Cannabinoids are compounds present in the Cannabis plant that bind to cannabinoid receptors and exert pharmacologic effects that stimulate appetite, act as antiemetics, and have analgesic effects. Cannabinoids approved for use in the United States include dronabinol and nabilone. Cannabis compounds studied for symptom management in patients with cancer have been in oral forms, oral spray, or ingested through smoking. It should be noted that not all Cannabis formulations or methods of ingestion necessarily provide the same effects and results.
Cotter, J. (2009). Efficacy of crude marijuana and synthetic delta-9-tetrahydrocannabinol as treatment for chemotherapy-induced nausea and vomiting: A systematic literature review. Oncology Nursing Forum, 36, 345–352.
To determine if oral synthetic tetrahydrocannabinol (THC) and smoked marijuana are effective in the treatment of chemotherapy-induced nausea and vomiting (CINV), and to evaluate the side effects and patient preferences for treatment
Databases searched were MEDLINE (1966–present), CINAHL (1982–present), and the Cochrane Library. A search of article reference lists also was performed.
Search keywords were nausea, vomiting, cancer, chemotherapy, cannabis, marijuana, and dronabinol.
Studies were included in the review if they
The author retrieved 18 relevant citations, 10 of which were clinical trials and included in the review. The author evaluated the quality of the reference based on strength of evidence, study design, sample size, and purpose. Specific criteria were not described.
Nurses need to review potential sides effects. Individual patients can have differing concerns as a result of other problems or preferences. Oral THC may be the best option for use among patients with cancer.
Davis, M.P. (2008). Oral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain. Expert Opinion on Investigational Drugs, 17(1), 85-95.
Keywords searched were cannabinoids, nabilone, nausea, pain, tetrahydrocannabinol, and vomiting.
This was a review of published English literature, including reviews, meta-analysis, and treatment trials from 1975–1997 on using cannabinoids to control or prevent chemotherapy-induced nausea and vomiting (CINV), with very few trials found after 1997. From this review, 30 randomized control trials were found that looked at cannabinoids to control or prevent CINV. Overall, the trials received low scores for adequacy of randomization, blinding design, and description of withdrawal. Three cannabinoids were studied: nabilone (16), dronabinol (13), and levonantradol (1). The medications were compared to prochloperazine (12), placebo (10), metochlorpramide (4), chlorpromazine (2), domperidone (2), alizapride (1), thiethylperazine (1), and haloperidol (1). Twelve studies involved various scoring systems. No clear separation existed between acute and delayed CINV.
The trials included 1,760 patients, with 394 excluded.
Cannabinoids, like nabilone, may have a role in reducing delayed or refractory CINV, but more evidence is needed.
Keeley, P.W. (2009). Nausea and vomiting in people with cancer and other chronic diseases. BMJ Clinical Evidence, 2406.
To determine the effects of treatments for nausea and vomiting either as a result of the disease or its treatment in adults with cancer and other chronic diseases
Databases reviewed searched were MEDLINE, Embase, and the Cochrane database. Harm alerts from the Food and Drug Administration (FDA) and the United Kingdom regulatory agency also were reviewed.
No separate description of the volume of literature evaluated or the specific evaluation process was provided. The Grading of Recommendations Assessment, Development and Evaluation (GRADES) system was used for rating the evidence, and these results were provided. The literature review was completed as of April 2008.
The study reported on 13 randomized, controlled trials (RCTs), representing more than 14,000 patients with cancer. These included studies of nausea and vomiting as a result of disease or treatment.
Results indicated that 5-HT3 RAs + dexamethasone was beneficial.
The following were identified as likely to be beneficial.
Cannabinoids were identified as being a tradeoff between benefit and harm.
The following were determined to have unknown effectiveness.
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
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.
Schussel, V., Kenzo, L., Santos, A., Bueno, J., Yoshimura, E., de Oliveira Cruz Latorraca, C., . . . Riera, R. (2017). Cannabinoids for nausea and vomiting related to chemotherapy: Overview of systematic reviews. Phytotherapy Research, 32, 567–576.
STUDY PURPOSE: To present the findings and conduct a critical appraisal of systematic reviews focusing on the effects of cannabinoids as a treatment for nausea and vomiting in patients with cancer during chemotherapy.
TYPE OF STUDY: Meta analysis and systematic review
DATABASES USED: EMBASE, PEDro, CINAHL, Cochrane Database of Systematic Reviews, LILACS, Medline, PsycINFO
YEARS INCLUDED: 2001 to 2015
INCLUSION CRITERIA: RCTs only, SRs focusing exclusively on cannabinoids for the treatment of CINV
EXCLUSION CRITERIA: Studies registered in PROSPERO and not completed or published by the date of search
TOTAL REFERENCES RETRIEVED: 2,206
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: AMSTAR and PRISMA. Average AMSTAR score was 5, with low of 1 and high of 11. Max score of 11. Average PRISMA score was 13.2, ranging from 1 to 25. Max score of 27.
