[PAGE 1]
GUARTEOLY REFORT luly 1 - Sestember 30, 1953.

Sectlon on Addietlag Drugs, Lsboretory of.Pharmacology NtiH Addictlon Ressarch Center, PH3 Hossital Laalngtos, Kantuchy.

FE 1977 187475 date

[PAGE 2]
A. GENERAL

During the last of lune and the first part of July, l933, the procesaing of purchese vouchers and of personnzl payralls was transferred from the hospltaits odmiaistrative division to ihe National Instltuts of Hental Hraita. This edminlstretive change has functloned very welt and only mlnor difflculties heve been encountered. Uncertalnttes elth respsct to the budget for the current fiseal yeer have hampered purehaslng to some extent. The projéct being carried on for the Department of Dafunss wes raactivated durlng the month of July. The project is stlll concerasd wlth the develosment of a synthetic sutsfltuie for codeine.

Cltalcal-sfudles durlng tht quarter eerg largely concerned
with continuing sesrch for codeine substitutes, the eddictioa
Ilebilliy of nixtures of aorphine and Natline, addictlon to
meperidine, with the clialcel endocrinology of addictlon, and with
with chronic Inloxication ax the disthylamide of lyscrglc acid
ILSD-251. Another phase of studles en the elialesl. cndocrin
cioçy of addiciioa sas coepletad during ths quarter. it was
found thet thz sdrunels and the festus wlll resoond to stimulo
tion ty the speelfie odrenocerticstropic end canadotropic
hormones of the aaterlor pitultory duriag malataleed morphiae

A66

CUARTERLY REPORT

Deciassifiad by 1874r5 data

4 FEB 1977

[PAGE 3]
addictlon. Iosofar'as can bs deteralnsd by the measuces emoloyed, rasooases during aidlction are la the normal range. This auggests that the reeson far decreased 17-ketosterold excretlon durlng addictlon ls due to e block at ths atbuitazy level.

The Neurophysiological Sectioa has been concerned elth orellmlnary experiments on the develorment of a test for physical dependence liabillty le dogs, with. aaperidine addietlon in docs, and elth the interrelatlenshlps oi morphine and Nalline. 19111031

The Paychological Syction bas ahown a morked rejuctlon in conditloaed inhtbitlch la rats while under the lnfluence of morphine. 2

four papsrs by members of the untt wers pubilshed in the quarter and tuo iactures were presented befeee sclentlfic soctetlss. kotlon pictures concernsd wlth eddtetion ware exhibited to tuslye audlonces.

3. OL CICAL STUDVES CF 2EICTIC

1. Card Studies d.. Addietlen llesltity ef Nav Subotances. ili A.end d 2.N-dimethyt-3ekydroxymorvhinan bydrechtoride INo. 2o 1-73e3 and Ns, Ro 1-73o3). These substanccs ere dcing examiaed az cotentlel synthetic substitutes for codeine. Slagle Gosas of tha l ltoner varying between

4-65

4 FEB 1977

[PAGE 4]
2.5 to 0 mg-.veregdministcred to 17 nontolerant addlets. Definite evidence of morphine-ilke euphorle begen to appeer ot the 30-mg- level. Euphoria was dlstlac. and pronounced at thz d0-ag. level. Euphorls was alss observed when 60 to 75 mg. rere adalnistered orelly. No untoward toxlc reactlons were observed. Sixty to 75 mg. of the levo lsomer every four heurs caused marked suporesslon af abstinence waen substltuted for morphins in 2 strongly addicted patlents. No evidence of morphine-like euphorlo was seca xith the dsxtro comoound, and no suosression of abstlnencs was obssrved duriag e short
2
substttutlon for morphlne. Although the number of pattanir tested is tos small to drow definite conclusions, the results indicate that the levo lsener will cossdes addtetion llability whlch wlll excced that of codeiag.

