S an Fernando Va l l ey S tate College
A
SURVEY OF RESEARCH
o/
A Cr iti que o f S e l e c ted Re search Con c e r ning
E f f e c t s of Ly s e r g i c Acid D ie thy lamide
( L . S . D . -2 5 )
A The s i s Submitted i n P a r t ial Sa tis f a ction o f the
Requireme n t s for the Degree of Master of Science in
H e a l th S c i ence
by
Bern i c e V ivian Bou s ta n i , R . N . , B. s.
June ,
1 968
The the s is o f Bernic e Vivian Bou s tani is approved :
S an Fernando Val l ey State Col l e ge
June ,
19 68
TABLE OF CONTENTS
PAGE
ACKNO W"LEDG.rviE NT S .
iv
.
v
ABSTRACT
•
•
.
C HAPTE R
I.
II .
INTRODUC T I ON
1
S t a tement o f Purpo s e .
2
Impor t a n c e o f the S tudy.
2
De fi n i t i on s o f Term s .
3
S tudy D e s ign .
4
Na ture o f the Rema inder o f the Report .
5
REVIEW OF SELECTED S T UD I E S PUBL I S HED O N
6
L .S . D . -25 I N THE PAST 1 0 YEARS
•
.
E ffe c t s o f L . S . D . - 2 5 on th� V is ua l Sys tem . .
,,.._
E ffec ts o f L . S .D . - 2 5 o n the Brai n
Nervou s Sys tem ) .
.
6
( o r C entr a l
16
.
E f fe c t s o f L . S . D . -25 on the Endo c r i n e Syst e m
( o r Me tabo l is m ) .
.
37
.
E ffec ts o f L . S . D . - 25 and To l er a nc e
49
S tudi e s o n Sid e Eff e c t s o f L . S .D.- 2 5
53
S tud i es o n Other E f fe c t s o f L . S . D . -25 .
III .
.
61
D I S CU S S I ON .
75
SU MMARY .
88
B IB L IOGRZ\PHY .
89
.
iii
ACKNOWLEDGMENT S
I wi s h to expr e s s m y a p p r ec i a t ion t o memb e r s o f
m y The s i s C o mmi tte e , D r . Jl1ary E l l en Weber a nd Mr .
'fhoma s
Torpy , for the i r a s s i s tance and e spe c ia l ly to my C o m�i tte e
C h a i rman , D r . Don S . Dor s ey , for h i s continued i ntere st
and a va i lab i l i ty f o r h e l p when i t wa s needed .
iv
AB S T RAC T
A C r i t i que o f S e l e c te d Re s e ar ch Conce rn ing
E ffe c t s of Lyse r g i c A c i d D i e thy l amide
(L. S . D . - 2 5 )
by
B e r n i c e Vivian B ou s t ani , R . N . ,
B.
S.
Ma s ter o f S c i enc e i n He a l th S c ience
June 1968
The pur p o s e of thi s s tudy wa s t o eva l u a te fi fty s e ­
l e cted s tud i e s with r e spect t o adequacy o f r e s e a r c h de s ign ;
and s ec o n dl y ,
to a n a l y z e the degree o f agreement among
the s e s e l e c t e d s tud i e s as they de t a i l the e ff e c t s o f
L . S . D . -25 .
F i fty s tud i e s pub l i s hed during the p a s t ten
y e a r s we re reviewed , d i s cu s se d and c r i ti que d .
As wi l l be
s e e n , the s e studi e s vary cons iderably in ade quacy o f s c ien­
t i fi c a ppro a c h as we l l a s in de gree of a c c e p t a bi l i ty of
conc l u s i o n s r e ached .
I n mo s t o f the s e s t udi e s , L . S . D . - 2 5
wa s found t o h ave a p r o f ound e ffe ct on the centr a l nervous
s y s tem; howev e r , the manner in wh i c h t he se effe c t s were
S o me s tudi e s sugge s t that
produced are s t i l l un s o lve d .
the drug fun c t i o n s as an e n z yme , whi l e othe r s show it s
a c t i o n a s a n a n t i e n z yme .
A mo ng t h e s tud i e s on the e ffe c
' t
o f L . S .D . - 2 5 o n the e lectr oencephal ogram
v
( EEG )
there were
c o n fl i c t s be tween the EEG r e s u l t s o f s tud i e s in an i ma l s
and the ob s e r va ti on s o f the e f f�c t s i n man a s we l l a s
inte r s pe c i e s c o n fl i c t s.
The drug c ould b e found t o e ff e c t
cerebra l fun c t i o n s i n both d i r e c t ions o f e ff i c acy a s i t s
s e ru m l e v e l e i th e r r o s e or fe l l .
One s t udy s howe d a
functi on ing r e t i n a wa s prerequ i s i te to the app e a r ance o f
L . S . D . - 2 5 t r ig g e re d h a l luc i n a t i on s ; whi l e another found
that a funct ioning r e t i n a wa s not nece s sa r y f o r p r oj e c t i on
o f h a l luc i na t i o n s .
L . S . D . - 2 5 doe s not appe a r to be phy s i o ­
logi c a l ly add i c t i ng b u t t o l e r ance to t h e drug a ppe a r s t o
d e v e l op r a p i d ly i n hu ma n sub j e c ts a n d i n s ome anima l s .
Among s tud i e s inve s t i g a t ing s ide e f fe c t s , one c a s e study
d emons tr at e d chr o mo s o ma l d a ma g e in huma n leuk ocyte s induced
by L . S . D . -2 5 ; whi le another c a se s tudy conc luded tha t the
drug may h a ve induced s e i z ur e s in one hu man subj ec t .
In
a n o t h e r s t udy s e i z ure - l ike a c t i vity wa s produ c e d in a n i ma l s
wi th a very low d o s e o f L . S . D . - 2 5 .
F r o m the report s r e v i ewed , i t a pp e a r s that ob j ec­
t i v i ty is hard to a c h i e ve in s tud i e s inve s t i g ating the
e f fe c t s of L . S.D . - 2 5 .
S o me o f tho s e a c t i ve l y in v e s tigating
the drug h a ve thems e l ve s beco me u s e r s .
s tud i e s re v i ewe d ,
In mo s t o f the
the s amp le s we r e sma l l and fre qu e n t ly
the me thod o f s amp le s e le c t ion wa s not s t ated in the report .
I n s o me r epor ts t he i mp r e s s ion d e r i ve d from d at a p resented
did not s upport the con c l u s ions t he i n v es t i g �tor s re ached
i n the ir report s .
Many t he o ri e s deve loped in these studie s
vi
h ave not been s u ff i c i e n t l y supported by c o l l abor ative
s tu d i e s .
The true c l in i c al potent i al o f L . S . D . -2 5
r e ma i n s m aske d by a l ack o f we l l d e s i gned and we l l
c ontr o l led r e s e ar c h .
..
vii
CHAPTER 1
INTRODUC T I ON
L . S . D . - 2 5 , d -ly s er g i c a c id d i e thylamide,
i s one o f
four s t e r e r s i some r i c a l k a l o i ds which can be synthe s ized
from l y s e r � i c a c i d , a d e r ivat ive of ergot .
synthe s i ze d by Alb e r t Hofman ,
L . S . D . -25 was
a Swi s s b i o c he mi s t ,
in
1938 ,
but Hofman d i d not d i s cover i t s p sychotom i me t i c e ffec t s
unti 1 19 4 3 .
( 3 0 : 112 )
For twenty y e a r � L . S . D . -25 remai ned
r e l a tive ly unknown to the genera l p u bl i c a l t hough it wa s
u s ed to s ome extent .
In minu te a moun t s L . S . D . - 25 i s
r eported t o b e c a pab l e o f produc i n g change s i n thoug ht ,
per ception , mood , and memory d i stu rbanc e .
The d a n ge r s a nd
abuse s a s s oc i a te d with thi s d rug gave c au s e for Fede r a l
Laws t o b e p a s sed in 1 9 6 5 making s a l e o r manufac ture o f
L . S . D . - 2 5 i llega l with i n the Uni ted St ate s .
Sandoz
Labor ator ie s , the only l e g a l manufa c turer of L . S . D . - 2 5 in
thi s country ,
s topped the produc t ion of thi s d r ug and
turned ove r the i r ent i r e s t o c k to the Nat ion al I ns t i tute
of Ment a l Heal t h .
(91 : 49)
Enhanced by t he wid e s pr e a d pub l ic i ty gi ven L . S.D .-25
through the ma s s med i a ,
s e r i ou s c on t r ove r s i es have deve l op �
over e th i c a l u s e and mis u se o f this drug .
Ne wspape r s ,
mag a z ine s , r ad i o and te l ev i s ion ne t works have feature d
1
2
lead art i c l es and program s on the d nnger and a bu s e s a s
we l l a s the therapeut i c bene f i t s c la imed for the u s e o f
L. S . D . -25.
Statemen t o f Purpo s e
The purpo s e o f thi s s tudy wa s t o e va luate f i f ty
s e l e c t e d s tud i e s w i th r e spect to adequacy o f r e s e ar ch
de s ign� and s e cond ly to analy z e the degree o f a greement
among the s e s e l e c te d s tudi e s as they detai l the e f f e c t s
o f L .S . D . - 2 5 .
Importance o f the S tudy
There have been increa s ing number s o f p a t i e n t s
t r e a t e d i n t h e p sychiatr i c c l i ni c s a n d med i c a l emergency
rooms a c ro s s the n a t i on for prob lems f o l lowing inge s t ion
of L . S . D . - 2 5 .
F i s he r
(90 : 109 )
Ac c o r d i ng to a s tudy by Unge r l e i d er and
an a verage of one p a t i e n t a month wa s
s e e n a t the P sychia ·t r i c Emergency Room and A.dmi tting Of f ice
o f the Neurop sych i a t r i c In s t i tute a t the Uni versity of
Cal i f or n i a in L o s Ange le s Med i c a l C enter prior to S e pt e mb e r
o f 1 9 6 5 , f o r c ompl i ca t i o n s f o llowing L . S . D . - 25 ingest i o n .
For a s e ven month p e r i od fo l l owing th i s dat e the average
had i n c r ea s ed f rom one to f i ve and l ater to f i f teen pat ie nts
a month f o l lowing i ng e s t io n o f L . S . D . -2 5 .
Due to the
increa s ing number of people t ak ing L .S . D . -25 a nd the
occurrence o f a cute · s i de e f f e c t s s u ch as h a l luc ination s ,
anx ie ty to the po i n t o f panic ,
s evere depr e ss ion w i th
3
s u ic id a l a tt emp t s and confu s ion
(91 : 52 )
it i s important
t o have d e t a il e d under s tandi ng o f the exa c t p sycho log i c a l
and p hy s i o log ic a l e f f e c t s thi s d r u g i s capable o f p roduc i n g
in man .
In order
to provide a c l earer v i ew o f wh at i s
known and what is not known o f the behavio r a l and
phy s io l og i c a l e f f e c t s of L . S . D . - 2 5 , we mu s t look at the
r e s e ar ch that h a s been done .
What are the b e l i e fs a s
supported by r e s earch f inding s ?
D e fi n it io n s o f T e r ms
L . S . D . - 2 5 wa s l ab e l e d " ha l l u c inogenic " or " p sychotomime t
. i c " owing t o i ts property of produc ing a psychotic
or s ch iz ophr en i c - l ike s tate i n a n orma l per son .
o f the s e term s are a c curate .
d e f i ned by Web s te r a s :
( 2 4 : 38 2 )
Ne ither
Ha l luc inat i on i s
" pe rception of obje c t s wi th no
r e a l i ty , or exp e r ience o f s e n s a t ion wi thout an e xternal
c au s e , u s ua l ly arisin g f r om d is order of the nervo u s s ys te m . "
Per s on s who s e e o r h e a r thin g s a f te r tak ing L . S.D . -2 5
f requently d i s to r t "ac tua l " ob j e c t s
c on s t itute i l l u s i on s ,
ha l lu c in a t io n s .
t a k in g L . S . D . - 2 5 .
or
sounds.
These
l ik e a mirage r ather than true
True h a l l u ci n a t i on s occur r a r e ly a f ter
The term " p sychoto mime t i c " r e f l e c ts
o n l y a part of the a c t iv ity o f this drug - l imiting i t t o
m i rnic k ing ment a l i l lne s s .
T h e pre ferred term "ps ychede l ic " , .
o r m ind-man if e s t ing , wa s c o i n e d in 1 9 5 7 by Osmond
(24:383)
and is a neutr a l term that s imp ly r e f l e c t s the occurre nce
o f menta l and perceptual change .
4
S·tudy D e s ig n
Engl ish l a nguage jour na l e n�r i es appe ar i ng in a te n
year per i od from 1 9 5 7 to 1 9 6 7 cons t ituted the s tudy popu l a t io n .
I nc luded wer e r e po r t s c o �c e rn i ng dire c t phy si o-
l o g ic a l and behavior a l e f fe c t s o f L . S .D . - 25 ; a nd exc luded
were repor t s d e ta i l ing therapeu t i c , and s u bje c t i ve
e xp e r ie nc e s o f subje c t s .
F if ty s tu di e s se le c ted at ra nd om
f r om jou r na l s h e ld by the B i o - me d ic a l L i biary, C enter f o r
Hea l th Sc ie nce , U nive r s i ty o f C a l i f o rni a , Lo s Ange le s ,
9 0 0 2 4 , c ompr i s e d the r e s e arch s amp l e .
Stud i e s were reviewed a nd c l a s si f i e d .
The
f o l l owing c r it ic a l que s tions were e xamin e d conc er ni ng
each s tudy:
The obje c t ive o f the s tudy .
1.
Purp o s e :
2.
Popu l a t i o n :
The ge neral type a nd number
or
spec i e s u s ed in the s tudy .
3.
Me thod :
The ma nner a nd c ondit ions under wh ic h
the s tudy wa s c o nduc t ed .
4.
Re s ul t s :
Conc l us io n s , o r what
was
l e arned
from the s tu d y .
5.
De f i c ie nc i e s :
Brief comments
on
study vli th
de s i gn prob l em s that we re thought to effect t he
re s u l t s o f the s tudy ,
s uch a s :
a..
Ad equacy o f s ample s electi or.. proc edu res .
b.
Adequac y o f sample s i z e .
c.
U s e of c ontrol s , when 4ppropr iate .
5
d.
U se o f doub l e - b l ind procedur e s , when
appropr i ate .
e.
Obvious d e f i c i e n c i e s in r e search
proc e d ur e s .
f.
Repor t e d i n terms o f s t a t i sti c a l
sig n i f i canc e .
Na t ur e o f the Rem a i nder o f the Repor t
Chapter II conta ins t h e review o f the stu d i e s
c l assi f i e d in t h e f o l lowing order :
E f f e c t s o f L . S . D . -2 5 o n :
1.
V i sua l system .
2.
B r a in
3.
Endo c r ine system
4.
S tud i e s on t o l erance .
5.
Stud i e s on side e f f e c t s .
6.
s -t ud i e s on o ther e f f e c t s .
( o r c e nt r a l nervous sy s tem ) .
( or metabol i sm) .
Chapter III conta i n s a d i sc u s si on and s uremar y o f
t h e studi e s r e v i ewe d .
C HAPTE R I I
REVIEW O F S TU D I E S PUBLI SHED ON L . S . D .- 2 5
IN THE PAST T EN YEARS
Due to i t s unique a c t i o n on the centra l ne rvous
s y s tem , the prob l ems o f evaluat ing L .S . D .- 2 5 p re s ents
spec i a l p rob lems f rom t ho s e o f a s s e s s in g other typ es of
d rug s .
Unt i l 1 9 5 0 only s ix s tud i e s had been pub l ished
conc e rn i ng the e f fe c t s o f L.S . D . -2 5 .
F rom 19 5 0 to 1 9 5 7
the re we re app roxima t e ly 4 0 0 p ub l i shed .
S inc e 1 9 5 7 t he re
h a ve been about 1 0 0 s tud i e s pub l i shed annu a l ly.
( 4 0 : 183 )
F i f ty o f tho s e s tud i e s pub li shed b e tween 19 5 7 and 1 9 6 7
we re rev i ewed i n th i s rep o rt .
S tud i e s c o n c e rn ing the e f fe c t s o f L.S . D . - 2 5 on the
v i s u a l s y stem a re outl ined b e l ow .
The E f fe c t o f the Ha l lu c inoqenic D ru 2, I�..:S ·-P-..:. .:= 2 5 ��� �
.
Me s c a l ine o � t h e �l e c t ro re �i�og ram .
(l.-� pter and Pfe iffer,
1957)
Purp o s e �
T o i nve s tigate the extent t o wh ic h t he ret i na i s
i nvo lved i n t h e p roduc tion o f v i s u a l h a l lucinati on s .
Popu l a t i o n :
T h i �ty-s i x c at s we re i n v o lved in mak ing f o ur
s ep a ra te mea s u re me nt s .
Me thod :
{1 ) Three c a t s were u s ed to de t ermine a d os age
of L . S . D . -2 5 that wou ld be non- tox i c to c a t s , and t o
d ete rmine whe the r c a t s e xpe rienced v i su a l h a l luc ina t i o ns
6
7
(2)
w i t h the drug .
S evente en c a t s had two e l e c trode s
s utured to the s c l e r a which r e c e ived e le c t r i c a l pote n t i a l s
from t h e r e t i na .
(3)
I n the third group o f nine ca t s ,
two e le c trode s we r e wound around the opt i c nerve o f one
eye .
I n the s e c a t s a l l mu s cu l ar and nerve conne c t i o ns o f
that eye were s evered to e l iminate any contribution tha t
nonv i s u a l .e leme n t s might produc e in s t i mu l a t i ng nerve ­
a c t ion p o ten t i a l .
The o ther eye o f each c a t had e le c trodes
a pp l ie d in the s ame manner as in me thod two .
(4)
In s even
c a t s two e l e c tr od e s wer e p laced on e a c h eye as in method
two and at the s ame time a b ipo lar e l e c trode wa s p l ac e d
o n t h e oc c i p i ta l ,
or vi s ua l , c o r t e x .
o f t h e c a t s r e c e ived only L . S . D . - 2 5 .
r e c e ived pentobarb i ta l ,
and L . S.D . - 2 5.
tone a l ly .
Groups 1 , 3 ,
and 4
C a ts in Group 2
s od i um m e s c a l ine , dihydrocannab ino �
Al l med i c a t i o n s were i njected in traper i ­
Th i s s tudy was b a s ed on the p r inc i p l e that an
e l e c t r i c a l potent i a l a c c omp an i e s activity in any nervous
e l ement .
E le c t r o r e tinograms were re corde d b e f o r e and
a f ter admi n i s t r a t i on of drug s .
Re s u l t s :
(1)
C a t s a r e c apab l e o f having h al lu cin a t i o n s
a s a r e s u l t o f a nontox i c d o s e o f L . S . D . - 2 5 .
(2)
Pento -
barb i t a l s od i um d id not induce spontaneou s e le c tr i c a l
potent i a l i n the r e tina o f the anes thet i z ed c a t s .
L . S . D . - 2 5 produced spontaneous a c t ion potent i a l s in
s pur t s .
I n two o f the c a t s t he pi ckup wa s ide nt ic al
f ro � the o � t i c n erve and from the s c lera .
(3)
Sponta neous
8
a ct i on poten t i a l s do o r i ginate i n the re tina i tse l f and
not f rom extra oc u l ar mu s c l e or pup i l l ary a c t iv i t y .
( 4 ) Large sp ike s appe ared on the v i s u a l c o r t ex o f the
c a t , the s e s p i k e s wer e h igher and s harper th an the
r e t i n a l potent i a l s and they d i sappeared when the optic
nerve s we re cut .
A fun c t i on a l r e t i na i s nece s s ary f or
v i s u a l h a l l u c in a t i on s .
D e f i c i enc i e s :
(5)
P opul ation wa s smal l f o r making four
s eparate meas urement s .
I n an obj e c t ive s t ud y i t i s
que s tionable t o a s sume that c at s are ha l lu c i n ating b y
the i r b �havior .
A s y e t we have no s cien t i f ic way o f
d e t e rmin ing whe t h e r a n animal i s expe ri e n c i ng v i s u a l
h a l lu c ination s .
Re s u l t s were not reported i n te rms o f
s ta t i s t i ca l s ign i f icanc e .
L ys e r g i £ Ac id and _!!-s E f fe c t s o n V isua _l Di s c r imina·t i on
i n �?n ke y s .
Purpo s e :
( F u s te r , 1 9 5 9 )
To s tudy the e f f e cts o f l y s e r g i c a c i d d i ethy l ­
a mide upon the c ompl ex behavior o f monk e y s who we re
t r a i n e d t o d i s cr iminate vi sual s t imu l i pre s ente d
t a ch i s to s c o pi c a l l y .
P opu l at i o n :
rive Rh e su s monk ey s ,
three mal es and two
fema l e s .
Me thod :
S ub j e c t s were trained to d i s c r iminate be t ween
g o eme tr i c ob j ec t s pre sen t ed in p a i rs ta c h i s t o s c op i c a lly ,
d u r i n g br i e f e xpo sure s .
T r a i n ing a s we l l a s the actua l
e xper iment s are acc ompli shed b y pre s e nting to the anima l
a p a i r o f s te r e o me tr i c ob j e c t s o f d i f f e rent s hape but
9
s imi l ar pr opor t i on s , i n a s er i e s o f �on s ecutive tri a l s .
The animal had a c c e s s t o e ither o f the two ob j e c t s by
p a s s ing a hand through a hole a t the bott om of the one-way
One o f the obj e c t s w a s a s s o c i a te d w i th
v i s i o n screen .
food by rewarding i t s s e le c ti on with
a
p i e ce o f a pp l e .
A f t e r the anima l s were trained to d i s c r iminate tach i s ­
t o s c op i c a l ly b e tween the ob j e c t s , e ac h animal wa s te sted
by a s e s s i on of 5 0 c ontro l t r ia l s .
control t r i a l s ,
One hour a fter the
a sma l l d o s e of L . S . D - 2 5 was i n j ected
intramu s c u l a r l y and a s e c ond s e rie s o f 5 0 t r i a ls were
done .
T h i s p r o cedure wa s repeated one week later wi th
the s ame anima l s and the s ame do s e o f L . S . D . - 2 5 .
