IZ N IT el.,VI c@N Adft --- - ------ oll ly ei rt, ---------- 7 ......... . 00 0, .0. 0 Cl This File- as reviewed oil w 1 5 juN 1971 --for Drug/Behavior liodification material-responsive to FOIA requests. /-7 N6thing-responsive was found. 0 The-f6liowing documqn"-were considered responsive aiid sa.nitized for release or released-unsaniltized lk f,7 oil Now VERSITY 1(:L or. CONI ROLLEit April-29j 1960 We are PA-tolosil -fit P---icial- @g@@our2 1 1959 to Febriiai-y 293 1960o :Lo eLteiT,-'oer d S Sincerely yours$ 9 Assistprit r Financial Statein--nt Septen-iLer 1: 1959 to February 21), 1960 Baln.nee -'ucust 31, 1959 15)02.5,00 Salaries 0 711 :-;qUp.nent 25,423-LO Supplit--s 2 tl7o67 TNTAL Expenclit-,ires Balp.-,ce -2ebruary 29, ig6o (.oeficit) :4, (471-07) In(--d alna apyroyed the eubmit'od OXOLM 2 TSSICIIQ,,,)Ical Divir3i.On NIVF.RSITY- ol@, coN TROLLLF, November il., 1959 We ,@re enclosing our financial stiten-on't covering r the year ended Auurtist 31P tant Controller UIIMPSITY Financial-state.ni@,,nt- Septeiii'op,r,l.. 1958 to August 3ki, 1959 $10,815-09 -palance Au,,-uet 31, '@958 53 2 Funds Rece-,@v@-4 j-9P-.2 - 00 7417S7--0-9 $3lp963-76 Fellovships 1)000.00 556-05 2 Travel .rquipw.ent 11.,351-03 4 851-25 supplies _@9 722-._09 Total Expenditures 5 B,-le.nce August 31ii 1959 @O tD CIL UNIVERSITY--- Ap,-t-il 28, 1,D.6,L Drr Staf.1-1;@s ini-orred ne - u-r office hn@s 'never for 40 the yee,, 1957-'@8., c,),zeriiie, c-xr)endti-. 4lbil 0 III o at-tlialt-I tinie under 'k,he directi.on of @@-e Ve o2--@-e enclosinc a copy of 'Llhat-f iiliich our records sho@.., was for@-i-arded on-l@p@il 13,-1959- If we can be of fu-rther assistance, pi.ease 6o not he@,@-it-@Lte 't-lo call ol us. 9 Sincei-el,, ,c),lrs Rese.-@rch sor F.ne. COPY rinanci-al 1, 1.957 tO 1957 t, '15,053 .(O Received 35 3'@0-00 2 50)3@')3-90 3x i-e@- Jr, L-811..14 667-00 4$C)52-59 4,589-90 2 4,800.18 Reno,,,Ielli-nf-- Ani- I!o-.".se 93967-00 To,te.1 LO E,al;,@nce A!-I@,7st 31,) 195@A 4 tIl 27 DeceTiber 1960 tient you ploo.,sesetid us a c-Ony of the fiLi),-lncial State Will of the 1957 7-to 31 AuZ4$t 1958-- In e'P-eck through (ur project-files ve find the abOvO decount- is sincerely yoursy -M- D UNIVERSITY 4.)F C(NI V,01 1.1:y February 3) 1958 Ife a-re en(-losina our fi a,acial statement covering the t-',Iie period June 1, 15"5' to Au,@u@,t 31, 19'57- iquid@it.on of a L outgtanding will-be reported at August 31, 1958- Assistant zt @Sil"Y Financial St-iterient -to August 31., 1957 June 1, 1956 r,alance Jt)r@e 1, l@056 157-13 2 30j'l(") - 00 Funds received 30,557-13 Expenditures: Salaries $7,875-82 EqL@ipoierit 2 ((3 -)@l Suppl-ics 2 Y,aintenance 1,214.69-- - lkrave-.'L 0 Total expenditures $15,053.,00 Balance Au.-Ust 31, 1957 it, ou2tst-anding co@ i, R,@nts: suppl-,Ie,4 and $4,131.84 Rerr,odL@ling aiiiiril l@,ou*e 11)2qo!i.- LO - 14jl l.P-4 Total colilini 9 922.o6 Unco-,-,,riitted balance AuGust 31, 1957 I have examin,@@d .14 approved tho expenditurc3- 6 April 1960 'ianol at tile r.-,,etat,)oli^@m on,ett Yotir roeicarc'ii prc>.rj-,DDa 2 K6.@rovc.@cl-by oor f)oard of A ch--c@. for dad herewith. i3 fO&-k-la-IC Tiie abova iisor .ioo ,,ro of your alc(>1101 2 niet-,bOli;3m studies aid are for a- poriod of -one year. tt,.it a 0 be rr--tdered 3t %ry ,iccounting It i-9 reqa-3 2 -v4hic,i w@is ei,totided utitil tha reoidual balance -v-ins on tiie rosearc%i in i3@-,ofyresa. -Jrcemcnto relatiti-,, T* i-s furtlier 7 cccour-tin,7,8 is well as t.