Machado Rocha, F.C., Stefano, S.C., De Cassia Haiek, R., Rosa Oliveira, L.M., & Da Silveira, D.X. (2008). Therapeutic use of cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: Systematic review and meta-analysis. European Journal of Cancer Care, 17, 431–443.

To use a systematic literature review and meta-analysis to evaluate interventions using Cannabis sativa in the treatment of chemotherapy-related nausea and vomiting

Databases searched were MEDLINE, Embase, PsycINFO, LILACS, and the Cochrane Collaboration Controlled Trials Register (12-2006).

Searched keywords were Medical Search Headings (MeSH) therapeutics, drug therapy, chemical and pharmacologic phenomena, neoplasms, antineoplastic and immunosuppressive therapy, marijuana abuse, cannabis, randomized controlled trials, and clinical trials.

Studies were included in the review if they

• Were randomized clinical trials (RCTs).
• Involved people with any type of cancer receiving chemotherapeutic treatment of low-, moderate-, or high-emetic potential.
• Were published in peer-reviewed journals.
• Evaluated pharmacologic interventions based on substances derived from Cannabis sativa or smoked Cannabis.

Studies were excluded from the review if they involved patients receiving radiotherapy.

The initial search yielded 12,749 papers. After scanning titles for inclusion, 735 abstracts were evaluated. Of these, 96 papers were reviewed and a final sample of 30 RCTs were included in the review.  RCTs that were appropriate for meta-analysis numbered 13. Studies were rated for quality using the Cochrane Manual for methodological quality evaluation in terms of bias risk.

• A final sample of 30 studies was included in the systematic review, and 13 studies were included in meta-analysis.
• Sample sizes varied among studies, with only six studies involving more than 100 patients.
• Across studies, the total sample size was 1,719.

• Two studies comparing dronabinol to placebo showed a trend favoring dronabinol, but it was not significant (p = 0.10).
• In five studies comparing dronabinol to neuroleptics, dronabinol was significantly better than the comparisons (relative response [RR] = 0.67, p = 0.03).
• In six studies comparing nabilone to neuroleptics, no significant differences were found.
• Four studies comparing levonantradol to neuroleptics showed no differences.
• In 18 studies composed of 1,138 patients, participants had a significant preference for cannabis (RR = 0.33, p < 0.00001).
• All of the studies had low or only moderate risk of bias.
• Patients taking cannabinols had a higher number of collateral effects and tended to have higher symptom intensity.

• Most patients preferred cannabis-based treatment when asked about their preferred drug.
• Different cannabis derivatives demonstrated different effectiveness when compared to standard treatment used at the time.
• Newer and more effective approaches for management of nausea and vomiting have emerged in practice since these studies were conducted.
• Comparative effectiveness of cannabis derivatives versus these approaches is unknown.

• If patients do not respond to antiemetics or they experience increased emesis after taking antiemetics, increased dosage or frequency of administration is not recommended.
• Because cannabinoids appear to act through different mechanisms than other drugs, they may be effective for people with nausea and vomiting that does not respond to other management approaches. 
• Clinical trials comparing cannabinoids to modern antiemetics are warranted.