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January 1 - March 31, 1954

Section on Addieting Drugs, Laboratory of Pharmacology, NUH Addietion Rescarch Caater, PHS Hbspital. Loxington, Kentucky.

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GUARTERLY REPCRT

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A.GENERAL

No admlnlstretive difftculiles worthy of pote were encountered during fhts quarter. Handllng of payroll and payment of vouchers by the Nattonat lnstitute of Mealel Hicalth is nou functloaing smoothly Occasionally, mlnor errors have becn commltted because of the dif\~ ferences beteeen Hbspltal Divislon and NllH practlces, but as time goes on thesc errors should be ellminated.

Clinical studles durtng the quarter were largely conceraed with contlnulng search for codetae substitutes, the addictios llabillty of morphlna-Nalilãe mixtures, studles on ner morphtac sutagonistss Intoxication wlth diethylamlde of lysergle acld, and with the clinicel endocrinology of addicflon. If:nou appeers certuln that the addlctlon Ilabll1ty cf L-2-N-dloethyl-3-hydroxy-morphinaa and of 4=4=diphenyl-é-dlncthylemino-hexanone-3 exceed that of codclne. These drugs cannot be regarded as safe codeine substltutes. lt hos been shown that a mlxfure contalning i mg. of Nalorphine for cach 10 mg. of moephine can be used for periods of 30 deys, provided the dosoge is held at tO og. every four houra. Chether pala reltef by such mlxtures 1s loss than that obtalaed with morphlae, end whether tolerance to the paia relieving effects devalops as rapldiy must be deterninad In other lnstitutlons. It ts,however, certain that this mlxturc could not be obused by oplate eddicts. Coaslderable work eas acconplished vith respect fo the effecte of morpirire addiction on the activlty of the putultery and adrenal giands. Coth these

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QUARTERLY REPCRT

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projccts are belag cerrled out In collaboratlon vith other iobora-. torles (Corccster Foundatlon for Expcrlmental Biology, Shrewsbury, Mass., and thz NaticnaF Cancer Institute, Bethesda, MaryloadJ. Ths results are not vct avallable.

The neurophysiologtcal sectlon has now succecded In demonstratlas physlcal dependenec on meperidlne In dogs. This sectlon has also been attempttng to coapletely prevent morphIne-induced depresslon In dogs by adnfnlstrctlon of very large amounts of Nalllne at Intervals of three hours. If is hoped that this experiment will constitutc a test of the "adaptatlon" bypothesls of the development 生 of physical dependencc.

The psychologleal sectlon has Inltlated a study on the personalify charocteristics of physlclan addlets. Thts project Is of great theoretlcal Importance becaust of the great dlfferences with respect to avallabtllty of drugt, soclal, economlc end educatlonal staius, aad outlook on áddlction in physiclans, as compared wlth other addlcts.

Two papers by members of the uait were publishcd during the quarter. Seventeen lectures vere presented beforc sctentiflc audlences. One of thoss was a report for tho entlre calendar year 1953 to the Comnltfec on Drug Addletlon cnd Nareoties of ths National Research Council. There were 36 motlon plcture showings.

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B.CLINICAL STUDIES CF ADDICTICN

1. Vard Studlet

a. Addictlon Lloblllrles of Nsw Substences

{1) L and D 2, N-dtmethyi-3-hydroxy-eorphinan

bydrochlorides (Rol-7362 and Rol-7363l. Vork prevlously reported with these compounds vas confirmed during thls quarter. Abstlacace was complctely suppressed In 2 patleats who vere strongly addicted, when 60 og. of the I-lsomer wes adminlstered eyery four hours. The d-lsomer vas completeiy laactlve Io suppresslng ebstlnsnce et thts dose level. It was, therefore, concluded that the levo-isomer has hlgh addietloa Ilabllity vhlch excceds that of codetnc; vhereas the d-isoner, a very taert corpoued, ls davold of addtetlon llabiltiye 1o1 44-dirhaavt.6-dimethvlaniao-hexan0ac-3 (105021.

