LSD — My Problem Child
Albert Hofmann
1. How LSD Originated
In the realm of scientific observation, luck
is granted only to
those who are prepared.
—Louis Pasteur
Time and again I hear or read that LSD was discovered by
accident. This is only partly true. LSD came into being within a systematic
research program, and the "accident" did not occur until much later: when LSD
was already five years old, I happened to experience its unforeseeable effects
in my own body—or rather, in my own mind.
Looking back over my
professional career to trace the influential events and decisions that
eventually steered my work toward the synthesis of LSD, I realize that the most
decisive step was my choice of employment upon completion of my chemistry
studies. If that decision had been different, then this substance, which has
become known the world over, might never have been created. In order to tell the
story of the origin of LSD, then, I must also touch briefly on my career as a
chemist, since the two developments are inextricably interrelated.
In the spring of 1929, on concluding my chemistry studies at the
University of Zurich, I joined the Sandoz Company's pharmaceutical-chemical
research laboratory in Basel, as a co-worker with Professor Arthur Stoll,
founder and director of the pharmaceutical department. I chose this position
because it afforded me the opportunity to work on natural products, whereas two
other job offers from chemical firms in Basel had involved work in the field of
synthetic chemistry.
First Chemical Explorations
My doctoral work at Zurich
under Professor Paul Karrer had already given me one chance to pursue my
interest in plant and animal chemistry. Making use of the gastrointestinal juice
of the vineyard snail, I accomplished the enzymatic degradation of chitin, the
structural material of which the shells, wings, and claws of insects,
crustaceans, and other lower animals are composed. I was able to derive the
chemical structure of chitin from the cleavage product, a nitrogen-containing
sugar, obtained by this degradation. Chitin turned out to be an analogue of
cellulose, the structural material of plants. This important result, obtained
after only three months of research, led to a doctoral thesis rated "with
distinction."
When I joined the Sandoz firm, the staff of the
pharmaceutical-chemical department was still rather modest in number. Four
chemists with doctoral degrees worked in research, three in production.
In Stoll's laboratory I found employment that completely
agreed with me as a research chemist. The objective that Professor Stoll had set
for his pharmaceutical-chemical research laboratories was to isolate the active
principles (i.e., the effective constituents) of known medicinal plants to
produce pure specimens of these substances. This is particularly important in
the case of medicinal plants whose active principles are unstable, or whose
potency is subject to great variation, which makes an exact dosage difficult.
But if the active principle is available in pure form, it becomes possible to
manufacture a stable pharmaceutical preparation, exactly quantifiable by weight.
With this in mind, Professor Stoll had elected to study plant substances of
recognized value such as the substances from foxglove (Digitalis),
Mediterranean squill (Scilla maritima), and ergot of rye (Claviceps
purpurea or Secale cornutum), which, owning to their instability and
uncertain dosage, nevertheless, had been little used in medicine.
My first years in the Sandoz laboratories were devoted almost exclusively
to studying the active principles of Mediterranean squill. Dr. Walter Kreis, one
of Professor Stoll's earliest associates, launched me in this field of research.
The most important constituents of Mediterranean squill already existed in pure
form. Their active agents, as well as those of woolly foxglove (Digitalis
lanata), had been isolated and purified, chiefly by Dr. Kreis, with
extraordinary skill.
The active principles of Mediterranean
squill belong to the group of cardioactive glycosides (glycoside =
sugar-containing substance) and serve, as do those of foxglove, in the treatment
of cardiac insufficiency. The cardiac glycosides are extremely active
substances. Because the therapeutic and the toxic doses differ so little, it
becomes especially important here to have an exact dosage, based on pure
compounds.
At the beginning of my investigations, a
pharmaceutical preparation with Scilla glycosides had already been introduced
into therapeutics by Sandoz; however, the chemical structure of these active
compounds, with the exception of the sugar portion, remained largely unknown.
My main contribution to the Scilla research, in which I
participated with enthusiasm, was to elucidate the chemical structure of the
common nucleus of Scilla glycosides, showing on the one hand their differences
from the Digitalis glycosides, and on the other hand their close
structural relationship with the toxic principles isolated from skin glands of
toads. In 1935, these studies were temporarily concluded.
