Can dronabinol help with nausea?

Can Dronabinol Help Nausea?

Yes, dronabinol is FDA-approved and recommended by ASCO for treating chemotherapy-induced nausea and vomiting (CINV), particularly for rescue and refractory cases that have failed conventional antiemetics. 1, 2

Primary Indication: Chemotherapy-Induced Nausea and Vomiting

Dronabinol is specifically recommended for breakthrough and refractory CINV when first-line antiemetics (5-HT3 receptor antagonists, NK1 receptor antagonists, dexamethasone, and olanzapine) have failed. 1, 3

When to Use Dronabinol for CINV:

• For patients experiencing nausea or vomiting despite optimal prophylaxis who have already received olanzapine, dronabinol may be offered as an additional agent of a different class while continuing the standard antiemetic regimen 1
• The ASCO Expert Panel specifically recommends either dronabinol or nabilone when a cannabinoid is chosen for rescue and refractory use 1, 3
• Dronabinol has demonstrated efficacy in clinical trials, with FDA approval based on studies showing effectiveness in patients who failed to respond adequately to conventional antiemetic treatments 2

Evidence Quality Considerations:

• The evidence quality for dronabinol in breakthrough CINV is rated as intermediate by ASCO 1
• Historical trials (1975-1991) showed cannabinoids may be useful for refractory CINV, though these studies did not compare against current antiemetic regimens 1
• More recent combination studies demonstrate that dronabinol combined with prochlorperazine resulted in only 29% of patients experiencing nausea versus 47% with dronabinol alone and 60% with prochlorperazine alone 4

Dosing and Administration

The typical starting dose is 2.5-5 mg administered 1 hour before meals or at bedtime, with flexible dosing up to 10-20 mg daily based on tolerance and response. 2, 5

• For CINV, studies have used 10 mg every 6 hours or flexible dosing of 10-20 mg daily 4, 5
• For appetite stimulation (the other FDA-approved indication), the initial dose is 5 mg/day in divided doses (2.5 mg before lunch and dinner), which can be reduced to 2.5 mg/day as a single evening dose if CNS side effects occur 2
• Early morning administration is associated with increased adverse effects compared to later-day dosing 2

Non-Chemotherapy Related Nausea

For nausea unrelated to chemotherapy, the evidence is limited to case reports, though dronabinol may be considered for refractory cases when conventional antiemetics have failed. 3, 6

• A case report demonstrated dramatic response in a patient with peritoneal carcinomatosis and refractory nausea and vomiting 6
• Dronabinol is not FDA-approved for non-chemotherapy related nausea, but may be beneficial in select refractory cases 3

Important Caveats and Side Effects

CNS side effects (feeling high, dizziness, confusion, somnolence, dysphoria) are common and occur in approximately 18% of patients, requiring dose reduction in many cases. 2, 4, 7

Key Safety Considerations:

• Oral dronabinol has high pharmacokinetic variability with peak plasma concentration variability estimated between 150-200% 7
• Adverse effects are more common with dronabinol compared to conventional antiemetics, including dizziness, hypotension, and dysphoria or depression 7
• Combining dronabinol with prochlorperazine appears to decrease the frequency of dysphoric effects seen with dronabinol alone 4, 8
• Oral dronabinol has slower time to peak concentration and lower systemic availability compared to IV or smoked THC 7

Medical Marijuana vs. Dronabinol

ASCO states that evidence is insufficient to recommend medical marijuana in place of FDA-approved cannabinoids (dronabinol and nabilone) for CINV. 1

• Unlike dronabinol and nabilone, which have precisely defined doses and schedules, this information is not available for various preparations of medical marijuana 1
• The exact mechanisms by which marijuana may prevent or treat nausea remain uncertain 1

Clinical Algorithm for Use

1. First-line: Use guideline-recommended antiemetics appropriate for emetic risk (5-HT3 antagonists, NK1 antagonists, dexamethasone) 1
2. Second-line breakthrough: Add olanzapine if not already given prophylactically 1
3. Third-line refractory: Consider dronabinol or nabilone as an additional agent when patients have failed optimal prophylaxis including olanzapine 1, 3
4. Start low: Begin with 2.5-5 mg doses, preferably later in the day to minimize CNS effects 2, 5
5. Titrate carefully: Adjust dose based on response and tolerability, up to 10-20 mg daily if needed 5