QUARTERLY REPORT -- JULY 1 - SEPTEMBER 30, 1953.

• Document Type: SPECIALCOLLECTION
• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): 00153392
• Release Decision: RIPPUB
• Original Classification: U
• Document Page Count: 24
• Document Creation Date: January 21, 2025
• Document Release Date: January 15, 1983
• Publication Date: October 1, 1953

CUART721Y krT
y 1 ScAcmber 30, t953.
Section on Addictine Druezi Le)oratory of 'Pharmaclior:
M4,11 Addiction 2cscarch Ceater,ri Hos:7;1tci
Ont.,0**711;.,
Declassified 187475,�.
4 tbyE 1977 L
"date
A.
0,1u 1'1A1
vi.smLtif.
CUARTt:RLY
,
During the last of junc aad thc first part of July? 1953,
the procvssinz of purchase vouchtrs and of personnel pevrolls
was transferred from the hospital's administrative division to
the National lnitItute of 1,3'...;ntal Health* This administrative
change has functioned very volt and only minor difficulties
have been encountered. Uncertainties with respect to th udgt
for the current fisc41 year have hpered purchasing to 301,1Z
extent. The prolli,ot beinc carried on for the Departmcni of
A-
Dgfznse was reactivated &Irins, tile month of July. The prcf
is still .concerned with the develoment of a synthetic suUstitute
for codeine.
Clinical-studies during tht gusrier were 1ar4nely conc4rnzd
with continuing s4-arch for Codeine Substitutes..? the addiction
liability of tnixtures of mor;)hine and hotline, addicticn lo
mcperidine? with the citalcal endocrinoloy of addiction, ailA
wt F h
with chronic ir�oica-tiOn 21Z the dizthylami.ic of lys.zrAc
41. klot%er phase of stLdics on the clInicat docrin-
otc.cy ot a-ddiciiln W41 cd durin *he quarter. 1.
found that fhz adrunats and the -tasts will resond to stimula.
tion t;y the 3 adrencrticotrc�,oic end ..P.Jdotroic
homones of the ar!terior Ituit4ry durir; maintained mor?nine
Declassified by
date �
4 FEB 1S.77
�
addiction., Insofar 44* can he determined by the measure&
emoloyed, re3r3onses durin,3 aJdiction are in the normal range.
This aviicests. that te retson for decreas4�1 17-keto3terold
excretion during addiction is dt.,c to block at the Pii,vitaTy
level.
The Neurohysiolopical Section has been concernd with
orelimlnary experimentu on the r.!eveloment of a test for
physical dependence liability in dogss with. meperldite addiction
in does, 6nd, with the InterrelatiOnships of morphine and
Nalline.
The .!.,y..tholecal inc..shown m4rked rcthi(;tioa
In cc:nditioned inhtbitioit in raf$ r1411-e under the Influence
of morphInc.
Four by membcr:. o7 tht unit VITC publislled in ti,e
quarter and two lectures were-presented beftee scientific
societigs. Vlotion pictures concerned with addietin wzre
e:thibitetl to 1.4"e audiances.
cji
!!-)173 72F
Vcrd StuJis
Hi 3 d r d :,;':-dimethyi-3-hydroxymorMinan
2�16
hydrochloride iNo. Zo 1.73C1 znd 'co I-73,;3). Ts
subst4nc,:5 4rei exai7,;(1cd 7;-o-t-e-tatai sul4It1tul-s5
fz..r
Sigi4r ti4;,1 1 1.15:r varytnr; 'vrt-tvzzn
Declassified by
late
4 FEB 1977'
1
�
�
2.5 to 63 mg.. were .min-isf.-:red to 17 nontolerant adOcia.
.Definite evidence of morphinc-like euphoria began to appear
=7;t�the 30-mg. level* Euphoria was distine. znd pronounced
at the 6.0.;mg* level* Euphoria vas also observed when 60 to
75 m2. were administered orally. No untoward toxic reactions.
were observed. Sixty to 75 mg. of tha [cc/0 isomer every four
hours Caused marked suppression of abstinabee when. substituted
for morphine in 2 sfron2Iy addicted patienta. NO evidence of
morphine.like eUAzoria Was secn with the dextro cont:,ound, and
no su) ression of abstinence. izas ob�rvd tivrig a- short
substitution forinonlhine, Althouch th(; number of
testc.J Is too small to draw definite
conclui
rtfo
t4-0 rgsuits
N "
htdicate thlt the tevo will ,..osscs adictic-n
which w! I exceed that of code- ln,4.
