Alprazolam Interactions

Alcohol and alprazolam (Xanax) both depress the central nervous system through GABA-A receptor potentiation, producing additive sedation, profound respiratory depression, and impaired psychomotor function. The combination significantly increases risk of overdose death, even at moderate doses of each substance.

Kava contains kavalactones that potentiate GABA-A receptor binding, producing additive CNS depression when combined with alprazolam, a benzodiazepine that also enhances GABA-A activity. A published case report describes a 54-year-old man who became semi-comatose after taking alprazolam with kava for three days.

Melatonin and alprazolam both promote sleep and can produce additive sedation, impaired alertness, and reduced motor coordination when used together. The combination may increase next-day drowsiness and risk during activities like driving.

Grapefruit juice contains furanocoumarins that inhibit intestinal CYP3A4, the enzyme that partially metabolizes alprazolam. The interaction can raise alprazolam blood levels and prolong sedation, although the magnitude is modest compared to other benzodiazepines because alprazolam has high oral bioavailability.