SRs. The evidence certainty (GRADE) for the effects of cannabinoids is not high for any of the outcomes identified. Evidence certainty was moderate for the following: (a) cannabidiol appears to be beneficial for quality of life but increases the risk of adverse events in ulcerative colitis; (b) cannabinoids in general appear to have no clinically important benefit for chronic non-oncologic pain, spasticity-related pain in multiple sclerosis, or for acute post-operative pain; (c) cannabinoids in general appear to have a benefit in reducing chemotherapy-related nausea and vomiting. For all other outcomes from remaining comparisons, the evidence certainty was low, very low, or not evaluated, which prevents recommendations for or against their routine use.
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Affiliation(s)
- Rachel Riera
- Health Technology Assessment Centre, Hospital Sírio-Libanês, São Paulo - SP, Brazil.,Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo - SP, Brazil
| | - Rafael Leite Pacheco
- Health Technology Assessment Centre, Hospital Sírio-Libanês, São Paulo - SP, Brazil.,Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), São Paulo - SP, Brazil.,Centro de Pesquisa Médica, Centro Universitário São Camilo (CUSC), São Paulo - SP, Brazil
| | - Ângela Maria Bagattini
- Health Technology Assessment Centre, Hospital Sírio-Libanês, São Paulo - SP, Brazil.,Instituto de Medicina Tropical e Saúde Publica, Universidade Federal de Goiás (UFG), Goiânia - GO, Brazil
| | - Ana Luiza Cabrera Martimbianco
- Health Technology Assessment Centre, Hospital Sírio-Libanês, São Paulo - SP, Brazil.,Mestrado Profissional em Saúde e Meio Ambiente, Universidade Metropolitana de Santos (Unimes), Santos - SP, Brazil
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19
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Sexton M, Garcia JM, Jatoi A, Clark CS, Wallace MS. The Management of Cancer Symptoms and Treatment-Induced Side Effects With Cannabis or Cannabinoids. J Natl Cancer Inst Monogr 2021; 2021:86-98. [PMID: 34850897 DOI: 10.1093/jncimonographs/lgab011] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 09/02/2021] [Indexed: 01/06/2023] Open
Abstract
Cannabis and cannabinoids are increasingly being accessed and used by patients with advanced cancer for various symptoms and general quality of life. Specific symptoms of pain, nausea and vomiting, loss of appetite and cachexia, anxiety, sleep disturbance, and medical trauma are among those that have prompted patients with cancer to use cannabis. This conference report from the National Cancer Institute's "Cannabis, Cannabinoid and Cancer Research Symposium" on the topic of "Cancer Symptom/Treatment Side Effect Management" is an expert perspective of cannabis intervention for cancer and cancer treatment-related symptoms. The purpose of the symposium was to identify research gaps, describe the need for high-quality randomized prospective studies of medical cannabis for palliative care in patients with cancer, and evaluate the impact of medical cannabis on cancer survivors' quality of life. Further, education of clinicians and affiliated health-care providers in guiding cancer patients in using cannabis for cancer care would benefit patients. Together, these steps will further aid in refining the use of cannabis and cannabinoids for symptom palliation and improve safety and efficacy for patients.
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Affiliation(s)
- Michelle Sexton
- Department of Anesthesiology, Division of Pain Management, University of California, San Diego, CA, USA
| | - Jose M Garcia
- Department of Medicine, Division of Geriatrics, University of Washington and Geriatric Research Education and Clinical Center, Puget Sound Veterans Administration Health Care System, Seattle, WA, USA
| | - Aminah Jatoi
- Department of Oncology, Mayo Clinic, Rochester, MN, USA
| | - Carey S Clark
- Department of Nursing, Pacific College of Health and Science, San Diego, CA, USA
| | - Mark S Wallace
- Department of Anesthesiology, Division of Pain Management, University of California, San Diego, CA, USA
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20
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Steinberg S, Meng Y, Kapanen AI, Reardon J, Yuen J. Impact of recreational cannabis legalization on patient self-reporting of cannabis use at a pharmacist-led primary care clinic. J Am Pharm Assoc (2003) 2021; 61:813-818.e1. [PMID: 34275731 DOI: 10.1016/j.japh.2021.06.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 06/04/2021] [Accepted: 06/29/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND The Cannabis Act, introduced in Canada in 2018, legalized the use of recreational cannabis. The impact of the announcement and implementation of this act on patient self-reporting of cannabis use has not been explored. OBJECTIVE The study objective was to determine if patient self-reported cannabis use increased after the announcement and implementation of legislative changes to legalize recreational cannabis. METHODS A repeated cross-sectional design was used for a retrospective chart review of patients seen at a pharmacist-led primary care clinic. A convenience sample of patient records was divided into 3 panels, corresponding with the preannouncement (November 1, 2013-October 4, 2015), postannouncement (October 5, 2015-October 16, 2018), and postimplementation (October 17, 2018-October 17, 2019) stages of the legalization of recreational cannabis. Search terms used included cannabis, marijuana, marihuana, recreational drugs, natur∗, medicinal, pot, joint, oil, butter, brownies, edibles, cannabin∗, THC, tetrahydro∗, sativa, and indica (∗ = string wild card). The frequency of reporting use and the number of queries related to cannabis were assessed. The analysis of variance test and Pearson correlation (chi-square) were used to compare the 3 panels. RESULTS A total of 298 patient charts were included in the analysis. One hundred, 99, and 99 patient charts corresponded with panels 1, 2, and 3, respectively. At each time point, 6%, 8%, and 14% of the patients reported cannabis use (P = 0.03). A statistically significant increase in topical oil use and a decrease in prescription tablet or capsule use between panels 1 and 3 (P = 0.036) were identified. CONCLUSION This study found an increase in self-reporting of cannabis use across the 3 consecutive panels. The change in the product formulations used may reflect the various products available. Frontline pharmacists are encouraged to initiate conversations regarding cannabis use as part of routine practice.
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21
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Rock EM, Limebeer CL, Pertwee RG, Mechoulam R, Parker LA. Therapeutic Potential of Cannabidiol, Cannabidiolic Acid, and Cannabidiolic Acid Methyl Ester as Treatments for Nausea and Vomiting. Cannabis Cannabinoid Res 2021; 6:266-274. [PMID: 34115951 DOI: 10.1089/can.2021.0041] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Introduction: Nausea and vomiting are the most distressing symptoms reported by oncology patients undergoing anticancer treatment. With the currently available treatments, vomiting and especially nausea remain problematic, highlighting the need for alternative treatments. Discussion: Here we review in vitro and in vivo evidence for the effectiveness of the nonpsychoactive cannabinoid cannabidiol (CBD) in managing nausea and vomiting. In addition, we also review the evidence for CBD's acidic precursor, cannabidiolic acid (CBDA), and a methylated version of CBDA (CBDA-ME) in these phenomena. Finally, we explore the potential role of CBD in the treatment of cannabinoid hyperemesis syndrome. Conclusions: CBD has demonstrated efficacy in reducing nausea and vomiting, with CBDA and CBDA-ME being more potent. The data suggest a need for these compounds to be evaluated in clinical trials for their ability to reduce nausea and/or vomiting.
