Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis

Linda Rider
  • 1.

    Park, J. Y. & Wu, L. T. Prevalence, reasons, perceived effects, and correlates of medical marijuana use: A review. Drug. Alcohol. Depend. 177, 1–13. https://doi.org/10.1016/j.drugalcdep.2017.03.009 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 2.

    Epidyolex|European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/EPAR/epidyolex (2021).

  • 3.

    Anwar, A., Saleem, S., Patel, U. K., Arumaithurai, K. & Malik, P. Dravet syndrome: An overview. Cureus https://doi.org/10.7759/cureus.5006 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 4.

    Asadi-Pooya, A. A. Lennox-Gastaut syndrome: A comprehensive review. Neurol. Sci. 393(39), 403–414 (2017).


    Google Scholar
     

  • 5.

    Swaminath, A. et al. The role of cannabis in the management of inflammatory bowel disease: a review of clinical, scientific, and regulatory informationcommissioned by the crohn’s and colitis foundation. Inflamm. Bowel Dis. 25, 427–435. https://doi.org/10.1093/ibd/izy319 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • 6.

    Aran, A., Cassuto, H., Lubotzky, A., Wattad, N. & Hazan, E. Brief report: Cannabidiol-rich cannabis in children with autism spectrum disorder and severe behavioral problems-a retrospective feasibility study. J. Autism Dev. Disord. 49, 1284–1288. https://doi.org/10.1007/s10803-018-3808-2 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • 7.

    Ben-Zeev, B. Medical cannabis for intractable epilepsy in childhood: A review. Rambam Maimonides Med. J. 11, e0004. https://doi.org/10.5041/RMMJ.10387 (2020).

    Article 
    PubMed Central 

    Google Scholar
     

  • 8.

    Tramèr, M. R. et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: Quantitative systematic review. Br. Med. J. 323, 16–21. https://doi.org/10.1136/bmj.323.7303.16 (2001).

    Article 

    Google Scholar
     

  • 9.

    Pacher, P., Kogan, N. M. & Mechoulam, R. Beyond THC and endocannabinoids. Annu. Rev. Pharmacol. Toxicol. 60, 637–659. https://doi.org/10.1146/annurev-pharmtox-010818-021441 (2020).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 10.

    Skrypek, M. M., Bostrom, B. C. & Bendel, A. E. Medical cannabis certification in a large pediatric oncology center. Children 6, 79. https://doi.org/10.3390/children6060079 (2019).

    Article 
    PubMed Central 

    Google Scholar
     

  • 11.

    National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. 58,91,97,245 (Washington, DC: The National Academies Press. 2017), DOI: https://doi.org/10.17226/24625.

  • 12.

    Bourgeois, F. T. et al. Pediatric versus adult drug trials for conditions with high pediatric disease burden. Pediatrics 130, 285–292. https://doi.org/10.1542/peds.2012-0139 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 13.

    Mueller, B. U. et al. Principles of pediatric patient safety: Reducing harm due to medical care. Pediatrics 143, 2. https://doi.org/10.1542/peds.2012-0139 (2019).

    Article 

    Google Scholar
     

  • 14.

    Volkow, N. D., Baler, R. D., Compton, W. M. & Weiss, S. R. B. Adverse health effects of marijuana use. N. Engl. J. Med. 370, 2219–2227. https://doi.org/10.1056/NEJMra1402309 (2014).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 15.

    Kelly, B. F. & Nappe, T. M. Cannabinoid Toxicity. Treasure Island (FL): StatPearls (StatPearls Publishing, 2019). PMID: 29489164.

  • 16.

    Martín-Gómez, A., Palacios-Gómez, M. E. & García-Marcos, S. A. Severe intradialytic hypoglycemia associated with marijuana use. Nefrologia. 35, 328–329. https://doi.org/10.1016/j.nefroe.2015.02.001 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • 17.

    Naji, L. et al. The association between cannabis use and suicidal behavior in patients with psychiatric disorders: an analysis of sex differences. Biol. Sex Differ. 9, 22. https://doi.org/10.1186/s13293-018-0182-x (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 18.

    Ragazzi, T. C. C., Shuhama, R., Menezes, P. R. & Del-Ben, C. M. Cannabis use as a risk factor for psychotic-like experiences: A systematic review of non-clinical populations evaluated with the Community Assessment of Psychic Experiences. Early Interv. Psychiatry 12, 1013–1023. https://doi.org/10.1111/eip.12693 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • 19.