-12) .Methy1- -0-desoxymorphine (MK-571.

it has previously becn showa that this drug proouced tntense suphorla ia former morphiae sddists and wes very sffzctlve in suporessing abstinence fron morphine. The human phermocoiopy oī ihe drus has tow beea studied in greater detell. la lo atients It Induced marked ouulllary coastrlctien sad markad pesplrotory deorcssion. The cat of thase eifects eas observed i5 alautes after adnlalstretion of the drug sad vss asseciated

A-64

Declassified by 187475 date

FEB 1977

[PAGE 5]
with the develoomant of intense cuiboria. Cne potient mes directly readdicted to Mx-57 for a period of 17 days. Tha dose was lnoreesed froa E ng. evcry three hours to o mg. every Ilhree hours. Even after this very short perlod of addiction, definite abstlnance appearsd on ebrupt withdrawal. Abstinence was evijent in four hours, severe by elçht, and had subsided after foriyelght hours. The rssults confirm our Impresslon that this drug has high addicfien llabiilty.

(3) dl-l-methyl-4-phenyl-4-carbethoxy ezscycloheptane Iho. S835). Caly preliminary work elth thls compound, which is in the meosridips series, has been coasleted. Single doses varylng between 25. fo l20 microgrens heve been adminisiered to 22 nontoleraat forser addicts. Evldence of morohineelike euphorla wos observed in only 2 of these uatlents. No untowerd toxic resctlons have beza encountered and the dose is still being clevated.

141 4-4=d1pheayl=c-dtmethylenino-hexeaoae-3 Itb. l0seel. This compzoad, e menber ot the methadope surits, Is beleg examined at the roquest of the Drug Addietloa Caanlttse, cince It is bzlng narketed la Lsrzany.. The nanufscturer has ladicated that & combinatlon of thls drug plus Suprifen fpekydroxy ephedrinel dees net possess sddietfoa llability. às yet coly prelisinary date are availeble. Siagle doses have becn odnlaistered to 7 nentolsrant morphine eddicta. Evidenes of mild

4-63

Declassified by 187475 date

4 FEB 1977

[PAGE 6]
morohlne-llke eu atria ves evident at the 30-mç.leval. Further studies are in orogress.

Milzturez. Twa of ths oailents who were eddicted to ths t-to-5 mixture of corphine-Nailine have been reeddicted to morphine and to Naltine in separate experlments, uslag the some dosages of both drugs that were present In the mixture. fotlosing withdrsuat of morphine, abstlaeaee sas far more iniense thon folloslag withdrauet of the mixture. Following althdraval of Nailine, no clear-cut eyidence cf sbstinenca wss observed.

c. Meperiding (Demerol) Addiction.

This stydy is belng undarteken as a ceoperatlve preject wlth the cilaical steff of thehospitet. The study was iniilated becouse the President ond President=elact of the Ansrican Medtcal Assoclation aporoached the Surgean Censral and exoressed -coacern about ths Increaslng lacidonce to meveridine in rivate oracttee. Followiag receint of tetters fron heedquartsrs soncersing thts matter it was doalded that a prolest concernlng mezerldinc addictioa be inltieted and carriêd cut inradiateiy. This projeet alll irelude, on the pari of the hospital, a survey of the records of all patients Giving historles ef asperidine addiatlon. Ths Information pothered from the rscords wlll Include dota oa ege, ssx,

