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

It is strongly discouraged to consume moderate to heavy dosages of these substances together.


This page has not been approved by the PsychonautWiki administrators.

It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks.

The structure of barbituric acid

Barbiturates (also known as barbs and barbies) are a class of psychoactive substances that act as depressants of the central nervous system. They produce a variety of sedative-hypnotic effects including sedation, anxiety suppression, muscle relaxation, and seizure suppression when administered.

Barbiturates have been largely replaced by benzodiazepines in routine medical practice, generally because benzodiazepines have lower toxicity compared to barbiturates. However, they are still used today for limited medical purposes, particularly as general anesthetics.

It is worth noting that the sudden discontinuation of barbiturates can be dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.[2]


Barbiturates are based on the barbituric acid molecule. Commonly, two hydrocarbon substitutions are present at carbon R5. of the pyrimidine ring. It also contains three double-bonded oxygen substitutions at R2, R4 and R6.


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This pharmacology section is incomplete.

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Barbiturates act as positive allosteric modulators, and at higher doses, as agonists of GABAA receptors.[1a] GABA is the principal inhibitory neurotransmitter in the mammalian central nervous system (CNS). Barbiturates bind to the GABAA receptor at multiple homologous transmembrane pockets located at subunit interfaces,[2a] which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABAergic effect, barbiturates also block AMPA and kainate receptors, subtypes of ionotropic glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABAA receptors and inhibit excitatory AMPA receptors can explain the superior CNS-depressant effects of these agents to alternative GABA potentiating agents such as benzodiazepines and quinazolinones. At higher concentration, they inhibit the Ca2+-dependent release of neurotransmitters such as glutamate via an effect on P/Q-type voltage-dependent calcium channels.[3a] Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.[4a][5a]

Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. This superfamily of ion channels includes the neuronal nACh receptor channel, the 5-HT3 receptor channel, and the glycine receptor channel. However, while GABAA receptor currents are increased by barbiturates (and other general anaesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR channels are blocked by clinically relevant anaesthetic concentrations of both thiopental and pentobarbital.[6a] Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.[7a] This is the mechanism responsible for the (mild to moderate) anesthetic effect of barbiturates in high doses when used in anesthetic concentration.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death. These effects are listed and defined in detail within their own dedicated articles below:

Physical effects

Paradoxical effects

Cognitive effects

Toxicity and harm potential


This toxicity and harm potential section is a stub.

As such, it may contain incomplete or even dangerously wrong information. You can help by expanding or correcting it.
We also recommend that you conduct independent research and use harm reduction practices when using this substance.

Barbiturates are toxic at higher dosages.[citation needed] Barbiturates have a greater addiction potential than benzodiazepines. Overdose can be achieved much more easily with barbiturates than with benzodiazepines. Some barbiturates, such as phenobarbital, have been linked to the development of cancer. Using barbiturates concurrently with other depressants can be considered extremely dangerous even when taken in lower doses, and may lead to severe negative side effects such as respiratory depression, coma, and death.[citation needed]

Tolerance and addiction potential

Barbiturates can be considered extremely physically and psychologically addictive. Shorter-acting barbiturates are significantly more addictive than longer-acting barbiturates.[citation needed]

Tolerance will develop to the sedative-hypnotic, anxiolytic, and euphoric effects of barbiturates after prolonged use.[citation needed] It is unknown exactly how long it takes for tolerance to reach baseline after continued use. All barbiturates present cross tolerance with each other, meaning that tolerance to one barbiturate will lead to tolerance of all other barbiturates.


Barbiturate withdrawal is a medically serious condition and can potentially cause life-threatening withdrawal symptoms such as seizures, psychosis, and death.[citation needed] Drugs which lower the seizure threshold such as tramadol and amphetamine should be avoided during withdrawal. If an individual is addicted to a shorter-acting barbiturate such as pentobarbital, switching to a longer-acting barbiturate such as phenobarbital may prove beneficial.[citation needed]


Barbiturate overdose may occur when a barbiturate is taken in extremely heavy quantities or concurrently with other depressants. Combining barbiturates with other GABAergic depressants such as benzodiazepines and alcohol is particularly dangerous because they all work in a similar fashion but bind to distinct allosteric sites on the GABAA receptor, thus potentiating one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABAA receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer[3]. Barbiturate overdose is a medical emergency that is commonly known to induce coma, permanent brain injury, and death if it is not treated promptly by medical professionals. Barbiturate overdose has an increased frequency of serious adverse effects when compared to other depressants.[citation needed]

Symptoms of a barbiturate overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death[4].

See also

External links


Löscher, W.; Rogawski, M. A. (2012). "How theories evolved concerning the mechanism of action of barbiturates". Epilepsia. 53: 12–25. doi:10.1111/epi.12025. PMID 23205959.
Chiara, D. C.; Jayakar, S. S.; Zhou, X.; Zhang, X.; Savechenkov, P. Y.; Bruzik, K. S.; Miller, K. W.; Cohen, J. B. (15 May 2013). "Specificity of Intersubunit General Anesthetic-binding Sites in the Transmembrane Domain of the Human α1β3γ2 γ-Aminobutyric Acid Type A (GABAA) Receptor". Journal of Biological Chemistry. 288 (27): 19343–19357. doi:10.1074/jbc.M113.479725. PMC 3707639 Freely accessible. PMID 23677991.
Brunton, Laurence L.; Lazo, John S.; Parker, Keith L.; Goodman, Louis Sanford; Gilman, Alfred Goodman (2005). Goodman & Gilman's Pharmacological Basis of Therapeutics. McGraw-Hill. ISBN 0-07-142280-3.
Neil Harrison; Wallace B Mendelson; Harriet de Wit (2000). "Barbiturates". Neuropsychopharmacology. Retrieved 15 July 2008. ...Barbiturates therefore promote entry of GABA-activated channels into a long-lived open state, whereas [benzodiazepines] increase only the frequency of channel opening into the initial open state. These mechanistic studies reveal interesting details of the changes in channel gating caused by barbiturates but as yet have yielded no insights into the molecular sites of action. An additional interesting effect of barbiturates is direct gating of the channels, i.e., the barbiturates may open the channel even in the absence of GABA. This usually occurs at significantly higher concentrations than those that potentiate the actions of GABA; these concentrations also are generally higher than those required for clinically effective anesthesia.
Siegel, George J.; Bernard W. Agranoff; Stephen K. Fisher; R. Wayne Albers; Michael D. Uhler (1999) [1998]. "Part 2 Chapter 16". Basic Neurochemistry - Molecular, Cellular and Medical Aspects (Sixth ed.). Lippincott Williams and Wilkins. ISBN 0-397-51820-X. Retrieved July 2008. Check date values in: |accessdate= (help)
Weber, M; Motin, L; Gaul, S; Beker, F; Fink, RH; Adams, DJ (January 2005). "Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons". British Journal of Pharmacology. 144 (1): 98–107. doi:10.1038/sj.bjp.0705942. PMC 1575970 Freely accessible. PMID 15644873.
Franks, NP; Lieb, WR (23 November 1998). "Which molecular targets are most relevant to general anaesthesia?". Toxicology Letters. 100–101: 1–8. doi:10.1016/S0378-4274(98)00158-1. PMID 10049127.
  1. Risks of Combining Depressants (Tripsit) |
  2. Barbiturate withdrawal effects |
  3. Barbiturates and benzodiazepine effects |
  4. Barbiturate Overdose |