- .t2) . hy 1--41 -6-desoxymorphi ne (MK-57 )*
it has previously been shown that this druo oroduced intec:e
euphoria in former morphine addicts and ws very effectiv in
sup:)ra'ssing abstinence from m,,rnhinc.
,oe hu,-pari
c17 iht dr:vz has- now been studied in v-zafer detail* la 10
.)aticnt'S It induced mark.v.i r;u:;111,7:ry r4r!;-ad
rcryciz2reasla,
ze S � Vital. 0' rved
13 minutes after adinistrtion of the drug 4nd was assaci4rgd
.Deciassified by �187475�
:date
OE1977
�
with the develomant of intelise_ta)horta. Cne. tms
directiy readdicted to MK-S7 for a-period of 17 days. .Tha dose
vas incresed from C mg. every three hours to mg. every ihree
hours. Even after this very short .period of addiction, definite
abstinence appeared on abrupt withdrawal. Abstinence was evident
In four hours, severe by eisht, and had subsided aftcr forty-
eisht hours.* The results confirm our impr sston that this drug
has-hloh addiction liability.
13J d1.1-methy1.4.pheny1-4-carbethoxy azacyclo-
hentane 58351. Cniy preliminary work It h this comound, . .
which I: 11 the me-,)Irldip,:- s,:rte.s, has be(In acim:Aeted,
doses varying between 21. to 120 micrograms have been administard
to 22 nontolcrant forc; i addicts., E4Hence of morJh!nc-like
esvAloria ws observsd in only 2 of these :atients N., unto:lard
toxic reactions have been encountered and. the dose Is 001
beinc eld.vated.
(4J 4.4-di2hanyl.f.C7-dimethylnino.hexonone..3
a ot thr. mcth,z(!on,!
Is belno exartined at th,- rec,uett of f!-..1.! Dr vr Ac:dietic,n
;t :.anuy.3,7.ttirer
indicated that is c::-.1..dination of this drug pl.;s Zu?rifi-.1 c:rxy
ehedrine) d,:cs
preliminary data arc available. c1-2
isterf,:d to 7 nif,IrphInc addicts. Lvidence of
Declassified by 1.87475�,
..date�
4 FEB 1977
mlld
7s)
morohing.tike CUT ria was vident- at the 3C�mc.leval.� Further'
studies are in -.3rzNgress.
44; Addiction Liabilities of morohine�Naltinc
1.11xtures. Two of the oailents who were addicted to th4 t�to-5
mixture of morhine.Nalline have-been recddicted to morphine
and to Nailing in separate experfmnts� usinc the same dosages
of both.druga that were prescnt in the mixture. Following
withdraual of morphine, Abstinence wai far more intense then
frAlowin withdrsawal of tle mixture. Following withdrawal of
Nailing, no clear.cut evidence of abstinence was- observed.
Ca gaeperidine (Demeroll Addiction.
This stUdy i bein9 undIrtakon as a ctcperetive
project with the clinical staff of fllespital. The stu-iy
w25 iftlitatZd because the ercsidert and ?rf:SleCtlfm+41:.Cf of
the American tdic I Association aporoached the SurGeon
Cencral and cx1ressed.conctrn about the increazinc incidenc2
to me)eridine In ,:rivate ;-,ractiee. Followin9 recel;It of
4.
r&
� � �� zj � I. It All � 4.1. .41,4
that a .)roject concerning me..,..arldine tidfletion be inith:tied
c5irrtJ cut i7--c:7;ial:iy. ireiu, on 1-%--4
part of the hospital, a survey of Fe rccords of all patients
civinc histories o'F' meperidine addiction. 'Olt InT'omatin
gathered from the records will inclu.2c date cn isx,
�
Declassified by
'date
1,87475--
4 FEB 1977 ,
a
occup,Atin, ge2raphica1 lecationt stated reason for addloWn,
other druri u!edi etc. in addition-to surveying. the .rcoords.v.
