A Biochemical Bridge to the Embodied Psyche:
LSD Research 1945-1965
Kim Hewitt is pursuing a doctorate in American Civilization at the University of Texas at Austin. Her email address is firstname.lastname@example.org. This project is supported in part by MAPS. Comments or further support would be greatly appreciated.
I am writing a cultural studies dissertation that explores how
psychedelics helped facilitate a shift in American ideas about mind-body
interaction. It is well known that Aldous Huxley's publication of The
Doors of Perception in 1954 sparked renewed interest in psychedelics and
speculation that both religious experiences and madness could be
chemically induced, forcing a reconfiguration of mind-body interaction. It
is less well known that knowledge about the chemical structures and
properties of psychedelics played an important role in changing
psychiatric ideas about mental function. As researchers began to construct
a model of mental illness that acknowledged a physiological factor, the
Cartesian duality between mind and body began to crumble, as did the
plausibility of Freudian psychoanalytic techniques for serious mental
disorders. One of the aims of this project is to educate both the academic
community and the general public about the immense cultural impact of
psychedelic drug research, not only in shifting psychiatric views, but in
mainstream ideas about consciousness.
The story of LSD's contribution to psychiatry is a historical strand
distinct from the use of LSD as an adjunct tool for psychotherapy, which
was also hotly debated during the postwar decades. Specifically, LSD
research proved crucial to the development of a biochemical theory of
psychosis and the link between serotonin and mental disorders. The
implications of a physiological element of consciousness--that madness,
and perhaps even religious experience, are inseparable from the body--have
since become commonplace, with widespread repercussions in American life.
More accurate discussion of these ideas by cultural critics and historians
is long overdue, but has become more possible through interdisciplinary
work that reconciles the humanities with research from hard sciences such
as chemistry, biology and neuroscience.
Cultural context influences how we interpret experiences. Prior to
knowledge about the biochemical component of mental illness -- and prior
to knowledge about changes in perception and cognition induced by
psychedelics -- how would we have interpreted the following report?
When I am melting I have no hands. I go into a doorway in order not to be
trampled on. Everything is flying away from me. In the doorway I can
gather together the pieces of my body. It is as if something is thrown in
me, bursts me asunder. Why do I divide myself in different pieces? I feel
that I am without poise, that my personality is melting and that my ego
disappears and that I do not exist anymore. Everything pulls me apart...
The skin is the only possible means of keeping the different pieces
together. There is no connection between different parts of my
As recently as the late 1970s, some psychiatrists would have considered
this experience of schizophrenia a result of a functional disorder -- one
caused by psychological maladjustment to the environment. Yet, mental
disorders and psychedelic experiences have both consistently acted as
catalysts to question the Cartesian duality between mind and body and
explore consciousness. Much postwar research with psychedelic drugs was
based on the psychomimetic properties of the drugs. Because researchers
believed that the psychedelic state mimicked psychosis, they hoped to
understand schizophrenic episodes by studying the "LSD psychosis." Many
psychologists and psychiatrists hoped that by taking LSD they might better
understand their mentally ill patients. Researchers conducted many studies
to test the perceptual and cognitive changes induced by LSD. The idea that
mental illness might be chemically induced spurred re-evaluation of the
etiology of mental disorders, and the workings of the human mind-body --
and forced us to consider holistic mind-body interaction as a possible
model of consciousness. Gradually, we have come to accept that
consciousness has a physiological element, and that the human mind is
inseparable from bodily functioning. By forcing us to reconsider the basis
of everyday functioning, LSD research has prompted us to consider
mind-body holism in relation to mental health, the concepts of identity
and personality, the nature of religious experience, the possibilities for
human pharmacological self-creation, and ultimately of our social
construction of "reality."
