RESEARCH DATA ON D-LYSERGIC ACID DIETHYLAMIDE (LSD-25)/POTENTIAL FOR BW AND CW

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• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): CIA-RDP80-00809A000500200004-2
• Release Decision: RIPPUB
• Original Classification: S
• Document Page Count: 19
• Document Creation Date: December 15, 2016
• Document Release Date: June 28, 2001
• Sequence Number: 4
• Publication Date: September 29, 1953
• Content Type: REPORT

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a. LSD-25
hundrel
and ps,
is normally a nontoxic material. whichiLs very potent, about one
times stronger r.han menca.line and dives nirailar physiological
Chic reac1.ic-
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h. LSD-25 has the potential of being an aid in the treatment of mental
patients.
c. LSD-25, if improperly used is a dangerous material -- it creates serious
mental confusion and makes the human mind temporarily susceptible! to
suggestions. No research has been done to determine what permanent
damage could be done to the human mind if the material was administered
over extended periods.
I
d. LSD-25 could be used in the interrogations of unwilling subjects for the
purpose of getting them to "coni'e as the material stimulates subjects
to tall, more freel;.
e. LSD-25, because of its po teary, _c,,J pc sibis be used in the contamina-
tion of food and water for the p:arp-,se of rendering whole groups of
people (including troops) mentally 1r:-iifferent. rc their surroundings
and situation.
Our inveatigation:, thus far substant-Lat.c me ft:.ingo of other investigators but
we have carried our research on animals much further t.. _r others working on LSD-25-
We can take no serious exception to the printed material furnished us by Sandoz
Ltd which gives a summary of extensile research or. LSD-2r e of November 1952 and
is quoted below:
"D-LYSERGIC ACID DIETHYLAMIDE (LSD-25)
"CHEMICAL CONSTITUTION:
D-lysergic acid diethylamide is a partially ayntbctic derivative obtained by
condensing D-lysergic acid, ex`ratted from ergot of rye, with a secondary amine,
1
diethylamine . Thus LSD-25, fi.rF?. prepared i n 1935 by A Stoll and A Hofmann i ,
Lee notes at end of repor] F-e1ong to the ergonovine Croup. LSD-25 is soluble
in distilled water, a process facilitated by adding crystalline tartaric acid
(four parts of tartaric acid to one of LSD).
"EFFECTS OF LSD ON ANIMALS:
In certain respects LSD resembles ergonovine. It exerts a uterotonic action
(the uterotonic effect of LSD on the rabbit uterus in situ is 710 of that of
ergonovine). LSD exerts no adrenosympathicolytic action (a contrast to theI
alkaloids of the ergotamine and ergotoxine groups) and its toxicity is similar
to that of ergonovine and ergotamine (the LD 50 In mice of intravenous LSD-25
is 65 mg/Kg, of intravenous ergotamine 84 and of intravenous ergonovine
125 mg/Kg.)
However, LSD-25 may be clearly distinguished from all the other ergot alkaloids
so far investigated in other respects. The injection of a small dose of LSD-
25 into the anaesthetized rabbit produces motor excitation. In the dog the
first appsrcnt effects of LSD-25 are of a vegetative nature, e g copious
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salivation, without any significant change in affective behavior.
LSD-25, like bulbocapnine,
ixvestigated, nicotinic acid, dihenurn!n?s, nexamethonium, prircol and alcohol
i
verso atoz substances
(progressive, setting in after approximately one minute and lasting one - two
hl urs. The effect was!( clear-cut ev,::_: aitr:r dcse, as, small as 18-20 mg/Kg. An
;identical affect was noted after massive do es (300_600 riJKs). There was
simultaneous marked motor hyperexcitabiLit.y.
FD inhibited the spontaneous rhythmic activity; it did not prevent the response
electrical stimulation, the epileptic. spikes; the bursts of rapid spikes
pFoduced by barbiturates or cortical trauma Of tr d
l
I. aused marked or even complete flattening of the tracing. The effect, was
Doses of 40 mg/Kg (average) injected intravencus1-, n_ the 'carotid artery
f
e of LSD cr. the olect;rocorticogran of the rabbit.
