Sedative-hypnotic abuse
Sedative-hypnotic abuse refers to the misuse of medications that are designed to induce sedation or promote sleep, including barbiturates, benzodiazepines (BDZs), and non-benzodiazepine depressants (NB-NBDZs). These drugs are typically prescribed for medical conditions such as anxiety, insomnia, and seizures but are often abused for their euphoric and calming effects. While the overall rate of abuse may be less than 1% of the general population, individuals with a history of substance use disorders are at a higher risk, particularly those aged 18 to 49. Different classes of sedative-hypnotics have varying potential for addiction and overdose, with serious risks associated with long-term use, including withdrawal symptoms and life-threatening overdose.
The historical context of these drugs shows that while barbiturates were once the go-to treatment, their potential for dependency led to a decline in their prescription, with BDZs largely replacing them since the 1970s. However, both barbiturates and BDZs are still subject to misuse, particularly in combination with alcohol. Drugs like flunitrazepam and gamma-hydroxybutyric acid (GHB) have been notably associated with recreational use and incidents of drug-facilitated sexual assault. Ultimately, the abuse of sedative-hypnotics poses significant safety concerns, including potential drug interactions and severe health risks, particularly in vulnerable populations such as older adults and pregnant women.
Sedative-hypnotic abuse
ALSO KNOWN AS: Barbiturates (barbs, block busters, Christmas trees, goof balls, tooies, Mexican yellows, phennies, pinks, purple hearts, reds, red birds, red devils, yellows, yellow jackets); BDZs (benzodiazepine, benzos, downers, Mexican Valium, rope, wolfies, zanies); NB-NBDZs (methaqualone, ludes, quaalude, sopors)
DEFINITION: Barbiturates, BDZs, and NB-NBDZs are groups of drugs within the class known as sedative-hypnotics or central nervous system depressants. This class has sleep-inducing and anxiety-decreasing (sedative, tranquilizing) effects because of its capacity to enhance the effects of gamma-aminobutyric acid, the most prominent inhibitory neurotransmitter in the central nervous system.
STATUS: Prescription-only drugs accepted for medical use worldwide
CLASSIFICATION: Barbiturates are Schedule II, III, and IV controlled substances; BDZs and some NB-NBDZs (such as zolpidem, zopiclone, chloral hydrate, paraldehyde, meprobamate) are controlled in Schedule IV; glutethimide (originally a Schedule III drug) was upgraded to Schedule II; methaqualone and gamma-hydroxybutyric acid are Schedule I controlled substances in the United States
SOURCE: Legally available through prescription; illegally purchased without a prescription
TRANSMISSION ROUTE: Ingestion; intravenous and intramuscular administration; suppository
History of Use
Bromide, the first sedative-hypnotic, originated in 1838 and was followed by chloral hydrate, paraldehyde, and barbiturates. Bromide compounds were frequently used as sedatives and anticonvulsants in the nineteenth and early twentieth centuries.
Barbiturates were first introduced for medical use in the early twentieth century. Since then, approximately fifty barbiturates have been marketed, but few remain in medical use. Barbiturates became popular in the 1960s as a treatment for anxiety, insomnia, and seizure disorders, but the dependence-producing potential and the dangers of overdose restricted their use significantly. Since the 1970s, barbiturates were largely replaced by the safer BDZ group.
The first BDZs, chlordiazepoxide and diazepam, were introduced in clinical practice in the early 1960s. Although more than two thousand different BDZs have been synthesized, fewer than fifteen are approved in the United States. BDZ usage increased dramatically in the 1970s, with total sales accounting for about 10 percent of all prescriptions in many Western countries. The perceived desirable properties of anxiety alleviation, euphoria, disinhibition, and sleep promotion have led to the compulsive misuse of virtually all of the drugs classed as sedative-hypnotics.
Individuals between eighteen and forty-nine most often abuse this class of drugs, although adults over fifty are prescribed these drugs most often. Though the total abuse rate is estimated to be less than 1 percent of the total population, individuals who already use illicit drugs or have a substance use disorder, particularly intravenous drugs, are at an increased risk, with 6 percent using sedative-hypnotics. Other risk factors include unemployment, poor healthcare access, being female, being White, and having at least one prior psychiatric diagnosis.
Effects and Potential Risks
Graded, dose-dependent depression of the central nervous system (CNS) function is characteristic of sedative-hypnotics. At low doses, they produce sedation (relieving anxiety and promoting relaxation), whereas at higher doses, they have a hypnotic effect.
Barbiturates
Barbiturates are classified in three ways. Those three ways, and the associated barbiturate, are ultrashort-acting methohexital (Brevital), thiamyl (Surital), and thiopental (Pentothal); short- and intermediate-acting amobarbital (Amytal), pentobarbital (Nembutal), secobarbital (Seconal), butalbital (Fiorinal), butabarbital (Butisol), talbutal (Lotusate), and aprobarbital (Alurate); and long-acting phenobarbital (Luminal) and mephobarbital (Mebaral). In the mid-2020s, barbiturates in clinical use that were approved by the US Food and Drug Administration (FDA) included phenobarbital (Luminal), methohexital (Brevital), butalbital (Fioricet), pentobarbital (Nembutal Sodium), primidone (Mysoline), and amobarbital (Amytal), butabarbital (Butisol), and secobarbital (Seconal).
Barbiturates produce a wide spectrum of CNS depression, from mild sedation to coma, and are used as sedatives, hypnotics, anesthetics, and anticonvulsants. The ultrashort-acting barbiturates produce anesthesia within one minute of intravenous administration and are used for minor surgery or as preoperative anesthetics for major surgery. The long-acting barbiturates are used in some forms of epilepsy or to treat convulsions caused by cocaine and other stimulant drugs. Barbiturates have a narrow therapeutic index and can cause coma or death if taken inappropriately, especially in children and older adults.