R e su l t s
o f 1 0 0 c ontro l s a n d 1 0 0 exper ime ntal trial s v1ere c o l lected
f or each a n ima l .
Re s u l t s :
L . S . D . - 2 5 at l ow d o s age a l ter s the behavior o f
the anima l s i n the two con s idered a s pe c t s o f the exp eri ­
mental s i tua t i on :
r e a c t i on t ime i n the p e r formance ,
wh i c h i s pro l onge d ;
and , the thr e s h o l d o f tachis t os cop i c
d i s cr imination, wh ich i s r a i s e d .
Whi l e the percentage o f
c o r re c t r e s p o n se i s lowered , t h e r ea c t ion time i s
cons i d erab ly incr e a s ed b y L .S . D . - 2 5 .
The e ff e c t s are
prop o s e d to b e exp l a in e d by a � inh i b i tory a c t i on of
L . S.D . - 2 5 upon the axonde ndr ite s ynap s e s o f the centr a l
nervous s y s tem .
D e f i c i enc i e s :
(34)
Popu l a t i on wa s sma l l .
Alter ria ti on o f the
s equence o f contr o l and exper ime ntal tr i a l s would have
10
been de s ir eab l e .
Re s u l t s wer e not repor ted in te r ms o f
s t a t i s t i c a l s ign i f i canc e .
T h i s s tudy wa s one o f the few
u s ing anima l s where the s ame expe rime nt wa s repe ated and
s imi l ar r e s u l t s obt a i ned .
E f f e c t s � f Ha l lu c i n o ge n i c Agen t i n TotallY ?l ind ?L�e���­
( Kr i l l , Alpert , and O s t fe ld ,
1963)
To c l a r i fy the r o l e o f a funct ioning ret ina in
Purpos e :
the introduc t ion o f L. S .D . -2 5-induced v i s u a l change s .
P opu l a t i o n :
Twe nty- four bl ind human vo lu n·te er subj e c t s
Four s �b j e c t s were b l ind by the age o f two
were u s ed.
and vver e de s i gnated a s " c ongen i ta l ly b l ind " and the o i:.:her
twen ty s u bj e c t s d id not b e c ome tota l ly b l ind until l ate in
c h i ldhood .
Me tho d :
A l l s ub je c t s wer e h o s p i ta l i z e d and had ge ne r a l
med i c a l h i s t.or i e s t aken a nd phy s i c a l exa w.i na tions inc ludin�J
c omp le te neuro l og i c a l eva lua t i on s .
A l l d a ·ta we re tape
re corded i n a s emi s oundp r o of r o om by the
same
in"l:.er vie,..' er .
Tape r ecordings sub s equent l y wer e eva luated sep a r ate l y by
two r a t er s .
Sub j e c t s wer e given e i ther a p la c ebo or
L. S . D . -2 5 accord ing to d o ubl e - b li n d s tu dy pro cedure s .
Interv i ew s v;rere r e corded ifl.trri.edi ate l y a f te r s u bjec t s had
taken L . S . D . - 2 5 o r the p l a c e bo a nd a t thir ty minu te
interva l s for three and one -ha l f hour s a f terward. L.S . D . -2 5
and the p la c ebo wer e given or a l ly i n a he avy syrup.
Re s ult s :
Th irtee n subje c t s reported v i s u a l a lter at i o ns
a f t e r L . S . D.- 2 5 .
E l even s ubje c t s repor t e d si mpl e
,_
11
h a l lucin a t ion s , two subj e c t s r epor ting comp lex
ha l lu c i n a tion s and de s c r ibe d c o lo r .
No subje c t s
repor t e d s ub j e c t ive v isua l phenoma whe n t he p l acebo
tr ia l preceded the drug .
f o l lowed L . S . D . - 2 5 ,
ha l lu c inatio n s .
When the p l a c ebo tria l
thre e s ub j e c t s repor ted v is u a l
Subj e c t s reporting no p r ior visua l
e xp e r ience d id not report drug- induce d v isual h al l u ­
E l e ctrore t inograms in two b l ind s ub j e c t s
c in a t io n s .
with tot a l o p t ic atrophy were s im il ar to t hos e change s
noted in n o rma l s ighted s ub j e c ts repo r t ing v isua l
h al lu c in a t ion s .
L . S . D . -2 5 - induced v is u a l h a l lu c inations
can o c cur w ithout a fun c t ioning r e t in a .
D e f ic ienc ie s :
s tudy .
None .
(58)
A we l l de s igned and d o c umented
The author s u s ed caution in interpre tation o f
data .
L . S . D . -2 5 and Acco ��o d a t iv e Converqence Ra tios .
( P ayne ,
Purpo s e :
19 6 5 )
T o evaluate the e f f e c t o f L . S . D .-2 5 o n the
a c c o mJ.-r,oda t ive mechanism by mea sur ing the c hange in the
Ac commoda t ive C o nvergence/.hc c ommodat ion r a t io
Popu l a tion :
(AC/A r a t:id
Ten h e a l thy ma l e s , who s e a g es range d
betwe e n 1 7 a n d � 4 y e ar s .
Me thod :
Af ter thorough p sy c h iat r ic and o c u l ar
examination s ,
subje c ts c on s id e re d to be psy c h i atri ca l ly
" norma l " and s t ab l e , with r e l at iv e ly n o rma l cond it ion
o f the eye w ith r e spe c t to re f r a c t ion w e re u s e d .
12
Control AC/A r a ti o s were d e termined before and at l e a s t
o n e wee k a fter a s ub j e c t was g iven L . S . D . - 2 5 .
AC/A
r a t io s were me a s ur e d on each subje ct thre e hour s after
admi n i s tr a t i o n o f L . S . D . - 2 5 .
Re s u l t s :
There i s a sma l l d e t e c t a bl e inc r e a s e in the
AC/A r a t io in humans under the inf luence of L . S . D . - 2 5 .
Thi s increas e i n the AC/A r a t io wa s par t ial l y due to
p ar a l ys i s o f the c i l ia r y mus c l e .
The s e chang e s ind i c ate
that the c il i ar y mu s c l e is a f f ec ted by L . S . D . - 2 5 .
D e f ic ienc i e s :
( 7 1)
There w a s no c or r e l ation betwe en d o s e o f
L . S . D . - 2 5 and t h e increa s e in t h e AC/A r a t i o .
Samp l e
s i z e c o n s t itute s a l imi t ation , a n d t h e re s u l t s wer e not
reported in terms of s ta t i s t i c a l s ign i f i c a nc e .
E ff e c t s o f L . S . D . - 2 5 on the E E G and Photic Evo ked
Re spon s e s .
( Rodin and Lub y,
1966)
To a s c e r t a i n whe ther the v is u a l l y evoked
Purpo s e :
potenti a l wou l d b e al i.:e r e d in a c on s i s tent manner b y
L .S .D . - 2 5 .
Populati on :
Me thod :
E ight h e a l th y y oung volunteer adult mal e s .
After the pup i l s wer e f ix ed in a d i l ated st ate
by u s e of c yc l opento l at e , e le c trode s wer e a pp l i e d i n a
b i l ate r a l l y s ymme -t r i c a l manner to the occ i pi i:a l and the
p ar i e t a l are a s as we l l as the s uproaorbit a l r egio n s of
the head ,
in order to record the e le ct r o re tinogram
S igna l s were amp l ified b y an e l e c troenc e ph a l ograp h .
(ERG ) .
13
Contr o l ob s erva ti on s were obtained and then L . S . D . -2 5
was s ta r ted through intravenous d ri p .
Evok ed r e s p on s e
pho t i c s t imu l at i o n s were c a r r i e d out and EEG re cordings
were mad e .
F i f te e n minute s later EEG recordings were
taken w i th pho t i c s t imu l at i o n .
Thi s s e r i e s w a s repeated
with incre a s e in pho t i c s t imu l at i o n .
Re s u l t s :
The EEG s howed progr e s s iv e d e synchron i z at ion ;
s i owe r f reque nc i e s were mor e a f f e c t e d .
D a t a on the
frequency ana l y s i s of the EEG and the chang e s in the
ERG s howed that the mos t pronounc e d e f f e c t s o c curr e d at
·the t ime when the e l ec tr ograph i c t e s ting was terminated .
Th i s was th irty t o f or ty mi nut e s a f te r c e s s a t io n o f d rug
infu s i on .
Th i s sugge s t s tha t the me chan ism for the
p sychomime t i c a c t ion of L . S . D . -2 5 l i e s in a l terat io n s o f
t h e b o d y me tabo l i te s rather than in a d i r e c t a c t ion o f
the drug o n the b r a i n .
D e f i c i en c i e s :
s tudy .
(78)
The s amp l e was sma l l for th i s type o f
A s the autho r s p o i n t out , there a re conside rab l e
var i a t i o n s in the pho t i c evoked r e spon s e s o f norma l
ind i v i dua l s .
The conc l u s ion s u g g e s t i on that the
p syc homime t i c a c t i on o f L . S . D . - 2 5 l i es in a l te r a tion
o f the body me t ab o l i t e s rather than i n t he brain canno t
b e s u ppor ted by a s tudy o f t h i s nature .
No report in
terms o f s t at i s ti c a l s ig ni f i can c e wa s inc luded in s tudy .
14
Re t i n a l E f fe c t s of Hig� Do s e � o f L . S . D . - 2 5 i n the C a t .
( Sc hwa rt z and Cheaney , 1 9 6 4 )
Purp o s e :
To te s t the hypothe s i s that if l ow d o s e s o f
L . S . D . - 2 5 induce a low- f li c ke r e f fect , h igh d o s e s s hou ld
p roduce an e f fe c t re s embling the o ne d e rived by s t im­
u la ti ng w i th h igh f li c ke r rate s or s t e ady c o ns tant
i llumination .
I t wou ld b e e xp e c ted that h igh do s e s o f
L . S . D . - 2 5 wou ld d e c re a s e the t on i c d i s c ha rg e le ve l o f
t he opt i c t ra c t a n d late ra l ge n i c u late , in contra s t to
low d o s e s .
Popula t i on :
Method :
Twenty c a t s .
Bip o la r e l e c trode s we re p laced in the optic
t ra c t and late ra l gen i cu late nuc l eu s in prepa ration for
twe lve acute and e ight chron i c expe rime n t s .
contro l re ad ing s 've re t a ken ,
wer e p re s en ted .
L i gh t a dapted
as changing v i s u al s t imu li
L . S . D.- 2 5 wa s g iven intra venou s ly and
me a s u remen t s s ta rt e d ten minu t e s a fte r drug i n jec tion .
Ret ina l a c t iv i ty w a s mea s u red by the average t oni c
d i s charge leve ls p e r un i t t ime o f the o p t i c t ra c t .
Cats
emp loye d a s own c o n t ro ls .
Re s u lt s :
High d o s e s o f L . S . D . - 2 5 produc e d re t i n a l
chang e s in a s s oc i a t i on wi th behavio ra l v i s u a l unr e spon­
s it iv i ty .
No a lt e r a t i on o f the tonic a c t iv i ty appe ar s
upon s t imu l at i on wi th c hanging v i s u al s timu li .
d a t a ind i c a te d a d i re c t a c tion o f L.S . D .-2 5;
The
howeve r,
·'
15
the behav i o r a l v i sual unrespons i t iv i t y doe s not appear
to be due to r e t i n a l chang e s a l o n e .
D e f i c i e nc i e s :
The s amp le wa s sma l l .
(81)
Twenty c a t s were
broken d own into sub- group s mak ing an even sma ll e r
popu l a t i on for e a c h m e a s ureme n t .
E f fe c t s o f L . S . D . - 2 5 on the T �n i c A c t i v i t y oz the
Vi s u a l P athwa ys of the C a t .
Purpo s e :
( Sc hwart z and Cheaney , 1 9 6 6 )
To examine the aver age ma s s uni t o f ton i c
a c t iv i t y l eve l o f t h e o p t i c t r a c t a n d later al gen i cu l ate
bo dy of the c e rebral corte x i n the c a t .
Popu lati on :
Metho d :
E ighteen c a t s .
Ten ane s the t i z ed and e ight chroni c a l l y i mp lan ted ,
unane s the t i ze d c a t s were u s e d f o r th i s stud y .
Bipolar
e l e c trode s were p la c e d in the optic tract and l a t e ra l
g e n i c u l a te bod y o f the b r a i n .
Recordings wer e made
be fore and a f t e r intraper i tone a l i n j e ct i o n s of L .S . D . - 2 5 .
A l l o f t he chr on i c and mo s t o f the acute e xper imen ts
were c a rr ied out in a s oundproo f ,
l i ght-proof chamber .
L i ght-adapted r e c or d s were taken a f t e r 5 to 1 5 mi nute s
expo sure to room l i gh t .
Re s ul ts :
I n l S_out o f 2 0 exper ime n t s , L.s . b . -2 5 r e s u l ted
i n an incr e a s e i n the tonic a c t i v i t y l e �e l of the optic
tract and latera l gen i c u l a te body .
c as e s
( c hronic imp l a nt s )
In two e xcepti ona l
t he ge ni c u l a te body s howed a
d e c r e a s e i n the t o ni c a c t i v i t y leve l i n the d a r k a f ter
16
drug inj e ct i on .
N o eye movements Her e ob served in •che
ane sthe t i ze d c a t s,
e i ther be f ore or a f te r L . S . D . - 2 5 .
The t ime c ou r se of the inc r e a sed ton i c a c t iv i ty leve l s
appeared t o d i f f e r f r om the so-c a l l e d hal lucinatory
behav i or i n the c h r on i c c a t s .
L . S . D . - 2 5 a f fe c t s the
r e t ina in a manner wh i c h may r e su l t i n the expe r i ence
of simp le ha l luc i n a ti on s , but the ove r t behav i or of the
c a t c on sequent to drug adm i n i str a ti on may be independent
of the change p r oduced in the v i sual system .
(82)
D e f i c ienc i e s :
A sma l l samp l e was u se d t o make twenty
me a sureme n t s .
N o c ontr ol group s were u s ed on the se
mea suremen t s .
T h e unane sthe ti z e d c a t s showed incre ase d
h e a d movemen t s wh i c h c ould have e f f e c t e d t onic act i v i ty .
Th i s appe ar s t o b e �n ope r a t i n g var i ab l e other than
the exper iment a l f a ct or .
As w i th many of the r e se ar c h i nve st i g a t i o n s t o be
r e p or te d here ,
the imp l ic a t i on s f or man are unk nown
b e c a u se of the p r ob l ems i nv olved i n g e n e r a l i zing re su l t s
obt a ined i n stud i e s emp l oy ing a n ima l samp l e s .
T h is t ype
of d e f i c iency wi l l b e d i sc uss e d further i n Chapter
E f f e c t s of L . S . D . - 2 5 on the C e n tr a l Nervous S ystem
Abl a t ion .
( Ba l dwin, e t
Pur p ose :
the b r a in .
�l·'
195 9 )
T o l oc at e the site of L .S .D . -2 5 �f f e c t s
ln
17
Popu l a t i o n :
Me thod :
Fi fteen ch impanze e s .
E ach an ima l wa s obs e rved for a t l e a s t one year
be fore e xp e r ime n t a l u s e .
Lobotom i e s i n varying c o mb i ­
nat i o n s wer e p e r formed on the ch impan z e e s p r i or t o the
adm i n i s tr a t i on of L . S . D . - 2 5 .
Amo ng the type s of oper­
ations wer e f ront a l and temporal l o be c t o mi e s 1 b i l a te r a l
r emov a l o f me s ia l tempora l s t r u c ture s , a n d b i l a te r a l
abl a t i on o f the temporal s tr u c tur e s .
Each p r epa r a t ion
wa s u n i l ate r a l a t f i r s t and e a c h a n imal rece ived L.S . D .- 2 5
af ter u n i latera l an d b i l at e r a l ablations a s we l l a s before
L . S .D . -2 5 wa s admi n i s tered ora l ly .
ope r a t ion s .
Re su l ts :
A f t e r b i la te r a l f rontal lobectomy the r es pon se s
t o ord inary s i tu a t i o n s are rad i c a l l y c ha nged , but n ot the
react i on to L . S . D . - 2 5 .
After b i l a t e r a l temporal lobectomy
the r e a c t ion t o L . S . D . - 2 5 changed .
Un i la tera l t empor a l
lobectomy doe s not change t h e an ima l s ' r e a c t i on ·to
L. S . D . -25 .
I t appe ar s that one o f the tempor a l l obe s
i s e s s en t i a l for an L .S .D . - 2 5 r e ac t ion among Chimpan zees .
A s a n e xamp l e :
p an i c o r perceptual abera tion doe s not
i nc r e as e i n the p o s tope r at i ve drug rea c t i on .
Th i s may
po s s i bl y i n d i c a te that L.S . D . - 2 5 d i s tu rbs perceptua l
me c hanism s repre s ented i n the grey mantle o f the
tempor a l l ob e .
De f i c i e n c i e s :
in thi s r e po rt .
(9)
Method o f s e l ec t ing s am ple
was
n ot g i ve n
Becau s e o f the u s e o f sub-group� samp l e s
we r e inadequate i n t erms o f s ize :
e.g.,only on e
18
c h impan z e e had a b i l a t e r a l te mporal lobe c t omy .
From
the report of thi s e xp e r iment thi s s tudent f e l t the
autho r s be c ame too i nvo lved with the i r sub j e c t s to
repor t obje c t ive l y on them .
Chimp an z e e s ' n ame s wer e
u s ed i ns te a d o f numbering e a c h expe r i ment .
repo r t i n g b ehavi o r o n Samp s o n :
Exampl e s o f
" When he l anded , Beebie
moved t o h i s s ide and hugged h im w i th her r ight arm .
She l o oked d ir e c t l y at the photographer a s she d i d t h i s . " ·
(9: 4 7 3 )
A report i n terms o f s ta tis t i c a l s i gn if i c ance
wa s not inc luded i n thi s repor t .
Expe r iment a l Ana ly s i s o f i:he I nh iJ? i tory Action o f
L . S. D . - 2 5 on Cor t i c a l D endr i t e �c t iv i ty .
Purpo s e :
( Purpur a , 1 9 5 7 )
The hypo th e s i s wa s advanced that L . S . D . - 2 5 i n
l o w concen trations i s dependent on t h e nature o f the
predominant synap t i c inter r e l a t i on p re sent in any p a t hway .
Pop u l a t i o n :
Unane s thet i z ed-para l y z e d cat s , number not
r e porte d .
Method :
Sub j e c t s wer e prepared for c ro s s -p e r f us ion
e xp e r iment :
doub l e f emora l artery-to-vein c ann ula ti ons
wer e e f fe c te d a f te r d e e p he pa r in i z at ion .
Stimula t i on o f
the pyrami d a l t r a c t in t he medulla w a s 2.c compli s he d by
i n s e r t i on �f a p a i r o f f i ne Te f lon-c o a ted s i lve r wire s
from the dor sum a t mid o l ivary l eve l o f the med u l l a .
Imp ul s e s conduc ti n g i n a d i r e c tion oppo s i te o f norma l
or impuls e s cond u c t ing i n a norma l d ir e c t i o n could be
19
obtained by s t imulat ing the motor cortex and f rom
s timul a t j.ng the med ul l a r pyramid .
L . S . D . - 2 5 wa s
admin i s tered intraveno us ly and the e le c trocard iograms
taken .
Re s ul t s :
I t wa s demon s trated that dendr i t e s a re on ly
synap t i ca l l y e x c i tab l e and cannot b e a c t ivated by d i r e c t
s t imul a t i on o r b y c ond uc t ing imp ul s e s in a d i re c t i on
o p po s i te o f nor ma l f r om ce l l bodi e s .
Thi s f indi ng
i nd i c ate s a synapt i c s ite o f a c tion o f L . S . D . -2 5 and
that , p ar t i c ul a r l y i n the c a s e o f a p i c a l dendr ite s ,
i s an inh i b i tory a c t i on .
De f i c ie n c ie s :
it
(74}
T o t a l number o f c at s used i n the s e
mea s ureme n t s w a s not i nc l uded in th i s repor t .
No
conc l us io n s are j us t i f i ab l e wi tho ut c o n s ideration o f .
s amp l e s i z e .
( Monroe and Heath, 196 1 )
P urpo s e :
Th i s s t udy att empted a g ro s s corr e la t ion
be twee n hype r synchrono us a c t ivi ty i n the r h inenceph a l i c
s tr uc t ur e s and t h e ove r t behavior o f the Mac a c a mulatta
monkey .
P o p ula tion :
Six Mac a c a m u!- a�. ta monkey s .
Six �1_�c a c 9- mul atta monke y s had chro n i c a l l y
imp lanted e le c t r o d e s over t h e f r o n t a l a n d o c c i p i t al
c o r t e x , and in the s e p ta l , caudata and hippocampal
20
r e g i o n s o f the b r a i n .
P l a cement wa s de termined
h i s t o l o gic a l ly a t autop s y .
The s ub j e c t s rema ine d f r e e
in the i r cage s except dur i ng ·the exper iment when they
wer e p a r ti a l ly r e s tr ained ln a cha i r w i th a c o l l a r
wh i c h prevented them f rom r e a c h ing t h e e l e c trode w i re s .
A crud e behav i o r a l rat i ng wa s ke pt o n the subje c ts .
After the e le c trogr am s r e turned t o nor ma l f o l l owing
s urgery , e a c h s u b je c t was g iven L . S . D . - 2 5 or one o f
i t s various d e r ivative s and e le c trogram s were cont i nued .
The s u b je c t s wer e s tu d i ed over a per i od o f one t o thre e
month s w i th 3-2 0 stud i e s per formed o n each subje c t .
Re s u lt s :
A good corr e l a ti on c o u ld be e s tab l i s he d b e tween
the behavi o r a l e f f ec t s in the sub je ct s and rhinence ph a l i c
paroxysm a l hyp e rs ynchronous a c t i vi ty .
Sub je c t s s hmving
c ataton i c behavior a l s o s howe d e le c t ro ph y s io l ogi c a l
c hange s i n the s e p t a l region .
I f subje c t s s howe d
a g i t a t i o n a n d aggr e s s ivene s s , t here wa s hype rsynchronou s
a c tivi ty in the hippocampal r e g i on .
vJh e n no e le c tro-·
gr aph i c c hang e s o ccurred , there s e emed to be no change s
i n b e hav i or .