    Lev-Ran, S. et al. The association between cannabis use and depression: A systematic review and meta-analysis of longitudinal studies. Psychol. Med. 44, 797–810. https://doi.org/10.1017/S0033291713001438 (2014).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 20.

    van Gastel, W. A. et al. Change in cannabis use in the general population: A longitudinal study on the impact on psychotic experiences. Schizophr. Res. 157, 266–270. https://doi.org/10.1016/J.SCHRES.2014.04.023 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • 21.

    Appelboam, A. & Oades, P. J. Coma due to cannabis toxicity in an infant. Eur. J. Emerg. Med. 13, 177–179. https://doi.org/10.1097/01.mej.0000194405.38206.f2 (2006).

    Article 
    PubMed 

    Google Scholar
     

  • 22.

    Carstairs, S. D., Fujinaka, M. K., Keeney, G. E. & Ly, B. T. Prolonged coma in a child due to hashish ingestion with quantitation of THC metabolites in urine. J. Emerg. Med. 41, 3. https://doi.org/10.1016/j.jemermed.2010.05.032 (2011).

    Article 

    Google Scholar
     

  • 23.

    Bonkowsky, J. L., Sarco, D. & Pomeroy, S. L. Ataxia and shaking in a 2-year-old girl: Acute marijuana intoxication presenting as seizure. Pediatr. Emerg. Care. 21, 527–528. https://doi.org/10.1097/01.pec.0000173349.38024.33 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • 24.

    Richards, J. R., Smith, N. E. & Moulin, A. K. Unintentional cannabis ingestion in children: A systematic review. J. Pediatr. 190, 142–152. https://doi.org/10.1016/j.jpeds.2017.07.005 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • 25.

    Corsi, D. J. et al. Maternal cannabis use in pregnancy and child neurodevelopmental outcomes. Nat. Med. 26, 1536–1540. https://doi.org/10.1038/s41591-020-1002-5 (2020).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 26.

    Sadhana, D., Kathleen, M. & Jonathan, D. K. Marijuana and the pediatric population. Pediatrics https://doi.org/10.1542/peds.2019-2629 (2020).

    Article 

    Google Scholar
     

  • 27.

    Wong, S. S. & Wilens, T. E. Medical cannabinoids in children and adolescents: A systematic review. Pediatrics 140, 5. https://doi.org/10.1542/peds.2017-1818 (2017).

    Article 

    Google Scholar
     

  • 28.

    Devinsky, O. et al. Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. N. Engl. J. Med. 376, 2011–2020. https://doi.org/10.1056/NEJMoa1611618 (2017).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 29.

    Porcari, G. S., Fu, C., Doll, E. D., Carter, E. G. & Carson, R. P. Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center. Epilepsy Behav. 80, 240–246. https://doi.org/10.1016/j.yebeh.2018.01.026 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • 30.

    Devinsky, O. et al. Effect of cannabidiol on drop seizures in the lennox-gastaut syndrome. N. Engl. J. Med. 378, 1888–1897. https://doi.org/10.1056/NEJMoa1714631 (2018).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 31.

    Lattanzi, S. et al. Efficacy and safety of cannabidiol in epilepsy: A systematic review and meta-analysis. Drugs 78, 1791–1804. https://doi.org/10.1007/s40265-018-0992-5 (2018).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 32.

    de Carvalho, R. R., Almeida, K. J., da Silva, L. L., de Melo Mendes, C. M. & Bor-Seng-Shu, E. Efficacy and adverse event profile of cannabidiol and medicinal cannabis for treatment-resistant epilepsy: Systematic review and meta-analysis. Epilepsy Behav. 102, 106635. https://doi.org/10.1016/j.yebeh.2019.106635 (2020).

    Article 

    Google Scholar
     

  • 33.

    Liberati, A. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339, b2700. https://doi.org/10.1136/bmj.b2700 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 34.

    Ouzzani, M., Hammady, H., Fedorowicz, Z. & Elmagarmid, A. Rayyan-a web and mobile app for systematic reviews. Syst. Rev. 5(210), 1. https://doi.org/10.1186/s13643-016-0384-4 (2016).

    Article 

    Google Scholar
     

  • 35.

    Sterne, J. A. et al. ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355, i4919. https://doi.org/10.1136/bmj.i4919 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 36.

    Higgins, J. P. T. et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343, i7829. https://doi.org/10.1136/bmj.d5928 (2011).

    Article 

    Google Scholar
     

  • 37.