@ic return to of enq ttic to.-minztlond@@, 1;knl)r to RECEIPT I hereby acrnowledge receipt of -the followii-.g checks,. Cashierl:a Check No. A239594, dated April 5, 1960, drawn on the @in the nqW amount of $17, 940. 00, inade payable to them@4@@@ Official Check of the No, G40663, dated April 6. 1960, in the amount of $717. 60, payable to the to COliFIDEill@TIAL FUNDS POSTING VOUCH'CR VRUCJIER NO. 7@ I Z DATE 2- 6 VOUCHER NO. 7-12 43 4 7- 5 2 5b-67 68-70 71,80 2 153 54-57 A.0 UNT DE$CRIPTION-ALL 07HER ACCOU14TI 13-.3 34 45-A6 410 .1,2F OBLIC,. ALLOT. OR COST ;UE 2 'PAY REF. NO. ACCT. NO. DATE D u GENERAL .......... ...... 62-67 OESCRIPT ON- 2 CODE CA LEDGER ADVANCE ACCOUNTS 13-27 0 1 a I v C P E 0 1 T PL El IPI CK.NO, OBJECT . YR ACCT. NO. 2 ........ ....... C D f 0: CL,%Ss bLS3,p;;J,Ecy No. -FY x REF. N D 0 A T 2 11 p s . . . . . . . . . . 7-T EXPLANATION OF ENTRY TOTALS ---JREVIEWED n't 2 ERTIFIEO FOR DATE REPARED SY DATE c PAYhiE,'AT OR CREDIT DATE IG@NATUFE OF CERTIFYING OFFICER 4 C iC.-AP) use pol.lous toolle*S. in p Zo .1@I.-kreh 1960 10"4 U. Z,. i Z C;T 1-1,1-"U.LT,.%A, 56. 1-4voice iio t )A 0. p -ayable kill to tO C"teA @6 3 ID C-'l Z., It C@-.1 FJ 9 a n by il. 0. t.-ivt@ic-,. 4ioviever. Esi.rce it ls-zotic-.F"@_tod A e ri r, D r, ASS 8 2 TSD/GB LI i@-t-. r look INVOIC-,R r service!3 ....................................... ......... T I' Ai (1) It is it@---re-av cort'%."icd th-@t ttils Is iTi-olylij to SLbpirojectl 56 of tti@at LqLervicei3 ire in accoru'a-aco-viitli zi-iL4tual a de'vailc,-l aqc,-tda of' it'-ic 2 is filc:%-14 iki tlkl,--@t tl-.i-3 bill is j#3ot n,-] correct that ,roayznoo%' t'tiieroof tiao no'll yet bc-on made. Ct T6D/Ciiciin.c 17@.;, a (Z) It i-I tll,-At t.1113 !!IVOICO to .00tlbnrojoet 56 %z.,as dtily a@ip.-oved %r.6 t@.@it the project is C- 7 t-t-d - 7@@ .Irk@m t.@ic DCI of this ,*y A Eta No. Cost Account Object Class Obligations Obligations Unliquidated Date Ren-tarks and References Incurred Liquidated Balance -4,o APR -4 @@,"Arch 1960 ';AT ek at,,* Lou of t tL,3 @ricl to tlio 2.,v -z.-a t%ljd 'to gul-@>7 @@cttti a ',-.o u -4L PIAS:L .0 maw1 V of: 977 D R A F T 9 blarch 1960 MEMORANDUM FOR: THE RECORD-f@@@ ------ ---- SUBJECT Mi',@-ULTRA.-SubprojectNo. 56- 1. The purpose of this project to provide funds t2o continue a rese-arch program This program is designed to exploit-all the knowledge and facil!ties-avallable at the in Rrqvyi@d@iniz information of direct interest to the Agency in the area of alcohol--inl%"oxication. Specifitally basic- ----information requijred to-2-provide practical ansv-iers will be developed,-- A proposal for an extension-of the--work during the coming year- has-been eubi.iiitted and ia attached herewith. Ek@e@tive of the Department of Neurology at the was the principal investigator on this project.' the dir2ection of the research-in the hands of the Acting Executive of the Department of N.eurology, @lt has been deterrnin-ed th,-tt the research program to be pursued under the budget propos@d herewith will be pursued in a diligent and fruitful manrier. 3. The ikiti.@s for this project will l@@@ftfred using the 0 t in the usual manner, ltv of: 499kfw 71' 4. costs for this program for a period of one year are ,estimated to be 17, 940. 