(3) Benzylmorchlne myristyl ecter (59EG-Al. lh1s compound gas syatheslzrd in France, Is lrsoluble In water, and can be Injccted only In oll. For this rceson, ell the work carsled out has been by the oral route. Doses rongtng up to 60O wg. did not Inducs any definlte morphina-like effects ta apntolorent addicts.

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Vitbr GoO-sa. coses, ansieat shia crupttons conslsting of blotchy erythene end vhealsre observed in all pailents. Suffictznt date ore not yet at hand fo pirmtt an evaluaflon of lts addictlion liabllity . 14) Beta-dl-nethadol 145431. This compound 1s

belng investigated at the specific request of the Coonissloner of NarcotIcs. Although It can readily be converted Into beta-di-acatyimethedol, a compound eith knowa high addiction liabillty, it connot liself be subjected to the controls of the Narcottc Act wtthout praof of lts addictlon llability. la doses ranging betueen 30 to l00 mg. orally and subcutancously. it has Induced no Immediate or delayed corphlne-llke effects in 10 nontoleraat addicts. Vork is 2
not complcte and as yct ao dcftalte opinics concarnlng lts eddictlon Ifabilliy cen be rondered.

b. Addietion Cloblllttes of Horphlne and Nalline

(1) I to l0 aizture., Six patioats bove been addtcted In randoaized ordar to 10 ng. morphine plus 1 mg. of Nalorphine every four hours for 30 days, end in a control experiment to tO mg. of eorphine cvery four bours for 30 days. This cxporimaat wes dosigaed fo doieraine whether or not thts nixture eooid be uaed for the 'relief of chroalc pola. The vafcserd sldo cffects nrted phen "addieting" dose scheduies of ths mixture vere used In prevtous experimonts did not appcer sith thls 2 rticular dasaga sahedute. Dafiaite aild absfisenee was seen after vlthdrawot of bath the nixrure, end the mrphlne. Thether abstlaence vas stider fallowiap wlihdrcvel

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of tbe mixturc ls not yei known, sime the dete bas not beon completely analyzed.

c. Korphlac Antagonlsts

thts conpound have been conftrned. It Is extremely potent ia preclpltoting abstlnence fron morphins In addicted patleats, regerdless cf the route of adminlstratlon (subcutaneous or orall. It aiso appears fo be more potent and more toxic than fblorphinc.

(3) -Levatiometherpkan. 15759). This compouad 1s
the ne thyl-ether of Levallorphen ead wes syathesized for us by
Dr. Lyndoa F. Snall of the liatlonal Insiltute of Arthrltls aad Mete
boilc Diseases In the hope that lt would be orally effcctlvs and
long: lastina. The drug has proved to be a very effecttve aatagontst
both subcutaneously and oraliy. liowover, It eppears to be more
cffective when admialstered sutcutencously and lts langth of sctlon
appears to be no lorger thaa that of tar perent compousd,bevallorphaa. 1413-hydrexy-a-propargyl-rorphiaan 1Re1-77001.

This ts a poy anteconist lo thelorohluaa ceries. lt ls of paritsvler interest slnce, according te Dr. Hathoa B. Ecdy of the Notlonal Instltuic of Arthriltis and Vetabolte Dlssases, It bas "enalgasic

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cifacts which are obout equel to those of meperidlne In mice. So far, only dats conceraing the slde reactlons In mon are avsllable. In doses of 4 to 0 ng. it Induces giddincss, dlzzlness, pallor, neuscs and sleeplness. These effects are quite marked wlth the S-mge dose. The compound appears to be much loss actlve orally, slnce equivolent cffects were not obtalned with doses of 50 to 60 ne. orally. The anfagonlstlc properties of the drug bave not yet been tested.

d. .Diethylamide of Lysergle Acld ILSD-251..

The data ca Poplllary clze, kaee jerks and bleod pressure vere plotred ond the areas of the curve measured wlih a planimcter, thus reducing the total timo-actlon courss to a singlg area flgure.

