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Pentobarbital

Pentobarbital molecule structurePentobarbital molecule structure
5-Ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
Pentobarbitone, Nembutal, Yellow Jackets
Chemical Class
Barbiturate

Pentobarbital is a short-acting barbiturate1 that produces potent sedative, hypnotic, anxiolytic, muscle relaxant, and amnesic effects. It is used medically for the short-term treatment of insomnia,1 as an emergency anticonvulsant,1 and to induce medical comas.2 Pentobarbital acts on GABA-A receptors at a distinct allosteric site from benzodiazepinescitation needed and is characterized by a relatively prompt onset of action. It is classified as habit-forming1 and is internationally scheduled as a controlled substance.citation needed

Dosage & Duration

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~25 mg
Light25-100 mg
Moderate100-200 mg
Strong200-300 mg
Heavy300+ mg
Bioavailability
70-90%

Duration

Onset15-60 minutes
Peak1-3 hours
Offset1-2 hours
After Effects1-36 hours
Total4-6 hours
Half-life
5-50 hours

Subjective Effects

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

The experience is dominated by heavy central nervous system depression, producing drowsiness, relief of tension and nervousness, and an intoxication broadly comparable to alcohol in character. Unlike opioids, pentobarbital provides little pain relief, and its use in the presence of significant pain can paradoxically result in excitation rather than calm. As the dose climbs, coordination, speech, and judgment deteriorate progressively, and at overdose levels the state shades into stupor, coma, and dangerously shallow breathing.

Physical

The body feels heavy, relaxed, and sedated, with incoordination and a staggering gait emerging as doses increase. Breathing becomes shallow at high doses, which is the primary driver of its overdose lethality.

Dangerous

Impairment

Sedation

Cognitive

The headspace is slowed and clouded, with sluggish thinking, impaired judgment, and a marked reduction in anxiety and tension. Recall of the period under the drug's influence becomes unreliable at higher doses.

Suppressions

Disinhibition

Pharmacology

Pharmacodynamics

Pentobarbital acts primarily as a positive allosteric modulator of the GABA-A receptor, binding at the barbiturate site to prolong the duration of chloride ion channel opening.citation needed At higher concentrations, it is capable of directly activating the channel in the absence of GABA.3 This potentiation of GABAergic inhibitory tone is associated with marked decreases in GABA-sensitive neuronal calcium conductance. Pentobarbital also directly inhibits excitatory AMPA-type glutamate receptors, suppressing glutamatergic neurotransmission,4 and acts as an antagonist at NMDA receptors, kainate receptors, and neuronal nicotinic acetylcholine receptors (α4 and α7 subunits).citation needed

Pharmacokinetics

Pentobarbital undergoes first-pass metabolism in the liver and possibly the intestines via the hepatic microsomal enzyme system, with subsequent renal excretion.citation needed Oral bioavailability is approximately 70-90%, with 45-60% protein binding. The elimination half-life is dose-dependent, ranging from 5 to 50 hours.

Metabolitesnone documented yet

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.

DissociativesStimulants

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.

1,2-BenzodiazepineAbacavirAbaloparatideAbataceptAbemaciclib
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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-hypnotic effects develops after prolonged use. Clinical observations indicate that pentobarbital may lose its effectiveness for sleep induction by the second week of continued administration.
Cross Tolerance

Barbiturates

Baseline Reset
The exact duration required for tolerance to return to baseline is unknown.

Harm Potential

Addiction & Dependence

Psychological

Extremely High

Pentobarbital is deemed extremely psychologically addictive, with compulsive redosing commonly reported.citation needed Short-acting barbiturates carry particularly high abuse potential, and the substance was widely abused beginning in the late 1930s.

Physical

Extremely High

Pentobarbital produces severe physical dependence with chronic use.citation needed Barbiturate withdrawal is medically serious and can cause a life-threatening syndrome including seizures, psychosis, and death with abrupt discontinuation.

Toxicity

Respiratory

Respiratory depression is the primary acute toxicity and can progress to respiratory arrest and death, particularly at higher doses or when combined with other CNS depressants.citation needed

Carcinogenicity
Possible

Studies have linked barbiturate use with the development of cancer,citation needed though phenobarbital has been particularly implicated; evidence specific to pentobarbital is limited.

Psychosis Risk

Psychosis may occur as part of the life-threatening barbiturate withdrawal syndrome in dependent individuals.citation needed During intoxication, delusions of sobriety are reported at heavy doses, representing impaired reality testing rather than true psychosis.

