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Delorazepam

Delorazepam molecule structureDelorazepam molecule structure
Delorazepam
Chlordesmethyldiazepam, Nordiclazepam, EN, Dadumir
Chemical Class
Benzodiazepine

Delorazepam is a benzodiazepine derivative of desmethyldiazepam, primarily used in the treatment of anxiety disorderscitation needed and alcohol withdrawal.1 It is marketed in Italy and is notable for its exceptionally long half-life of 60 to 140 hours.citation needed Delorazepam also serves as an active metabolite of both diclazepam2 and cloxazolam.3 Like other benzodiazepines, it possesses anxiolytic, muscle relaxant, hypnotic, and anticonvulsant properties,citation needed and carries a risk of dependence with repeated use.4

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~0.25 mg
Light0.25-0.5 mg
Moderate0.5-1.5 mg
Strong1.5-2 mg
Heavy2+ mg
Bioavailability
~77%

Delorazepam is approximately ten times more potent than diazepam on a milligram-per-milligram basis. The risk of memory impairment and amnestic blackouts increases significantly at higher doses.

Duration

Onset30-60 minutes
After Effects72 hours
Total12-16 hours
Half-life
80-115 hours

Subjective Effects

Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.

The experience is dominated by anxiety relief, sedation, and muscle relaxation, following the classic profile of a long-acting benzodiazepine with hypnotic and anticonvulsant properties. Disinhibition, increased talkativeness, and mild euphoria can accompany the calm, while memory formation becomes unreliable at higher doses. Due to its long duration of action, residual hangover-type drowsiness and impairment can persist well after the main effects subside.

Physical

The body feels heavy, relaxed, and sedated, with skeletal muscle relaxation, dizziness, and unsteady, uncoordinated movement. Respiratory depression becomes a concern at high doses or in combination with other depressants.

Impairment

Dizziness

Sedation

Cognitive

The headspace is calm and disinhibited, with suppressed anxiety, impaired judgement, and pronounced short-term memory impairment. Paradoxical reactions of increased anxiety, excitation, or aggression can occur, particularly in elderly, pediatric, and schizophrenic users, and depressive symptoms may emerge with continued use.

Emotional

Euphoria

Suppressions

Pharmacology

Pharmacodynamics

Delorazepam acts as a positive allosteric modulator at the GABA-A receptor, binding at the benzodiazepine site.citation needed This enhances the inhibitory signaling of GABA, producing the anxiolytic, sedative, and muscle relaxant properties characteristic of benzodiazepines.

Pharmacokinetics

Delorazepam is well absorbed after oral administration, reaching peak plasma levels within 1 to 2 hours, with a bioavailability of approximately 77%.citation needed It undergoes slow hepatic metabolism, producing lorazepam as an active metabolite that represents about 15 to 24 percent of the parent compound. The elimination half-life is reported as 80 to 115 hours, though one study found an average of 204 hours in healthy patients.5 Significant accumulation occurs with repeated dosing due to this slow metabolism.citation needed The elderly metabolize delorazepam and its active metabolite more slowly than younger individuals; liver disease profoundly extends the half-life, with one report showing values reaching approximately 395 hours.5 Delorazepam is itself an active metabolite of both diclazepam and cloxazolam.

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
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Tolerance

Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.

Full Tolerance
Tolerance to the sedative and anxiolytic effects develops with repeated use, as is characteristic of benzodiazepines. Due to the exceptionally long half-life of delorazepam, tolerance may develop more gradually compared to shorter-acting benzodiazepines, though accumulation with repeated dosing can complicate this pattern.
Cross Tolerance

Benzodiazepines, GABAergic depressants (barbiturates, alcohol, GHB/GBL), Z-drugs (zopiclone, zolpidem, zaleplon)

Harm Potential

Addiction & Dependence

Psychological

Moderate

Delorazepam is classified as habit-forming with recognized abuse potential.citation needed Patients with a history of substance or alcohol use are believed to have an increased risk of abuse. Non-medical use in prescribed patients has been documented and generally develops slowly, becoming evident only after months or years of therapy.

Physical

Extremely High

Physical dependence is the most serious effect of long-term use, with withdrawal symptoms that mimic delirium tremens.citation needed Although withdrawal effects are generally less severe than shorter-acting benzodiazepines, they can be life-threatening. Slow tapering over weeks or months is recommended to minimize withdrawal severity. Psychological effects such as rebound anxiety and insomnia may persist for months after physical dependence has been treated.

Toxicity

Central Nervous System

Long-term use has been associated with cognitive deficits that may persist longer than six months, with some researchers suggesting these effects could be permanent;6 short-term use carries minimal risk of lasting cognitive impairment.

Psychosis Risk

Paradoxical reactions including increased anxiety, excitation, aggression, and hallucinations may occur but are uncommon. These reactions are more frequent in elderly, pediatric, and schizophrenic patients.citation needed In rare instances, delorazepam may cause suicidal ideation and actions.4 Contraindicated in patients with severe schizophrenia or schizo-affective disorders.

