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Review
. 2015 Nov 12;2015(11):CD009464.
doi: 10.1002/14651858.CD009464.pub2.

Cannabinoids for Nausea and Vomiting in Adults With Cancer Receiving Chemotherapy

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Free PMC article
Review

Cannabinoids for Nausea and Vomiting in Adults With Cancer Receiving Chemotherapy

Lesley A Smith et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use.

Objectives: To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer.

Search methods: We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication.

Selection criteria: We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy.

Data collection and analysis: At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI).

Main results: We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results.

Authors' conclusions: Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.

Conflict of interest statement

The authors have no conflicts of interest.

Figures

Figure 1
Figure 1
Identification and selection of randomised controlled trials for review inclusion.
Figure 2
Figure 2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included trials.
Figure 3
Figure 3
Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.
Analysis 1.1
Analysis 1.1
Comparison 1 Cannabinoid versus placebo, Outcome 1 Absence of nausea.
Analysis 1.2
Analysis 1.2
Comparison 1 Cannabinoid versus placebo, Outcome 2 Absence of vomiting.
Analysis 1.3
Analysis 1.3
Comparison 1 Cannabinoid versus placebo, Outcome 3 Absence of nausea and vomiting.
Analysis 1.4
Analysis 1.4
Comparison 1 Cannabinoid versus placebo, Outcome 4 Depression.
Analysis 1.5
Analysis 1.5
Comparison 1 Cannabinoid versus placebo, Outcome 5 Dysphoria.
Analysis 1.6
Analysis 1.6
Comparison 1 Cannabinoid versus placebo, Outcome 6 'Feeling high'.
Analysis 1.7
Analysis 1.7
Comparison 1 Cannabinoid versus placebo, Outcome 7 Paranoia.
Analysis 1.8
Analysis 1.8
Comparison 1 Cannabinoid versus placebo, Outcome 8 Sedation.
Analysis 1.9
Analysis 1.9
Comparison 1 Cannabinoid versus placebo, Outcome 9 Participant preference.
Analysis 1.10
Analysis 1.10
Comparison 1 Cannabinoid versus placebo, Outcome 10 Withdrawal for any reason.
Analysis 1.11
Analysis 1.11
Comparison 1 Cannabinoid versus placebo, Outcome 11 Withdrawal due to adverse event.
Analysis 1.12
Analysis 1.12
Comparison 1 Cannabinoid versus placebo, Outcome 12 Withdrawal due to lack of efficacy.
Analysis 2.1
Analysis 2.1
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 1 Absence of nausea.
Analysis 2.2
Analysis 2.2
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 2 Absence of nausea (subgroup analysis 2).
Analysis 2.3
Analysis 2.3
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 3 Absence of vomiting.
Analysis 2.4
Analysis 2.4
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 4 Absence of vomiting (subgroup analysis 2).
Analysis 2.5
Analysis 2.5
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 5 Absence of nausea and vomiting.
Analysis 2.6
Analysis 2.6
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 6 Absence of nausea and vomiting (subgroup analysis 1).
Analysis 2.7
Analysis 2.7
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 7 Absence of nausea and vomiting (subgroup analysis 2).
Analysis 2.8
Analysis 2.8
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 8 Dizziness.
Analysis 2.9
Analysis 2.9
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 9 Dysphoria.
Analysis 2.10
Analysis 2.10
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 10 Euphoria.
Analysis 2.11
Analysis 2.11
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 11 'Feeling high'.
Analysis 2.12
Analysis 2.12
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 12 Hallucinations.
Analysis 2.13
Analysis 2.13
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 13 Postural hypotension.
Analysis 2.14
Analysis 2.14
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 14 Paranoia.
Analysis 2.15
Analysis 2.15
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 15 Sedation.
Analysis 2.16
Analysis 2.16
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 16 Depression.
Analysis 2.17
Analysis 2.17
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 17 Participant preference.
Analysis 2.18
Analysis 2.18
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 18 Withdrawal for any reason.
Analysis 2.19
Analysis 2.19
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 19 Withdrawal due to adverse event.
Analysis 2.20
Analysis 2.20
Comparison 2 Cannabinoid versus other anti‐emetic agent, Outcome 20 Withdrawal due to lack of efficacy.
Analysis 3.1
Analysis 3.1
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 1 Absence of nausea.
Analysis 3.2
Analysis 3.2
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 2 Absence of vomiting.
Analysis 3.3
Analysis 3.3
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 3 Absence of nausea and vomiting.
Analysis 3.4
Analysis 3.4
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 4 Depression.
Analysis 3.5
Analysis 3.5
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 5 Dizziness.
Analysis 3.6
Analysis 3.6
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 6 Dysphoria.
Analysis 3.7
Analysis 3.7
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 7 Paranoia.
Analysis 3.8
Analysis 3.8
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 8 Sedation.
Analysis 3.9
Analysis 3.9
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 9 Withdrawal for any reason.
Analysis 3.10
Analysis 3.10
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 10 Withdrawal due to adverse event.
Analysis 3.11
Analysis 3.11
Comparison 3 Cannabinoid plus other antiemetic agent versus other antiemetic monotherapy, Outcome 11 Withdrawal due to lack of efficacy.

Update of

  • Cochrane Database Syst Rev. doi: 10.1002/14651858.CD009464

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