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Affiliation(s)
- Erin M Rock
- Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, Ontario, Canada
| | - Cheryl L Limebeer
- Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, Ontario, Canada
| | - Roger G Pertwee
- School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom
| | - Raphael Mechoulam
- Institute for Drug Research, Medical Faculty, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Linda A Parker
- Collaborative Neuroscience Program, Department of Psychology, University of Guelph, Guelph, Ontario, Canada
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22
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Albelo FD, Baker M, Zhang T, Schneider MB, Jauregui JJ, Nadarajah V, Meredith SJ, Packer JD, Henn RF. Impact of pre-operative recreational marijuana use on outcomes two years after orthopaedic surgery. INTERNATIONAL ORTHOPAEDICS 2021; 45:2483-2490. [PMID: 34052856 DOI: 10.1007/s00264-021-05069-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 05/07/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE The purpose of this study was to investigate the relationship between recreational marijuana use and patient-reported outcomes two years after orthopaedic surgery. We hypothesized that pre-operative recreational marijuana use would be associated with less pain, better function, and better mental health measures two years after orthopaedic surgery. METHODS Patients were retrospectively analyzed from a prospective orthopaedic registry at a single urban institution. A total of 1710 patients completed the pre-operative assessment and 1103 patients (64.5%) completed the two-year follow-up questionnaires. The cohort was then divided into two groups based on reported preoperative recreational marijuana usage, and statistical analysis was performed to determine if marijuana use was associated with two-year outcomes. Multivariable analysis was used to control for confounding variables. RESULTS Marijuana use was reported by 47 (4.3%) patients. Significantly worse scores for two-year PROMIS Anxiety (53.2 vs. 49.2, p = 0.005), PROMIS Depression (51.1 vs. 46.5, p = 0.001), Met Expectations (63.1 vs. 74.4, p = 0.024), Surgical Satisfaction Questionnaire-8 (71.7 vs. 80.4, p = 0.005), and Numeric Satisfaction Scale (75.6 vs. 83.1, p = 0.041) were associated with marijuana use. Marijuana users also had less improvement of Numeric Pain Scores at the operative site (- 1.8 vs. - 2.7, p = 0.037) and greater decrease in Marx activity scores for lower extremities (- 12.3 vs. - 3.9, p = 0.024). Marijuana use was not an independent predictor of any outcome measure in the multivariable analysis. CONCLUSION Marijuana use was associated with worse mental health scores, lower activity level, less pain relief, and worse satisfaction two years after orthopaedic surgery. However, after controlling for confounding variables, marijuana use was not predictive of any two-year outcome measure. STUDY DESIGN Cross-sectional study.
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Affiliation(s)
- Fernando D Albelo
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA
| | - Mitchell Baker
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA
| | - Tina Zhang
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA
| | - Matheus B Schneider
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA
| | - Julio J Jauregui
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA
| | - Vidushan Nadarajah
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA.,Department of Orthopaedic Surgery and Rehabilitation Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA
| | - Sean J Meredith
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA
| | - Jonathan D Packer
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA
| | - R Frank Henn
- Department of Orthopaedics, University of Maryland School of Medicine, 2200 Kernan Drive, Baltimore, MD, 21207, USA.
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23
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Schloss J, Lacey J, Sinclair J, Steel A, Sughrue M, Sibbritt D, Teo C. A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas. Front Oncol 2021; 11:649555. [PMID: 34094937 PMCID: PMC8176855 DOI: 10.3389/fonc.2021.649555] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 04/22/2021] [Indexed: 11/13/2022] Open
Abstract
Background Cannabis for cancer is very topical and, given the use of illicit cannabis preparations used in this vulnerable population, research investigating standardised, quality-assured medicinal cannabis is critical to inform clinicians and assist patient safety. Methods A randomized trial involving adult patients diagnosed with a high-grade glioma, no history of substance abuse, liver or kidney damage or myocardial infarction were eligible for inclusion in a tolerability study on two different ratios of medicinal cannabis. Baseline screening of brain morphology, blood pathology, functional status, and cognition was conducted. A retrospective control group was used for comparison for secondary outcomes. Results Participants (n=88) were on average 53.3 years old. A paired t-test assessed the Functional Assessment of Cancer Therapy for Brain Cancer (FACT-Br) between groups from baseline to week 12 found that the 1:1 ratio favoured both physical (p=0.025) and functional (p=0.014) capacity and improved sleep (p=0.009). Analysis of changes from baseline to week 12 also found 11% of 61 participants had a reduction in disease, 34% were stable, 16% had slight enhancement, and 10% had progressive disease. No serious adverse events occurred. Side effects included dry mouth, tiredness at night, dizziness, drowsiness. Conclusion This study demonstrated that a single nightly dose of THC-containing medicinal cannabis was safe, had no serious adverse effects and was well tolerated in patients. Medicinal cannabis significantly improved sleep, functional wellbeing, and quality of life. Clinical Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373556&isReview=true, identifier ACTRN12617001287325.
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Affiliation(s)
- Janet Schloss
- National Centre for Naturopathic Medicine, Southern Cross University, Lismore, NSW, Australia.,Office of Research, Endeavour College of Natural Health, Brisbane, QLD, Australia.,Australian Research Centre in Complementary and Integrative Medicine, University of Technology, Sydney, NSW, Australia
| | - Judith Lacey
- National Institute of Complementary Medicine (NICM) Health Research Institute, Western Sydney University, Sydney, NSW, Australia.,Supportive Care, Chris O'Brien Lifehouse Cancer Hospital, Sydney, NSW, Australia.,Clinical School of Medicine, University of Sydney, Sydney, NSW, Australia
| | - Justin Sinclair
- National Institute of Complementary Medicine (NICM) Health Research Institute, Western Sydney University, Sydney, NSW, Australia
| | - Amie Steel
- Australian Research Centre in Complementary and Integrative Medicine, University of Technology, Sydney, NSW, Australia
| | - Michael Sughrue
- Prince of Wales Private Hospital, Centre for Minimally Invasive Neurosurgery, Sydney, NSW, Australia
| | - David Sibbritt
- Australian Research Centre in Complementary and Integrative Medicine, University of Technology, Sydney, NSW, Australia
| | - Charles Teo
- Prince of Wales Private Hospital, Centre for Minimally Invasive Neurosurgery, Sydney, NSW, Australia
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24
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Gavioli EM, Guardado N, Haniff F, Deiab N, Vider E. The Risk of QTc Prolongation with Antiemetics in the Palliative Care Setting: A Narrative Review. J Pain Palliat Care Pharmacother 2021; 35:125-135. [PMID: 33974499 DOI: 10.1080/15360288.2021.1900491] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Nausea and vomiting are common within the palliative care population. Antiemetic agents may help control symptoms, but may also place patients at risk for QTc prolongation. This article reviews pharmacotherapy agents including anticholinergics, antihistamines, antidopaminergics, 5-HT3 receptor antagonists, dronabinol, and medical marijuana and their associated risk of QTc prolongation. A clinical treatment pathway is provided to help guide clinicians in choosing the most appropriate antiemetic based upon patient specific factors for QTc prolongation.
