What is Marinol (dronabinol)?

What is Marinol (Dronabinol)?

Marinol is the brand name for dronabinol, a synthetic form of delta-9-tetrahydrocannabinol (THC), which is FDA-approved for treating chemotherapy-induced nausea and vomiting that has not responded to standard antiemetics, and for treating anorexia and weight loss in patients with AIDS. 1, 2

Chemical Composition and Formulation

• Dronabinol is synthetic delta-9-tetrahydrocannabinol (delta-9-THC), chemically designated as (6aR,10aR)-6a,7,8,10a-Tetrahydro-6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]-pyran-1-ol 2
• The drug is formulated as a light yellow resinous oil in sesame oil, packaged in gelatin capsules available in 2.5 mg, 5 mg, and 10 mg strengths 2
• It is insoluble in water and has high lipid solubility, with an octanol-water partition coefficient of 6,000:1 at pH 7 2

FDA-Approved Indications

Dronabinol has two specific FDA-approved uses:

• Refractory chemotherapy-induced nausea and vomiting: For patients who have failed to respond adequately to conventional antiemetic treatments 1, 2
• AIDS-related anorexia and weight loss: To stimulate appetite and prevent weight loss in patients with AIDS 1, 2

Mechanism of Action and Pharmacology

• Dronabinol is an orally active cannabinoid with complex effects on the central nervous system, including central sympathomimetic activity 2
• It acts through cannabinoid receptors discovered in neural tissues, which may mediate its therapeutic effects 2
• After oral administration, onset of action occurs at approximately 0.5 to 1 hours, with peak effect at 2 to 4 hours 2
• Duration of psychoactive effects is 4 to 6 hours, but the appetite stimulant effect may continue for 24 hours or longer 2
• The drug is 90-95% absorbed after oral administration, but due to first-pass hepatic metabolism and high lipid solubility, only 10-20% reaches systemic circulation 2

Clinical Efficacy and Limitations

For chemotherapy-induced nausea and vomiting:

• Evidence supporting dronabinol for cancer pain is extremely limited and conflicting 1
• When combined with prochlorperazine, dronabinol shows enhanced efficacy with decreased psychotropic side effects 3
• It is generally reserved for refractory cases after failure of standard antiemetics (5-HT3 antagonists, NK1 antagonists, dexamethasone) 1

For appetite stimulation:

• In cancer patients, dronabinol is inferior to megestrol acetate for appetite stimulation 4
• In a randomized trial of 469 cancer cachexia patients, dronabinol (2.5 mg twice daily) showed less appetite and weight gain compared to megestrol acetate (800 mg/day) 1
• Evidence for cannabinoids improving appetite or anorexia in cancer patients is insufficient and inconsistent 1, 5
• In open pilot studies with HIV patients, dronabinol caused weight gain in 7 of 10 patients and improved appetite at well-tolerated chronic doses 3

Important Safety Considerations

Cardiovascular effects:

• Dronabinol-induced sympathomimetic activity can cause tachycardia and conjunctival injection 2
• Orthostatic hypotension and syncope may occur upon abrupt standing 2

Central nervous system effects:

• Reversible effects on appetite, mood, cognition, memory, and perception occur in a dose-related manner with significant inter-patient variability 2
• Common adverse effects include drowsiness, euphoria, dizziness, confusion, somnolence, and fatigue 1

Tolerance and dependence:

• Tachyphylaxis and tolerance develop to cardiovascular and CNS effects within 12 days of chronic use 2
• However, tolerance does not develop to the appetite stimulant effect, which can be sustained for up to 5 months 2
• Physical dependence can develop with chronic use, and withdrawal symptoms (irritability, insomnia, restlessness, hot flashes, sweating, anorexia) may occur after abrupt discontinuation of high doses 2

Abuse potential:

• Despite being a Schedule III controlled substance, dronabinol has very low abuse potential 6
• There is no evidence of abuse, diversion, or street market for dronabinol 6
• The slow onset of action, weak reinforcing effects, and generally dysphoric effects make it unappealing for recreational use 6

Clinical Context and Alternatives

When dronabinol is NOT recommended:

• Medical marijuana has not been FDA-approved for any indication and remains a Schedule I substance federally, despite state-level legalization 1
• Evidence is insufficient to recommend medical marijuana over FDA-approved cannabinoids like dronabinol 1
• For appetite stimulation in cancer patients, megestrol acetate (400-800 mg/day) or corticosteroids (dexamethasone 2-8 mg/day) are preferred first-line options 4, 5

Important clinical pitfall: Providers should assess for cannabinoid and medical marijuana use in all cancer patients, as 24-40% report using marijuana, and provide education on state and federal regulations 1