00. To this- sum must be added. a four per -cent making a total amount of $18,657.608 fee to ale against Allotment.,0525-1009-49oz. Charges should be m a2s requestea accounting on an SN"Oalmmmwmww to submit to them a alimtnar)y Any unexpended Sig of all rn(ckies recvived-from anaual ba turned to the fun2ds remaining ormination ill be re tt,,Isl informal accounting on the part 6. The requirement for a six rnon of the principal investigator i!3 waived,------ Title tc# any-permanent equipment purchased by -flinds granted 2 shall be retzkane-d- lbkia lieu of higher overhead rates. 8. In connection -,,vith travel undor this projectt it is agreed that the Agency will accept the trav 1-doca-menta-ilioa-and accoul)ting wi-iich conform with the practices 9. It is agreed that technical2 r'eports reflecting the progress of am shall be submitted at mutually -Lcceptabile interval the research progr 10. The project is unclassifitd after it lc,%ves ",@>ROVED FO]l OBLIGATION OF FUNDS: Cficf TSD/Clieniieal Bra1ncti Attachinclit: Proposal & 13udget OP V. PROPOSAL We are desirous of continuing our research activities on measures aimed at permitting conntxmption of larger amounts -of ethanol without an increase in overall nervous system depression. -Our research to --date (see technical reports) has brought us to a better understanding of the intermediary metabolierii of etha2nol. As previously reported, it appears that the limiting factor-in tiie-rate of disappearance of ethanol from the body is due to the 'relative rat* of conversion of ethanol to acetaldehyde. - Any measures that can -incr6ase- the rate of this reaction would certai-.,-ly reduce the overall effects of ethanol-upon the nervou's system. - 2 -@;f Currently, we have established a- coordinated clinical program of invegtipatioti with human volunteer subjects in the, 'ed and affilial. This, of course, would o-pon 'up many new vistas-and avenues-of approach and investigation. Therefore, it is our proposal-to-continue to conduct our -research activities as foli',ows: The continuing program-of work. ill be biologi- call.y and enzymologically. oriented to-determine the steps involved in the intermediary m,,-tabolism of alcohol. 14 A. A cornaari3On-Of the-incorporation2-of acetate I-C and 1-.; ethanol I.C in fat fractions will be rnade to determine whether-the pathway of ettianol metabolism enters-the acetate stage. B. In view of the fact that large doses of ethanol will inhibit----- methanol met,@bolism, attempts will al-s--O--b-e-made to compare the path--2- ways of methanol vs. ethanol metabolism. The influence and effects of catalase, botti in vivo and in vitro, upon metllianol and/or ethanol metabo-. lism will be itive3tigated. C. The role of alcohol dehydrogenase in reducing glyceral- dehyde to glycerol and its relationship to the- effects of fructose in in- - creasing the rate of ethanol me0tabolism will also be !nvestigated. The - iniplications in this specific instance hold-great promise towards devising' an antagonist ctgainat the depressant effects of ethanol. WI 11 t'; 0 T AND BUDGET 1. PERSO&NNEL Professional Services Neurologist (,t%-I.D 1/4 tirno Neurophysiologist (M. D-.) 1/4 tirne- -O- Enz)nnolcgi5t (Pli" 0") full time 2 8,600 Reaearch Aesistant, full tirno 4. 200 Subtotal $ la, 800 11. Su olies .@@ (expendable) Chemicala, -lassware- ztc. $ at 0020 Ill. Experiment-:kl Anit-ials vm*ll) 800. $ 158 600 uni""itT@6V@hi" 15010, 2,340 $ 17,940 5 G iNO'l C. 27 Novomber 1959 lia3 .n a sezisp, "loft the ohl? rudd!