Psychiatric "realities" are in large part determined by conceptions of
mind-body interaction, and my completed dissertation will include a
history of ideas of mind-body in psychiatry. In the early twentieth
century, Freudian psychoanalytic theories began to pose non-somatic
explanations for many disorders. A prime example was hysteria, named by
the Greeks for the part of the body where it supposedly originated, the
uterus. Freud relocated the origin of this illness from the body to an
unhealthy psyche, which then affected the woman's behavior and
Although Freud's theories admitted that the mind and body are entwined,
the foundation of his model is a psyche, formed by childhood events,
reigning over the body. Although doctors never lost sight of the
possibility that mental disorders could be caused by an organic lesion, in
the early twentieth century Freudian theory had shifted the emphasis to
psychological factors. Renewed interest in somatic theories during the
1930s was sparked--and complicated by--advances in endocrinology,
biochemistry, genetics and neurology, as well as interpretations of mental
illness from the fields of sociology and anthropology.3
During the 1930s institutions began administering new treatments to
patients diagnosed with mental illness. A brief glimpse at these
treatments illuminates the state of psychiatry before a plausible
biochemical theory was developed. That doctors employed these stringent
techniques in the absence of a conceptual theory for how and why they
worked illustrates the crucial importance of even the slightest bit of
information that could explain the etiology of mental disease. Although on
rare occasion one of these treatments affected a cure, without a clear
idea of what caused the condition diagnosed as schizophrenia or
manic-depression, doctors could not understand how or why a treatment was
Beginning in the 1930s, a patient institutionalized for depression might be
subjected to insulin injections, each one of which would induce a
temporary coma, or a series of electroshock treatments, during which
electrical current would be conducted through the patient's head, jolting
the patient into convulsions and unconsciousness. Although these
treatments often stabilized the individual, they were not pleasant
experiences. As Sylvia Plath described in lines of poetry that were likely
inspired by her electroshock therapy, "By the roots of my hair some god
got hold of me, I sizzled in his blue volts like a desert
prophet."4 Side effects could entail spinal fractures or other
broken bones suffered during the electrically induced convulsions.
For intractable cases of severe mental illness, the last resort was a
procedure developed by two Portuguese doctors in 1936. This
"psychosurgery" was called lobotomy because it destroyed the cortex of the
frontal lobe of the brain. By 1947, doctors in the United States had performed
2,000 lobotomies.5 However, Drs. Walter Freeman and James
Watts, pioneers of lobotomy in the United States, pointed out in The
American Journal of Psychiatry, that lobotomy was definitely not a cure.
Rather, it was a "decidedly practical" effort to help the patient adjust
to his environment. Freeman and Watts admitted the limited benefits of
lobotomy by emphasizing "above all we do not speak of recovery." Rather, a
fair result would be the ability of the patient to live outside the
hospital, while a good result would enable the patient to "earn a living
or manage a household." Individuals who suffered from schizophrenia
benefited least from prefrontal lobotomy, and the majority of these
patients were never capable of leaving the hospital, even after
psychosurgery. However, the doctors noted that the surgery made the
patients more docile on the hospital ward.
Although psychosurgery did not usually reduce hallucinations or other
symptoms of psychosis, it certainly reduced the extremities of emotion and
behavior for some patients. Their violent outbursts diminished and were
replaced by apathy and inertia.6 This may have improved the
tenor of life for these patients, or at least for those surrounding them.
or not quality of life improved is debatable. At the time, doctors, or at
least Freedman and Watts, did not dwell on the tragic price paid to remove
the most extreme antisocial behaviors associated with mental illness. The
usefulness of lobotomy lay in the reorientation of the patient, who turned
away "from the self to the environment. The patient takes his cue from
those around him. He is cheerful when they are cheerful, playful when they
are playful, sympathetic when they arouse his sympathy, apologetic when
they show him how he has transgressed." In short, the lobotomy quelled
behaviors society could not tolerate, and created a pliable individual, no
longer absorbed in the suffering of his illness, but responsive to the
needs of the environment. "He is unconcerned about himself and unworried
about the future. If he is no longer able to paint pictures, write poetry
or compose music, he is, on the other hand, no longer ashamed to fetch and
carry, to wait on table or make beds or empty cans. If he has suffered
some reduction in his personal dignity and vanity, he has gained in social
Thus were the hopes for otherwise intelligent and talented individuals who
suffered from severe mental illness in 1945. Today, mental disorders still
cause abysmal suffering, while treatments remain experimental and
problematic. Even the best drug therapies often incur side effects, some
of which can be devastatingly disruptive. Many cases of manic-depression,
schizophrenia, and other chronic illnesses still remain unresponsive to
any treatment. The unfortunate reality remains that today the exact causes
of mental illness remain a mystery. However, the biochemical theories
postulated in the 1950s began to steer doctors and therapists -- as well
as the general public -- away from theories that blamed childhood trauma,
the schizogenic mother or dysfunctional family, social maladjustment or
In The Doors of Perception, Huxley revealed that he felt strongly that his
mescaline state bordered at moments on madness, although he noted "most
takers of mescaline experience only the heavenly parts of
schizophrenia."8 Huxley sketched out Humphry Osmond's
adrenochrome theory. Osmond, then working at a psychiatric hospital in
Canada, had noted the similarity between the chemical compositions of
mescaline and adrenaline. Since the mescaline molecule could produce a
state similar to psychosis, Osmond wondered if psychosis was a result of
a malfunction of adrenaline production in the human body. Perhaps a toxic
biochemical was produced as nor-adrenaline changed into adrenaline.