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Analysls ef the resuas Indicaied highly sigalflcant changet In blood prcssure andhlllary slzc at doses of O.5 mcg./kg. and better. Aizhough the khce lirk data shoved. Inergases at all dosoge levela, these changes were slgnlflcant ststlstlcally at uniy three of ths six dosage ievels. À very good correlaflon between the logarlthn of the lose and the degrec of effect was obtained ln the case of pupillary size and blood pressure. Slmllar curves rere obtained when totel nunber of poslttve aasvers vere plotted against the log of dose or the estimated clinlcal grode of mepfal effect. A hlgh. correlatlon between puplllary, blood pressure and mental cffects is. evidcnt ia the data.

We have now studted the subjcctive changas. laduacd by LSD-25 in rore then 50 forner morphlne addlcts. The sympfons observed apoear to be Identlcal wtth those observed fa groups on nonoddicts of fer different composifion vith respect to race, age, sociol and econonie statys, and pcrsonalliy types. Ia other words, ths effvets of LSD-25 sppear fo be speclftc and are not relatcd to any of fhe foctors menttoned above. This Is a natier of great iaterest, since the sublectlve cffects .laduced by LSD-25 hava beca studled ncre inien-iveiy and more thoroughiy in a greatcr diversity of popuiaticas then any other drog vlth whkh ve are faalllar, tncludlcg morpklne end alcchol.

(2) Tolerance to L5D-25. Tolarance cxperimunts descrlbed in the onnual reperi were confirned ta 2 additlonal pattents in addttton. we bave conflrmed the devaiopaaut of toicrauce in 15

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other paticnts who ware haadted on an "out-patient" bacls. Appnrenfly. a stgnlficoat degree.of tolcrancc can be obtalned by admlnlstering 10, 20 aad 30 esg. of LSD-25 iwice daify fer os llttle as thrce deys. .Doses of thls order Iaduce only aild effects.

3. Chlorpromazine (5KF-2601). Thls compound is varlously knowo os Largactll, Thorazine, and by other names. Chemlcelly If Is related to the phenothtazine group of antlhistamlnlc drugs. It has been reported to be an.edrcaclytlc, parasympatholytic, anticinetlc, and hlghly sedatlve drug which, la addifion, markediy poteatlates the effectsrof oplatcs, barblturates ond generai anesthetics. It Is under latensive investigation as a sedative asent for varloue psychlatrlc disordçrs end hes been reported to grcatly ameltorate symptoms of withdraral fros oplafes and related drugs. luvestigotlon of thls conpound hos been undertakep at the reguest of the World Hizalth Crganizatton. Because of reoorts of the potentletion of narcofics, studles of the drug heve been carrled out In on.extremaly careful manner. The cffeets of single, or of ropeated dosos are siallar to those described clsewhere. Doses of 50 mg. orally threz timas dally Indnce sensations of wcoknoss, Iethargy and drowslascs. In our patients, no morked effects ln body tomperature, blood pressure, puise rote, ett., have boun noted with cosss of this slzo. tb untowerd aifects hava eppsared càen 30 no. of rorohine were comblned with 50 mg. of chlororomazins. Ten mg.of the drug three fimes daliy has Induced no untovard effects In Individuals stroncly depcadent on morpline. Tork wlth thts compouad Is coitinulng.

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2, Blochenlcal Studies

a. Cllnical Endocrinoiogy ofAddtction

(l) Lack of effect of chorlonlc gcnadotropln after ulihdrovol of morphlne. In 2 of the pofients who were given chortonlc gonadotropin before and during e cycle of addicilon to morphine, admintstrotion of ICoO unlts of chorloalc gonadotropln daily for five days did not Induce a significant rlse in l7-ketosterolas. This was aof due to Cecrease la astivity of the preparatlon used, since It tnduced thc expected rlse Ia tndividuals wha had aot been readdicted. An additlcnal patlent was, therefore, put through a cycle of readdictlon aad. tested vlth charboalc gonadsteapin before, durlng, and after fhe eddiefion cyele. The sama dininlshed rosponse fo chorlonic gonadotroptn.vas seeh followlog uithdroval of morphiuc. The reason for thls chango.Is obscure.

