For patients with an incurable life-threatening illness, palliative care can help manage distressing symptoms so that the patient can be more comfortable and benefit from an improved overall quality of life.
Some medical cannabis products have shown good promise in combating symptoms that are commonly addressed by palliative care, such as nausea in cancer patients and weight loss associated with HIV/AIDS. As a result, many studies have tried to investigate whether medical cannabis could be used in palliative care settings to ease the symptom burden of patients.
Now, a new review published in the Journal of Pain and Symptom Management has concluded that while positive treatment effects have been reported for some medical cannabis formulations, there are significant quality problems with current evidence. As a result, the reviewers say that more high quality and unbiased evidence is needed before medical cannabis can be supported for use in palliative care.
Cannabis may help with pain, nausea, and appetite
The review searched several databases looking for articles on cannabis in a palliative care setting published between 1960 and late-2021. After screening through additional refinement criteria – such as the need for a comparison to be made to a placebo, another treatment option, or the patient’s baseline status – the reviewers were left with a total of 52 studies.
Of these studies, 20 were randomized controlled trials (RCTs) with the remaining 32 studies made up of non-randomized trials, case reports, and case series. These studies included a total of 4,786 participants, nearly 4,500 of which having been diagnosed with cancer. The next most common diagnosis was AIDS, followed by dementia.
Statistically significant positive effects were seen in the treatment of pain, nausea and vomiting, appetite, sleep, fatigue, taste and smell perception, and night sweats in the cancer patients. Appetite, nausea, and vomiting were also improved in the patients with AIDS, with positive effects seen in appetite and agitation among dementia patients. Other symptoms either demonstrated inconsistent responses to medical cannabis treatment or no response.
Forty-four studies reported adverse events experienced by the participants. Generally, the most frequently reported side effects were tinnitus, blurred vision, nausea, dry mouth, and dizziness. Cannabis extract products tended to result in more cases of nausea and fatigue, and the synthetic cannabinoid nabilone elicited more dizziness than standard care interventions. However, a more detailed comparison of side effects was not possible due to significant differences in how these studies recorded adverse events.
Significant problems seen with evidence quality and bias
While these studies of medical cannabis for palliative care did reveal positive and statistically significant effects in multiple domains, the clinical significance of these findings is still uncertain.
Of the 20 RCTs identified in the review, only two were considered to have a low risk of bias as per the Cochrane Risk of Bias tool. A further six had some concerns, with the remaining 12 studies considered as being at a high risk of bias. Similar observations were seen with the non-randomized studies, which were measured using the Risk Of Bias In Non-Randomized Studies of Intervention (ROBINS-I) tool. Here, three were at moderate risk of bias, ten were at serious risk, seven were at critical risk.
“Consequently, any evidence for outcomes relating to MC [medical cannabis] use in the palliative care setting is at best limited, and results we have categorized as positive-, inconsistent- and no- treatment effect must be interpreted with extreme caution,” the reviewers wrote.
Based on the GRADE (grading of recommendations, assessment, development, and evaluations) scoring framework, the reviewers gave a low score to the quality of evidence for medical cannabis in managing quality of life in cancer patients, and nausea and appetite in AIDS patients. For managing pain, nausea, sleep, affective functioning, and appetite loss in cancer patients, the evidence quality was determined to be very low.
Only one RCT and one non-randomized trial used previously validated outcome measures to assess overall quality of life among palliative care patients.
Evidence quality not strong enough to support medicinal use, scientists say
The review notes some limitations. For example, the original literature search was limited to studies published in English and that specifically referred to their patient population as being terminal or in palliative care. As a result, non-English language studies and studies which featured only a smaller proportion of palliative care patients will have been excluded.
Still, based on the evidence collected, the reviewers believe that more high-quality research is still needed before medical cannabis is widely used in palliative care settings. Further research on medical cannabis as an adjunctive treatment could also be a valuable addition to the literature, they say.
“In conclusion, despite a range of positive treatment effects reported in the included studies, the quality of the evidence assessed does not support recommendations for the use of medicinal cannabis in the palliative care setting,” the review authors wrote.
“To inform evidence-based practices, researchers should carefully consider aspects of high-quality trial design, including participant, intervention and comparator selection and validated outcome reporting to improve the quality of the evidence and allow effective meta-analysis of their findings.”
This is not the first review to come to this conclusion. An earlier Rapid Response Report from the Canadian Agency for Drugs and Technologies in Health also concluded that the current evidence base is mostly of low quality. The report identified two evidence-based guidelines addressing the use of medical cannabis in a palliative care setting. The first explicitly recommended against the use of cannabis, whereas the second advocated for only using cannabis as a last resort after other treatment avenues have failed.