Appetite Stimulation

S3 guideline of the DGEM/DGHO/ASORS/AKE (Clinical Nutrition in Oncology). Recommendation 23 (grade C, strong consensus): Cannabis preparations can be considered for appetite improvement in tumour cachexia and taste disorders. The evidence is inconsistent: one RCT (n=164, advanced carcinoma) showed no effect on appetite in two dosage forms; another RCT found under 2×2,5 mg THC/day in anorexia and taste disorder an improvement in taste and appetite with good tolerability (no increased side effects compared to placebo, better sleep quality and relaxation). Compared to progestins, cannabis preparations had a weaker appetite-stimulating effect, but led less frequently to impotence; other side effects (vomiting, fluid retention, central nervous system symptoms) occurred at the same frequency. Possible adverse effects: central nervous system effects, changes in consciousness, anxiety, at high doses hallucinations; prescription only per BtMVV.

Moderate evidence for chronic pain and spasticity, low evidence for nausea/vomiting, weight gain and sleep disorders; increased risk of side effects.

Comprehensive SR across 79 RCTs (n=6.462) on medical cannabis; for appetite stimulation in HIV/AIDS, cannabinoids were explicitly named as one of the evaluated indications. Systematic assessment showed improvements in disease-specific symptoms, though statistical significance was not achieved in all trials. Common side effects: dizziness, dry mouth, nausea, fatigue, somnolence, euphoria.

Meta-analysis shows no significant benefits of cannabinoids for appetite, weight gain and quality of life in cancer-associated cachexia; moderate-quality evidence even suggests significantly worse quality of life.

SR + meta-analysis on cannabinoids in cancer cachexia; k=10 studies (4 RCTs + 6 NRSIs). Meta-analysis showed NO significant appetite benefit vs. control (SMD=-0.02; 95% CI: -0.51, 0.46; p=0.93, very low quality of evidence). Quality of life significantly worse under cannabinoids vs. control (SMD=-0.25, moderate evidence). Only patient-reported NRSIs reported subjective appetite improvement.

One high-quality RCT showed a weight gain of 1 kg over placebo in 4 weeks, another RCT with a higher THC dose showed no effect.

Systematic review (PRISMA, PROSPERO CRD42019141293) on cannabinoids in anorexia nervosa; k=2 original RCTs included (Δ9-THC or dronabinol). The only adequately powered, low-bias study showed an additional weight gain of +1 kg over 4 weeks vs. placebo under dronabinol; the second study (high-dose Δ9-THC) showed no effect. Level of evidence low (Level I, few studies).

Cannabinoids do not improve appetite, oral food intake, weight, taste function or appetite-related quality of life in cancer patients.

Systematic review on cannabinoids in cancer-associated anorexia; k=6 RCTs over 20 years. Cannabinoids showed NO improvement in appetite, oral food intake, weight, chemosensory function or appetite-related quality of life. Limitations: small sample sizes, lack of confounder adjustment.

Dronabinol was significantly inferior to megestrol acetate in the treatment of tumor-related anorexia; the combination provided no additional benefit.

n=469 patients with advanced cancer and anorexia, randomized to megestrol acetate 800 mg/d vs. dronabinol 2,5 mg 2×daily vs. combination. Megestrol acetate superior to dronabinol: appetite improvement 75% vs. 49% (p=0,0001), ≥10% weight gain 11% vs. 3% (p=0,02). Combination therapy without additional benefit over megestrol acetate monotherapy.

Dronabinol showed significant improvement in appetite (38% vs. 8%, p=0,015) and reduction in nausea (20% vs. 7%, p=0,05), but no statistically significant difference in body weight (stable vs. -0,4 kg, p=0,14).

RCT with n=88 AIDS patients (>2,3 kg weight loss), dronabinol 2×2,5 mg/day vs. placebo over 6 weeks. Dronabinol group: appetite increase 38% vs. 8% placebo (p=0,015), stable weight vs. -0,4 kg placebo (p=0,14), 22% weight gain ≥2 kg vs. 10,5% placebo (p=0,11). Side effects mild-moderate (euphoria, dizziness), discontinuation rate 8,3% vs. 4,5% placebo.

Dronabinol showed consistent improvement in appetite over 12 months, with appetite improvements of 48,6-76,1% in previously dronabinol-treated patients and 48,5-69,9% in previously placebo-treated patients, as well as stable body weight over at least 7 months.

Open-label long-term extension over 12 months with n=94 AIDS patients (mean CD4 count 45/mm³), dronabinol 2×2,5 mg/day (90%) or 1×2,5 mg/day (10%). Consistent appetite improvement: VASH increase of 48,6–76,1% (in patients with prior dronabinol therapy) and 48,5–69,9% (in patients with prior placebo, especially months 1–4). Weight stability for ≥7 months. Adverse effects primarily CNS-related.

