LSD was originally synthesized at the Sandoz Pharmaceutical Company, in Switzerland, as part of a long project begun in the 1930s. The aim was to develop useful medications that were derived from ergot, a fungus (Clavicepspurpurea) that infects such grasses as rye. Some of these compounds were found to be useful in medicine—such as methysergide, for the treatment of migraine headaches, and ergotamine, which is widely used in obstetrics to induce contractions of the uterus and stop bleeding after the delivery of a baby. These medications do not have hallucinogenic properties.

The chemist in charge of this drug development project was Albert Hofmann. In 1943, he synthesized a compound he called LSD-25, since it was the twenty-fifth compound made in this series of ergot derivatives. He accidentally ingested some of it and within forty minutes had the first LSD "trip." He told his colleagues he was not feeling quite right and got on his bicycle to go home. Later, he carefully described the vividly clear flood of perceptions that are characteristic of the "mind manifesting'' or psychedelic drug. This, then, was a complete surprise. Thereafter, the drug and various substitutions of different atoms on the basic molecule were extensively tested for medical uses in the late 1940s and in the 1950s. No specific medical use of LSD or its psychedelic variants has been found.

Because of its potency and the extensive reports of laboratory studies in animals and in the clinic, LSD has become the prototypical hallucinogen, or psychedelic drug. It also became the emblem of a social movement—which, in fact, was a confluence of various movements that had begun in the early 1960s; they peaked in the late 1960s. By 1973, the "acid culture" had subsided into a small but still active subculture of various psychedelic drug devotees seeking meaning and profound insights. The feeling of a "great discovery'' about such drugs and the human mind had occurred as early as the nineteenth century; artists and writers, such as Baudelaire and Rimbaud in Paris, had discovered HASHISH and the altered, somewhat dreamy, states of consciousness and euphoria produced by this potent form of MARIJUANA—the active ingredient of which is Tetrahydrocannabinol (THC). For a period, they became absorbed with hashish and wrote about its alluring effects. The drug scene

evoked the promise that the human mind must contain remarkable powers. Toward the beginning of the twentieth century, MESCALINE, the active hallucinogenic compound in the PEYOTE cactus, similarly was tried by a few explorers in medicine and in the arts. In New York City, during the early part of World War I, many influential people and intellectuals took either peyote ''buttons'' (the dried tops of the peyote cactus) or mescaline (the synthesized active ingredient of the buttons) and called it a ''dry drunk.'' Similarly, after World War II, LSD caused a flurry of excitement among some professionals, and its medical value was tested in psychiatric patients. Writers such as Aldous Huxley wrote exciting books about the effects of mescaline and, later, LSD—yet there was still no widely popular movement until 1960.

Then Timothy Leary, a young psychology instructor at Harvard, explored the Mexican or ''magic'' mushroom, Psilocybe mexicana, and its active ingredient, PSILOCYBIN—and later LSD— claiming criminals became loving and peaceful and others more creative. He popularized this on campus and, when he was not reappointed to the faculty, proclaimed himself to be a martyr to his cause. Between 1960 and 1966, the media repeatedly ''discovered'' LSD—in effect, advertising it. As publicity increased, subcultures experimenting with mushrooms and LSD grew up in the East and West Coast cities. Musicians, rock music, the hippie lifestyle, ''flower children,'' and many in the various protest movements against the Establishment and the VIETNAM War were loosely joined to Leary's attempt to lead affluent and middle-class youth. Well-publicized festivals celebrated LSD and marijuana, such as the Summer of Love in the Haight-Ashbury section of San Francisco. Leary's challenge was for youth to ''turn on, tune in and drop out'' with acid. As more and more youth were curious to try experiences their parents had never dreamed of, rebellion led not only to acid experiments but to extensive POLYDRUG ABUSE—the extensive use of marijuana and various street substances. Either LSD or some variant and even heroin were tried. In addition, the search for new drugs with different and improved characteristics (more or less euphoria, hallucinogenic activity, or stimulant properties), literally hundreds of so-called DESIGNER DRUGS were synthesized (DOM, MDMA, DMT, etc.). Because any drug can have bad effects, the unsupervised use of all of these compounds led to frequent ''bad trips'' (which fundamentally were panic reactions) that brought people to emergency rooms. This generated widespread concern that all American youth (and, later, those in Europe) would become dreamy and ''way-out acid heads.'' In 1966, the Sandoz Laboratories ceased distribution of the drug because of the often-exaggerated bad reactions and the public concern. As the claims for enduring LSD insights proved transient, research with LSD in humans essentially stopped.

Thus, one of the ways people use the effects of drugs that seem to enhance the clarity of mentation (mental activity) and perception (while not producing confusion, dreamy-euphoria, or overseda-tion) is to become absorbed in periods of intense exploration with a few others ''in the know.'' Those with such inside information form a kind of cult and then advertise, but they eventually see some bad effects (the wrong people taking the drug in the wrong circumstance with unfortunate consequences) and sooner or later see little real use for the drugs. The minor or major epidemics then die down, only to recur as later generations rediscover the compounds.

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