What is the role of dronabinol in appetite stimulation?

Dronabinol for Appetite Stimulation

Current guidelines do not support the routine use of dronabinol for appetite stimulation due to insufficient and inconsistent clinical evidence, with superior alternatives available. 1

Evidence Against Routine Use

The most recent ESPEN guidelines (2021) explicitly state there are insufficient consistent clinical data to recommend cannabinoids including dronabinol to improve taste disorders or anorexia in cancer patients. 1 This recommendation is based on:

• A large multicenter RCT (n=164) showing THC 5 mg/day for 6 weeks failed to improve appetite or quality of life in advanced cancer patients with anorexia-cachexia syndrome 1
• Inconsistent trial results where one small pilot RCT showed improved chemosensory perception and pre-meal appetite with THC 2.5 mg twice daily for 18 days, but this contradicts the larger, higher-quality trial 1
• High dropout rates due to adverse events in phase II trials, with only 68% showing reduced anorexia but significant tolerability issues 1

Specific Population Considerations

Dementia Patients

Dronabinol should not be systematically used in dementia patients. 1 The evidence base is extremely limited:

• Only one small RCT (n=12) in Alzheimer's disease showed increased body weight and triceps skinfold thickness after 6 weeks, despite unchanged caloric intake 1
• One retrospective chart review (n=40) reported improved meal consumption, but this is weak evidence without placebo control 1
• Potential for delirium induction in elderly patients is a critical safety concern 2

AIDS-Related Anorexia

The FDA label indicates dronabinol is approved for AIDS-related anorexia based on a study of 139 patients where 2.5 mg twice daily showed statistically significant appetite improvement (38% vs 8% for placebo, P=0.015). 3, 4 However:

• Weight remained stable rather than increasing significantly 3, 4
• 18% of patients required dose reduction to 2.5 mg/day due to side effects (feeling high, dizziness, confusion, somnolence) 3
• This represents the strongest evidence for dronabinol, but is limited to this specific population 3, 4

Superior Alternatives

Megestrol acetate (400-800 mg/day) demonstrates superior efficacy compared to dronabinol for appetite stimulation. 5 In a head-to-head RCT of 469 cancer cachexia patients:

• Megestrol acetate showed greater gains in appetite and weight compared to dronabinol 2.5 mg twice daily 1
• The combination of megestrol acetate plus dronabinol showed no additional benefit over megestrol acetate alone 1
• Approximately 1 in 4 patients experience increased appetite and 1 in 12 gain weight with megestrol acetate 5

Mirtazapine (7.5-30 mg at bedtime) is recommended as first-line for patients with concurrent depression, addressing both conditions simultaneously with mean weight gain of 1.9 kg at 3 months. 5

Adverse Effect Profile

Dronabinol carries significant neuropsychiatric risks that limit its clinical utility:

• Euphoria, hallucinations, vertigo, psychosis, and cardiovascular disorders are main adverse events 1
• Cannabis prescription must follow strict narcotic and psychotropic drug regulations 1
• Slow onset of action and dysphoric effects in many users limit reinforcement 6
• No evidence of abuse or diversion in clinical practice, but effects are often unappealing to patients 6

Clinical Algorithm

When considering appetite stimulation:

1. First, address reversible causes: pain, constipation, nausea, depression, oral candidiasis 2
2. For patients with concurrent depression: Use mirtazapine 7.5 mg at bedtime initially, titrating to maximum 30 mg over 4-8 weeks 5
3. For patients without depression: Use megestrol acetate 400-800 mg daily as first-line pharmacological intervention 5
4. For short-term use in limited life expectancy: Consider dexamethasone 2-8 mg/day for rapid onset 5, 2
5. Avoid dronabinol unless other options have failed or are contraindicated, given the inconsistent evidence and availability of superior alternatives 1, 5

Key Pitfalls to Avoid

• Do not use appetite stimulants systematically in dementia patients without concurrent depression, as risks outweigh uncertain benefits 1, 5
• Do not expect significant weight gain with dronabinol; evidence shows appetite improvement but minimal weight change 3, 4
• Do not overlook non-pharmacological interventions such as fortified foods, oral nutritional supplements, and behavioral strategies at mealtimes, which can be equally or more effective 5, 2
• Do not continue dronabinol long-term without reassessment, as the evidence for sustained benefit is lacking 1