Declassified by 187475 date

4 FEB 1977

[PAGE 7]
eccupatlon, gecgrephical location, stated reason for addletion, other drugs used. etc. ta addltlon to surveyiag the Fecords, the. psyehlatric staff of the hosoital wili undertake tntenslve case studies of a number of meverldlne addlcts. The Nl'H Addlciion Research Canterts part of the program Is io estobllsh the presence of physlcst deoendence in "orimary" addicts and to study meperidine addictlon in dags. The methed far proving thet absilnenes occurs in "primery" meperldlae addtcts utllizes the staadard techaic of Hizaelsbach. Patients with histories of addiction ie meperidioe but of.addletlon to na other drug sre selected for study, These patlents ara sfedllleed on 二 Is abruptiy ithdrara,and observations for slgns of abotinence ore carried out. At the height of abstinence from meperidine, doses of peperldine ere is be administercd aad the rellef of wlihdrawet symptons observed. there posslble, attomoted prccisltailoa of obstineace from mayeridtee with Nalling wtti be corrled out. Confirmatlon of ths catlent's siory of addletlon io meperidine only Is aacessary for fnciusion in the szrlzs, and will bs cbtained by iatervlewinc or wrliiso to the tientit cslotives end hysiel=a. To date, o suitalie potlents have beer studled. All showed vary definite absiinence oa withdreval of seperidins. Tosls manifesteiions, uhile

Declassified by —187475. date 4 FEB 1977

[PAGE 8]
recelving. large ahunts-of meperldine, mere appareat In all 6 cases. Oae patlent who was recelving 300 mg. of msoeridihe every three hours hed e convuislon. 'ractlcally all potlents exhlblted Involuntary Jerking end twltchiag of muscle grouaa. Abstlacnce could not be preclpitoted wlth Naillne in eay of these oatlents.

Studles on meperidlne addiction ere descrlbed la the Neuroshyslological Sadtlon.

d. Chronle Intoxtcetlon with the Diethylealde of lysarglc Acid' ILSD-25l.

Fhis druc ls a semlesyathetio meaber of the ercot serles ehich aroduces sstoxlc ssychosis In doses of oniy 20 to o0 mlerogreas. Th: effecis of siagle doses of the drug hove bezn extenalveiy studjed beth in the Uaited Staies and Europe, uplng both peychctic and nonpsychotic potlaats. Many psychiatrists have descrlhed the nental effects produced by the drug es resombling these seen in schizophrenla ond Sone tevs goae to fer as to catt l3D-prndueed paychesis "exserimental schlzooarenla. No human experimentation on chrenic intozication with this iotatestiag crmnound tas baen corrlzd out. it eas, therefore, fclt ttat the siudy of chronic lotsslcatlon wlih tha connound uas extronely Im ortsat.

A-60

Declassified by 187475 date4 FEB 1977

[PAGE 9]
Six patlents, all negro male former addicts, voluntaered for the exertient. ln juiy, ceatrol observotions were obtalaed. These included hysical, psychologlcal, psychistric exaainatlons, clinlcel otservatloss thres timzs dally, etectre cardlograas, electrocncephalograns, blood chenistry, and Ilver funcflon fests. Fotlowing the control partod, an etiempt vas made fo determine the fhreshoid dose (dose shlch voutd just. Induce mlld subjectivs effects) fer esch paticnt. l'a this preliminary expeplment, the drug was given dally. Initlally, doses af 20 to 40 micrcgrams were admlaisterad and the dose was lacrcascd each day. Very few effects were cbserved until the doss had been Increesed to-lo0 alcrograms. At this polat, mlid subleetivs sffeofs were okserved vhich, however, were not pressat vnaa additieral doses wcre giveá on subseqvuat days. Admialstratlonof l00 to 120 mlerograss fo patients who-had : not been recelviag ths drug dally iaduced powerful susjective effects.. it wes, therefore, felt that satients mlght have develeped toleranee durtng the sretimlaary eriod. Catly adninlstratloa of t5D-25 was therefore discontinued wlthout ins ajientis keosiedce, and, after six days, baguo ogain. irnediately. very siriking reectjons were observed. For thls reasoa it sss necessary to obtaia data on the efiact of siocla lsclated deses vhlch vere soaced at least thres days apcrt.

Deciassified by 187475
date 4-FES 1977

[PAGE 10]
Crdar these condltlons a very coaslsteat pattera ai drug effect emerged. The degree and duration of the reactlons wers related to the dose. The amount of drug secassory to elicit the cfioct varied widsly in different patlents, the range extending from 90 to 300 mlerograms.