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Affiliation(s)
- Elizabeth M Gavioli
- Elizabeth M. Gavioli, PharmD., Nerli Guardado, BA, Farah Haniff, BS, Nouran Deiab, BPS, and Etty Vider, PharmD, are with Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA
| | - Nerli Guardado
- Elizabeth M. Gavioli, PharmD., Nerli Guardado, BA, Farah Haniff, BS, Nouran Deiab, BPS, and Etty Vider, PharmD, are with Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA
| | - Farah Haniff
- Elizabeth M. Gavioli, PharmD., Nerli Guardado, BA, Farah Haniff, BS, Nouran Deiab, BPS, and Etty Vider, PharmD, are with Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA
| | - Nouran Deiab
- Elizabeth M. Gavioli, PharmD., Nerli Guardado, BA, Farah Haniff, BS, Nouran Deiab, BPS, and Etty Vider, PharmD, are with Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA
| | - Etty Vider
- Elizabeth M. Gavioli, PharmD., Nerli Guardado, BA, Farah Haniff, BS, Nouran Deiab, BPS, and Etty Vider, PharmD, are with Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA
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25
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Shakil SSM, Gowan M, Hughes K, Azam MNK, Ahmed MN. A narrative review of the ethnomedicinal usage of Cannabis sativa Linnaeus as traditional phytomedicine by folk medicine practitioners of Bangladesh. J Cannabis Res 2021; 3:8. [PMID: 33741060 PMCID: PMC7980557 DOI: 10.1186/s42238-021-00063-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 03/05/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There is a worldwide interest in the use of Cannabis sativa for biomedicine purposes. Cannabis has ethnomedicinal usage as a natural medicine in Bangladesh and cultivated during the British Empire period for revenues. OBJECTIVE Folk medicine practitioners (FMPs) from different districts of Bangladesh have been using Cannabis sativa, but until now there have not been any compiled studies particularly regarding this practice. Hence, this review is an effort to retrieve the traditional usage of Cannabis sativa as a phytomedicine from published ethnomedicinal studies. METHODS AND MATERIALS Information was searched by using the search terms "ethnomedicinal Cannabis sativa and Bangladesh"; "Bangladesh cannabaceae and ethnomedicinal survey"; "ganja, bhang and folk medicine Bangladesh"; "tetrahydrocannabinol (THC), cannabinoid and therapeutic, clinical trial"; and "cannabis and pharmacological/biological" and retrieved from ethnobotanical articles available on PubMed, Scopus, Science Direct, and Google Scholar databases. A search of the relevant scientific literature also was conducted to assess the efficacy of the ethnomedicinal usage of Cannabis sativa. RESULTS While reviewing over 200 ethnomedicinal plants' survey articles, we found that FMPs of Bangladesh from 12 different districts used Cannabis sativa to treat cited ailments like sleep-associated problems (n=5), neuropsychiatric and CNS problems (n=5), and infections and respiratory problems (n=5) followed by rheumatism, gastrointestinal, gynecological (n=4 each), cancer, sexual, and other ailments including hypertension, headache, itch, increases bile secretion, abortifacient, dandruff, fever, and urinary problems (n=1 each). There are a total of 15 formulations identified from the 11 out of 18 ethnomedicinal plant survey reports. The leaf was the main plant part used (53.8%), followed by root (23%), seed (7.7%) and flower, inflorescence, resin, and all parts 3.8% respectively. CONCLUSIONS Sales and cultivation of Cannabis are illegal at present in Bangladesh, but the use of Cannabis sativa as a natural phytomedicine has been practiced traditionally by folk medicine practitioners of Bangladesh for many years and validated through relevant pharmacological justification. Although Cannabis sativa possesses ethnomedicinal properties in the folk medicine of Bangladesh, it is, furthermore, needed to conduct biological research to consolidate pharmacological justification about the prospects and challenges of Cannabis and cannabinoids' use in Bangladesh as safer biomedicine in the future.
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Affiliation(s)
| | - Matt Gowan
- The Canadian College of Naturopathic Medicine, Toronto, Ontario Canada
| | | | - Md. Nur Kabidul Azam
- Department of Genetic Engineering & Biotechnology, Jashore University of Science & Technology, Jashore, Bangladesh
| | - Md. Nasir Ahmed
- Biotechnology & Natural Medicine Division, TechB Nutrigenomics, Dhaka, Bangladesh
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26
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Waissengrin B, Mirelman D, Pelles S, Bukstein F, Blumenthal DT, Wolf I, Geva R. Effect of cannabis on oxaliplatin-induced peripheral neuropathy among oncology patients: a retrospective analysis. Ther Adv Med Oncol 2021; 13:1758835921990203. [PMID: 33613702 PMCID: PMC7876573 DOI: 10.1177/1758835921990203] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 12/31/2020] [Indexed: 01/04/2023] Open
Abstract
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dosage-limited oxaliplatin-related toxicity. To date, there are no successful interventions for CIPN prevention or treatment. A therapeutic role for cannabis in diabetic and HIV-related peripheral neuropathy and a protective role in CIPN have been suggested. We examined the effect of cannabis on oncologic patients with CIPN. Methods: Medical records of 768 consecutive patients treated with oxaliplatin and 5-fluorouracil-based combinations at a tertiary medical center from October 2015 to January 2018 were reviewed. Excluded patients were those with pre-existing neuropathy or patients who received fewer than two cycles of oxaliplatin treatment. CIPN grade, oxaliplatin cumulative dose, and neuropathy-free survival were evaluated. The patients were divided based upon the exposure to cannabis: prior to oxaliplatin (cannabis-first), cannabis following the initiation of oxaliplatin treatment (oxaliplatin-first), and no exposure (control). Results: In total, 513 patients met the inclusion criteria, of whom 248 were treated with cannabis and 265 served as controls. The cannabis-first group included 116 (46.7%) patients and the oxaliplatin-first group included 132 (53.3%) patients. Demographic parameters were comparable between groups. There was a significant difference in CIPN grade 2–3 between cannabis-exposed patients and controls (15.3% and 27.9%, respectively, p < 0.001). The protective effect of cannabis was more pronounced among cannabis-first patients compared to oxaliplatin-first patients (75% and 46.2%, respectively, p < 0.001). The median oxaliplatin cumulative doses were higher in the cannabis-first versus the oxaliplatin-first versus the control groups (545 mg/m2, 340 mg/m2, and 425 mg/m2 respectively, p < 0.001). Conclusion: The rate of neuropathy was reduced among patients treated with cannabis and oxaliplatin. This reduction was more significant in patients who received cannabis prior to treatment with oxaliplatin, suggesting a protective effect. A large prospective trial is planned.
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Affiliation(s)
- Barliz Waissengrin
- Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Dan Mirelman
- Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Sharon Pelles
- Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Felix Bukstein
- Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | | | - Ido Wolf
- Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Ravit Geva
- Oncology Division, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 6423906, Israel
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27
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Abu-Amna M, Salti T, Khoury M, Cohen I, Bar-Sela G. Medical Cannabis in Oncology: a Valuable Unappreciated Remedy or an Undesirable Risk? Curr Treat Options Oncol 2021; 22:16. [PMID: 33439370 DOI: 10.1007/s11864-020-00811-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 01/11/2023]
Abstract
OPINION STATEMENT The use of the cannabis plant by cancer patients has been rising significantly in the past few years worldwide, primarily driven by public demand. There is an obvious need for more reliable scientific data, pharmacology information, a better understanding of its mode of action, and available clinical evidence supporting its robust use. Physicians must complete a thorough medical assessment, screening for potential drugs, or treatment contraindications before allowing its consumption. In light of the growing popularity of cannabis usage, it is highly essential that, in the near future, the medical community will be able to provide practical recommendations and explicit guidelines, including doses, and that cannabinoid concentrations in the used products are defined regarding its prescription before any medical procedure involving its usage is authorized. Here, we review and describe the favorable outcomes demonstrating the benefits of cannabis as an adjunctive treatment to conventional medicines for chemotherapy-induced nausea, vomiting, and cancer-related pain (primarily refractory chronic or neuropathic pain). Although not yet substantial enough, the treatment of anorexia, insomnia, depression, and anxiety is also seemingly favorable. To date, reports regarding its anti-neoplastic effects or its potent immunosuppressive properties influencing response to immunotherapy are still very conflicting and controversial. Thus, with the current state of evidence, cannabis use is not advisable as initial treatment, as an adjunct or an advanced line of care. In the coming years, we expect that preclinical data and animal models will shift to the clinical arena, and more patients will be recruited for clinical trials, and their reports will advance the field. Thus, physicians should prescribe cannabis only if careful clarification and consideration is provided together with a follow-up response evaluation.
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Affiliation(s)
- Mahmoud Abu-Amna
- Cancer Center, Emek Medical Center, 21 Yitzhak Rabin Blvd, 1834111, Afula, Israel
| | - Talal Salti
- Cancer Center, Emek Medical Center, 21 Yitzhak Rabin Blvd, 1834111, Afula, Israel.,Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 320002, Haifa, Israel
| | - Mona Khoury
- Cancer Center, Emek Medical Center, 21 Yitzhak Rabin Blvd, 1834111, Afula, Israel.,Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 320002, Haifa, Israel
| | - Idan Cohen
- Cancer Center, Emek Medical Center, 21 Yitzhak Rabin Blvd, 1834111, Afula, Israel
| | - Gil Bar-Sela
- Cancer Center, Emek Medical Center, 21 Yitzhak Rabin Blvd, 1834111, Afula, Israel. .,Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 320002, Haifa, Israel.
