THE CNS ACTION OF D-LYSERGIC ACID DIETHYLAMIDE (L.S.D.-25)

• Document Type: CREST
• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP83-00423R000600150003-6
• Release Decision: RIPPUB
• Original Classification: K
• Document Page Count: 2
• Document Creation Date: November 9, 2016
• Document Release Date: March 12, 1999
• Sequence Number: 3
• Content Type: NOTES

Approved For Releas'6 1999/09110
CIA-RDP83-0423R000600150
Prepared by the Committee on Pharmacy and Therapeutics
University of Illinois College of Medicine, Chicago 12
I1 TELLCEF~`, 21
The CNS Action of
.b4.3rl
25X1A2g
CPYRGHT
D-lvseraic Acid Dieth ylamide L.S. D. -25)
Approved For Release 1999/09/10 : CIA-R
ERGOT of rye has long been of
great interest to medical science
and there is some evidence that ergot
was used in the Eighteenth Century
by the French midwives to hasten
labor. The specific alkaloid involved
is ergonovine which produces contrac-
tions of the human uterus. The in-
gestion of large quantities of ergotized
rye produces an acute toxic effect to
which Mezerary in his history of
France gave the name St. Anthony's
Fire when describing epidemics of
ergotism. The constituents of ergot
have been divided by chemists into
two classes, i.e. the alkaloids (active
and inactive), and the amines and
nrhnr nitrntrannnc rmm~nnn is It iS
from the active alkaloid ergonovine,
alluded to, that d-lysergic acid diethyl-
amide is derived. Lysergic acid is the
base of this compound as it is of all
the ergot group. The substance under
consideration is the synthetic amide
CII2
of d-lysergic acid with diethylamine.
The structural formulas of d-lysergic
acid and of d-lysergic acid diethyl-
amide are shown below.
The diethylamide was obtained for
the first time in 1938 by W. A. Stoll
and A. Hofmann.
The quantities of this drug neces-
sary to produce a demonstrable effect
are extremely minute; it was estab-
lished by Stoll that an oral dose of
0.000020 gm. (20 micrograms) ad-
ministered in water solution was suf-
ficient to obtain threshold effects. The
usual doses administered are from 10
to 60 micrograms. The effects of the
drug are noticeable in one-half to one
and one-half hours, with the maximum
effectiveness in from two to two and
one-half hours, and usually persists for
four hours. While the drug effect may
persist for as long as eight hours, this
is unusual. There are sometimes de-
monstrable after-effects lasting as long
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as a week. Forrer and Goldneporr
from studies carried out on la6dt'atory
animals that the lethal dose intrave-
nously is 65 mg. per kilogram and the
lethal subcutaneous dose 285 mg. per
kilogram. This indicates that d-ly-
sergic acid diethylamide is a relatively
nontoxic drug. It appears to be quite
safe since the usual dosage is from
10 to 60 micrograms.
PHYSIOLOGICAL EFFECTS
The systemic effects of the drug,
as reported in the literature, are varied
and often contradictory. Most in-
vestigators seem to be in agreement
that a dilation of the pupils is pro-
duced and Forrer and Goldner noticed
only a slight dilation when L.S.D: 25
was instilled directly into the.conjtigc-
tival sac, which observation' indicates
that the dilation is due primarily' to
the central effects of the' drug. The
pulse rate increases, and hypersaliva-
tion occurs, the latter increasing di-
rectly with theamountof the: drug. ad-
ministered. Gastric distress, nausea
and occasional vomiting have often
been reported, as have skin flushing
and a slight ataxia. Increased lacrima-
tion, hyperreflexia, chilliness, muscle
irritability and hot and cold "flashes"
may also occasionally be noted. Stoll
mentions indistinct and blurred speech
and vision as well as disturbances in
tactile perception. No urinary changes
were noticed but a dose of 1 micro-
gram per kilogram was reported by
Forrer and Goldner to produce a de-
finite leukocytosis. These investigators
also found that atropine did not pro-
duce its customary drying of the mu-
cous membranes of the mouth when
the atropine was followed by L.S.D.-25.