Seizure Risk

Pentobarbital has anticonvulsant properties and suppresses seizures during use. However, abrupt discontinuation in dependent individuals may cause potentially fatal seizures as part of the withdrawal syndrome.citation needed Drugs that lower seizure threshold should be avoided during withdrawal.

History & Culture

Discovery and Development

Pentobarbital was developed by chemists Ernest H. Volwiler and Donalee L. Tabern at Abbott Laboratories in 1930.5 That same year, physician John S. Lundy began clinical use of the compound and coined the brand name Nembutal, an amalgamation derived from the

Legality

International

UN Convention on Psychotropic Substances 1971 (Schedule III)

By Country

Illegal1
Switzerland flagSwitzerlandIllegal
Controlled / restricted5
United States flagUnited StatesRestricted
Canada flagCanadaRestricted
Germany flagGermanyRestricted
Russia flagRussiaRestricted
United Kingdom flagUnited KingdomClass B
Prescription1
Australia flagAustraliaPrescription only

References

Source Pages

  1. DanceSafe: Harm Reduction Resources
  2. DrugBank
  3. Erowid: Barbiturates Vault
  4. Erowid: Pentobarbital Experience Reports
  5. Isomer Design (TiHKAL/PiHKAL)
  6. PsychonautWiki
  7. PsychonautWiki: Dangerous Combinations Chart
  8. TripSit Factsheets
  9. TripSit: Combination Chart
  10. TripSit: Wiki Drug Combinations
  11. Wikipedia

Citations

  1. Nembutal sodium- pentobarbital sodium injection. DailyMed (31 December 2016). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c380ab0-4386-48b6-80ab-ca594b23bc7412345
  2. Pentobarbital - StatPearls. NCBI Bookshelf (n.d.). https://www.ncbi.nlm.nih.gov/books/NBK545288/1
  3. Pentobarbital Produces Activation and Block of α1β2γ2S GABAA Receptors in Rapidly Perfused Whole Cells and Membrane Patches. PMC / Journal of General Physiology (n.d.). https://pmc.ncbi.nlm.nih.gov/articles/PMC2638204/1
  4. Barbiturates. ACNP: Fifth Generation of Progress (n.d.). https://www.acnp.org/g4/GN401000173/CH169.html1
  5. The history of barbiturates a century after their clinical introduction. Neuropsychiatric Disease and Treatment (n.d.). https://pmc.ncbi.nlm.nih.gov/articles/PMC2424120/1
  6. Kathleen Cooney, & Lianna Titcombe. (February 2022). Lessons and Recommendations from a Pentobarbital Shortage: US and Canada 2021. Animals, 12(3), 365. https://doi.org/10.3390/ani120303651
  7. Lethal Injection: Ohio Carries Out First Pentobarbital-Only Execution. Death Penalty Information Center (n.d.). https://deathpenaltyinfo.org/lethal-injection-ohio-carries-out-first-pentobarbital-only-execution1
  8. Texas Will Change Its Lethal Injection Protocol. The Texas Tribune (2012). https://www.texastribune.org/2012/07/10/texas-changing-its-lethal-injection-protocol/1
  9. Therapeutic Goods (Poisons Standard—June 2026) Instrument 2026 - Federal Register of Legislation. legislation.gov.au (n.d.). https://www.legislation.gov.au/F2026L00633/latest/details1
  10. Therapeutic Goods (Poisons Standard—June 2026) Instrument 2026. legislation.gov.au (n.d.). https://www.legislation.gov.au/F2026L00633/asmade/2026-05-28/text/original/epub/OEBPS/document_1/document_1.html1

Further Reading

  1. RollSafe Drug Harm Reduction Guide

Article Status

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Recent changes8 human edits · latest

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21 August 2026

  1. Lyrea · Changed a word in Dosage & Duration › Routes 1 › Dose ranges › Threshold

  2. Lyrea · Reworded 2 words in Pharmacology › Pharmacokinetics

  3. Lyrea · Updated the article

  4. Lyrea · Changed a word in Dosage & Duration › Routes 3 › Dose ranges › Heavy

  5. Lyrea · Changed a word in Dosage & Duration › Routes 3 › Dose ranges › Light

  6. Lyrea · Changed a word in Dosage & Duration › Routes 3 › Dose ranges › Light

24 January 2026

  1. Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more

  2. Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more

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