The objective effects of L5D-25 Include elevation of gystollc ead dlsstolic blood pressure, dilatetlon of pupils (measured in coatrolled llght), lncressed teadon reflexes, and decreased abdonlnat skin reflexes. Cooseflesh, fine intentlon tremor of tha fingers, ankle clonus, end tremor of large muscle groups were lets coasistently cbsgrved.

The mentcl gfiects of LSD-25 were very striking end varied from oerson ta person. to obvious correlation with personcllty nattaras wis eoaereut. Ths mentel effccts consisfently Included enxiciy, s feslins of unreality,end varlous haotis sensstices Iformlcatlon, feeiings of elcctric shocks on the skia, tingling sensations, chokingl. Toste and smell aopeared to be unoffectedy noises vars reported to be loud and dlfficult to dlstinçuish; chançes in the patientts body laage, aad in the body Iniage of othar percons vere frzqueatly reported; the patient's hands and faat appzured to grow, or decrease la size. Narked changes In. visual percestion were reoorted. These Included blurring of vision, aboormal coloratlon of fanlllar objects lhonds turning surole, creen, etal, douts of palat on the soit, fiickeriag

A-5

DetlassifiedFEB 1977187475

[PAGE 11]
shadows, danclng dots of licht. ond spinning ctrcizs af color. frequently. Ineniaate obiscts uere dlatorted and changsd in slze. Cecasionaliy. patlents reported seeing vislons conslst-Ing of repidly chosgiag featastic scenes which resembled "welt Disney hovles." Patleats had dlfficuliy in descrlbing fhess sensetioas while under the iaflcsnce of LSD-25 (tlackiagi) end were much more likely to glve good descrlptlons the day followinc the experlment. They complalned of difficulty in conccniratlon and of a "rush of thoughts." Patlents were uewally esathetle and somewhet eithdrawn during the helght of the osychosis,Inslphfwes aiwdys raintained.

The effects usually bsgan"30 mlnutes fo one hour after edmtnistretlon of the drug end oeak effect was usually raoched In cne and cae-haif fo three hours; thereafter, effects Sradually subsided and vtre com>lstely dissiceted afier elcht fo \$lxteea hours. Cccaslonolly petlants reported hongovars" lastiny for ane to severel deys.

Electcasncaohalenroms were not ersatiy changed by LSo-23, but syachronizattos of the eiectrovacephaiegrzs by rhythmic photio stimulatlon was enhonced..hotie sttnuiation elso sppearéd to enhance perception of eolors, pettzrns, ete., foltovinc aleialsiretion of (sD-2i.

Declassified by187475 date 4 FEB 1977.

[PAGE 12]
We canpol agr that the lSD-psychosls rasembles schizophrenle. Certaln tsoisted symotoms that are obssrved In schlzophrenle, such as decerscnalizetlon, dereallzetion and hallucinatlons ere observed under L5D. Hosever, Insight is always aalnteined and affect ls usually aporoprlate. The total picture of LSO-intoxlcatlon constitutes & distinct and recognizadle cllaicel entlty, which we feel could be confused only with intoxicstion wlth mescallne. In fact, iSD-intoxlcatlon rasembies intoxlcatlon wlth coeoine more than schizophrenla.

The experlment cn chronls lafoxlcatiaa has deea completed in 3 patlents. Dpe potient wiihdrew aftsr six deys ehronic Intoxication end the cxperimcatis still in progress in the 2 ecaaining patients. Araold decllas jn the effect shen one doce of LSo-25 was given dolly wes otserved In all 3 patlents who comoieted the experiment. Initial doses were 1.5 to 2 mcg./kg. [90 to l30 aleroçrens totel dosel administered onca dsily. The first dose ieduced tha vsuat shsnges la meetetion, vereestlon, blcod eesture, coslltary sltc, cas tcadua rafixzte.ertiai tolerance to thls dose ves evldent by the second day of adninistratlen eni appvared ts tz corelats after frur dars cd:ialstrailoni At this point the dose wos lncreased, end after 7 to l0 days, tolersncs appeared ts be cempleie to 3 mcg./kg. (total dose of about l80 mlerocransd. The dloinished effsct