@@r". I I-ave been -C. @ive of t-he De2art- o,@@ i,.Ieltrclo-Y in2 tnd unavoidable -aa resiiltcd in @ily d--liy ii-i preparing mmopm previf4 1959. It was 0".@. r.,Lo for bot-@, resc,,,rch s.O2cLce and peraoz-U-L@.,l been ire-r stii3jf:!ct to yoti.r is of to rrleat o--ir cur@7,1!r.4 @Z, erefore, I your -ant 2 on-lit\:re:3 us @-ii c@ ye,-.rls th.t, ,sued. ))u@a to ef t!-.0 Nnd tlie cortinuance 2 enclositig tv.-o rlcr y,)i:tr Qur e r. cli-ii--al proL-;rai-ii of iiive--l"icl Your suil-,ort L)f III-Ls h@@.pa -v.-c able ('@o yo@,,r u@-id continue to Very t-ruly yoir.9, 30 September 1959 -,1,4EMORANDUM @FOR: THE RECORD SU13JE6T - : Extension of Subproject 0566 expiring 30 September 1959, is extended without add;-tional funds for a period not to exceed eight moaths or until the balance as-of August 31- 1959 i-e--e-x--p---e-0-ndcd--- Chief TSD/CK@6Mical-Braiich RECEIPT I hereby acluiowleda ,,a receipt of the follcving two checks --dated Octob Cashior's Check No. A209-870 8 drawn on tl-ie in t2he amoi-int '7f $-5@@22, @a e@jay-abl-e to Che *%-PJMW i official Check of the No. 209-345465, dated Se-otemb in the amoi-int0 8, payable to -30, f $2,15 7 Date: i ii: !limb - - ----- ----- - - - - - - - - - - - - - - - - * lying to @,roioo l@10. 2 tiu 56 COX-e-^Ct li@- t@s b,@zr.Ay ii-io iwloica to Subproj@,.Ct 56 r-@d 2 o'v- It r, 13 19';3 ti@,3 WI to oz rate t of: smmdw e 1)77-- 17 Septeeoer 1958 bTtIORAMM FOR,. THE RWORD -SubiroJect tio 56 SV@@t, 'XT RAULTRA, 1., Th2e purpos.- of-tbia-project is to provide-funde-to contiuue the research -.oro at -program-is designed to exploit all tthe-knovlE-Wand-fddiliti6474"ilable to-ite-director--- in pro2viding answers to interest to the AZ--ney in-the area of-alcohol intoxication.--rn 6dditi6d@@tb666 areas of basic knowledge requir@.%d@@@ido-these practical answers -will be developed. 2. has submitted the attache2d progress report-and a p,-orosal for an extension of the-Vbrk duriWtbe-coming-year,-----It@-@ should be noted that three I)iibliati6db@- bai@dd766--the material covered in the short proe@-ess report-are--r)resently in proS3.-Inaltided as a2 a- proposal ft@@ ---part-of this project is who is working in IF laboratory woef. vill make available a much better indicator of ftlcoholic into;tication then is now available.--.Pi-csumably it will 3 Talce possible an absolute a-,e"ure of phyriological impaiment due to alcohol vloic-h will In tura materiall-ly aid in the final pbp-r.,es of the g(.,,nortLl vor'K. ty of; 4'tte: DOV,,N by 'tut yof 77 2 CL 12 The funds for this project-vill be transferred using the - cutout in the I usua 2 one year beginning-7 4.- Costs for this or ALlgus t31, 1958 ar--,,-estimated to b-- $53)922.00 to vhich must be added a four percent (4%) fee to-the-im $2,156.88), making-the,, total amount $56)078.828.-..,Cbargei3 should be made against Allotment 9-2502-15-90-5.-- 5. has requested we to submit to them a zummary accounting on an e=ual ved-from ##IN bqsis of all-monlet recei Also; it has bee)n requested that any unexr-nded funds-t@@@@@th6-@@ of the year. 6. informal accounting on- thA. iert 7.