Osmond called this unknown biochemical "substance M," and theorized that
it was a cause of psychosis.9 Although this theory was never
proven, it was among the first specific biochemical theories of mental
illness. At the Rockefeller Institute for Medical Research in New York, chemists were following a similar train of thought as they pondered the similarity between the molecular structures of LSD and serotonin. The theories they produced have proven fruitful for psychiatric research.
The new ideas about the etiology of mental disorder hinged on the
discovery of serotonin in the late 1940s. Maurice M. Rapport and his
coworkers Arda Alden Green and Irvine H. Page had isolated serotonin from
beef serum in 1948, and demonstrated its ability to contract the smooth
muscles lining the walls of blood vessels in rabbit ear tissue. This
vasoconstriction narrowed blood vessels, raising blood pressure. As
Rapport and his fellow researchers tested the newly isolated
vasoconstrictor, they noted that its chemical and biological activity
resembled that of epinephrine -- also called adrenaline -- although its
vasoconstrictor action was twice as powerful.10] In 1949,
Rapport confirmed the chemical formula for serotonin and called it
Several chemists at the Rockefeller Institute based their research on
Rapport's findings. In an attempt to find a treatment for high blood
pressure, D.W. Woolley and E. Shaw searched for serotonin antagonists,
agents that would block the vasoconstrictor action of the serotonin
molecule. The most likely candidates were serotonin metabolites -
chemicals with molecular structure similar to serotonin, which would take
the place of the serotonin molecule in living tissues.12 Among
metabolites Woolley and Shaw isolated as possible treatments for
hypertension were the ergot alkaloids, including LSD, which has a chemical
structure similar to serotonin.13 Although another chemist in
was simultaneously proving that LSD antagonized serotonin, his results
were published somewhat later than Woolley's.14
In 1954, after determining that several hallucinogenic drugs, including
the ergot alkaloids, the harmala alkaloids, and yohimbine, were also
serotonin antagonists; Woolley and Shaw formulated a theory of the
etiology of mental disorders. Published as an article in Science in 1954,
and as a book in 1962, Woolley and Shaw's theory proposed that serotonin
mediated mental processes, and that psychosis was caused by a disturbance
in serotonin in the brain.15 Woolley was unsure whether over or
underproduction of serotonin was the culprit, but showed evidence that
serotonin was vital to mental functioning. This serendipitous biochemical
discovery of the physiology of "mind" and mental disorder resulted from
scientific experimentation with LSD as one of a number of serotonin
In 1957, the March issue of the Annals of the New York Academy of Science
was dedicated to research with hallucinogens. Articles by Humphry Osmond,
Woolley and Shaw, and others discussed research methodology, findings,
implications, ethics, and future directions. Hudson Hoagland pointed out
the role psychomimetic drugs played in reawakening interest in biochemical
psychiatric research. Without dismissing environmental factors, Hoagland
put forth a new paradigm for "mental" functioning that considered
neurochemical factors, even as he recognized the limits of a strictly
physiological model for behavior.