A-5

Declassifiedrpy 1977-187475 date

[PAGE 13]
included not ealy s dcclina ia fhe maatdl effecfs but also decreases la the effecis on blood pressure, pualllory stzx end deco fendon rcfiexes. No abstincacs occurred on wlthdravel of LSD-25 after l4 days edministratlon. Develonment of totersnce to LSD-25 occurs more raoldly and aooears to be more comolete than with aay drug ee have evar studled. The raoldity of the roturn of the affects remains to be determined.

2.Siochemlcel Studies

in the last quarterly report sas completad during thls quarter. In geaersl, the éxaretion of 17-ketosteralds folioving E-hour infusions of Ieternetiogel urlts of ActH durlng matntalned eddicfion was lese in fetms of mifligrams than prlor to addiction-However the Incresse in tarms of percentsge of the vsval daily exeretlon was greater during maintelned addictlon. In addltion, 17-ketosteroids laereased afier infusions of only 5 and 2.3 Internotlonal units of the preparatloa of AcTH used in fhesa experimants. slth the excepiion of.one test on one man, the incrvese of i7-katosteroid exeretion after ACTH fall wlthla the normal renye. incrzasz in encretion of uric acid aftar Infuslons of Acti apeared to be as great during malntalned addiction as orlor to addietios. The decline la sostnoshtl

K-55

Declassified by 187475 date - 4FE15 1977

[PAGE 14]
ecunt during timed AcTH lnfustont was somewhat- slower during maintalned addlictlon, but always felt to' zero (or ngarly so} in clght hours.

Increase in excretlon of l7-ketosterolds after the injection of loo0 iaternatlonal untts of chorlonic gonadotropln for five consecutive days was as great in terms of milligrams and in terms of percentage chance fron fhe usuel excretion during addtction as during the control perlod.

The dota definitely show that the testes and the adrenal glands are capable of responding to the specific pitultery hormones during addiction to morohine. Nevertheless, excretion of 17-ketosterords is markedly reduced during addictlon and eahanced during wlthdratol. Dr. Dorfmann,of ihe Worccster foundatlon for Exoerimental Bloloty, kiadly analyzed s few semoles of urine for us on petients who were addicted to morohine, and durlng acute wlthdrawal of morphine. The excretlon of corticolds is much lower during msiatainzd addiction. The most reasonable hypothesis explainiag the facts known to dote is e biosk at the pituitary level during morphine eddiciion.

future work wlil include determlnotlon of tetel adrenalcorticold excretlon Iprovided a suiteble meihod can bo developed); e frecflonatlon oi urinery corttcoids by Dr. Dorfmenn; and chorlonic gonadotropln deterninations Ito be done by the Natlonsl Cancer Institute, provided certain technicel difficultiss

A-5

Declassified by, FED19775 date

[PAGE 15]
at Lexlagten cen taovercome. Te also hobe to svsluate thyrold status during msiateined addiefion, uaing ssrumsrotain bovnd lodine end Hils as tha ladices.

b. Serum Electroshoretie Potterns.