D e f i c i en c i e s ;
(65)
'The s am p l e was v ery sma ll.
3 - 2 0 s tud i e s p e r formed on e a ch anima l .
T here we re
s·tud i e s wer e
d o n e a s c l o s e a s 4 8 h ou r s apa rt a n d t he c r ite ria for
s ta r t i ng another mea s urement wa s that the baseline
e l ec t r o g rams h a d returned t o n o rma l whi ch did not
r u l e ou·t c o mp l e t e l y ove r l app ing o f drug a ct i on i n studie s.
21
Re l i ab i l ity o f b ehavio r a l r a t i n gs not e s tab l i shed .
Total
number of s tud i e s done w a s not g i ven in th i s repor t .
No
r e port of s ta t i s t ic a l s ign i f i c ance wa s inc luded in thi s
re por t .
The E f f e c t s o f L . S . D . - 2 5 , P s i l o �b i n , and P s i lo c i n on
T emp o r a l Lob e EEG P atter n s a nd Le arned Behav i �� i n the
Cat .
(Ade y , e � a l . ,
Pur po s e :
1 9 62 )
To s tudy the e f fe c t o f L . S . D - 2 5 , p s ilocybin ,
and ps i lo c i n on p attern s o f r e st ing a c t i v i ty , a nd on
the l e arned behavior i n c a t s .
Popul a t ion :
Me thod :
E ighteen c a t s were u se d for th i s exper iment .
E ighte en sub j e c t s wer e implanted with e le c trode s
i n the amygda la , hippocampa l , and in the a d jacent
entor h i n a l area of the pyr i f orm c o r te x .
Two tra in i n g
s i tu a t i o n s w e r e u s e d , o n e i nvo lved train i ng in a T -na z e ,
with approach to a food r eward on the b a s i s of a vi sua l
cue .
T he othe r i nvolved d e l ayed-r e sponse trai ning , with
a p proach to a concealed food rewar d a fter an interva l o f
f iv e t o t e n s e c o nd s .
intrap e r i t one a l ly .
A l l drug administrati on s were made
EEG r e co rd i ng s o f neur ophy s i o l og i c
a c ti v ity a n d mov i e s taken s imu l taneou s l y wer e synchroniz e d
whi c h permi tted a c l o s e corre l a t i o n o f be ha vi o r and
e le c tr i c a l act iv i ty .
Re s u l ts :
C h ar ac t er i s t ic c ha ng e s f o l lo wed the admi n i s ­
tr at ion o f L.S.D . - 25 , such a s kangaroo p o s ture , head
s hak ing , and a l o s s o f norma l r espon se s .
With L . S . D . - 2 5
22
do s age aroun d 2 5 ug per k i lo gr am o f body we igh t , b r i e f
s e i z ure - l i ke e p i sode s we re s e e n in EEG rec ord s in a
q u i e t e nv i ronment .
L . S . D . - 2 5 in d o s e s o f 10 0 ug p e r
k i logram o f body we i g h t produced se i z ure s in a we l l - l i t
e nv i ronment and d i s rupted a d e l ayed re s po n s e per formanc e
when the s e i zure e p i sode encroached o n the t ime when
d i s c r iminat ive per f ormance was required .
a
P s i locyb i n and
p s i lo c i n r e s emb le d L . S . D . - 2 5 in the i r gene r a l ef fe c t s
b u t d i f fe r e d i n the brev ity o f the i r a c tion .
De f i c i e n c ie s :
The s amp l e vva s sma l l .
( 3)
Total n m11be r o f
me a s urements tak e n wa s not inc luded i n thi s r e por t .
The
n umber o f c a t s u s e d for contro l s and mea surement s wa s
not g iven .
A report o f s t a t i s t i c a l s ign i f i c ance was not
i nc l uded i n th i s repor t .
i n the D e c e r ebrate C a t .
Purpo s e :
To s tudy po s s ib l e vag a l e f fe c t s o f L . S.D . - 2 5
and bromi d l y s er g i c a c id
Po pu l a t ion :
Metho d :
( C e rvoni , e t a l . , 1 9 6 3 )
( BOL- 1 4 8 )
i n the dec erebrate c a t .
Forty c a t s .
Trachea l , a r te r i a l and venous c annul a t i on s and
p l a c emen t o f subcutaneo u s e l ectrodes we re car r i ed o ut
under e ther ane s the s i a .
Decerebration was ac compl i s he d
b y s u c t i o n through t h e sup e r i o r c o ll i cu l i f o l l owing
l i ga t ion of the c o mmon caro t id arte r i e s and c ompre s s i on
o f ·the v ertebra l arte r i e s .
Ade quacy o f dece rebrat ion
23
and intac tn es s o f the l ower bra i n stem wer e j ud g ed by
the p r es en c e o f d ec er ebr a t e r i g i d i ty and rhythmi c
s pontaneous br eathing .
Fo l l owing dec er ebration , a t
l ea s t o n e hour el ap s ed b efor e giving v ar io u s do s es o f
L . S . D . - 2 5 and BOL- 1 4 8 b y i ntravenous i n j ec t i on .
E l ec tro­
cardiograms and v i t a l s igns w er e r ec o r d ed b ef o r e and
a f t er i n j ection o f drug s .
Resu l t s :
The anima l s g iv en L . S . D . - 2 5 in do s es of 0 . 2 ,
0 . 3 , and 0 . 4 ug/kg show ed bradycard i a , hypoten s i o n and
d ec r ea s ed r a t e of r es p i r a t i on .
I n l a r g e dos es , mar ked
c onduc t i on d i s turbanc es w er e not ed .
With BOL- 1 4 3 only
mild t emporary hyp o t en s ion and bradycard i a wer e noted
with no changes i n r hy thm .
L . S . D . - 25 appea r s to have
a medul l ary s t imu l ating a c t i on whi l e BOL-1 4 8 has d i r ec t
c ar di a c tox i c i ty i n l ar g e do s es ,
s econd d eg r ee h ea r t b l ock .
D ef i c i en c i es :
v er y sma l l .
such a s p roduc ing a
( 19 )
Samp l es for the var i o us exp er i ment s wer e
Var i o u s do s es o f L . S . D . - 25 w er e u s ed in
mak i ng d i f f er ent m ea surem en t s .
wer e u s ed in some mea s ur em en t s .
As f ew a s four c at s
The number o f c a t s
u s ed f o r maki ng mea sur emen t s w i t h BOL-14 8 was n o t
inc l u d ed in th i s r eport .
The r esu l t s of thi s study
d i d not inc lud e a r eport in ter ms of stati s t i c al
s ig n i f i c a nc e .
24
The E f f e ct o f L.S� . -2� on the S l e e p �ycle o f the C a t .
{Hob s on , 1 9 64 )
Purpos e :
T o s tudy the a ction o f L . S . D . -25 upon the s l eep
cycle o f the cat , and to te s t the hypothe s i s tha t
moderate d o s e s wou ld i nterfere with sleep genera l ly ,
but t ha t sma l l d o se s would s e l e ct i v e l y augment low
v o l t age f a s t s le e p.
Popu la t i on :
Method :
E ight adu l t cat s wer e u s e d .
Sub j e ct s wer e imp l anted with e l e ctro de s .
One
or mor e days p r i o r to r e cording , the cat wa s placed on
a
tre a dmi l l whi ch rotated a t a r ate of 3 0 ·t ur n s per hour ,
and e xe r ci s e d con t inuou s ly f o r 1 5 hour s .
Then L . S .D. - 2 5
was i n j e ct e d intr aper i tone a l ly i n some cat s and a s a l i ne
pla cebo in o the r s .
The ca t s wer e then pla ced i n a s ound­
proo f , d imly i l lumi na ted box for 2 - 4 hour s of cont inu o us
e l e ctrographi c r e cording and o b s e r v at ion rrom the dar kened
exp e r iment a l room via a one-way wind ow .
Re s u lt s :
L .S .D .- 2 5 in·ter f e r ed wi th s leep genera l ly and
reduce d l ow v o ltage f a s t s leep s e l e ct iv e l y i n the cat s .
T h e me chan i sm o f the e f f e ct o f L . S .D . -25 wa s not
e lu ci d a te d .
The a n ima ls g iven L .S .D.-25 seemed to b e
more s en s i t ive to aud i tory arou sa l .
The d a ta r efute
the hy pothe s i s that L.S .D .-2 5 enhance s the p rod ucti on
of l ow vo l tage f a s t s leep . ( 3 9 )
D e f i cienci e s :
The s amp l e wa s ve ry smal l .
me a su rement s we re t ak e n.
Two se par a te
In e xp erime n t I tvJO c at s were
25
u se d with no contr o l group .
Exper ime nt II us ed s ix
c a t s with p l acebo i n order to perm i t genera l i z ation ,
whi c h i s que s t i on ab l e with s u c h a sma l l popu l ation .
The r a t i ona l e f o r the r e s u l t s obt ained wa s not cl ear .
D i f ferenti a l E f f e c t o f L . S . D . - 2 5 �pon Hab i tuatin� and
Extingui sh i n g Evoke d Respons e s .
( Sh e a t z and Bogdan sk i ,
196 4 )
Purpo s e :
To examine the e f f e c t s o f L . S . D . - 2 5 on
d i f f e r e n t i a t i ng b e tween the s t a t e s of h ab i tu ation and
extinction change s in the central nervou s s y s tem by
noting the d i f ferenti a l upon the EEG r e spon s e s to
aud i tory s t imu l i by c l i c k s
Popu l a t i on :
Metho d :
( sic ) .
E ight monkeys and s even c a t s .
E a c h s ub j e ct had e l e c trode s i mp lanted 1 n a t ot al
o f 4 2 b r a i n l o c a t i on s .
E le ctrode l ocati o n s were ver i f i ed
po s t mor tem by h i s to l o gi c technique s .
Stat i s t i c a l
anal y s i s wa s made on amp l itude mea sureme n t s f rom a ll
a c t ive brain are a s .
Record i n g s were taken i n s eve r a l
or a l l o f t h e f our p sy c ho l o gi c a l state s r e la te d to
s t imu l u s : nove l , hab i tuate d , cond i ti oned ,
and extingu i she d.
Hab ituation o f e xt inction we re a ch i eved by pre se ntation
of the c l i cks f o r per iod s o f hour s o r months .
Con­
d i t ioning was obtained by a puff o f air de l ivered to
the s ub j e c t s f a c e by blowing into a 1 0 -foot tube at the
s ound o f the cl ick .
L . S . D .-2 5 was g iven in-travenou s ly
26
or by intrapulmonary intuba t i o n .
The s t a t e o f con­
d i t ioning o r ext i nc t i on wa s g auged by f e a ture s of the
EEG r e s p on s e to c l i ck s .
Re s u l t s :
D i f fe r e n t l eve l s o f central ner vous s y s tem
r e a c t i v i ty to the hab i tuating and ext ingu i s h ing re spon s e s
t o L . S . D . - 2 5 were d e mon s tr a te d .
doses
L . S . D . -2 5 in sma l l
( 1 0 ug/k g ) which a f fe c t behavior only i n the ab s ence
of an a c t i on environment and wh ich only m i n ima l ly a l ter
the s pontaneous EEG , draw s a c l ear d i s ·tin c t i on b e twee n
hab ituating a n d extingui sh i n g evoked aud i to r y re spon s e s
b y p r eferent i a l ly f a c i l i t a t i ng the latte r .
It also
e s tab l i she s a c o nd i t i on f a vorable t o pro long a ti on o f
o s c i l l a t i o n o f the r e spons e .
De f i c i e n c i e s :
(84)
The s amp le wa s very sma l l .
It a ppea r s
t h a t t he above r e s u l t s w e r e b as ed on mea s u re ments u s i ng
only the monkeys .
Stat i s ti c a l d a t a from the cat s t ud i e s
were not i n cl ud e d except f o r o n e ob s e r va t i on :
only in
two o f the cats w a s pote n t i a t i o n of the h ab ituating
r e spon s e c le a r e nough to be not i c e ab l e upon c au s a l EEG
i n s pe ct i on .
N o c ontr o l g roups wer e u s e d .
The number
o f mea s ur emen t s made wa s not inc lude d i n this s tudy .
T h e s tud i e s wer e not r e ported in term s o f s ta t ist i c a l
s ignif i cance .
(Mori l lo , §_:!:._ a l . , 1964)
Purp o s e :
To i n7e s t igate t h e a ct i on o f L . S .D . -2 5 upon
27
evoked potent i a l s s imu ltaneou s ly r ecorded from the l ater a l
funic u l u s a t i nter co l l i c u l a r level .
Popu lat ion :
Method:
E ighteen intact adu l t c a t s .
Sub j e c t s were ane s thetiz e d and tracheoti mi z ed ,
one o f the i r femora l ve ins was c annu l a ted and a s c ia t i c
nerve wa s d i s s e c te d f r e e .
E l ectr o d e s were sterotaxi c a l ly
p l a c e d through a burr h o le into the me s e ncepha l i c r e t i c ­
u l ar f o r mati on a t interc o l l i c u l ar l eve l .
E l ectrode s in
the mid b r a i n wer e locate d c o ntr a l a te ra l ly to the d i s ­
s e c ted s c ia t i c nerve .
E l e c tr od e s wh i c h were in s e r te d
i n t o t h e later a l fun i cu l u s o f the sp i n a l co rd at the
l eve l of the s econd cervi c a l s e gme nt ,
the s t imu lated s c i a t i c ner ve .
ips i lateral to
The dorsal c o lumn s were
s evered one s e gment be low the r ec o r d i n g e le ctr ode in the
spi n a l cord to rule out the po s s ib i l i ty o f cont ributing
to the s e evoke d potentia l s .
Whe n the r e s pcn s e s had
attained the i r c ontr o l va l u e s a f t e r r e c o very from the
a c ti o n o f the drug , the s p in a l c o rd wa s c ar e fu l ly
s e c t ioned at the leve l o f the f i r s t cervic a l ver tebra
as a contr o l mea sure to d i s card centr ifuga l component s
o f the r e spon s e s in the l at e r a l f un i c u l u s .
L.S.D . - 2 5
and P e ntotha l were i n j e c te d through the C annulate d
Femora l Vein .
Re s ul t s :
L . S .D . - 2 5 h ad no e f f e c t upon the evo ked
potentia l s in the l a t e r a l f un i c u l u s of the s p inal
cord , but depre s sed the r e s p o n s e in the midbrain
28
re ti cu l a r f orma t io n .
The e f f e c t o f L . S . D . - 2 5 is exerted
a t midbrain l e ve l .
De f i c ienc i e s :
I t wa s d i f f ic u l t t o t e l l f rom th i s report
how many exp e r imen ts were done , the nur�Jer o f s ub j e c t s
u s ed in e a c h one , a n d how many v a r i e d do s e s o f L . S . D . - 2 5
were u se d .
Re s u l t s were not reporte d i n terms o f
s tat i s t i c a l s ign i f i c anc e .
E f fe c t -of a Chem i ca l __.._
l v _ -Depre s se d
-----
Jl..mygd a l a
on -the
-
Behav�o r a l Man i f e s t a t i o n s Produced i� �at s b y L . S . D . - 2 5 .
( Barratt and P r ay ,
P ur p o s e �
196 5 )
T hi s s tudy
t e s ted the hypothe s i s that SQ 1 0 , 496 ,
an exper ime n t a l antidepre s sant chemi c a l , produce d by
E . R.
S qu ibb
i n cats .
&
Son , wou l d b l o ck the e f fe c ts o f L . S.D . -2 5
A s econdary purpo s e was to c ro s s v a l id a te the
e f fe c ·t of SQ 1 0 , 4 9 6 on the s t i r�ml a-tion threshold for
produc ing amygdalo i d s e i zure s in c a t s .
P op u l at ion :
Method :
Re s ul t s b a s ed o n four c a t s .
E le �trode s wer e imp lanted stereotax i ca l ly ,
b i p o l ar l y , into the b a s ol a t e r a l par t s o f th e amygda la
and into po s te r i o r hypotha lami.
a l l owed f o r r e covery .
E ight days were
E l e c trode p lacemen t s were ve r i f i ed
hi s tolo gic a l l y a t autop s y .
E E Gs were obta ined w i th the
l e a d s atta che d to a s lop r ing to p ermi t free movement
without entangling the l e ad s .
No i s e wa s introduc e d into
the soundproof c ub i c l e with a one ·-way mirror for
..
29
ob servati cn .
A s tab l e s t imu l a t i on thr e shold for
e l i c i t ing amygda l o i d s e i zure w a s d etermined , fo l l ow i ng
which , L . S . D . - 2 5 and SQ 1 0 , 4 9 6 we r e admin i stered
intraper itonea l ly.
Re s u l t s :
S Q 1 0 , 4 9 6 r a i s e d the thresh o l d f o r e l e c tr i ­
c a l ly i nduced amy g d a l o i d s e i z ur e s .
Pretreating w i th
SQ 1 0 , 4 9 6 b lo c k e d the behavior a l e f f e c t s o f L . S .D . - 2 5 .
Very l i t t l e change i n spontaneous a c t iv i ty o f the
amygda l a was noted under L . S . D . - 2 5 .
D e f i c ienc i e s :
{l l )
Very sma l l p op u l a t io n .
Re s u l t s wer e
b a s ed on o ne s tudy u s ing f ou r c a t s and s uppo r t e d by a
s tudy u s ing e l even c a t s i n whi c h other d r ug s we r e
t e s te d .
A contr o l group o f c a t s wa s not me ntioned in
thi s repor t .
N o r e p o r t of s ta t i s ti c a l s ig ni f ic ance -
included i n th i s report o f exp e ri ment.
T ime- s e r i e s , F r e quency Analys i s , ?Ed E �e c -t����s i s o f
t h � E E G .s o f Norma l and P s yc h o t i c Be fore
( P f e i f f er , e t a l . ,
Purpo s e :
��1�
Af ter Dr ug_§_.
1965)
T o pre s e nt a surve y o f r e c e n t and curr e nt work
on quan t i ta t ive e le c troence ph a lography and p sy c ho tropi c
d r ug s .
P opul a tion :
P s ychoti c p a t i e n t s a nd nonp sychotic
vo lunteer s , t o t a l numb e r i n g 2 0 1 .
Me thod:
Thre e groups o f subje c ts were u s e d .
Group
one wa s comp ose d of 5 1 ma l e pre - r e l e a s e d inma te s of a
30
r eformatory .
Group two wa s c omp o s ed o f 4 4 vo l unteer s
from the :i.. a boratory s t a f f .
Group thr ee w a s c ompos ed
o f 1 0 6 m a l e chron i c s c h i z ophren i c pat i en ts .
A l l EEG
r ecordings wer e monopo l a r , w i t h el ectrod es on the l ef t
a n d r i gh t o c c i p i ta l , par i et a l , t empo r a l , a n d fronta l
a r ea s .
A f t er a t en m i nute contro l l ed r ecording w a s
obt a i ned , the s u b j ec t s wer e g iven d r u g s o r p l a c ebos
ac cording to doub l e- b l ind pro c edur es .
T en minute
r ecordings wer e then taken at hour ly or h a l f - hourly
interval s ther ea f t er , ext ending t o four ,
hour s .
s ix o r eight
Drugs u s ed i n thi s s tudy wer e phenobarb i ta l ,
meprobamat e , c h l o r d i a a eprox i d e , orphenadr ine and L . S . D . - 2 5 .
Resu l t s :
Ant ip sy c h o t i c drugs produce su b s t a ined changes
in the EEG s .
The ef f ec t o f L . S . D . - 2 5 i n norma l s ub j ec t s
i s t o product E E G s quan t i tative l y s imi lar to tho s e o f
s c h i z ophren i c pat i en t s .
D ef i c i en c i es :
(72)
C r i teri a f o r s el ec t ing the thr ee groups
wa s not inc l ud ed i n t h i s r epor t .
F ormer pr i s oner sub j ec t s
c o u l d n o t b e a c c ep t ed a s normal s , n o r c o u l d the group o f
l aboratory worker s who vo lunteer ed .
The authors point
out that i t is impo s si b l e t o f ind a c l ea r de f in it i on
for a norma l EEG yet they s et up their own c r i t er i a for
a ba s el in e norm a l EEG and u s ed it as s t a ndard m e a surement .
31
The Hippoc ampu s and the Or i e n t i ng Re f lex .
( Rad u l ovacki
and Adey ,
19 6 5 )
Purpo se :
To s tudy the e l e c t r i c a l activity in the e at ' s
hippocampu s i n a lert but nonp e r f o rming anima l s , and in
both the c o u r s e o f d i s c r iminat ive ta s k p e r f o rmance , and
dur ing o r i en t i ng behavi or .
Popu l a t i o n :
Method :
F ive adu l t c a t s .
B i l at e r a l e l e c trodes wer e imp l anted i n the
d or s a l area of the h ippocampu s .
Behavior training
required the cats to make a d i re c t approach to the l i ght
s id e of a T-box to s e cure a conc e a l e d food reward .
Opening o f the door s in the box wa s r e i nforced by a tone
that per s i s te d f o r the dur a t i o n of the approach t r i a l s .
Dur i ng ori e n t i ng t r i a l s the door s o f the s tart box
rema ined c l o s e d , but the s ub j e c t s wer e ab l e to hear the
r e i n f o r c i ng tone , and ob s e rve the amb ient i l lumination
i n the reward area f rom the cue l i ght .
Wi th three
s ub j e c t s , o r i en t i ng tr i a l s wer e introduced at the s tart
o f tr a ining ; wh i le with the other two s ub j e c t s the s e
we re wi thh e ld unti l a h i gh leve l
approach p e r f o rmanc e .
(90%)
wa s reached i n
P sychotro p i c agents wer e
admin i s te r e d i n s in g l e i ntrape ri ton e a l d o s e s a t i nterv a l s
o f not l e s s t h a n 2 1 day s .
Ear l y e f fe c t s o f drugs we r e
a s s e s se d b y comp a r i s on o f 2 0 pre -drug t r i a l s w i t h the
s ame numb e r pre sented 4 5 - 6 0 minute s after i n j e c t i on .
L . S . D . - 2 5 wa s g iven i n d o s e s o f 7 0 - 9 0 ug/kg .
CL - 4 0 0
32
( c yc lohexy l amine monohydreochlor ide ) was g iven i n 2 .
mg/kg .
Re s u l t s :
K:� G r e co r d i n g s wer e taken .
