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Fatal overdose may occur when benzodiazepines are combined with other depressants such as opiates, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.[1]

It is strongly discouraged to combine these substances, particularly in common to heavy doses.


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It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks. It may also not meet PW style and grammar standards.

Summary sheet: Midazolam
Chemical Nomenclature
Common names Midazolam, Versed
Substitutive name Midazolam
Systematic name 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine
Class Membership
Psychoactive class Depressant
Chemical class Benzodiazepine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.

Bioavailability 40%
Threshold 1 mg
Light 2.5 - 5 mg
Common 5 - 15 mg
Strong 15 - 30 mg
Heavy 30 mg +
Total 2 - 4 hours
Onset 30 - 60 minutes
Come up 30 - 60 minutes
Peak 1 - 2 hours
Offset 1 - 2 hours

Threshold 1 mg
Light 1 - 2 mg
Common 2 - 4 mg
Strong 4 - 5 mg
Heavy 5 mg +
Total 2 - 6 hours
Onset 5 minutes
Peak 1 - 4 hours
Offset 1 hour

DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.


Midazolam (trade name Versed) is a depressant substance of the benzodiazepine class. It acts as a GABA receptor agonist.

Midazolam was patented in 1974 and was adopted for medical use in 1982.[2] It is used for anesthesia, procedural sedation, trouble sleeping, seizures, and severe agitation.[3] It is on the World Health Organization's List of Essential Medicines.[4]

Subjective effects include sedation, anxiety suppression, disinhibition, muscle relaxation, respiratory depression, and moderate euphoria. It can be administered orally, intravenously, or by injection into a muscle.

Additionally, it should be noted that the sudden discontinuation of benzodiazepines can be dangerous or even life-threatening for individuals for heavy or long-term users. As a result, individuals who are physically dependent on this substance are advised to taper their dose by gradually lowering the amount taken each day over a prolonged period instead of stopping use abruptly.[5]

It is strongly advised to use harm reduction practices if using this substance.



This chemistry section is incomplete.

You can help by adding to it.

Midazolam Hydrochloride is the hydrochloride salt of the short-acting benzodiazepine derivative with an imidazole core structure, making it an imidazobenzodiazepine. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. The pK of midazolam is 6.15, which permits the preparations of salts to be water soluble. The parenteral solution of midazolam used clinically is buffered to an acidic pH of 3.5.[6]


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This pharmacology section is incomplete.

You can help by adding to it.

Midazolam is a short-acting benzodiazepine in adults with an elimination half-life of 1.5–2.5 hours.[7] Midazolam is metabolised into an active metabolite alpha1-hydroxymidazolam. However, the active metabolite of midazolam is minor and contributes to only 10 percent of biological activity of midazolam. Midazolam is poorly absorbed orally, with only 50 percent of the drug reaching the bloodstream.[8]

Midazolam is metabolized by cytochrome P450 (CYP) enzymes and by glucuronide conjugation. The therapeutic and adverse effects of midazolam are a result of its effects on the GABAA receptors; midazolam does not activate GABAA receptors directly but, as with other benzodiazepines, it enhances the effect of the neurotransmitter GABA on the GABAA receptors (↑ frequency of Cl− channel opening) resulting in neural inhibition. Almost all of the pharmacokinetic properties can be explained by the actions of benzodiazepines on GABAA receptors.

Subjective effects

People experiencing amnesia as a side effect of midazolam are generally unaware their memory is impaired, unless they had previously known it as a side effect.[9]Long-term use of benzodiazepines has been associated with long-lasting deficits of memory, and show only partial recovery six months after stopping benzodiazepines. It is unclear whether full recovery occurs after longer periods of abstinence. Benzodiazepines can cause or worsen depression. Paradoxical excitement occasionally occurs with benzodiazepines, including a worsening of seizures.[9]

Toxicity and harm potential


This toxicity and harm potential section is a stub.

As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
Note: Always conduct independent research and use harm reduction practices if using this substance.

Dependence and abuse potential

Benzodiazepine dependence occurs in about one-third of individuals who are treated with benzodiazepines for longer than 4 weeks, which typically results in tolerance and benzodiazepine withdrawal syndrome when the dose is reduced too rapidly. Midazolam infusions may induce tolerance and a withdrawal syndrome in a matter of days.

The risk factors for dependence include dependent personality, use of a benzodiazepine that is short-acting, high potency and long-term use of benzodiazepines. Withdrawal symptoms from midazolam can range from insomnia and anxiety to seizures and psychosis. Withdrawal symptoms can sometimes resemble a person's underlying condition.

Gradual reduction of midazolam after regular use can minimise withdrawal and rebound effects. Tolerance and the resultant withdrawal syndrome may be due to receptor down-regulation and GABAA receptor alterations in gene expression, which causes long-term changes in the function of the GABAergic neuronal system.[8]


A midazolam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. Benzodiazepine overdose in healthy individuals is rarely life-threatening with proper medical support; however, the toxicity of benzodiazepines increases when they are combined with other CNS depressants such as alcohol, opioids, or tricyclic antidepressants. The toxicity of benzodiazepine overdose and risk of death is also increased in the elderly and those with obstructive pulmonary disease or when used intravenously.

Dangerous interactions

Protease inhibitors, nefazodone, sertraline, grapefruit, fluoxetine, erythromycin, diltiazem, clarithromycin inhibit the metabolism of midazolam, leading to a prolonged action. St John's wort, rifapentine, rifampin, rifabutin, phenytoin enhance the metabolism of midazolam leading to a reduced action. Sedating antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opioids, antipsychotics and alcohol enhance the sedative effects of midazolam.[8]

St John's wort decreases the blood levels of midazolam. Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations.

Legal status


This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

  • Sweden: Midazolam is a prescription only medication.
  • Brazil: Midazolam is a prescription only medication.
  • United States: Midazolam is a Schedule IV substance.[citation needed]

See also

External links


  1. Risks of Combining Depressants - TripSit 
  2. Fischer, J., Ganellin, C. R. (2006). Analogue-based drug discovery. Wiley-VCH. ISBN 9783527607495. 
  3. "Midazolam Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 5 September 2015.
  4. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  5. Kahan, M., Wilson, L., Mailis-Gagnon, A., Srivastava, A. (November 2011). "Canadian guideline for safe and effective use of opioids for chronic noncancer pain. Appendix B-6: Benzodiazepine Tapering". Canadian Family Physician. 57 (11): 1269–1276. ISSN 0008-350X. 
  6. Basu, S., Bandyopadhyay, A. K. (September 2010). "Development and Characterization of Mucoadhesive In Situ Nasal Gel of Midazolam Prepared with Ficus carica Mucilage". AAPS PharmSciTech. 11 (3): 1223–1231. doi:10.1208/s12249-010-9477-x. ISSN 1530-9932. 
  7. "Midazolam Injection" (PDF). Medsafe. New Zealand Ministry of Health. 26 October 2012. Archived from the original (PDF) on 22 February 2016.
  8. 8.0 8.1 8.2 Riss, J., Cloyd, J., Gates, J., Collins, S. (August 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics". Acta Neurologica Scandinavica. 118 (2): 69–86. doi:10.1111/j.1600-0404.2008.01004.x. ISSN 0001-6314. 
  9. 9.0 9.1 Merritt, P., Hirshman, E., Hsu, J., Berrigan, M. (January 2005). "Metamemory without the memory: are people aware of midazolam-induced amnesia?". Psychopharmacology. 177 (3): 336–343. doi:10.1007/s00213-004-1958-8. ISSN 0033-3158.