Cannabinoids Show Modest Promise for Cancer-Related Appetite Loss in Older Adults, but Evidence Remains Thin

A 2024 systematic review examining cannabinoid interventions for cancer-related anorexia in adults aged 60 and over finds preliminary signals of benefit across six small studies, but the evidence base is too limited and heterogeneous to support clinical guidelines or pooled analysis.

Why This Matters

Anorexia of aging affects up to 63% of older adults and becomes significantly more dangerous in the context of active cancer, where malnutrition accelerates functional decline, treatment toxicity, and mortality. No pharmacological therapy is currently recommended for cancer-related appetite loss in this population, leaving clinicians without evidence-based tools for a pervasive and consequential problem. As interest in cannabinoid therapeutics grows among patients and providers alike, a rigorous accounting of what the existing research actually shows, and where it falls short, is clinically essential.

Clinical Summary

Cancer-related anorexia in older adults remains an undertreated condition with no approved pharmacological standard of care. Cannabinoids have attracted interest as potential appetite stimulants based on the known role of the endocannabinoid system in energy balance, food reward signaling, and gastrointestinal motility. A 2024 systematic review by Maia and colleagues, published in the Journal of Geriatric Oncology, searched five major databases through November 2023 and applied PRISMA and MOOSE guidelines to identify studies of cannabinoid use for anorexia specifically in adults aged 60 and over with cancer. From over 6,100 records, only six studies met inclusion criteria: five randomized controlled trials and one prospective observational study, involving a total of 869 participants across five countries.

Findings were heterogeneous and dose-dependent. Megestrol acetate at 800 mg per day outperformed dronabinol at 2.5 mg twice daily in a head-to-head trial. Low-dose nabilone (0.5 mg daily) failed to beat placebo, while escalating nabilone (up to 1.0 mg over six weeks) was associated with significantly increased caloric and carbohydrate intake versus placebo. THC at 5 to 10 mg per day produced at least 10% weight gain in 17.6% of patients, and THC at 2.5 mg improved chemosensory perception and pre-meal appetite compared to placebo. No significant adverse effects in older adults were reported across included studies, though the very small evidence base limits the strength of safety conclusions. The authors concluded that further research with larger sample sizes and standardized endpoints is essential before clinical guidelines can be developed.

Dr. Caplan’s Take

This review does what good systematic reviews are supposed to do: it reveals how little we actually know. The mechanistic case for cannabinoids in cancer-related anorexia is real, and the scattered positive signals here are not nothing. But when six small trials spanning nearly two decades, using different cannabinoids at different doses with different endpoints, are the best available evidence, we are still at the hypothesis stage. Patients ask me about this regularly, and an honest answer requires acknowledging both the biological plausibility and the reality that we cannot yet identify a preferred compound, dose, or patient profile.

In practice, I treat cancer-related anorexia in older adults with a multimodal approach that prioritizes nutritional counseling, exercise where feasible, and symptom management of contributing factors like nausea or depression. When patients express interest in cannabinoids, I discuss the limited evidence openly, consider individual risk profiles carefully, and if a trial is warranted, start at low doses with close monitoring. I do not treat cannabinoids as a first-line appetite strategy in this population based on current evidence.

Clinical Perspective

This systematic review sits very early in the research arc for cannabinoid use in geriatric oncology. It confirms that the endocannabinoid system is a plausible pharmacological target for cancer-related anorexia, but it does not confirm clinical efficacy for any specific cannabinoid formulation or dose. The finding that megestrol acetate outperformed dronabinol in direct comparison, and that low-dose nabilone failed to beat placebo, should temper enthusiasm. The dose-dependent signals with higher-dose nabilone and THC are worth pursuing in adequately powered trials, but they do not constitute evidence sufficient for patient-facing recommendations. Clinicians should not cite this review as support for prescribing cannabinoids for appetite stimulation in older cancer patients.