A l e r t but non- p e r forming c at s exhib i te d a wide
spectrum of theta wave activity , with appearance of
bur s t s of wave s i n a narrow s p e c t r a l r an g e .
This
a c t iv i ty p e r s i s t e d i n e p o c h s b e twe e n d i s c r iminat ive and
ori ent ing tr i a l s throughout many month s of train ing .
Imlwe l l in g l e ad s in the ba s a l part s o f the dentate
gyr u s and s ub i c u lum we r e characte r i z ed by f a s t ,
v o l t ag e a ct iv i ty .
low ,
O r i enting b ehav ior wa s a s s o c iated
w i th s l ower and le s s r e gular c omputed ave r a ge s .
S i ng l e
do s e s o f L . S . D . - 25 w e r e fo l l owed by pro longed d i s­
inhib i t io n o f inhib i t ed or i e nt ing behav i or , and the
gradua l appe arance of a r egu lar EEG average duri ng
ore inta t i on f iv e - t e n day s af ter the drug .
a c t iv i ty was s e en with CL- 4 0 0 .
A s im i l ar
The auth o r s c ond lud e d
t h a t wi thin a s in g l e b r a i n s y s t em , t h e r e i s a c lear
c apac i ty for p a r t i c ip a t i o n i n r e l at e d but d i f f e r ent
behav i o r a l r e sponse s , with i nduc t i o n of grea tly d i f fer ing
EEG patterns in d i s cr imin a tive .::m d ori enting re spon s e s .
(75 )
Def i c ie nc i e s :
thi s s tudy .
Sma l l numbe r o f sub je c t s were u s e d for
Re s u l t s were not reporte d i n · terms of
s t a t i s t i c a l s ig n i f i canc e .
33
A l t e r a t im_:.s in the Nocturna l S le e:e_ fyc l e Re§u l t i n51 from
(Mu z io , e t a l . ,
L . S . D . -25 .
Purpo s e :
19 6 6 )
T o i nve s t i ga t e the e nhan cement o f REMS
interv a l s c h a r a c te r i z ed by
a
( the
r e l a tivel y l mv vo l tage ,
f a s t , non- s p ind l i n g EEG , ac comp an ied by rapid eye
movemen t s
( REI'1s ) , and l o s s o f tonus o f the he ad and
neck mus c u l a ture - d e s i gnated as REM S l eep
( REMS ) by
L . S . D . -2 5 .
Popu l a t ion :
Method:
Twe lve p sy c h i a tr i c a l ly s ound individual s .
The s ub j e c t s were re que s ted to maintain their
s leep r ecords a t the amount they r ep orted a s typ i c a l for
them s e lv e s for three nights p r i or t o every s e r i e s o f
exper ime n t a l n i g h t s and t o ab s t a i n f r om a l c oho l , other
s t imu lant bever a ge s , and f ood for three days pr i or to
'ce s t s .
Sub j e c t s wer e to ld e a c h n i gh t b e f or e going to
bed that about one hour a f t e r f a l l ing a s l e ep they would
b e awakened and g iven an ounce o f f l uid to d r i nk .
They
were info rmed that the f luid wou l d contain e ither a
s t imu l an t o r a s ed a t ive , L . S . D . - 2 5 , or p l a i n wa te r .
Ac tua l ly the de s ign provided that e a c h n ight e ac h
s ub j e c t would r e c e iv e only d i s ti l le d wat e r p la cebo o n
a l l nights except f o r the n i gh t ,
i n e a c h s e r ie s , when
L . S . D . - 2 5 wa s added as a c o lor l e s s , ta s te l e s s and
odor l e s s l iquid .
Results :
On nights
f o l l owing the admi n i s tr a t ion o f
L . S . D . - 2 5 a pro longation o f e i th e r the f i r s t o r s e cond
34
REMS
p e r iod was obs e rved ; howeve r th e r e was no con s i stent
inc r e a s e i n tot a l REMS .
L . S . D . - 2 5 d id not alter tlte s l eep
EEG c y c l e but c au s e d mode r ate inc r e as e s o f body mob i l ity .
(67 )
D e f i c ienc ie s :
S amp l e was smal l .
Me asuremen ts wer e made
u s i ng groups o f s ix s ub j e c t s e ach .
sma l l d o s e s ,
L . S .D . -25,
eve n i n
c o u ld b e r e cogn i z ed b y the s ubj e c ts due ·to
i t s p r o f ound a c t io n on the c entr a l nervous s y s tem .
E s tab l i shmen t o f c o nt r o l s leep r e c o r d i ng s we r e poo r ly
No report i n terms o f s t ati s ti c a l s ig n i f i c ance
d e s igned .
w a s inc luded i n th i s r epor t .
(Rev z in and
Jl,rms ·t rong ,
Purpo s e :
196 6 )
The s e exper imen t s wer e per f ormed to determ ine
whe ther the e f fe c·ts of L . S . D . - 2 5 on evoked e l e c trop o t e n t i a l s i n the ·h ippocampu s vve r e s im i l ar t o t.h.o s e
produced by re s e r p ine ,
.
·'a ,.�ypO GeDS lV8
arug ,
�
c ap ab l e o f
produc ing s e i zure s .
P opul a·t ion :
Me ·thod :
Twe lve adu lt c a t s were u s ed .
The sub j e c t s were ane s the t i zed wi th e·ther and
p l ac e d i n a s te r e o t ax i c ins tr umen·t .
The me senceph a l i c
r e t i c u l a r form at io n w a s then de s tr oyed b y e le c t r ic
c au·tery .
W i th ant. ib i o t i c s and f l u i d s ·the unc on s c ious
c a t could be k ept i n g ood c ondi·t i on for about
a
week ,
35
thu s d r us s could be compared free from ane sthe t i c
E le ctrode p a i r s were p l aced b i l ater a l ly
inte r f e r enc e .
i n ventr o. l h ippo c ampu s , and i n the r ight latera l amygdalar
nuc l e u s , and the r i ght sep t a l a r e a .
All e l e c trode p o si ­
t i o n s we re c on f i rmed h i st o l og i c a l ly at autop sy .
Control
recordings wer e taken f o r 2 - 3 hour s , L . S . D . - 2 5 was
i n j e c te d and r e c o r d i n g s c on t i nued for 4 -6 hour s .
Re su l t s :
L . S . D . - 2 5 doe s fac i l i tate the amygdala­
h ippo c amp a l evoked pote n t i a l .
The data are interpre ted
to ind i c ate that L . S . D . - 2 5 i s a pure ly i nh i bi tory
c ompound i n the h ippoc ampus . However , the pre sent study
d o e s not e xp l a i n the mode o f a c t i on of re serpine on the
h ippoc ampu s .
(77)
S amp l e w a s sma l l .
De f i c i en c i e s :
Thi s r eport d i d not
ment ion the numbe r of c a t s u s ed i n each me a suremen t .
Only two c a t s we r e u sed a s c ontro l s .
Data o n c a t s
r e c e iv ing re se r p i n e w e r e not inc luded i n thi s repor t .
Re su l t s were not reported i n terms o f stati stic a l
sig n i f i c ance .
E l e c troencepha log raphi c
EfJ:�-
��ych i a t r i c Imp l i c a t i on s .
Purpose :
?f L . S . _!2_� 2 5 , and Some
( We rr e ,
196 3 )
To study the r e l a t i o n ship
between EEG and
p sych i c change s .
Popu l a t i on :
Th irty- thr ee hea lthy indivieu a l s were u s ed
for one study .
S even h e a l thy nur se s ,
seven neurot i c
36
p a t i e nt s ,
and twe lve p sychoti c p at i e n t s we re u s e d for
another s tudy .
Method :
The f i r s t s tudy c on s i s t e d o f two groups o f
norma l s ub j e c t s .
The f i r s t group o f e i ght s ub j e c t s and
t he s e cond group of twe n ty - f ive s ubj e c t s had EEG s t.aken
in the c onvent i on a l manner be fore and f o l lowing the
o r a l admi n i s tr at i on o f L . S . D . - 2 5 .
In the s e c ond s tudy
t he thre e groups of EEGs were s tud ied without L . S . D . - 2 5
adm i n i s t r a t i o n .
The group s were compared w i tb in e a c h
s tudy a nd t h e n e ach study c ompared .
Re s u l ts :
I t w a s shown that the s i ze o f the EEG change
c au s ed by L . S . D . - 2 5 can be predi c te d .
A gener a l
c omp ar i s o n o f the EEG and p sychic c hange s , c a u s e d by
L . S . D . -25 ,
showe d that there is
a
c o rr e l at i on in terms
of t ime and inte n s e p sy c h i a tr i c sympt:.oms .
The mo s t
profound EEG chang e s and p sy c h i c symptoms oc curred one
and one - ha l f to four hour s a ft e r the admin i s tr a t i on o f
L . S . D . -25 .
A c omp ar i s o n o f the second group ,
h e a l thy nur s e s 1
Sf:!Ven neur o t i c p a t i e n·t s
1
s even
and twe lve
p sy c h ia tr i c p a t i e nt s , w a s d i s cu s sed with conclu s i o n s
drawn a s t o how s pe c i f i c p sychot i c s would r e spond to
drug s that a l te r ed the EEG p a t te r n .
D e f i c i enc ie s :
P opul a t i on wa s sma l l i n both s tudie s .
A
report o f s t a t i s t i c a l s ig n i f i c a nc e wa s n o t inc luded in
the r e s u lt s .
S ince the c or r e l a t i on b e tween EEGs and
p sychotic change s due to L . S . D . - 2 5 were gene r a l and
37
not spe c i f i c , i t appe ar s that any pred i c t i o n s a s to
how p s y c hotic s would r e s p ond to a spe c i f i c drug wou ld
The con c lu s io n s appeare3 t o be mor e spe culative
be r i sky .
than emp i r i ca l .
E f f e c t s o f L . S . D . - 2 5 on Me tab o l i sm
The E f f e c t s o f L . S . D . - 2 5 on Cerebral C irculation and
Over - a l l Metabo l i sm .
Purpo s e :
( Sokolo f f , e t a l . , 1 9 5 7 )
To d e te rmine the e f f e c t s o f L . S . D . - 2 5 on
c e r e b r a l c ir cu l a t i on , and oxygen and g l u c o s e me tabo l i sm
o f i nd ividua l s a c tively demo n s trating the behavi o r a l
c hange s produced by t h e drug .
Popula t i o n :
Thirteen normal s ub j e c t s and n i ne
s ch i z ophrenic p at i ent s .
Method :
A c ontr o l s tudy c on s i s ted o f b i oc hemic a l
determinat i o n s o f cerebr a l b lood f l ow , oxygena t i on ,
and g l u c o s e me tabo l i sm , and a symptom que s t ionna ire
admin i s tered be f o r e L . S . D . - 2 5 i n j e c t i on .
At the he ight
of a c t i on f o l l owing L . S . D . - 2 5 i n j e c t i o n another
d e termination wa s made of cerebral b l ood f l ow , oxygenation
and g l uc o s e metabo l i sm .
Re s u l t s :
No apparent change s wer e c au s ed by admi n i s ­
t r a t i on o f the drug i n c e rebral b lood f low , oxygenation ,
or g lu c o s e me Jcabo l i sm .
Except for mydr i a s i s ,
a
s l ight
e leVa t i on i n me an �rter i a l b l ood pre s sur e , and a sma l l
i ncre a s e in arte r i a l hereoglobin c oncentrat ion , L . S . D . - 2 5
38
produced no phy s i o lo g i c a l c h an ge s in e ither group .
D e f i c i enc ie s :
(89)
None , an exce l lent d e s c r iption o f the
s tudy .
�he D i s tr ibution and Metabo l i sm o f L . S . D . - 2 5 .
(Axe l rod ,
et al . , 1 9 57 )
Purpo s e :
To d e s c r ibe a spec i f i c method for the e st ima tion
of L . S . D . - 2 5 in b io lo g i c a l ma te r i a l s and use th i s method
to determine the d i s t r ibuti on of L . S . D . - 2 5 in
repr e s entative t i s s ue s of d i f ferent s p e c i e s .
Popu l a t io n :
One c a t , three monkey s , one guinea pig ,
and a mou s e .
Method :
Four d i f ferent method s were de s c r ibed s eparate ly ;
however , b r i e f l y , the a n ima l s were i n j ected with L . S . D . - 2 5
and s h o r t ly a f terwards were s a c r i f i c e d and t i s s ue s amp l e s
wer e taken .
T i s s u e s amp l e s were prepared f or analys i s by
homog en i z a t i on i n a War i ng b lender with five volume s o f
wate r .
Results :
A spec i f ic and s e n s i t ive method f o r the
e s t imation of L . S . D . - 2 5 in b i o l ogic a l mate r i a l wa s
d e s c r ibed in deta i l .
L . S . D . - 2 5 was f ound in the c at
i n the f o l l owing order o f d e c re a s ing c oncentra t i on s :
b i le , p l a sma ,
lung ,
l iver , k idney , b r a i n , inte s t ine s ,
s p lee n , cerebr o s p i n a l f l u id , mu s c le , and f a t .
( 5 0 per c e nt d i s aopearanc e )
�
-
Ha l f - l i fe
in the s e spec i e s was :
monkey 1 0 0 minute s , cat 1 3 0 minute s , and the mou s e seven
minute s .
L . s . n � - 2 5 was found to be a lmo s t c omp l e te ly
.3 9
metabol i z e d i n the body , sma l l amount s o f the drug
be ing exc r e ted i n the urine and s t o o l s .
Deficiencies :
S amp l e wa s very smal l .
(6)
S tudy can be
cons idered only as e xp l ora tory r e s e a r c h .
A report in
terms o f s t a t i s t i c a l s ig n i f i c an c e w a s not included in
th i s repor t .
S tud i e s on Ly s e r g i c Ac id D i ethy l amide :
Attem� !O
Attenua_te !he L . S . D . - 2 5 Re a c t i on i n Man by Pret:re atmen t
( I sb e l l , �t_ a l . , 1 9 5 9 )
Purpo se :
To de termine whe ther neurohumor a l blocking
agents wou l d attenuate or enhance the L . S . D . - 2 5 rea ction
i n man .
Popu l ation :
Adu l t m a le s ,
in e xc e l lent phy s i c a l he a lth
with no e v idence of p sycho s i s in any of the subj e c t s ;
howeve r , a l l were d i agno s ed a s having charac ter d i s orde r s
and a l l wer e previ o u s narco t i c add i c t s ,
s e rv i ng
s e ntences
for v i o l a ti ng Feder a l Narcotic Laws .
Method :
A l l d r u g s wer e given o r a l l y in cherry s yr u p to
ma s k the t a s te .
Appropr i ate identical pl acebo s were
u s e d as c ontr o l d e v i ce s i n a l l expe rime n t s .
A
cro s s- over
d e s ign , i n wh i c h each p e r s on s erved as h i s own c ontrol ,
v1a s u s ed .
The order i n wh i c h neuro humoral b J.ock ing agen·t s
a n d L . S . D . - 2 5 were admin i s te=ed wa s r andomi z ed .
The
b lock i ng exper ime n t s a lway s i nvo lved f our separate d rug
c omb ina t i o n s in the s ame group of sub j ects :
L. S . D . -25
40
p l u s b locker p l ac ebo ; L . S . D . - 2 5 p l u s b locker pl acebo ;
L . S . D . - 2 5 p l u s b l ocker ; and L . S . D . - 2 5 p l acebo p l u s
blocke r .
N e ither s ub j e c t s n o r ob s s rve r s were aware
o f the nature of the med ic a t i o n dur ing the e xperiments .
Re s u lt s :
BAS
Pretre a tme nt o f p a t i e n t s w i th phenoxybe n s ami n ,
( a s erotonin antagon i st ) , and s c op o l amine
(a
cho l in e r g i c b l ock ing agen t ) , had n o s ign i f i c ant e f fe c t
on the L . S . D . - 2 5 r e a c t i on i n the s e subj e c t s .
The d ata
do not s upport nor d i sprove hypothe s e s attr ibut ing the
L . S . D . - 2 5 p sycho s i s to b l ockage or ac c e n tuat i on o f
neurohumo r a l transm i s s ion i n centr a l nervous s y s tem .
(45)
D e f i c i en c i e s :
The number o f sub j e c t s u s ed in the s e
exper ime n t s was not inc l uded i n th i s report .
Gene r a l ­
i z at i o n o f re s u l t s obtained from s ub j e c t s s erving ·
s ente n c e s i n a F ed e r a l pri son to other p e r s o n s from
d i f f e r e n t env i ronments and background s i s r i sky .
There
were operat ing var i ab l e s other than the exp e r imenta l
f a c tor s i nc e i t i s obv i o u s to t h e ob s e rver and to the
sub j e c t s when they r e c e ive L . S . D . - 2 5 due to i t s evok ing
p s yc h i c s ymptoms such as de l u s i o n s , h a l luc ination s , and
deper s o na l i z at i on .
However , the r e s e arch de s ign emp l oyed
was highly sophi s ti c ated , and with the exception of the
de f i c i enc i e s noted about it might serve as a mode l for
further r e s earch .
41
The E f f e c t s o f L . S . D . - 2 5 on the Cho l ine s te r a s e s and
Monoamine Ox i d a s e in the Spi n a l Co:rd :
I n the Mechan i sm of Ha l luc i na t ion .
A Po s s ib l e Factor
{Nand y and Bourne ,
1964)
To inve s t i gate the s i te s o f l o c a l i z at i on o f
Purpo s e :
spec i f i c e n z yme s ;
in
c ho l ine s te r a s e , and monoamine oxida s e ,
the s p i n a l cord and spina l gang l i a in norma l rats
and i n tho s e r e c e iving L . S . D . - 2 5 .
Young adul t r a t s , number u s ed wa s not s t ated
Pop u l ation :
in the pub l i shed r eport of th i s exper iment .
Method :
Exper iment w a s c ar r i ed out i n three s er i e s o f
s ub s t ud i e s .
cardiac ,
(1)
L . S . D . - 2 5 wa s i n j e c ted
by intra -
intravenous , or i ntrape r i tonea l rout e s a t the
do s e of 0 . 1 mg/kg of body we ight and the r a t s wer e
s a cr i f i ced within o n e hour .
The s p i n a l cord and gangl i a
o f an u n i n j e c ted l itter-mate r a t were s tud i e d a s contro l s .
(2)
S e c t i o n s o f the s p i n a l c ord and gang l i a o f norm a l
r a t s we r e incubated w i t h t h e r e spect ive sub s trate , a s
we l l a s the drug in t h e d o s e o f 0 . 1 mg/ 1 0 m l . o f the
f i n a l i ncubating mixtur e , a t 3 7 ° C . , the s e ctions i ncubated in
contro l s .
a
s imi l ar s o lution wi th the drug a c ting as
(3}
S ome s e c t i o n s wer e pre-treated with the
drug in norma l s a l ine for one hour and f i na l ly incubated
in the r e s pe c t ive i ncubat in g mixtur e s , othe r s were
pre- treated with norma l s a l ine w i thout the drug , for
42
the s ame period o f t ime before i ncuba t ion .
The l at ter
a c te d a s contro l s .
Re s u l t s :
The neurons o f the s p in a l c ord s howed a s trong
r e ac t ion for s p e c i f i c c h o l ine s te r a s e and a lmo s t none for
monoamine ox i da s e .
The s p in a l gang l i a s howe d s trong
r e a c tion for both .
Rea c t i on for non- s pe c if i c cho l in e s -
ter a s e w a s l oc a l i z ed in t h e b l ood ve s s e l s only .
Inhib-
i ti o n o f s p e c i f i c c h o l ine s te r a se and monoamine ox idase
in the neur o n s o f the sp inal gang l ion and d0r s a l horn
may r e s u l t i n the entry of a g r e a t e r s tr e am o f impul s e s
to the central nervou s sy s tem , whi ch may f i na l l y reach
the cer ebr a l c or te x and produce var i o u s p sy ch o t i c
symptoms .
( 68 )
D e f i c i e nc i e s :
report .
The s amp l e s i z e wa s not i n c l uded i n thi s
Compar i ng data of r a t s w i -th human s i s que s t ion�-
ab l e owing t o s p e c i e s d i f f er e nc e s ; . s amp l i ng o f r a t s
may n o t be a r ep r e s e nta tive s amp l i n g for men .
A report
in terms of s ta t i s t i c a l s i gn i f i cance was not inc l uded
in t h i s report .
F ea tur e s o f ��e r imen t a l
Ne���
P r oduced B y L . S . D . -- 2 5
( Ivanova and M i l ' shte i n , 1 9 6 2 )
Purpo s e :
To s tudy the e f f e c t o f L . S . D . - 2 5 on s ome forms
of l e arned behav i or in d o g s and on the b iochem i c a l
ind ic e s tha t provide a c o n s i d e r ab l e ind i c ation o f the
s t a g e s of s e r o t i n , a c e ty l c ho l ine , and e p inephrine
metabo l i sm .
43
Popu l a t i on :
Method :
S i x adul t d og s .
S ub j e c t s were t r a i ned to run a ma z e qu i c k l y to
reach a f e e d i ng r eward .
B e f or e L . S . D . - 2 5 wa s g iven the
sub j e c t s had l earned to p a s s through the ma z e i n
f ive - s ix s e c o nd s .
L . S . D . - 2 5 w a s given intramu s c u l ar l y
in d o s e s rang ing f r om 0 . 1 mg/kg ·to 2 mg/kg .
F o r the
second par t of th i s study the anima l s wer e s a c r i f iced
by e le c tr o cut i o n 5 0 - 9 0 minut e s a f ter i n j e c ti on o f
L . S . D . - 2 5 a n d a quan t i t a t ive d eterminations o f s erotonin ,
monamine o x i da s e , c e r u l op l a smin ,
s e r um oxidation o f
ep inephr ine , and acetycho l ine concen trati on s wer e
performe d .
Re s u lt s :
L . S . D . - 2 5 in d o s e s o f 0 . 1 mg/kg produce d no
obs ervab l e behavior change s .
L . S . D . - 2 5 in doses of 0 . 2
mg/kg gave r i s e to d e f i n i te s ympt oms f
such a s unre s i: ' or
apathy , inadequate r e a c t i on to s t imu l i , purpo s e l e s s
bark in g , atax i a , and weakn e s s i n h ind l e g s .