Looking for a new field of research, I asked Professor Stoll to let me continue
the investigations on the alkaloids of ergot, which he had begun in 1917 and
which had led directly to the isolation of ergotamine in 1918. Ergotamine,
discovered by Stoll, was the first ergot alkaloid obtained in pure chemical
form. Although ergotamine quickly took a significant place in therapeutics
(under the trade name Gynergen) as a hemostatic remedy in obstetrics and as a
medicament in the treatment of migraine, chemical research on ergot in the
Sandoz laboratories was abandoned after the isolation of ergotamine and the
determination of its empirical formula. Meanwhile, at the beginning of the
thirties, English and American laboratories had begun to determine the chemical
structure of ergot alkaloids. They had also discovered a new, water-soluble
ergot alkaloid, which could likewise be isolated from the mother liquor of
ergotamine production. So I thought it was high time that Sandoz resumed
chemical research on ergot alkaloids, unless we wanted to risk losing our
leading role in a field of medicinal research, which was already becoming so
important.
Professor Stoll granted my request, with some
misgivings: "I must warn you of the difficulties you face in working with ergot
alkaloids. These are-exceedingly sensitive, easily decomposed substances, less
stable than any of the compounds you have investigated in the cardiac glycoside
field. But you are welcome to try."
And so the switches were
thrown, and I found myself engaged in a field of study that would become the
main theme of my professional career. I have never forgotten the creative joy,
the eager anticipation I felt in embarking on the study of ergot alkaloids, at
that time a relatively uncharted field of research.
Ergot
It may be helpful here to give some background
information about ergot itself.[For further information on ergot, readers should
refer to the monographs of G. Berger, Ergot and Ergotism (Gurney and
Jackson, London, 1931 ) and A. Hofmann, Die Mutterkornalkaloide (F. Enke
Verlag, Stuttgart, 1964). The former is a classical presentation of the history
of the drug, while the latter emphasizes the chemical aspects.] It is produced
by a lower fungus (Claviceps purpurea) that grows parasitically on rye
and, to a lesser extent, on other species of grain and on wild grasses. Kernels
infested with this fungus develop into light-brown to violet-brown curved pegs
(sclerotia) that push forth from the husk in place of normal grains. Ergot is
described botanically as a sclerotium, the form that the ergot fungus takes in
winter. Ergot of rye (Secale cornutum) is the variety used medicinally.
Ergot, more than any other drug, has a fascinating history, in
the course of which its role and meaning have been reversed: once dreaded as a
poison, in the course of time it has changed to a rich storehouse of valuable
remedies. Ergot first appeared on the stage of history in the early Middle Ages,
as the cause of outbreaks of mass poisonings affecting thousands of persons at a
time. The illness, whose connection with ergot was for a long time obscure,
appeared in two characteristic forms, one gangrenous (ergotismus
gangraenosus) and the other convulsive (ergotismus convulsivus).
Popular names for ergotism—such as "mal des ardents," "ignis sacer," "heiliges
Feuer," or "St. Anthony's fire"—refer to the gangrenous form of the disease. The
patron saint of ergotism victims was St. Anthony, and it was primarily the Order
of St. Anthony that treated these patients.
Until recent
times, epidemic-like outbreaks of ergot poisoning have been recorded in most
European countries including certain areas of Russia. With progress in
agriculture, and since the realization, in the seventeenth century, that
ergot-containing bread was the cause, the frequency and extent of ergotism
epidemics diminished considerably. The last great epidemic occurred in certain
areas of southern Russia in the years 1926-27. [The mass poisoning in the
southern French city of Pont-St. Esprit in the year 1951, which many writers
have attributed to ergot-containing bread, actually had nothing to do with
ergotism. It rather involved poisoning by an organic mercury compound that was
utilized for disinfecting seed.]
The first mention of a
medicinal use of ergot, namely as an ecbolic (a medicament to precipitate
childbirth), is found in the herbal of the Frankfurt city physician Adam
Lonitzer (Lonicerus) in the year 1582. Although ergot, as Lonitzer stated, had
been used since olden times by midwives, it was not until 1808 that this drug
gained entry into academic medicine, on the strength of a work by the American
physician John Stearns entitled Account of the Putvis Parturiens, a Remedy
for Quickening Childbirth. The use of ergot as an ecbolic did not, however,
endure. Practitioners became aware quite early of the great danger to the child,
owing primarily to the uncertainty of dosage, which when too high led to uterine
spasms. From then on, the use of ergot in obstetrics was confined to stopping
postpartum hemorrhage (bleeding after childbirth).
