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.
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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.
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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
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DOI: https://doi.org/10.1007/s00482-015-0092-3
Keywords
- Cannabinoids
- Systematic review of systematic reviews
- Randomized controlled trial
- Chemotherapy-induced nausea and vomiting
- Tolerability
- Safety