DRONABINOL

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Partial agonist at cannabinoid receptors CB1 and CB2; mimics endogenous cannabinoids, inhibiting adenylate cyclase and modulating neurotransmitter release (e.g., GABA, glutamate).

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

CNS depressants including alcohol can cause additive sedation Can cause profound psychological effects.

Breastfeeding

Dronabinol is excreted into breast milk. The milk-to-plasma ratio (M/P) is not established but cannabinoids are highly lipophilic and concentrate in milk. Effects on the nursing infant are unknown; however, potential for adverse effects on neurodevelopment exists. Breastfeeding is not recommended during dronabinol therapy.

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.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	appetite stimulation
Serious Effects

Absolute Contraindications

["Hypersensitivity to dronabinol or any component of the formulation","History of hypersensitivity to marijuana or cannabinoids","Breastfeeding (due to potential infant exposure)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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