L . S . D . -25
in d o s e s o f 0 . 1 mg/kg d e r anged 1Che acquired behavior
pattern i n a l l anima l s , w i th i n 15 minu t e s of the inj e c tion
two of the s ix animal s took cons iderab l y l onger
( up to
55 to 8 0 s e cond s as a g a i n s t 5 - 7 s e c ond s under norma l
cond i t i on s )
to f ind the i r way through the ma z e and the
remaining four d o g s l o s t t h i s ab i l i ty ent i r e l y .
The
serotonin content in the b lood wa s s t a t i s t i c a l l y
ln­
s ign i f i c ant .
Monamine oxid a s e a c t iv i ty wa s about the
s ame a s the c ontro l s .
C e r u l o p l a smi n \'-la s d e 'cerm i ne d
44
by the COfper c ontent o f the blood and th i s increa s ed
1 5 0 - 2 0 0 % in e ight out o f e leven sub j e c t s .
No e f fe c t wa s
noted on the r a te o f ep inephrine oxidation .
There wa s
a n i nc r e a s e o f a c e ty l cho l in e s t e r a s e in s ome are a s o f the
b r a i n , yet there wa s no c hange in the acetylchol ine
c ontent o f the b r a i n .
The mo s t regu l arly o c cur r i ng and
pronounced change in the b i ochem i c a l i nd i c e s s tud ied
was incre a s ed s e r urn cerulopla smin ac·t i v i ty , and t h i s
c onf i rm s t h e sugge s t i on made b y Ho lmberg and Srnyth i e s
that there may b e a conne c t i on betwe en thi s e n z yme and
the deve l opment of the neur o t i c s ta te s .
De f i c i e n c i e s :
(47)
The s amp le wa s very sma l l .
No report o f
s t a t i s t i c a l s ign i f i c ance w a s inc luded in th i s report .
The f ind ing s i n th i s r epor t d o not appear to support the
sugg e s t i on that there may be a c onnec t ion between · s e rum
c e r u lop l a smin and the deve lopment o f the neurot i c state .
P er s i s tence o f_ L y s e r g i c ��ic! D i e_thy l arn �d e in the P l a sma
o f Hum�� S u�t s .
P op u l a ti on :
Method :
(Agha j an i an and B ing ,
1964)
F ive normal human sub j e c t s .
The s ub j ec t s were g iven L . S . D . - 2 5 intravenou s ly
and b l ood s amp l e s were dr awn a t 5 ,
15 ,
30, 60,
and 4 8 0 minu ·te s f o l l owing the inj e ct ion .
120 ,
240
The s e s amp l e s
were hepar i n i z ed , c e n t r i fuged , and then p l a sma separated ,
f r o z e n , and later ana l y z ed f o r L . S . D . - 2 5 concen tratio n .
S ub j e c t s were given a ser i e s o f equiva lent t e s t s ,
45
c o n s i s t ing o f s imp l e add i t i on problems after each s amp le
o f b lood wa s drawn .
Re s u l t s :
F or the f i r s t thirty minute s after admi n i s -
t r a t i o n , s amp l e s drawn reve a led a sharp de c r e a s e i n
p l a sma leve l s o f L . S . D . - 2 5 b u t then fe l l gradua l ly
ther e a f te r unt i l the end o f the te s t per i od .
C on-
comita n t ly , p e r formance te s t s s howe d a rapid d e c rement
unt i l the l owe s t l eve l was r e a c he d at approxima t e l y
t h i r ty m i nute s .
L . S . D . - 2 5 w a s found to be pre sent in
human p l a sma in r e l at i v e l y l arge quant i t i e s during the
period of peak e f f e c t .
d i sappearanc e )
The h a l f - l i f e
o f L . S . D . - 2 5 i n human p l a sma wa s
c a l cu l ated to be 1 7 5 minute s .
De f i c i en c ie s :
( 5 0 per c e n t
(4)
The s amp l e wa s sma l l .
T h i s s tudy wa s not
r epor ted in terms o f s ta t i s t i c a l s igni f i c ance .
and the Re s i s tance o f Male Rats to H i s tamine Stre s s .
(We l tman and S a c k l e r ,
Purpo s e :
19 6 5 )
To s tudy body growth and f ood me tabo l i sm
c hange s produced by L . S . D . - 2 5 i n ma le r a t s , a s we l l a s
a lter a t i o n s i n the r e s i s tance o f r a t s t o h i s tamine
s tre s s conferred by pro longed admin i s tr a t ion o f L . S . D . - 2 5 .
P opu l a t i on :
Me thod :
Two hundred and ten r a t s wer e u se d .
An ima l s were d ivided r andomly into thr�e group s .
Group s A and B r a t s r e c e ived i n j e c t i on s of L� S . D . - 2 5
46
( 5 0 0 o r 7 5 0 meg/kg body we ight ) d i s s o lved i n l rn l . o f
norm a l s a l ine and G roup C r e c e ived l m l . o f norm a l s a l ine
and s e rved as the cont r o l popu l at icn .
E ight i n j e c ·t ions
wer e g iven to e a ch g roup ove r a ·twc week per iod .
Twenty­
four hour s a f t e r the f i n a l i n j e ctions o f L . S . D . - 2 5 ,
r at s
w e r e s e lected for t e s t i ng o f r e s i s t ance t o h i s t amine
str e s s .
Body we i ght and food consumpt ion were me asured
week ly dur ing the two week expe r ime n t a l per i o d .
Re s ul ·t s :
The r e was a s ign i f i c an t r eduction i n the final
body weights ,
·t o t a l body weigh·t g ai n ,
t o t a l food con­
sump·t i o n and a lo s s o f e f f i c i ency in food ut i l i z a t ion
pr oc e s s e s by the r at.s .
It
was s ·tr ong ly sug·ge s ·t ed th a t
adm i n i s t r at i o n o f L . S . D . - 2 5 inc r e a s e d to le r an c e to
h is t amine s tr e s s .
The tr e ated r at s showed an inc r e a s e d
ab i l i ty t o to ler ate h i s ·t amine s ·t re s s .
D e f ic ie n c i e s :
None .
H i s ·t amine--b i nd in_g_ Ac·t ion o f .:!;:ys e rgj.c Ac id pi.;:: ·thyl am i de .
( S iv a S ank ar ,
P urpo s e :
e ·t .
�;!._ .
,
1 96 3 )
T o inve s ·t ig a·te ·the e f fe c t o f L . S . D . - 2 5 on ·the
leve l s o f f r e e and bound h i s ·tam i ne in fre sh o r g an t i s sue s .
Popul at ion :
Method :
Adul t , male albino :r abb it s .
S ub j e c t s were g iven h i. s ·t am ine ,
and n ine·t y
m i nu·t e s J. a·t er one group r e ce ive.d s al ine wi·th L . S . D . - 2 5 ,
a nd ·the c o n t �c o l g r oup r ec e ived o n ly s al ine .
�.1 1 s ub j e c·t s
we re k i l led b y a i r embo l i sm th i r ty m i nu t e s a fter the las·t
47
intravenou s i n j e c t io n .
T i s s u e s were i so l ated and
homogen i z e d , and h i s tamine l eve l s were a s s ayed by
s pe c tr opho t o f l u o r ime tr i c t e chnique s .
Re su l t s :
The e f f e c t o f L . S . D . - 2 5 on the hi s tami ne c ontent
r e s u l te d i n a d e c r e a s e in a l l t i s sue s exc ept in the live r ,
kidney and s p l e e n .
I t i s po s s ible that the d e c r e a sed
l eve ls o f bound h i s tamine and bound s erotonin rr�ay be
r e spon s ib l e for the anaphy l a c t i c a ction of L . S . D . - 2 5 .
(85)
D e f i c i e nc i e s :
The numbe r o:E r abb i t s used in thi s
i nve s t igation was not inc luded i n thi s report , nor was
thi s s tudy reported i n terms o f s ta t i s t i c a l s ign i f i c anc e .
There wa s noth ing in th i s report to s upport the
p r e s umpt i on for anaphy l a c t i c a c t i on of L . S . D . - 2 5 .
Regio f!: a l L o c a l i z a t i o n o f L . S . D . - 2 5 i n ·the
�?_I!.E_�y )?ra il� .
( Snyder and Reivi c h , 1 9 6 6 )
Purpo s e :
To e xamine the e f f e c t s o f L . S . D . - 2 5 on spe c i f i c
are a s o f c e r ebra l funct io n i ng ; the r e l ation , and c ap a c i ty
t o s how concentra t i on in s pe c i f i c r e g i o n s o f the b r a i n .
Popul a t ion :
Method :
Pour adul t s qu i r re l monk e y s were u s e d .
L . S . D . - 2 5 i n do s e s from 0 . 5 to 2 mg/kg o f body
we i ght wer e adm i n i s te r ed by a s l ow intravenous i n j e c tion
over a ten minute per i od and the an ima l s were ki l l e d
twe nty minute s a f te r the i n j e c t i on .
A spec i f i c f luoro ­
meJc r i c method f o r the meas urernent o f unch anged L . S . D . - 2 5
wa s u s e d .
The
subce l lu l ar loca l i z a tion o f L . S . D . - 2 5 in
48
s ever a l a r e a s o f the brain was examine d .
Re s u lt s :
L . S . D . - 2 5 was unequa l ly d i s tr ibuted in the
d i f ferent a r e a s of the brain .
The h i ghe s t c oncentrations
o f the drug we r e f ound in the p i tu i tary and pineal g l and s .
The s e concentr a t i o n s wer e s even to e i ght t ime s the amount
f ound in the c e r eb r a l c or tex .
Among the deep c e r eb r a l
s tructur e s , L . S . D . � 2 5 concentration wa s found two t o f ive
t ime s greater in the v i sua l and aud i t ory are a s and hypo­
tha l amu s than in the c ortex .
The br ain stem c ont a i ned
concentrations o f L . S . D . - 2 5 s imi lar to that found in
the cortex .
I n one animal the concent r a t i on o f L . S . D . - 2 5
i n the i r i s wa s f ound to b e e ightee n t ime s a s h i gh a s that
of the cortex .
No c on c l u s i o n s we r e dr awn f r om th i s
inve s t i ga t i on a s t o the mode o f a c ti o n o f L . S . D . - 2 5 i n
produc ing its characte r i s t i c e f fe c t s .
D e f i c i e n c ie s :
(88)
Popu l a t i on wa s very sma l l .
One anima l
wa s u s ed to make one mea s ureme n t and thr e e an ima l s rece iv­
ed d i f ferent do s e s of L . S . D . - 2 5 in mak ing the s e c ond
m e a sureme n t , mak ing a tot a l popu l a t i on of one for e ach
mea s ur ement .
A r ep o r t in terms o f s t a t i s t i c a l
s igni f i c an c e w a s n o t p o s s ib le in a s tudy o f th i s natur e .
49
S tud i e s on T o l erance to L . S . D . - 2 5
Cro s s T o l e r a n c e Betwe en L . S . D . - 2 5 3.nd P s i l ocyb i n .
( I s be l l ,
Purpo s e :
et a l . ,
1961)
•ro d e t e rmine i f " c r o s s to l e r anc e " e x i s ts
between L . S . D . - 2 5 a nd P s i locybin .
Popu l at ion :
Ten volunteer adul t s , f ormer opi ate add i c t s ,
s erving s entenc e s for v i o l ation o f Fed e r a l narco t i c l aws .
Sub j e c t s we r e phy s i c a l ly he a l thy ma l e s and none showed
any evidenc e o f the ma j or p sycho s e s .
A l l had rece ived
L . S . D . - 2 5 i n previous exp e r iment s .
Me thod :
Ten s ub j e c t s wer e u sed i n two exper imen t s .
cro s s - over de s i gn u s ing e a c h patient a s h i s
w a s emp l oye d .
ovm
A
contr o l
I n both exp e r ime nts me a s uremen t s were
obta i n e d a f te r the te s t d o s e o f p s i l oc yb in and L . S . D . - 2 5
a s f i r s t c ontr o l .
Sub j e c � s r e c e ived e i ther p s i l ocyb i n
o r L . S . D . - 2 5 a s f i r s t c hr o n i c admi n i s tr a t i on ; once d a i ly
in do s e s incre a s ing to the test leve l ove r a per i od of
s ix - t·.,;e l ve days .
c ro s s to leranc e ,
I n the f i r s t te s t o f t o le rance and
sub j e c t s wer e c h a l lenged with the drug
they had not been tak ing .
T h i s wa s f o l l owed by with-
drawa l for tho s e vo luntee r s r e c e iving p l acebo s or no
drug i n order to l o s e t o l e r anc e .
Thi s w a s fo l l owed by
a s e c ond cont r o l p e r iod whe r e the te s ·t d o s e of L . S . D . -- 2 5
o r p s i locybin wa s repeated and then the se cond chron i c
admi n i s tration a n d t h e se c ond c ha l lenge .
50
Re s u l t s :
A
high degr ee o f d i r e c t ::o lerance t o L . S . D . - 2 5
deve loped i n both exper imen t s .
The deve lopme nt o f c ro s s
t o l e r an c e b e tween L . S . D . - 2 5 a nd p s i l ocybin r e i nforc e s
the ide a that the s e two drug s cause p sych i c d i s turbanc e
by a c t i ng o n s ome c o:m..rn on mechan i sm o r o n mechani sms
acting through a c ommon f in a l pathway .
De f i c i e nc i e s :
The s amp l e was sma l l .
(46}
Imp r i s oned f orme r
opiate add i c t s a r e not r epre s entat ive o f a free non- op i ate
add i ct popu l a t i on and may not be u se d as a r e p r e s entat ive
s amp l i ng .
Admin i s tr a t i o n o f L . S . D . - 2 5 a n d D eve lopment o f T o ler ance
to L . S . D . - 2 5 .
Purpo s e :
( Jo n a s and Downer ,
19 6 4 )
T o s tudy the e f f e c t s o f L . S . D . - 2 5 on l earning
and memory in the Macaca monkey and obtain further
in f o rma t io n about the deve lopment of tolerance to L . S . D . 25 .
Popul a t i on :
Me thod :
Three immature f ema le monkeys .
The s ub j e c t s we re i n j e cted with L . S . D . - 2 5 ,
1 mg/kg o f body weight , i ntra p e r i t one a l ly a t interva l s
o f f i r s t s ix d a y s , four days , three days , two days , and
f ina l ly for four c o n s e cu t ive day s .
For the th ird s ub j e c t
·the s ix days , f our d a y s interva l s were omi tted a nd
o b s e rvations were made d ir e c t l y from t he thr ee day
interva l s .
A t o t a l o f twenty- f ive i n j e c tion� were made
in the three anima l s .
51
Re s u l t s :
Mark e d behavi o r a l c hange s were ob s e rved within
one to e i g h t minute s after i n j e c t i on with L . S . D . - 2 5 .
V i s u a l percept i on d i s appe ared a f te r approximate ly ten
minute s f o l l owing i n j e c t i on and this l a s te d for
twenty- f ive minute s .
The s ub j ec t s became tame and
p a s s iv e , and s howed both s a l ivation and p up i l lary
d i l at a t i o n .
A d o s e o f 1 mg/kg o f L . S . D . - 2 5 does not
produ c e tolerance as measured by change s in gro s s
behavior , over a four-day cour s e o f d a i l y in j e c t i on s .
(SO)
De f i c i e nc i e s :
repor t .
Very sma l l samp le u s ed in th i s re search
Contro l procedur e s appear inadequate .
A
report in terms o f s ta t i s t i c a l s i gn i f i c ance wa s not
inc luded in th i s repor t .
S tud i e s on �y s e r g i c ��id a�d D i et hy l amid e :
E f ��!:�� in
F o rmer
( I sbe l l , e t a l . , 1 9 6 5 )
Purpo s e :
To d e s c r ibe the r e a c t i on induced by L . S . D . - 2 5
i n f ormer morph ine add i ct s ,
o f the a c t i on i s me a surab le ,
to show that the in t e n s i ty
and to repori.: on the r apid
deve lopment o f t o lerance to L . S . D . - 2 5 vlhe n the d rug
wa s admj. n i s tered d a i ly during a per i od ranging from three
t o e ig h ty - f ive d a y s .
Popu l a t i o n :
Twenty - four vo lunt e e r m a l e adu l t s , twe lve
wh i te and twe lve b l ack , o f wh ich a l l had been d i agno sed
a s having charac ter d i s o r d e r s or inadequate personal i t i e s ;
however , none were d i agn o s e d a s psycho t i c .
Me thod :
'T he exper iments we re conduc ted in a c lo s ed ward
devoted to c l in i c a l r e s earch .
were give� or a l ly .
A l l drugs and p l acebos
Re s u l t s were contr o l l e d by the u s e
o f p l ac ebos and a randomi z e d order o f adm i n i s tr a t i on o f
L . S . D . - 2 5 a n d p l a cebo s i n a l l exper iments .
Vi t a l s i gn s
were taken hour ly f or two hour s b e fo r e and f o r e i gh t
hour s a f ter adm i n i s tr a t i on o f e i ther p l a c ebo or L . S . D . - 2 5 .
P sych i at r i c exami nations wer e c a r ri ed out a ft e r admini s tr a t i on o f the drug and neuro l o g i c a l examinations and
t e s t s were c a r r i ed out hour ly .
S ix o f the negro mal e s
were g iven a b a t tery o f p sycho l o g i c a l te s t s be fore and
after admi�i s tr a t i on of L . S . D . - 2 5 .
Re s u l t s :
T o l e r an c e to b o th s ub j e c t ive and ob j e c t ive
measurab l e e f f e c t s o f L . S . D . - 2 5 deve l oped rapid l y in
p a t i e n t s who r e c e ived 1 . 2 8 ug to 1 . 5 5 ug/kg d a i l y .
Tolerance wa s l o s t a s r a p i d ly a s i t was ga ined .
Compar-
i s ons o f te s t p e r f orman c e s be fore and a fter L . S . D . - 2 5
admi n i s trat i on s howed th e verba l I . Q . decre a s e d 9 . 6 3
p o i nt s , the p e r f ormance I . Q .
scale I . Q .
7 . 4 3 points .
6 . 0 7 p o i n ·t s , and the fu l l
The s e d e c r e a s e s probab l y
repre s e n t a s ub s t an t i a l impa i rment o f inte l l e c tual
func t ion .
(44)
De f i c i e n c i e s :
Method o f s e l e c ting s amp l e wa s not g iven .
S amp l e wa s sma l l .
� l though i t was s tated that the s e
53
s ub j e c t s ezpe r i e n c e d the s ame r e a c t ions to L . S . D . - 2 5 as
we r e n o t e d in the othe r s tud i e s where p o s t add i c t i on was
not a f actor ,
i t c annot be as s umed that the s e add i c t s
a r e a r epr e s ent at i ve s ample o f a non- add i c t popul a t i on .
I t was no t r eported i f ·th e s e add i c ts h ad re covered from
phy s i c a l dependence upon morph ine .
I t w a s reported that
they h ad been abs t inent from op ia ·te s for a pe r i od o f thr ee
rnon·th s .
S tud i e s on S ide E f f e c t s o f L . S . D . - 2 5
A C l a s s i f i c at ion o f L . S . D . - 2 5 �l ic at i on s .
( C ohen ,
1966 )
To rev i ew and c l as s i fy compl i ca t ions r e s u l t ing
Purpo s e :
from the ing e s t ion o f L . S . D . - 2 5 .
Popula·t ion :
Mul·t i p l e c as e h i s tor i e s p r e s ented in review
o f l i ter atur e s .
Me ·thod :
The author c l a s s i f i e s ·th e s e comp l i c at io n s i n
thr e e c ateg or ie s :
( l ) P sy chot i c D i sorde r s ;
p sychot ic D i s order s ;
Re s u lt s :
(3)
(2)
Non­
Neur o l og i c Re a c t i on s .
P sychot i c D i s order s :
A c c i dent al L . S . D . - 2 5
in tox i c a t io n among ch i ldren pr oduced h a l lu c in a·tory
r e ac t i on s ,
anx i e ty .
and a d i s s oc i at i o n s t at e accompan ied by
Chr on i c i n to x i c ation v-Ias s e e n in one man who
bu i l·t h i s d a i ly d o s e up to 4 0 0 0 ug/kg du.r ing a f ive d ay
p e r iod and then r epe ated the e n t i r e rou t ine .
S ch i zo­
phr e n i c r e ac·t ions h ave been s e e n ·th at. ar e indi s t i ngu i sh able
54
from paranoid ,
phre n i a .
s c h i z oa f f e c tive or c a t atonic s ch i z o-
Acute parano i d state s are tran s ient e p i s ode s .
Nonp sycho t i c D i s order s :
Chr o n i c anx i e ty may be the mo s t
c omnlon o f th e p r o longed adver se e f f e c t s o f L . S . D . - 2 5 .
The per s on o f t e n exper i ence s v i s u a l d i stortion and body
image change s for s e v e r a l month s a f te r tak ing the drug .
Acute p a n i c s t a t e s are not unu s u a l expe r i enc e s .
Dy s s o c i a l
behav i o r can oc c ur w i th h i gh do s e s o f L . S . D . - 2 5 , s u c h a s
a comp l e te l o s s o f prev i ou s ly h e l d value s .
Ant i so c i a l
behav i o r may o c cur wher e c u l tur a l value s a r e ob l i terated
and cause the L . S . D . - 2 5 user to g e t into d i f f i cu l t i e s
w i th the l e g a l author i t i e s .
Neur o l o g i c Reac t i on s :
Convu l s ions or s e i z ur e s hav e been repor·t ed immed i a t e l y
f o l l owing the inge s t i on o f L . S . D . - 2 5 .
I t i s not po s s ible
at thi s t ime t o o f f e r an opinion on permanent brain
damage .
(29 )
D e f i c i e n c ie s :
S tu d i e s r e v i ewed were mo s t ly s ing l e c a s e
s tud i e s wh ich c o n s t i tute s a very sma l l popu l a t i o n s amp l e .
F irm c o n c l u s ion s cannot b e v a l id ly drawn f rom c l i n i c a l
i nve s t igations o f t h i s type .
N o s ta t i s t ic a l c onc lu s ion
may be formu l ated for s tudi e s o f thi s type .
The Dance r s o f L . S . D . - 2 5 .
