Cannabinoids for Chemotherapy-induced Nausea and Vomiting: Overview of Systematic Reviews
Chemotherapy-induced nausea and vomiting (CINV), one of the most distressing chemotherapy-related adverse events (AEs), affects about 75% of patients undergoing chemotherapy. Antiemetic drugs are considered first-line treatments, while cannabinoids are considered an option to be used if other antiemetics fail. The cannabinoids used for CINV include tetrahydrocannabinol (THC) and analogs of THC. The US Food and Drug Administration (FDA) approved the first synthetic cannabinoid as a prescription drug for the treatment of CINV in 1986. [Note: Dronabinol, synthetic THC (Marinol) was approved in 1986, not 1985 as the text states, as a schedule II drug. In 1999, the Drug Enforcement Administration (DEA) transferred it from schedule II to schedule III. Non-synthetic THC (i.e., the kind in the plant) remains a DEA schedule I drug (no medical use).] In this overview, the authors summarize evidence from and critique the quality of published systematic reviews (SRs) of cannabinoids in CINV.
CINAHL, Cochrane Database of Systematic Reviews, EMBASE, LILACS (Latino-American and Caribbean Literature in Health Science), MEDLINE, PEDro (Physiotherapy Evidence Database), and PsycINFO (American Psychological Association Database) were searched for SRs focusing exclusively on cannabinoids in CINV, published in any language. Study participants in qualifying SRs had to present with nausea and/or vomiting while undergoing any type of chemotherapy and be given THC, dronabinol (synthetic THC), levonantradol, or nabilone. Any pharmacological or non-pharmacological comparator, and any outcome related to efficacy and/or safety was considered.
Five SRs fulfilled the inclusion criteria. The qualifying SRs were published between 2001 and 2015. All five assessed only randomized controlled trials (RCTs) and three SRs included meta-analyses (MAs). The five SRs evaluated a total of 37 RCTs. Thirty RCTs were included in two or more SRs. One SR included only seven RCTs.
The 11-item Assessing the Methodological Quality of SRs (AMSTAR) and the 27-item Preferred Reporting Items for SRs and MAs (PRISMA) checklists were used to evaluate methodological and reporting quality. For the five SRs, the average AMSTAR score was 5; the lowest score was 1 and the highest score was 11. Average PRISMA score was 13.2; the lowest score was 1 and the highest score was 25. The same two SRs scored the lowest and highest in both assessments. Only one SR was of high quality while the remaining SRs were of low (n=2) to moderate quality (n=2).
In general, the SRs found cannabinoids superior to placebo and comparable to standard antiemetics used alone or in combination for CINV. Patients tended to prefer cannabinoids over other antiemetics despite a higher rate of AEs. The most common AEs reported were euphoria, drowsiness, dizziness, and postural hypotension. The chances that participants withdrew from RCTs due to AEs were generally the same among all therapies studied, with a slightly higher chance when cannabinoids were combined with prochlorperazine. The SR with the highest methodological quality concluded that cannabinoids were superior to placebo and equal to prochlorperazine for CINV; however, the patients preferred cannabinoids to prochlorperazine and had no preference between cannabinoids and metoclopramide. Combining cannabinoids with either antiemetic was not superior to monotherapy.
The authors of this overview conclude that cannabinoids “represent a valuable option for treating CINV, despite the adverse events related to treatment, such as drowsiness and cognitive impairment. However, it is not entirely clear whether cannabinoids are
superior to traditional antiemetics.” They recommend that in clinical practice, the choice of using cannabinoids should be tailored to each patient. The authors point out that the major limitation of this overview is the methodological quality of the included SRs. Considering the lack of high-quality evidence, better-designed RCTs with clinically relevant outcomes are needed to assess the efficacy and safety of cannabinoids for CINV.