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28
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Nabata KJ, Tse EK, Nightingale TE, Lee AH, Eng JJ, Querée M, Walter M, Krassioukov AV. The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord Injuries: A Systematic Review. Curr Neuropharmacol 2021; 19:402-432. [PMID: 32310048 PMCID: PMC8033968 DOI: 10.2174/1570159x18666200420085712] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 03/12/2020] [Accepted: 04/15/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND People with spinal cord injuries (SCI) commonly experience pain and spasticity; limitations of current treatments have generated interest in cannabis as a possible therapy. OBJECTIVES We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use in people with SCI. METHODS PubMed, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature databases were queried for keywords related to SCI and cannabinoids. RESULTS 7,232 studies were screened, and 34 were included in this systematic review. Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity. The most common method of use was smoking. Relief of pain, spasticity and recreation were the most common reasons for use. A statistically significant reduction of pain and spasticity was observed with cannabinoid use in 83% and 100% of experimental studies, respectively. However, on examination of randomized control trials (RCTs) alone, effect sizes ranged from - 0.82 to 0.83 for pain and -0.95 to 0.09 for spasticity. Cannabinoid use was associated with fatigue and cognitive deficits. CONCLUSION Current evidence suggests that cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance are unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Long-term, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understand the effects of cannabinoid use in people with SCI.
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Affiliation(s)
| | | | | | | | | | | | | | - Andrei V. Krassioukov
- Address correspondence to this author at the International Collaboration On Repair Discoveries (ICORD), University of British Columbia (UBC), Vancouver, Canada; E-mail:
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Aviram J, Lewitus GM, Vysotski Y, Uribayev A, Procaccia S, Cohen I, Leibovici A, Abo-Amna M, Akria L, Goncharov D, Mativ N, Kauffman A, Shai A, Hazan O, Bar-Sela G, Meiri D. Short-Term Medical Cannabis Treatment Regimens Produced Beneficial Effects among Palliative Cancer Patients. Pharmaceuticals (Basel) 2020; 13:ph13120435. [PMID: 33265945 PMCID: PMC7761379 DOI: 10.3390/ph13120435] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 11/25/2020] [Accepted: 11/27/2020] [Indexed: 12/14/2022] Open
Abstract
In the last decade the use of medical cannabis (MC) for palliative cancer treatment has risen. However, the choice between products is arbitrary and most patients are using Tetrahydrocannabinol (THC)-dominant cannabis products. In this study, we aimed to assess the short-term outcomes of MC treatment prescribed by oncologists in relation to the type of cannabis they receive. A comparative analysis was used to assess the differences in treatment effectiveness and safety between THC-dominant (n = 56, 52%), cannabidiol (CBD)-dominant (n = 19, 18%), and mixed (n = 33, 30%) MC treatments. Oncology patients (n = 108) reported on multiple symptoms in baseline questionnaires, initiated MC treatment, and completed a one-month follow-up. Most parameters improved significantly from baseline, including pain intensity, affective and sensory pain, sleep quality and duration, cancer distress, and both physical and psychological symptom burden. There was no significant difference between the three MC treatments in the MC-related safety profile. Generally, there were no differences between the three MC treatments in pain intensity and in most secondary outcomes. Unexpectedly, CBD-dominant oil treatments were similar to THC-dominant treatments in their beneficial effects for most secondary outcomes. THC-dominant treatments showed significant superiority in their beneficial effect only in sleep duration compared to CBD-dominant treatments. This work provides evidence that, though patients usually consume THC-dominant products, caregivers should also consider CBD-dominant products as a useful treatment for cancer-related symptoms.
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Affiliation(s)
- Joshua Aviram
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; (J.A.); (G.M.L.); (Y.V.); (S.P.); (O.H.)
| | - Gil M. Lewitus
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; (J.A.); (G.M.L.); (Y.V.); (S.P.); (O.H.)
| | - Yelena Vysotski
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; (J.A.); (G.M.L.); (Y.V.); (S.P.); (O.H.)
| | - Anton Uribayev
- Department of Oncology, Galilee Medical Center, Nahariya 22100, Israel; (A.U.); (A.L.); (L.A.); (D.G.); (N.M.); (A.K.); (A.S.)
| | - Shiri Procaccia
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; (J.A.); (G.M.L.); (Y.V.); (S.P.); (O.H.)
| | - Idan Cohen
- Cancer Center, Emek Medical Center, Afula 18101, Israel; (I.C.); (M.A.-A.)
| | - Anca Leibovici
- Department of Oncology, Galilee Medical Center, Nahariya 22100, Israel; (A.U.); (A.L.); (L.A.); (D.G.); (N.M.); (A.K.); (A.S.)
| | - Mahmud Abo-Amna
- Cancer Center, Emek Medical Center, Afula 18101, Israel; (I.C.); (M.A.-A.)
| | - Luiza Akria
- Department of Oncology, Galilee Medical Center, Nahariya 22100, Israel; (A.U.); (A.L.); (L.A.); (D.G.); (N.M.); (A.K.); (A.S.)
| | - Dmitry Goncharov
- Department of Oncology, Galilee Medical Center, Nahariya 22100, Israel; (A.U.); (A.L.); (L.A.); (D.G.); (N.M.); (A.K.); (A.S.)
| | - Neomi Mativ
- Department of Oncology, Galilee Medical Center, Nahariya 22100, Israel; (A.U.); (A.L.); (L.A.); (D.G.); (N.M.); (A.K.); (A.S.)
| | - Avia Kauffman
- Department of Oncology, Galilee Medical Center, Nahariya 22100, Israel; (A.U.); (A.L.); (L.A.); (D.G.); (N.M.); (A.K.); (A.S.)
| | - Ayelet Shai
- Department of Oncology, Galilee Medical Center, Nahariya 22100, Israel; (A.U.); (A.L.); (L.A.); (D.G.); (N.M.); (A.K.); (A.S.)
| | - Or Hazan
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; (J.A.); (G.M.L.); (Y.V.); (S.P.); (O.H.)
| | - Gil Bar-Sela
- Cancer Center, Emek Medical Center, Afula 18101, Israel; (I.C.); (M.A.-A.)
- Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 32000, Israel
- Correspondence: (G.B.-S.); (D.M.); Tel.: +972-4-6495723 (G.B.-S.); +972-77-8871680 or +972-525330031 (D.M.)
| | - David Meiri
- Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; (J.A.); (G.M.L.); (Y.V.); (S.P.); (O.H.)
- Correspondence: (G.B.-S.); (D.M.); Tel.: +972-4-6495723 (G.B.-S.); +972-77-8871680 or +972-525330031 (D.M.)
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Abstract
Cannabinoids have been known as the primary component of cannabis for decades, but the characterization of the endocannabinoid system (ECS) in the 1990s opened the doors for cannabis' use in modern medicine. The 2 main receptors of this system, cannabinoid receptors 1 and 2, are found on cells of various tissues, with significant expression in the gastrointestinal (GI) tract. The characterization of the ECS also heralded the understanding of endocannabinoids, naturally occurring compounds synthesized in the human body. Via secondary signaling pathways acting on vagal nerves, nociceptors, and immune cells, cannabinoids have been shown to have both palliative and detrimental effects on the pathophysiology of GI disorders. Although research on the effects of both endogenous and exogenous cannabinoids has been slow due to the complicated legal history of cannabis, discoveries of cannabinoids' treatment potential have been found in various fields of medicine, including the GI world. Medical cannabis has since been offered as a treatment for a myriad of conditions and malignancies, including cancer, human immunodeficiency virus/acquired immunodeficiency syndrome, multiple sclerosis, chronic pain, nausea, posttraumatic stress disorder, amyotrophic lateral sclerosis, cachexia, glaucoma, and epilepsy. This article hopes to create an overview of current research on cannabinoids and the ECS, detail the potential advantages and pitfalls of their use in GI diseases, and explore possible future developments in this field.