--
----
Purpo s e :
-
( Unger l e ider and F i sher ,
19 6 6 )
To p r e s ent S ome c h a r a c te r i s t i c s o f s i�e e f f e c t s
f o l l owing inge s t i on o f L . S . D . - 2 5 .
55
S eventy p a t i e n t s who exp e r i e nced s e r i ou s
Populi::t 'l:: io::1 :
r ea c ti o n s f o l l owing the i ng e s ti o n o f L . S . D . - 2 5 .
were predomi nant l y s in g l e , wh ite , ma l e and young
They
( aver age
age 2 1 ) .
Meth o d :
C a s e h i s to r i e s o f sub j e c t s t r e a te d at the UCLA
Med i ca l Center in L o s Ange l e s , C a l i f o r n i a for
o f seven month s .
a
p e r i od
A l l p a t i en t s obtained L . S . D . - 2 5 from
i l l ic i t sour c e s and we r e not unde r med i c a l s uperv i s ion
at ·t ime of u s e .
Re s u l t s :
p sy c ho t i c ;
Twen ty- f ive o f the p a t i en t s were d i agno s e d a s
fifteen a s neurot i c ;
t h i r t e en a s having
c h a r a c t e r d i s or de r s ; and e ig· h t mul t i p l e d i ag·no s e s .
Twent:y-­
f ive o f the p a t i e n t s had u s ed mar i j uana , e ight had u s e d
amphe t amine s ,
four had u s ed h e r o in a n d barb iturat e s . .
T h i r ty-three had taken n o dru g s o ther than L . S . D . - 2 5 .
None had prev i o u s admi s s i o n s f o r p r i o r drug expe r i ence s .
S ome p a t i e n t s had more than one S:"y""n:p tom but the mo s t
c ornmon one w a s h a l l u c i n a t i o n s f o l l owed b y anx i e t.y ,
depr e s s ion and c o n fu s ion .
Deficiencies :
author wer e :
S ome d e fi c ienc i e s brought out by the
a l l sub j e c t s obta ined L . S . D . - 2 5 f r om
i l le g a l s o u r ce s ;
que s tionab l e .
(96)
there f o r e , the p u r i ty o f drug wa s
None o f the sub j e c t s took the dxug in
a med i c a l- experimenta l s e t t i n g .
There wa s no proof
the i r s ymptom s were caused by L . S . D . - 2 5 .
1here wa s
..
no
56
way o f know ing how many o f the sub j e c t s were a l r e ady
emotiona l l y d i s turbed b e f or e taking L . S . D . - 2 5 .
I s Ly s e r g i c -Ac i d D ie thy l amide a Teratoqen?
______...__
( Z e l lweger ,
et al . , 1967)
Purpo s e :
To examine the c a se h i s t ory o f a g i r l who had
t aken L . S . D . - 2 5 during her pre gnancy and a s c e r ta i n
' +=
l .L
L . S . D . - 2 5 h a d c au s ed the ma l format ion o f h e r b aby .
Popu l a t i o n :
Me thod :
One n i ne te e n year o l d g i r l .
A c a se s tudy wa s pre sented o f a nineteen year
o l d g i r l who had taken L . S . D . - 2 5 four t ime s dur ing her
pregnan c y , the f i r s t t ime on the 2 5 th day a f ter her l a s t
men s tr u a l period and three t ime s betwe en the 4 5 th and
9 8 th d a y s o f pregnancy .
Re s u l t s :
The mother gave b irth to a b aby g i r l with a
m a l f ormed r i ght l e g .
S ince there wa s no h i s tory o f
ma l f ormit i e s in e i ther f am i ly ,
i t w a s p r e s umed t h a t the
L . S . D . - 2 5 c au s e d the ma l format ion of the r i ght l e g
e spec i a l ly a s t h e mother took the s e c ond d o se o f L . S . D . - 2 5
i n the p e r i od c r i t i c a l for the produc t i on o f leg
d e formi t i e s .
(sic)
re lationshi p .
D e f i c i e n c ie s :
d r awn .
I t i s not unr e a s on ab l e to s u s pect c a u s a l
(96)
S amp l e o f one , no c onc l u s ion rnay be
A l though the f am i l y h i s tory was negative w i th
r e sp e c t to ma l formations and her e d i t a ry cond i t ions, a
s amp le o f one doe s not r u l e out chance o c currence o f
,.
57
s pontane c u s ma l f o rma t i o n s in b a b ie s .
c au t i o n in interp r e ta t i o n o f d a t a ;
Author s u s ed
however , more stud i e s
a r e needed on bab i e s b o r n t o moth e r s who have taken
L . S . D . - 2 5 to c ome to any de f i n i te c o n c lu s io n s .
� rand M a l S e i z u r e Fo l l owing _Inge s ti on o f L . S . D . - 2 5 .
( F i sher and Ung e r l e i de r ,
Pur p o s e :
1967)
To r ep o r t a c a s e of g-r and m a l s e i zure f o l lowing
the ing e s t io n o f L . S . D . - 2 5 .
P opu l a t i on :
Method :
One a du l t ma l e .
A th i r ty - two y e a r o ld c a uc a s ian male graduate
s tudent , who worked as a n i gh t wa t c hman , h ad a grand ma l
s e i z ur e about f i f ty minu t e s a f ter t ak ing L . S . D . - 2 5 f or
the f i r s t t ime .
vvhen he took the drug for t.he s i xth
t ime he had ano th e r grand ma l s e i z ur e .
no p a s t h i s tory of such occurrenc e s .
T h i s man had
Neuro l o g i c a l and
e l e ctroenceph a l o graph i c e v a l u a t i on s howed n o apparent
abnorma l i t i e s .
D i l antin w a s pr e s c r ibed f o r o�e month
and at the e nd of that t ime he s topped tak ing d i l a t i n
a s no s e i z u r e s had o c c urred .
He h a s not had L . S . D . - 2 5
a g a i n and n o s e i z ur e s have o c c u r r ed .
Re s u lt s :
I t i s r e a sonab l e to p r e sume that L . S . D . - 2 5 may
h ave r e d u c ed the s e i z ur e th r e s ho ld .
D e f i c ie nc i e s :
be dr awn .
With a s amp l e o f one ,
(33)
no c onc lu s i on s may
Other ope r a t i ng var i ab l e s rtot accounted for
such as p r e s sure s
n f school and work ing n ights may
have h ad s ome e f f e c t on the re s u l t s .
58
C hromo s orPa l Damage in Hu� Leukocyte s In�uced
( C ohen and Mar ine l lo ,
L . S . D . -25 .
Purpo s e :
e_y
1967)
To s tudy the e f f e c t o f L . S . D . - 2 5 o n human
l eukocyte s in v ivo and in v i tr o .
Popu la tion :
E i g ht h e a l thy ind ividu a l s and one s ch i z o ­
phr e n i c p a t i e n t who h a d r e c e ived L . S . D . - 2 5 on a n extens ive
tre atment b a s i s .
Method :
B lood s amp le s were t aken from e i ght hea lthy
individua l s and s ix of the s amp le s wer e u s ed as control s .
C u l t ur e s 1-fere prepared from t he two he a l thy ind ividua l s
and L . S . D . - 2 5 w a s added i n var i o u s c oncentrat i on s
ana incub a te d f o r s eventy-two hour s at 3 7 ° C .
B l ood
s amp le s we re taken from a s c h i z ophr e ri i c pat ient , who
had r e c e ived f i fteen t r e a tme nt s with L . S . D . - 2 5 , and we re
exruained f or chromo s omal d amage .
Re s u lt s :
When L . S . D . - 2 5 wa s added to c u l tur e s o f human
leukocyte s , a marked i n c r e a s e in fre quency of chromo soma l
break s took p la c e .
A r e l a t io n s h ip between d o s e and
r e spon s e wa s dependent upon e xpo sure t ime e xcept in the
c a s e of the l a r g e r d o s e s wh ich c au s ed greater d amage
i n the shorter in cuba t i on per i od s .
concent r a t i on
( 1 0 ug/rnl )
The h i g h e s t
c au s e d g r e a t e r damage i n
shor te r i ncub a t i o n t ime s � an ind i c at ion t h a t t h e l onger
expo sur e may h ave c a u s e d c e l lu lar aberra tion :
In 4 8
hour s , breakage per numbe r o f c e l l s 111a s 1 5 / 1 6 4 - i . e . ,
out o f 1 6 4 c e l l s the re were 1 5 c hromo s oma l b reakage� .
59
For 2 4 hour s 2 2/ 2 0 0 and four hour s 3 8/ 1 5 0 .
l ug/ml , br e akage wa s for 4 8 hour s 1 5 / 1 9 4 ,
4 6/ 1 2 5 , four hour s 1 8 / 2 0 0 .
U si n g
2 4 hour s
I n the s c h i z ophren i c p a t i en t ,
chromo s ome b r e ak a ge wa s 1 2 % i n c ompar i so n to the norma l
3 . 7% .
L . S . D . - 2 5 i s appar e n t l y
an
agent c apab l e o f
produ c ing chromo s oma l damage i n v i t r o .
Defic iencie s :
(22)
Very we l l d ocumented s tudy .
The author s
u se d c auti on i n pre s enti ng the ir f in d i ng s ; however
d o s e s of L . S . D . - 2 5 used i n s tudy , except for the very
sma l l d o s e s
u s e� were much larger than is given t o
p a t i en t s i n therapy .
The one c a s e o f chromo s omal d amage
i n v iv o i s too sma l l a s amp l e e x c e p t t o s erve a s a
j u s ti f i c at i o n f o r furthe r r e s e ar c h i n th i s area .
( L ienert ,
196 6 )
Purpos e :
To i nve s t igate the e f fec t o f L . S . D . - 2 5 on
r e gr e s s i o n i n int e l l e c tua l fun c t io n i n g .
Popu l a t i o n :
S ixty- f ive c o l l e g e s t ud e n t s w i th a me a n
a g e o f 2 4 . 3 year s .
Method :
S ub j e ct s wer e f i r s t te s te d und e r control
c ondi t i o n s and then und e r the e xper ime n t a l cond i t i on s
i nvo l v i n g admin i s tr at i o n o f L . S . D . - 2 5 .
The Inte l l i ge n z -
S tructur- Te s t c on s i s ting o f n i ne subte s t s ,
Gr:11c� r a l
I n f ormat i o n , Verb a l Re l a t i on s � Memory f o r Concept s ,
A.r ithm e t i c a l P.ea s o n i ng ,
Numbe r
Ser i e s ,
S p a t i a l H e l a t i on s ,
60
and Cube Ro t a t i on was u s e d .
S ince the sub j e c t s had to
have pr ior expe r i en c e w i th the te s t s , rand om s equence in
t.he exp e r iment a l c ond i t io n could n o t be r e a l i z ed .
L . S . D . - 2 5 , 1 . 2 5 ug/kg o f body we i ght , wa s g iven o r a l l y
and te s t s w e r e s tarted ab out two h ou r s a f te r or a s soon
a s L . S . D . - 2 5 intox i c a t i o n had s ub s ide d .
c edure la s t e d a b o u t two hour s .
The te s t p r o -
E a c h s tudent s e rved a s
h i s own contr o l .
Re s u l t s :
Under the L . S . D . - 2 5 cond i t i on the l eve l o f
performance d e c r e a s ed .
The f ind i n g s we re interpreted
i n terms o f men t a l age regre s s i o n ; howeve r ,
it i s
sugg e s te d that the regre s s ion e f f e c t i s n o n spe c i f i c and
i nduced e i ther b y pharma c o l o g i c a l or by phy s i o lo g i c a l
stre s s , d u e to s imi lar r e s u l t s o c c ur r i ng whe n sub j e ct s
per f ormed under inf lue n c e o f a l c oho l , o r c ond i t i on s
invo lving s leep depriva t i on .
De f i c i e n c i e s :
(59)
I t appear s from the de s i gn o f the
exper iment that a p la c e b o gr oup wa s i nd i c a ted .
the s tudent s take the s ame t e s t a s c ontro l s and under
L . S . D . - 2 5 permi tted p o s it ive tran s fe r e f fe c t s wh ich were
s uppo s e d t o c ounterb a l a n c e the d e c r e a s e of performance
under L . S . D . - 2 5 .
T h i s app e a r s to be an uncontr o l l e d
var i ab l e that m i g h t e f fe c t the r e s u l t s o f th i s s tudy .
61
S tud i e s o n Other E f f e c t s of L . S . D . - 2 5 ·
The I n t e r a c t i o n � f L . S . D . - 2 5 and S en s o ry Depr iva·t i on :
P hys i o l o g i c a l C o n s ideration s .
Purpo s e :
( Cohen and E dward s , 1 9 6 3 )
I t wa s hypothe s i z e d that s e n s ory depr ivation
wou l d inten s i fy the L . S . D . - 2 5 exper imental s ta te .
Ten h � a l thy volunteer sub j e c t s who had not
P opu l a t i o n :
r e c e ived h a l l u c i n ogen i c s previou s ly .
Method :
The se s ub j e c t s wer e s tudi e d a t week ly interva l s
unde r f our cond i t i o n s i n random s eque nce :
1 2 5 ug o r a l l y , p lu s s e n sory n orma l cy ;
L . S .D. -25,
L . S . D . - 2 5 ug ora l ly ,
p lu s s e n s ory deprivation ; ident i c a l p l acebo , p l u s s e nsory
depriva t i o n ;
i de n t i c a l p lacebo , p l u s sen s ory n orma l cy .
Phy s i o l o g i c a l · mea s ure s wer e mon i tored ;
i n c l uding heart
r ate , r e s p i r a t i o n rat � , p l e thysmograp h s , G a lvani c s k in
re s i s tance and EEGs .
Re s u l t s :
The hypo the s i s , that s e n s ory deprivation would
int en s i f y the L . S . D . - 2 5 s t a t e , wa s not supported by the
sub j e c tive reports or the phy s i o lo g i c a l d a t a .
D e f i c ie n c ie s :
(26 )
Var i ab l e s o ther t h an the experime n t a l
f ac t o r m ay have b e e n operating .
For examp l e , i t i s
d i f f ic u l t t o d i s gu i s e and c ompare L . S . D . - 2 5 with a p lacebo
due to i t s c apab i l i ty of evo k i n g such pro found p sychic
s ympt oms .
In addi t i on , the s amp l e wa s sma l l .
A report
in te rm s of s ta t i s t i c a l s ign i f ic ance wa s n o t i nc lud e d for
th i s expe r imen t .
62
Effects
�!_
D - Ly s e r g i c A c i d D ie ·thy 1 amide on OJ?_�ra_nt
Behavior in the Rat .
Purpo s e :
( Jarrard ,
1S 6 3 )
To dete rmine the d o s e and t ime - r e spon s e
r e l at i on s h ip s f o r L . S . D . - 2 5 .
A s e c ond purpo s e wa s to
c ompare the e f f e c t s of d i f ferent d o se s o f L . S . D . - 2 5 on
behav i o r mai n t a i n e d by po s i t ive r e i n forcement w i th the
e f fe c t s on behav i or maintained by negative r e i n f orcement .
Popu lati on :
Method :
Twe lve alb ino r a t s .
Sub j e c t s wer e divided into two group s o f s i x .
One group wa s t r a i ned with a s hock avoidance procedure
and the other group wa s trained to pre s s
a
bar for food .
Training wa s c onducted through a 2 1 d ay p e r i od .
L . S . D . - 2 5 wa s i n j ected i ntrap e r i tone a l ly .
Then
Each sub j ect
s erved as h i s own contr o l , three control s e s s i ons with
no i n j e c t i on s were run betwee n e a c h drug s e s s ion .
Sub-
j e c t s were in j e c t e d with s a l ine or L . S . D . - 2 5 and immed i at e l y a f t e r i n j e c t i on they we re p l aced in a Sk inner
box for the two hour s e s s ion .
Ha lf o f the sub j e c t s were
trained to pre s s a bar for f ood on a per i od i c s c hedule
and ha l f wer e tr a i ned with a S i dman- type avo idance
procedure to p re s s a bar to avo i d shock .
A
La t i n Square
d e s ign wa s emp l oy e d in wh i c h e a c h s ub j e c t served as h i s
own cbntro l .
Each s ub j e c t was i n j e c te d wi th e ither
s a l i ne s o lution o r L . S . D . - 2 5 in d o s e s ranging from 0 . 0 5
to 0 . 8 0 mg/kg .
63
Results :
There wer e s i g n i f i c ant d i f fe r e nc e s among
e f f e c t s o £ the d i f ferent drug do s age s and there were
s ig n i f i c ant c hange s over t ime .
Ob s erva t i on o f the
anima l s i nd i c ated that with 0 . 8 0 mg/kg d o s e , per formanc e
was s evere l y impai r e d .
D o s e s o f 0 . 2 0 mg/kg were f ound
to p r o duce s i gn i f i cantly f ewer r e spon s e s than 0 . 0 5 rng/kg .
(49)
De f i c ienc i e s :
The s amp le wa s sma l l .
The E f fect o f P sychotoge n s on Appro a c h a n d Avoid ance
--
----
--
Behav i o r .
Purpo s e :
-
---------
( Ray ,
-----�-�-·
19 6 3 )
To s tudy the e f fe c t s o f L . S . D . - 2 5 , me s c a l ine ,
seroton i n , amphe tamine and ipron ia z id in a behavi o r a l
procedure t h a t c oncomi tantly te s te d
a p pr o a c h
behavior ,
con t r o l led by po s i tive re inf orcement and avoidance
behavior contro l l ed by negative aver s ive - r e inforcement .
Popu l a t i on :
Method :
Rat s , numbe r not s tated .
Food d e pr ived sub j e c t s were tra ined and t e s ted
in a s o und r e s i s tant chamber cont a i n i n g two contro l
l ever s .
Aud i tory s i gna l s wer e u s ed to d i s cr iminate
reward s .
A l l drugs wer e i n j e cted intrap e r i tone a l ly .
Re s u lt s :
A l l drugs s tu d i e d had the s ame genera l e f fect
o n the c l a s s e s
of be havi o r ana l y z ed i n the se stud ie s .
The e f fe c t s s e emed to c o n s t i tute a b locking e f f e c t on
p o s i t iv e l y mo t i v a ted behavi or ,
mo t ivated behav i o r .
as we l l as negative ly
The f ind i n g s p o i n t to
a
probable
64
exp l anat i o n o f vlh y p sychotic p a t i e n t s wou ld react
favorably t o tranqu i l i z er s .
D e f i c i enc i e s :
(76)
S i z e o f s amp l e not g iven .
No c onc l u s ions
may be drawn w i thout s amp le s i z e .
No contr o l group o r
p lacebo s w e r e u se d in th i s s tudy .
No support was f ound
in th i s report to j u s t i f y the hypothe s i s that p sychotic
patients wou ld r e a c t f avorab ly to tranqui l i z er s .
E f f e c t � o f Lysergic �c i d D ie thy l amide an� Qther !?rugs
on Trop i c a l F i s h .
Purpo s e :
( Ch e s s ick , et_ a l .
,
196 3 )
T h i s s tudy wa s de s igned to i nv e s t igate :
the
e f f e c t o f L . S . D . - 2 5 on s ever a l s p e c i e s of trop i c a l f i s h ;
the e f f e c t o f temperature on the drug r e a c t i on on
trop i c a l f i sh ;
the e f f e c t of s imul taneou s tre atment of
trop i c a l f i sh w i th L . S . D . - 2 5 and r e s er p ine , L . S . D . - 2 5
and nor e p inephr ine , L . S . D . - 2 5 and serotonin , and the
e f f e c t of s od ium and pota s s ium cya.. nide on t r op i c a l fi s h .
Popu l a t i on :
Me thod :
Two hundr e d and twenty- four t rop i c a l f i sh .
Thirty spec i e s o f trop i c a l f i s h we re s creene d ,
u s ing e ight f i s h o f e a c h s p e c i e s ,
for the s e stud i e s .
The f i sh wer e p l ac e d in s o lu t i o n s c onta i n ing the drug s
be ing u se d in the s tud ie s .
Re s u lt s :
O f the thirty s p e c i e s te s te d only e l even were
found to h ave r e p eated r e a c t i o n s t o L . S . D . - 2 5 .
Behavior
chang e s c ommon t o a l l s p e c ie s were swimming at the
s ur f a c e r.ln d an i nc r e a s e in b ackward swimr..:li n g .
Serotonin
65
and r e s er9ine ne i ther b locked nor potentiated the r e ­
actions o£ L . S . D . - 2 5 .
The L . S . D . - 2 5 r e a c t ion i n the
S i ame s e F ighting F i s h c on s i s te d o f " ba r r e l ro l l s " ,
" no s e - up - ta i l -d own " vert i c a l s inking to the bottom
and r i s ing t o the top .
o f the body c o lo r .
D e f i c i e n c ie s :
They a l s o deve l oped a darkening
( 21 )
A l £ hough c ontro l s were u s e d i t i s doubtful
if a l l ope r a ti ng var i ab l e s other than the exper imental
f a c to r app l i e d to th i s s tudy .
The method o f me a sur ing
the f r e quency of v a r i o u s behavior p a t t e r n s were not
d e t a i l e d in th i s report .
Stereotyped Behav i o r and Cyc l i c Chan<I§� in Re S£�
Produced
e.Y.
Purpo s e :
L . S . D . - 2 5 in Goat s .
( Ko l l a ,
e� a l . ,
19 6 4 )
To i nve s t i gate the inf luende of L . S . D . - 2 5 in
s ingle and r ep e a t e d dose s on the wa lk ing pattern o f goats .
Popul a t io n :
S ix o r s even fema le adult g o a t s .
Numb e r
unce r t a i n .
Metho d :
Sub j e c t s we re s tud i e d in an open f i e ld te s t
with l ight we i gh t harne s s str apped around the che s t and
conne c te d by one - f o o t a l uminum rod ·to moveable j o in t s
mounted i n the c e n t e r o f the exper imental room , and the
animal ' s movemen t s we r e r e corded on t r ac ing paper .
The
contr o l p e r i o d con s i s t e d of s ix c o n s e cu t ive f ive minute
p e r i od s whi l e the an ima l s '"a l k e d a ro und the room a·t wi l l .
L . S . D . - 2 5 wa s given intravenou s ly and r ec o r d ing s were
continu e d for twe lve p e r i od s o f f ive minute s e ach .
