Skip to main content
SpringerLink
Log in

Efficacy, tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting—a systematic review of systematic reviews

Wirksamkeit, Verträglichkeit und Sicherheit von Cannabinoiden für die Therapie von Chemotherapie-induzierter Übelkeit und Erbrechen: eine systematische Zusammenfassung systematischer Reviews

  • Schwerpunkt
  • Published:
Der Schmerz Aims and scope Submit manuscript

Abstract

Background

There is growing public and legislative body support for the medical use of cannabis products, for example, for chemotherapy-induced nausea and vomiting (CINV), in Germany.

Methods

A comprehensive literature search until November 2015 was conducted in MEDLINE, DARE and Cochrane libraries for systematic reviews of randomized controlled trials (RCTs) comparing herbal or pharmaceutical cannabinoids (CB) versus placebo or conventional antiemetics for CINV. Outcomes were reduction of CINV for efficacy, drop-out rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the systematic reviews was evaluated by the tool assessment of multiple systematic reviews (AMSTAR).

Results

Six systematic reviews of RCTs included the pharmaceutical CBs dronabinol, levonantradol, and nabilone or whole plant extract (e.g., nabiximol) compared with placebo or conventional antiemetics. There was moderate quality evidence on the efficacy of CBs compared to placebo and conventional antiemetics for CINV. There was moderate quality evidence that pharmaceutical CBs were less tolerated and less safe than placebo and conventional antiemetics in CINV. One RCT examining whole plant extract was included into the systematic reviews. No RCT was found comparing CBs with neurokinine−1 receptor antagonists.

Conclusions

With safe and effective antiemetics available, CBs cannot be recommended as first- or second-line therapy for CINV. Some guidelines recommend pharmaceutical CBs as third-line treatment in the management of breakthrough nausea and vomiting. Due to the lack of RCT data and safety concerns, herbal cannabis cannot be recommended for CINV.

Zusammenfassung

Hintergrund

Die medizinische Anwendung von Cannabispräparaten erfährt aktuell eine zunehmende Unterstützung in der Literatur und auch beim Gesetzgeber, z. B. für die Indikation Chemotherapie-induzierte Übelkeit und Erbrechen (CINV).

Methoden

Eine umfassende Literaturrecherche bis einschließlich November 2015 wurde in einschlägigen Datenbanken (MEDLINE, DARE und Cochrane Datenbanken) durchgeführt, um systematische Reviews von randomisierten kontrollierten Studien (RCTs) zu identifizieren, die pflanzliche oder pharmazeutische Cannabinoide hinsichtlich Wirksamkeit, Nebenwirkungen und Verträglichkeit sowie von schwerwiegenden unerwünschten Ereignissen mit Placebo oder herkömmlichen Antiemetika verglichen. Die methodische Qualität der systematischen Übersichtsarbeiten wurde durch ein validiertes Instrument bewertet (AMSTAR).

Ergebnisse

Sechs systematische Übersichtsarbeiten schlossen RCTs mit den Wirkstoffen Dronabinol, Levonantradol und Nabilon sowie ein Pflanzenextrakt (Nabiximol) im Vergleich zu Placebo oder herkömmlichen Antiemetika ein. Die Arbeiten ergaben eine moderate Qualität der Evidenz der Wirksamkeit von Cannabinoiden im Vergleich mit Placebo sowie herkömmliche Antiemetika für die Indikation CINV. Weiterhin besteht eine moderate Qualität der Evidenz, dass Cannabispräparate weniger verträglich und sicher sind als Placebo und herkömmlichen Antiemetika. Insgesamt schlossen die Übersichtsarbeiten eine RCT mit cannabishaltigem Pflanzenextrakt mit ein, dagegen wurde keine Studie identifiziert, die Neurokinin-1-Rezeptorantagonisten mit Cannabisprodukten verglich.

Schlussfolgerungen

Für die Indikation CINV sind sichere und wirksame Antiemetika verfügbar, so dass Cannabinoide nicht als Erstlinien- oder Zweitlinien- Therapeutika empfohlen werden können. Einige Leitlinien enthalten den Hinweis, dass pharmazeutische Cannabinoide in der Indikation Durchbruch –CINV als Drittlinientherapie berücksichtigt werden könnten. Aufgrund der eingeschränkten Datenlage und Sicherheitsbedenken kann pflanzlicher Cannabis nicht für die Therapie von CINV empfohlen werden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ablin JN, Buskila D (2010) Emerging therapies for fibromyalgia: an update. Expert Opin Emerg Drugs 15:521–533

    Article  CAS  PubMed  Google Scholar 

  2. Aromataris E (2014) Joanna Briggs Institute Reviewers’ Manual: 2014 edition/Supplement. In:Joanna Briggs Institute

  3. Basch E, Hesketh PJ, Kris MG et al (2011) Antiemetics: American society of clinical oncology clinical practice guideline update. J Oncol Pract 7:395–398

    Article  PubMed Central  PubMed  Google Scholar 

  4. Craver C, Gayle J, Balu S et al (2011) Clinical and economic burden of chemotherapy-induced nausea and vomiting among patients with cancer in a hospital outpatient setting in the United States. J Med Econ 14:87–98

    Article  PubMed  Google Scholar 

  5. Davis MP (2008) Oral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain. Expert Opin Investig Drugs 17:85–95

    Article  CAS  PubMed  Google Scholar 

  6. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066

    Article  CAS  PubMed  Google Scholar 

  7. Hesketh PJ (2004) Understanding the pathobiology of chemotherapy-induced nausea and vomiting. Providing a basis for therapeutic progress. Oncology (Williston Park). 18:9–14

