CIA Director Allen Dulles authorized the MKULTRA program in April 1953, out of concern for rumors that POWs were being brainwashed by communists during the Korean War. The program was supposed to be an experiment in mind-control that would publicly humiliate foreign world leaders who were in opposition to the US. The most widely-known of the MKULTRA experiments was the usage of LSD. The CIA hoped they would eventually be able to use the drug to manipulate foreign world leaders such as Fidel Castro, and to make people talk during interrogations. A memorandum dated January 1952 outlined the project's objective: "Can we get control of an individual to the point where he will do our bidding against his will and even against fundamental laws of nature such as self-preservation?"

Most of the CIA researchers tried LSD themselves, and one man who was working on the project was slipped LSD into his drink. Dr. Sidney Gottlieb, Head of the CIA's Technical Services Staff had acquired an amount of LSD and secretly tested it on Dr. Frank Olson during a meeting. Other CIA researchers observed his behavior, one labelling it as "psychotic". Nine days later, Olson jumped from his hotel window and fell ten floors to his death. Gottlieb and Dulles covered up the events leading to Olson's death for over twenty years.

The LSD experiments were performed on prisoners and, during an experiment in Kentucky, 7 volunteers were given LSD for 77 consecutive days. In some cases, the prisoners were rewarded for their cooperation with injections of high-quality morphine. The CIA put forth millions of dollars into researching methods of mind control that would gain the US the upperhand in psychological warfare, most of their experiments being performed on non-volunteer subjects. Members of the CIA travelled all over the world, testing interrogation techniques while subjects were under the influence of marijuana, LSD, heroin, mescaline, sodium pentathol (the 'truth drug') and many others. One goal of the project was to brainwash people into becoming spies without their knowledge.

Most of the documents on MKULTRA were destroyed by the CIA in 1972, but many have been the subject of historical research, having gotten to the hands of investigative reporters.

One CIA auditor wrote later on:

"Precautions must be taken not only to protect operations from exposure to enemy forces, but also to conceal these activities from the American public in general. The knowledge that the agency is engaging in unethical and illicit activities would have serious repercussions in political and diplomatic circles."

An excerpt from CIA Director Stansfield Turner's Testimony during the 1977 Senate Hearing on MKULTRA:

Senator INOUYE. A sad aspect of the MKULTRA project was that it naturally involved the people who unwittingly or wittingly got involved in experimentation. I would appreciate it if you would report back to this committee in 3 months on what the Agency has done to notify these individuals and these institutions, and furthermore, to notify us as to what steps have been taken to identify victims, and if identified, what you have done to assist them, monetarily or otherwise.

Admiral TURNER. All right, sir. I will be happy to.

Senator GOLDWATER. Will the Senator yield?

Senator INOUYE. Yes, sir.

Senator GOLDWATER. I wonder if he could include in that report for our information only a complete listing of the individuals and the experiments done on them, and whether they were witting or unwitting, volunteer or nonvolunteer, and what has been the result in each case. I think that would be interesting.

Admiral TURNER. Fine. Yes, sir.

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In 1977 Victor Marchetti, a CIA veteran of 14 years, said that the CIA's claims of ceasing the project were false. Another CIA veteran, Miles Copeland, stated that after 1963 the project was focusing more on mind-control with the use of electronics. Others believe the focus was placed on other such experiments involving religious cults, such as the events of the Jonestown Massacre.