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Principles of Health: Pain Management

Barbiturates

by Mihaela Avramut, , MD, PhD, Bryan C. Auday, , PhD

CATEGORY: Class of Drug

ANATOMY OR SYSTEM AFFECTED: Central nervous system

History of Use

In 1903, Emil Fischer and Joseph von Mering discovered an effective sedative, diethylbarbituric acid or barbital, which entered medicine under the trade name Veronal. Another barbiturate, phenobarbital (Luminal), was introduced in 1912 and continues to be used as an anticonvulsant. By the mid-twentieth century, barbiturates became the most widely used sedative-hypnotic medication and the most popular substances of misuse. Collectively referred to as “downers” because they were effective in depressing the central nervous system, barbiturates were taken alone or with alcohol (ethanol) to produce a feeling of relaxation and euphoria. In the United States, barbiturate misuse and addiction markedly increased in the 1950s and 1960s. The drugs became especially popular with people who experienced high levels of stress, anxiety, or panic attacks.

The beginning of the twenty-first century saw a modest increase in usage of barbiturates as substances of misuse. Some drug specialists attribute this increase to the desire of drug users to seek out the relaxing, calming, and disinhibiting effects of barbiturates as a means to counteract stimulant drugs such as cocaine and methamphetamines. According to a national survey on drug use and health by the US Substance Abuse and Mental Health Services Administration, an estimated 3.1 million people (approximately 9%) age twelve years and older had misused barbiturates.

Barbituric acid, the parent structure of all barbiturates. (Manuel Almagro Rivas via Wikimedia Commons)

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Barbiturates today are used clinically for treatment of seizures that last longer than five minutes or occur close together before a person regains consciousness (status epilepticus). Barbiturates are also used for anesthesia, pediatric sedation, migraines and insomnia. One particular barbiturate, pentobarbital, is the drug of choice for veterinary anesthesia and euthanasia.

Pharmacological and Psychological Effects

Barbiturates are classified according to their duration of action. The effects of ultra-short-acting drugs, such as Pentothal (used in surgical settings as an anesthesia), last less than one hour. Short-acting barbiturates (such as Nembutal and Seconal) act for three to four hours and are more likely to be taken for recreational purposes. The effects of intermediate-acting barbiturates (such as Amytal) last for six to eight hours, and the effects of long-acting barbiturates (such as Veronal and Luminal) that are taken as anticonvulsants last approximately twelve hours. Like other sedative-hypnotic drugs, barbiturates produce relaxation or sleep. Barbiturates are not analgesic. If an individual is experiencing moderate or high levels of pain, they will be less effective in producing sedation or sleep. The mechanism underlying their effect is thought to be an enhancement of the neural inhibition induced by the neurotransmitter gamma-aminobutyric acid (GABA) at the receptor. Additionally, barbiturates directly open the chloride channel on cell membranes without GABA.

Although barbiturates can produce sleep, the quality of sleep can be far from normal. The stage of sleep referred to as rapid eye movement (REM) is markedly suppressed. Since this stage is associated with dreaming, the frequency of dreams can be dramatically reduced. For individuals experiencing withdrawal, dreaming can become excessive and more vivid during this period where the brain attempts to make up for lost time spent in REM. The term “REM rebound” is used to describe this phenomenon and it can frequently bring on insomnia. However, more significant and noticeable changes brought on by barbiturates include their capacity to act as a cognitive inhibitor. Memory functioning can be compromised along with alterations of judgment, decision making, insight, and planning. An above-regular dosage of barbiturates induces a state of intoxication similar to that caused by alcohol. Mild intoxication is characterized by drunk-like behavior with slurred speech, unsteady gait, lack of coordination, abnormal eye movements, and an absence of alcohol odor. Driving prior to the drug being completely metabolized and eliminated is considered dangerous.

At regular doses, the effects of barbiturates vary depending on the user’s previous experience with the drug, the setting of use, and the mode of administration. A particular dose taken in the evening, for example, may induce sleep, whereas it may produce relaxed contentment, euphoria, and diminished motor skills during the day. Some users report sedation, fatigue, unpleasant drowsiness, nausea, vomiting, and diarrhea. A paradoxical state of excitement or rage also can occur. Users may experience a “hangover” phenomenon the day after drug administration. Hypersensitivity reactions, sensitivity to sunlight (photosensitivity), decreased sexual function, and impaired memory also have been reported.