,. I
+~vina..uv, t;t~x1.C:1'1'1 25) ..
is 3.5
DELAY et al studied *h f
~*
ncrease the general excitatory state. but with simultaneous suppression of
High doses oJ'
dog and cat, a condition
On the normal mouse, ILSD has a weak excitatory action which appears only at a
subtoxic dosage level'. Mice with hereditary waltzing anomaly are more sensitive
to this drug. Subcutaneous doses of nc more than three percent of the LD 50
r i
eminiscent of catatonic
d not modify the effect of LSD. AceLylchcline, given Intravenously, in doses
Ott 20-40 mg/Kg, caused the reappearance of iour~ tq of basal rhythm. Urethane and
c loralose did not modify the effect cf LSD.
n
SECTS OF LSD ON HUMAN :BEINGS:
Thl above mentioned animal. experimerits do not giro any hint whatsoever as to
mental effects exerted by LSD in hush: beings. Hofmann discovered these
L
ects by accident and' then carried out in:~stidarions on hi;.tself which were
re ooted by W Stoll . Studi:s on he effects of LSD 25 in normal subjecte have
2 6 3 10
n carried out by W Stoll , Condrau , Becker , Georgi et al , Kinkel et al
11 171 1a
Matkfi , Mayer-Gross ; Weil and other research workers, whose reports have not
yep been published.
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and Belsanti Rostafinski has made some experiments with LSD in epileptic
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2
The effects of ISD have been investigated in psychotic patients by Stoll
3 4 5 7, I 19 24
De Giacono , Forrer and Goldner , Condrau , Busch and Johnson , Hoch et al , Savage
27 9 ~
As far as systemic effects are concerned, both normal and psychopathic subljects
respond in almost the same manner to LSD and may, therefore, be considered as one
group. However, this is not the case with the mental effects, andtheref dire
normal and psychopathic patients have to be considered separately in this respect.
a. Active and maximum dosess Up to the present, LSD has always been\admin-
istered orally, Generally in the morning on an empty etcoach. LSD in active in
very small doses. In certain subjects the characteristic effects are observed
after the administration of a dose as small as 20 g :microgram _I 0.02 I). A
dose of 40-100pg (about 1 pr./K body Wright.) is active in mss cast s. Doell s as
high as 500 Pg (- 0.5^mr,) or b 1 ,Kg body weight have been well tolerated by
In general psychopathic patients show greater reeis`:ance to the systemic and
b. Onset and duration of actions The first. effects of an active dose of
LSD generally appear within one-half - one hour (maxuawn three hours). Maximum
effectiveness is reached, on an average!, after two :.our!' and the effects persist
for,three - six hours. Delayed effects may to observed for one or mo'e days 'but
13
rarely for more than one week. i;Lnkel et. a] r co ntze four phases is the
reaction to LSD. Phase I, the prociromal phase. represents the period betwee.,.l
the administration of the drug and the he 1 ht of the reaction. It lasts about
one hour. Phase II represents the height of the reaction, occurring nine-five)
hours after the drug had been given. Phase III was the period from the end ofl
the height of the reaction until evening. Phase IV comprised after-effects last-
ing one to several days.
c. Systemic effects:. Distinction may be drawn between vegetative symptom ,
fairly slight effects on metabolism and motor symptoms.
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Vegetative symptoms:
2,5,7 5,10 2,5,7
Giddiness , "empty-headedness" , occasionally headaches In
2,5 6 5,10 5
isolated cases general malaise , feeling of weakness , fatigue , tremor and
10
shaking
Effects of LSD on:
(1) Cardiovascular system:
Blood pressure: Slightly increased, within physiological limits
10 I 2,5
or not modified ; lees frequently slightly decreased
Heart rate: increased or not modified
2,3,5
Iln isolated
Vasomotor functioncz flushes of vasodilatation or facial
5
pallor, sometimes acrocyanosis
2,5
Subjective impressions: sometimes palpitations or
5
discomfort
Two patients given LSD
24 I
III
Only very niight changes observed. Whereas the usual laboratory
tests such as the Takata-Ara and the Hijmans v d Borg reactions,
the Quick test (excretion of hippuric acid following ingestion of
sodium benzoate) or the caphaltn-cheleeterol flocculation test
3, 3,27
show no change , the Snapper test (determination of
glucuronic acid in the urine e tur administration ox' cinnamic acid)
8,27
reveals slight, t:e:nporary dieturhanCe of hepatic function it
should be noted that the Q uLck tea'. and the Snapper' test are
positive in schizophrenia and mescaline intoxication Subjects
in whom even only a slight modification of hepatic !function is
present (e g cases where there are protractedgsequOllae of infectious
hepatitis) make a very marked response to LSD
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developed profound circulatory deprr::'ion
4,7,8, 12. 10
occasionally vomiting
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(4) Respiration:
2,3,4,)
Usually not changed ; re3piration sometimes deer ? and
2,3,5
slower
No changes in composition of urine . iiuresia sometimes increased
2
In isolated cases retention of urine followed by polyuria when
6
(6) Genital system:
110
In isolated cases uterine cramps .