It was not
until ergot's recognition in various pharmacopoeias during the first half of the
nineteenth century that the first steps were taken toward isolating the active
principles of the drug. However, of all the researchers who assayed this problem
during the first hundred years, not one succeeded in identifying the actual
substances responsible for the therapeutic activity. In 1907, the Englishmen G.
Barger and F. H. Carr were the first to isolate an active alkaloidal
preparation, which they named ergotoxine because it produced more of the toxic
than therapeutic properties of ergot. (This preparation was not homogeneous, but
rather a mixture of several alkaloids, as I was able to show thirty-five years
later.) Nevertheless, the pharmacologist H. H. Dale discovered that ergotoxine,
besides the uterotonic effect, also had an antagonistic activity on adrenaline
in the autonomic nervous system that could lead to the therapeutic use of ergot
alkaloids. Only with the isolation of ergotamine by A. Stoll (as mentioned
previously) did an ergot alkaloid find entry and widespread use in therapeutics.
The early 1930s brought a new era in ergot research, beginning
with the determination of the chemical structure of ergot alkaloids, as
mentioned, in English and American laboratories. By chemical cleavage, W. A.
Jacobs and L. C. Craig of the Rockefeller Institute of New York succeeded in
isolating and characterizing the nucleus common to all ergot alkaloids. They
named it lysergic acid. Then came a major development, both for chemistry and
for medicine: the isolation of the specifically uterotonic, hemostatic principle
of ergot, which was published simultaneously and quite independently by four
institutions, including the Sandoz laboratories. The substance, an alkaloid of
comparatively simple structure, was named ergobasine (syn. ergometrine,
ergonovine) by A. Stoll and E. Burckhardt. By the chemical degradation of
ergobasine, W. A. Jacobs and L. C. Craig obtained lysergic acid and the amino
alcohol propanolamine as cleavage products.
I set as my first
goal the problem of preparing this alkaloid synthetically, through chemical
linking of the two components of ergobasine, lysergic acid and propanolamine
(see structural formulas in the appendix).
The lysergic acid
necessary for these studies had to be obtained by chemical cleavage of some
other ergot alkaloid. Since only ergotamine was available as a pure alkaloid,
and was already being produced in kilogram quantities in the pharmaceutical
production department, I chose this alkaloid as the starting material for my
work. I set about obtaining 0.5 gm of ergotamine from the ergot production
people. When I sent the internal requisition form to Professor Stoll for his
countersignature, he appeared in my laboratory and reproved me: "If you want to
work with ergot alkaloids, you will have to familiarize yourself with the
techniques of microchemistry. I can't have you consuming such a large amount of
my expensive ergotamine for your experiments."
The ergot
production department, besides using ergot of Swiss origin to obtain ergotamine,
also dealt with Portuguese ergot, which yielded an amorphous alkaloidal
preparation that corresponded to the aforementioned ergotoxine first produced by
Barger and Carr. I decided to use this less expensive material for the
preparation of lysergic acid. The alkaloid obtained from the production
department had to be purified further, before it would be suitable for cleavage
to lysergic acid. Observations made during the purification process led me to
think that ergotoxine could be a mixture of several alkaloids, rather than one
homogeneous alkaloid. I will speak later of the far-reaching sequelae of these
observations.
Here I must digress briefly to describe the
working conditions and techniques that prevailed in those days. These remarks
may be of interest to the present generation of research chemists in industry,
who are accustomed to far better conditions.
We were very
frugal. Individual laboratories were considered a rare extravagance. During the
first six years of my employment with Sandoz, I shared a laboratory with two
colleagues. We three chemists, plus an assistant each, worked in the same room
on three different fields: Dr. Kreiss on cardiac glycosides; Dr. Wiedemann, who
joined Sandoz around the same time as I, on the leaf pigment chlorophyll; and I
ultimately on ergot alkaloids. The laboratory was equipped with two fume hoods
(compartments supplied with outlets), providing less than effective ventilation
by gas flames. When we requested that these hoods be equipped with ventilators,
our chief refused on the ground that ventilation by gas flame had sufficed in
Willstatter's laboratory.
