IDEAS home Printed from https://ideas.repec.org/a/plo/pmed00/1003524.html
   My bibliography  Save this article

Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis

Author

Listed:
  • Latha Velayudhan
  • Katie McGoohan
  • Sagnik Bhattacharyya

Abstract

Background: Cannabinoid-based medicines (CBMs) are being used widely in the elderly. However, their safety and tolerability in older adults remains unclear. We aimed to conduct a systematic review and meta-analysis of safety and tolerability of CBMs in adults of age ≥50 years. Methods and findings: A systematic search was performed using MEDLINE, PubMed, EMBASE, CINAHL PsychInfo, Cochrane Library, and ClinicalTrials.gov (1 January 1990 to 3 October 2020). Randomised clinical trials (RCTs) of CBMs in those with mean age of ≥50 years for all indications, evaluating the safety/tolerability of CBMs where adverse events have been quantified, were included. Study quality was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers conducted all review stages independently. Where possible, data were pooled using random-effects meta-analysis. Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs), serious AEs (SAEs), and death and risk ratio (RR) for withdrawal from study and reported separately for studies using tetrahydrocannabinol (THC), THC:cannabidiol (CBD) combination, and CBD. A total of 46 RCTs were identified as suitable for inclusion of which 31 (67%) were conducted in the United Kingdom and Europe. There were 6,216 patients (mean age 58.6 ± 7.5 years; 51% male) included in the analysis, with 3,469 receiving CBMs. Compared with controls, delta-9-tetrahydrocannabinol (THC)-containing CBMs significantly increased the incidence of all-cause and treatment-related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78]) and (IRR: 1.60 [95% CI, 1.26 to 2.04]); THC:CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98]) and (IRR: 1.70 [95% CI,1.24 to 2.33]), respectively. IRRs of SAEs and deaths were not significantly greater under CBMs containing THC with or without CBD. THC:CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE-related withdrawals. CBD alone did not increase the incidence of all-cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16]) or other outcomes as per qualitative synthesis. AE-related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03] and THC:CBD combination treatment ([QM (df = 1) = 4.554, p = 0.033]. THC-containing CBMs significantly increased incidence of dry mouth, dizziness/light-headedness, and somnolence/drowsiness. Study limitations include inability to fully exclude data from those

