Lorazepam

Ativan, Temesta, Tavor, Orfidal, Lorsilan

Psychoactive Class

Depressant Anxiolytic Sedative GABAergic Muscle Relaxant

Chemical Class

Lorazepam is a short-acting depressant of the benzodiazepine class¹. First marketed by Wyeth Pharmaceuticals in the United States in 1977, it is prescribed for the short-term treatment of anxiety, insomnia¹, acute seizures, and sedation of hospitalized patients. It is characterized by its relatively rapid clearance compared to many other benzodiazepines. Like all benzodiazepines, lorazepam carries a significant risk of physical dependence² and habit formation³ with repeated use.

Dosage & Duration

Dosage

Threshold~0.1 mg

Light0.1-0.5 mg

Moderate0.5-1.5 mg

Strong1.5-2 mg

Heavy2+ mg

Bioavailability

90%

Duration

Onset5-30 minutes

Peak1-3 hours

Offset4-8 hours

Total4-8 hours

Half-life

~8 hours

Subjective Effects

Effects vary widely by individual, dose, and context.

Physical

The physical effects of lorazepam can be broken down into several components which progressively intensify proportional to dosage.

Motor control loss Muscle relaxation Dizziness Respiratory depression Seizure suppression

Cognitive

The cognitive effects of lorazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of lorazepam is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical depressant cognitive effects.

Anxiety suppression Thought deceleration Disinhibition Information processing suppression Euphoria Amnesia Compulsive redosing

Forked from Subjective Effect Documentation

by Josie KinsSeptember 2015.

Reagent Testing

Loading reagent data

Expected colorimetric results are being prepared.

Pharmacology

Pharmacodynamics

Lorazepam is a high-potency benzodiazepine that acts as a positive allosteric modulator at the benzodiazepine binding site of the GABA-A receptor.^? By binding to post-synaptic GABA-A ligand-gated chloride channels throughout the central nervous system, it increases the frequency of chloride ion channel opening in the presence of GABA, enhancing inhibitory neurotransmission through cellular hyperpolarization.^? Lorazepam is reported to have a relatively high affinity for the GABA-A benzodiazepine site compared to other benzodiazepines. Its anticonvulsant properties may additionally involve binding to voltage-dependent sodium channels.

Pharmacokinetics

Lorazepam is readily absorbed orally with an absolute bioavailability of approximately 90%,^? and is completely and rapidly absorbed when administered intramuscularly.^? It is hepatically metabolized primarily through direct glucuronidation to the inactive metabolite lorazepam-glucuronide,^? with CYP450 isoenzymes also reported to be involved. The glucuronide metabolite is eliminated by the kidneys, and lorazepam has no active metabolites.^? The elimination half-life is approximately 8 hours following oral administration,^?4 11 hours for sublingual dosing,⁴ and 14 hours when given parenterally.^?

Interactions

Dangerous

Highest risk

These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.

AlcoholGHB/GBLOpioidsTramadol

Unsafe

Avoid

There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.

DiphenhydraminePCP

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

DXMKetamineMXE

TripSit

Tolerance

Full Tolerance

Sedative-hypnotic tolerance can appear after only a few days of uninterrupted use.

Cross Tolerance

Benzodiazepines

Baseline Reset

Tolerance typically returns to baseline within 7-14 days after cessation, though this may take significantly longer in proportion to the duration and intensity of long-term use.

Harm Potential

Addiction & Dependence

Psychological

Extremely High

Lorazepam is described as extremely psychologically addictive with a very high dependence potential.^? Compulsive redosing is commonly reported, and the risk of abuse is increased in individuals with pre-existing substance dependence or psychiatric disorders.⁵

Physical

Extremely High

Physical dependence develops rapidly, with withdrawal symptoms possible after as little as one week of therapeutic use.⁵ Discontinuation can be life-threatening without proper medical tapering, with serious risk of seizures, hypertension, and death.^? As a potent short-acting benzodiazepine, lorazepam carries the highest risk of dependence within its class.⁶

Toxicity

Central Nervous System

Long-term use may cause cognitive deficits, particularly affecting memory and new memory formation; these effects may persist for at least six months after discontinuation and may only be partially reversible, especially in elderly users.⁷

Psychosis Risk

Psychosis is rare during therapeutic or recreational use but can occur as a withdrawal symptom following abrupt discontinuation after chronic use.⁵ Paradoxical reactions including hallucinations and delirium occur in less than 1% of the general population⁹ but are more common in recreational abusers, individuals with psychiatric disorders, children, and those on high-dose regimens.