- Title to any_ rmment o ipp@@ purchased by furds granted be retai--ed- by in lieli of bi8her NNW overhead rates. In-coanection with travel under this rroject it is agreed----- tbat the Agency vill accept the@trdVV1 dddUd@@@ion and accounting-wblch---- 7Conform with the practice-s of 9. It is agreed that-t4cbnical reporte-reflecting the progres-a of the research progrrtm-6haU be-tubmittdd at mutually acceptable intervals. D eed to by out I dtit(,@: ju! 977 loss& @AC.A to: 6 . . . .; t j.X 1)77 - --------------- '10 is cle,-xed through TOP SECRET and is aware ---of the true purposes of the prog - He ha4-also agreed to comply ram. 2 -of the Vomorandum of Agre6W t. vith the requirements n Chief TSS/Chemical DiVigiOd APPROVED FOR OBLIGATION Op MW' arc.h 4 Date: @'i Attachment: Pro&ress Report-and Proposal- Distribution-. Original by, (!O@ t OrIty. of: swap ID7? PROGRESS REPORT -7 Research on AjitaWnists to the Depressant Effect of Ethyl Alcohol As an informal interim progress report, the followlnc., research for this year has been complete2d and is in preparation for publication. The prominence attributed to the use of tri-iod-D@thyronine as an agent for rapid "soberip-g up"- has- not -bee-ii-substaii-ti-ated in our laboratories. 'Flie dosa,(,re@Tof tri-iodotliyroiiine used exl)crinientall-@ in our dog2s were, astrt-viion.i.ical in relation to the usual therapeutic dose in man. Amazili, y, the (logs tolerated the hi,,Yh dosage quite well and manifested only a rise in body temperature and ircreased p,@Lntii-ig. The effect of tri-iodotliyronine on the rat2e of alcohol oxidation was neglegilile and certainly not, more than that noA-Mally catised by tl,.e increase in body temperature. 2. Pyridoxine TIv effectiveness of pyridoxine or vitiniin B6 is essentially the same as that of tri-iodotbyronine. It is difficult to accotl2-it for the reputation recently gained by both pyrilloxine and tri-ioeotliyroiiine in ttie press witli- out the support of critical ex-perimeiitat data. Perhaps this can be accounted for by the fact that the effect of a rib-i-lig concerltration of alcohol in the Liloofd c!oes not have a linear relationship to nervous system depression, bLt rather a lo-arilhmic one. Therefore, there is a critical concentration below which the iticlividti,-d may appear relatively sober iiid ibove which, by c very small niar,,-iTi, a few niilli- grii.ms/100ce, a coiisiderable doitioiifti:ak)lc dc--re-c of intoxication is present. I'llerefore, any a(,eiit, witli or without any appreciable effects on the rate of alcohol iiietal-)olism and/or concentration, c,,-iveii at 7tiiis critical level, may give a spurious impression of an exec-lic.,it alcoliol antagonist. AN') @)LVEI) 3. Alcohol metabolism in mice The effects of glucose, fructose, pyruvates alanine, glycine, glutai-nine, gititaniie acid and aspartic acid on the rate of ethanol metabolism in vivo we-re studied in mice,%vitli equivocal results.- Data obtained were extremely 2 variable from mouse to mouse, as well as fi:otii week to week, in spite of the large number of animals used. There is strong indication,@that the mouse may possess metabolic patlinvays for ethanol that are unique to that specie. 4. Alcohol metal)olisin in-dogs Various compounds istudied showed a def!Dite effect in promoting an increase in the rate-of alcohol-me-tabolisni. Glvcine-shoNed an increase of --- 25-50@o'; alanine 25-6070, and fructose, v-ihicli gave an increase of about 2507 Glucose, pyruvate, tri- iodotityronine and pyrido.,tine slio%ve-d no increase. - In the case of acetate, the converse, a slonvliii-q of alcohol nietabolisni-seen-ed to result. S. In vitro studies on rat and mouse liver slides 13y.perime-nt@s,,.,iith liver slices shoNved-V@ia'L-Iiver from a fasti2ng animal metabolizes alcdiiol about one hilf as rapidly as that. from nornial-anin-lals.