12) Effects of mrphine addictloa on exeretlon of cortlcolds. In collaboratlon wtth Dr.Ralph l.Oorfman of the Worcester Foundattoa for Exprlmental Blologv, fraciionation of thg steroids cxcreted In the urlne duriag cycies o? morphiae addlctton is beiag carricd out. Tho rosults are not yat avallabiz. Simuiiancousiv. we are ettematlan to sot up a method for tho datcrnlnatton of storoids dertved only fron the adrenal cland.. Foraldable techateal difflculties have been cncsuntored alth fhts nethod, Lbtch ars telas slcviy resolyed. The best data obtained fo dafe insiccfe marked Increaac of cortiecid excretlon durlug vltidrsvat.

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lrultary gonadotropin excrs duriug cycles of addiction In collaborotlon wlth Dr. Roy Hertz of the Nattonal Cancer. Iosiute, determlnations of plfuttury gonadotropia excretlon, during cycles of addiciloa are bclng carricd out, using 2 male sublects. The NiH Addiciion Research Center collects urines, precipltates thz gonadotropla, dries the extracts and forwards them to the Natlonel Cancer Institute where the assays arc made. As yet the resulis are not avallable.

b. Studtes In Matebollsm of Ethyl Alcohol. A consIderable number of determlnations of the rate at which ethyl alcohol disappears froa thc blood were carrled out early In the quarter. Two aualyttcal nethods were used. Cne of these metmode iawolved fhc deferntnatlon of çoncentratlons of alcohol In the brestht thc cihor, dzteralnafton of blcod alcohol diractly, usleg a dichropate oxidatlon and itiratioa meihod. Technlcel difficultles vore expcrleaced with both methods. Uarellablc results were obtalacd with the breathmefer, unless It vas callbrated datly. Unexplalned discrcpancies occurred ta the dichronate fltratlon method, which wers probably relatad to difficuities in getiing quantltatlve disttllatlons of the alcchol from blood. Results on the metaboiie rate of alcohel obtalned wlth the breathmeter fall viihla the cange reported In the Iltereture. Varlaftonsln tha same ladividual et different times de sot cacced 2O por cent, an ecceptable Fange for blologlcal sork. Feuding of 200 crans of laan beefsteak laduccd no great chonge in the rote of aicohol nctaboltsn.

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c. Serum Electrcphoretis Patteras In Addtction.

Work la this fleld Is continulne. If now appears that the pollo of early gamma globulln to bets globu!ln fends fo Increose duriag the/phose of tolerancc to morphlne and to cecrease following wlthdrawal of morphlne. Thls phenomena may posslbly be ilnked to the effect of addictton on the endocrine system.

C.EXPERIMENTAL NEUROPSYOHIATRY

I.Nourophystology

a. Rebound Loverlng of Threshold which Underlles Convulslons Produced by Electrical Stlmulation of Thalamle Intrelaminar Nuclel lu Cats Durlag Recovery fron Pentobarbltal Apesthesla. In cats In whtch bipolar electrodes were Implanted in the thalamie Intraleainar nuctà under deep pentobarbital enesthesla, progressive decrease Ia the amount of clectrlcal sttmuiatfon required fo Induce convulslons ves observed 20 to 30 hours after Inducflon of tho anesthesla. Thls lowerlng of threshold parslsted for about 42 hours and had disappedred after 72 hours. This work 1s to bo extended to other oreos of the braln.

b. Morphine-ilalorphine Mlxtures. An ettempt Is being made to addict chroale spinal dogs to aixtures of morphlae end Nolllno la such a wey that depression of the ipstlaterat flexor snd crossed 'exiensor ruflex ls nevar observed ioxccot for ths mlld depresston produccd by ths Nalbine alonet, Admintstratton of 5 ng./kg. of Nalline every thsce hours and 2.5 mg. morphine cvery slx hours appears to be a sultable schsdule. After 2l deys addicilon, no abstinence was evideni above ths levet of transuelton.

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The rasulis co far Maport the "adaptutloa" theory of physlcal depeacence and refute thegdual.actlon" theory.

