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Beat comedian Lord BuckleyL ysergic acid diethylamide had been around since 1938, when Dr. Albert Hofmann serendipitously formulated the first dose at Sandoz. Hofmann was experimenting with derivatives of ergot, a rye fungus, in an attempt to develop a circulatory stimulant. Instead, what he discovered in his 25th attempt (the official name of the drug would become LSD-25) was a substance of extremely peculiar qualities. The story of the first acid trip ever is now famous: Hofmann unknowingly absorbed the experimental compound through his fingers. "As I lay in a dazed condition with eyes closed," he would recall, "there surged up from me a succession of fantastic, rapidly changing imagery of a striking reality and depth, alternating with a vivid, kaleidoscopic display of colors." Two days later, Hofmann deliberately swallowed a miniscule 250 micrograms (a millionth of an ounce), which launched him on an even more dramatic head trip. "I had great difficulty in speaking coherently," hed later say of that session. He managed to ride his bicycle home, but was soon enduring the worlds first bad trip, wondering if he was going insane: "I thought I had died. My ego was suspended somewhere in space, and I saw my body lying dead on the sofa." Hofmann survived the ordeal, and soon returned to the realm of pleasant hallucinations. So began the era of academic experimentation with the unusual compound. By 1965, researchers had published more than 2,000 papers describing the treatment of 30,000 to 40,000 patients with psychedelic drugs, including mescaline and psilocybin, but mostly with LSD. Among the more stunning results were studies in which LSD was given in high doses to children suffering from schizophrenia and autism. One such study reported that for a group of young autistic children with speech difficulties, "the vocabularies of several of the children increased after LSD." Whats more, "several seemed to be attempting to form words or watched adults carefully as they spoke; many seemed to comprehend speech for the first time." The autistic children all "appeared flushed, bright-eyed and unusually interested in the environment." Even more dramatic were the successes during the 1950s and 1960s in treating chronic alcoholics at Hollywood Hospital in British Columbia and at Spring Grove State Hospital in Baltimore. After ingesting relatively large doses of LSD (up to 800 micrograms, in some cases) and undergoing directed therapy, about half of all patients "were able to remain sober or to drink much less," according to pioneers Bernard Aaronson and Humphry Osmond (who coined the word "psychedelic") in their book Psychedelics (1970). Often after only one dose patients remained totally abstinent. "This seems to be a universal statistic for LSD therapy," they reported. Exactly how LSD worked for alcoholics, heroin addicts and schizophrenic children remains something of a mystery. One school of thought advanced the theory that a "peak" LSD experience can be as nerve-rattling as a case of the delirium tremens, which many reformed alcoholics cite as the nadir before they decided to stop boozing. Others noted that patients werent likely to experience a dramatic recovery unless the LSD experience was guided by a skilled therapist. In fact, to this day scientists know little about how LSD interacts with the human brain on a neurological level. The ban on human research with LSD is partly to blame. But beyond that, LSD operates in mysterious ways. The drug remains in the brain for a relatively short period, disappearing at about the time the mental light show begins. This short half-life of the drug suggests that the hours of hallucinations and consciousness-warping experienced by acid eaters is due not to the drug itself, but to some little-understood neurochemical chain of events unleashed by LSD. Research on animals has suggested that LSD stimulates the serotonin receptors of the brain the same neurological connections that Prozac and other new antidepressant drugs zero in on. "Why a drug that stimulates a serotonin receptor should effect changes in consciousness and perception is the thing that we dont actually know," says David Nichols, founder of the Heffter Research Institute, a nonprofit group that funds and conducts clinical studies of psychedelic substances. "One could look at LSD as having an action somewhat like an antidepressant," says Richard Yensen, a pioneering LSD researcher and psychologist who successfully treated alcoholics at the Maryland Psychiatric Research Center, on the grounds of Spring Grove State Hospital. But, he adds, "LSD belongs to a unique family of drugs that are first and foremost sensitive to the way they are given. And the mechanism of cure has not to do with whether the person got the drug or not, but with whether the person had a transcendental experience with the drug." After decades of experimentation clinical and otherwise its clear that LSDs effect on individuals varies hugely. A persons response depends not only on his or her mental state or "set," but also on a multitude of other factors, including the setting in which the drug is taken, the influence of others in the room and even the prevailing cultural climate. For instance, during the late 1960s, after the frenzy of hyperbolic media reports on the dangers of LSD, the numbers of illegal users experiencing the proverbial "bad trip" multiplied. Many observers suspected a direct relationship between the upswing in "bummers" and the surge of acid scare stories. (The fact that the doses available then were often more than twice as high as todays street-grade hits may also account for the higher incidence of bad trips.) Undoubtedly, LSDs mercurial nature has a lot to do with why it became so controversial so quickly, and why it was never fully accepted as a worthy addition to the store of mainstream pharmacopoeia. I thought I was the quickest the quickest the quickest mind alive and the quickest with words but words cannot catch up with these changes, these changes are beyond words, beyond words, beyond words. While I repeated these words I felt the waves of pleasure like those of the most acute pleasure of lovemaking . . . I felt the impossibility to tell the secret of life because the secret of life was metamorphosis, transmutation, and it happened too quickly, too subtly.