Reprinted from The MODERN HOSPITAL, January 1953
7
 De:hon, Rinkel and Solomon re-
ported that the autonomic nervous
system exhibited signs of greater la-
bility during the height of the reaction
to the drug. The tests were carried
out with adrenalin and atropine. They,
as well as other investigators, report
slight changes in the electroencephal-
ogram records of patients under the
influence of L.S.D.-25 but these
changes seem insignificant when com-
pared to the magnitude of the clinical
reaction.
Undoubtedly, the most striking
physiological effect of the drug is the
production of vivid visual hallucina-
tions in a large number of the cases
reported. These are actually pseudo-
hallucinations since the subjects are
aware that these images are subjective.
These hallucinations are best experi-
enced in a darkened room and are
rather specific in character. That is,
they consist mostly of geometrical
patterns and designs and of flashing
whirling and dancing patterns of light.
All of these forms are perceived as
being in motion and, in addition, this
motion seems either to flow toward
the subject or away from him. Bril-
liant hues and colors characterize these
images and they may best be approx-
imated -by indicating their similarity
to the images that are seen in part
of Walt Disney's motion picture
"Fantasia."
Stoll noticed that the colors are de-
finitely influenced by the mood of the
subject, being bright when the sub-
ject is euphoric and mostly confined
to somber hues of blue and dark green
when a psychic depression is experi-
enced. Less frequently, the hallucina-
tions are more organized, landscapes,
vistas and buildings being perceived.
In the light, the incidence of
hallucinations is lessened and often
visual illusions take their place. Ob-
jects are perceived as very tiny and
distant or distorted and out of propor-
tion. Gross disturbances of perspective
are reported. It has also been reported
by Stoll that there are occasionally
synesthetic effects of noise upon visual
hallucinations.
In addition to distortions and dis-
turbances of visual perception, there
are, although less frequently encount-
ered, auditory hallucinations and illu-
sions of a simple nature and a hyper-
sensitivity to auditory stimuli in gen-
eral. Some gustatory. hallucinations
(metallic taste) are also reported.
Tactile hyperesthesia and paresthesia
have already been alluded to.
PSYCHIC'EFFECTS
L.S.D.-25 produces a marked eu-
phoria of mood with increased ami-
ability and alterness. This euphoria,
however, alters easily and may be trans-
formed into a depression in which
suicidal tendencies appear. Whether
in a euphoric state (by far the most
common) or a depressed state, the
mood may be either agitated or apa-
thetic. Time perception is often dis-
turbed with a feeling that a tremen-
dous amount of time has elapsed since
the first administration of the drug.
Temporal perception may also be con-
siderably shortened and, in some in-
stances, there is reported a feeling of
the cessation of time.
These temporal distortions are sim-
ilar to those observed in marihuana
intoxication. The thought processes
are accelerated but there is noticed an
increased distractability and a difficulty
in concentrating. Moreover, the
thought processes often become jumpy
and exhibit little coherence. A certain
clouding of consciousness may occur
but this is not very pronounced and
the subjects seem at all times to be in
good contact with their environment.
Self-observation is often distorted with
feelings of curious detachment and
estrangement; the subjects often report
a feeling of being outside of them-
selves.
At times, in contrast to a flight of
ideas , a distinct poverty of thought
and apathy paralleling certain schiz-
ophrenic states may be induced by
L.S.D.-25. One group of experimen-
ters administered a Rorschach exam-
ination to five normal subjects, four
of whom had control while in a nor-
mal state. All of the tests showed
distinct abnormalities during the
height of L.S.D. intoxication. Three
records were definitely schizoid; one
frankly paranoid record was obtained,
and one record indicated borderline
symptoms not definitely assignable to
any psychiatric classification. These
results lead one to ponder the possi-
bility that perhaps the endogenous re-
lease of a similarly acting compound
might account for schizophrenic reac-
tion types. In addition, the use of
L.S.D.-25 may have use in the further
investigation of the Rorschach test it-
self. Another often reported effect of
the drug is the irrepressible desire to
smile and laugh although no humorous
situation has occurred. Self-control can
not at times be adequately maintained.
Euphoria is the most pronounced and
most often reported psychic effect.
i fichricRelease 1999/
CONSIDERATIONS
The administration of L.S.D: 25"to
schizophrenic patients, as- reported by
Scholl, Forrer and Goldner and Busch
and Johnson, may produce striking
effects. The chief changes seem to be
an increased activity and euphoria and
an increased effect. In addition, they
exhibit evidence of having visual
hallucinations and they undergo most
of the physiological effects seen in nor-
mal persons although they seem to
have a higher tolerance and the total
picture is blander than in normal per-
sons. Patients have seemed to exhibit
a more adequate response to external
stimuli and seem to come into closer
contact with their environment. Some
who had previously refused discussed
their difficulties at length. The changes
produced, while not always predict-
able, seem to have in common an in-
creased and more realistic effect.