During the last years of World War
I, Professor Stoll had been an assistant in Berlin and Munich to the
world-famous chemist and Nobel laureate Professor Richard Willstatter, and with
him had conducted the fundamental investigations on chlorophyll and the
assimilation of carbon dioxide. There was scarcely a scientific discussion with
Professor Stoll in which he did not mention his revered teacher Professor
Willstatter and his work in Willstatter's laboratory.
The
working techniques available to chemists in the field of organic chemistry at
that time (the beginning of the thirties) were essentially the same as those
employed by Justus von Liebig a hundred years earlier. The most important
development achieved since then was the introduction of microanalysis by B.
Pregl, which made it possible to ascertain the elemental composition of a
compound with only a few milligrams of specimen, whereas earlier a few
centigrams were needed. Of the other physical-chemical techniques at the
disposal of the chemist today—techniques which have changed his way of working,
making it faster and more effective, and created entirely new possibilities,
above all for the elucidation of structure - none yet existed in those days.
For the investigations of Scilla glycosides and the
first studies in the ergot field, I still used the old separation and
purification techniques from Liebig's day: fractional extraction, fractional
precipitation, fractional crystallization, and the like. The introduction of
column chromatography, the first important step in modern laboratory technique,
was of great value to me only in later investigations. For structure
determination, which today can be conducted rapidly and elegantly with the help
of spectroscopic methods (UV, IR, NMR) and X-ray crystallography, we had to
rely, in the first fundamental ergot studies, entirely on the old laborious
methods of chemical degradation and derivatization.
Lysergic Acid and Its Derivatives
Lysergic acid proved to
be a rather unstable substance, and its rebonding with basic radicals posed
difficulties. In the technique known as Curtius' Synthesis, I ultimately found a
process that proved useful for combining lysergic acid with amines. With this
method I produced a great number of lysergic acid compounds. By combining
lysergic acid with the amino alcohol propanolamine, I obtained a compound that
was identical to the natural ergot alkaloid ergobasine. With that, the first
synthesis—that is, artificial production—of an ergot alkaloid was accomplished.
This was not only of scientific interest, as confirmation of the chemical
structure of ergobasine, but also of practical significance, because ergobasine,
the specifically uterotonic, hemostatic principle, is present in ergot only in
very trifling quantities. With this synthesis, the other alkaloids existing
abundantly in ergot could now be converted to ergobasine, which was valuable in
obstetrics.
After this first success in the ergot field, my
investigations went forward on two fronts. First, I attempted to improve the
pharmacological properties of ergobasine by variations of its amino alcohol
radical. My colleague Dr. J. Peyer and I developed a process for the economical
production of propanolamine and other amino alcohols. Indeed, by substitution of
the propanolamine contained in ergobasine with the amino alcohol butanolamine,
an active principle was obtained that even surpassed the natural alkaloid in its
therapeutic properties. This improved ergobasine has found worldwide application
as a dependable uterotonic, hemostatic remedy under the trade name Methergine,
and is today the leading medicament for this indication in obstetrics.
I further employed my synthetic procedure to produce new
lysergic acid compounds for which uterotonic activity was not prominent, but
from which, on the basis of their chemical structure, other types of interesting
pharmacological properties could be expected. In 1938, I produced the
twenty-fifth substance in this series of lysergic acid derivatives: lysergic
acid diethylamide, abbreviated LSD-25 (Lyserg-säure-diäthylamid) for laboratory
usage.
I had planned the synthesis of this compound with the
intention of obtaining a circulatory and respiratory stimulant (an analeptic).
Such stimulating properties could be expected for lysergic acid diethylamide,
because it shows similarity in chemical structure to the analeptic already known
at that time, namely nicotinic acid diethylamide (Coramine). During the testing
of LSD-25 in the pharmacological department of Sandoz, whose director at the
time was Professor Ernst Rothlin, a strong effect on the uterus was established.
It amounted to some 70 percent of the activity of ergobasine. The research
report also noted, in passing, that the experimental animals became restless
during the narcosis. The new substance, however, aroused no special interest in
our pharmacologists and physicians; testing was therefore discontinued.