Seizure Risk

Lorazepam has anticonvulsant properties and suppresses seizures during active use. However, abrupt withdrawal after regular use poses a significant seizure risk that can be life-threatening.^? Paradoxical worsening of seizures may rarely occur, particularly in individuals with epilepsy. Gradual tapering under medical supervision is essential to prevent withdrawal seizures.

History & Culture

Lorazepam was initially patented in 1963 and is considered one of the "classical" benzodiazepines alongside diazepam, clonazepam, oxazepam, nitrazepam, flurazepam, bromazepam, and clorazepate. The compound was developed by D.J. Richards, who served as president of research at Wyeth…

Legality

International

1961 Single Convention: not internationally scheduled.

1971 Convention on Psychotropic Substances: Schedule IV.

1988 Convention: not listed as a controlled precursor.

By Country

United StatesPrescription onlySchedule IV

21 CFR 1308.14⁶⁶⁶⁷

Controlled under the Controlled Substances Act as a Schedule IV depressant.^?68 Possession without a valid prescription is illegal, as is sale without appropriate licensing.

AustriaPrescription onlyPsychotropic · No repeats

Psychotropenverordnung, Anhang 1 and § 10 Abs. 4^17181920

Lorazepam is expressly listed in Annex 1 to Austria's current Psychotropenverordnung, which defines the listed substances as psychotropic substances under the Suchtmittelgesetz. BASG identifies lorazepam as a psychotropic 1,4-benzodiazepine and states that benzodiazepines other than flunitrazepam are prescription-only medicines under § 10(4), with repeat dispensing prohibited. Flunitrazepam alone is identified by BASG as subject to the separate Suchtgiftrezept regime, so that special regime should not be attributed to lorazepam.

CanadaPrescription onlySchedule IV

Controlled Drugs and Substances Act²²²³

Listed in Schedule IV of the Controlled Drugs and Substances Act alongside other benzodiazepines.²⁴ Requires a valid prescription for lawful possession.

DenmarkPrescription onlyListe E

Bekendtgørelse om euforiserende stoffer²⁸²⁹³⁰

Lorazepam is listed in List E of Denmark's Executive Order on Euphoriant Substances. The order permits possession only for persons and institutions receiving euphoriant substances under a prescription, requisition, or other specified authorization, and regulates their medical dispensing through authorized suppliers.

GermanyPrescription onlyAnlage III

Betäubungsmittelgesetz, Anlage III; Arzneimittelverschreibungsverordnung, Anlage 1³³³⁴³⁵

Lorazepam is listed in Anlage III to Germany's Betäubungsmittelgesetz. Preparations containing no other Annex I–III substance and no more than 2.5 mg lorazepam per divided form are expressly excepted from that narcotics listing; lorazepam medicines remain prescription-only under the Arzneimittelverschreibungsverordnung. Preparations above the exception threshold are subject to the BtM prescription regime.

MexicoPrescription onlyGrupo III

Ley General de Salud³⁷

Lorazepam is included in Mexico's official psychotropic-substances list. Its supply is subject to the General Health Law's prescription controls for psychotropic medicines.

New ZealandPrescription onlyClass C

Misuse of Drugs Act 1975⁴¹⁴²

Controlled as a Class C drug under the Misuse of Drugs Act 1975. Prescription required for lawful possession.

PolandPrescription onlyIV-P

Regulation of the Minister of Health on the list of psychotropic substances, narcotic drugs and new psychoactive substances⁴⁶⁴⁷

Controlled under the psychotropic substances act as a Group IV-P substance, designated as having low potential for abuse. Legal for medical, scientific, and manufacturing purposes with appropriate authorization.

RussiaPrescription onlyList III

Government Resolution No. 681 of 30 June 1998⁵¹⁵²

Classified as a Schedule III controlled substance since 2013. Requires prescription for lawful possession and use.

SpainPrescription onlyPsicótropos

AEMPS CIMA marketing-authorisation record for LORAZEPAM CINFA 1 mg COMPRIMIDOS EFG⁵⁶⁵⁷

The Spanish Agency of Medicines and Medical Devices (AEMPS) records LORAZEPAM CINFA 1 mg COMPRIMIDOS EFG as an active marketed medicine subject to medical prescription and classified as a psychotropic medicine. The record identifies lorazepam as the active substance and marks the product as prescription-required.

TurkeyGreen prescription only

Requires a 'green prescription' (special controlled substance prescription). Possession or sale without valid prescription is prohibited.

United KingdomPrescription onlyClass C

Misuse of Drugs Act 1971 and Misuse of Drugs Regulations 2001⁶²⁶³

Under the Misuse of Drugs Act 1971, lorazepam is classified as a Class C drug.⁶⁴ The Misuse of Drugs Regulations 2001 place it in Schedule IV, Part I as a CD Benz POM,⁶⁵ with possession allowed when there is a valid prescription.