These studies have been exicaded and more sottsrnz have been collected on former addlcts and on nonaddicts. All determinatlons are belag done la berbital bufier, rafhor than shosphote bufier, as heretofore. The dlfferencs in the ratlo of bets blobulln to gamame globulla prevloualy reported (ratio greaier than I In addlctsi less then I lo nosaddteisi hes been confirmed and isgstatistlcally significant of a p-levei of lets thea O.Oi. There ts, however; an averlop, somd former addlcts shoving "normat". patterns end some noneddicts showing "addict".patierns. The slgnificance of-the chaagzs In servaprotein pattera renalas obscure. C.EXPERRENTAL NEUROPSYCHATRY

1.Naursnhysleleaicel Studies

4. The relatlon oi morohiae-kallies dosa sromurilvus to degeee of antagoniotic cffaets. Ths degrzs qf antegaaism of cor hiae by Naitine hee buen studted in the i.sliatoral fixzes reflanes of 4 spinal dogs, uslag Jases of Nalline rencing bctsa 0.0s to 15 mg./kg. Aithough more exseriments need to be dane ct

Declassified by 187475 date -—4 FEB 1977

[PAGE 16]
et the verlous dose lcvsis, the experiments so for. indlcote that a largs dose of Nalline antagonizes the depressont effects of morpline mors than does a small dose. Coaversely, a lsrge dose of morohlne antaconizes thc effects of a fixed dost of Natllne more than dozs a saall dose.

b. Addictton af Chronic Splnat. Dogs to morphine-Nalline Mixtures. Two chronic splnal dogs were Given 3.75 mg./kgof morphine and 1.2s mg./kg. of Nalline 1mixture of 3-to-l). After three weeks ediictlon to this mixture. there was no evidence of tpleraoce to the daressant effects of ths mixture on the flazor rogfiea. This Is o striking obseryation sincs, alth mor hine aloee, matked tolerance would hsvs bech exuecied. la all does hyocrreilexta sad soontanzaus ruaning mavements becan to apzear befusea the Sth and lStà days, ianediately after each dose of fhe mizture. Abays the tevsl of secticn, mydriasls,tremor. rhinorrhea, sallvetlon, ete, appeared soopgr than did hvperreflexla or runaing movenents ia tha hiadlinbs. Fladicas in the dant cenflra thoca berotoforo observed In aana They Indicete that chronle use of morphiae-Nelline minturts wovis be assoolated with the develenent c4 unplaesant stue etfects iprecipitatlon of alid abstinence by each laiectloe oi the mixturel.

Declassified by, -187475 date 4-FEE 1977

[PAGE 17]
e. Determiaing Addietion Elablllty ln Dogt, Using Nalline. Ee ars studying the zosslblllty of developing o short zst for addiction lutysical decendencel llebiiity In dogs, uslng kalllne. Se have carrled out arelimlnary ex:eriments uslan two methods. Tha first method involves fhe lnjcctlon of lorce amounts of the drug under study ance daily for three io ftve deys cfter which ls ag./kg. of Nalllne are adainistored. After lalection of 50 ma./kg. of morphine for three to flve days, Naltine coysed deflnite changes in the behavlor of dogs. After adminlstretion of Relline thz dogs become rastless, sometimes vomltesi, developed tranors, and consisteatiy sovld dig a hole st the fcundation of the buliding snd tic In lr. Thase changes wore aot dboerved after elther morphine er Nalline ssperotely. Erratic results vere sesn efter injcetion of sinole doses of methadone for three to five days. in the ether mzthod, druos were given aeveral fises daily. %hen 5 me./tn. of morphlne was administared four times daily, Nalllne prealoiteted digntao end otber changes after thres to seven dava of addictlon. lntaasity of the changes -hes bean steadily iacraattng as noruhine dssietloa srecegded. ahen 2 to 5 nc./ka, of methadcne were ad lalaterad four tines daily, Nalline crecipitated the dlegins end other chsages ofter thrce to seven days of addiction. Such chsegas have nnt been observed ln docs that are baing exnerhasntatiy addlcted to lo ap./ag. of aeperidine evary three hours for 30 lays.

