What palliative care is
Palliative care is the medical speciality focused on improving quality of life for people with serious or life-limiting illness. It addresses pain, nausea, breathlessness, fatigue, appetite loss, anxiety, and other physical and psychological symptoms. Palliative care is not limited to end-of-life care; it can be provided alongside disease-directed treatment at any stage of a serious illness. The goal is symptom control and support for patients and their families. Multiple organ systems and symptom clusters are typically involved, which means treatment decisions must balance competing priorities. Cachexia — the wasting syndrome of advanced illness involving loss of muscle and fat — is a particular challenge because it responds poorly to most interventions.
Cannabis research on Palliative care
The research on cannabinoids in palliative care settings falls into several symptom-specific areas, with varying levels of evidence.
Chemotherapy-induced nausea and vomiting (CINV) is the most studied indication. A 2022 systematic review conducted for the Multinational Association of Supportive Care in Cancer, by Alderman and colleagues, identified 36 randomised controlled trials (RCTs) of cannabinoids for gastrointestinal symptoms in cancer patients, 31 of which addressed CINV. The review found that THC (dronabinol) and nabilone were more effective than placebo for preventing CINV, but were not more effective than other antiemetic medicines. Of 21 trials comparing cannabis-based treatments to standard antiemetics, only 11 favoured cannabis. A single study found that adding a THC:CBD combination to standard antiemetics reduced nausea in patients with refractory CINV. Overall, the guidance concluded that evidence was insufficient to recommend cannabinoids as first-line treatment for CINV, nausea, anorexia-cachexia, or taste disturbance.
For pain in palliative populations, the evidence is drawn mainly from broader chronic pain literature rather than palliative-care-specific RCTs. A 2015 systematic review and meta-analysis of 79 RCTs, published in JAMA by Whiting and colleagues, found moderate-quality evidence supporting cannabinoids for chronic pain: the odds ratio for a 30% or greater reduction in pain was 1.41 (95% CI 0.99-2.00) compared with placebo. A 2023 BMJ umbrella review of 101 meta-analyses confirmed this finding and graded the evidence as high quality: cannabis-based medicines or cannabinoids increased the likelihood of a 30% pain reduction, with an equivalent odds ratio of 0.59 favouring treatment. However, most included studies were not in palliative populations specifically, and the BMJ review also found high-grade evidence that cannabis-based medicines increase central nervous system adverse events (odds ratio 2.84).
For cancer-related anorexia and cachexia, the evidence is thinner. Dronabinol (synthetic THC) has been studied in several RCTs for weight gain in cancer and AIDS-related cachexia. Results have been mixed: some trials showed modest weight gain or appetite improvement, while others found no difference from placebo. A 2020 review on cannabis for symptom management in older adults, published by Levy and colleagues, found insufficient evidence to determine the effectiveness and safety of cannabinoids for most reviewed indications in palliative contexts, with the exception of chronic pain.
A 2002 comprehensive review by Bagshaw and Hagen examined the broader medical efficacy literature and noted that dronabinol and nabilone were licensed for CINV unresponsive to conventional antiemetics. This remains their primary evidence-supported use in palliative symptom management.
Compounds studied for Palliative care
THC is the component most studied in palliative symptom management. Dronabinol, a synthetic THC formulation, and nabilone, a synthetic THC analogue, have been tested in multiple RCTs for CINV and appear more effective than placebo. The evidence does not show superiority over modern antiemetics. THC has also been studied for pain, appetite stimulation, and, less conclusively, for cancer-related cachexia.
CBD has been studied in combination with THC for pain and for CINV in a small number of trials. Isolated CBD has not been tested in dedicated palliative care RCTs. Its non-intoxicating profile means it appears in some combination products used in observational studies, but the specific contribution of CBD in these mixtures has not been isolated in controlled trials.
CBN is a mildly psychoactive cannabinoid formed as THC degrades. It has been studied in preclinical models for its sedative properties. Interest in CBN for sleep disturbance in palliative populations is based on preclinical and anecdotal reports; no human RCT has tested CBN for this purpose.
Beta-caryophyllene is a CB2 receptor agonist. CB2 activation is associated with anti-inflammatory effects in preclinical models. Since inflammation contributes to cancer-related symptoms and pain, CB2 agonism is a biologically plausible pathway, but this remains at the laboratory stage.
Myrcene has been studied in animal models for analgesic and sedative effects. No human palliative care data exists.
Limonene has shown anxiolytic and mood-elevating effects in preclinical models. Anxiety is common in palliative populations, but limonene has not been tested in human trials for this indication.
Limits of the evidence for Palliative care
The evidence for cannabinoids in palliative care is fragmented across symptom-specific studies rather than holistic palliative care trials. The strongest controlled evidence exists for CINV, where THC and nabilone outperform placebo but do not outperform modern antiemetics. For pain, moderate- to high-quality evidence from broader chronic pain RCTs exists, but most participants in those trials did not have advanced illness — extrapolation to palliative populations should be explicit about this gap.
For anorexia-cachexia, the RCT evidence is inconsistent. Some trials show modest effects; others show none. No cannabinoid has been shown to reverse cachexia or improve survival in advanced cancer.
The central nervous system adverse event signal is well-established: cannabis-based medicines consistently increase rates of dizziness, somnolence, confusion, and cognitive effects. In palliative populations, where polypharmacy and organ impairment are common, these risks are material.
No large, multi-site RCT has tested a cannabis-based medicine against best supportive care for overall palliative symptom burden. The existing evidence addresses individual symptoms (pain, nausea, appetite) in isolation, and most trials excluded patients with advanced organ failure, cognitive impairment, or frailty — precisely the characteristics of many palliative care patients.
Sources
1. Alderman B, et al. Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer. Support Care Cancer. 2022;31(1):39. Study record 2. Whiting PF, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456-2473. Study record 3. Solmi M, et al. Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies. BMJ. 2023;382:e072348. Study record 4. Levy C, et al. Cannabis for symptom management in older adults. Med Clin North Am. 2020;104(3):471-489. Study record 5. Bagshaw SM, Hagen NA. Medical efficacy of cannabinoids and marijuana: a comprehensive review of the literature. J Palliat Care. 2002;18(2):111-122. Study record