- - Steps were initiated to-ti-etermine,*vliere the block in alcohol metabolism by liver slices from fasting rats maTQccQr. The -most likely startijig place seemed to be the first step in oxid2ation, the conversion of alcohol to acetalde- hy(le. Since the necessary coenzyme of the enzyme mediating this step is diphosphopyridiiie riticleotide, or DPN,--tlid-first experiments were designed to determine whether the coenzyme is deficient in tl--e livers of fasting animals. 2 Our exl)eriiiiental measurements shonve-d that DPN W as not deficient in tii-c livers of fasting aiiinials. Attent:io.i.i was next directed to the enzyme itself, al'cohol deliydrogenase. Livers were assayed for total content of glcoliol deliy(Trogeiia2se and it was determined that fat3titig aitimals had a higher concentration of the enzyme. Sin-te the equilibrium constant for alcohol dehyd-toa,-enaqe is far to the left in favor of alcohol, it would appeir that if the concentration of acetalde- 2 I-,,yde rises, the rate of alcoh(.)l oxidation would I)c slowed. ThL@refore, seiiii- c.arb,aizide, -,vhicli couples with acetaldelilde, was ad-clod to the incubitin,,T nictiiutii. Our data slionvs tliit the addition of sen-iicarbizide L2lid not clialiae the rate of oxid,-ttioii. Moreover, tlic-. addition of eitlier acet,-ddeliyde or acetate did not change tl-io relationship. Thus it-would seem that the accumulation of acetalde4yde did not iiiflueitce the rate of alcohol metaL)ol.isiii. 3 (TICE %IVA Rt\li -2- GE-'.NCE NXIOLVED -'I'Iie posqibility that the rate of oxidation and reduction od DPIN may have a direct relationship to the rate of alcohol metabolism was investigated. The reduced DPN molecule (DPNH) must be reoxidized to DPN before it -is available to oxidize another molecule of etl-ianol. Three compounds 2 capal-jle of reoxidizina any DPNH v;l-tich mietit accumulate were tested niethylei-ic blue N%,I-iieh acts as a short circuit betnvoon the flavin systerti and oxygen ; ferricyaitide which directly link-s DPN'LL and oxygen ; and py-ruvate which in the process of being 2enzyiiiaticall.v reduced to lactate oxidizes DPNII. Experiments show that py'ruvate increased tl-.ic rate of' iiietabolism in both the fed and fasting animal livers. Mothylene blue and ferricyaiiide raised the rate in the fasted animal livers, ibtit not in the fed. From the promising leads above, inves2tigation of the actual state of - oxidation and reduction of the DPN in liver was underta.'-,en and is noNv in progxess. S. Radioactive alcohol and acetate The deposition of radioactive carbon in the tissues of mice fed r,,adio- active alcohol or radioactive acetate i4ndicate that the metabolic pathvlays for both alcohol and acetate were very si.miltr.- A TICE 'F'; A.%C@ NVCL.VRD August 22, 1958 Genaemen We are desirous of ct)jitiiiuin-a our,;,iork- further on measures aimed at 0 peryiiittin,@, cinsuii-tptioii of larger aiiiotiiils of 2ethanol without an increase in 0 nervous system depression. - ConsideraLle progress has been made in our research pro,,-,rarki since September l-,- 1957 'llie attached pro,@-,ress report summarizes our r@search completed to date. Di the2 past year, -Nye have made tremendous strides towards a better widersttincling of the intermediary metabolism of otlialiol. 