DRONABINOL
Clinical safety rating
avoidContraindicated (not allowed)
Partial agonist at cannabinoid receptors CB1 and CB2; mimics endogenous cannabinoids, inhibiting adenylate cyclase and modulating neurotransmitter release (e.g., GABA, glutamate).
| Metabolism | Hepatic via CYP2C9 and CYP3A4; major metabolite 11-hydroxy-dronabinol (active); further oxidation to 11-nor-9-carboxy-dronabinol. |
| Excretion | Primarily hepatic metabolism followed by biliary and fecal excretion. Approximately 65% eliminated in feces and 35% in urine, mostly as metabolites. Less than 5% of unchanged drug is excreted in urine. |
| Half-life | Terminal elimination half-life is approximately 25–36 hours in chronic users due to extensive tissue distribution and slow release from fat stores; in naive users, half-life is shorter, around 20–30 hours. The prolonged half-life contributes to accumulation with repeated dosing. |
| Protein binding | Highly protein-bound: >95% bound primarily to albumin and, to a lesser extent, lipoproteins. |
| Volume of Distribution | Extremely large, estimated at 10–30 L/kg due to high lipophilicity and extensive tissue uptake, particularly into adipose tissue and brain. This accounts for the slow elimination and prolonged action. |
| Bioavailability | Oral bioavailability is low and variable, approximately 10–20% due to extensive first-pass hepatic metabolism. There is significant interindividual variability based on metabolism and formulation. |
| Onset of Action | After oral administration, onset occurs within 30–60 minutes. Peak effects are seen at 2–4 hours. For oromucosal or inhalation routes, onset is more rapid (minutes) but dronabinol is only approved for oral use. |
| Duration of Action | Clinically significant effects last 4–6 hours after a single dose, but psychoactive effects and appetite stimulation can persist for up to 8–12 hours. Duration is dose-dependent and may be prolonged due to the long half-life. |
| Molecular Weight | 314.46 |
2.5-10 mg orally twice daily, titrated to effect; maximum 15 mg per day in divided doses.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment necessary for GFR >30 mL/min; insufficient data for GFR <30 mL/min, use with caution. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce starting dose to 1.25-2.5 mg twice daily and titrate cautiously; Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for use in children under 18 years due to lack of safety and efficacy data. |
| Geriatric use | Initiate at 1.25-2.5 mg twice daily; monitor for CNS effects and falls; titrate slowly. |
| 1st trimester | Contraindicated due to teratogenic effects and potential for fetal cannabinoid syndrome. |
| 2nd trimester | Contraindicated; may impair neurodevelopment and growth. |
| 3rd trimester | Contraindicated; risk of neonatal withdrawal and long-term neurobehavioral effects. |
Clinical note
CNS depressants including alcohol can cause additive sedation Can cause profound psychological effects.
| Placental transfer | Dronabinol crosses the placenta readily, with fetal plasma levels approximately 10% of maternal levels; high lipid solubility leads to accumulation in fetal tissues. |
| Breastfeeding | Dronabinol is excreted into breast milk and may accumulate due to high lipid solubility. Long-term neurobehavioral effects are possible. Avoid breastfeeding during therapy. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Dronabinol is a synthetic cannabinoid. Data on human pregnancy are limited. Animal studies show developmental toxicity at high doses. First trimester: potential risk of fetal abnormalities cannot be excluded; avoid unless benefit outweighs risk. Second and third trimesters: may cause fetal neurobehavioral effects; use only if clearly needed. Late pregnancy: associated with neonatal withdrawal symptoms and possible long-term neurodevelopmental effects. |
| Fetal Monitoring | Monitor maternal vital signs and mental status for CNS depression, dizziness, or dysphoria. Assess fetal growth and well-being via ultrasound and fetal heart rate monitoring if used chronically. Observe neonate for signs of withdrawal (irritability, tremors, hypertonia) and respiratory depression after delivery. |
| Fertility Effects | Animal studies show reversible impairment of fertility (reduced sperm count, motility, and increased abnormal sperm) in males and disrupted estrous cycles in females. Human data are limited but cannabinoids may adversely affect gametogenesis and implantation. Use with caution in individuals planning conception. |
■ FDA Black Box Warning
None
| Common Effects | appetite stimulation |
| Serious Effects |
Hypersensitivity to dronabinol or any cannabinoidSevere hepatic impairment
| Precautions | Central nervous system depression (e.g., dizziness, drowsiness, impaired coordination), Paradoxical reactions (e.g., increased nausea, vomiting), Risk of abuse and dependence due to psychoactive effects, Cardiovascular effects (e.g., tachycardia, hypotension), May cause seizures in patients with history of epilepsy, Not recommended for chemotherapy-induced nausea in patients receiving concomitant central nervous system depressants |
| Food/Dietary | High-fat meals may increase absorption; take consistently with respect to meals. Avoid grapefruit juice as it may increase dronabinol levels. |
| Clinical Pearls | Dronabinol is synthetic THC, used for chemotherapy-induced nausea and vomiting (CINV) and appetite stimulation in AIDS wasting. Onset is 0.5-1 hour orally; titrate slowly due to psychoactive effects. May cause euphoria, dizziness, and cognitive impairment. Use with caution in patients with psychiatric disorders, seizure disorders, or history of substance abuse. Monitor for hypotension and tachycardia. Avoid concurrent use with other CNS depressants. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency. · Avoid driving or operating heavy machinery until you know how this medication affects you. · This drug may cause dizziness, drowsiness, or confusion; avoid alcohol and other CNS depressants. · Report any mood changes, hallucinations, or unusual thoughts to your healthcare provider. · Keep out of reach of children and store in a cool, dry place. · For nausea, take at least 1 hour before chemotherapy (if used as prophylaxis). · For appetite stimulation, take before meals. |
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