Prescription ·Strong evidence ·Reviewed May 2026
Prescription benzodiazepine (Schedule IV controlled substance) approved for anxiety disorders, acute alcohol withdrawal, muscle spasm, seizure disorders, and as a preanesthetic agent. One of the oldest and most well-studied benzodiazepines with the longest half-life in its class. Its active metabolite desmethyldiazepam further extends its duration of action. Dosage must be determined by your prescribing physician.
The bottom line
Evidence rating strong. Most-documented uses: anxiety relief, muscle spasm reduction, acute alcohol withdrawal management. 10 sources indexed (1975–2023), with 5 interaction records on file.
Core mechanism
Binds to the benzodiazepine site on GABA-A receptors, enhancing GABA-mediated inhibitory neurotransmission. Produces anxiolytic, sedative, anticonvulsant, and skeletal muscle relaxant effects. Highly lipophilic with rapid CNS penetration. Metabolized to active metabolites (desmethyldiazepam, temazepam, oxazepam) that prolong clinical effects.8,9
Rapidly and completely absorbed orally. Can be taken with or without food. Rectal gel available for acute seizure rescue.
FDA Black Box Warning: Concurrent opioid and benzodiazepine use can result in profound sedation, respiratory depression, coma, and death. Morphine and diazepam both have long durations of action, compounding the risk.
Recommendation: Avoid combination. If absolutely necessary in a monitored setting, use lowest possible doses with continuous pulse oximetry monitoring.
St. John's Wort induces CYP3A4 and CYP2C19, both of which metabolize diazepam. This can reduce diazepam levels, causing breakthrough anxiety or seizures in epilepsy patients.
Recommendation: Avoid combining. Abrupt reduction in diazepam levels can cause withdrawal symptoms or seizures.
Both diazepam and valerian enhance GABA-A receptor activity. Combined use creates additive CNS depression and excessive sedation.
Recommendation: Avoid combining valerian with diazepam. The additive sedative effect can impair breathing and cause excessive drowsiness.
Apigenin has benzodiazepine-receptor and GABA(A)-modulating activity in preclinical studies. One receptor study specifically found that apigenin enhanced diazepam's positive modulation of GABA(A) receptor activation. In people, this could mean more sedation, impaired coordination, or slowed reaction time, although direct clinical interaction trials are lacking.
Recommendation: Use apigenin cautiously if you take diazepam, especially when starting either product or increasing doses. Avoid alcohol and other sedatives, and do not drive until you know how the combination affects you. Stop apigenin and contact your prescriber if sedation, confusion, or balance problems increase.
Alcohol and diazepam together produce additive psychomotor impairment, slowed reactions, memory problems, and excessive sedation. Diazepam and its active metabolites last a long time, so alcohol can interact the same day and sometimes the next day. The combination is especially unsafe before driving or in people at fall or respiratory risk.
Recommendation: Do not drink alcohol while taking diazepam. Avoid driving if you have taken diazepam and consumed alcohol within the same day. Get urgent help if you develop severe drowsiness, confusion, or slow breathing.
Numbered references. Citations throughout the page link here.
Stone RH, Abousaud M, Abousaud A et al.. A Systematic Review of Intravaginal Diazepam for the Treatment of Pelvic Floor Hypertonic Disorder. Journal of clinical pharmacology. 2020
Wu W, Zhang L, Xue R. Lorazepam or diazepam for convulsive status epilepticus: A meta-analysis. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2016
Nimmaanrat S, Charuenporn B, Jensen MP et al.. The anxiolytic effects of preoperative administration of pregabalin in comparison to diazepam and placebo. Scientific reports. 2023
Hawksworth G, Betts T, Crowe A et al.. Diazepam/beta-adrenoceptor antagonist interactions. British journal of clinical pharmacology. 1984
Verrotti A, Milioni M, Zaccara G. Safety and efficacy of diazepam autoinjector for the management of epilepsy. Expert review of neurotherapeutics. 2015
Murphy A, Wilbur K. Phenytoin-diazepam interaction. The Annals of pharmacotherapy. 2003
Kleinknecht RA, Donaldson D. A review of the effects of diazepam on cognitive and psychomotor performance. The Journal of nervous and mental disease. 1975
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