tNe: psychiatric staf1 of the hospital will under takc intensive
case studies of a number of me-)cridine addicts, The
Addiction Research Centvrls part of
the -)rooram is to establish
the 3resence of physical delendcnce In "orimary" addicts and
to stuly oe3cridind �Jddiction in dogs. The method for 1)roving
that abstinence occurs in 'primary" meperldine addicts utilizes
the standard technic of Himelsbach. Patients with histories
of addiction tc, meperidine but of .addiction to r.4z, otr drug
are selected for study. These patients are sfsbilized on
me7Jcridine fzr perioJ of 7 to 10 days than the neisiTit.line
Is abr,Iptly withdrawn,,and oLservations for slizns of absi-incnce
arc carried cwt. At t-hehc lh of.absitinence fr3m mzperiJin,
doses of mcperijine. arc to be alinistercd and the relief of
withdrawal "sym;Itons observed. there posible, attom-pfzd
!.,reci...dtailon of abstinence from me2aridine with Nalline will
rvy04.11,-.4
se -.,, & 4 ���- 4t � nt
-r
0 0%�..V
addiction to meperidine only Is necessary for inclu:ic,n in
thr.: szr125.1 and will .be obtained by intqrviewine.--Or
ft
;Ind
patients have been sturlied. All showed vIry definite abstinence
elA liFldrays1 of eperidin,I. 'Toxic 71-Inif4s1-411ns.
�
�
Declassified by 187475
date
-� 4 FEB 1977
retelOno ler4le a unts-of aleperldine��.viere dpparent In-all
6. cases. .0nu pant wt1=. W4S rCCOVinG .100 ms., of intocridino
.every three'hours had a convulsion. ?ractIcally all patients
exhibited involuntary jerkins 4nd twitchins of muscle grou;1..
Abstinence could not be preci3Itated with Nalline In any of
these ;34tients:
Studies on meperidinc addiction are described in the
NeuroAlysiolosical Sedtion.
d. chronic Intoxication with the Dlothylamide
of Lysergic AcidALSD-2510
druf7 Is 4 semi.synihetic membt'r of
erLot series which ..:ITIu'acsIcpIye:Ic.,5if, in Ozz.ses of
onIV 20 to (.-0 miCros;r1s. Th;.. effects of siacie doses of Ole
drvv tolve t7ecn exter..stvely s tJJd bnt.h in� the State
and Europe, usloc both. psychotic 4nd nonpsychotic.ptients.
Many psychiatrists have ck..scril�d ttle mental effects produced
th.e du ri as reseblins those seen- in schicapilrenia and
"eX
for �ri01 1.1-I.e5rnd-tic4A 02tycht,sis
erirnental schlzo.:Arenia.' No human ux;:erimenialion on
int-:)xicatton wiih
crrz uf. t was, therefor� ielt thai'
enic irt.-;ntcation wIth thc cound vas extreyiely
Declassified by �.�.-187475
date FEB 1977
bz,;71
Six pattenii all negro male former ad lett, rizi
for the eerLen.1-. in July, control observations were
obia!ned. Thesc.t. inciuded hyicI psycholocical, psychiatric
cr,ainations� clinical observatiOns three ti;ras daily., electro�
cardiograms, electrocncephalocras, blood chemistry, and liver
funcfion tests. Following fhe Control period, an attempt was
made VD deter7line the threshold dose (dose which would jusf.
Induce mild subjective eff ots) for each patient. En
preliminary experIment, the drug was-gtven daily. Initialiy�
doses of 20 to 40 micrcorams were administered and the dose
as incrcasrA c401 day. Very few effects were observed until
the dose hild been increased tolf,0 micrc,crams. At this point,
mild subjtotIve -.ffect's'were oerved which, however, wen.: nof
prv4ent vi)a1 de tralvin on subseziunt days.
Ad.-ninistration,,of 100 to 120 micrograms to ?silents .whohod
not' been
effgets lt iu,,1%erefore� felt thaf :atiants it have
recalving the drug daily induced powerful subjective
� t..��� io
o. . ow 0 0...0 �
., It" a sIs.s 7
� � t
�--J 43 II I y
,2dministrztion of LZT)-23- was Clerefore Cisentinued 1/1111,!3ut
,and, after si:4
viry striking reactions wzre observed. For this
reason it .4145: necessary to obta.la c;ata on the effect of sin!7ic
11^,olated dc!ses which were scci at least three days aperf.
Declassified by 18745____
date 4 FEB 1977
S
-thele conditions 4 very cOnIrStent pattern oC drug effect
emersgd. Tdegrrre and duration of the reactions were rcl:Ited
the t:kse. The-elnr:unt of drug necessary to eilii the effeci
vari 4 widely in different patients, the rance extending from
90 to 300 micrograms..