Ce Diphesie Actlon with Doses of Moperidino In Dogs. Single doses of 75 mg./kg. produce typlcal morphlne-like effects In the hlndlimb reflex of chronic spinal dogs. After 6 to ll hours reversal occurs ond, In addicilon, "strychnlne-llke" effects eppeer. These resemble In every respect the hyper-lrritebility scen during chronic adalnlstretion of meperldine In smaller coses.

d. Meperidine Addiction In Dogs. Te are now able to conslstontly precipltate abstinence from meperidine la dogs that were recelviag meperldine chronlcally.. Thts hoe beso mads posslbls by adainlsterlng meperidine every these hours gad rolstng tlie doses to the level just short of that whlch Induces gzand mal coavutstons. These experlments ladicate that the "depandence producing" snd "toglc" doses of mepertdine ape vory close. The sane eppeers to be truc ln man.

e. Meperldine-Nalline Antagoaism. Using rclattvaly small doses of mspertdtne, no ontagoalstic sctlon of Nalline upon meperldine effect of hindlimb reftexes could be demonstrated lsce annuat raport, 1953i. Vhen, howaver, 75 mg./kg. of meperidine were glven, t5 mn./kg. of Nallline aategonlzed the deprcssaat effecis of meperlline on the Ipsilaterel flexor refiex and the crosaed extensor Feflex.

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7. Short Tests fer Physlcal Dependence Liabiitty In Dogs. In 2 dogu,.dosage of orphlne was papidly lncressed from 5 to 12 mg./kg. in a 6-day period. On ihs 8th day of addlctlon, i5 mg/kg. of Nalline preclpitated typlcal abstipence symptome. In 2 additlonal dogs, dosage of methadone was tacreased to 17 mg./kg. In a 6ndoy psrlod. Oa the Oih day, 15 mg./kg.of Nalllne preclpitated typical ebstlnance. These results indicate fhat It is very llkety that a short, slmpls test, which could be used by pharmacological houses for 4 determlnatlon-of physlcal dopeadence llebllity of new analgesles, can be developed.

g. Studies on the Relatlonshtps Befwsen Coadltioning end Extlnctlon of Alpha Blockade: and Vtsuat-Hand Reactlen Time In Man. Merreli has reporfed that ?avlovlan "extlnctlon" Is dus to cortical Inhlbifion. The theory advanced by thls Inyestigator Is besed on the observafion fhat, as aipha bioctade In the EEG was cxtlogulshed by nca-relaforcenent, visual-hand reactlon times becane prolonged. Sincs In Merrellts technic, two verlables - non-rclnforcement o? EEG blockede by llght and non-relnforcement of voluntary hand responses to the same stimuius - were altezed stmultansouslys on experlnent zas deslgned to koep the voluntary haad Felaforced, but to exliaguish the alpha blockade at the sanc tins. This tavolved alteration of bicrreliis techaie by reeordinj, along wlth the CEG, hand respcnses to din Iighf lnot blocking cutl and haad responses te brlcht: flickorlog Iight twhlch blocked ciphal, preecdlag the Hlght siiaull in bofh cases by a low tone. This icst was madc ca 15 subjects.

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Results Indica that alphe blcckade Is an "orlentlng" response end as suchaanot be coadltloned. As the stlmulus whlch Induces the alpha blcckede Is confiaued, blocking of alphe gradually disappears. Thls Is true, regordloss of the nature of the sti mulus -- llght or sound induces fhz same effects. lf thc stimulus is discontinued, alpha blocking reappeers when the stImulus Is relntroduced, only to agaln slowly disappear.