Potential Risks, Drug Misuse and Dependence

Although barbiturates have been around for over 100 years, there has been a steep and rapid decline in their clinical uses. Compared to the number of prescriptions written for barbiturates during the 1970s, today, they are rarely used. Two primary factors are responsible for the change. First, safer drug alternatives have been developed. An example of this would be the use of benzodiazepines in the treatment of anxiety disorders. Secondly, barbiturates, overall, have been found to be extremely dangerous to use effectively. They have become associated with numerous deaths, widespread dependency and misuse, and have been found to interact deleteriously with many other drugs. Barbiturates are extremely dangerous when combined with alcohol since both drugs are central nervous system depressants and they produced a synergistic, exaggerated effect when taken together.

One reason these drugs pose a significant risk is due to the fact the therapeutic dosage of any barbiturate is close to its lethal dose. Because of this narrow therapeutic window, severe intoxication or drug-induced death can easily occur. Intentional or accidental overdose results in extreme drowsiness, respiratory depression (with slow breathing), hypotension, hypothermia, renal failure, decreased reflexes, and, ultimately, coma and death. In addition, taking barbiturates over a period of months can induce tolerance whereby the sedative effects (not so much the depressant effects on respiration) diminish over time. This requires higher dosages to achieve the same clinical benefits. Eventually, the therapeutic window mentioned above is narrowed even further making barbiturate usage unacceptably dangerous.

Both physical and psychological dependence can result with normal clinical doses. This potential for misuse, particularly for short and intermediate acting barbiturates, contributed to the medical communities’ movement away from using barbiturates if other drug alternatives were available. Physical dependence is characterized by withdrawal symptoms during periods of drug cessation. Withdrawal symptoms may include restlessness, disorientation, hallucinations, hyper-excitability, delirium, convulsions, and possibly death. Barbiturate dependency, followed by abrupt termination of drug use, can be extremely dangerous. Persons who want to stop taking these drugs should do so under medical supervision only.

The amount of barbiturates needed to reach a toxic dose which causes an overdose can vary considerably. However, in most circumstances, a dose of one gram of the majority of barbiturates leads to serous poisoning. Ingesting two to ten grams frequently causes death. A person with suspected barbiturate overdose should be seen by a physician without delay. In a 2016 study published about 277 people admitted to a hospital emergency room for drug overdose, investigators found that 19.5% had taken barbiturates. It was also found that these individuals needed to be monitored more closely since they had a higher risk for incurring additional medical implications. In some instances, the overdose was a deliberate attempt to die. Among advocates of euthanasia and among those who commit suicide, barbiturates remain one of the most commonly employed drugs.

Medicines Classified as Barbiturates

Amytal sodium

Butisol sodium

Luminal

Nembutal sodium

Phenobarbital

Seconal sodium

References

1 

Cordovilla-Guardia, Sergio, et al. “The Effect of Central Nervous System Depressant, Stimulant and Hallucinogenic Drugs on Injury Severity in Patients Admitted for Trauma.” Gaceta Sanitaria, vol. 33, no. 1, 2019, pp. 4–9., doi:10.1016/j.gaceta.2017.06.006.

2 

Davis, Kathleen. “Barbiturates: Uses, Side Effects, and Risks.” Medical News Today, MediLexicon International, 25 June 2018, www.medicalnewstoday.com/articles/310066.php.

3 

Gokhale, Sankalp, and Ciro Ramos-Estebanez. “An Interesting Case of Barbiturate Automatism and Review of Literature.” Case Reports in Neurological Medicine, vol. 2013, 2013, pp. 1–2., doi:10.1155/2013/713065.

4 

Lafferty, Keith A., et al. “Barbiturate Toxicity.” Medscape, 14 Jan. 2017, emedicine.medscape.com/article/813155-overview.

5 

López-Muñoz, Francisco, et al. “The History of Barbiturates a Century after Their Clinical Introduction.” Neuropsychiatric Disease and Treatment, vol. 1, no. 4, Dec. 2005, pp. 329–343.

6 

Oakley, Simon, et al. “Recognition of Anesthetic Barbiturates by a Protein Binding Site: A High Resolution Structural Analysis.” PLoS ONE, vol. 7, no. 2, 16 Feb. 2012, doi:10.1371/journal.pone.0032070.

Citation Types

Type
Format
MLA 9th
Avramut, Mihaela, and Bryan C. Auday. "Barbiturates." Principles of Health: Pain Management, edited by Michael A. Buratovich, Salem Press, 2020. Salem Online, online.salempress.com/articleDetails.do?articleName=POHPain_0098.
APA 7th
Avramut, M., & Auday, B. C. (2020). Barbiturates. In M. A. Buratovich (Ed.), Principles of Health: Pain Management. Salem Press.
CMOS 17th
Avramut, Mihaela and Auday, Bryan C. "Barbiturates." Edited by Michael A. Buratovich. Principles of Health: Pain Management. Hackensack: Salem Press, 2020. Accessed September 19, 2025. online.salempress.com.