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.
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Research Evidence Summaries
Strasser, F., Luftner, D., Possinger, K., Ernst, G., Ruhstaller, T., Meissner, W., . . . Cerny, T. (2006). Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: A multi-center, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. Journal of Clinical Oncology, 24, 3394–3400.doi: 10.1200/JCO.2005.05.1847
Intervention Characteristics/Basic Study Process:
After 7–14 days of baseline assessment, patients were randomized to treatment with cannabis extract (CE) (standardized for 2.5 mg of delta-9-tetrahydrocannabinol [THC] and 1 mg of cannabinoid) or THC (2.5 mg), or placebo.
Assessments were performed every two weeks during clinic visits at screening, and patients maintained a diary at weeks two, four, and six.
- The study reported on 243 randomly assigned adult patients with advanced cancer.
- Patients had cancer-related anorexia-cachexia syndrome, weight loss of more than 5% over six months, and an Eastern Cooperative Oncology Group performance status of 2 or less.
- A total of 164 patients completed treatment.
The study was conducted in 30 centers in Germany, Switzerland, and the Netherlands.
A multicenter, phase III, randomized, double-blind, placebo-controlled, parallel study design was used.
- Appetite was measured using a visual analog scale (VAS), with 0 mm indicating the worst and 100 mm indicating the best; appetite values were calculated as the mean of daily appetite scores for the seven days of week two in each biweekly period.
- Patients’ estimation of food intake was measured daily using a VAS.
- Mood was assessed using a VAS monitored daily.
- Nausea was assessed using a VAS monitored daily.
- Quality of life (QOL) was assessed using questions on global health status and QOL on the European Organization for Research and Treatment Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) transformed into a single functional scale ranging from 0–100.
No differences between groups were noted at baseline in terms of age, sex, weight loss, performance status, antineoplastic treatment, appetite, or QOL. Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. An independent data review board recommended termination of recruitment because of insufficient differences between study arms.
Researchers concluded that there was no difference in either appetite or QOL outcomes between the CE, THC, or placebo groups.
- The study lacks a constitutive definition of anorexia.
- Adverse events included nausea, fatigue, pain, anemia, dizziness, dyspnea, diarrhea, and constipation.
- The multicenter design (n = 30) may have contributed to some of the variation in data, although statistical procedures were used to address this limitation, and investigators were trained in outcome measurement procedures.
Yavuzsen, T., Davis, M.P., Walsh, D., LeGrand, S., & Lagman, R. (2005). Systematic review of the treatment of cancer-associated anorexia and weight loss. Journal of Clinical Oncology, 23, 8500–8511.doi: 10.1200/JCO.2005.01.8010
Studies were included in the review if they reported on
- Adult patients older than 18 years of age
- Patients with nonhematologic malignancies
- Patients with anorexia or symptoms of anorexia, such as lack of appetite, weight loss, poor performance status, and decreased quality of life.
The review involved only prospective, randomized controlled trials (RCTs; double- and single-blind or unblended and phase III trials). The quality of studies was assessed using the validated scale published by Jadad et al. (1996).
There were 55 studies reviewed that met the eligibility criteria.
Multiple RCTs have been conducted to investigate the safety and efficacy of pharmacologic agents to stimulate appetite. Only two therapeutic interventions for cancer-related anorexia demonstrated enough evidence to support their use in patients with cancer: corticosteroids and progestins. Other studies had mixed outcomes, positive results in only a single randomized trial, or were not placebo-controlled.
There is strong evidence supporting the use of progestins in patients with cancer, of which the most commonly reported drugs were MA and MPA. There was increased weight with both progestins; there was also evidence of a dose-response, but higher doses did not confer any additional benefit with regard to appetite. Metaclopromide is effective for nausea and early satiety but has not been shown to directly stimulate appetite.
The RCTs did not show sufficient evidence to justify the use of dronabinol, EPA, EPO, ghrelin, interferon, melatonin, nandrolone, NSAIDs, or pentoxyfilline in cancer-related anorexia. Cyproheptadine is a weak appetite stimulant, but side effects are limiting.
The optimal dose, start time, and duration of treatment for many appetite stimulants are still unknown. A more systematic approach to research methodology is needed. In addition, uniform outcome measures to better assess the value of various appetite stimulants are needed. These should include subjective ratings of appetite and associated symptoms (e.g., early satiety) and objective measures (e.g., food consumed, weight gain, weight loss).