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Matowa PR, Gundidza M, Gwanzura L, Nhachi CFB. A survey of ethnomedicinal plants used to treat cancer by traditional medicine practitioners in Zimbabwe. BMC Complement Med Ther 2020; 20:278. [PMID: 32928194 PMCID: PMC7488988 DOI: 10.1186/s12906-020-03046-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 08/05/2020] [Indexed: 01/24/2023] Open
Abstract
Background Traditional medicine plays an important role in health care provision in the developing world. A number of cancer patients have been found to be using traditional medicine as primary therapy and/or as complementary medicine. Cancer is one of the leading causes of morbidity and mortality globally among the non-communicable diseases. The aim of this study was to identify the plants used by traditional medicine practitioners (TMPs) in Zimbabwe to treat cancer. Methods A structured questionnaire was used to interview consenting registered TMPs on ethnomedicinal plants they use to treat cancer. A review of published literature on the cited plants was also carried out. The practitioners were asked about the plants that they use to treat cancer, the plant parts used, type of cancer treated, other medicinal uses of the plants and preparation and administration of the plant parts. Results Twenty (20) TMPs took part in the study. A total of 18 medicinal plant species were cited. The commonly treated types of cancer were breast, prostate, colon, skin and blood cancers with most plants being used to treat skin, blood and breast cancers, respectively. Of the medicinal plants cited, 44.4% were used to treat all cancer types. The most used plant parts were the roots (72.2%) and leaves (72.2%) followed by the bark (38.9%). The medicinal plants were used for multiple ailments. The most common plant preparation methods were infusion (72.2%) and decoction (66.7%) and the oral route of administration, as extracts and powder put in tea and porridge, was the most used. Conclusion The frequently used plant parts were leaves and roots. The traditional uses of the medicinal plants cited in this study resonate well with their reported uses from other ethnopharmacological studies done in other parts of the world. The plants used by TMPs to treat cancer in Zimbabwe, if adequately explored, can be instrumental in the discovery and development of cancer drugs.
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Affiliation(s)
- Patrick Rutendo Matowa
- Clinical Pharmacology Department, University of Zimbabwe, Mt Pleasant, Harare, Zimbabwe.
| | - Mazuru Gundidza
- Pharmaceutical Technology Department, Harare Institute of Technology, Belvedere, Harare, Zimbabwe
| | - Lovemore Gwanzura
- Medical Laboratory Sciences, University of Zimbabwe, Mt pleasant, Harare, Zimbabwe
| | - Charles F B Nhachi
- Clinical Pharmacology Department, University of Zimbabwe, Mt Pleasant, Harare, Zimbabwe
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van Egmond N, Straub VM, van der Stelt M. Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors. Annu Rev Pharmacol Toxicol 2020; 61:441-463. [PMID: 32867595 DOI: 10.1146/annurev-pharmtox-030220-112741] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (-)-trans-Δ9-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB1 receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.
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Affiliation(s)
- Noëlle van Egmond
- Department of Molecular Physiology, Leiden University, 2333 CC Leiden, The Netherlands;
| | - Verena M Straub
- Department of Molecular Physiology, Leiden University, 2333 CC Leiden, The Netherlands;
| | - Mario van der Stelt
- Department of Molecular Physiology, Leiden University, 2333 CC Leiden, The Netherlands;
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Kopjar N, Fuchs N, Brčić Karačonji I, Žunec S, Katić A, Kozina G, Lucić Vrdoljak A. High Doses of Δ 9-Tetrahydrocannabinol Might Impair Irinotecan Chemotherapy: A Review of Potentially Harmful Interactions. Clin Drug Investig 2020; 40:775-787. [PMID: 32696321 DOI: 10.1007/s40261-020-00954-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
This review proposes the hypothesis that the effectiveness of irinotecan chemotherapy might be impaired by high doses of concomitantly administered Δ9-tetrahydrocannabinol (THC). The most important features shared by irinotecan and THC, which might represent sources of potentially harmful interactions are: first-pass hepatic metabolism mediated by cytochrome P450 (CYP) enzyme CYP3A4; glucuronidation mediated by uridine diphosphate glycosyltransferase (UGT) enzymes, isoforms 1A1 and 1A9; transport of parent compounds and their metabolites via canalicular ATP-binding cassette (ABC) transporters ABCB1 and ABCG2; enterohepatic recirculation of both parent compounds, which leads to an extended duration of their pharmacological effects; possible competition for binding to albumin; butyrylcholinesterase (BChE) inhibition by THC, which might impair the conversion of parent irinotecan into the SN-38 metabolite; mutual effects on mitochondrial dysfunction and induction of oxidative stress; potentiation of hepatotoxicity; potentiation of genotoxicity and cytogenetic effects leading to genome instability; possible neurotoxicity; and effects on bilirubin. The controversies associated with the use of highly concentrated THC preparations with irinotecan chemotherapy are also discussed. Despite all of the limitations, the body of evidence provided here could be considered relevant for human-risk assessments and calls for concern in cases when irinotecan chemotherapy is accompanied by preparations rich in THC.
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Affiliation(s)
- Nevenka Kopjar
- Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
| | - Nino Fuchs
- Department of Surgery, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Irena Brčić Karačonji
- Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
| | - Suzana Žunec
- Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
| | - Anja Katić
- Analytical Toxicology and Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
| | - Goran Kozina
- University Centre Varaždin, University North, Varaždin, Croatia
| | - Ana Lucić Vrdoljak
- Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia
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Inglet S, Winter B, Yost SE, Entringer S, Lian A, Biksacky M, Pitt RD, Mortensen W. Clinical Data for the Use of Cannabis-Based Treatments: A Comprehensive Review of the Literature. Ann Pharmacother 2020; 54:1109-1143. [DOI: 10.1177/1060028020930189] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective: To compile and synthesize the available literature describing medical cannabis use across various disease states. Data Sources: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords. Study Selection and Data Extraction: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019. Data Synthesis: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care. Relevance to Patient Care and Clinical Practice: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria. Conclusions: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.
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Affiliation(s)
| | | | | | | | - Anh Lian
- Intermountain Healthcare, Taylorsville, UT, USA
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35
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Farra YM, Eden MJ, Coleman JR, Kulkarni P, Ferris CF, Oakes JM, Bellini C. Acute neuroradiological, behavioral, and physiological effects of nose-only exposure to vaporized cannabis in C57BL/6 mice. Inhal Toxicol 2020; 32:200-217. [PMID: 32475185 DOI: 10.1080/08958378.2020.1767237] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Objective: The rapid increase of cannabis consumption reinforces the need to elucidate the health hazards of this practice. The presence of fine particulate matter in cannabis smoke and vapor poses a major concern, as it may contribute to cardiopulmonary disease. To facilitate the assessment of risks associated with cannabis inhalation, we developed and characterized a method for exposing mice to cannabis in a way that mimics the delivery of the drug to the airways of smokers. Materials and Methods: Cannabis (10.3% THC, 0.05% CBD) was vaporized to generate aerosols with a reproducible particle profile. Aerosols were acutely delivered to male, adult C57BL/6 mice via a nose-only exposure system. Serum THC levels were measured for increasing cannabis doses. Blood pressure and heart rate were recorded at baseline and following exposure. Behavioral response to cannabis inhalation in the open field was documented. Awake neurological activity upon cannabis exposure was monitored using BOLD fMRI.Results and Discussion: Cannabis aerosols contained particles with count median diameter of 243 ± 39 nm and geometric standard deviation of 1.56 ± 0.06. Blood serum THC levels increased linearly with aerosolized mass and peaked at 136 ± 5 ng/mL. Cannabis inhalation decreased heart rate and blood pressure but promoted anxiety-like behavior. Observed differences in BOLD activation volumes linked cannabis to increased awareness to sensory stimuli and reduced behavioral arousal.Conclusions: Quantified physiological, behavioral, and neurological responses served as validation for our mouse model of cannabis inhalation. Animal models of aerosol exposure will be instrumental for uncovering the health outcomes of chronic cannabis use.