The objective effects of LS).-25 include" elevation of
systolic e3nd diast,Aie blood pr sure, dil4tation of pupils
(measured in controil(!d- light), increased tendon reflexes, and
decreased 4bdom1nal skin reflexes. Coo:seficsh, fine intentioq
trerr.r of the finrs� ankle clnnus, and tremor of large
muscle Groups were lets consistently observed.
The ment,...1 74ffects of LSD-25 were very striking end varied
from oerson to person, o obvious correlation with ,Iersonalify
w21 :The ment*1 eft...cots consistcntly included
anxiciyt a faeliv4 of-unrealityllnd various haotic sensations
(formicatiOn, feclinr:s of electric shocks on the skin, tinoling
sensations, choking). T stc and smell appeared to be unaff-zoted;
noises were re:1,,orted to be loud 443nd difficult In distinuish;
chances in The par;nt s tody a;14 in the body of
other perons vere fre;uently re2crted; the patientls hands
and fc t e;.-1z.:ared to j dzerase in s L.
_4.14rkcd elenf7e
vistrat peree3t1on were reorted. These includedliurrinn
of vision, abnormal coloratin of f o:ijects U!anc!s turnirv;
=:Jur1t1 /2rcen, efoi� daubs of :::aint on the wail, flickerin
Declassified by 187475
date 4 FEB 1977
shadows-, dlncing ofs of lightt and a?i_ning circles of color.
Frequcmtlyt inanimate objects wer distorted ind changed in
Ccessionallyt patients reported se; ng visions consist.
1n,-; of rapidly chaning fantastic scenes which resembled rctl.
Disney Wovics." ?aticnts had difficulty in describing these
sensations ,echie under the' it.J1ence. of 1.517P-25 (b1 ckIn) and
were much more likely to give Good descriptions the day
6-flowin9 the experiment. They complained of difficulty-in
conecntration and. of a 7rush of thouchts." ?atients were usually
soathetic and somewhat withdrawn dutinn the height of the 7sy.
chosls.
Insichiss-always raintained.
The effects usualli began-30 mInutts to one hour after
aeministr tica of the drug and 7.,,cak off,ect veJs usually rcbed
In one -and one-half fq three ho;Jrs; thereafter, effects f:J-adually
subsided and_rtre corolotely dissittled afi.cr cisht to sixteen
hours. Cteas-1,5nally 2afil.nts reprted '%,:novarsw tasting for
one te, several t-lys.
Illectzoericolldic rams ware n.7.t 'fraatly chano by
.bui sycr z'fio o t1�; eiccii-o-.!.neephlin by rilythrnic
phntic,stir.luiatinn sti,nulafir)n aitto
appearid to enhance perccotion of colors, petf rns.,
f...11n% A):�;:lnrr o T23.
Declassified by 187475
date 4 FEB 1977
5
Wit cannot a
Wei the LSD.)sychosis sembles schizo.
phrenta.� Certain isolated sym:Joms that are observed In
schizoohrenla, such as de:le- scnalization� dcreallzation and
hallucinations ere observed under LZD. However, insiGht. is
always maintained and affect Is usually -ap-)ropriate. The tote! 7
picture of LSD�Intoxication constitutes a distinct and recniz.
ic clinical entity, which we feel could be confused only
with intoxication with mescaline. In fact, LSDoxication
resembles intoxication with cocaine more than schizophrenia.
The experiment on chronic Intoxication has been completed
In 3 patients. patient withdrew afts:r six days chrt,nic
intoxication end the experimentis still in prooress to the
2 renaIninn patients. Xraiid decline in the effect when ont
ds-r.eof 123wa: sive!: da ly otserved In all 3 ;:atients
who com:Aeted t,he ex,)eriment. Initial doses were 1.5 to 2 'cg./k.
ICO to 130 microcrams total dose} adfclinisterzd once daily. The
first dose .i(tducc.c1 tha:ulval cil-n:;ts. In mzntatIon,
t�reA,
w + -a � s,41, f
%-� � � �
Z
i4cRAc411.
tolerance. to this ts evident by th,7 szcoild� nf
tr ,nenrj afr
traticin: At this point the dose was Inc eascd, and after
.7 to 10 days,. tolerance cocared t7:0 be ceplete to 3 mcg../1:0.
itta! dose of about IF;;0 microcramal.iL hieffzct
rieclassifipi!Ftg 197-187475
date
ncluded !1St oaly 4 decrine'in'the To4ntJi effecY: but also
decreases In the effects on blood prcYssurc, uUry Fr
aad deca tendon rcflees, Lo bltincece occurred on zlihr.:rawal
of LSD-25 after 1 inistration. Develo:Iment of toler�
ance to LZD.25 occurs more ra.)idly and ao.lears to be more
comAete than with any drug we have ever studied. The ralidity
of the rsturn of the affects remains to be determined.