For the next five years, nothing more was heard of the
substance LSD-25. Meanwhile, my work in the ergot field advanced further in
other areas. Through the purification of ergotoxine, the starting material for
lysergic acid, I obtained, as already mentioned, the impression that this
alkaloidal preparation was not homogeneous, but was rather a mixture of
different substances. This doubt as to the homogeneity of ergotoxine was
reinforced when in its hydrogenation two distinctly different hydrogenation
products were obtained, whereas the homogeneous alkaloid ergotamine under the
same condition yielded only a single hydrogenation product (hydrogenation =
introduction of hydrogen). Extended, systematic analytical investigations of the
supposed ergotoxine mixture led ultimately to the separation of this alkaloidal
preparation into three homogeneous components. One of the three chemically
homogeneous ergotoxine alkaloids proved to be identical with an alkaloid
isolated shortly before in the production department, which A. Stoll and E.
Burckhardt had named ergocristine. The other two alkaloids were both new. The
first I named ergocornine; and for the second, the last to be isolated, which
had long remained hidden in the mother liquor, I chose the name ergokryptine
(kryptos = hidden). Later it was found that ergokryptine occurs in two isomeric
forms, which were differentiated as alfa- and beta-ergokryptine.
The solution of the ergotoxine problem was not merely scientifically
interesting, but also had great practical significance. A valuable remedy arose
from it. The three hydrogenated ergotoxine alkaloids that I produced in the
course of these investigations, dihydroergocristine, dihydroergokryptine, and
dihydroergocornine, displayed medicinally useful properties during testing by
Professor Rothlin in the pharmacological department. From these three
substances, the pharmaceutical preparation Hydergine was developed, a medicament
for improvement of peripheral circulation and cerebral function in the control
of geriatric disorders. Hydergine has proven to be an effective remedy in
geriatrics for these indications. Today it is Sandoz's most important
pharmaceutical product.
Dihydroergotamine, which I likewise
produced in the course of these investigations, has also found application in
therapeutics as a circulation- and blood-pressure-stabilizing medicament, under
the trade name Dihydergot.
While today research on important
projects is almost exclusively carried out as teamwork, the investigations on
ergot alkaloids described above were conducted by myself alone. Even the further
chemical steps in the evolution of commercial preparations remained in my
hands—that is, the preparation of larger specimens for the clinical trials, and
finally the perfection of the first procedures for mass production of
Methergine, Hydergine, and Dihydergot. This even included the analytical
controls for the development of the first galenical forms of these three
preparations: the ampoules, liquid solutions, and tablets. My aides at that time
included a laboratory assistant, a laboratory helper, and later in addition a
second laboratory assistant and a chemical technician.
Discovery of the Psychic Effects of LSD
The solution of
the ergotoxine problem had led to fruitful results, described here only briefly,
and had opened up further avenues of research. And yet I could not forget the
relatively uninteresting LSD-25. A peculiar presentiment—the feeling that this
substance could possess properties other than those established in the first
investigations—induced me, five years after the first synthesis, to produce
LSD-25 once again so that a sample could be given to the pharmacological
department for further tests. 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.
Nevertheless, in the
spring of 1943, I repeated the synthesis of LSD-25. As in the first synthesis,
this involved the production of only a few centigrams of the compound.
In the final step of the synthesis, during the purification
and crystallization of lysergic acid diethylamide in the form of a tartrate
(tartaric acid salt), I was interrupted in my work by unusual sensations. The
following description of this incident comes from the report that I sent at the
time to Professor Stoll:
Last Friday, April 16,1943, I was forced to interrupt my work in
the laboratory in the middle of the afternoon and proceed home, being affected
by a remarkable restlessness, combined with a slight dizziness. At home I lay
down and sank into a not unpleasant intoxicated-like condition, characterized
by an extremely stimulated imagination. In a dreamlike state, with eyes closed
(I found the daylight to be unpleasantly glaring), I perceived an
uninterrupted stream of fantastic pictures, extraordinary shapes with intense,
kaleidoscopic play of colors. After some two hours this condition faded away.