After 8 weeks, nabilone led to significantly increased caloric intake (+342 kcal) and carbohydrate intake (+64 g) as well as improvements in several quality-of-life dimensions (role function, emotional function, social function, insomnia) compared to placebo.

n=47 patients with advanced NSCLC and anorexia, randomized to nabilone (0,5 mg/2 weeks, then 1,0 mg/6 weeks) vs. placebo over 8 weeks. Nabilone group increased caloric intake by 342 kcal and carbohydrate intake by 64 g (p=0,040). Significant QoL improvements in role function (p=0,030), emotional function (p=0,018), social function (p=0,036), pain (p=0,06) and insomnia (p=0,020).

Dronabinol led to a significant weight gain of 0,73 kg over placebo (p < 0,01) without serious adverse events, but without significant improvement of psychopathological features (EDI-2).

n=24 (double-blind crossover RCT), dronabinol 2×2,5 mg/day over 4 weeks in severe, long-standing anorexia nervosa: weight gain +0,73 kg vs. placebo (t=2,86, df=22, p<0,01); no significant psychotropic side effects, good tolerability.

All participants perceived improvements in eating, in two cases due to nausea reduction rather than appetite stimulation; psychoactive effects were well tolerated, but transient burdens such as throat irritation and unpleasant taste/smell effects were reported.

n=16 (10 patients with advanced cancer + 6 caregiving family members), vaporised cannabis flowers for tumour-associated anorexia; all respondents perceived improvements in eating, whereby in two cases this was attributed to nausea reduction rather than appetite stimulation. Psychoactive effects well tolerated; transient burdens due to throat irritation and taste.

Both dronabinol and cannabis dose-dependently increased daily caloric intake and body weight in HIV-positive individuals, were well tolerated, and showed comparable effects, with improvement in sleep ratings only from higher-dose cannabis.

n=10 HIV-positive cannabis users, placebo-controlled cross-over study of dronabinol (5/10 mg) and cannabis (2,0%/3,9% THC) 4×daily over 4 days each. Both cannabinoids dose-dependently increased caloric intake and body weight compared to placebo; both well tolerated with comparable efficacy, only cannabis (3,9% THC) additionally improved sleep quality.

THC increased appetite in 13 of 18 evaluable cancer patients with anorexia and showed good tolerability.

Phase II study (n=18 evaluable) on THC 2,5 mg t.i.d. for tumor-associated anorexia; 13/18 patients (72%) reported improved appetite after 28 days; 4 patients grade I toxicity; no serious adverse events; THC well tolerated at this low dose.

In a subset of patients a clinically relevant weight gain and reduced appetite loss were observed, however with considerable study attrition and without a control group.

n=17 cancer patients with CACS, THC/CBD capsules (5–10 mg THC 2×daily); appetite loss symptoms significantly improved after cannabis treatment (p=0,05 per self-report); 3/6 study completers achieved weight gain ≥10%; self-reported appetite improvement documented in the majority of participants.

Dronabinol significantly improved appetite (71% → 26% loss of appetite after 1 month, p<0,001) and enabled weight stabilization or gain in 63% of the 117 patients with weight loss, with mean weight gain of 3,7 lb over 1 year.

Retrospective chart review of n=117 HIV/AIDS patients with weight loss before baseline, dronabinol 3–12 months (1993–2003). 63% of patients with weight loss maintained weight or gained weight; mean weight gain after 1 year +3,7±10,6 lbs. Loss of appetite decreased significantly from 71% (baseline) to 26% (month 1, p<0,001) and decreased further. Nausea decreased from 38% (baseline) with a significant difference from month 6 (p=0,031).

52,5% of patients achieved pain relief of more than 30%, 10% of more than 50%; approximately four symptoms or side effects from previous treatment were positively affected.

Retrospective data on dronabinol in geriatric pain and palliative care patients; appetite stimulation documented as a relevant palliative outcome in cachexia/anorexia, but primarily pain-focused; geriatric population with polypharmacy and multimorbidity.

The majority of patients reported significant appetite increase and nausea decrease under dronabinol, although the effects decreased with disease progression.

Case series n=7 patients with metastasized malignant melanoma and liver metastases; dronabinol (Marinol) led to significant appetite increase and nausea reduction in the majority over several weeks. All patients reported mild to moderate dizziness, however without treatment discontinuation. Effects diminished with disease progression.

Narrative review on oral dronabinol solution (synthetic THC) for anorexia and weight loss in the context of HIV/AIDS and cancer. Dronabinol acts centrally on appetite and vomiting centers and increases appetite; it is approved in the USA for the treatment of anorexia and weight loss in HIV/AIDS, but there is no approved indication for cancer-related anorexia/cachexia. The oral solution approved in 2016 offers an alternative that is easier to swallow than the capsule. No pooled quantitative effect estimates, purely narrative summary of available data; low strength of evidence.