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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