Historically, people of almost every culture have used chemical agents to induce sleep, relieve stress, and allay anxiety. While alcohol is one of the oldest and most universal agents used for these purposes, hundreds of substances have been developed that produce central nervous system (CNS) depression. These drugs have been referred to as "downers," sedatives, hypnotics, minor tranquilizers, anxiolytics, and antianxiety medications. Unlike most other classes of drugs of abuse, depressants, except for methaqualone, are rarely produced in clandestine laboratories. Generally, legitimate pharmaceutical products are diverted to the illicit market.

Although a number of depressants (i.e., chloral hydrate, glutethimide, meprobamate and methaqualone) have been important players in the milieu of depressant use and abuse, two major groups of depressants have dominated the licit and illicit market for nearly a century, first barbiturates and now benzodiazepines.

Barbiturates were very popular in the first half of this century. In moderate amounts, these drugs produce a state of intoxication that is remarkably similar to alcohol intoxication. Symptoms include slurred speech, loss of motor coordination and impaired judgment. Depending on the dose, frequency, and duration of use, one can rapidly develop tolerance, physical dependence and psychological dependence on barbiturates. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that can produce coma and death. Although many individuals have taken barbiturates therapeutically without harm, concern about the addiction potential of barbiturates and the ever-increasing numbers of fatalities associated with them led to the development of alternative medications. Today, only about 20% of all depressant prescriptions in the United States are for barbiturates.

Benzodiazepines were first marketed in the 1960s. Touted as much safer depressants with far less addiction potential than barbiturates, these drugs today account for about 30% of all prescriptions for controlled substances. It has only been recently that an awareness has developed that benzodiazepines share many of the undesirable side effects of the barbiturates. A number of toxic CNS effects are seen with chronic high dose benzodiazepine therapy. These include headache, irritability, confusion, memory impairment, depression, insomnia and tremor. The risk of developing over-sedation, dizziness and confusion increases substantially with higher doses of benzodiazepines. Prolonged use can lead to physical dependence even at recommended dosages. Unlike barbiturates, large doses of benzodiazepines are rarely fatal unless combined with other drugs or alcohol. Although primary abuse of benzodiazepines is well documented, abuse of these drugs usually occurs as part of a pattern of multiple drug abuse. For example, heroin or cocaine abusers will use benzodiazepines and other depressants to augment heir "high" or alter the side effects associated with over-stimulation or narcotic withdrawal.

There are marked similarities among the withdrawal symptoms seen with all drugs classified as depressants. In it mildest form, the withdrawal syndrome may produce insomnia and anxiety, usually the same symptoms that initiated the drug use. With a greater level of dependence, tremors and weakness are also present, and in its most severe form, the withdrawal syndrome can cause seizures and delirium. Unlike the withdrawal syndrome seen with most other drugs of abuse, withdrawal from depressants can be life-threatening.