2.Experlmental Psychology

a.  Hospltal Project for Evaluation of Pzychotherapy. The experimental psychologlst vas "loaned" to the cliulcal divislon of the hospltal to asslst In formulating plans for cveluation of the effects of psychotherapy on the relapse rate. In addloter About two end one-helf months of the quartep wore spent In thls fask. The prellninary pllot study whlch Is belng carried out by cllntcal divislon personnel and whtch Is deslgned fo determine the degree of ameneble in all adnissions Is currently underway.

b. -Minnesota Multiphasle Personallty Inveatorles of Physlclan Addicts. The tasting of a sampie of physlcien addicts with the taiPl has been started for the purpose of determinln3 sona of the relatlopshies between addiction ond soclo-econonlc stcius, speclal group attitudes, cnd avatlabillty of drugs. The physlelon addict apocars fo prcsent a uaique Opportunity to study such rolailonships. For physiclans in neneral, the group attltudz toward addieticn and enttscclal behavtor Is negative, tec., physleians arc opposed to such bohavior. Ca the other hoad, the avallabilliy of nercotlcs ls

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posltive for both adoiet and nonaddicf phyalcians. Should the physicians
post-addict/nuve profllcs, which are simllar to those of the average eddict In the hospital populatlon, It mlght be Inferred thst pcrsonallty characterisfics are rclattvely more important In the etiolog of addictlon than are the avallabllity of drugs or speciel group aititudss. To dote, 13 proflles.have been obtalned on physlclan addicts. As patlents become avallable a group sufflclent to pormlt significant comparison with the hospltol propulation witl be bullt up.

c. Psychologlcal Dats DurIng Chronic Alcoholic Iatoxication. The data. obtained durlng-the chronic alcohotlc Intoxication study has been fully analyzcd. The most interesting ftnding is concerned .uith morked clevetlon of all clinlcal scales le the MPl durIng chronic Intoxlcatlon.

d. Psychological Changes Durlng Intoxicatlon vith lSD-25. To date fhe most slgaificant findings in this study heve been chonges In many of the laPl scoles. Tuenty-five patlents ere currently being fested.

3. Blophystcs

o. Rot Cooditlonlng Apparatus. Nunarous changes are being made in the "Sklaner box" whlch is used for study In condltionin: experiments wlth rots. The pellet feeder is being charged to a rotailng disc type; the pressure required to throy the switch when tha bar Is pressed. ls belng lowered by substitutiag s cercury swiich for the mechenical cont oct sultch3 and botter soundprooflng 1s belng edded to the box.

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be "Improvemsats bive been made ta the neurophyslo-

loglcol stimulator. It wos found that ths output Impedance of the prevlous stimulators was so high fhat the ouiput dropped to almost zero when the output Ieads wore conaected to the animal. Another output stage was added to fhe stimulator to decrcase- the Impedance. This Improved the mltage deiivered to the eaimal, but some volfage drop stlll resulied when the lcads were connected to fhe animel. This can be obviafed by monltorlag the stimulator with an osclllo :
scope.

c. Copsidarable equlpaent was consiructed for use the studles on the relatioashlp of olpha blockade fo Faviovian "extinction." t

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Medicat: Dlrector Herris labell:

"Chronic Alcohollc Intoxicatton." Dept. of Pharnecol. Untversity of Cincinnati Collcge of Nedicine, Cinclnnatl, Chio, arch 3, 1954.

"Cłialcol lualfcstattons of Drus Addicties," lualor Studeats, Cincinnatl College of Wedicine, Cincinnatt, Chio, March 10, 1054.

"Chronle Berbiturete Imfoxication.". Departnent of Pharnacology, Venderbilt Uaiversity, Nashville, Tena., Jenuo9y 20, 1054.

Badlcal Director Abraham Wikler:

C hys 2 1 +0% é ad P 1e 0 lenics # A F i524 1÷ 心 4 1 E z 5 1 inciana v+π CC41+ 5àì 主

A sgries of nian lecturas to Juator Students, Univarslty of Ciecinnatt Coilege of Redleins, during Pebrvary end Karch, 1254, as followat

A102

DISSEHINATION CF INFCRMATION

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4.Perscnnel Honors

Kedtcal Director Harris Isbell:

e., Invited to partictoate la Symposlun ca Alcohol, prior to ceeticg of laterneilenol Health Congress, Toronto, Canada, 9 August 1954.

b. Invlted to parttelpote in Symposlum on Alcchol, Joint Comnltice on Alcchol and Alcoholisa, Vorld Health Crgantzatlon, Ualred Nations, Geneve, Switzerian September 1954.

