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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