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Affiliation(s)
- Yasmeen M Farra
- Department of Bioengineering, Northeastern University, Boston, MA, USA
| | - Matthew J Eden
- Department of Bioengineering, Northeastern University, Boston, MA, USA
| | - James R Coleman
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA
| | - Praveen Kulkarni
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA
| | - Craig F Ferris
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA
| | - Jessica M Oakes
- Department of Bioengineering, Northeastern University, Boston, MA, USA
| | - Chiara Bellini
- Department of Bioengineering, Northeastern University, Boston, MA, USA
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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 2020; 18:1534735419881498. [PMID: 31595793 PMCID: PMC6785913 DOI: 10.1177/1534735419881498] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Background: Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients. Methods: The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline. Results: Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients’ self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated. Conclusions: Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.
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Affiliation(s)
- Gil Bar-Sela
- Emek Medical Center, Afula, Israel.,Technion-Israel Institute of Technology, Haifa, Israel
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Jin D, Dai K, Xie Z, Chen J. Secondary Metabolites Profiled in Cannabis Inflorescences, Leaves, Stem Barks, and Roots for Medicinal Purposes. Sci Rep 2020; 10:3309. [PMID: 32094454 PMCID: PMC7039888 DOI: 10.1038/s41598-020-60172-6] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 02/06/2020] [Indexed: 11/29/2022] Open
Abstract
Cannabis research has historically focused on the most prevalent cannabinoids. However, extracts with a broad spectrum of secondary metabolites may have increased efficacy and decreased adverse effects compared to cannabinoids in isolation. Cannabis's complexity contributes to the length and breadth of its historical usage, including the individual application of the leaves, stem barks, and roots, for which modern research has not fully developed its therapeutic potential. This study is the first attempt to profile secondary metabolites groups in individual plant parts comprehensively. We profiled 14 cannabinoids, 47 terpenoids (29 monoterpenoids, 15 sesquiterpenoids, and 3 triterpenoids), 3 sterols, and 7 flavonoids in cannabis flowers, leaves, stem barks, and roots in three chemovars available. Cannabis inflorescence was characterized by cannabinoids (15.77-20.37%), terpenoids (1.28-2.14%), and flavonoids (0.07-0.14%); the leaf by cannabinoids (1.10-2.10%), terpenoids (0.13-0.28%), and flavonoids (0.34-0.44%); stem barks by sterols (0.07-0.08%) and triterpenoids (0.05-0.15%); roots by sterols (0.06-0.09%) and triterpenoids (0.13-0.24%). This comprehensive profile of bioactive compounds can form a baseline of reference values useful for research and clinical studies to understand the "entourage effect" of cannabis as a whole, and also to rediscover therapeutic potential for each part of cannabis from their traditional use by applying modern scientific methodologies.
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Affiliation(s)
- Dan Jin
- Biomedical Engineering Department, University of Alberta, Edmonton, Alberta, Canada
- Labs-Mart Inc., Edmonton, Alberta, Canada
| | | | - Zhen Xie
- Labs-Mart Inc., Edmonton, Alberta, Canada
| | - Jie Chen
- Biomedical Engineering Department, University of Alberta, Edmonton, Alberta, Canada.
- Electrical and Computer Engineering Department, University of Alberta, Edmonton, Alberta, Canada.
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38
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Panozzo S, Le B, Collins A, Weil J, Whyte J, Barton M, Coperchini M, Rametta M, Philip J. Who is asking about medicinal cannabis in palliative care? Intern Med J 2020; 50:243-246. [DOI: 10.1111/imj.14732] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 07/08/2019] [Accepted: 07/12/2019] [Indexed: 12/01/2022]
Affiliation(s)
- Stacey Panozzo
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
- Department of MedicineThe University of Melbourne Melbourne Victoria Australia
- Palliative Medicine Research Group, St Vincent's Hospital Melbourne Victoria Australia
| | - Brian Le
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
- Palliative and Supportive Care, Royal Melbourne Hospital Melbourne Victoria Australia
| | - Anna Collins
- Department of MedicineThe University of Melbourne Melbourne Victoria Australia
- Palliative Medicine Research Group, St Vincent's Hospital Melbourne Victoria Australia
| | - Jennifer Weil
- Palliative Care, St Vincent's Hospital Melbourne Victoria Australia
| | - Jan Whyte
- Western and Central Melbourne Integrated Cancer Service Melbourne Victoria Australia
| | - Michael Barton
- Western and Central Melbourne Integrated Cancer Service Melbourne Victoria Australia
| | | | - Meri Rametta
- Peter MacCallum Cancer Centre Melbourne Victoria Australia
| | - Jennifer Philip
- Department of MedicineThe University of Melbourne Melbourne Victoria Australia
- Palliative Medicine Research Group, St Vincent's Hospital Melbourne Victoria Australia
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Prospéro-García O, Ruiz Contreras AE, Ortega Gómez A, Herrera-Solís A, Méndez-Díaz M. Endocannabinoids as Therapeutic Targets. Arch Med Res 2020; 50:518-526. [PMID: 32028095 DOI: 10.1016/j.arcmed.2019.09.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 08/01/2019] [Accepted: 09/30/2019] [Indexed: 12/22/2022]
Abstract
Most of the drugs of abuse affect the brain by interacting with naturally expressed molecular receptors. Marihuana affects a series of receptors including cannabinoid receptor 1 (CB1R) and CB2R, among others. Endogenous molecules with cannabinoid activity interact with these receptors naturally. Receptors, ligands, synthesizing and degrading enzymes, as well as transporters, have been described. This endocannabinoid system modulates behaviors and physiological processes, i.e. food intake, the sleep-waking cycle, learning and memory, motivation, and pain perception, among others. The rather broad distribution of endocannabinoids in the brain explains the different effects marihuana induces in its users. However, this very same anatomical and physiological distribution makes this system a useful target for therapeutic endeavors. In this review, we briefly discuss the potential of small molecules that target the endocannabinoids as therapeutic tools to improve behaviors and treat illnesses. We believe that under medical supervision, endocannabinoid targets offer new advantages for patients for controlling multiple medical disorders.
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Affiliation(s)
- Oscar Prospéro-García
- Departamento de Fisiología, Laboratorio de Canabinoides, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
| | - Alejandra E Ruiz Contreras
- Laboratorio de Neurogenómica Cognitiva, Facultad de Psicología, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Alette Ortega Gómez
- Laboratorio de Medicina Traslacional, Instituto Nacional de Cancerología, Ciudad de México, Mexico
| | - Andrea Herrera-Solís
- Laboratorio Efectos Terapéuticos de los Canabinoides, Subdirección de Investigación Biomédica, Hospital General Dr. Manuel Gea González, Ciudad de México, Mexico
| | - Mónica Méndez-Díaz
- Departamento de Fisiología, Laboratorio de Canabinoides, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
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Montero-Oleas N, Arevalo-Rodriguez I, Nuñez-González S, Viteri-García A, Simancas-Racines D. Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews. BMC Complement Med Ther 2020; 20:12. [PMID: 32020875 PMCID: PMC7076827 DOI: 10.1186/s12906-019-2803-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 12/22/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps. METHODS We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios. RESULTS A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores. CONCLUSIONS Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.