The toxicity of barbiturates is likely when the dose exceeds five to ten times the hypnotic dose. The potentially fatal dose for phenobarbital is 6 to 10 grams, but only 2 to 3 grams for pentobarbital or secobarbital. Barbiturates also are addictive if taken daily for longer than about one month and can cause a life-threatening withdrawal syndrome upon discontinuation.
Symptoms of withdrawal include tremors, difficulty sleeping, agitation, hallucinations, high temperature, and seizures. In pregnant women, barbiturates can cause dependence and newborn withdrawal syndrome. Barbiturates are commonly used in suicide attempts. Although the medical use and street abuse of barbiturates declined after the 1970s, surveys suggest that abuse began rising again in 2000. Barbiturates are commonly abused to counteract the symptoms of such stimulating drugs as cocaine and methamphetamine.
BDZs
BDZs (also known as minor tranquilizers) are effective in a wide range of medical and psychiatric conditions, such as anxiety and sleep disorders, panic attacks, agoraphobia, acute stress reactions, convulsive and spastic disorders, presurgical sedation, and detoxification from alcohol. They are usually classified by their duration of action, which ranges from less than six hours to more than twenty-four hours, as ultra-short acting midazolam (Versed), triazolam (Halcion), remimazolam (Byfavo); as short-acting alprazolam (Xanax), lorazepam (Ativan), estazolam (ProSom), temazepam (Restoril), and oxazepam (Serax); and as long-acting chlordiazepoxide (Librium), diazepam (Valium), clonazepam (Klonopin), flurazepam (Dalmane), and clorazepate (Tranxene).
BDZs are widely prescribed, and four of them—alprazolam, clonazepam, diazepam, and lorazepam—are among the top forty prescription medications sold. Alprazolam and diazepam are the two most frequently encountered BDZs on the illicit market.
Signs and symptoms of acute toxicity or overdose may include drowsiness, confusion, dizziness, blurred vision, weakness, slurred speech, lack of coordination, difficulty breathing, and coma. Fatal overdoses usually involve a combination of BDZs and alcohol. When used for longer than four to eight weeks, BDZs can be addicting. BDZs, particularly those having a rapid onset—the highly lipophilic (such as diazepam) and the short-acting/high-potency BDZs (such as alprazolam or lorazepam)—are the most reinforcing and, therefore, most likely to be associated with abuse. They are used recreationally to induce relaxation and are abused to produce a euphoric effect.
BDZs also are used to augment alcohol’s effects and to manage withdrawal states. BDZs have a relatively low potential for abuse in persons without a history of substance use disorders but moderate-to-high potential for people with a history of substance abuse or dependence.
NB-NBDZs
NB-NBDZs include chemically heterogeneous compounds that do not fall into either the barbiturate or the BDZ group. Chloral hydrate (Somnote, Aquachloral) is a fast-acting sedative-hypnotic with long-lasting effects. It had widespread use (including recreationally) in the late nineteenth century. A solution of chloral hydrate in alcohol was known as knock-out drops or Mickey Finn (a drink designed to incapacitate the person who drinks it).
Methaqualone (Quaalude) possesses sedative-hypnotic, anticonvulsant, antispasmodic, local anesthetic, antitussive, and weak antihistaminic properties. It produces a dissociative high that resembles that of opiates (heightened sensitivity and euphoria) without the drowsiness caused by barbiturates. Methaqualone became a popular recreational drug in the 1960s and 1970s. Because of its high abuse potential, methaqualone has been removed from the market in many countries. In the United States, the marketing of methaqualone stopped in 1984.
Other Uses of Sedative-Hypnotics
Some of the sedative-hypnotics are used to commit sexual assaults. Because these drugs are sedating and induce temporary amnesia, they are sometimes added to alcoholic beverages and soft drinks to incapacitate the intended victim of rape. Flunitrazepam (Rohypnol), also known by the street names rophies, roofies, and roach, roche, ruffles, and the forget-me drug, is a long-acting BDZ used as a favored sedative of abuse among adolescents and adults, and it is typically used in combination with alcohol as a party drug and a date rape drug.
Flunitrazepam has never been approved for medical use in the United States. Gamma-hydroxybutyrate acid (GHB), also known as sodium oxybate or the brand name Xyrem, is a natural CNS depressant resulting from the metabolism of the inhibitory neurotransmitter GABA, emerged as a significant drug of abuse in the 2010s. It gained popularity for recreational use because of its pleasant, alcohol-like, hangover-free high with aphrodisiac properties.
Body-builders abuse GHB for its alleged utility as an anabolic agent. GHB is often taken by young polydrug abusers (who are called clubbers and ravers) in combination with amphetamines to produce euphoria and a hallucinatory state. Because of concerns about GHB abuse and date rape usage, in 2000, this drug was made a Schedule I controlled substance. Because flunitrazepam and GHB are illegal in the United States, they are available only through the underground market.
Those who chronically abuse sedative-hypnotics prefer the short-acting barbiturates, the barbiturate-like depressants glutethimide and methaqualone, and the faster-acting BDZs diazepam, alprazolam, and lorazepam. Persons who abuse sedative-hypnotics are most likely to be those who use drugs to relieve stress; who use drugs to counteract unpleasant effects of other drugs of abuse; and who combine CNS depressants with alcohol or opiates to potentiate their effects.
Significant safety concerns with sedative-hypnotics include important drug interactions (for example, the inhibitors of drug metabolism such as antifungals, erythromycin, clarithromycin, or cimetidine significantly prolong their effect and increase their toxicity) and their appropriate use in special populations (older adults, pregnant women, and persons with a history of substance abuse). Overdosing on sedative-hypnotics is among the most common methods for attempting suicide.
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