66
F ive to ten minute s a f t e r the admi n i s trat ion of
Re s u l t s :
L . S . D . - 2 5 the ma j or i ty o f the anima l s produced tracings
o f r e c tangu lar s hape ,
c lockwi s e pattern s .
i n d i c a t ing c l ockw i s e or counte r ­
Each p attern was f ound t o be
s p e c i f ic for each anima l and d i d not change with
s ub s equent i n j e c t i on s .
The s te r e o typed walk ing patterns
s upport the v iew � f a stab i l i z ing and a r i g i d i f yi ng
a c t i o n on L . S . D . - 2 5 behav i or .
D e f i c i enc ie s :
(57)
S i z e o f s amp l e was sma l l .
It was d i f f i c u l t
to t e l l how many g o a t s were u s e d i n t h i s s tudy , the
r epor t f o l l owed s ev e r a l s pe c i f i c s tud i e s not i nc luded in
t hi s exper iment .
The one contro l p e r i o d o f f ive minute s
p r i o r t o i n j e c t i on o f L . S . D . - 2 5 d i d not appear adequate
s ince the drug p e r i o d was taped for 6 0 to 9 0 minute s .
L . S . D . -25 .
Purpo s e :
( Mc D o n a l d and H e imstr a , 1 9 6 4 )
To inve s t i gate and to d e termine the e f f e c t s o f
L . S . D . - 2 5 on s o c i a l d ominance in t h e g r e e n sun f i s h .
Populatio n :
Method :
E ighty green sunf i sh .
The subj e c t s were d iv i d e d into twenty group s .
Ten group s wer e d e s ignated a s c ontro l s and the other ten
group s as exper imental group s .
The f i sh were l e f t a l one
for s even days t o e s tab l i s h h ierarc h i e s .
At the e nd o f
th i s t ime the f i s h wer e marked f o r i d e nt i f ic a t ion .
The
f i s h were ob s e rved for three d a y s and behav ior rec orded .
67
The s o c i a l d omi nance h i er a r c hy wa s d etermined on the
b a s i s of the d a t a obtained during the o b s ervation s e s s i on s.
I n a l l group s i t wa s p o s s ib l e t o d e termine a f i sh that wa s
a ttacked by the other f i sh i n the group and d i d not
r e c i procate .
f i sh o f
a
T h i s f i s h was de s ignated as the s ubmi s s ive
group .
A submi s s ive f i sh wa s i n j ected w i th
2 . mg/kg o f L . S . D . - 2 5 and a subm i s s ive f i s h from the
c o ntro l le d group wa s i n j e ct e d with a s a l ine p l acebo and
p la c e d back in r e s p e c t ive tank s .
F i f ty m i nute s a fter the
f i s h wer e r e turne d , a ten minute ob s ervat ion was h e ld and
the f r e quency o f a tt ack behavior r e corde d .
Re s u lt s :
L . S . D . - 2 5 greatly incr e a sed the frequency o f
attack behavior sh own b y the submi s s ive f i s h .
D e f i c ie nc i e s :
(60)
A report i n t e rm s o f s ta t i s t i c a l
s ign i f i c ance wa s n o t i n c luded in thi s s tudy .
( Ka s t and C o l l in s , 1 9 6 4 )
Purpo s e :
To t e s t L . S . D . - 2 5 a s an analge s ic agent .
Popul a t i o n :
F i f ty grave l y i l l ho s p i t a l i z e d pat i e nt s .
The d i agno s e s o f the s e p a t i e nt s r anged from cancer o f
the b r e a s t w i t h met a s t a s e s , cance r o f the c e rvix wi th
meta s ta s e s , c a n c e r of the l iver , c an c e r o f the panc r e a s ,
c a n c e r o f the lung , t o He r p e s Z o s te r w i th s evere burn .
Me thod :
D i l aud id , Demero l and L . S . D . - 2 5 were adrnin-
i s tered t o the s e sub j e c t s f or control of intense p a i n .
D i laudid and Deme r o l wer e a dmi n i s tered i n
a
doub l e - b l ind
68
s tudy pattern ;
however , due t o the p sych i c and vegetat ive
a c t ion of L . S . D . - 2 5 i t wa s g iven f o l l owing the doub le­
b l i nd pattern as the th i r d drug i n the s tudy whe n pat ients
comp l a i ne d o f p a i n .
P a t i e n t s we r e ob s e rved every twenty
m i nute s for thr e e hour s fo l l owing med i c at i on and the
degree o f p a i n wa s r a t e d in four ca tegor ie s wh ich w e r e
m i ld , mode rate i s evere , a n d v e r y s evere .
vatio n s c on s i s ted o f :
The s e ob s e r -
the ob s e rve r ' s opinion o f the
inte n s i ty o f the p a i n , the p a t i ent ' s sta teme nt about the
pain he f e lt , the ob j ec t ive s i gn s o f pain d i stre s s , and
s t a t ement s f r om p a t i e n t s in ne i g-hb o r i n g b e d s and hou s e
s ta f f member s .
Re s u lt s :
The f i r s t hour there wa s no s i gn i f i c ant
d i f f e r e n c e i n the thr e e drugs .
I n the s e c ond hour
D i l aud i d was more e f f e ct ive f o r redu c i ng p a i n than
L . S . D . - 2 5 wa s s l ower i n
e i ther D i l aud i d and D emo ra l .
o n s e t o f the r a p e u t i c a c t ion t h a n e i ther o f t h e other
drug s .
( 51 )
D e f i c i e nc i e s :
The repor t i ng o f th i s exper iment d i d not
inc l ude the method of admin i s t e r i ng the s e d r u g s wh i c h
wou l d not o n l y i n f luence the t ime f a c tor , b u t a l so the
degree o f r e l i e f from p a i n .
Only two o f the drug s wer e
adm in i s tered i n a doub l e - b l ind s tudy .
L . S . D . - 2 5 , due t o
i t s pro longed a n d pro found e f fe c t , v<a s c on s i.d.:o red
u n s u itable for a doub le -b l i nd s tudy d rug .
e f f e c t s o f L . S . D . - 2 5 , p a t i en t s
as
we l l
as
Due to the s e
s ta f f memb e r s
69
were aware o f when i t wa s admin i s t0 r e d , wh i c h c o u l d have
s ubcon s c i ou s ly inf luenc e d the r a t i ng of L . S . D . - 2 5 .
No
c ontro l group o r p l a cebo u se d in thi s s tudy .
C l i n i c a l Syndrome from L . S . D . - 2 5 C ompare d with
Ep inephrine .
Purpo s e :
( Ho l l i s te r , 1 9 6 4 )
To c ompa r e the e f f e c t s o f L . S . D . - 2 5 with
Ep inephr ine becau s e o f the many c l ini c a l man i fe s tation s
o f L . S . D . - 2 5 that r e s emb l e tho s e o f symp a thetic
s tirr,u l at i on .
Popu l a t i on :
Me thod :
Thirteen human s ub j e ct s .
A l l subj e c t s were treated with ep i nephr ine or
L . S . D . - 2 5 in a r andom ly a s s i gned order of admini s tr at ion .
Ep inephr i ne 3 meg/kg and L . S . D . ·- 2 5 2 meg/kg v1er e admin­
i st e r e d subcutaneou s ly .
Two me a su r i ng d ev i c e s we re u se d ,
the C lyde Mood S c a l e and a 7 5 - i t em que s t i onnaire regarding
p sychotomim e t i c d ru g exp e r i e n c e .
Re s u l t s :
E p i nephr i ne r e s emb l e d L . S . D . - 2 5 only in reg ard
to c er t a i n symp athe t i c e f fe c t s , p l acebo e f fe c t s from t he
drug were spar s e .
L . S . D . - 2 5 produ c e d u n f avorab le re­
s pon s e s on the C lyde Mood S c a le ;
impa i rment o f thinking ,
De f i c ienc ie s :
inc r e a s e d aggre s s i on ,
s l e e p i ne s s , and d i z z i ne s s .
( 41)
. S amp l e o f th i r t e e n s u b j e c t s wa s sma l l .
T e s t s were admini s te r e d e ight hour s a f te r L . S . D . - 2 5
wa s g i ven ; however , n o t ime wa s reported f o l l owing the
admi n i s tration of e pinephrine and the time t e s t s were
70
g ive n .
B e c a u s e e p inephr ine mirnic s the c l i n i c a l syndrome
from L . S . D . - 2 5 s o poor ly ,
metab o l i c e f f e ct s ,
as we l l a s having pro found
i t i s not s u i tab l e as a c ompar i s on
agent for contr o l l e d s tud i e s o f thi s type .
Comp a r i son o f Two Drug_§_ with �omime t i c E �_f� c t s
( L . S . D . - 2 5 a n d D itran ) .
Purpo s e :
( vJi l s on and Shaga s s ,
19 6 4 )
To c omp a r e the e f fe c t s o f D i tran and L . S . D . - 2 5
o n two quan t i f ia b l e behav i o r a l t e s t s .
D i tran has been
r e p o r t e d to produce important a s pe c t s o f natura l l y
o c c ur r i ng s chi z ophre n i a .
A s econdary pur p o s e was t o
ob tain ob j e c t ive d ata concerning t h e antidotal proper t i e s
o f THA
( -tetr ahy d r o aminacr i n )
for D itran and o f sodium
s u c c i na te for L . S . D . - 2 5 .
E l ev e n p a t i ent s with psyc h i a t r i c d i agnos e s
Popu l a t i on :
a s p s yc honeuro s e s , and p e r s o na l i ty d i s o rd e r s .
Method :
The procedure w a s e xp l a ined to the patients and
they were told that s ome might bene f i t from the s e drug s ,
but that the e f f e ct was var i ab l e .
The procedur e was
c a r r i e d out with the inv e s t ig ator and one h o s p i t a l
attendant p r e s e nt i n the r o om .
L . S . D . - 2 5 wa s given
intr avenou s ly and D i tran intramu s c u l ar ly .
L. S . D . - 25 ,
F o l lowing
sod ium s u c c i nate wa s g iv e n intramu s cu la r ly
but wa s d i s con t i nued due to the d i s c omfort i t cau s e d
t h e p a t i e nt s .
D i tran .
THA was g ive n i nt r avenou s ly f o l lowing
•r he orde r o f a.dmi n i s tr a tion o f D itran and
71
L . S . D . � 2 5 w a s a l t e rnated among subj e c t s .
The te s t
battery wa s f i r s t adm i n i stered p r � or t b d r ug inj e c tion
and the second t ime thirty minute s a f ter i n j e c ti on o f
L . S . D . - 2 5 a n d D i tran .
After c omp l e tion o f t h e te s t
battery , t h e a n t i d o te w a s a dmi n i s te r e d .
Then one hour
after the a n t i d o te wa s admi n i s te r e d the te s t battery
was again r e p e a te d .
I n add i t ion t o the Bende r - ge s t a l t
a n d the Draw- a p e r s o n te s t , Jarvik ' s Que s t ionnaire wa s
u se d .
Re sul t s :
There was marked d i f ference be twe e n L . S . D . - 2 5
and D i tran .
�he latter produced marked behav i or a l
chang e s in a l l s ub j e c t s , c r ea t i n g a s tereotyped s e r i e s
c lo s e ly re s embl ing a " tox i c -- organic 1 1 re action accompanied
by a r i s e in b lood pre s sure and apraxi a .
Perf ormance on
the d r awing te s t wa s imp a i r e d by both d rugs but impair­
ment wa s g r e a te r with D i tr a n .
L . S . D . - 2 5 c a u s e d greater
chang e s i n the p e r ce p t u a l s p h e r e .
'r HA and s o d i um
s u c c inate tended t o reve r s e the c l i n i c a l and te s t chan g e s
produ c e d b y the two d r ug s .
Pre s e n t d a t a d id not s upport
the concept o f a gene r a l f ac t or govern i n g ind ividu a l
s u s c e p t i b i l ity t o p s y c hotom i me t ic agent s .
D e f i c ienc ie s :
The s ampl e w a s sma l l .
(95)
D i f f e rent route
of admi n i s ter i n g drugs � ompr i s e s a potent i a l spur ious
var i ab l e .
T e s t s wer e g iven t h i r ty minute s after drug
adm i n i s tr a t ion wh ich may in p a r t , have a c c ount e d for
the observed d i f ferenc e s a s L . S . D . - 2 5 g iven intravenou s ly
72
i s ab s orbed immed i a te l y wh i l e D itran g iven intramu s c u l a r l y tak e s 2 0 - 3 0 minute s to be ab s orbed .
Sub j e c t s
were unab le to r e spond at t ime s f o l l owing inj e c t ion o f
D i tran , mo s t o f the te s t r e s p on s e s we r e obtained during
b r i e f luc i d i nterva l s a l l owing inadequate contro l o f
var iable s .
D e lay e d Aud i tory F eedback i n 9chi_�e n i a and L . S . D . - 2 5
I nduced S tate .
Purpo s e :
(Vinar , e t a l . , 1 9 6 5 )
To t e s t the hypothe s i s that after inge s t i on o f
L . S . D . - 2 5 , d i s turbance in d e l ayed audi tory f e edback i s
greater among hea l thy s ub j e c t s than among s c h i z ophreni c s .
Popul at ion :
E leven h e a l thy women s ub j e c t s with mean age
2 7 and thirteen s c h i z ophr e n i c p a t ient s , who s e age s and
sex wer e not give n .
Me thod :
S e l e c te d text wa s u s ed with de layed aud i tory
f eedback .
Re su l t s :
No s upport o f the hypothe s i s .
D e f i c i en c i e s :
(92)
The r eport o f t h i s s tudy wa s too b r i e f
t o provide a b a s i s f o r evalua tion .
Age and sex o f
s c h i z ophr e n i c p a t i e n t s w a s n o t s t at e d .
The de s ign
and e xper ime n t a l cond i t i o n s were not s t a te d .
Purpo s e :
To te s t the e f f e c t s o f L . S . D . - 2 5 on body
sway sugge s t ib i l i ty in a group o f ho s p it a l patient s .
73
P opu l a t i on :
Thirty- s ix men and wome n , c on s i s ting o f
e l even ne�r o t i c s ,
f i fteen depre s s ed and ten s c h i z ophrenic
p a t i e n t s were u s e d for th i s s tudy .
Me thod :
Each subj e c t vla s te s t e d three t ime s in r andom
order f o r body sway s ugge s t i b i l i ty :
(1)
one and one - ha lf
hour s after an i n j e c t i on o f 7 5 ug . o f L . S . D . - 2 5 ;
( 2 ) one
and one - h a l f hour s a f te r 3n i n j e c tion of 1 cc . o f s te r i le
water ;
( 3 ) w i thout an i n j e ct i on .
A l l d rugs i n u s e at
the t ime wer e d i s c on t inued for a 4 8 hour per i od p r i or to
the s tudy and 4 8 hour s wa s a l l owed between each te s t .
Sub j e c t s we r e i n s tructed t o s tand s t i l l with eye s c l o sed
a f te r a c otton thread was attached to the c o l l a r of
each s ub j e c t .
A tape r e cording o f sugg e s t ion s wa s played
to a l l sub j e c t s and r e c orded on a kymo gr aph which was
c onne cted t o the sub j e c t s by the cotton thr e a d .
R e s u lt s :
The neurot i c group s h owed an inc re a s e in body
sway a f te r the s te r i le water i n j e c t ion and a gre ate r
i ncre a s e a f t e r L . S . D . - 2 5 .
s core s o n a l l three te s t s .
The depre s s ive group had l ow
The s c h i z ophr e n i c group
s cored h igh on e a c h t e s t w i t h l i ttle evidence o f
a
re l a t i o n s h ip b e tween swaying and t ape rec orded sugge s t ions .
(64)
D e f ic i e n c ie s :
By g iving L . S . D . - 2 5 in r andom orde r , a
per iod o f 4 8 hour s d o e s not exc lude the po s s ib i l i ty o f
c o n t i nued d r u g a c t i o n .
L . S . D . - 2 5 produc e s s u c h profound
74
p s yc h i c change s that r a te r s and sub j e c t s may iden t i fy
the p la c ebo .
Thi s s amp le was n o t a r epre sentat ive
s amp l e o f h o s p i ta l i z ed p a t i e nt s .
CHAPTER I I I
D I SC U S S I ON
The unknown , the unprove n , the m i s c oncept ion s ,
and the rumo r s concerning the phy s i o logi c a l e f fe c t s of
L . S . D . - 2 5 are overwhe lming in c ompar i s on wi th what i s
known f a c t .
A s ampl ing o f pub l i shed s tud i e s p r e s ents
c onf l i cting c on c l u s ions wh i c h appear to have engend ered
the mu l t i p l e theor i e s conc e rn ing the phy s i o log i c a l e f f e c t s
o f thi s drug .
The more
c ommon phy s i o l og i c a l
a g r e e d upon by mo s t author s we re � d i l a t a t i on
e f fe c t s
of
the
pup i l s , r i s e in b lood p r e s sur e , r i s e in b l ood su gar , and
·tachycar d i a .
Beyond t h i s i t b e c ome s d i f f i c u l t to evaluate
the s tud i e s due to
conf l i cting
a l low for much l a t i tude in
r e su l t s obta ined wh ich
i n t e r p r e ·ta t i o n .
'l' he s e
interpr e t a t i o n s vary c o n s iderably with a lmos t eve ry report
l-�.greement and D i s agreem e n t.
----�-----..-
·----
·-
Amo n g
--�---
F ind i na s
----------4---
I n one study u s ing c a t s , P f e i f fer
d e s c r ibed
vi sua l
l arge
( 7 2 : 1155 )
o s c i l l o s cop i c s p ik e s a pp e a r ing f r om the
c o r tex and d i s appe a r i ng when the opt i c ne rve
s evered .
He reached the
conclus ion
that
was
spontane o u s
a c t iv i ty in the v i s u a l s y s tem i n i t i ated hy L . S . D . - 2 5
s ta r t s in the r e t i na .
Wh i le
Kr i l ' s
twe n ty- four b l ind human sub j e c t s
h a l l uc i n a t i o n s
can
cccur
( 5 8 : 18 5 )
s tudy u s ing
f o u nd L . S . D . - 2 5 i nd u ce d
without a func t i on ing r e t i n a .
75
76
S chwa r t z
( 81 : 2 8 3 )
f ound c a t s with e nuc l e ated o rb i t s
behaved in the s ame manner a s norma l anima l s d i d a f ter
r e c e iving L . S . D . - 2 5 .
The per iphera l l y b l ind cat
demon s trated head movemen t s and pa� f l i ck e r ing in­
d i s t i ngu i shab l e f r om the behav i o r exh ib ited by the
non- enuc l e a te d c a t .
The manner i n wh i c h L . S . D . - 2 5 induce s hal luci­
n a t i o n s is impor tant , s ince the d e s ignation of this drug
a s p sychotomime t i c ,
is based on the premi se that the
central nervo u s s y s tem p a r t i cipate s i n , or generate s the
produc t i o n of h a l luc inati ons .
The s e s tud i e s s t i l l le ave
open the pos s ib i l i ty o f a central me chani sm part i c ipating
in the e f fe c t o f L . S . D . - 2 5 o n the r e t i n a .
P ayne
(71 : 85 )
f ound a sma l l d e te c t able i n c r e a s e
1n t h e Ac com..'Uoda t ive Convergence/A c c ommodation r a t i o i n
human s under the inf luence o f L . S . D . - 2 5 , a s ind i cated
by a r educed ab i l ity ·to r e ad a t the near point , whi ch
he be l i eved to be due to paral y s i s o f the focu s in g
me chani sm o f t h e c i l iary body .
The se change s ind i c a te
that the c i l iary mus c l e i s a f fe c t e d adve r s e ly reducing
the s ub j e ct ' s r e ad ing ab i l ity .
E l e c troencephalogram
( EEG ) make s po s s ible s tud i e s
o f the amount o f quant i t a t ive v a r i a t ion o f spon tane ous
·'
e le c t r i c a l e nergy of the brain in te rms of bas e l ine
s e t t i n g s and contr o l me a su r ement .
The s e potenti a l s are
77
e xc e e d i ng l y sma l l and the s e vo l tage d i f ference s are
c ompared ' Jith a s ta b l e r e f erence be fore and a f ter
L . S . D . - 2 5 admin i s tr a t i on .
Among the s tu d i e s on the
e f f e c t of L . S . D . - 2 5 on the EEG there were conf l i c t s
b e tween the E E G r e s u l t s o f s tud i e s in an ima l s and the
o b s e rvat i o n s of the e f fe c t s in man as we l l as i nter­
spec i e s conf l ic t s .
Seve r a l s tud i e s sugge s t change s due to L . S . D . - 2 5
and p sy c h i c chang e s are r e l a t e d .
( 7 2 : 115 5 )
Pfei ffer , et a l . ,
f ound the e f f e c t s in norma l s i s t o produce
EEGs quan t i ta t ive l y s imi l a r t o t ho s e of s c h i z ophr e n i c
p a t i e n t s w i thout L . S . D . - 2 5 .
The s e were d e s cr ibed a s
hyper- regul a t e d , a s though unde r the inf luence o f
unrem i tting s t imul at i on .
Werre
( 93 : 524)
found that the
s i z e of the EEG c hange c au s e d by L . S . D . - 2 5 can be
pred i cted and there is a c orre l a t i on in t ime and i nten s i ty
o f p sy c h i a tr i c s ympt orns .
The mo s t prof ound EEG change s
and p sy c h i c s ymptom s occurred one and one-ha l f hou r s to
four hour s after adm i n i s trati on of L . S . D . - 2 5 .
there wa s
no
corre lat ion exi s t ing b e tween the degree o f
E E G c hange and p sy c h i c impai rment .
(65 : 82 )
However ,
Monroe and Heath
found an ima l s s how ing c at a t on i c - l ike behavior
a l s o s howed e l e c tr op hy s j _ o l o g i c a l c hange s in the s ep t a l
r e g i on .
In
a s tudy on e ight hea l thy young adu l t s te s ted
by Rodi n and Luby ,
( 7 8 : 4 4 1 ) a d o s e o f 1 ug / k g of
78
L . S . D - 2 5 produc e d progre s s ive d e s ynchron i z ation .
Bra z i e r
( 15 : 10 6 )
revi ewed the e f f e c t s o f L . S . D . - 2 5 on
the EEG ,
" Al though there have been many repor t s o f the
e ff e c t of L . S . D . - 2 5 on the EEG of anima l s ,
s im i l a r s tudi e s in man are s p a r s e .
