"Truth serum" is a colloquial name for any of a range of psychoactive drugs used in an effort to obtain information from subjects who are unable or unwilling to provide it otherwise. These include ethanol, scopolamine, 3-quinuclidinyl benzilate, midazolam, flunitrazepam, sodium thiopental, and amobarbital, among others.

Although a variety of such substances have been tested, serious issues have been raised about their use scientifically, ethically, and legally. There is currently no drug proven to cause consistent or predictable enhancement of truth-telling. Subjects questioned under the influence of such substances have been found to be suggestible and their memories subject to reconstruction and fabrication. While such drugs have been used in the course of investigating civil and criminal cases, they have not been accepted by Western legal systems and legal experts as genuine investigative tools. In the United States, it has been suggested that their use is a potential violation of the Fifth Amendment of the U.S. Constitution (the right to remain silent). Concerns have also been raised through the European Court of Human Rights, arguing that use of a truth serum could be considered a violation of a human right to be free from degrading treatment, or could be considered a form of torture, and has been noted as a violation of the Inter-American Convention to Prevent and Punish Torture.

"Truth serum" was previously used in the management of psychotic patients in the practice of psychiatry. In a therapeutic context, the controlled administration of intravenous hypnotic medications is called "narcosynthesis" or "narcoanalysis". Such application was first documented by Dr. William Bleckwenn. Reliability and suggestibility of patients are concerns, and the practice of chemically inducing an involuntary mental state is now widely considered to be a form of torture.

Sedatives or hypnotics that alter higher cognitive function include ethanol, scopolamine, 3-quinuclidinyl benzilate, potent short or intermediate acting hypnotic benzodiazepines such as midazolam, flunitrazepam, and various short and ultra-short acting barbiturates, including sodium thiopental (commonly known by the brand name Pentothal) and amobarbital (formerly known as sodium amytal).

While there have been many clinical studies of the efficacy of narcoanalysis in interrogation or lie detection, there is dispute whether any of them qualify as a randomized, controlled study, that would meet scientific standards for determining effectiveness.

India's Central Bureau of Investigation has used intravenous barbiturates for interrogation, often in high-profile cases. One such case was the interrogation of Ajmal Kasab, the only terrorist captured alive by police in the 2008 attacks in Mumbai, India. Kasab was a Pakistani militant and a member of the Lashkar-e-Taiba terrorist group. On May 3, 2010, Kasab was found guilty of 80 offenses, including murder, waging war against India, possessing explosives, and other charges. On May 6, 2010, the same trial court sentenced him to death on four counts and to a life sentence on five counts.

The Central Bureau of Investigation also conducted this test on Krishna, a key witness and suspect in the high-profile 2008 Aarushi-Hemraj Murder Case to seek more information from Krishna and also determine his credibility as a witness with key information, yet not known to the investigating authorities. Per unverified various media sources, Krishna had purported to have deemed Hemraj (the prime suspect) as not guilty of Aarushi's murder, claiming he [Hemraj] "treated Aarushi like his own daughter".

On May 5, 2010 the Supreme Court Judge Balasubramaniam in the case "Smt. Selvi vs. State of Karnataka" held that narcoanalysis, polygraph, and brain-mapping tests were to be allowed with the consent of the accused. The judge stated: "We are of the considered opinion that no individual can be forced and subjected to such techniques involuntarily, and by doing so it amounts to unwarranted intrusion of personal liberty."