Lorazepam

7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Overview

Lorazepam belongs to Depressants / Benzodiazepines.

Key safety note: Lorazepam's main dangers are dependence and dangerous combinations.[3][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • Calming and relief of anxiety, drowsiness and sedation, muscle relaxation and, at higher doses, sleep. A sense of emotional 'blunting' is common.
  • Anterograde amnesia (difficulty forming new memories), impaired coordination and balance, dizziness, slurred speech and slowed reaction time are typical, especially early in treatment or at higher doses.
  • Tolerance to the sedative and hypnotic effects and physical dependence develop with continued use. Paradoxical reactions (agitation, irritability, disinhibition) occur in a minority, and a 'hangover' of grogginess can follow.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral tablets (0.5, 1, 2 mg) and oral solution. Also given intramuscularly and intravenously in hospital settings. Prescription-only. The figures below are medical reference ranges from the drug label and StatPearls, not recreational guidance. Lorazepam is potent and its effects are strongly amplified by alcohol and other CNS depressants, and it must never be combined with opioids. Oral use for anxiety is meant to be short-term (the FDA advises against use beyond about four weeks). Doses are individualised and must be tapered slowly, never stopped abruptly, after regular use.

Dose ranges

Anxiety (oral, adult)

0.5–1 mg two to three times daily, increase as needed to a maximum of 10 mg/day in divided doses

Anxiety-related insomnia (oral)

2–4 mg at bedtime

Status epilepticus (IV)

0.1 mg/kg (maximum 4 mg per dose)

Anaesthesia premedication (IM)

0.05 mg/kg ~2 h before surgery (maximum 4 mg)

Duration

onset

Oral ~20–30 min, IV 1–5 min, IM 15–30 min

total

Intermediate-acting: clinical effect ~6–8 h (elimination half-life ≈10–20 h)

after effects

Residual drowsiness, grogginess and impaired coordination or memory. Rebound anxiety or insomnia after regular use

Chemical & Physical Properties
FormulaC15H10Cl2N2O2
Molar mass321.16 g/mol
StateSolid
Melting point166–168 °C
Boiling pointunavailable: true. reason: the only figure available is a software prediction (~534 °C at 1 atm), which is not physically meaningful: lorazepam is a crystalline solid that thermally decomposes well before boiling, so no reliable experimental boiling point exists
DensityNot reported
Vapor pressureNot reported
pKa13
LogP2.39
Solubility80 mg/L, 1.76×10⁻² g/L
Refractive indexNot reported
Identifiers & Synonyms
CAS846-49-1
CAS (enantiomer)
PubChem CID3958
InChIKeyDIWRORZWFLOCLC-UHFFFAOYSA-N
InChIInChI=1S/C15H10Cl2N2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20)
SMILESC1=CC=C(C(=C1)C2=NC(C(=O)NC3=C2C=C(C=C3)Cl)O)Cl

Synonyms

  • Ativan
  • Temesta
  • Lorazepam
  • Tavor
Pharmacodynamics & Biochemistry

Lorazepam is a high-potency, intermediate-acting benzodiazepine. It binds the benzodiazepine site of the GABA-A receptor, the interface between an α (α1/α2/α3/α5) subunit and the γ2 subunit, and acts as a positive allosteric modulator: it does not open the channel itself but increases the frequency with which the endogenous transmitter GABA opens the chloride channel. The greater chloride influx hyperpolarises the neuron and dampens its firing, producing anxiolytic, sedative, hypnotic, anticonvulsant, muscle-relaxant and amnesic effects. It is a high-affinity (low-nanomolar), non-subtype-selective agonist that binds α1-, α2-, α3- and α5-containing receptors with broadly similar affinity, which is why it produces the full range of benzodiazepine effects rather than a subtype-selective one. No cleanly curated per-subtype binding constants are catalogued for it in the major open pharmacology databases, so a quantitative binding table is deliberately not shown. Compared with diazepam it is considerably less lipid-soluble, so it enters the brain a little more slowly but also redistributes out of it less. This gives lorazepam a longer duration of central action than its serum half-life alone would suggest, and is a reason intravenous lorazepam is a preferred first-line drug for status epilepticus. In-vitro receptor screening also identifies lorazepam as a positive allosteric modulator of the proton-sensing receptor GPR68, and reports only very weak, clinically irrelevant activity at an α1B-adrenoceptor (Ki ≈ 160 µM). Neither is thought to contribute to its clinical effects, which are GABAergic.

Biological targets

  • GABA-A

Binding & functional measurements

TargetMeasurementSpecies
GABA-A α1β2γ2 receptorEC50 5.0 nMHuman
Pharmacokinetics
BioavailabilityOral ≈90%
Tmax≈2 h
Half-life≈10–20 h
VdNot reported
Protein binding≈85%
MetabolismHepatic glucuronidation (no active metabolites, CYP-independent)
ExcretionRenal
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Lorazepam's main dangers are dependence and dangerous combinations. Physical dependence and a withdrawal syndrome develop in a substantial minority of people treated for more than a few weeks, and because lorazepam is relatively short-acting the withdrawal can be brisk and severe, rebound anxiety and insomnia, tremor, and in serious cases seizures and psychosis, so it must be tapered slowly and never stopped abruptly after regular use. Its abuse and dependence liability is high for a benzodiazepine. The gravest acute risk is additive central-nervous-system and respiratory depression when it is combined with opioids (the subject of an FDA boxed warning), alcohol, or other sedatives: a leading cause of benzodiazepine-related overdose deaths. It commonly causes drowsiness, dizziness and marked anterograde amnesia (pronounced relative to other benzodiazepines), impairs coordination and driving, and raises the risk of falls and hip fractures in older adults. Paradoxical excitement, agitation or disinhibition occur in a minority. Use in late pregnancy can cause neonatal sedation and withdrawal ('floppy infant syndrome').[3][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Opioids Additive sedation and respiratory depression that can be fatal (FDA boxed warning). The combination should be avoided.[3][4]
Alcohol, Benzodiazepines, Gabapentinoids (gabapentin, pregabalin) Additive sedation, respiratory depression, amnesia and disinhibition, including with z-drugs, barbiturates and sedating antihistamines.[3]
Antipsychotics Clozapine and other sedatives have rarely been linked to marked hypotension, respiratory depression or arrest when combined with parenteral lorazepam.[4]

Contraindications

Known hypersensitivity to the drug hypersensitivity to benzodiazepines.[3]
Respiratory disease or sleep apnoea severe respiratory insufficiency or sleep apnoea syndrome.[3]
Closed-angle glaucoma acute narrow-angle glaucoma.[4]
Myasthenia gravis[4]
Kidney or liver impairment severe hepatic insufficiency, though its glucuronidation route makes it one of the safer benzodiazepines in milder liver disease.[3][4]
Combining with alcohol or other CNS depressants concurrent alcohol or other CNS depressants.[3][4]
Usage & Context
  • A prescription benzodiazepine (Ativan, Tavor, Temesta) for the short-term relief of anxiety and anxiety-related insomnia, and as premedication before surgery or procedures for its sedative and amnesic effects.
  • Intravenous lorazepam is a first-line treatment for status epilepticus, and it is widely used for alcohol-withdrawal syndrome, acute agitation, catatonia and chemotherapy-related anticipatory nausea.
  • Like other benzodiazepines it is also misused recreationally and to 'come down' from stimulants. Its high potency and dependence liability make non-medical use and long-term daily use particularly risky.
Sources & Evidence

Further Information