(8) Saliva secretion:
7,5,6,8,10
Often increased
(9)? Sweat secretion:
2,5,6,8,10
Often increased
1l.
4
increased by 1 F . Feeling of
10,19
sometimes periods of shivering
(12)
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No change, in exceptional cases
2,5,6.19 2,5,6,7,1
warmth or cold ,
2,4.7,8,10,11,19
Generally dilatation , sometimes impairment of
4
reaction to light ; mydriusis leles pronounced when LSD instilled
4
into the conjunctival sac
Blood picture:
Temporary inereaoe in total white blood cell count without
27
modifications in the differential count or relative neutrophilia
Slight increase in potassium blood values, no change in calcium
3,27 24
blood values Savage observed some tendency for anaemia to
appear during prolonged treatment (20-100 ug daily for one month).
(13) Blood augur:
Slight rise, within physiological limits ; less frequently a fall
17,21
In 24 subjects Mayer-Gross et al found that LSD caused a slight,
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I
transitory increase in the glucose and hexoeemenophos hate levels
in the blood. Otherwise carbohydrate metabolism was not affected.
This group of invesItigators believe that by an anti-enzyme action,
ISD inte]rupte the break down of glycogen at the hexolemenophoaphate
otate. the intravenous injection of 33% glucose solution modified
H 21
the reaction to IUD
Aggregate of vegetative)I'nfSects:
LSD tends to produce amphotonia. The increase in blood pressure and heart
rate and the dilatationl',ofthe pupils suggest an increase in sympathetic tenus.
The nausea and the peri~ds of vbsodilation suggest para:~,;-c:ipathetic hyperactivity.
However, it shc,'".d be noted that there are great. differenced from indi-
produces vegetative-. instability which may t
sympathicotonia or to v gozonia, depending on the. individual subject
Motor symptoms:
LSD causes dis!.~rbances of voluntary motor functions
modifications Of reflexec .
Ataxi&: gener3.l:ly not, pronoun.:e:d, lack of precision in intentional
movements, elig t decree of incoordination, occasionally cuts earliness of
2,1,5,6,8,1 2, .8,10
gait Occasionally faulty speech articulation
25,2
5,21
Romberg's sign: sometimes slichtly positive Sometimea tremor of
5,?x,3,27
the bend and twLtching of t.he eyelids Often facial clonism,
2,5,6,7,8,10
cracnps of the ,7~Lws,, t.rismus and forced 1-_:u,,hter Sometimes
2,1.5 3,5,7,10
hyperactivity of tendon reflexes Sometimes motor excitement
in exceptional ases athetoxic movements In certain cases high doses
(300-500 mC) produce catatonic conditions witn a lack of fa~ral expression
and perservatio
of body posture
Aggregate of motor symp OMs:
The most frequelt motor effect of LSD may be described as a flight degree
of muscular hyperexcitability accompanied by more or less pronounced signs of
incoordination. The caatonic effect of high doses has, as yet, onl~ been studied
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cases.
Mental effects in normal subjects:
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Consciousness orientation: Consciousness is generally maintained but occasionally
2,
slightly; clouded ; a feeling of intoxications, often occurring in a wave
6 2
pattern of outbursts . In exceptional cases short periods of confusion
As a rule, judgment and memory are not impaired. The subject is conscioue
of his
is due
condition and does not lose sight of the fact that
to the drug ingested 2,5,6,8,10,11
patial orientation remains
what he is experiencing
6
self-oboe-vation and introspection are increased
often disturbed, time seeming to pass too quickly or too
i?.