    Busner, J. & Targum, S. D. The clinical global impressions scale: Applying a research tool in clinical practice. Psychiat. Edgmont 4(7), 28–37 (2007).


    Google Scholar
     

  • 38.

    European Medicines Agency. Important medical event terms list (MedDRA version 23.0, updated). https://www.ema.europa.eu/en/documents/other/important-medical-event-terms-list-version-meddra-version-221_en.xls (2020).

  • 39.

    Viechtbauer, W. Conducting meta-analyses in R with the metafor. J. Stat. Softw. 36, 1–48. https://doi.org/10.18637/jss.v036.i03 (2010).

    Article 

    Google Scholar
     

  • 40.

    Balduzzi, S., Rücker, G. & Schwarzer, G. How to perform a meta-analysis with R: A practical tutorial. Evid. Based. Ment. Health 22, 153–160. https://doi.org/10.1136/ebmental-2019-300117 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • 41.

    Rücker, G., Krahn, U., König, J., Efthimiou, O. & Schwarzer, G. Package ‘netmeta’ title network meta-analysis using frequentist methods. Epidemiol. Health https://doi.org/10.1007/978-3-319-21416 (2020).

    Article 

    Google Scholar
     

  • 42.

    McGrath, S., Zhao, X., Steele, R. & Benedetti, A. Package ‘metamedian’ Title Meta-Analysis of Medians. (2020). https://doi.org/10.1002/sim.8013.

  • 43.

    Copenhagen Trial Unit. Trial Sequential Analysis Viewer. (2016).

  • 44.

    Wetterslev, J., Thorlund, K., Brok, J. & Gluud, C. Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Med. Res. Methodol. 91(9), 1–12. https://doi.org/10.1186/1471-2288-9-86 (2009).

    CAS 
    Article 

    Google Scholar
     

  • 45.

    Borenstein, M., Hedges, L., Higgins, J., Rothstein, H. & Biostat Englewood, N.J. Comprehensive Meta-Analysis 3. (2013).

  • 46.

    Dean, A.G., Sullivan, K.M., Soe, M.M. OpenEpi: Open source epidemiologic statistics for public health, Version. www.OpenEpi.com, updated 2013/04/06, accessed 2021/10/16.

  • 47.

    Page, M. J. et al. Epidemiology and reporting characteristics of systematic reviews of biomedical research: A cross-sectional study. PLOS Med. 13, e1002028. https://doi.org/10.1371/journal.pmed.1002028 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 48.

    Chan, S. G., Correia, A. J. & MecLeod, M. S. Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: A double-blind, crossover trial. Pediatrics 79(6), 946–952 (1987).

    CAS 
    PubMed 

    Google Scholar
     

  • 49.

    Dalzell, A. M., Bartlett, H. & Lilleyman, J. S. Nabilone: An alternative antiemetic for cancer chemotherapy. Arch. Dis. Child. 61, 502–505. https://doi.org/10.1136/adc.61.5.502 (1986).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 50.

    Miller, I. et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in dravet syndrome: A randomized clinical trial. JAMA Neurol. 77, 613–621. https://doi.org/10.1001/jamaneurol.2020.0073 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • 51.

    Fairhurst, C., Kumar, R., Checketts, D., Tayo, B. & Turner, S. Efficacy and safety of nabiximols cannabinoid medicine for paediatric spasticity in cerebral palsy or traumatic brain injury: a randomized controlled trial. Dev. Med. Child Neurol. 62, 1031–1039. https://doi.org/10.1111/dmcn.14548 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • 52.

    Efron, D. et al. A pilot randomised placebo-controlled trial of cannabidiol to reduce severe behavioural problems in children and adolescents with intellectual disability. Br. J. Clin. Pharmacol. 87, 436–446. https://doi.org/10.1111/bcp.14399 (2021).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 53.

    Aran, A. et al. Cannabinoid treatment for autism: A proof-of-concept randomized trial. Mol. Autism 12, 1–11. https://doi.org/10.1186/S13229-021-00420-2 (2021).

    Article 

    Google Scholar
     

  • 54.

    Devinsky, O. et al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology 90, e1204–e1211. https://doi.org/10.1212/WNL.0000000000005254 (2018).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 55.

    Chesney, E. et al. Adverse effects of cannabidiol: A systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology 45, 1799–1806. https://doi.org/10.1038/s41386-020-0667-2 (2020).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 56.