A-51

Declassifièd by187476 date 4 FEB 1977

[PAGE 18]
d. Addiction to lézpcriding Ia Chronic Splnai Cogs. In 2 noatolarant splnol dors slngie doses ef 10 ag./kg. of meperldlae prcduced alfects on the hindlimd reflexes shich uere stailar to those produced by 0.75 mg./kg. of morphine. After a week co lO ng. of msperidine cvery slx hours, tolerance to the depressant efiects was evident, At this time 15 mg./kg. of Nalliae dtd not-presioitate runntag povements. Ga the contrary, the flezor refiex was deoressed cnd the dog aopeared to bs sedated after Naillne. Whea the number oi doses of miperidins lncreased froa four fo eight dallys peculier changes were observed lo the paralyzed hindhiabe. Thase chesges lae 3 cluded marked hyperactlylty ofythz lpsliateral, fiexor snd crossed extensor reflexes, Irreguiar spoataneous trsmors, end twiches and masslve exíensor reilcxes ellclied by tepplng eny bony-proof protuberance beloy the level of cord sectlon. After sixteen deys ot addletlon, abrupt withdrowal was corried out for 24 hours. The changes abserved persisied with increessd laterslty for 6 te t2 hrurs, thea sybaided moderateiy. bafore ths dogs were reelaeed on me eridine. At the moment, we ore unsure whather tho chapges seen la the dogs eddicted to meneridine ranresent toxic effzdts er abstlaoned syeotons. e. Efiecis ot Pizthytanide of tyssrgic Acid (L5o-25) on the Buman Electsoeneephalcgran. Ia G aubjests, single descs of LsD-25 varying from 90 to 150 aleröçrans produeed tittls

187475 date

[PAGE 19]
chenge In the Elc Syachrcnization of the electrosnceohalne cres by photle stimulatioa appears to be enharczd after LS0-25 but the statlallcal signlficancs of the chançes observed remalas to be evaluated. Horever, photic stimulation deflnifely enhsnced sercestion of optical pseudo-hallucioatiens.

2. Exueriaental Psvcholocy

a. Effects of Morphins on Condifluned lnhibltlon la Rats ("pala anxiety"l. The ourposs ef this esperlmsnt was to attempt to develop an enalgesic testing method ln rats, based on the sane priacipls.os fhat canonstroiad. in mua - the reducfloa of anscipstory aaxlety assoclefed with psin. Ths method ysed was ag follóws: Asult rals were fed 70 par cent of the emouat of food required to:melatals thale body weight. Rats were thes placed ln a modified Skinner box cad traincd to press a ber which relcased small pellets of foed. kotivatiee uader these condltioas wes, of caurse, hvnger. After the rats had been tralned and had ettained s constaat rate of bar Fesslng, rats wars conditioned by souuding an slettrie buzzer terainated by an elzctrie sheck. After conditlening occvrred, the rata of bar oressint becane for iess during the terioe pí tha tuzz, but aiter ths cizctric shsek tha rot wovld roeieo to sress ths bar and cbtala food pelleis at hla noral rate. Cace statlz caasltleeing had bsen cetiolisbed, asr-hiia vis

Declassified by187475
date 4FEB 1977

2

[PAGE 20]
siven every 7 to 10 hours la the following order: 3, 10, ó, 11.4. 5. 14, 12 and it mg./kg. 1t sas found that the adaia-Istretlon of morphine merkedly affected ths degres of inhibitlon of bar pressiag. As the dose of morphine was lncreased the rate of bar presslng during the sounding of the buzzer tended to approach the controi rate. An almost lincar dose-effect was obtelned belwcen S and lO mç.kgo of marohlne. The daie obtained ara consistent with the hyoothesls prevlously devetosed in human studiess marphlne telleves aein by reduclag anticiostor. anxisty caused by salniul stimuii. Followias furfher improvenent ln our aoparstus, we lntend to study ths effecis of other 3
drugs, such as pzntobarpliel, aaghetáalne, aspirin, eta.. end to study the effects of-morphine co extlaetion.