Patients were able to experience and
express relevant emotion, and many
patients, following administration of
the drug, strive to establish interper-
sonal relationships which they had
hitherto ignored. The patients thus
become more accessible to the psychia-
trist and better able to reveal and
discuss their problems. This may lead
to a shortened term of psychotherapy.
The toxic effect of the drug seems to
break down the barriers of repression.
In general, according to W. A. Stoll,
the effects of d-lysergic acid diethyl-
amide seem to be those of a delirious
intoxication. This intoxication has
many features which parallel the
actions of ethyl alcohol, marihuana,
mescaline, opium and cocaine. Per-
haps it produces a depression as does
ethyl alcohol since the euphoria, in-
creased emotional lability, dilation of
the pupils, increased deep reflexes, and
increased salivation seem to indicate
this. The blocking of cortical inhibi-
tion would produce some of the effects
noticed during the height of the reac-
tion to this drug. Some investigators
envision a selective inhibitory effect
upon the sympathetic intracortical cir-
cuits and/or sympathetic projections
to or from the telencephalon. Brodman
areas 18 (secondary visual cortex) and
19 (tertiary visual area), the stimula-
tion of which produces unformed
hallucinations of light and hallucina-
tions of formed images, respectively,
appear to be particularly involved.
Since some auditory and gustatory
phenomena are also encountered, it
is probable that the cortical areas in-
Approved For Release 1999/0
CPYRGHT,
Pa;94 J309A@AQs15PP0AA
affected.
11 seems from the foregoing that the
effects of L.S.D. are not specific since
the symptomatology observed may
also be seen following the administra-
tion of mescaline and other phantas-
tica. One very important -difference
is to be noted, however, and that is
the minute amount of L.S.D. required
to produce an effect. In regard to
this, it may be possible to trace L.S.D.
in its course through the organism by
radioactive tagging as suggested by
W. A. Stoll. Research on the effects
of the drug will probably follow two
main courses. First, the drug will be
administered to patients suffering from
mental illness as it has some demon-
strable therapeutic effects in that it
renders schizophrenics more accessible
and increases in some patients the abil-
9/10 : CIA-RDP83-00423R000600150003-6
ity to relive past traumatic experiences
and to reevaluate their present difficul-
ties in terms of recalled past experi-
ence. Research with the drug is also
indicated with psychoneurotics and
with forms of psychoses other than
schizophrenia. The second main line
of research will probably be concerned
with the effects of L.S.D. on normal
individuals especially in regard to the
reproduction of schizophrenic-like re-
action types. The use of psychological
tests of personality, intelligence and
learning in conjunction with L.S.D.
on normal subjects would seem to be
fruitful and a start in this direction
has already been made. More purely
physiological testing of reaction times
and reflex actions are also desirable.
Finally, an attempt must be made to
trace the drug through the organisms
and to determine, if possible, its site
CPYRGHT
of action and method of action. Animal
experimentation is imperative. L.S.D.
is a drug of extreme interest, especial-
ly from a psychiatric standpoint;
further intensive research is definitely
indicated.-RICHARD SMITH, B.A.
REFERENCES
Busch and Johnson: L.S.D.-25 As an Aid
in Psychotherapy. Diseases of the Nervous
System. Aug. 8, 1950.
Forrer and Goldner: Experimental Phy-
siological Studies with Lysergic Acid Di-
ethylamide (L.S.D:25), Arch. Neurol. and
Psychiat. May 1951.
DeSchon, J. H., Rinkel, M., and Solo-
mon, H.: Mental Changes Experimentally
Produced by L.S.D. Psychiat. Quart. Janu-
ary 1952.
Stoll, W. A.: L.S.D.-25, A Phantasticum
of the Ergot Group. Schweizer Archiv. fur
Neurologie u. Psychiatric 1947.
Witt, P. N.: L.S.D.-25 Tested in
Spiders. Experientia, 7:310-311, 1951.