FINAL NUMBER STUDIES INCLUDED: 5
TOTAL PATIENTS INCLUDED IN REVIEW: Not included
KEY SAMPLE CHARACTERISTICS: Participants presenting nausea and/or vomiting attributed to any type of chemotherapy for cancer. Treatment included: THC, nabilone, dronabinol, and levonantradol compared to any pharmacologic or nonpharmacologic intervention.
PHASE OF CARE: Not specified or not applicable
Cannabinoids seem to be superior to placebo and equal to prochlorperazine in reducing nausea and vomiting, and, in general, are similar to standard antiemetics alone or in combination. Patient-reported outcomes indicated that patients tend to prefer cannabinoids over placebo and other antiemetics, but cannabinoids have a higher rate of adverse events when compared to traditional antiemetics.
Cannabinoids may be considered a therapeutic option for treating CINV. However, it is unclear from this analysis where cannabinoids are superior to traditional antiemetics in effectiveness or safety. There is a shortage of high-quality evidence to clarify these questions.
Cannabinoids may be effective and superior to placebo to treat CINV. Although adverse events were more frequent in patients treated with cannibinoids, patients preferred cannibinoids over other antiemetics. More studies are needed to evaluate the effectiveness and safety of cannabinoids in CINV.
Smith, L.A., Azariah, F., Lavender, V.T., Stoner, N.S., & Bettiol, S. (2015). Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database of Systematic Reviews, 11, CD009464.
STUDY PURPOSE: To evaluate the effectiveness and side effects of cannabinoids for chemotherapy-induced nausea and vomiting (CINV) in adults with cancer
Nine trials compared cannabis with placebo. Two trials showed no difference between groups in complete absence of nausea, three trials showed likelihood of absence of vomiting with cannabinoids compared to placebo (RR = 5.7, 95% CI [2.6, 13]), and three trials showed more chance of complete absence of nausea and vomiting with cannabinoids (RR = 2.9, 95% CI [1.8, 4.7]). Patients tended prefer cannabis to placebo. Cannabinoids versus prochlorperazine: nine trials with 1,221 patients compared these two. No significant differences in risk of CINV were found. Patients preferred cannabis in seven trials. Few very small trials of other drug comparisons were reviewed. Overall analysis of comparison with other antiemetic drugs showed the effectiveness of cannabis; however, the quality of the evidence was low to moderate level.
Analysis showed that cannabinoids were more effective than placebo and were similar to a few antiemetics for the management of CINV.
The study quality was low overall. Comparison antiemetics in included trials were not the most current and highly effective medications.
Cannabis-based medicines may be useful adjuncts for the management of CINV. More current research comparing cannabinoid efficacy alone or as adjunctive treatment with agents such as NK1 and 5HT3 would be useful. Some of the cannabis-related research has suggested effectiveness with nausea, which has not been managed as well as vomiting with current regimens.
Tafelski, S., Häuser, W., & Schäfer, M. (2016). Efficacy, tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting—A systematic review of systematic reviews. Der Schmerz, 30, 14–24.
STUDY PURPOSE: To summarize systematic reviews that compared the efficacy, tolerability, and safety of cannabinoids with placebo or other antiemetics among patients of any age with any type of cancer
TYPE OF STUDY: Systematic review
PHASE OF CARE: Active antitumor treatment
APPLICATIONS: Pediatrics, elder care, palliative care
Moderate quality evidence exists that pharmaceutical cannabinoids are less tolerated and less safe than placebo or conventional antiemetics. Insufficient evidence exists to determine if cannabinoids are more efficient than newer antiemetics. The number needed to treat with cannabinoid compared to placebo or conventional antiemetics to achieve complete control of CINV is four patients. The number needed to harm with cannabinoid compared to placebo or conventional antiemetics is six patients.
A narrow range of patients achieve complete control of CINV with cannabinoid versus patients who experience harm with cannabinoids. Insufficient evidence exists regarding the efficiency of cannabinoids versus newer antiemetics.
Cannabinoids should be considered for the treatment of uncontrolled or breakthough CINV but not as a first-line antiemetic for CINV.
Duran, M., Perez, E., Abanades, S., Vidal, X., Saura, C., Majem, M., … Capella, D. (2010). Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. British Journal of Clinical Pharmacology, 70, 656–663.
To evaluate the effect, toleration, and pharmacokinetics of dose titration of cannabis oral spray added to standard therapy to control chemotherapy-induced nausea and vomiting (CINV) in patients receiving a moderately emetogenic regimen
They study was conducted at multiple outpatient settings in Barcelona, Spain.
All patients were in active treatment.
This was a randomized, double-blind, placebo-controlled, parallel, phase-II trial.
Complete response was defined as no vomiting and a mean nausea score of ≤ 10 mm.
Partial response was defined as vomiting 1-4 times daily and a mean nausea score of ≤ 25 mm on a 100-mm visual analogue scale (VAS).
The following additional measurement instruments were used.
The addition of this formulation of Cannabis to standard antiemetic treatment appears to improve control of delayed nausea and vomiting with MEC.
Meiri, E., Jhangiani, H., Vredenburgh, J.J., Barbato, L.M., Carter, F.J., Yang, H.M., Baranowski, V. (2007). Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Current Medical Research and Opinion, 23(3), 533-543.