This was, altogether, a remarkable
experience—both in its sudden onset and its extraordinary course. It seemed to
have resulted from some external toxic influence; I surmised a connection with
the substance I had been working with at the time, lysergic acid diethylamide
tartrate. But this led to another question: how had I managed to absorb this
material? Because of the known toxicity of ergot substances, I always maintained
meticulously neat work habits. Possibly a bit of the LSD solution had contacted
my fingertips during crystallization, and a trace of the substance was absorbed
through the skin. If LSD-25 had indeed been the cause of this bizarre
experience, then it must be a substance of extraordinary potency. There seemed
to be only one way of getting to the bottom of this. I decided on a
self-experiment.
Exercising extreme caution, I began the
planned series of experiments with the smallest quantity that could be expected
to produce some effect, considering the activity of the ergot alkaloids known at
the time: namely, 0.25 mg (mg = milligram = one thousandth of a gram) of
lysergic acid diethylamide tartrate. Quoted below is the entry for this
experiment in my laboratory journal of April 19, 1943.
Self-Experiments
4/19/43 16:20: 0.5 cc of 1/2 promil aqueous solution of
diethylamide tartrate orally = 0.25 mg tartrate. Taken diluted with about 10
cc water. Tasteless.
17:00: Beginning dizziness, feeling of anxiety, visual
distortions, symptoms of paralysis, desire to laugh.
Supplement of 4/21: Home by bicycle. From 18:00- ca.20:00 most
severe crisis. (See special report.)
Here the
notes in my laboratory journal cease. I was able to write the last words only
with great effort. By now it was already clear to me that LSD had been the cause
of the remarkable experience of the previous Friday, for the altered perceptions
were of the same type as before, only much more intense. I had to struggle to
speak intelligibly. I asked my laboratory assistant, who was informed of the
self-experiment, to escort me home. We went by bicycle, no automobile being
available because of wartime restrictions on their use. On the way home, my
condition began to assume threatening forms. Everything in my field of vision
wavered and was distorted as if seen in a curved mirror. I also had the
sensation of being unable to move from the spot. Nevertheless, my assistant
later told me that we had traveled very rapidly. Finally, we arrived at home
safe and sound, and I was just barely capable of asking my companion to summon
our family doctor and request milk from the neighbors.
In
spite of my delirious, bewildered condition, I had brief periods of clear and
effective thinking—and chose milk as a nonspecific antidote for poisoning.
The dizziness and sensation of fainting became so strong at
times that I could no longer hold myself erect, and had to lie down on a sofa.
My surroundings had now transformed themselves in more terrifying ways.
Everything in the room spun around, and the familiar objects and pieces of
furniture assumed grotesque, threatening forms. They were in continuous motion,
animated, as if driven by an inner restlessness. The lady next door, whom I
scarcely recognized, brought me milk—in the course of the evening I drank more
than two liters. She was no longer Mrs. R., but rather a malevolent, insidious
witch with a colored mask.
Even worse than these demonic
transformations of the outer world, were the alterations that I perceived in
myself, in my inner being. Every exertion of my will, every attempt to put an
end to the disintegration of the outer world and the dissolution of my ego,
seemed to be wasted effort. A demon had invaded me, had taken possession of my
body, mind, and soul. I jumped up and screamed, trying to free myself from him,
but then sank down again and lay helpless on the sofa. The substance, with which
I had wanted to experiment, had vanquished me. It was the demon that scornfully
triumphed over my will. I was seized by the dreadful fear of going insane. I was
taken to another world, another place, another time. My body seemed to be
without sensation, lifeless, strange. Was I dying? Was this the transition? At
times I believed myself to be outside my body, and then perceived clearly, as an
outside observer, the complete tragedy of my situation. I had not even taken
leave of my family (my wife, with our three children had traveled that day to
visit her parents, in Lucerne). Would they ever understand that I had not
experimented thoughtlessly, irresponsibly, but rather with the utmost caution,
an-d that such a result was in no way foreseeable? My fear and despair
intensified, not only because a young family should lose its father, but also
because I dreaded leaving my chemical research work, which meant so much to me,
unfinished in the midst of fruitful, promising development. Another reflection
took shape, an idea full of bitter irony: if I was now forced to leave this
world prematurely, it was because of this Iysergic acid diethylamide that I
myself had brought forth into the world.