2,5,6,8,10,11
slowly
Ideation?, may be accelerated, accompanied sometimes by incoherence, and "running
2,5,10
away" of ideas ; in other cases ideation is slowed down and the faculty of
2,8,10 2,5
onproesir~ninhibited . Often a tendency to preoccupation with one idea
2,5,6,8,11
Attention and concentration are reduced
AffectivitY and behavior: Several types of reactions may be observed:
1) Marked euphoria made evident by disordered activity, manic behavior,
more or loan unmotivated attack of laughter, or even involuntary
2,5,6,lO,lt1,17
maniacal laughter Lear; frequently the euphoria it
3,10,11
passive, apathic and hebephren:C
(2) Depression which may be demonstrative with tears, resentment,
2,6,10,14
aggressiveness or passive with negative withdrawal into the
2,6,10
self, autism, apathy and even complete indifference , some-
2,o
times suicidal ideas
2,5,17
(3) Alternate phases of euphoria and depression
24
In addition to these effects, there is sometimes associated anxiety
13
paranoid trends , or the fear that the abnormal state will persist or will be
2,5,6
noted by third party
I general, under the effect of LSD an enhancement of the previous
5,6
affective state whether constitutional or tenpo:arv may be observed . The
2.3,10
euphoric reaction seems, however, moot frequent
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Behavior ~s controlled by effectivity. In cases of hyvomanic euphoria,
the disordered activity s often accompanied by lo6orrheea id loss of inhibition;
2,5,6
the subject cannot prevent himself from saying what he ':thinks and seeks
effective contacts. On the other hand, in cases of depressive schizoid reaction
often all affective contact is suppressed and the apathy may even develop into
6,10
a state oflstupor
2
Sedative effects on sexuality
li
Sensory perceptions: Disturbances of perception are frequent and sometimes very
pronounced.' Either the object perceived is distorted or there are hallucinations
generally of an elementary nature.
Vision: Often the objects appear distorted, perspective ie incorrect, distances
are overestimated, colors seem brighter, shadows very intense and contours very
2,5,6,8,11,14
clear-cut Leas frequently the outline of the object seen is loss
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9 -
6
distinct and colors are dull
Certain subjects experience hallucinations especially if they are in the
dark and their eyes are cloead. These hallucinations generally consist of
flashes of light, lines, patcres of color, eouotirros more complex geometrical
2,5,8,10,11
figures, objects, flowers and animals . In exceptional cases the
2
visual hallucinations are Provoked by auditory stimuli
2,5,6,8,10,11,19
'Iffioxinal Often hyperacuoia and false interpretation of noises
6,10
Lose frequently true auditory hallucinations, e g sound of a bell
Tote and small: Taste is often affected. Food and cigarettes seem tasteless.
2,5,6,8,10
8omatimes metallic or bitter'!taste . In rare cases olfactory
11
hallucinations, o g garlic odor
Touch% Frequently distortion, hypoeothosia and pareetheaia: things fool
2,6
different In isolated cages true tactile hallucinations, e g sensation of
10
being vat from urine
General bodil #salings: Feeling of strangeness or distortion of certain parts
2,5,6,$;10,14
of the body : the !Isub,ject has the impression that his head is
enormous, that one limo is excessively long or ooperated from the body, that
his nose is not in its right place, that his arm "no longer belongs to him"
or that his body weight has decreased or increased.
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Personality: In certain subjects LSD produces a feeling of depersonalization or cf
2,5,6,10
split personality of aclearly schizophrenic nature Impression of looking
at one's self from a distance, of having lost control of one's real self, of having
changed and become more or leas unreal and cut off from the rest of the wnrld.
These phenomena are generally associated with the cenesthetic disorders as well as
with autism, withdrawal and indifference. These personality disorders are less
frequent in subjects who make a manic euphoric or depressive response to LSD.
10,13
Psychological tests: Hinkel carried out Rorschach's test on five subjecte
under the influence of LBD. The results of the teat confirmed the clinical
observations of the effect of LSD in each of the five ir,-tviduals: autism,
negativism, weakening of powers of logical reasoning, anxiety, depression, and
aggresuiveness. Another test ("concrete-abstract thinking") consisting of noting
the reactions of the subjects to a series of aphorisms also gave responses
reminiscent of those oil, schizophrenic patients, (nredominar.ce of concrete re-
sponses; abstract responses could be obtained with effort but were characterized
by overgeneralized and tangential thinking).
Rirmrtel did not iemploy these tents in persons who made a manic depressive
response to LSD. In ani alcoholic, n itor?'ac ha, 1: ' ; test, carried out just after the
26
subsidence of the ISi) effects showed profo_rrd chai%,ges over the previous tests
11
Matkfi studied the effects of LSD on himself. He made a series of
drawings supposed to represent: the sacs person r,Ze.ichente:ot') while under the
influence of LSD ana found that.. his ot.roke3 bec._:re quicker, sometimes stereotyped,
the drawing became larger, and even went, off the paper. In spite of all his
efforts, he could not coordinate tris drawing with what. he saw, whether it was
normal or not. When the height of the LSD effect was reached, he made a drawing
i
of his visual hallucinations.
