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

A systematic review of six studies finds some appetite and quality-of-life benefits from THC and nabilone in older cancer patients, but small samples, heterogeneous interventions, and mixed results preclude clinical recommendations and underscore the need for larger, more rigorous trials.

Why This Matters

Anorexia of aging affects up to 63% of older adults and is strongly associated with malnutrition, sarcopenia, and increased mortality, yet no pharmacological intervention has achieved guideline-level evidence for this population. Cancer-related anorexia-cachexia syndrome compounds these risks, accelerating functional decline and worsening treatment tolerance. Cannabinoids have long been discussed as potential appetite stimulants, but their evidence base in older adults specifically has never been systematically evaluated until now. This review arrives at a moment when clinician interest in cannabinoid therapeutics is outpacing the evidence available to guide prescribing decisions in geriatric oncology.

Clinical Summary

Cancer-related anorexia-cachexia syndrome remains a significant contributor to morbidity and mortality in older adults, yet pharmacological options are limited and poorly studied in geriatric populations. A 2024 systematic review by Papadopoulos and colleagues, published following PRISMA and MOOSE guidelines, synthesized evidence from six studies (five randomized controlled trials and one prospective observational study) involving 869 older cancer patients aged 60 and above. The review examined several cannabinoid formulations, including dronabinol (synthetic THC), nabilone, THC capsules, and cannabis extract containing both THC and CBD. The mechanistic rationale centers on cannabinoid receptor type 1 (CB1) activation in the hypothalamus and gastrointestinal tract, which modulates appetite signaling, energy balance, and hedonic aspects of eating, pathways that are dysregulated in cancer-related wasting.

Key findings were mixed and dose-dependent. Nabilone at escalating doses up to 1.0 mg over six weeks produced significant increases in caloric and carbohydrate intake compared to placebo, while a fixed low dose of 0.5 mg per day did not outperform placebo. THC at 2.5 mg improved chemosensory perception and pre-meal appetite, and THC at 5 to 10 mg daily yielded at least 10% weight gain in 17.6% of patients. However, megestrol acetate at 800 mg per day outperformed dronabinol at 2.5 mg twice daily for appetite stimulation in a direct comparison, suggesting cannabinoids are not clearly superior to existing agents. No significant adverse effects were reported across studies. The authors acknowledge that the small number of heterogeneous studies, absence of meta-analytic pooling, and wide date range of included studies (2002 to 2019) render these conclusions preliminary, and they call for larger, well-designed trials before clinical guidelines can be developed.

Dr. Caplan’s Take

This review honestly reflects where we are with cannabinoids for cancer-related appetite loss in older adults: there are plausible mechanisms, some encouraging signals, and not nearly enough evidence to act on confidently. Patients in my practice ask about cannabis for appetite frequently, especially when they are losing weight during cancer treatment and feel they have exhausted conventional options. The honest answer is that while cannabinoids appear reasonably tolerable at the doses studied, we do not yet have the data to tell them which formulation, dose, or duration is likely to help, and at least one trial showed a conventional agent working better.

In practice, I approach these conversations with transparency about the evidence gap. For patients who are already using cannabis or cannabinoid products, I focus on safety monitoring, potential drug interactions with their oncology regimen, and realistic expectations. I do not initiate cannabinoid therapy specifically for appetite stimulation as a first-line recommendation. Instead, I prioritize nutritional counseling, address reversible contributors to appetite loss, and coordinate closely with the oncology team. When patients want to try cannabinoids, I support informed shared decision-making at conservative doses with close follow-up.

Clinical Perspective

This systematic review represents the first attempt to consolidate cannabinoid evidence specifically for older cancer patients with anorexia, but it arrives at a point in the research arc that is still early and exploratory. The six included studies span nearly two decades, use different cannabinoid formulations and dosing strategies, and measure different outcomes, making it impossible to draw consistent conclusions about efficacy. The finding that megestrol acetate outperformed dronabinol in a direct comparison is important context: it suggests that cannabinoids have not yet demonstrated superiority or even clear equivalence to existing pharmacological options. At the same time, the absence of significant adverse events across studies is a genuinely useful data point for clinicians who worry about cannabinoid tolerability in frail older adults.