    Malyshevskaya, O. et al. Natural (∆ 9 -THC) and synthetic (JWH-018) cannabinoids induce seizures by acting through the cannabinoid CB 1 receptor. Sci. Rep. 2017(7), 1–8. https://doi.org/10.1038/s41598-017-10447-2 (2017).

    CAS 
    Article 

    Google Scholar
     

  • 57.

    FDA Approves First Drug Comprised of an Active Ingredient Derived from Marijuana to Treat Rare, Severe Forms of Epilepsy. FDA https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms (2018).

  • 58.

    Ruggiero, A. et al. Acute chemotherapy-induced nausea and vomiting in children with cancer: Still waiting for a common consensus on treatment. J. Int. Med. Res. 46, 2149–2156. https://doi.org/10.1177/0300060518765324 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 59.

    NICE. Cannabis-based medicinal products: [A] Evidence review for intractable nausea and vomiting NICE guideline NG144 Evidence review underpinning recommendations 1.1.1 and 1.1.2 in the NICE guideline. (2019).

  • 60.

    Huestis, M. A. et al. Cannabidiol adverse effects and toxicity. Curr. Neuropharmacol. 17, 974–989. https://doi.org/10.2174/1570159×17666190603171901 (2019).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 61.

    Stockings, E. et al. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J. Neurol. Neurosurg. Psychiat. 89, 741–753. https://doi.org/10.1136/JNNP-2017-317168 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • 62.

    Wiley, J. L. et al. CB1 cannabinoid receptor-mediated modulation of food intake in mice. Br. J. Pharmacol. 145, 293. https://doi.org/10.1038/SJ.BJP.0706157 (2005).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 63.

    Jankowska, B. I., Jankowski, M. M. & Swiergiel, A. H. Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors. Neurosci. Lett. 490, 82–84. https://doi.org/10.1016/J.NEULET.2010.12.031 (2011).

    Article 

    Google Scholar
     

  • 64.

    Skluzacek, J. V., Watts, K. P., Parsy, O., Wical, B. & Camfield, P. Dravet syndrome and parent associations: The IDEA League experience with comorbid conditions, mortality, management, adaptation, and grief. Epilepsia 52, 95–101. https://doi.org/10.1111/j.1528-1167.2011.03012.x (2011).

    Article 
    PubMed 

    Google Scholar
     

  • 65.

    Bandini, L. G. et al. Changes in food selectivity in children with autism spectrum disorder. J. Autism Dev. Disord. 47, 439–446. https://doi.org/10.1007/s10803-016-2963-6 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 66.

    Di Marzo, V. & Piscitelli, F. The endocannabinoid system and its modulation by phytocannabinoids. Neurotherapeutics 12, 692. https://doi.org/10.1007/s13311-015-0374-6 (2015).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 67.

    Zou, S. & Kumar, U. Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. Int. J. Mol. Sci. 1, 9. https://doi.org/10.3390/ijms19030833 (2018).

    CAS 
    Article 

    Google Scholar
     

  • 68.

    Netzahualcoyotzi, C., Rodríguez-Serrano, L. M., Chávez-Hernández, M. E. & Buenrostro-Jáuregui, M. H. Early consumption of cannabinoids: From adult neurogenesis to behavior. Int. J. Mol. Sci. 22, 7450. https://doi.org/10.3390/ijms22147450 (2021).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 69.

    Solowij, N. et al. Therapeutic effects of prolonged cannabidiol treatment on psychological symptoms and cognitive function in regular cannabis users: A pragmatic open-label clinical trial. Cannabis Cannabinoid. Res. 3, 21–34. https://doi.org/10.1089/can.2017.004 (2018).

    CAS 
    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 70.

    Osborne, A. L., Solowij, N. & Weston-Green, K. A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia. Neurosci. Biobehav. Rev. 72, 310–324. https://doi.org/10.1016/j.neubiorev.2016.11.012 (2017).

    CAS 
    Article 
    PubMed 

    Google Scholar
     

  • 71.

    Sidik, K. & Jonkman, J. N. A comparison of heterogeneity variance estimators in combining results of studies. Stat. Med. 26, 1964–1981 (2007).

    MathSciNet 
    Article 

    Google Scholar
     

  • Next Post

    There are no ‘bad’ foods, says a new guide to heart-healthy eating

    There are no “good” foodstuff and “bad” meals. Fairly, it is your in general nutritional sample that issues most when it comes to healthful taking in. That’s the principal concept from the American Coronary heart Association in its most current nutrition rules to boost the hearts and wellness of Individuals […]

    You May Like

    Subscribe US Now