Research

Interest high, evidence low for medicinal cannabis in cancer


Interest in using medicinal cannabis to treat cancer patients may be growing but most of the evidence demonstrates low efficacy or of low-quality, a symposium has been told.

The Victorian Comprehensive Cancer Centre staged its Medicinal Cannabis Symposium last month to inform clinicians about the emerging area of medicine that is attracting intense interest from consumers and policy makers.

The line-up included Professor Jennifer Philip, chair of palliative medicine at the University of Melbourne, who summarised the state of evidence for cannabinoids to treat a range of cancer-related symptoms including pain, chemotherapy-induced nausea and vomiting, anorexia and insomnia.

Professor Philip told the symposium at this stage the evidence arrived at by research is based on particular compounds: nabilone (a synthetic derivative of tetrahydrocannabinol (THC)) dronabinol (synthetic THC) and nabiximols (equal proportions of THC and cannabidiol (CBD) making up at least 90% of the compound), was very limited in all indications except chemotherapy induced nausea and vomiting, for which it was moderately strong.

Cancer pain

There are two large studies which look at the effects of cannabinoids on cancer pain, she said.

One is a two-week double-blind trial published in 2010 in which 177 patients with cancer pain who were not getting adequate relief from opioids were randomised to receive THC:CBD extract, THC only or placebo.

In this study, the THC:CBD group showed a statistically significant reduction in pain severity when compared with placebo, with a reduction in mean pain NRS scores from baseline of 1.37 points on a 10-point scale.

Twice as many patients in the THC:CBD group achieved a 30% or greater improvement in their pain score, however the number of times breakthrough medication was used (the other primary study outcome) was not different between groups.

The second five-week randomised double blind placebo controlled trial of 360 patients with cancer pain experiencing inadequate relief from opioids, randomised to four groups: low dose, medium dose and high dose nabiximol or placebo, published in 2012.

A total of 263 completed and there was no baseline differences between the groups. The 30% reduction of pain, the primary outcome, was not significantly different for nabiximols versus placebo.  Secondary analysis revealed, however the average daily pain scores were less in the nabiximol groups, especially in the low-dose and medium-dose groups.

Chemotherapy-induced nausea and vomiting

 A Cochrane review published in 2015 suggests cannabinoids are more effective than placebo to treat chemotherapy induced nausea and vomiting, but have similar efficacy to conventional antiemetics, such as prochlorperazine.

There is weak evidence to support patient preference for cannabinoids, despite the treatment causing an increase in dizziness, dysphoria, euphoria and sedation. Cannabinoids have not been evaluated against newer, highly effective antiemetics.

The authors of the review suggest cannabinoids should not be considered a first-line antiemetic treatment, but may be a useful adjunct in moderate to highly emetogenic chemotherapy when all other options have been tried.

Anorexia

There is currently no evidence to show medicinal cannabis is useful to treat anorexia.

In a 2006 RCT patients who were randomised to receive THC/CBD, THC and placebo all had similar rates of increased appetite with no difference between the groups. An earlier study in 2002 concluded there was insufficient evidence that cannabinoids are effective to treat anorexia.

Insomnia

The research into cannabinoids and relief of insomnia does not have a cancer focus, Professor Philip said. In one study, patients with fibromyalgia were given nabilone or amitriptyline. The nabilone group reported less insomnia and improved sleep restfulness compared to baseline.

In a systematic review of 19 studies where sleep was a secondary outcome, cannabinoids (mostly nabiximols) were associated with greater average improvement in sleep quality and reduced sleep disturbance.

“In summary, there is moderate quality evidence of effect for chemotherapy-induced nausea and vomiting. However they are seemingly not more effective than conventional antiemetics and there’s not been a comparison with newer agents,” Professor Philip said.

“There is low-quality or limited evidence for effect for cancer pain, anxiety and sleep. Cannabinoids are associated with increased risk of short term adverse effects and future RCTs will need to be large because thus far the effect sizes have been small.

“Finally, we also need to think about these data with respect to cannabis itself.

“What is tested in these studies, the purified compounds of predictable constituents are not the same as cannabis taken informally.  There are many anecdotes of people with particular symptoms who report benefit. The studies that I have detailed today have not tested the cannabis that is the basis of the anecdotes.

“I think there are gaps in the data, including between what we have tested formally and what is taken informally, and also around what ratios of the various constituent active compounds we should be using for different indications.”

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