Suggested Citation

  • Latha Velayudhan & Katie McGoohan & Sagnik Bhattacharyya, 2021. "Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis," PLOS Medicine, Public Library of Science, vol. 18(3), pages 1-42, March.
    • Handle: RePEc:plo:pmed00:1003524
    DOI: 10.1371/journal.pmed.1003524
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003524
    Download Restriction: no
    File URL: https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003524&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pmed.1003524?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Viechtbauer, Wolfgang, 2010. "Conducting Meta-Analyses in R with the metafor Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 36(i03).
    2. Elizabeth Tipton & James E. Pustejovsky, 2015. "Small-Sample Adjustments for Tests of Moderators and Model Fit Using Robust Variance Estimation in Meta-Regression," Journal of Educational and Behavioral Statistics, , vol. 40(6), pages 604-634, December.
    3. James E. Pustejovsky & Elizabeth Tipton, 2018. "Small-Sample Methods for Cluster-Robust Variance Estimation and Hypothesis Testing in Fixed Effects Models," Journal of Business & Economic Statistics, Taylor & Francis Journals, vol. 36(4), pages 672-683, October.
    4. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mathilda Skeie-Larsen & Rebekka Stave & Janne Grønli & Bjørn Bjorvatn & Ane Wilhelmsen-Langeland & Amin Zandi & Ståle Pallesen, 2022. "The Effects of Pharmacological Treatment of Nightmares: A Systematic Literature Review and Meta-Analysis of Placebo-Controlled, Randomized Clinical Trials," IJERPH, MDPI, vol. 20(1), pages 1-16, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Welz, Thilo & Viechtbauer, Wolfgang & Pauly, Markus, 2023. "Cluster-robust estimators for multivariate mixed-effects meta-regression," Computational Statistics & Data Analysis, Elsevier, vol. 179(C).
    2. Piers Steel & Sjoerd Beugelsdijk & Herman Aguinis, 2021. "The anatomy of an award-winning meta-analysis: Recommendations for authors, reviewers, and readers of meta-analytic reviews," Journal of International Business Studies, Palgrave Macmillan;Academy of International Business, vol. 52(1), pages 23-44, February.
    3. Mahesh Shumsher Rughooputh & Rui Zeng & Ying Yao, 2015. "Protein Diet Restriction Slows Chronic Kidney Disease Progression in Non-Diabetic and in Type 1 Diabetic Patients, but Not in Type 2 Diabetic Patients: A Meta-Analysis of Randomized Controlled Trials ," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-17, December.
    4. Christopher Winchester & Kelsey E. Medeiros, 2023. "In Bounds but Out of the Box: A Meta-Analysis Clarifying the Effect of Ethicality on Creativity," Journal of Business Ethics, Springer, vol. 183(3), pages 713-743, March.
    5. Kelly R Moran & Sara Y Del Valle, 2016. "A Meta-Analysis of the Association between Gender and Protective Behaviors in Response to Respiratory Epidemics and Pandemics," PLOS ONE, Public Library of Science, vol. 11(10), pages 1-25, October.
    6. Sandra Feijóo & Raquel Rodríguez-Fernández, 2021. "A Meta-Analytical Review of Gender-Based School Bullying in Spain," IJERPH, MDPI, vol. 18(23), pages 1-13, December.
    7. Xizheng Xu & Zhiqiang Liu & Shaoying Gong & Yunpeng Wu, 2022. "The Relationship between Empathy and Attachment in Children and Adolescents: Three-Level Meta-Analyses," IJERPH, MDPI, vol. 19(3), pages 1-18, January.
    8. Kathrin Wunsch & Janis Fiedler & Philip Bachert & Alexander Woll, 2021. "The Tridirectional Relationship among Physical Activity, Stress, and Academic Performance in University Students: A Systematic Review and Meta-Analysis," IJERPH, MDPI, vol. 18(2), pages 1-18, January.
    9. Alan da Silveira Fleck & Margaux L. Sadoine & Stéphane Buteau & Eva Suarthana & Maximilien Debia & Audrey Smargiassi, 2021. "Environmental and Occupational Short-Term Exposure to Airborne Particles and FEV 1 and FVC in Healthy Adults: A Systematic Review and Meta-Analysis," IJERPH, MDPI, vol. 18(20), pages 1-19, October.
    10. Evangelos Danopoulos & Maureen Twiddy & Jeanette M Rotchell, 2020. "Microplastic contamination of drinking water: A systematic review," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-23, July.
    11. Claudia Menne-Lothmann & Wolfgang Viechtbauer & Petra Höhn & Zuzana Kasanova & Simone P Haller & Marjan Drukker & Jim van Os & Marieke Wichers & Jennifer Y F Lau, 2014. "How to Boost Positive Interpretations? A Meta-Analysis of the Effectiveness of Cognitive Bias Modification for Interpretation," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-26, June.
    12. José Felipe Orzuna-Orzuna & Juan Eduardo Godina-Rodríguez & Jonathan Raúl Garay-Martínez & Guillermo Reséndiz-González & Santiago Joaquín-Cancino & Alejandro Lara-Bueno, 2024. "Milk Yield, Composition, and Fatty Acid Profile in Milk of Dairy Cows Supplemented with Microalgae Schizochytrium sp.: A Meta-Analysis," Agriculture, MDPI, vol. 14(7), pages 1-13, July.
    13. Mikkel Helding Vembye & James Eric Pustejovsky & Therese Deocampo Pigott, 2023. "Power Approximations for Overall Average Effects in Meta-Analysis With Dependent Effect Sizes," Journal of Educational and Behavioral Statistics, , vol. 48(1), pages 70-102, February.
    14. Wei-Cheng Chang & Chin Lin & Cho-Hao Lee & Tzu-Ling Sung & Tao-Hsin Tung & Jorn-Hon Liu, 2017. "Vitrectomy with or without internal limiting membrane peeling for idiopathic epiretinal membrane: A meta-analysis," PLOS ONE, Public Library of Science, vol. 12(6), pages 1-18, June.
    15. Christopher Hansen & Holger Steinmetz & Jörn Block, 2022. "How to conduct a meta-analysis in eight steps: a practical guide," Management Review Quarterly, Springer, vol. 72(1), pages 1-19, February.
    16. Shaylea Badovinac & Jodi Martin & Camille Guérin-Marion & Monica O’Neill & Rebecca Pillai Riddell & Jean-François Bureau & Rebecca Spiegel, 2018. "Associations between mother-preschooler attachment and maternal depression symptoms: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 13(10), pages 1-27, October.
    17. Fazel, Seena & Burghart, Matthias & Fanshawe, Thomas & Gil, Sharon Danielle & Monahan, John & Yu, Rongqin, 2022. "The predictive performance of criminal risk assessment tools used at sentencing: Systematic review of validation studies," Journal of Criminal Justice, Elsevier, vol. 81(C).
    18. Amro Qaddoura & Payam Yazdan-Ashoori & Conrad Kabali & Lehana Thabane & R Brian Haynes & Stuart J Connolly & Harriette Gillian Christine Van Spall, 2015. "Efficacy of Hospital at Home in Patients with Heart Failure: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-15, June.
    19. Boshra H. Namin & Torvald Øgaard & Jo Røislien, 2021. "Workplace Incivility and Turnover Intention in Organizations: A Meta-Analytic Review," IJERPH, MDPI, vol. 19(1), pages 1-19, December.
    20. Ruohuang Jiao & Wojtek Przepiorka & Vincent Buskens, 2022. "Moderators of reputation effects in peer-to-peer online markets: a meta-analytic model selection approach," Journal of Computational Social Science, Springer, vol. 5(1), pages 1041-1067, May.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pmed00:1003524. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosmedicine (email available below). General contact details of provider: https://journals.plos.org/plosmedicine/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.