To compare the effectiveness of dronabinol alone or in combination with ondansetron versus ondansetron alone for delayed, chemotherapy-induced nausea and vomiting (CINV) among patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in multiple cancer centers
The study was conducted at multiple cancer centers.
This was a randomized, double-blind, placebo-controlled, parallel-group study.
The following measurement instruments were used.
Difficulties in enrollment led to early termination of this study.
National Comprehensive Cancer Network. (2016). NCCN Clinical Practice Guidelines in Oncology: Antiemesis [v.2.2016]. Retrieved from http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf
RESOURCE TYPE: Evidence-based guideline
PHASE OF CARE: Multiple phases of care
One hundred seventy-one articles were retrieved via aPubMed search. No information was provided regarding which articles were selected as relevant to these guidelines, and no discussion of any method used for rating the quality of included evidence exists.
Limited database used. Recommendations are a combination of evidence- and consensus-based suggestions, and most nonpharmacologic interventions are by consensus.
Provides multiple evidence- and consensus-based recommendations for prophylaxis and the management of nausea and vomiting due to chemotherapy or radiation therapy. Recommendations provide a list of chemotherapy agents, including oral agents and categorization as to emetic potential.
National Comprehensive Cancer Network. (2012). NCCN Clinical Practice Guidelines in Oncology: Palliative Care [v.2.2012]. Retrieved from http://www.nccn.org/professionals/physician_gls/pdf/palliative.pdf
The objective of the guidelines is to provide palliative care practice guidelines for patients with cancer, facilitating the appropriate integration of palliative care into oncology practice.
These are consensus-based guidelines.
Included in the guidelines are multiple phases of care with palliative care applications.
The NCCN made recommendations on the following symptoms.
Anorexia
Nutritional support, including enteral and parenteral feeding, should be considered. Appetite stimulants such as megestrol acetate and corticosteroids can be used when appetite is an important aspect of quality of life.
Chemotherapy-Induced Nausea and Vomiting (CINV)
Recommendations include prochlorperazine, haloperidol, metoclopramide, or benzodiazepines. Adding 5-HT3 receptor agonists, anticholinergics, antihistamines, corticosteroids, antipsychotics, and cannabinoids also can be considered. Palliative sedation can be considered as a last resort.
Constipation
Increase fluid intake, dietary fiber, and physical activity. Opioid-induced constipation should be anticipated and treated prophylactically with laxatives.
Dyspnea
Pharmacologic interventions include opioids or benzodiazapines. Scopolamine, atropine hyoscyamine, and glycopyrrolate are options to reduce excessive secretions.
Pain
Do not reduce opioid dose for symptoms such as decreased blood pressure or respiratory rate. Palliative sedation can be considered for refractory pain.
Sleep/Wake Disturbances
For refractory insomnia with no underlying physiologic cause, pharmacologic management includes diazepam, zolpidem, and sedating antidepressants. Cognitive behavioral therapy may be effective. If present, restless leg syndrome can be treated with ropinirole.
Recommendations provide expert opinion/consensus-level suggestions for management of various symptoms. Many recommendations, such as those for CINV, do not agree with current evidence in these areas.
Roila, F., Herrstedt, J., Aapro, M., Gralla, R.J., Einhorn, L.H., Ballatori, E., … ESMO/MASCC Guidelines Working Group. (2010). Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: Results of the Perugia consensus conference. Annals of Oncology, 21(Suppl. 5), v232–v243.
This Perugia consensus panel was composed of 10 committees that reported findings to a 23-member expert panel from 10 different countries. The panel determined level of evidence and made changes in 2004 guidelines if evidence supported a greater than 10% increase in benefit. Updates were approved by the European Society of Medical Oncology (ESMO) Guidelines Working Group. All author relationships were reported. The panel used MEDLINE and other databases, which were not specified.
Emetogenicity of agents:
Prevention of acute CINV:
Prevention of delayed CINV:
Refractory CINV and rescue:
Prevention of anticipatory CINV:
Prevention of CINV with high-dose chemotherapy:
Radiation-induced nausea and vomiting:
Antiemetics in children:
The guidelines provide a clear set of recommendations and review of the relevant evidence strength assessed for various cancer treatment scenarios.
A complete listing of databases used for evidence retrieval was not provided.
Control of emesis has markedly improved in recent years; however, nausea remains a challenge and future research should shift attention to this aspect. Current trials generally define complete response end points that exclude consideration of the experience of nausea rather than vomiting. Trials suggest that some agents are more effective for acute vomiting, others are more effective for delayed vomiting, and some may be more effective for nausea. Identification of these differences and incorporation into the rationale for treatment needs to continue.
Further research is needed in the areas of prevention with high-dose chemotherapy and stem cell support, combined chemotherapy and radiation therapy, and anticipatory nausea and antiemetic use in children. Practitioners need to be aware of the impact of oral therapy and chronic oral chemotherapy treatment on current approaches to antiemetic treatment, timing, and definitions of acute and delayed CINV. Practitioners also need to be aware that current chemotherapy risk determination does not apply to combined radiotherapy and chemotherapy.