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The Revival of Hallucinogen Research since the Decade of the Brain
By Nicolas Langlitz
UNIVERSITY OF CALIFORNIA PRESSCopyright © 2013 The Regents of the University of California
All rights reserved.
HOFMANN'S HUNDREDTH BIRTHDAY
13 January 2006. Guided by security personnel, Albert Hofmann, the father of LSD, bent by a century to a height of barely five feet, took the stage on crutches. Almost two thousand people rose from their chairs in the Basel Convention Center. Thunderous applause. Dozens of photographers and cameramen—professional and hippie—were jostling in front of the centenarian birthday boy (see figure 1). The LSD Symposium took place in honor of Hofmann's one-hundredth birthday. But it also served as a fair of the contemporary world of psychedelia, presenting itself in front of two hundred journalists who had come to cover the event. Fragile, but quite sprightly for his age, probably the only person in the hall wearing a tie, Hofmann brie y raised his hand to greet the crowd before sitting down with one of the organizers, a lively and stout middle-aged man with a full voice, president of the Psi Society Basel, a specialist for spiritual healing and otherwise involved in organizing trade fairs for esoterics. He asked Hofmann to tell one more time how he discovered his "problem child" and "wonder drug," LSD. Hardly a newspaper article or TV program preceding or following this spectacular celebration did not begin its report with this almost mythological origin story.
In the 1930s, the research chemist Hofmann developed new ergot alkaloids for the Swiss pharmaceutical company Sandoz. They were meant to stop bleeding after childbirth. Hofmann created a number of derivatives from lysergic acid, the molecular core of ergot. In 1938, he synthesized the twenty-fifth substance in this series of compounds: lysergic acid diethylamide, abbreviated LSD-25 (after the German Lysergsäurediäthylamid). The substance was tested on animals. They became restless and a strong effect on the uterus was established, but as neither the physicians nor the pharmacologists of Sandoz were particularly interested in the substance, these preclinical trials were discontinued. However, five years later—by now the rest of Europe was engulfed in war—Hofmann (1983: 14) followed what he called "a peculiar presentiment," a hunch, "that this substance could possess properties other than those established in the first investigations." He noted that "this was quite unusual; experimental substances, as a rule, were definitely stricken from the research program if once found to be lacking in pharmacological interest" (14). To make a long story short, Hofmann must have contaminated himself with a small amount of this highly potent substance, and he experienced an uninterrupted stream of fantastic pictures, extraordinary shapes with an intense, kaleidoscopic play of colors. Three days later, he conducted a self-experiment, ingesting what he (falsely) believed to be a small dose, and he experienced the first full-blown LSD trip in human history. The reason why this story is recounted over and over again is not the heroism of Hofmann's self-experiment—self-administration was not uncommon in pharmacology at the time—but his claim to have followed a "peculiar presentiment" when taking the seemingly insignificant compound from the shelf again (see, e.g., Nichols 2006). He discovered its mind-blowing effects accidentally because of a little sloppiness in his usually meticulous chemical bench work. This led Hofmann to conclude that he did not find LSD but that it was LSD that found him. It must have been divine providence, not scientific method, admitting us to the enchanted world behind the "doors of perception."
However, Hofmann, who had had his first mystical experience as a boy walking in the forest, was quick to add that one did not need LSD anymore once the gateway had been opened in one way or another. His greatest hope was that one day state-controlled meditation centers would provide LSD to facilitate the spiritual development of those seeking access to this experiential plane. But, he said, he did not want to be a guru telling others what to do. The organizer closed the opening ceremony by saying, "Dear Albert, you're certainly the very best example to show that what you discovered is no infernal stuff!" Hofmann was presented with an enormous bunch of red roses. He expressed his thanks by saying that he was particularly grateful for the flowers, as our connectedness with other life forms, including plants, had become more and more important to him in recent years: "The feeling of co-creatureliness with all things alive should enter our consciousness more fully and counterbalance the materialistic and nonsensical technological development in order to enable us to return to the roses, to the flowers, to nature, where we belong." Tumultuous applause again.
Many of the media reports on Hofmann, his pharmacological problem child, and the three-day conference, with its abundance of lectures, discussion panels, workshops, and stalls, proclaimed a comeback of hallucinogen research. After its discovery in 1943, the story went, LSD soon escaped the walls of the laboratory. Its propagation by irresponsible scientists like Timothy Leary and its widespread abuse by the hippies was said to have eventually led to the criminalization of LSD and other hallucinogens in the 1960s. After scientific research on this class of drugs had subsequently been repressed for more than two decades, a more pragmatic attitude had finally gained the upper hand. Since the 1990s, it had given rise to a revival of hallucinogen research. Thus the framing of the event.