2. Siochamictl Studies
a. Clinical Endocrinolocy of Addiction.
The phase of ti : particJ,er project Aescribtd
In the Izist quarterly report was completed durino this quarter.
72:
senerltl, fly! 17-ketoatcrol,4s i tzwhg -t,our
infusions of international wits of ACTH during maintained
addiction ics. in terMs of thsn prior
HoWever thk inorcase in terms of-ipercentacie of tha usual daily
. /
excretion was crater durino maintained addiction. in adeltion,
17-ketostcroids tz)cr=vised after infusion: of only 5 and 2.3
International units of the prcparation of A.'�.:TH used in th,eze
exp.erimens. "1th the exce3litlo of or test va e,r.e
increlse of 17-ketesteroi eAcrelion .1-fter ACTH fall .githin
ran::e. increase in elLcretiort af uric acid aii:iLr
�
infusion of ALT�a
NcHon ior
ared to be as .Great durinc maintsin.ed
to addict-. The decline in cfc!sinh11
Declassified by �L.18.7475----
date
4. fl::
7/_
�
count during timed Ai:.:TH infustonr Wai seMe.whal-slower during
maintained addiction, but always felt to zero for nearly &ol'
in crght hours.
Increas'e In excretion of 17�ketosterolds after the injection -
of 1000 international units of chorionic eonadotropin for five
consecutive days was at great in terms of milligrams and in
terms of percentage chance fro-, Ile usual excretion during
addiction as during the control period.
---.... The data definitely show that the testes and the adrenal
glands are capable of responding to the specific pituitary
hormones during addiction to morphine. Nevertheless,. excretion
of 17�ketostero&ls Is markedly reduced during addiction and
enhanced during withdraial. Dr. Dorfmann, of the Vorccater
toundation for Ex-)eripenal Bloiccy, kindly analyzed a few
sales of urine for -us on -.1atic-ots who were addicted to morAine,
and during actile withdrawal of morphine. The excretion of
corticoids is much lower during mlintained addiction. The most
reasonable hypothesis explaining the fact: known to date is
�ulook ine pitultary level during morphine addiction.
Future work will inciudo detennination of total adrenal�
corflcoid excretion (provided a suitable method can bo davalodi;
a fractionation of urinal./ corticoids by Dr. Dorfmann; and
chorionic gonadotrootn deterninations Ito be done by the
National Cancer institute, provided certain technical difficulti:ss
Declassified by 1.=.75
47Es
date
. .
at- Lexington cc:$.1 ,.'ve-rcome. al4o ho., to evaluate
thyroid status during msintaind addiziion, using scrum.
prof la bound iodine and aklas as th,7- lndiers.
�b. Serum Electro2horetic Pattgrils.
These studies have been extended and more .:.atterns
have been collected on former addicts and on nonaddicfs. Al!
determinations arc being done in�barbItal buffer, rather than .
ohos;3hate buffer, as heretofore. The diffrcnce in the raflo.
of beta blobulin ;to omma globulin previously report. (ratio
2reatcr-th4n 1 in addicis; le$s than n.?;.i.d.total has been
confirmed and is=statistically si.i7;nificant a p.icvel of
1Z-13 than 0.01. ThcTe Ls; tIcweicri dft CiNfCripi fortIr
addicts silt-Alinc; t'n'srm4tpatferns ,ar.d
'add"..pattern:s. The nificce ch5nzs
-_n serup.1�
protein patter9. CCM4thS obscure.
Me.
to di;rce. of antaG,,Jnistic cff4ct3. decce ent;
of 4.--ofAlintz by. Nallinc 1.1 .b:on sedic7J in 1-i'1,7.� 1
C.03 to 15ci42,/kc.
1-!St
2.7131SM
Althnv more ex..)eriments need to ii dc .t
Declassified by 187475
date ------4�FEEMS77--
J17
�
at the various dosz Iv.$s, tht expertmnts zo.far- :ndic,3te
that a larel Ooze of N3Iline 4ntaso.n1zes the depressant effects
of morpizine thf=rct than does a M411 dose. Conversely, a larce
dose of morphine anhaGonizes the effects of a fixed d sa, of
Nailing more than does a sall dose.
b. Addiction of Chronic Spinal-. Doss to morphine-
Nalline Mixtures.