    PubMed  Google Scholar 

  8. Higgins J, Green S (eds) (2011) Cochrane handbook for systematic reviews of interventions. The Cochrane Collaboration. Wiley-Blackwell, Hoboken

    Google Scholar 

  9. Hill KP (2015) Medical marijuana for treatment of chronic pain and other medical and psychiatric problems: a clinical review. JAMA 313:2474–2483

    Article  CAS  PubMed  Google Scholar 

  10. Hoch E, Bonnetn U, Thomasius R et al (2015) Risks associated with the non-medicinal use of cannabis. Dtsch Arztebl Int 112:271–278

    PubMed Central  PubMed  Google Scholar 

  11. Hocking CM, Kichenadasse G (2014) Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review. Support Care Cancer 22:1143–1151

    Article  PubMed  Google Scholar 

  12. Hutton B, Salanti G, Caldwell DM et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162:777–784

    Article  PubMed  Google Scholar 

  13. Jordan K, Jahn F, Aapro M (2015) Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review. Ann Oncol 26:1081–1090

    Article  CAS  PubMed  Google Scholar 

  14. Keeley PW (2009) Nausea and vomiting in people with cancer and other chronic diseases. BMJ Clin Evid 2009

  15. Kreienberg R, Albert US, Follmann M et al (2013) Interdisciplinary GoR level III Guidelines for the Diagnosis, Therapy and Follow-up Care of Breast Cancer: short version – AWMF Registry No.: 032-045OL AWMF-Register-Nummer: 032-045OL – Kurzversion 3.0, Juli 2012. Geburtshilfe Frauenheilkd 73:556–583

    Article  PubMed Central  PubMed  Google Scholar 

  16. Liu J, Tan L, Zhang H et al (2015) QoL evaluation of olanzapine for chemotherapy-induced nausea and vomiting comparing with 5-HT3 receptor antagonist. Eur J Cancer Care (Engl) 24:436–443

    Article  CAS  Google Scholar 

  17. Machado Rocha FC, Stefano SC, De Cassia Haiek R et al (2008) Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl) 17:431–443

    Article  CAS  Google Scholar 

  18. Palli SR, Grabner M, Quimbo RA et al (2015) The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting. Cancer Manag Res 7:175–188

    PubMed Central  PubMed  Google Scholar 

  19. Phillips RS, Gopaul S, Gibson F et al. (2010) Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database Syst Rev (9):CD007786

  20. Roila F, Herrstedt J, Aapro M et al (2010) Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 21(Suppl 5):v232–243

    Article  PubMed  Google Scholar 

  21. Santana TA, Trufelli DC, Matos LL et al (2015) Meta-analysis of adjunctive non-NK1 receptor antagonist medications for the control of acute and delayed chemotherapy-induced nausea and vomiting. Support Care Cancer 23:213–222

    Article  PubMed  Google Scholar 

  22. Seo HJ, Kim KU (2012) Quality assessment of systematic reviews or meta-analyses of nursing interventions conducted by Korean reviewers. BMC Med Res Methodol 12:129

    Article  PubMed Central  PubMed  Google Scholar 

  23. Shea BJ, Hamel C, Wells GA et al (2009) AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol 62:1013–1020

    Article  PubMed  Google Scholar 

  24. Smith LA, Azariah F, Lavender VT et al. (2015) Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database Syst Rev 11:CD009464

    PubMed  Google Scholar 

  25. Todaro B (2012) Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting. J Natl Compr Canc Netw 10:487–492

    CAS  PubMed  Google Scholar 

  26. Tramer MR, Carroll D, Campbell FA et al (2001) Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 323:16–21

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Van Den Elsen GA, Ahmed AI, Lammers M et al (2014) Efficacy and safety of medical cannabinoids in older subjects: a systematic review. Ageing Res Rev 14:56–64

    Article  PubMed  Google Scholar 

  28. Van Sickle MD, Duncan M, Kingsley PJ et al (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332

    Article  PubMed  Google Scholar 

  29. Wang XF, Feng Y, Chen Y et al (2014) A meta-analysis of olanzapine for the prevention of chemotherapy-induced nausea and vomiting. Scientific reports 4:4813

    PubMed  Google Scholar 

  30. Whiting PF, Wolff RF, Deshpande S et al (2015) Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 313:2456–2473

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Campus Virchow Klinikum und Campus Mitte, Berlin, Germany

    S. Tafelski & M. Schäfer

  2. Department Internal Medicine I, Klinikum Saarbrücken, Saarbrucken, Germany

    W. Häuser

  3. Department of Psychosomatic Medicine and Psychotherapy, Technische Universität München, Munich, Germany

    W. Häuser

Authors
  1. S. Tafelski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Häuser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Tafelski.

Ethics declarations

Conflict of interest

All authors declare that they have no conflicts of interest concerning the specific subject of this study. ST received lecture fees from Roche Deutschland GmbH and Pfizer Deutschland GmbH. MS received speaking fees from TEVA and Grünenthal and is a member of the committe of experts of the Federal Institut for Pharmaceuticals and Medical Products. Winfried Häuser has received speaking fees from Grünenthal, MSD Sharp & Dohme and Pfizer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tafelski, S., Häuser, W. & Schäfer, M. Efficacy, tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting—a systematic review of systematic reviews. Schmerz 30, 14–24 (2016). https://doi.org/10.1007/s00482-015-0092-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00482-015-0092-3

Keywords

Schlüsselwörter

Search

Navigation