From a pharmacological and safety standpoint, cannabinoids carry particular risks in older adults, including cognitive effects, dizziness, fall risk, and potential drug interactions with common oncology and geriatric medications such as anticoagulants, benzodiazepines, and CYP3A4-metabolized agents. The absence of significant adverse events in these six studies is reassuring but not definitive given the small combined sample and limited follow-up durations. One actionable step clinicians can take now is to systematically screen older cancer patients for anorexia using validated tools and to document appetite and nutritional status longitudinally, ensuring that when stronger evidence does emerge, their patients are positioned to benefit from evidence-informed intervention.

Study at a Glance

Study Type

Systematic review (narrative synthesis; no meta-analysis)

Population

Adults aged 60 and over with cancer-related anorexia (869 total participants)

Intervention

Cannabinoids including dronabinol, nabilone, THC, and cannabis extract (THC plus CBD)

Comparator

Placebo, megestrol acetate, or no comparator (varied by included study)

Primary Outcomes

Appetite, caloric intake, weight change, chemosensory perception, adverse effects

Sample Size

6 studies included from 6,100 screened records

Journal

Journal of Geriatric Oncology

Year

2024

DOI or PMID

PMID: 38614864

Funding Source

Not reported in available data

What Kind of Evidence Is This

This is a narrative systematic review conducted according to PRISMA and MOOSE guidelines, with dual-reviewer screening and validated risk-of-bias assessment. It sits above individual trials in the evidence hierarchy but below meta-analyses and pooled analyses. The critical inference constraint is that no quantitative pooling was possible due to the heterogeneity of cannabinoid types, doses, and outcomes across the six included studies, meaning all synthesis is qualitative and cannot produce effect size estimates or confidence intervals.

How This Fits With the Broader Literature

The findings align with the broader cannabinoid literature in showing inconsistent and dose-dependent effects on appetite and weight. The Jatoi et al. (2002) head-to-head comparison of dronabinol versus megestrol acetate, included in this review, remains a frequently cited finding in oncology appetite research and has contributed to megestrol’s continued use despite its own safety concerns in older adults. The more recent nabilone and THC studies add nuance by suggesting that higher doses or specific formulations may cross a threshold of clinical relevance, consistent with preclinical endocannabinoid data. However, compared to systematic reviews of cannabinoids for other indications such as chronic pain or chemotherapy-induced nausea, the evidence base for geriatric cancer anorexia is notably smaller and less mature.

Common Misreadings

The most likely overinterpretation is treating this review as evidence that cannabinoids “work” for appetite loss in older cancer patients. The review’s own abstract uses the phrase “cannabinoids offer promise,” which, if extracted without context, could imply a level of demonstrated efficacy that the underlying data do not support. Each positive finding derives from a single small trial, and the negative findings (dronabinol inferior to megestrol, low-dose nabilone no better than placebo) are equally valid parts of the evidence picture. The absence of reported adverse events should also not be read as proof of safety in this vulnerable population, given the limited sample sizes and follow-up periods.

Bottom Line

This systematic review confirms that dedicated research on cannabinoids for cancer-related anorexia in older adults is strikingly sparse. The six included studies generate dose-dependent signals of potential benefit but do not identify a preferred cannabinoid, dose, or treatment duration. The evidence is hypothesis-generating, not practice-changing. Clinicians should continue to manage cancer-related anorexia with established multimodal approaches while awaiting adequately powered trials designed specifically for this population.

References

1. Maia JMCN, Sousa LGDP, Guimarães NS, et al. Cannabinoid use for anorexia among older adults with cancer: a systematic review. Journal of Geriatric Oncology. 2024. PMID: 38614864.
2. Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. Journal of Clinical Oncology. 2002;20(2):567-573.
3. Turcott JG, Núñez MO, Flores-Estrada D, et al. The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial. Supportive Care in Cancer. 2018;26(9):3029-3038.
4. Brisbois TD, de Kock IH, Watanabe SM, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Annals of Oncology. 2011;22(9):2086-2093.