Medical Director Abrahamn Wikler:

Promoted fron Assistant Attending Nourologlat, Cincinnatl General Hospltal, to Attendlng teurologlst, March 1954.

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5. hotion Picturc Shovisas

a. "Cllnical Mantfestations of Drug Addictloo." Vanderbilt Uaiverslty, Dept. of Pharcacol.. Nashvtlle, Tenn. City of Detrolt, Narcotics Cilalc, Detrolt, Mich. Drake Uaiversity, Des Poines, ia. Harvard Medical School, Dept. of Pharmacology, Boston,Mass. Blucgrass Dental Assoclatlon, Lezington, Kentucky Vanderbllt Ualversity School of Med., Nashville,Tonn. Dept.of Pharmacol.& Chemlstry, Southern Collogc of 丸 Phormacolocy, Atlanta, Co. Medlcal College of the State of South Carolina, Dept. ofsfheraacciogy, Chorleston, S. C. Yankton Stafe Fospifal, School of Nursing, Yankion, S.D. The lastitutg of Pennsylvanja Hospitel, Phlladelphie, Pa. U. S. Naval Station, fongue Point, Astoria, Cregon. DHEW, Food & Drug Adalalstration, Minncapotls, Minn. Mif. Sinal Hospltal, New York Ctty, N. Y. Univarsity of Illinois Cotlege of Mediclne, Dept, of Pharmecole, Chiesoo, Ualversity of Nebreska Celltoge of Hed., Lincola, Nsb. Stritch Sctool of Modicine, Lovole Uaiverslty, Chiesgo Dept. oi Psychiatry, Uaiversity of Cincianati Sehool ledesincinacti, Uaiversity of Cinclanatl School of Ked., Cincianati, Chio Bedicel Stef? end Nursas, St. loseph tosaltol, Loategton, Keatucky

1 (ContInved)

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ic Curbitorate lntoxicetich Naitlcs Clinle, City of Detrolf, Detrolt, Mich. Untarstty of Vyomlng, School of Pharmacology. Laramle, Wyo.

DHEW Food & Drug Ada., Minneapolis,:Minn.

Ualversity of Utch, College of Phermacy, Salf Lake Clty, Utah

St. Johnts Unlverslfy College of Pharaacy, Brooklya, N.Y.

Dept. of Pharmacologya Ualverslty of lllinois College of liedicine, Čhlcago, 1.

Dept, of Psychlatry, Me. Stnal Hospltal, Nev York CITY, N.Y.

t Collcge of Pharmacy, Idaho State College, Pocatctlo, Idaho

Loyola University, Dept, of Pharmscology, Chicago, 1!l Sf. Anthony Hospltal, toulsville, Ky.

Vanderbikt Uaiversity Schcol of lediclne, Noshvltie, Tenn.

C. "precipltatlon of Agsilnencs Syndromes by use of Mallylnorncrphtne." Medical Divislon, herck & Company, Raheoy, N.J. Medical Divlsion, Sherp & Dohme, lac.s Cest Point, Pa.

"Experihentai Chronic Alcoholic Iatoxlcetlon." Untversify of. Illtaols Coilegs of Ned., Chicugo, Ili. Untversliy of Cincianati Collzge of Wed., Claclanetl, Chio,

C. "Lower Lieb Reflex Changes During oCycle of Addiction In toplnali Man. Nedtcal Division, Sharp & Doame, Ine., "est Polat, Po.

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Dr. Y. T. Cester I Strltch School of Madiclne;
Dr. Donal CtSyilivan Loyola Universlty, Chicago, Il. lanvary 1954.

Vanderbilt Unlverslty School of Medlcine, thashyille, Tean. January 1954 Vashington, D. C.

Dr: J. B. Kahn, Jr. 1 Untversity of Cincinnatt College of Dr. George H. Acheson: Medicine. March 1954

Long Istand Biclogical Assn, Long Istond, N.Y. March 1954

Visitors to Reseerc:

Herris labell, M.D. Dircctor of Rescarch