By the time the
doctor arrived, the climax of my despondent condition had already passed. My
laboratory assistant informed him about my self-experiment, as I myself was not
yet able to formulate a coherent sentence. He shook his head in perplexity,
after my attempts to describe the mortal danger that threatened my body. He
could detect no abnormal symptoms other than extremely dilated pupils. Pulse,
blood pressure, breathing were all normal. He saw no reason to prescribe any
medication. Instead he conveyed me to my bed and stood watch over me. Slowly I
came back from a weird, unfamiliar world to reassuring everyday reality. The
horror softened and gave way to a feeling of good fortune and gratitude, the
more normal perceptions and thoughts returned, and I became more confident that
the danger of insanity was conclusively past.
Now, little by
little I could begin to enjoy the unprecedented colors and plays of shapes that
persisted behind my closed eyes. Kaleidoscopic, fantastic images surged in on
me, alternating, variegated, opening and then closing themselves in circles and
spirals, exploding in colored fountains, rearranging and hybridizing themselves
in constant flux. It was particularly remarkable how every acoustic perception,
such as the sound of a door handle or a passing automobile, became transformed
into optical perceptions. Every sound generated a vividly changing image, with
its own consistent form and color.
Late in the evening my wife
returned from Lucerne. Someone had informed her by telephone that I was
suffering a mysterious breakdown. She had returned home at once, leaving the
children behind with her parents. By now, I had recovered myself sufficiently to
tell her what had happened.
Exhausted, I then slept, to awake
next morning refreshed, with a clear head, though still somewhat tired
physically. A sensation of well-being and renewed life flowed through me.
Breakfast tasted delicious and gave me extraordinary pleasure. When I later
walked out into the garden, in which the sun shone now after a spring rain,
everything glistened and sparkled in a fresh light. The world was as if newly
created. All my senses vibrated in a condition of highest sensitivity, which
persisted for the entire day.
This self-experiment showed that
LSD-25 behaved as a psychoactive substance with extraordinary properties and
potency. There was to my knowledge no other known substance that evoked such
profound psychic effects in such extremely low doses, that caused such dramatic
changes in human consciousness and our experience of the inner and outer world.
What seemed even more significant was that I could remember
the experience of LSD inebriation in every detail. This could only mean that the
conscious recording function was not interrupted, even in the climax of the LSD
experience, despite the profound breakdown of the normal world view. For the
entire duration of the experiment, I had even been aware of participating in an
experiment, but despite this recognition of my condition, I could not, with
every exertion of my will, shake off the LSD world. Everything was experienced
as completely real, as alarming reality; alarming, because the picture of the
other, familiar everyday reality was still fully preserved in the memory for
comparison.
Another surprising aspect of LSD was its ability
to produce such a far-reaching, powerful state of inebriation without leaving a
hangover. Quite the contrary, on the day after the LSD experiment I felt myself
to be, as already described, in excellent physical and mental condition.
I was aware that LSD, a new active compound with such
properties, would have to be of use in pharmacology, in neurology, and
especially in psychiatry, and that it would attract the interest of concerned
specialists. But at that time I had no inkling that the new substance would also
come to be used beyond medical science, as an inebriant in the drug scene. Since
my self-experiment had revealed LSD in its terrifying, demonic aspect, the last
thing I could have expected was that this substance could ever find application
as anything approaching a pleasure drug. I failed, moreover, to recognize the
meaningful connection between LSD inebriation and spontaneous visionary
experience until much later, after further experiments, which were carried out
with far lower doses and under different conditions.
The next
day I wrote to Professor Stoll the above-mentioned report about my extraordinary
experience with LSD-25 and sent a copy to the director of the pharmacological
department, Professor Rothlin.
As expected, the first reaction
was incredulous astonishment. Instantly a telephone call came from the
management; Professor Stoll asked: "Are you certain you made no mistake in the
weighing? Is the stated dose really correct?" Professor Rothlin also called,
asking the same question. I was certain of this point, for I had executed the
weighing and dosage with my own hands. Yet their doubts were justified to some
extent, for until then no known substance had displayed even the slightest
psychic effect in fraction-of-a-milligram doses. An active compound of such
potency seemed almost unbelievable.
Professor Rothlin himself
and two of his colleagues were the first to repeat my experiment, with only
one-third of the dose I had utilized. But even at that level, the effects were
still extremely impressive, and quite fantastic. All doubts about the statements
in my report were eliminated.
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