History & Culture

Delorazepam is an uncommon benzodiazepine that has been marketed primarily in Italy, where it is available under the trade name EN.citation needed The compound is notable for its relationship to other benzodiazepines in this class, serving as an active metabolite of both…

Legality

By Country

Illegal3
Finland flagFinlandIllegal
Netherlands flagNetherlandsIllegal
New Zealand flagNew ZealandIllegal
Controlled / restricted10
Australia flagAustraliaRestricted
Belgium flagBelgiumRestricted
Colombia flagColombiaRestricted
France flagFranceRestricted
India flagIndiaRestricted
Ireland flagIrelandRestricted
Japan flagJapanRestricted
Norway flagNorwayRestricted
Singapore flagSingaporeRestricted
United Kingdom flagUnited KingdomRestricted
Prescription11
United States flagUnited StatesPrescription only
Brazil flagBrazilPrescription only
Canada flagCanadaPrescription only
Chile flagChilePrescription only
Denmark flagDenmarkPrescription only
Philippines flagPhilippinesPrescription only
Poland flagPolandPrescription only
Portugal flagPortugalPrescription only
Spain flagSpainPrescription only
Thailand flagThailandPrescription only
Ukraine flagUkrainePrescription only

References

Source Pages

  1. Delorazepam - DrugBank Online
  2. Dextro.45. '5 Days Trip, No Benzos - interesting outcome' (experience report) Bluelight.org, 2023-06-18
  3. PsychonautWiki: Benzodiazepines
  4. Wikipedia

Citations

  1. Cazzato G, Gioseffi M, Torre P, & Coppola N. (Nov–Dec 1982). [Prevention and therapy of delirium tremens with tiapride and chlordesmethyldiazepam]. Rivista di Neurologia, 52(6), 331–42. https://pubmed.ncbi.nlm.nih.gov/6130594/1
  2. WHO Expert Committee on Drug Dependence. (2020). Critical Review Report: Diclazepam. World Health Organization. https://cdn.who.int/media/docs/default-source/controlled-substances/43rd-ecdd/final-diclazepam-a.pdf12
  3. Diogo Oliveira-Silva, Celso H. Oliveira, Gustavo D. Mendes, Paulo Alexandre R. Galvinas, Rafael E. Barrientos-Astigarraga, & Gilberto De Nucci. (December 2009). Quantification of chlordesmethyldiazepam by liquid chromatography-tandem mass spectrometry: application to a cloxazolam bioequivalence study. Biomedical Chromatography, 23(12), 1266–75. https://doi.org/10.1002/bmc.124912
  4. EN (Delorazepam) – Scheda Tecnica e Prescrivibilità. (n.d.). https://www.torrinomedica.it/schede-farmaci/en/12
  5. S.R. Bareggi, R. Pirola, P. Potvin, & G. Devis. (1995). Effects of liver disease on the pharmacokinetics of intravenous and oral chlordesmethyldiazepam. European Journal of Clinical Pharmacology, 48(3–4), 265–8. https://doi.org/10.1007/bf00198309123
  6. Barker MJ, Greenwood KM, Jackson M, & Crowe SF. (2004). Persistence of cognitive effects after withdrawal from long-term benzodiazepine use: a meta-analysis. Archives of Clinical Neuropsychology, 19(3), 437–454. https://pubmed.ncbi.nlm.nih.gov/15033227/1
  7. Customs (Prohibited Imports) Regulations 1956, Schedule 4 (Drugs). legislation.gov.au (n.d.). https://www.legislation.gov.au/F1996B03651/2026-03-26/2026-03-26/text/original/epub/OEBPS/document_1/document_1.html1
  8. Royal Decree of 6 September 2017 regulating narcotic drugs and psychotropic substances, Annex III. famhp.be (n.d.). https://www.famhp.be/sites/default/files/content/INSP/NARC/annex%20III_non%20official%20consolidated%20version.pdf1
  9. Royal Decree of 6 September 2017 regulating narcotic drugs and psychotropic substances, Annex III. etaamb.openjustice.be (n.d.). https://etaamb.openjustice.be/fr/arrete-royal-du-06-septembre-2017_n2017031231.html1
  10. Royal Decree of 6 September 2017 regulating narcotic drugs and psychotropic substances, Annex III. afmps.be (n.d.). https://www.afmps.be/fr/humain/produits_particuliers/subst_specialement_reglementees/stupefiants_et_psychotropes/substances1

Further Reading

  1. Albani et al. Pharmacokinetics of delorazepam after single and repeated oral doses. Eur J Clin Pharmacol 1983;25(1):101-6
  2. Delorazepam - PubChem (NIST)
  3. Delorazepam - Tripsitter Harm Reduction Guide
  4. Italian SPC - EN (delorazepam) 0.5 mg tablets, Chiesi Farmaceutici
  5. PubChem: Compound Summary for CID 4179 (Delorazepam)

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