b. Effects of Dietaylanide of Lysergle Acid on Psycholoclcal Issts. Siz subjects hava beca tested before end after the adninistratlon of lSO-2S. Testa used havs bazn the Rorschech, Ceschler Ballevus, Caldsteln-Scheerer aad tha Minnesota Vuitinhaslc.?ersonatlty Tavcgtery. Although thz records have not been conpteteiy anaiyzed, the foitowine trenss are balna obsarved: erioreanca on those svb-test4 of the cachatarebeltevue scele ehies reaulres sustaised ceaczntratian end attentlon Is conslsteatiy tover after LsD-25. Tha Coldstoina Scheerer test shoss no mcaatrabie Ia alreant cf abutract thick ing ablllty, No systematie chdo-ss have ouen saen ln thu Rociehach

Declassified by 187475
date 4 FE9 1977

[PAGE 21]
tests, exceot for an Inercase In the total numbet' of resoonsas,

and an increase In indicalors of anxieiy. ln the t't tasfs, elevatlon oi all clinical scoles was observed, the graatest lacreesgs being in the."schizophrenla" and "paranola" scaies. C. BIOPHYSICAL STLOIES

Considerabte time was spent ln instaliing apparatus for photie stimuiation in the electroencephaiographic room. At first, photlc stLauletlon induced artlfacis but fhts was ellminated by clevating the llght. Wc ere still sarking on the problem of lacreaslng the iateasiiy of lighi fo conocasate 3 for the grsater distanca.

The apparatus for msecurtng the conceniratlsn of alcohol ln the brcath wes recslved fren. the aaavufaeturer after ovar hayt and was stlll found fa be performlag poorty. After corresoondence wlth iha manufacturer, the entire lnstrunent was Ssns over, eircuiis treced snd the valves checked. The chtaf difflsulty aupsared to be à bad axclter lan>e

À ,hotngranhlc cooy staad was constructed with screp patertul.

Tte usuat ssryiees on lasirunznis snd epoaretus for the cotire unlt were Faedered.

-5

Declassified by —\_\_187476 date 4 FEB 1977.

[PAGE 22]
D.DISSEMINATICUNFCRMATION

Declassilied by 4 FE8 1927 187475 date

[PAGE 23]
3. kaetlags Attended Iceatinued)

Biachsatat Anne l. Elsenman sttended meetinrc of Internatlenal rhystolecical Congrass, onireal, Canzde, Aucust 30-5et. 4. 1753, aad the lateria Mestins, Soclety for charaacolory end Expsrimeatal Therapeutles, New Haven, Conne, Sept, C-9, 1253.

4.Motion Picture Showincs

6. "Cllnical Manlfestations of Drug Addictlon" Untveralty of Nebraska Colleçe of Modlcies, Lincaio, Neb.

2 Dept. of Phormacy, Harverd Medlcol School, Poston. State Hhspltal, Yonkton, S. O. Central Stata Haspital School of Parslag, Norosn, Ckl.. Cormissloner of Narcotles, Eashingion,D. C. 三

b. "Chronle Sarbltyrate Iatoxicetlen" Stete Holoital School of Nursing, Yankton, 5.D. Central State Hosoitsl School of Purslag, Poraan, Cki.. Dept. ef /hermacolocy, Harvard Medical Schosl, /Eoston, kass.

C. "Treataaat of Methadone Felsoniag with ti-Aliyle Bormsrphlne" Universlty of Itlinste, Cellege of medtelna, Chicega, li.

d. "Lozer Limb Reflex Changes Curing a Cycte of Ateictlos In 15otnalds." Cnivtrsity af Hiliesis College of kadieice, Chieaço,lil.

187475 Declassifiad by dato 4FEB1977

[PAGE 24]
tabell, H.: Conducted Semiaar, Uaiversity of Illlaois Medleat School, Chlcego, 1ll., Juiy, 1953.

EIkler, A.: Elected Councllor of Kentucky "sychlatrle Assoclatioa,September, 1953.

Harriz tsbett, ä.d. Ciractor oi Rassacch

Declassifled by187475
date 4 FEB 1977

E. PERSONNELHONORS