MKUltra was an illegal human experimentation program designed and undertaken by the U.S. Central Intelligence Agency (CIA) to develop procedures and identify drugs that could be used during interrogations to weaken individuals and force confessions through brainwashing and psychological torture. The term MKUltra is a CIA cryptonym: "MK" is an arbitrary prefix standing for the Office of Technical Service and "Ultra" is an arbitrary word out of a dictionary used to name this project. The program has been widely condemned as a violation of individual rights and an example of the CIA's abuse of power, with critics highlighting its disregard for consent and its corrosive impact on democratic principles.

Project MKUltra began in 1953 and was halted in 1973. MKUltra used numerous methods to manipulate its subjects' mental states and brain functions, such as the covert administration of high doses of psychoactive drugs (especially LSD) and other chemicals without the subjects' consent. Additionally, other methods beyond chemical compounds were used, including electroshocks, hypnosis, sensory deprivation, isolation, verbal and sexual abuse, and other forms of torture.

Project MKUltra was preceded by Project Artichoke. It was organized through the CIA's Office of Scientific Intelligence and coordinated with the United States Army Biological Warfare Laboratories. The program engaged in illegal activities, including the use of U.S. and Canadian citizens as unwitting test subjects. MKUltra's scope was broad, with activities carried out under the guise of research at more than 80 institutions aside from the military, including colleges and universities, hospitals, prisons, and pharmaceutical companies. The CIA operated using front organizations, although some top officials at these institutions were aware of the CIA's involvement.

Project MKUltra was revealed to the public in 1975 by the Church Committee (named after Senator Frank Church) of the United States Congress and Gerald Ford's United States President's Commission on CIA Activities within the United States (the Rockefeller Commission). Investigative efforts were hampered by CIA director Richard Helms's order that all MKUltra files be destroyed in 1973; the Church Committee and Rockefeller Commission investigations relied on the sworn testimony of direct participants and on the small number of documents that survived Helms's order. In 1977, a Freedom of Information Act request uncovered a cache of 20,000 documents relating to MKUltra, which led to Senate hearings. Some surviving information about MKUltra was declassified in 2001.

During the early 1940s, Nazi scientists working in the concentration camps of Auschwitz and Dachau during World War II conducted interrogation experiments on human subjects. Substances such as barbiturates, morphine derivatives, and hallucinogens such as mescaline were employed in experiments conducted on Polish, Russian, Ukrainian, and other nationalities' prisoners of war. The aim of these experiments was to develop a truth serum which would, in the words of one laboratory assistant to Dachau scientist Kurt Plötner, "eliminate the will of the person examined." American historian Stephen Kinzer said that the CIA project was a continuation of these earlier Nazi experiments, as evidenced by MKUltra's use of mescaline on unwitting subjects, replicating previous Nazi experiments conducted at Dachau.

American interest in drug-related interrogation experiments began in 1943, when the Office of Strategic Services began developing a "truth drug" that would produce "uninhibited truthfulness" in an interrogated person. In 1947, the United States Navy initiated Project CHATTER, an interrogation program which saw the first testing of LSD on human subjects.

In 1950, the Central Intelligence Agency under the direction of General Walter Bedell Smith initiated a series of interrogation projects involving human subjects, beginning with the launch of Project Bluebird, officially renamed Project Artichoke on August 20, 1951. Directed and overseen by Brigadier General Paul F. Gaynor, the objective of Artichoke was to determine whether an individual could be made to involuntarily perform an act of attempted assassination. Morphine, mescaline and LSD were all administered on unknowing CIA agents in an attempt to produce amnesia in the subjects. In addition, Project Artichoke aimed to employ certain viruses such as dengue fever as potential incapacitating agents.^{[better source needed]}

The project was headed by Sidney Gottlieb but began on the order of CIA director Allen Dulles on April 13, 1953. Its aim was to develop mind-controlling drugs for use against the Soviet bloc in response to alleged Soviet, Chinese, and North Korean use of mind control techniques on U.S. prisoners of war during the Korean War. The CIA wanted to use similar methods on their own captives, and was interested in manipulating foreign leaders with such techniques, devising several schemes to drug Fidel Castro. It often conducted experiments without the subjects' knowledge or consent. In some cases, academic researchers were funded through grants from CIA front organizations but were unaware that the CIA was using their work for these purposes.