Depressant is a chemical agent that diminishes the function or activity of a specific part of the body (see also sedative). The term is used in particular with regard to the central nervous system (CNS). Alcohol is the most common example of a depressant. Many depressants acting on the CNS do so by increasing the activity of a particular neurotransmitter known as gamma-aminobutyric acid (GABA), although other targets such as the NMDA receptor, mu opioid receptor and CB1 cannabinoid receptor can also be important, depending on which drug is involved.

GABA's task is to calm the CNS and to promote sleep. Drugs that stimulate the activity of this acid produce slowed brain function and a drowsy or calm feeling, and so depressants are generally prescribed to relieve symptoms of anxiety or insomnia. Internal systems regulate the body's production of GABA, but when medication is taken to stimulate GABA action, it is possible to induce hazardously high levels, which can dangerously slow breathing and heart rates, and may result in death.

CNS depressants require a period of adaptation. Typically, initial side effects include slurred speech, dizziness, and loss of coordination.

The most common medically used depressants generally fall into two classes, namely barbiturates and benzodiazepines. Other depressants include alcohol, narcotics (opiate derivatives), sedative-hypnotics, first-generation antihistamines (such as diphenhydramine,) and some anaesthetics (such as ketamine and phencyclidine).

Barbiturates are effective in relieving the conditions they are designed to address; they are also readily abused, physically addictive, and have serious potential for overdose. When, in the late 1960s, it became clear that the social cost of barbiturates was beginning to outweigh the medical benefits, a serious search began for a replacement drug. (See Methaqualone) Most people still using barbiturates today do so in the prevention of seizures or in mild form for relief from the symptoms of migraines.

Benzodiazepines mediate many of the same symptoms as barbiturates, but are far less toxic and have a strongly reduced risk of overdose. This is not to say they are not without their own risks; where barbiturates pose a greater "front-end" danger in that overdose or drug/alcohol interactions may result in fatality, benzodiazepines pose a greater "back-end" risk in the possibility of addiction, dependence, and serious physical and psychological withdrawal symptoms. Immediate cessation of long-term benzodiazepine use instead of tapering can be dangerous and have serious effects.

Combining multiple depressants is generally recognized as very dangerous because the CNS depressive properties often increase exponentially instead of linearly. This characteristic makes depressants a common choice for deliberate overdoses in the case of suicide. The use of alcohol or benzodizepines along with the usual dose of heroin is often the cause of overdose deaths in opiate addicts.