What are the indications for dronabinol in patients with cancer, AIDS, or neuropathic pain?

FDA-Approved Indications for Dronabinol

Dronabinol is FDA-approved for two specific indications: (1) anorexia associated with weight loss in patients with AIDS, and (2) refractory nausea and vomiting associated with cancer chemotherapy in patients who have failed conventional antiemetic treatments. 1

Primary FDA-Approved Indications

1. AIDS-Related Anorexia and Weight Loss

• Starting dose: 2.5 mg orally twice daily, administered one hour before lunch and dinner 1
• Dronabinol has demonstrated appetite improvement in patients with symptomatic HIV infection, with open pilot studies showing weight gain in 7 of 10 patients 2
• The medication improved appetite at doses well-tolerated for chronic administration in HIV patients 2

2. Chemotherapy-Induced Nausea and Vomiting (CINV)

• Indicated only for patients who have failed to respond adequately to conventional antiemetic treatments 1
• Starting dose: 5 mg/m² administered 1-3 hours prior to chemotherapy, then every 2-4 hours after chemotherapy, for a total of 4-6 doses per day 1
• First dose should be taken on an empty stomach at least 30 minutes before eating; subsequent doses can be taken without regard to meals 1
• Studies show similar or improved efficacy compared with conventional antiemetics for resolution of nausea and vomiting 3
• Combination with prochlorperazine enhances efficacy and appears to decrease psychotropic side effects 2

Important Clinical Context from Guidelines

Limited Role in Cancer Pain

• Data supporting cannabinoids as adjuvant analgesics for cancer pain are extremely limited and conflicting 4
• The NCCN (2019) notes that while nabiximols showed benefit in some trials, THC extract alone did not show significant benefit compared to placebo 4
• Dronabinol is not recommended as a first-line analgesic for cancer pain 4

Not Recommended for Appetite Stimulation in Cancer

• ESPEN guidelines (2017) explicitly state there is insufficient consistent clinical data to recommend cannabinoids for improving taste disorders or anorexia in cancer patients 4
• In a head-to-head trial of 469 cancer cachexia patients, megestrol acetate (800 mg/day) demonstrated significantly greater appetite and weight gain compared to dronabinol (2.5 mg twice daily), with dronabinol alone showing the poorest outcomes 4, 5
• A multicenter RCT of 164 patients with advanced cancer showed cannabis extract or THC at 5 mg/day for 6 weeks did not improve appetite or quality of life 4
• Megestrol acetate is superior to dronabinol for appetite stimulation in cancer patients 5

ASCO Guidelines on Cannabinoids (2024)

• For cancer patients with refractory CINV despite optimal prophylaxis, dronabinol may be considered alongside nabilone or quality-controlled oral 1:1 THC:CBD extract 4, 6
• The certainty of evidence for dronabinol in CINV is moderate 4
• Evidence for other outcomes (quality of life, anxiety, depression) is very low 4

Critical Safety Warnings

Neuropsychiatric Effects

• May cause psychiatric and cognitive effects and impair mental and physical abilities 1
• Avoid use in patients with psychiatric history 1
• Patients should not operate motor vehicles or dangerous machinery until reasonably certain dronabinol does not affect them adversely 1
• Cannabinoid administration in elderly patients may induce delirium 5

Cardiovascular Concerns

• Patients with cardiac disorders may experience hypotension, hypertension, syncope, or tachycardia 1
• Monitor for hemodynamic changes after initiating or increasing dosage 1

Seizure Risk

• Weigh potential risks versus benefits in patients with history of seizures or factors that lower seizure threshold 1
• Monitor patients and discontinue if seizures occur 1

Common Adverse Effects

• Most common adverse reactions (≥3%): abdominal pain, dizziness, euphoria, nausea, paranoid reaction, somnolence, abnormal thinking, and vomiting 1
• Oral cannabinoids are associated with greater incidence of adverse effects compared with conventional antiemetic therapy or placebo 3
• High dropout rates due to adverse events have been documented in clinical trials 4

Pharmacokinetic Considerations

• Oral THC has high pharmacokinetic variability, with variability in peak plasma concentrations estimated between 150-200% 3
• Slower time to peak concentration compared with IV or smoked THC, and lower systemic availability 3
• Dronabinol inhibits CYP3A4, CYP2C9, and CYP2C19 enzymes, which could affect metabolism of concurrent medications 6
• Avoid high-fat meals when taking oral cannabis products, as this significantly increases cannabinoid absorption 6

Abuse Potential

• Dronabinol has very low abuse potential 7
• No evidence of abuse or diversion; no street market exists for dronabinol 7
• Onset of action is slow and gradual, weakly reinforcing at most, with effects typically described as dysphoric and unappealing 7
• Cannabis-dependent populations have demonstrated no interest in abuse of dronabinol 7