WARNINGMIXING OR WITHDRAWAL CAN BE DANGEROUS
Ordinary doses in combination with other depressants can fatally stop breathing. After prolonged dependency, stopping suddenly can also cause seizures or delirium; seek medical help.
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Librium
Librium is a depressant1 of the 1,4-benzodiazepine class with sedative, sleep-promoting, and anxiety-reducing effects.2 It is used to treat anxiety,1 and withdrawal symptoms of acute alcoholism.1 It was the first benzodiazepine synthesized,3 was discovered by chance,4 and was approved for medical use in 1960.5 It is habit-forming1 and may cause amnesia2 and reduced inhibition.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
For equivalence purposes, 25 mg of chlordiazepoxide is roughly comparable to 10 mg of diazepam.
Duration
Subjective Effects
Pharmacology
Pharmacodynamics
Chlordiazepoxide positively modulates GABA-A receptors by binding to their benzodiazepine sites, increasing GABA binding and GABA-mediated chloride influx.6 The resulting membrane hyperpolarization strengthens neuronal inhibition and contributes to its anxiolytic, sedative, anticonvulsant, and muscle-relaxant actions. It also modulates the translocator protein. In animal nerve-terminal preparations, benzodiazepine-site activity has been associated with calcium-channel blockade and reduced calcium uptake. Chlordiazepoxide inhibits acetylcholine release in mouse hippocampal preparations, which may contribute to its anticonvulsant action, and has been reported to reduce serotonin turnover and prolactin release in rats.
Pharmacokinetics
Chlordiazepoxide undergoes hepatic metabolism7 and is a substrate of CYP3A enzymes, including CYP3A4. Reported elimination half-life ranges are 5-30 hours and 24-48 hours; an active metabolite has a half-life of 36-200 hours. Clearance of the parent drug slows in older adults, and clearance of the active metabolite is delayed in people over 60, favoring accumulation with repeated administration. Hepatitis and liver cirrhosis reduce elimination by a factor of two. Urinary excretion includes 1-2% unchanged drug and 3-6% as conjugate.1 Food does not affect absorption. Neonates have greater absorption across administered routes and preferential storage in some organs, including the heart. Chlordiazepoxide rapidly crosses the placenta and passes into breast milk.
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
Harm Potential
Addiction & Dependence
Psychological
Chlordiazepoxide is habit-forming and has potential for misuse;1 it is frequently detected in urine samples from drug users without a prescription.
Physical
Chlordiazepoxide can cause physical dependence1 and withdrawal symptoms, with greater withdrawal risk at higher doses and after longer use; symptoms can also occur at standard doses and after short-term use. Tolerance may develop with continued chlordiazepoxide therapy, and gradual dose reduction is recommended when discontinuing treatment.1 Exposure during pregnancy can cause neonatal benzodiazepine withdrawal.2
Toxicity
Chlordiazepoxide overdose can cause respiratory depression and coma. Use of sedative and sleeping medications, including chlordiazepoxide, has been associated with increased mortality, without establishing a causal relationship or a human lethal dose.
LD50 Data
| Species | Route | Value |
|---|---|---|
| Rat | Oral | 537 mg/kg |
Chlordiazepoxide overdose can cause hypoventilation and respiratory depression.
Chlordiazepoxide overdose can cause hypotension.8
Chlordiazepoxide overdose can cause marked somnolence, confusion, impaired motor function and reflexes, muscle weakness, and coma; laboratory studies in mice also found impaired latent learning.
Liver problems and jaundice are listed among common adverse effects of chlordiazepoxide.
Laboratory exposure of mouse spermatozoa to chlordiazepoxide caused toxicity, including abnormalities in sperm-head shape and size.
Chlordiazepoxide markedly reduced serotonin turnover in rats, a finding proposed as a contributor to depressive feelings in exposed rats.
History & Culture
Discovery and development
Chlordiazepoxide, initially called methaminodiazepoxide, was the first benzodiazepine synthesized.9 Its synthesis in the mid-1950s grew out of research on quinazoline-3-oxide dyes. Its therapeutic potential was recognized by chance in 1957 through animal screening
Legality
International
Chlordiazepoxide has approved, illicit, and investigational regulatory groupings.
By Country
United StatesIllegal
CanadaRestricted
SingaporePrescription onlyReferences
Citations
Article Status
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