From a pharmacological standpoint, clinicians should remain attentive to cannabinoid interactions with CYP3A4 and CYP2C9 substrates, which are common in oncology regimens, and to the potential for central nervous system effects including sedation and dizziness in patients already at elevated fall risk. Nabilone and dronabinol are Schedule II and III substances respectively in the United States, carrying prescribing and monitoring requirements that differ from state-level medical cannabis programs. The single most actionable recommendation at present is to document any patient-initiated cannabinoid use, screen for drug interactions with active cancer treatments, and set explicit follow-up intervals to assess appetite, weight, and tolerability rather than assuming benefit or harm.

Study at a Glance

Study Type

Systematic review with narrative synthesis (no meta-analysis)

Population

Cancer patients aged 60 years and older with anorexia or anorexia-cachexia syndrome (869 total participants)

Intervention

THC, dronabinol, nabilone, and cannabis extract (THC plus CBD) at varying doses

Comparator

Placebo and megestrol acetate, depending on individual study

Primary Outcomes

Appetite stimulation, caloric intake, weight change, quality of life, adverse events

Sample Size

869 participants across 6 included studies

Included Study Designs

5 randomized controlled trials and 1 prospective observational study

Databases Searched

Embase Ovid, Scopus, PubMed, Cochrane Library, Web of Science

Quality Assessment

Modified Jadad Scale for RCTs (mean 5.8 of 7); Newcastle-Ottawa Scale for observational study (score 6)

Year

2024

Funding Source

Not reported in available text

What Kind of Evidence Is This

This is a systematic review conducting narrative synthesis of six heterogeneous studies. While systematic reviews generally occupy a high position in the evidence hierarchy, the absence of meta-analytic pooling, the small number of included studies with variable designs and interventions, and the wide date range of primary research substantially reduce the precision and strength of its conclusions. The single most important inference constraint is that without quantitative pooling, all conclusions rest on qualitative cross-study comparison, which cannot reliably estimate effect sizes or adjudicate conflicting findings.

How This Fits With the Broader Literature

This review is broadly consistent with prior evidence suggesting that cannabinoids have modest orexigenic properties but do not clearly outperform established agents. The finding that megestrol acetate outperformed dronabinol echoes the landmark Jatoi et al. (2002) trial, which remains one of the largest direct comparisons and found megestrol superior for appetite and weight gain. More recent Cochrane reviews of cannabinoids in palliative care have similarly concluded that evidence is insufficient to recommend routine use.

What this review adds is a specific geriatric lens, highlighting that older adults did not appear to experience disproportionate adverse effects at the doses studied. This is a meaningful, if preliminary, addition to a literature that often excludes or underrepresents patients over 60. It does not, however, challenge the overall conclusion that cannabinoids for cancer-related anorexia remain an area of active investigation rather than established practice.

Common Misreadings

The most likely overinterpretation is reading this review as evidence that cannabinoids are effective and safe enough to recommend for older cancer patients with appetite loss. The review itself does not support that conclusion. Six small studies with different cannabinoid formulations, different comparators, different outcome measures, and no pooled effect estimates cannot establish efficacy. Similarly, the absence of reported significant adverse events should not be conflated with a confirmed safety profile; the sample sizes and follow-up durations were insufficient to detect uncommon or delayed harms. It is also important to note that all included studies enrolled cancer patients specifically, so the findings should not be generalized to broader anorexia-of-aging populations without cancer, despite the review’s framing suggesting broader applicability.

Bottom Line

This systematic review confirms that cannabinoids remain a biologically plausible but clinically unproven intervention for cancer-related appetite loss in older adults. Some formulations at certain doses show modest appetite and intake improvements, and short-term tolerability appears acceptable. However, the evidence base is too small, too heterogeneous, and too inconsistent to support clinical recommendations. Larger, well-designed trials with standardized dosing and outcomes are needed before cannabinoids can be considered for guideline inclusion in geriatric oncology supportive care.

References

1. Papadopoulos D, et al. Cannabinoids as a potential therapy for anorexia of ageing in older adults with cancer: a systematic review. BMC Geriatrics. 2024. (Systematic review of 6 studies on cannabinoid appetite stimulation in older cancer patients.)
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. J Clin Oncol. 2002;20(2):567-573. PMID: 11786587.
3. 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. Ann Oncol. 2011;22(9):2086-2093. PMID: 21343383.
4. Turcott JG, Del Rocío Guillen Núñez M, 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. Support Care Cancer. 2018;26(9):3029-3038. PMID: 29564625.
5. Mucke M, Weier M, Carter C, et al. Systematic review and meta-analysis of cannabinoids in palliative medicine. J Cachexia Sarcopenia Muscle. 2018;9(2):220-234. PMID: 29400010.