The proponents of this resurgence gathered at the LSD Symposium. A minority among the crowds of old hippies, New Age disciples, and psychedelic geeks, these brain researchers, pharmacologists, and psychiatrists used the occasion of Hofmann's hundredth birthday to demonstrate the restored vitality of their scientific field. Many of the preclinical and clinical studies conducted in recent years were, for the first time, presented to a broad audience and received a significant amount of media attention. Even though many of the so-called psychedelic elders were still present, a new generation of American and European hallucinogen researchers had taken over, introducing these "magic drugs" into the age of cognitive neuroscience.
THE HEYDAY OF HALLUCINOGEN RESEARCH
But what exactly was being revived? And how was the revival different from the historic era, which it sought to resume? In the mid-twentieth century, hallucinogenic drugs came to play a key role in psychiatric and psychopharmacological research. Much has been written about this important chapter in the history of science and medicine. Let me brie y recapitulate to lay the ground for my account of the current revival of psychedelic science.
Hallucinogens became an object of scientific investigation in the course of the nineteenth century as Europeans and Americans observed their uses in other cultures. The French psychiatrist Jacques-Joseph Moreau de Tours brought hashish from a trip to the Orient, which, in the 1840s, he used to both model and treat mental illness. The spreading use of peyote among Native Americans in the second half of the century led US and English researchers like Silas Weir Mitchell or Henry Havelock Ellis to study the effects of the cactus. Through a series of self-experiments, the German chemist Arthur Heffter identified and isolated mescaline as its pharmacologically active principle in 1897. And two decades later, his colleague Ernst Späth managed to synthesize the substance (Perrine 2001).
From the 1920s onward, German and French psychiatrists such as Kurt Beringer, Ernst Joëll, Fritz Fränkel, and Alexandre Rouhier returned to Moreau's psychopharmacological modeling of mental disorders, administering mescaline instead of hashish to healthy subjects. After LSD was discovered in 1943, it was first used in this tradition of experimental psychiatry. But Hofmann's chance find also marked the beginning of a profound transformation of the field. In the course of the 1950s, more than 750 scholarly articles were published on LSD alone. During this period, the first antipsychotic chlorpromazine and the first tricyclic antidepressant imipramine were discovered as well. This second wave of biological psychiatry differed from its predecessor in that the "psychopharmacological revolution" of the 1950s left behind the therapeutic pessimism prevalent in the late nineteenth century (Shorter 1997). The cerebral substrate of mental illness no longer seemed to be a matter of fate but rather a target of biomedical intervention (Rose 2007). When it was found that chlorpromazine could antagonize some of the effects of LSD, an experimental system emerged that seemed to allow exploration of causes as well as potential treatments of schizophrenia in the laboratory. Model psychosis research was no longer confined to mimicking the experience of mental illness but turned into a quest for its biochemical cause: a psychotogenic molecule resembling LSD or mescaline. Psychiatry finally seemed to get a chance to meet the scientific standards and therapeutic expectations set by other medical specialties (Caldwell 1970; Ulrich and Patten 1991; Novak 1997; Thuillier 1999; Vannini and Venturini 1999; Healy 2002: 107; Langlitz 2006a; Dyck 2008: 32–52).
In brain research, this sudden upswing of psychopharmacology supplemented anatomical and electrophysiological conceptions of the brain with a neurochemical one. In contrast to mescaline, which was only psychoactive in doses of several hundred milligrams, LSD was active in the microgram range. The fact that extremely low doses could have such profound pharmacological effects strongly supported the emergent theory of neurotransmission and spawned the "dream of molecular specificity": if the number of molecules were not enough to swamp the entire brain, there had to be specific sites of action; neurotransmitters and drugs had to t into receptors like keys into locks (Healy 2002: 180; Rose 2007: 199–200). The finding that LSD, with a core structure closely resembling that of serotonin, turned out to antagonize the effects of serotonin was soon used to explain its psychotomimetic qualities and helped to establish a tight connection between brain chemistry and behavior (Green 2008). The sociologists Joëlle Abi-Rached and Nikolas Rose (2010) have shown how this new "neuromolecular gaze," breaking up the holism of psychic life into a multiplicity of receptors, neurotransmitters, ion channels, second messengers, and membrane potentials, eventually led to the birth of the neurosciences in the 1960s.
One of the proponents of this molecularization of psychiatry was Humphry Osmond. Together with his colleagues at Saskatchewan Mental Hospital in Weyburn, Canada, the British physician investigated mescaline-like substances that cause a biochemical imbalance underlying schizophrenia. In her book Psychedelic Psychiatry, medical historian Erika Dyck (2008: 13–31) points out that this research on hallucinogens was supported by the leftist government of the province as part of its commitment to health-care reforms. Demonstrating the biochemical nature of mental illness entailed its destigmatization: psychiatric patients were meant to be treated just like any other patient population.