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Affiliation(s)
- Nadia Montero-Oleas
- Centro de investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud "Eugenio Espejo", Universidad UTE, Quito, Ecuador.
| | - Ingrid Arevalo-Rodriguez
- Clinical Biostatistics Unit, Hospital Ramon y Cajal (IRYCIS), CIBER of Epidemiology and Public Health, Madrid, Spain
| | - Solange Nuñez-González
- Centro de investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud "Eugenio Espejo", Universidad UTE, Quito, Ecuador
| | - Andrés Viteri-García
- Centro de investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud "Eugenio Espejo", Universidad UTE, Quito, Ecuador
| | - Daniel Simancas-Racines
- Centro de investigación en Salud Pública y Epidemiología Clínica (CISPEC). Facultad de Ciencias de la Salud "Eugenio Espejo", Universidad UTE, Quito, Ecuador
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Pratt M, Stevens A, Thuku M, Butler C, Skidmore B, Wieland LS, Clemons M, Kanji S, Hutton B. Benefits and harms of medical cannabis: a scoping review of systematic reviews. Syst Rev 2019; 8:320. [PMID: 31823819 PMCID: PMC6905063 DOI: 10.1186/s13643-019-1243-x] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 11/24/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition. METHODS A protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review. RESULTS After screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n = 36) or low/critically low (n = 35) quality. CONCLUSIONS Results from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits. SYSTEMATIC REVIEW REGISTRATION The protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).
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Affiliation(s)
- Misty Pratt
- Knowledge Synthesis Group, Ottawa Methods Centre, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8 L6 Canada
| | - Adrienne Stevens
- Knowledge Synthesis Group, Ottawa Methods Centre, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8 L6 Canada
- TRIBE Graduate Program, University of Split School of Medicine, Split, Croatia
| | - Micere Thuku
- Knowledge Synthesis Group, Ottawa Methods Centre, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8 L6 Canada
| | - Claire Butler
- Knowledge Synthesis Group, Ottawa Methods Centre, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8 L6 Canada
- Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3A 2B4 Canada
| | | | - L. Susan Wieland
- Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore, MD USA
| | - Mark Clemons
- School of Epidemiology and Public Health, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8 M5 Canada
- Division of Medical Oncology and Department of Medicine, University of Ottawa, Ottawa, Canada
| | - Salmaan Kanji
- School of Epidemiology and Public Health, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8 M5 Canada
- Department of Pharmacy, The Ottawa Hospital, Ottawa, Canada
- Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Canada
| | - Brian Hutton
- Knowledge Synthesis Group, Ottawa Methods Centre, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8 L6 Canada
- School of Epidemiology and Public Health, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8 M5 Canada
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Maguire WJ, Call CW, Cerbu C, Jambor KL, Benavides-Montes VE. Comprehensive Determination of Unregulated Pesticide Residues in Oregon Cannabis Flower by Liquid Chromatography Paired with Triple Quadrupole Mass Spectrometry and Gas Chromatography Paired with Triple Quadrupole Mass Spectrometry. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:12670-12674. [PMID: 31398037 DOI: 10.1021/acs.jafc.9b01559] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
A comprehensive multiresidue pesticide analysis for Cannabis flower matrices using quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation, liquid chromatography paired with triple quadrupole mass spectrometry (LC-MS/MS), and gas chromatography paired with triple quadrupole mass spectrometry (GC-MS/MS) was established and validated for 367 pesticides with excellent recoveries (70-120%) for over 99% of analytes included. This research demonstrates the viability of pesticide testing in Cannabis, with a wide scope of analysis mirroring the methodology used in food and crop analyses of pesticides worldwide, with tools most analytical laboratories possess. The method developed here was then applied to Cannabis flower samples from Oregon, and results were compared to existing state pesticide regulations. A total of 4 of these 100 samples analyzed contained pesticides unregulated in Oregon, while 3 samples contained regulated pesticides significantly above the regulated action levels of Oregon. These results suggest a need for more complete testing regulations surrounding Cannabis and highlight possible deficiencies in quality control and oversight among independent testing laboratories in states with mandatory Cannabis testing.
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Affiliation(s)
- Wesley J Maguire
- Columbia Food Laboratories , 12423 Northeast Whitaker Way , Portland , Oregon 97230 , United States
| | - Cameron W Call
- Columbia Food Laboratories , 12423 Northeast Whitaker Way , Portland , Oregon 97230 , United States
| | - Cornel Cerbu
- Columbia Food Laboratories , 12423 Northeast Whitaker Way , Portland , Oregon 97230 , United States
| | - Katie L Jambor
- Columbia Food Laboratories , 12423 Northeast Whitaker Way , Portland , Oregon 97230 , United States
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Monton C, Madaka F, Settharaksa S, Wunnakup T, Suksaeree J, Songsak T. Optimal condition of cannabis maceration to obtain the high cannabidiol and Δ9-tetrahydrocannabinol content. AN ACAD BRAS CIENC 2019; 91:e20190676. [PMID: 31618414 DOI: 10.1590/0001-3765201920190676] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 07/25/2019] [Indexed: 11/21/2022] Open
Abstract
The aim of this work was to optimize a maceration condition of cannabis (Cannabis sativa L.). A circumscribed central composite experimental design was applied in this work. Temperature and time were varied from 40-80 °C and 30-90 min, respectively. The three responses (i.e., extraction yield, cannabidiol content, and Δ9- tetrahydrocannabinol content) were predicted by computer software. The yield was high when cannabis was macerated using ethanol at high temperature and long duration time. While cannabidiol and Δ9- tetrahydrocannabinol content was high when macerating at a low heating temperature and short duration time. The optimal condition provided the simultaneous high of cannabidiol and Δ9- tetrahydrocannabinol content was 40 °C for 30 min. The prediction was accurate due to low percent error. This optimal condition could be used as a guide for maceration of cannabis to obtain the extract containing a high content of cannabidiol and Δ9- tetrahydrocannabinol.
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Affiliation(s)
- Chaowalit Monton
- Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand.,Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani, 12000,Thailand
| | - Fameera Madaka
- Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand.,Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani, 12000,Thailand
| | - Sukanya Settharaksa
- Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand.,Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani, 12000,Thailand
| | - Thaniya Wunnakup
- Drug and Herbal Product Research and Development Center, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand.,Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani, 12000,Thailand
| | - Jirapornchai Suksaeree
- Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani, 12000,Thailand.,Department of Pharmaceutical Chemistry, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand
| | - Thanapat Songsak
- Medicinal Cannabis Research Institute, College of Pharmacy, Rangsit University, Pathum Thani, 12000,Thailand.,Department of Pharmacognosy, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand
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Baron EP. Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science. Headache 2019; 58:1139-1186. [PMID: 30152161 DOI: 10.1111/head.13345] [Citation(s) in RCA: 127] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 05/09/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Comprehensive literature reviews of historical perspectives and evidence supporting cannabis/cannabinoids in the treatment of pain, including migraine and headache, with associated neurobiological mechanisms of pain modulation have been well described. Most of the existing literature reports on the cannabinoids Δ9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), or cannabis in general. There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics. Knowledge of the individual medicinal properties of the cannabinoids, terpenes, and flavonoids is necessary to cross-breed strains to obtain optimal standardized synergistic compositions. This will enable targeting individual symptoms and/or diseases, including migraine, headache, and pain. OBJECTIVE Review the medical literature for the use of cannabis/cannabinoids in the treatment of migraine, headache, facial pain, and other chronic pain syndromes, and for supporting evidence of a potential role in combatting the opioid epidemic. Review the medical literature involving major and minor cannabinoids, primary and secondary terpenes, and flavonoids that underlie the synergistic entourage effects of cannabis. Summarize the individual medicinal benefits of these substances, including analgesic and anti-inflammatory properties. CONCLUSION There is accumulating evidence for various therapeutic benefits of cannabis/cannabinoids, especially in the treatment of pain, which may also apply to the treatment of migraine and headache. There is also supporting evidence that cannabis may assist in opioid detoxification and weaning, thus making it a potential weapon in battling the opioid epidemic. Cannabis science is a rapidly evolving medical sector and industry with increasingly regulated production standards. Further research is anticipated to optimize breeding of strain-specific synergistic ratios of cannabinoids, terpenes, and other phytochemicals for predictable user effects, characteristics, and improved symptom and disease-targeted therapies.