Two chronic spinal do,-.1
wtre given
of, morphine and. I.2d mc./ks. of Nalline (mixture of 3-to-i).
After three weeks' addiction to this mixture, there was no
evidence of ttlierance to tht de7;ressant effects of thl mixturc
on the Tiemor rolleg. This Is a. striking observation since,
����
wIt h morhiniv. alone, m4kLed toicrznce would havc
ey.ectcd.
In all do.',;s hy.:..,::Trofl�:;xt4 and :..-.:,ontaneu: runninc movemtnts
ba to bc�if6In the Slh-arid 1S;t5 eav54 Jiy
after e4ch dose of the mixture. Above the level of section,
mydriasis, trcm1r# chino.rro-a, sailv-ttion, etc, appeared
sooner than ditl -hy?erreflexia r running movenznts in the'
t�
- tht
a.
4.*,,evOW
obszrved in 'min. They tni-!tcato, that chrille: use of morph
t7,11
unplazs%:nt ci:fccts ipz.ccipitation of mild tabs:it-If:once by
each Injection of the mixture).
,--
Declassified by 187475Iate
�
� �
4
. �
C. Dttermini.ng, Addiction Liability In
Nalitne. We arz studyino� th .7:ossibility of developing a
short ';es, for addiction !;;hysicat deendeneel liability in
dogs, Using Nalline. ;7.4: have carried out ...)rellminary exeri�
ments using, two methods. The first method involve; the injectio4
of large amounts of the drug under study once daily for three
jo five days cfter which 15 mq./ig. of NaIllne are administered.
After Injection of mg.Ag. of morphine for three to five
daYs� Nalline caused definite chaes In the behavior of doos.
After administration of NQI1Ine the dogs- b4: 4rae r2StieS3,
sometimes-vomite, developed tremors, and consistentl' would
dig a.1.11t at the fcundation orthe building 5ad tic la U.
These chans were,' not Observed after either morphine or.
Natline .,eparately. :Erratic resiill.s soon dfiter injcction
of siaete dose, of methadone for three to five days. In the
other method, druns were Elven ,teveral times daily. -11en:
mg4 of morphine was adPlinistercd four time: daily,
Nalline prcetted digrlinfl- end ott-,er chans aftcr ihr,T3
tcyzn d.1,14.; of 6dd;otion. 1;11-7ensity of the c:lanv.s h bacn
steadii-v icreasr s mohinc�adietloa "�3,heri
2-.to 5 of �e,,,aecnz were zd�inistercc! -Nur tt�,,s
Natlise 7.,rcel;:itated the di ginc and other clIznes aft-r tr
to se7en days r.Jf.addictrnoG Such eh;;Ifl,cz$ hlvt not bc,'n
in
of
clos that are hz;n0 ex-,eri:ricatally addicted
meperldinc -71,!zry thrce hours fcr 30 ,:ays.
Declassified by 187475--
date
- � 4 F.E8 7977 .
d. Addiction to Lep,:ridinl in Chronic E21nal
In 2 nantoleiiint sp1nidor7s sthsle doses of 10 mo.,/kg. of
meperkline produced etfczts on the hindlimb reflexes which
similar to those produced by 0.75 mg./kc.i. of morphine. After
a wcck on 10
of ine;-cridine cvzry six hours, tolerance to
the depressant affects was evident. At this time 15 mc./kg.
of Nalline d/..1 noi,-preci721tate r nning movements. .C1 the
contrary, the flexor reflex was de3ressed c-nd the dog appeared
fii-be sedated after Nalline. When the number of doses of
mlperidine increased from four fri eight daily, peculiar chanscs
were observed la. the paralyzed.41ndl4mba-. Th-.1.sa etdgWTS." In.
coded r;ark,zd hyperactirty of-t!,a ipsilatera1,. fl.expr and
crossed extensor refleX'cs, trresular spontaneous tretnore and
h.,,ficht5 ard r5 iv gm'c,:norrf1xez iliclicd by t-a7pirz.
any bony�proofe. oroiubcrace bcif.1-4 Ihe level of cord section.
