What is sedative-hypnotic abuse?

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 century.

Barbiturates were first introduced for medical use in the early twentieth century. Since then, approximately fifty barbiturates were marketed but less than fifteen remain in medical use. Barbiturates became popular in the 1960s as 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, less than twenty are currently 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.

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 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).

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 elderly persons.

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 has been rising since about 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) and triazolam (Halcion); 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 the combination of BDZ and alcohol. When used chronically, for longer than four to eight weeks, BDZ can be addicting. BDZ, particularly those having a rapid onset—the highly lipophilic (such as diazepam) and the short-acting/high-potency BDZ (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.

BDZ also are used to augment alcohol’s effects and to manage withdrawal states. BDZ 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 those 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 a temporary amnesia, they are sometimes added to alcoholic beverages and soft drinks to incapacitate the intended victim of a rape. Flunitrazepam (Rohypnol), also known with the street names rophies, roofies, and roach, 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-hydroxy butyrate (GHB), a natural CNS depressant resulting from the metabolism of the inhibitory neurotransmitter GABA, has emerged as a significant drug of abuse. 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 (elderly people, 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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