I n norma l
s ub j e c t s , o n l y a s l i ght incr e a s e in alpha
frequency and s ome incr e a s e in re spons ivene s s
to pho t i c s t imu lation h ave been noted .
The s e
s tu d i e s o f norma l s were on a sma l l popu l a t i on
only :
in a muc h l a r ge r number o f p sychot i c
s ub j e c t s , F orrer and Go ldner were unab le t o
f i n d any s igni f i c ant E E G change s with d o s e s a s
high a s 2 ug/p e r k i l ogram .
The s e re sult s are
contras ted t o the u s u a l l y reported ob servat ion s
o f EEG de s ynchron i z a t i on i n anima l s f o l l owing
L . S . D . - 2 5 adm i n i s tr a t i on . "
I n anima l s tu di e s , e l e c trode s were u s ua l l y p laced
d ir e c t l y in the d i f f erent brain t i s s u e s .
She atz , ( 8 3 : 5 9 2 )
u s ed monkeys and c a t s , and found that L . S . D . - 2 5 given
i n sma l l d o s e s d raws a c l e a r d i s t inc t i on between
habituating and e x t i ngu i s hing evoked aud i tory re spon s e s .
Hob s o n
(39 : 56 )
s howed L . S . D . - 2 5 in d o s e s o f 2 ug/kg
interfe red w i th s le e p gene r a l l y and reduced l ow vo l tage
f a s t s le e p s e le c t ive ly in e igh t c a t s wi th chro n ic a l ly
impl anted e l ec trode s .
Purpura
( 7 3 : 535)
activity in c a t s ,
L . S . D . -25 .
Eva r t s
demon s tr ated axon-dend r i te
ind i c a t ing a synap t i c s ite for
(32 : 481)
in h i s 1 9 5 7 review of the
neurophy s iologi c a l e f f e c t s o f L . S . D . - 2 5 c ame to the
conc l u s ion that i nte r ac t i o n
o f L . S . D . - 2 5 i n anima l s
doe s not a l l ow r e l i a b l e pre d i c t i o n s o f the interact ion
79
i n man .
Thi s prob l em o f applying f ind i n g s derive d from
anima l inve s t i ga t i o n s to man i s c �u c i a l .
Key s
(55 : 34)
c on c luded f rom h i s r ev i ew e nd e d i n 1 9 6 3 , that L . S . D . - 2 5
may be exertin� a s pe c i f i c a c t i on on und e f i ned neur o ­
p hy s i o l o q i c a l me chani sms , a n d t h e pre c i se mechani sms
under lying the c hange s are s t i l l open to c h a l lenge .
Other .neurophy s i o log i c a l s tud i e s on the e f fe c t s
o f L . S . D . - 2 5 p r e sent s u c h controve r s i a l r e s u l t s .
Ivanova
(47 : 271)
and h i s a s s o c i a te s found increa s ed
l eve l s of s e r um copper i n d o g s f o l l owing the admin-­
i s tr ation o f L . S . D . - 2 5 a nd c o n c l ud e d that th i s m ight
be a conne c t i o n b e twee n thi s e n z yme and the deve l opme nt
of neur o t i c s ta te s .
out ,
Howeve r , Gor i n
( 3 6 : 1 5 2 ) brought
i n a s tudy done on s c h i z ophrenic inma t e s o f a s tate
ho s p i t a l who had h igh s e r um copper leve l s that thi s
condi t i on wa s a s s o c i ated with l ow a s corb i c a c id leve l s
and whe n l ow v i tamin C l eve l s wer e corrected with a
proper d i e t the s erum copper leve l s re turned to norma l .
I t appears that h i gh s e r um copper l eve l s are a s soc iated
with l ow a s corb i c a c i d leve l s a n d a r e n o t a b iochemic a l
factor in s c h i z o phren i a .
Nandy
(68 : 266)
ob served i n
rats , inh ib i t i o n o f a l l s tud i ed e n z yme s a f t e r the
admini stration of L . S . D . - 2 5 ; he sugge s ted that the
inh i b i ·t ing of s p e c i f i c c h o l i n e s ·tera s e and mono amine
ox i d a s e in the neurons of the s p i n a l gang l ia and dor s a l
80
horns may r e s u l t i n the entry o f a greater s tr e am o f
impuJse s b J the c entra l nervo u s s y s ·t:. em .
a s tudy by G i arman and Freedman :
T o quote from
( 3 6 : 14 )
" The l i terature on the a c t ion o f L . S . D . - 2 5 on
chol ine s te r a s e s i s vo luminous and c ontradi ctory .
The r e a s o n f o r var i ab i l ity in re s u l t s i s probably
r e l a te d t o d i f fe r enc e s in sourc e s o f pur i ty o f
e n z yme .
Hh i l e mo s lt inv e s t iga tor s report s ome
degree of inhib i t i on , s ome have f a i l e d to f ind
any e f f e c t , and a few have ob s e rved s ome incre a s ed
a c t iv i ty i n the e n zyme by L . S . D . - 2 5 . "
Nandy
(68 : 266)
s u gg e s ted that L . S . D . - 2 5 may a c t by
i nhib i t i ng the en z yme mechan i sm whi c h c ontrol s the
p a s s age o f an exce s s o f impuls e s a c ro s s the s ynap s e and
a l s o by r a i s ing the l eve l s of ace ty l c ho l ine , adrena l in ,
and adrenochrome i n the b l ood .
I t appe a r s the se neuro-
p hy s i o l o g i c s tud i e s attempt t o c orr e l a te behavior c hange s
i nduced by L . S . D . - 2 5 w i t h the func t i on ing o f a p a r t i c u l ar
b r a i n mechan i sm when the fun c t i on s o f that p a r t i c u l ar
mechani sm are not we l l unde r s tood .
A s Unger l e i d e r and F i s h e r :
(90 : 50 )
h ave wr i tten
" Labor atory t e chnique s are not s e n s i t ive enough
to de termine the L . S . D . - 2 5 concen trati on in body
f l u i d s and t i s sue s , sc C l 4 - l ab e l e d L . S . D . - 2 5 h a s
been u s e d in an ima l s .
T h e h i ghe s t conce ntFat ion s
a r c found i n the hippocampu s , ba s a l gang l i a ,
tha lmi c nuc l e i , and c e rebral c o r te x .
Behavioral
change s o ccur a f t e r the brain concentr a t ion of
L . S . D . - 2 5 is dec i de d l y d e c re a sed .
Mo s t o f the
L . S . D . - 2 5 metabo l i -t e s are excreted in the f e c e s . "
The s tud i e s t h i s revi ewer ana l y z e d r e v e a l e d con f l i c t ing
f i nd ing s .
Examp l e s :
1\xe lrod , e -�� ·
( 6 : 4 4 4 ) deve l oped
·
a s p e c i f i c and s en s it ive procedure for me a suring as l i tt l e
81
a s 0 . 0 0 1 ug . /ml . o f L . S . D . - 2 5 .
'l'hey f ound c on s iderable
spec i e s d i f ferenc e s in rate s of biotrans formation o f
L . S . D . -25 .
U s i ng a c a t that had r e c e ived 1 mg . /k g . of
L . S . D . - 2 5 and then s acr i f i ce d n ine ty m inute s later ,
the
highe s t concentration was found in the b i l e and b lood
p l a sma with negl ig i b l e amou n t s f ound in the f e c e s .
monke y s ,
S nyde r and Rev i s h
(87 : 1094)
In
f ound L . S . D . - 2 5
unequa l ly d i s tr i bu t e d i n the d i f f e r e n t area s of the bra i n .
The h i ghe s t concentration of the drug was f ound i n the
p i tu i tary and p i n e a l bodie s .
Concentrations o f the drug
in the s e s tructu r e s were s even to e ight tim e s the amount
f ound in the c o r te x .
I n one anima l , L . S . D . - 2 5 c oncen-
tration i n the i r i s wa s e ighteen t im e s higher than in
the cortex .
Behavio r a l chang e s o c c ur r i ng a f te r the bra i n
concentration o f L . S . D . - 2 5 d e c r e a s ed wa s not i n k eep ing
with the f indings o f Agh a j anian and B i ng ,
( 4 : 6 1 4 ) who
f ound that L . S . D . - 2 5 doe s not rapid l y d i s appear from the
body b e f o r e p sy c h i c e f fe c t s a r e man i f e s ted but i n s te ad
that there i s a c l o s e r e l a t i o n s h i p between the presence
o f L . S . D . - 2 5 in the b lood p l a sma and the p sychic e f f e c t s
produc e d .
L . S . D . - 2 5 d o e s not appear t o be phy s i o l og ic a l ly
add i c t i ng but t o l erance to the dr u g appear s to deve lop
r a p i d l y in human s ub j e c t s and in s ome .::tn ima l s .
et al .
(44 : 47 8 )
I sbe l l ,
f ound r a p i d deve l opment of to l e r a n c e to
L . S . D . - 2 5 i n do s e s o f 1 . 2 8 ug/kg t o 1 . 5 5 ug/kg whe n the
82
drug wa s admin i s t e red to human sub j e c t s d a i ly f o r three
to e ighty - f ive d ay s .
P a r e nthe t i c a l ly ,
i t s hould be noted
that t o l er a n c e wa s l o s t a s r ap i d ly as it wa s g a i ned .
Jona s and D owner
(50 : 306)
u s ed monke y s and noted that
a do s e o f 1 mg . /k g . d i d not produce t o lerance ,
by c ha ng e s i n gro s s behavior , over
with d a i ly i n j e c t i o n s .
a
as measured
p e r i od of four days
_ F r eedman , _e t a l . ( 3 5 : 8 5 0 )
u se d
r a t s a n d n o t e d t h a t t o lerance d o e s not deve lop a s
mani f e s ted b y a l l behav i o r a l e f fe c t s o f L . S . D . - 2 5 .
I n a s tudy on c ro s s t o lerance be twee n L . S . D . - 2 5
and p s i locyb i n ,
I sbe l l , �t a l . ,
( 4 6 : 15 8 )
found a c ro s s
t o l er a n c e exi s te d between L . S . D . - 2 5 and p s i locyb i n which
r e i n fo r c e d the idea that the s e two drug s c a u s e p sy c h i c
d i s turba n c e s by a c t ing on s ome c ommon mec ha n i sm o r on a
me chan i sm a c t i ng through a common f i n a l pa·thway .
Comp l i c a t i o n s and s id e e f f e c t s a s s oc iated with
the u s e o f L . S . D . - 2 5 h ave been repor ted i n mag a z i ne
a r ti c l e s and the pop u l a r pre s s but very f ew o f the s e
phenomena have b e e n documented am ong the phy s i o l o g i c a l
s tud i e s concerned with L . S . D . - 2 5 .
Cohen
(22 : 418)
d emo n s tr ated chroma·t i d and i s o c hroma t i d breaks i n one
s ub j e c t who had taken L . S . D . - 2 5 over
und e rgo ing the r apy and i n
y_:_i tro
a
long period w h i l e
when L . S . D . - 2 5 wa s adde d
to c u l ture s from two human sub j e c t s .
Th i s may be
conce ived as a b r eakthrough , but Cohen h ims e l f wa rned
83
thi s wa s
a
sma l l p opul a t ion f o r s tudy , and r e s u l t s
s hould be i n te�pre te d w i th caution ,
and more s tud i e s
were needed t o conf i rm h i s i n i t i a l f i nd i ng s .
et al . ,
Z e l lwege r ,
( 9 5 : 1 0 6 6 ) d e s c r ibed the one woman who had taken
L . S . D . - 2 5 during the p e r i od c r i t i c a l for the production
of l e g d e formi t i e s i n her embryo and c ame to the
c onc l u s i o n that i t wa s not unre a s onab l e to s u s p e c t a
c au s a l
( s ic ) r e la ti o n s h i p b e tween L . S . D . - 2 5 a s the caus e
o f the d e formity .
Thi s wa s the f i r s t s tudy p u b l i shed on
11 L . S . D . - 2 5 Babi e s " and w i l l n e e d t o be c o n f i rmed by a
l ar g e r pop u l a t i on but n o doubt i t s erved a s
for fur ther r e s e ar c h on th i s chem i c a l a s
a
a
s t imul u s
teratogen ic
agen·t .
F i sher and Unger l e ider
(33 : 210)
r eported one
s ub j ect having two s e i z ur e s a f te r the inge s t i on o f
L . S . D . - 2 5 and c on c l uded that L . S . D . - 2 5 may have l owered
the s e i z ur e thr e shold .
Adey
(3: 602)
found L . S . D . - 2 5
i n sma l l d o s e s produc e d b r i e f s e i zure - l ike epi sod e s on
the EEG records bu 'c r.o t in overt ho l i s ·t i c action s ,
whi l e l arge do s e s produc ed s e i z ur e s that p er s i s te d i n
a qr:. i e t e nv i ronme n t .
T h i s s tudy brought to l i ght another
potent i a l adver s e e f f e c t of L . S . D . - 2 5 that may be
i nve s t igated with the po s s ib l e bonus of fr11 i t fu l r e s u l t s
·'
i n l aboratory s imu l a t i on o f e p i l e p t i c s e i z ur e s .
I n a s tudy by Lienert
(53 : 31)
mental age
r e gr e s s i on has been s hown on l eve l s of t e s t performan c e
84
a f te r L . S . D . - 2 5 i nge s t ion .
T h i s wa s exp l aine d on the
ba s i s of pharma c o l o g i c a l s tr e s s cau s ed by the drug .
Ma l i t z
(62 : 39)
f e e l s that L . S . D . - 2 5 may act a s a stre s s or
and evok e s a n i nd iv i dua l ' s characte r i s t i c r e spon s e to
Comp a r e thi s with Ka l l a ' s
s tr e s s .
(57 : 397)
s tudy on
goa t s under the i n f l uence o f L . S . D . - 2 5 wh ich incr e a s ed
the i r ambulatory a c t iv i ty and developed s tereo typed
wa lking patter n s ,
c on s i s ting o f s quar e s , c i r c le s , ova l s ,
and f igure e ig ht s .
E a c h pattern wa s found to be speci f i c
f o r e ac h animal a n d d i d n o t c hange w i t h subs equent
i n j e c ti o n s of L . S . D . - 2 5 .
Comp l i c a t i on s and s ide e f f e c t s
a s s o c i ated w i t h t h e u s e o f L . S . D . - 2 5 h av e b e e n reported ;
however , ·there have been no s tud i e s that l i nk L . S . D . - 2 5
with a ny permanent organi c b r a i n d amag e .
Ka s t
(51 : 291)
s tu d i ed the analge s i c e f fe c t s o f
L . S . D . - 2 5 , a n d compared L . S . D . - 2 5 w i t h D i l aud i d and
.
Demero l .
He found the f i r s t hour a f ter the drug s were
g iven there wa s no d i f fe r e nc e ; duri ng the s e cond hour
D i l aud i d wa s mor e e f fe c t ive than D eme r o l o r L . S . D . - 2 5 .
Dur i n g the third hour L . S . D . - 2 5 wa s
D i l aud i d or D emer o l .
more
e f f e c t ive than
A l though the ana lge s i c a c t i on o f
L . S . D . - 2 5 wa s p r o found , e i ght p a t i e n t s refu s ed the
s econd admi n i s tr a tion , th i r ty were i nd i f ferent and
twe lve reque s te d i t .
I t appe ar s L . S . D . - 2 5 i s not a s
s at i s fa c tory a n an� l ge s ic a s the p r e l iminary te s t
r e s u l t s might i nd i c a te .
However , when Ka s t ' s report
85
wa s r ev i ewed by H o f f e r
( 4 0 : 1 8 8 ) nothing wa s mentioned
about e ight patients i n pain r e fu s ing
a
s e c ond
admi n i s tr a t i o n of L . S . D . - 2 5 .
Adequacy o f Re s e arch 1>1 ethod o l o gy
From the stud i e s r ev i ewed i t app e a r s that
ob j e c t i v i ty i s hard to a c h i eve in s tud i e s u s ing L . S . D- 2 5 .
I t appear s that some o f tho s e a c t i v e l y inve s t igating
L . S . D . - 2 5 have them s e lve s b ecome u s e r s of L . S . D . - 2 5 .
As
s tated by C a r l L . P f e i f f er a t the New York Academy o f
S c i en c e s mee t i ng i n 1 9 5 7 " Thu s any s c ienti s t ·who can
spare e ight hour s f r om h i s b u s y l i f e and who h a s a good
f r i end a s h i s k e eper c an enj oy the f a s c i na ti ng
r eve l a t i oLs o f temporary i n s ani ty .
Your chairman has
exper i enced the e f f e c t of L . S . D . - 2 5 l n e f f e c t ive do s e s
1 6 o r more time s . "
(73 : 478)
Sc ienti s t s cannot af ford to condemn or condone
L . S . D . - 2 5 without f i r s t s ub j e c t i ng it to a s t r i c t
s c i e nt i f i c r igor a n d method o lo gy .
I t i s the r e spon s i b i l i ty o f the inve s t igator to
docume ni: the pha s e s invo lved i n te s t i ng h i s hypothe s i s ,
e s tab l i s h ing a s c i ent i f i c p rotoco l , make ob s ervat i o n s
and r ecord the s e obs erva t i on s .
pre s e nted in
an
The s e should be
organ i z e d manner w i th c la r i ty .
Mo s t
s c i e n t i f i c i nve s t igator s f o l l ow a s tandard forma t .
86
Thi s f orma t i s u s u a l l y d ivided into f ive s eparate
s e c ti o n s :
the i ntroduc t i on which should orient the
r e ad e r , conne c t the i nve s tigator to the current s i tua t i on ,
and u su a l ly s tate the hypothe s i s o r purpo s e o f the s tudy ;
the s amp l e or popul a t i o n emp loyed inc l ud i ng the number
o f sub j e c t s and me thod of s e l e c ti o n u s ed ;
a report of
data c o l l e c t io n proc edur e s whi c h s hould d e t a i l the
exper imenta l d e s i g n i n a manner a l lowing reade r s to
D a t a should be p re s ented i n order
j udge i t s v a l i d i ty .
obta ine d .
The a c tu a l d a t a s h o u l d be pre s ented upon
whi c h the conc l u s i o n s were b a s e d .
The conc l u s i on s mus ·t
be supported by the exper im e n t a l r e s u l t s o f the hypo·the s i s
unde r i nve s ti g a t i on .
I n the f i f ty s tud i e s r e v i ewed for th i s report . the
genera l l ev e l o f adequacy as t o r e s e arch d e s ign and
r e s e a r c h method o l o gy wa s poor .
I n mos t o f the s tud i e s
revie,/Jed , the s a.mp l e ;3 were f a r ·too sma l l a n d freqt::.ently
the method of s e l e c ti n g the s ampl e wa s not inc l uded in
the repor t .
I n many repor t s the method d i d not d e t a i l
c le ar l y the exper imenta l d e s ign .
Th i s mad e it very
d i f f i c u l t t o i d e n t i f y var i ab l e s that may have i n f l uenced
the outcome o f the s t.udy .
I n some s tudi e s the impn::: s s ion
g iven f r om data c o l l ec ·ted did not s uppor·t the conc l u s i on
the i nve s t i gator c ame to i n h i s report .
For an e xpe r ­
iment to b e v a l i d ,
to
the r e s u lt s .
i t should b e p o s s ib l e
reproduce
I n the o p i n i on o f t h i s r e v i ewer ,
th i s i s
87
not p o s s ib l e due to inadequate r ep�rting .
I n addi t i on ,
many o f the theor i e s deve l oped i n the s e s tud i e s have
not b e e n supported by c o l l abo r a t ive inve s t igation s .
Mo s t
s tud i e s have tot a l ly i gnor e d the p o s s ib i l i ty o f s purious
e f f e c t s o f exper imenter b i a s .
A l though the potent
e f fe c t s o f this chemic a l make human s tud i e s i nvo l v i n g
t h e u s e o f s u c h c ontr o l procedur e s as t h e " doub l e - bl ind "
exce e d i n g l y d i f f ic u l t ,
few o f the s tud i e s surveyed made
even rud imentary a ttempt s to employ contr o l s or contro l
group s .
The true c l in ic a l potenti a l o f L . S . D . - 2 5 r emai n s
m a s k e d b y a l ack o f we l l d e s i gned a n d we l l contro l l e d
research .
88
S UI'IJ.MARY
A s amp l i ng o f s tudi e s pub l i shed b e tween 1 9 5 7 and
1 9 6 7 concerned w i th the p hy s i o l og i c a l and behav i o r a l
e f f e c t s o f L . S . D . - 2 5 o n man , a n d laboratory anima l s ,
h ave been rev i ewed a nd d i s cu s s e d .
The mo s t out s tanding
f ind i ng wa s the equivo c a l nature of the results o r
i nterpreta t i o n s obtai ned .
I n ad d i t ion , whi le only
a
p or t i on o f the s tud i e s pub l i shed i n the pa s t ten year s
were r ev i ewed , gene r a l l y the s e i nve s ti g a t i o n s might
b e c l a s s i f ie d as p s eudo s c i e nt i f i c rather than s c ienti f i c .
I n many o f the s tud i e s r eviewe d ,
the number o f s ub j e c t s
u s ed f o r e a c h s tudy wa s i nadequa t e for a c c e p table
c onc l u s ion s .
I n s ome o f the s t ud i e s reviewed conc lus ions
In
r eached were b a s ed on a pop u l a t i o n of one s ub j e c t .
many instanc e s t h e inve s tigator mad e genera l i z ed im·­
p l i c a t io n s for man ba s e d on a s tudy u s i ng an ima l s a s
subj e c t s .
Obj e c t iv i ty o f the s e s tud i e s wa s que s t i onab l e
s ince some o f t h e i nve s t igator s ·thems e lve s b e c ame u s er s
of L . S . D . - 2 5 .
'rhe s omet. ime s exo t i c r e su l t s o f the s e
s tud i e s i n the over a l l p icture c annot b e v i ewed a s
be ing a c c e p t a b l e o r s a t i s f a c tory a t thi s t ime .
I 'c
appear s
that l aboratory i nve s tigators have b e e n r e t i cent i n
e s tab l i s h ing 'ch e pharrnacolo g i c a l a c ·t i o n s o f thi s drug .
B IBLI OGRAP HY
89
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