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20 The Use and Misuse of LSD by the U.S. Army and the CIA Mark Wheelis The use of chemicals to modify brain function is an ancient practice. For millennia, humans have employed alcohol, marijuana, coca leaf, psychedelic fungi, and other plant extracts for ritual, therapeutic, and recreational purposes. There have also been sporadic reports of the use of psychoactive drugs for hostile ends. A wide variety of drugs have been examined for their potential to incapacitate enemy soldiers , enhance the capabilities of friendly troops, assist in interrogation, and induce psychosis in enemy leaders.1 Chemicals studied for these purposes have been drawn largely from recreational or ritual drugs, as well as known categories of pharmaceuticals (the two categories overlap). This historical case study examines the efforts by the U.S. Army and the Central Intelligence Agency (CIA) during the 1950s to develop the hallucinogenic drug lysergic acid diethylamide (LSD) for chemical warfare and covert operations. The army and the CIA were attracted to LSD because of its extraordinary potency, dramatic disturbance of cognition and perception, and low lethality, which suggested that the drug might have potential as a military incapacitant and an agent for intelligence use. Although the mechanism of action of LSD was unknown when the programs took place, such understanding was not needed for the proposed applications. The army’s attempt to develop LSD into a battlefield weapon did not involve scientific innovation but simply extended traditional CW technology to a new agent. Ultimately the effort failed for the same reasons that have prevented many other chemicals from being developed as effective weapons, namely, the instability of the drug when dispersed as an aerosol and the difficulty and high cost of its synthesis. The CIA’s attempts to develop LSD as a mind-control agent, an interrogation aid, and a weapon to induce psychosis in enemy leaders were an extension of its previous development efforts with other psychoactive chemicals, such as mescaline, tetrahydrocannabinol (THC), scopolamine, and barbiturates. LSD was usually administered by adding it to a drink offered to an unwitting subject, an extremely low-tech delivery method. The CIA development program failed because the drug 290 M. Wheelis did not produce desirable effects in a reproducible manner and because of belated concerns about the legality of the program. Although U.S. experimentation with LSD as an agent for hostile purposes ended in the 1960s, military and intelligence agencies around the world continue to be interested in the development of other psychoactive drugs for riot control, counterterrorism , interrogation, and troop enhancement. The potential use of such chemicals raises serious ethical and legal issues about manipulating the mental function of individuals without their informed consent. Broader themes addressed in this case study include the interpretation of misuse, the importance of oversight, normative dynamics, human rights issues, and the role of individuals. Background on LSD LSD disrupts the perceptual and cognitive systems in the brain, leading to powerful visions and hallucinations. These effects are sometimes experienced as profoundly meaningful, creating a sense of cosmic unity.Alternatively, the hallucinations induced by LSD can be terrifying, particularly if the subject is unaware of having been drugged. It is now understood that LSD is structurally similar to the neurotransmitter serotonin and mimics its excitatory action at sites in the cerebral cortex called 5-HT2A receptors. LSD is therefore a serotonin receptor “agonist.” (An agonist is a compound that mimics the action of a natural signaling molecule, as opposed to an “antagonist,” a compound that blocks the action of the natural transmitter.) Because other 5-HT2A agonists do not all produce hallucinations, it is clear that some aspects of the mechanism of action of LSD are not fully understood. Recent research has begun to identify the specific cortical pathways that are responsible for the drug’s hallucinogenic effects.2 LSD was first synthesized in 1934 by Albert Hoffmann, a chemist at the Swiss pharmaceutical company Sandoz who was investigating derivatives of compounds isolated from ergot, a fungus that grows on rye and related plants, as possible drugs. Because lysergic acid is present in significant amounts in ergot-infected grains, Hoffmann extracted it and systematically synthesized derivatives of the molecule, including LSD. Several years later, in 1943, Hoffmann was renewing work with some of these derivatives when he suddenly felt dizzy and intoxicated in a way he had never experienced before. He left work early, bicycled home, and lay down. Several hours of vivid hallucinations followed before he gradually returned to normal. Hoffmann...

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