After slxteen days of addictions, .atzru.lf withdrawal was carried
out fr 24 hours. The, chs�cseevcd ,-,1-cr4istod with incrcazf.?d
nsity for to hfur
tht Jo-:. were
*
t!Ift m:omcn_t. v.,p1 klrz
.unsure wh-tfhtr thc',�eel; :11p in' th.l: dccsaTiictezi- to
ma.,tridine rrsent toxic gr!ffts sv-7
on thFluman
Efc.cci at Tztylc!z Atle
In 6 zvayjtsr sinic
of iSi-25 varying fr.: C;7). to .1.!;0 =14-'3 orcl4ctd
Declassified by 4-.F.F.,,187475--
4ate c 10' t977
�
change in: the Et�' Synchroniratton-of tho. electronce?hato�
grarn by phone stimulation apears to be enhanced afttr 1-25
but the statjatical significance of. the chances observed
remains to be evaluated. However, phone stimulation definitely
enhanced nercetion of 'optical pseudo�hallucinations.
2. Ex.lerimental ?sychoin
a.� Effects of uor:Aine on Condltiuned Inhtbition
In Rars. ("pain .anxiete). The put%lose of thls enp4riment was
to attempt to develop an analgesic testing method in rats,
based on the sere Princlp11.-as that c!e::;onstWit-d. lq Meta
reduction of ancipatory anxiety associeted with pain.
method used W3s as foll..6ws: Alt rats were fed 70 par
thm arlount of fo:Id ruired to:mainf,ain thrAr dy wel!=.t!t.
Rat& were then placed in a modified Skinner box and traincA.
to press a bar/which released small pellets of food. tvlotiva�
titn under these conditions -.oils, of course, huner. After the
rats had been trained and had attained. a constant rate of bar
lrz,rzt: were eonditif)n:id 4y s(-,uat.;infj bu7-Per
torminatd by an electric After conditioning occvrce...1,
fht ra.J.4., of bar :.:ress/n--; icsz. dvrIn
1-1.� 64 4 . �
t!v!. ccrrc
rlz rz.it
TO'
-- the
"t..1
4:Aa
,
to .::,ress the bar and food pellets at his noral rate.
race stablz mor7:hiT.z
�
Declassified by 187475_�..--
:date 4
�
given every 7 to 10 hours , t tollowing order4-3, 10, 6�
11-� 4, 14 12 and 11
U' v.as-found that the aenln.
Istration of morphine..mi)rk.cdly affected tire degree of :nhibition
of bar pressing. .As the dose of morphine was Increased thz.
rate of bar pressing durinG the sounding of the buzzer fend
to approach the control rate. An almost linear dose.effect
wit. obtained belween 5 and 10 mg.kt3, of morohine The data
obtained are consistent with the hy-,)othesis prevlousty developed'
In human studie� morphine relieves b7 rcducing
enx1,1ty caused by oainful stluft. Tollowing
ment In our (1:.)pa;refus� we intend to study ihcrTsefs-of other
drugb, such pZr.Ifot.:3rkqt41 at.;;;:rift5 qic�3 tInt4
to study the effeCts n.fi-mrphint .on v:ttIncf:cn.
b. Effects of 1-.)Ichy.16,, Idc:of .Lysi�.01c Acid on
Psychcicnice1 !7:1,1 subjects have been tested before
and after the administration of LSD-2S. Test; used have bz n
the Ror3chaeh, Wes,,.hicr Ofllevue2 the
.*--iangs6ta Jt 3.r.s.-11!fy
recx,rcis h4/va not tren.;
ara bzin,
scic
nc4. t 3t3 of
end attention Is c-.,,r.sisitrdly ftL Tht
Lchc-zr,z.r tcsi'
11 mast.,:rbi;1 z2L trct
s.T.c7.1
Declassified by 2---187475�....
date
-14
fsh,exce-A for an incrca In the total nunbef of fC5-111ZZS,
and an increase in indicatort of anxiety in the tests,
elevation of all clinical scales was-observed, the izrea.test
Increases being In the."schixo-)hrenla" and "paranoia" scales.
C. 6.10illYSICAL STUDIES
Considerable timt was s?ent. In Installing ap?aratus for
pholic stimulation in the electroencephalocraphic room. Al
first, phone stI;nulation induced artifacts but this was
eliminated by elevating the ii,2ht. re 4re still ri on
the probien-, of tpereasing the totenlily of 1T,-4:1 to co:t...)engate
for the fs;-eater disiancq.