But in the course of his exchange with Aldous Huxley, Osmond turned away from such reductionist accounts, reconceptualizing "hallucinogens" and "psychotomimetics" as "psychedelics" and paving the way for a spiritual explanation of their effects. Historian of psychopharmacology David Healy (2002: 202) emphasizes the Janus-faced character of this class of drugs: "It is probably no coincidence that biological thinking crept into psychiatry on the back of a group of drugs like the psychedelics, which gave rise to 'spiritual' thinking." Religious interpretations of the hallucinogenic experience also inspired the use of these drugs in the treatment of alcoholism, where LSD was administered to address addiction as a spiritual rather than biomedical condition. Considering that the scientific interest in psychedelics had been triggered by observations of their religious uses in other cultures, psychedelic therapists had come full circle (Dyck 2008: 53–78).
This association of hallucinogenic drugs with spirituality was primarily a North American phenomenon. The more secular Europeans mostly used them to facilitate psychoanalytically oriented psychotherapies, hoping that they would assist the unconscious to reveal its secrets (Passie 1997; Sandison 1997; Vannini and Venturini 1999; Snelders and Kaplan 2002; Roberts 2008). But the rationale of such narcoanalysis or psycholytic therapy was also of interest to the CIA and the US Army, who were looking for a "truth serum" to make interrogations more efficient. The brain was imagined as a locus in which truthfulness could be instilled and from where truth could be extracted. Eventually, the hallucinogen research program of the CIA was closed down in the late 1960s because the effects of these drugs on interrogations turned out to be unpredictable (CIA Historical Review Program 1977; Lee and Shlain 1992; Langlitz 2007; Tanner 2009).
By that time, most hallucinogen research had already been or was about to be terminated. Much of this was due to the politicotheological battles fought over psychedelic drugs in the 1960s, which will be discussed in the next section. But we should also note—and to many readers this might come as more of a surprise—that the field was already in decline before Timothy Leary entered the scene, at a time when the term hippie had not even been coined.
In the late 1950s, physicians' nonchalant dealings with pharmaceuticals, especially with not (yet) approved "investigational drugs," began to be problematized within the medical profession. In 1961, the thalidomide disaster came to the fore: 8,000 children with gross anatomical malformations, an unknown number of abortions, and many patients suffering from peripheral neuropathy. The US Congress passed the Kefauver-Harris amendments in the following year, giving the Food and Drug Administration (FDA) control over all investigational drugs (Daemmrich 2004: 60–69). LSD happened to be such an investigational drug just like thalidomide. A drug safety study on Hofmann's problem child, also published in 1962, warned against the risks of suicide and prolonged psychotic reactions (Cohen and Ditman 1962). Regulations were tightened. Consequently, researchers could no longer mail a form to Sandoz, receive LSD in return, and administer it to patients without even informing them about the experimental nature of their treatment. Now they had to undergo the newly created Investigational Exemption to the New Drug Application process. Henceforth, the FDA had to give prior approval for all testing of experimental drugs. Additionally, Sandoz had grown concerned about its reputation and restricted the provision of LSD in the United States to researchers associated with the National Institute of Mental Health, Veterans Affairs hospitals, and to state commissioners of mental health. As a result, the number of researchers who had access to psychedelics was reduced from several hundred to approximately 70 (or, according to another source, even 13). They were all scientists working within federal and state agencies or they had obtained grants or permissions from such agencies (Masters and Houston 1966: 66; Stevens 1987: 182–182; Novak 1997; Doblin 2000).
Up to this point the history of the medical uses of hallucinogens had been part of a much broader history of controlling pharmaceuticals in the United States. What was at issue when scientific applications of hallucinogens were subjected to a strict regulatory regime in the early 1960s was not spiritual liberation through consciousness-expanding drugs and their association with the politics of the counterculture, but medical paternalism and pharmaceutical marketing practices. After all, the distribution of thalidomide and LSD as investigational drugs primarily served to acquaint doctors with new products and to establish a lucrative therapeutic application from which industry could profit. The expansion of the FDA's duties and power was meant to protect American citizens from ruthless or adventurous physicians, scientists, and businessmen. It belonged to a profound transformation of medical decision making, challenging and curbing physicians' professional dominance with a commitment to individual rights. In the 1960s, trust in medical authority was shaken and thereafter doctors and researchers had to make their decisions about patients and test subjects, treatments and study designs alongside lawyers, judges, legislators, members of ethics committees, and FDA officers (Rothman 1991). These developments in the medical sector were part of an even more far-reaching restructuring of the governance of technological change in industrialized countries that was responding to public concern about the risks accompanying scientific and technological innovation (Brickman et al. 1985: 19). But this was only the beginning of the end of hallucinogen research.
Excerpted from Neuropsychedelia by Nicolas Langlitz. Copyright © 2013 The Regents of the University of California. Excerpted by permission of UNIVERSITY OF CALIFORNIA PRESS.
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