"(A)ll behavior... is a result of the organized activities of the brain
functioning in its internal environment in which the cellular dynamics
determined by enzyme constellations and a host of chemical determinants
are basic to the nature of behavior. The personal developmental history of
an individual in relation to his environment, can by conditioning, modify
within limits various aspects of the brain, but why some persons develop
schizophrenia in the face of life's stresses and others do not is the
prime unanswered question."16
Hoagland spent the major part of his article addressing the biochemical
findings of LSD research and their importance for a new model of mental
function and dysfunction. He clearly laid a groundwork for the larger
implications of these findings for understanding human behavior and human
nature, as he stated, "a behaving disembodied psyche is a meaningless
Likewise, the psyche eviscerated from its cultural milieu is
incomprehensible. Interdisciplinary cultural studies are seeking new
methods with which to understand individual and mass human behavior and
its contexts. Postwar research with psychedelic drugs, in science labs and
among intellectuals and others, provided an inchoate methodology that
includes embodied biochemical functioning. Today, when seeking to
understand mental disorder, one can no longer avoid the physiological
element. In Listening to Prozac, psychiatrist Peter Kramer has
characterized this trend as the "medicalization of
the philosophical implications extend even further. The psychedelic
research that narrowed the gap between mind and body may provide a
paradigm for interdisciplinary study as it seeks to encompass the embodied
human into cultural studies.
1 - Louis A. Sass, Madness and Modernism: Insanity in the Light of Modern Art, Literature, and Thought, (New York: Basic Books, 1992), 15.
2 - Barbara Ehrenreich and Deirdre English, For Her Own Good: 150 years of the Experts' Advice to Women (New York: Doubleday, 1978), 139.
3 - Madison Bentley and E.V. Cowdry, "The character of the problem," In: The Problem of Mental Disorder (NY: McGraw-Hill Book Co., Inc, 1934),1-6.
4 - Sylvia Plath, "The Hanging Man," Ariel (New York: Harper and Row, 1965), 69.
5 - James Peter Murphy, "Newer techniques in psychosurgery," J Nerv Ment Dis 1952 116(2): 125-130.
6 - James Peter Murphy, " Newer techniques in psychosurgery," J Nerv Ment Dis 1952 116(2): 125-130.
7 - Walter Freedman and James W. Watts, "Prefrontal lobotomy," Am J Psychiatry May 1945 101(6): 739-748.
8 - Aldous Huxley, The Doors of Perception (New York; Harper & Bros, 1954), 54.
9 - Humphry Osmond, "Schizophrenia: A New Approach," J Mental Sci 1952 98(411): 309-315, Abram Hoffer, Humphry Osmond, and John Smythies, "Schizophrenia: A New Approach II. Result of a Year's Research," J Mental Sci 1954 100: 29-45.
10 - Maurice M. Rapport, Arda Alden Green, and Irvine H. Page, "Serum vasoconstrictor (serotonin) IV. Isolation and characterization," J Biol Chem 1948 176: 1243-1251.
11 - Maurice M. Rapport, "Serum vasoconstrictor (serotonin) V. The presence of creatinine in the complex. A proposed structure of the vasoconstrictor principle," J Biol Chem 1949 180: 961-969.
12 - D.W. Woolley and E. Shaw, "Some anti-metabolites of serotonin and their possible application to the treatment of hypertension," Am. Chem Soc J June 5, 1952 74: 2948-2949.
13 - Ellicott Shaw and D.W. Woolley, "Yohimbine and ergot alkaloids as naturally occurring antimetabolites of serotonin," J Biol Chem 1953 203: 979-989.
14 - J.H. Gaddum, "Antagonism between lysergic acid diethylamide and 5-hydroxytryptamine," J Physiol London 1953 121: 15.
15 - D.W. Woolley and E. Shaw, "A biochemical and pharmacological suggestion about certain mental disorders," Science 1954 119: 587-588. D.W. Woolley, The Biochemical Bases of Psychoses (New York: John Wiley & Sons, Inc.: 1962).
16 - Hudson Hoagland, "A review of the biochemical changes induced in vivo by lysergic acid diethylamide and similar drugs," Annals NY Acad Sci March 14, 1957 66(3): 445-458.
17 - Peter Kramer, Listening to Prozac: A Psychiatrist Explores Antidepressant Medications and the Remaking of the Self (New York: Penguin Books, 1993), 37.