The ao2retus f r mrs'eri%0 thz cQnceniration of alc,-)hol
In the brzat,h was reclived frcm-the .71anUfacturer after over.
haul arr.! was s'Ill found to be 3erform1ng poorly. After
corres2ondcnce with the manufacturer, the entire instruflent
was on over, circuits traced and the valves checked. The
c-cared
&
,aik:r
A 1.;hotosra-7,hic co2y stand w,76 constructed with SCrt1;.)
� :27Y;CV4 1.nStrU:17ni ;;r1.1 a2-.).:Iratus for
entire unit were rzrdered.
Declassified by �187476
date
. 8 797 7
D. DISSEMI NATI INC'.TlCN
T
Pdoers ?,:sblisficd�
HUH, H. E..� 6nd Belleville, R. E. Effects oi
Chronic 3arbitur4te intoxication .on i'.',otivation 4nd
�Niuscular Coordination. Arch. Neurol. &esychltit..
70: Iso.tas (Aug.) 19534
Wikler, A., rrdaert H. F., and Isbell, -H.; N..Allyl�
normorphine: Effects of :31n0e ',:oses, and :='recipitation
of Acute 'Abstinence Syndror1es4 During i',diction
Llorphine, !.4ctliddone or. heroin In i.,'?;n tPc,si�dddicts).
J. eharmacol. &Eltper. TheTap., 14,2; (I)
1953.
Viklort,,A., and Cortert R. L.: Effects of SinGle
Doses of N�Allylnormor2hine on Hindlimb eflexes of
Chronic Soln4I i.�%aqs yetts of i4o.r;7.hine Addiction.
J. :harmdcol, Ex7)gr. IC'jt ft; ')3-t74a.
1SeA.1
l953.
Vikler, A.:- QeCentExrnt 3!�vdies aq4
An4lGes14. NCurolocy 3. tg) 6560 (Sept.) V33.
cr Lvctliy7.15
dlcal Director Herris' Isbell:, �
f"N.Allvinorm*rphine 6nd Othr Anta;7v)nists tc
Nirootic Drofjs." Universily of :�20)1Gcc
of Mtdicines Zhiedf3ot III., It.;ly 221,
�.cdicat Director H. F. Frdser;
of �f,,icis in
51 int-zrim
2
'1,'.ectin,7., too. ehlr71;lcol.- E4;-.r.
Nzw Ezven, )53.
r-irector H. i 7.r..1s.tr attnn:.:oti IA*c.!rin
14cd
Th-zra .zu'cie;s7
atizn.1.7.1
aid
Kzatt2c;!�y
;;..z.:ttvckyl 21,
Declassified by
date
�Ati-- �.;:"
-- I/
.211,
c f U:fcr7Lsk
3. Mt!etincs Attended tcont;nuedi
Biochl:m13t Anna, I. Eisenr,anndnrnf
1nrntI?hysiolorlcal Conss, YoIirez0,
Canda, AuE,:osi 4, 1;53, and thz interi:1
U.cetin� Society for ;-har;.laco1o�7y and Exp,zrimqntal
Therapeutics., N4w Faven� Conn., Sept. 1)53.
4. Motion ?i=tureShwn
�����ft
at � "Clinical Manifestations of Drug Addiction'
t2niw.rsity (II' Nebraska College of ;..',edicirs'�
Uncoin� Neb.
Dept. of i'harmacy, Harvard Medical School, l'oston.
State ti,spital� Yariltton, S. D.
Central SI.ate Hospital School of Norm,3n,FJ
Commissioner .of Narcotics, 'z'ashini'4',
b. "chric Z'arbitw.atc intoxicaticn"
St(�e H'51:11fal ,:chool oftursinn- Yariktoll
� P
(� I��� "Lel '� f e CairO/ '5fate Ho3-4ital of ,J;:rs,.-
Dept, of ?hermacology� Harvard f-:.cd1.11 School,
Ec t 6 k!ass.
C. "Trestent of Lleflia one ''cisoning wit?: N,Alivl-
n-r.-;h1n"
s � ���%4 V 4 '4. S :4
"Lo-zer Limb f'c cir'urinc a Cycle CT
In
f
.
Declassified by 1E17475
date
6) �
497,,
,
4s.
RS
klers A.:
tiltrn
Seriln4r, UniveTsity of Illinois
medical Scoor0 ;.:1.ticaco0 111.0 Juiy, 1953.
E1ccted L.ouncllor of Kentucky i'sychlatrIc
Association, Septealber, 1953.
HzIrri?
D1rzc-c..4 R4..acch
Declassified by 187475
date
1977
,