ArgentinaPrescription onlyLista IV

Law No. 19.303 and ANMAT special-control medicines register¹⁴¹⁵¹⁶

Lorazepam is a Lista IV psychotropic substance under Argentina's special-control medicines regime. Law No. 19.303 requires dispensing of Lista III and Lista IV psychotropic substances on a retained prescription, and ANMAT's registered-product listings identify lorazepam products as sold under retained prescription.

BrazilPrescription onlyLista B1

Portaria SVS/MS No. 344/1998²¹

Lorazepam is listed in Brazil's List B1 of psychotropic substances subject to prescription notification. Its dispensing is regulated under the controlled-medicines rules.

ChinaPrescription onlyCategory II

Catalogue of Medicinal Psychotropic Substances²⁵²⁶²⁷

Regulated as a Class II psychotropic substance under national drug control laws. Prescriptions are generally limited to a seven-day supply.

FrancePrescription onlyListe I

ANSM public medicines database record for LORAZEPAM VIATRIS 1 mg, comprimé pelliculé sécable³¹³²

The ANSM public medicines database records LORAZEPAM VIATRIS 1 mg as containing lorazepam and classifies the authorised medicine in Liste I. The current record states that its prescription is limited to 12 weeks. The medicine is therefore supplied under France's prescription-only regime for Liste I medicines.

IrelandPrescription onlySchedule 4

Misuse of Drugs Regulations 2017³⁶

Lorazepam is listed in Schedule 4, Part 1 of the Misuse of Drugs Regulations. Its supply and possession are regulated as a controlled drug, with lawful medical supply through the prescription system.

NetherlandsPrescription onlyLijst II

Opiumwet and Opiumwetbesluit³⁸³⁹⁴⁰

Lorazepam is listed in Lijst II of the Dutch Opiumwet. The current Opiumwetbesluit places the substances on Lijst II, other than hashish, in its prescription annex and requires established pharmacists to dispense opium-law medicines only on a prescription. Netherlands-authorised medicines classified UR are available only on prescription.

PhilippinesPrescription onlySchedule IV psychotropic substance

Republic Act No. 9165 (Comprehensive Dangerous Drugs Act of 2002), sections 5, 18, 19 and 40; Schedule IV⁴³⁴⁴⁴⁵

The Dangerous Drugs Board-hosted text of RA 9165 lists lorazepam in the Act's Schedule IV. Section 5 makes sale, administration and dispensation of a dangerous drug unlawful unless authorised by law; section 40 prescribes the required three-copy prescription process for dangerous drugs, while sections 18 and 19 regulate prescriptions for such drugs. This supports prescription-only lawful medical supply; it does not support the prior erroneous Schedule II designation.

PortugalPrescription onlyPrescrição obrigatória

INFARMED list of active substances subject to mandatory prescription⁴⁸⁴⁹⁵⁰

Lorazepam is included in INFARMED's list of active substances subject to mandatory prescription. INFARMED states that medicines subject to medical prescription may be dispensed by pharmacies only on presentation of a prescription issued by an authorized prescriber. Current INFARMED medicine records list authorised lorazepam products.

SingaporePrescription onlyThird Schedule

Poisons Rules⁵³⁵⁴⁵⁵

Lorazepam is listed in the Third Schedule to Singapore's Poisons Rules. Rule 15 provides that a poison in that Schedule may be sold only on and in accordance with a prescription given by a medical practitioner, dentist or veterinary surgeon. Lorazepam is therefore supplied through the prescription-only medicines regime.

SwitzerlandPrescription onlyVerzeichnis b

Betäubungsmittelverzeichnisverordnung⁵⁸⁵⁹

Specifically named as a controlled substance under Verzeichnis B of Swiss narcotics legislation. Medicinal use is permitted with appropriate authorization.

UkrainePrescription onlyTable III

Cabinet of Ministers Resolution No. 770 and Law of Ukraine No. 60/95-VR⁶⁰⁶¹

Lorazepam is listed in Table III of the Ukrainian list of narcotic drugs, psychotropic substances and precursors approved by Cabinet of Ministers Resolution No. 770. The Law of Ukraine on narcotic drugs, psychotropic substances and precursors provides that citizens may acquire narcotic drugs or psychotropic substances included in Tables II and III only on a doctor's prescription. Lorazepam is therefore available only through the prescription-controlled medical system.

References

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Citations

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Lorazepam

Ativan, Temesta, Tavor, Orfidal, Lorsilan

Psychoactive Class

Depressant Anxiolytic Sedative GABAergic Muscle Relaxant

Chemical Class

Benzodiazepine