Related Pages Coping with Cancer Managing side effects and complications caused by cancer and its treatment. Supportive Care Trial Results Provides links to clinical trial results about supportive care (care given to improve a patient's quality of life).

Key Words

Palliative care, supportive care, cannabis, THC, nausea. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

A randomized trial in Europe of advanced cancer patients with reduced appetite found that delta-9-tetrahydrocannabinol (THC) alone, or combined with another marijuana compound that reduces THC’s psychoactive effects, did enhance patients’ appetite, but not more than a placebo.

Source

Journal of Clinical Oncology, July 20, 2006 (see the journal abstract)
(J Clin Oncol. 2006 Jul 20; 24(21): 3394-3400.)

Background

Cancer and its treatments often affect a patient’s appetite, causing nausea, vomiting, anorexia, and cachexia (a loss of muscle mass and bodyweight). These symptoms in turn can lead to fatigue, depression, loss of some normal functions, an intolerance to treatment, and ultimately to poorer survival.

For centuries, smoking marijuana has been anecdotally known to enhance appetite. The herb comes from Cannabis (sativa or indica), a natural plant family containing a number of compounds collectively known as cannabinoids. Research since the 1980s has identified a number of cannabinoid receptors in brain cells and other cells of the body that are involved in mood, appetite, and nausea. This discovery has prompted more scientific studies of the medical use of marijuana, which remains an illegal drug in the United States and most countries in the world.

In 1985, the U.S. Food and Drug Administration approved dronabinol (Marinol®) to treat nausea and vomiting (emesis) caused by chemotherapy in cancer patients who had not responded to other standard anti-emetic drugs. Dronabinol contains a synthetic form of delta-9-tetrahydrocannabinol (THC), an active cannabinoid in marijuana. Since that time, more effective drugs to counteract these cancer-related symptoms have been developed that do not contain any cannabinoids.

By the late 1990s, the National Academy of Sciences’ Institute of Medicine and the National Institutes of Health had developed reports on the medical use of marijuana. The drug’s benefit in some medical settings was confirmed, more studies were called for, and distinctions were made between smoked marijuana and chemically refined by-products that could be taken by mouth.

Researchers with the European trial described below conducted smaller studies in the late 1990s to try to determine the most effective cannabis ingredients and the proper dosages for treating loss of appetite in advanced stage patients with cancer-related anorexia-cachexia syndrome (CACS).

Based on those earlier studies, this trial tested two forms and dosages of cannabinoids: 5 milligrams (mg) of THC alone, and a combination of 5 mg of THC mixed with 2 mg of another cannabinoid called cannabidiol (CBD). CBD is believed to moderate some of the known effects of THC on patients’ minds. In this trial, the combination of THC and CBD is referred to as cannabis extract (CE).

The researchers wanted to see if the two cannabis groups developed better appetites, and experienced greater quality of life, than the placebo group.

The Study

Between October 1999 and September 2002, 243 adult patients with a variety of advanced incurable cancers and a life expectancy of three months participated in this randomized phase III trial taking place at 30 centers in Germany, Switzerland, and the Netherlands. All patients had involuntarily lost five percent or more of their bodyweight in the previous six months, and thus were candidates for appetite stimulation.

Patients were randomly assigned to receive two pills each day of either THC alone (100 patients), the CE combination (95 patients), or a placebo (48 patients) for a total of six weeks of treatment.

Patients were asked to keep a daily diary and to assess their appetite on a scale from worst (0) to best (100). Patients were also asked about their mood, any feelings of nausea, and their food intake during the previous 24 hours. During clinic visits every two weeks, patients filled out questionnaires and were assessed by researchers with regard to appetite and weight loss, toxic effects known to be associated with cannabinoids, and other quality-of-life issues. At each visit patients were given another two weeks’ supply of pills to take themselves.

The study’s senior author is Florian Strasser, M.D., from the Cantonal Hospital in St. Gallen, Switzerland. The study was sponsored by the Institute for Clinical Research in Berlin, and conducted by the Cannabis-In-Cachexia-Study-Group.

Results

A majority of patients complied by taking at least 90 percent of their study medication. Most patients completed the whole study: 69 percent of the placebo group, 69 percent of the CE group, and 65 percent of the THC-only group.

However, during a planned midstudy review, the independent board monitoring the trial determined that no meaningful differences were emerging from the three groups, and so researchers stopped the trial early.

Most patients in all three groups reported increased appetite: 73 percent in the CE group, 58 percent in the THC group, and 69 percent of those taking a placebo – differences that were not statistically significant. There were also no significant differences between the groups in terms of nausea and mood, though improvements were seen in about half of all patients. Quality of life that was related specifically to symptoms of anorexia and cachexia improved for all three groups, about 5 percent in the first two weeks, and another 5 percent over the next four.

Certain adverse events, however, were statistically higher in both cannabis groups, including diarrhea, severe constipation, pain, and fatigue. Overall, those taking CE were nearly twice as likely to have adverse events than those taking placebo.

Comments

The cannabis products tested in this trial proved no better than placebo, notes Edward Trimble, M.D., M.P.H., of the National Cancer Institute’s Cancer Therapy Evaluation Program. “These results highlight the need to pursue more treatment options for cancer-related cachexia, especially for patients for whom standard treatments are not working.”

Strasser and colleagues wrote, “our trial reflects the challenges of a symptom-control trial in patients with advanced cancer.” Among these challenges were an unusually high placebo effect; a high dropout rate due in part to the psychoactive effects of the THC; and “the clinical reality of interfering symptoms and complications, adverse effects, and interactions of other medications.”

The six weeks that patients were on the study was a shorter time than other similar studies with cannabinoids, they noted, some of which have shown THC to have more positive results on appetite.

“While these results may have been affected by the relatively small number of patients and the short duration of the trial,” said Trimble, “it is ethically necessary to stop any human study when a futility analysis shows you can’t prove the impact of what you are testing.” He added that the psychotropic effects of THC are well known to be troublesome in some patients, which remains a hurdle for researchers trying to demonstrate the value of specific medical uses of marijuana.

Back to Top