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Affiliation(s)
- Eric P Baron
- Department of Neurology, Center for Neurological Restoration - Headache and Chronic Pain Medicine, Cleveland Clinic Neurological Institute, Cleveland, OH, 44195, USA
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45
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Pi S, Rosenfeld G, Enns R, Bressler B, Wong A, Enns C, MacDonnell C, Leung Y. Patterns and motivations of
Cannabis
use amongst patients with inflammatory bowel disease. ACTA ACUST UNITED AC 2019. [DOI: 10.1002/ygh2.338] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Steven Pi
- Department of Medicine University of British Columbia Vancouver British Columbia Canada
| | - Greg Rosenfeld
- Division of Gastroenterology, Department of Medicine University of British Columbia, St. Paul’s Hospital Vancouver British Columbia Canada
| | - Robert Enns
- Division of Gastroenterology, Department of Medicine University of British Columbia, St. Paul’s Hospital Vancouver British Columbia Canada
| | - Brian Bressler
- Division of Gastroenterology, Department of Medicine University of British Columbia, St. Paul’s Hospital Vancouver British Columbia Canada
| | - Amy Wong
- Pacific Gastroenterology Associates Vancouver British Columbia Canada
| | - Chasyn Enns
- Pacific Gastroenterology Associates Vancouver British Columbia Canada
| | - Chris MacDonnell
- Pacific Gastroenterology Associates Vancouver British Columbia Canada
| | - Yvette Leung
- Division of Gastroenterology, Department of Medicine University of British Columbia, St. Paul’s Hospital Vancouver British Columbia Canada
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Cannabis: From a Plant That Modulates Feeding Behaviors toward Developing Selective Inhibitors of the Peripheral Endocannabinoid System for the Treatment of Obesity and Metabolic Syndrome. Toxins (Basel) 2019; 11:toxins11050275. [PMID: 31096702 PMCID: PMC6563239 DOI: 10.3390/toxins11050275] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 05/10/2019] [Accepted: 05/12/2019] [Indexed: 12/15/2022] Open
Abstract
In this review, we discuss the role of the endocannabinoid (eCB) system in regulating energy and metabolic homeostasis. Endocannabinoids, via activating the cannabinoid type-1 receptor (CB1R), are commonly known as mediators of the thrifty phenotype hypothesis due to their activity in the central nervous system, which in turn regulates food intake and underlies the development of metabolic syndrome. Indeed, these findings led to the clinical testing of globally acting CB1R blockers for obesity and various metabolic complications. However, their therapeutic potential was halted due to centrally mediated adverse effects. Recent observations that highlighted the key role of the peripheral eCB system in metabolic regulation led to the preclinical development of various novel compounds that block CB1R only in peripheral organs with very limited brain penetration and without causing behavioral side effects. These unique molecules, which effectively ameliorate obesity, type II diabetes, fatty liver, insulin resistance, and chronic kidney disease in several animal models, are likely to be further developed in the clinic and may revive the therapeutic potential of blocking CB1R once again.
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Makary P, Parmar JR, Mims N, Khanfar NM, Freeman RA. Patient Counseling Guidelines for the Use of Cannabis for the Treatment of Chemotherapy-Induced Nausea/Vomiting and Chronic Pain. J Pain Palliat Care Pharmacother 2019; 32:216-225. [PMID: 31070496 DOI: 10.1080/15360288.2019.1598531] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The use of cannabis medications has grown in recent years for the symptomatic relief of chemotherapy-induced nausea/vomiting (CINV) and chronic pain (cancer-related and non-cancer-related). As states legalize the use of cannabis, it is important for pharmacists and other health care professionals to be aware of how to counsel patients receiving prescriptions for cannabis medications. The aim of this study was to develop patient counseling guidelines for the use of cannabis products in treatment of CINV and chronic pain. A literature search was performed using Medline/PubMed resources and Google Scholar between July 2015 and August 2018 using broad search terms, e.g., cannabinoids adverse effects, cannabis, natural cannabinoids, and tetrahydrocannabinol. Using the American Society of Health-System Pharmacists patient counseling guidelines and medical information on cannabis medications gathered from drug databases, a comprehensive counseling guideline was developed. Medical evidence of the use of natural cannabis medications that are smoked or orally ingested have not been studied as extensively as oral therapeutic agents currently available. Cannabis medications have become more prevalent by approval of legislators in several states. Hence, pharmacists and health care professionals should counsel patients effectively on its use. This guideline needs to be tested to assess its utility in patients.
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Mortimer TL, Mabin T, Engelbrecht AM. Cannabinoids: the lows and the highs of chemotherapy-induced nausea and vomiting. Future Oncol 2019; 15:1035-1049. [PMID: 30720344 DOI: 10.2217/fon-2018-0530] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Despite remaining one of the most widely abused drugs worldwide, Cannabis sativa exhibits remarkable medicinal properties. The phytocannabinoids, cannabidiol and Δ-9-tetrahydrocannabinol, reduce nausea and vomiting, particularly during chemotherapy. This is attributed to their ability to reduce the release of serotonin from enterochromaffin cells in the small intestine, which would otherwise orchestrate the vomiting reflex. Although there are many preclinical and clinical studies on the effects of Δ-9-tetrahydrocannabinol during nausea and vomiting, little is known about the role that cannabidiol plays in this scenario. Since cannabidiol does not induce psychotropic effects, in contrast to other cannabinoids, its use as an anti-emetic is of great interest. This review aims to summarize the available literature on cannabinoid use, with a specific focus on the nonpsychotropic drug cannabidiol, as well as the roles that cannabinoids play in preventing several other adverse side effects of chemotherapy including organ toxicity, pain and loss of appetite.
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Affiliation(s)
- Toni Leigh Mortimer
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch, 7600, South Africa
| | - Tom Mabin
- Department of Medicine, Division of Cardiology, University of Cape Town, Observatory, 7925, South Africa
| | - Anna-Mart Engelbrecht
- Department of Physiological Sciences, Stellenbosch University, Stellenbosch, 7600, South Africa
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Turgeman I, Bar-Sela G. Cannabis for cancer - illusion or the tip of an iceberg: a review of the evidence for the use of Cannabis and synthetic cannabinoids in oncology. Expert Opin Investig Drugs 2018; 28:285-296. [PMID: 30572744 DOI: 10.1080/13543784.2019.1561859] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
INTRODUCTION A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes. Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines. AREAS COVERED The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids are classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products is discussed in the clinical context and data regarding chemotherapy-induced nausea and vomiting, cancer-related pain, anorexia, insomnia, and anxiety are presented. Moreover, immunological and antineoplastic effects in preclinical and clinical trials are addressed. Concepts such as synergism or opposition with conventional treatment modalities, the sequence of administration and dosage, molecular cross-talk and malignancy-cannabinoid congruence, are explored. Finally, side-effects, limitations in trial design and legislation barriers are related. EXPERT OPINION Sufficient evidence supports the use of Cannabis for palliative indications in oncology; however, patients should be carefully selected, guided and followed. Promising research suggests the potent antineoplastic activity, but more data must be accrued before conclusions can be drawn.
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Affiliation(s)
- Ilit Turgeman
- a Division of Oncology , Rambam Health Care Campus , Haifa , Israel
| | - Gil Bar-Sela
- b Center for Malignant Diseases , Emek Medical Center , Afula , Israel.,c Faculty of Medicine , Technion-Israel Institute of Technology , Haifa , Israel
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50
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Zivovinovic S, Alder R, Allenspach MD, Steuer C. Determination of cannabinoids in Cannabis sativa L. samples for recreational, medical, and forensic purposes by reversed-phase liquid chromatography-ultraviolet detection. J Anal Sci Technol 2018. [DOI: 10.1186/s40543-018-0159-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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