Electroenccphalogram: EEG tracings have beer. take n, as yet, in only about 15
10,13 10;13
cases. There have been slight or no trance's. Rinkel found, in general,
an increase in alpha rhy't?hru of one-three waves per second, but in one very
relaxed subject the alpha rhythm was slowed by t.wo waves per second. In eight
cases out of nine he noted a pronounced increase in muscle activity.
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Delayed Effects: The 'intoxication'
hours, but in practically every case
for one-half to one day and sometimes
In the evening after
concentrations'and sometimes
- 11 -
of LSD generally wears off within
z._;:-eight
the experiment, euphoria, logorrhoea,
sleep well, but the following
similar to that produced by
most subjects have
6
several days
returned
6 Less frequently
morning certain of them complain of a "hangover,"
excessive amounts of alcohol. However, by this time
2
to their normal starus .
a depressive
One subject exhibitea periods of
is obeer::d .
dreaminess (with feelings of
ness, of "de,ja'vu" and disturbed general bodily
6
feelings), alternating with phases
of depression after a single dose: of LSD. These delayed effects
13 often occurred
in waves
A g g r e g a t e effects in normal sut?iects: The symptoms produced by LSD
have been considered by W Stoll as the expression of an acute exogenic psychosis,
analogous to those produced by alcohol, opium, cocaine, hashish, mescaline and the
amphetamines (however, all these 23
substances are only active in far higher doses ).
There is no uniform reaction to LSD. Two main types may he distinguished
6,10
manic, expansive reaction with psychomotor excitement, euphoria and
less frequently depression,
(2) a schizophrenic reaction with slowing of mental 'nrocesses, inhibitions,
autism, depersonalization and hallucinations.
6 The majority of sun'jects present a mixture of these two extreme types.
Becker attributes the manic response to the action of LSD on the sphere of
intention and the schizophrenic reaction to he action of LSD on the sphere of
In general, LSD tends to reinforce pre-existing tendencies, producing a
5
caricaLL-re of the subject :the cyclothy,nic patient often becomes euphoric and
6
expansive while the schizoid becomes a true schizophrene . Thus LSD reveals latent
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II
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tendencies and its effect may be considered, to a certain degree, as a personality
2,5,6
test)
II
LSD makes it possible for the psychiatrist to study in himself some of
tile mental symptoms which he; is called upon to analyze and treat in his patients.
2,6
This Ilexperience is often instructive
1 I
LSD 25 and Mescaline; The f!rst workers to carry out research were struck by the
analogy between the 'intoxication' produ:cd b, LSD and mescaline delirium, although
the active doses of these two products are quy:t.e different (mescaline at least 0.2
g s c, LSD generally less than 0.0001. 100 An analogous relationship has
been found when comparing there nxici-t.y of the two :.:% str, cep in
animals. The lethal dose of mescaline, in tadpoles, is i(--)U-1030 times greater than
8
that of LSD
that the mental effects cf the two substances are not. absolutely identical:
8 11
ISD produces, above all else, manic depressive or hebephrenic. symptoms
In other words, an expansive r,t
Payehotic. ph,nno:aena and a1t'eritic.ne of the autono.nicl nervous system
:;era observed. The pay.&otio phenomena wor.-: predontnanUy schizophrenia-
like symptoma.'thett were manifested in diotarbancca of tlo;.ght and speech,
changoo`in affect and mood, altered perception, production of hall.:ceinetions
41Jiicvlties,_iri,..t.1ti,cinrr~ v1tH r etardattinnj blooking, autism. Affect ./'
wax rhallcw or.or.ourly blunted. ;'enlingn of lnail.ffek-tilCiland-"trnrn-n2-itT--
with suspiciouonere, hostility &ut' ros?,nti,,nat recurred. 'Thcre were, to
a 1esuor c?rgrea, aiiiilas'ittas to c,.:#ur.?lenecl Latoiapillluoio.ial misinter-
pr?ta.tione being nct7 infrequent. ;: f N can-c nhc. cd similrritinc to
raa.nie-doprnaniva ut. toe. Dglueionr of L;rxndie?ar or perni'ecutcry. netture
worn not oboorved.
Dioturbi ncn of they autonomic norvcue ayst