'it appears that t'!-"e limiting factor in the rate of disappearance of ethai-iot from the body is due to tiie rate of conversion of ethanol to-a.cetaldeliyde. Aiiy measures that can in- crease the rate of this reaction would -reduce the overall elf-ects of ethanol on nervous system depression. Moreover, we are noiv in the position-of belng al@le to conduct clinical experiments N-vith human volwi.teer subjects. TI-tis, of course, opens up many iie,w avenues of approach and investi,-ation. Provided,.ve are able to obtain a sl,,pplemental r --:w @,iak-llmm .-- .. IqW.fcr the comiii,- yea vilid-l@ at milow 2 call onduct a series of experiments to dtert-iiine whether or not tr@i.nqtiilizers exert a synergistic arid/or supplemental effect or action upon the usual rate ijid degree of a!cqhol intoxication, 7 L v SINS EL c L 3 OLVLD 'Merefore, it is our proposal to continue to conduct our next year s investigation alorg the following lines 1. Expedite the removal of alcohol from the Illood stream tlirough -selective metabolic patliways. Prel,im,inary- studies indicate that glyc2itie . alanino and fructose m@Ul increase the rate of alcoliol metabol.isni. We plan to determine whether or not these effects are statistically significant.' We also intend to continue studies on the interiyediary metabolism of alcohol. Experiments have been forinulttted to cletertn2ifie the effects -i;- the effects of pyruvate on of lactate on the speed 6f alcohol nietabolisn the DPN/DPiNH ratio and the use of another eazyii-ie system, such as the oxalo-acetate-mal:ate one, to reoxi(lize the DriN coenzyme so necessary to convert alcohol to acetaldehy(le. 'nic use of radioactive alcohol will be continued in the study of intermediary n-,tetabolism'pathx@,a, s@@After iiic,,-estion of radioactive alcol-iol, varicustissues and fractions, including the -%Nater soluble fraction, pliospliolipids, non-sapo-,i.ifiable f ractioii and fatty acids will be isolated and their specific activities determined. 2. Determine the effectivenessof various types of fat and fat products in delaying the absorption of alcohol from the gastrointestinal tract. 2 Preliniinary,%vork demonstrated that fat will delay the absorption of alcohol from the gastrointestinal tract. We intend to initiate clinical studies on the various types of fat in this respect Expressed fats and ofls, tlieobroixia, butter, suet, -lanolin,- kaolin-and gastric rtiuciti will be6 investigated. The effects of wine buffers on the rate of absorption will also be iti:vestigated clinically. .2- XIV t,@ R sc@)SI'Tlkl[ L C - S il,4 D t,'. 1-i'VOLVED ru in 3.--Deteriiine the effectiveness of sympathominictic d gs in delay g the absorption of alcohol from the gastrointestinal traot. --------Sincetheabt;oj-i)tionotalcoholf,-2conitliagastrobitestinaltractis related to the emptying time of the stomach, the effectiveness of various syn-tpattaotti,imetic drugs, such as iiallijic, Donamitic,, epliddrine and others, "I be investigated. Il2le fonoxviig is the liroposed yearly budget: I Professional services Ne-Pirologist ( MD ) half time $ 5,000.00 Fe.ilo-,Y, neuropliysiologist ( MD 2/3 time 7,200.00 F,n:,.ymolo-ist PliJ3 ) f"l time 81500.00 R Teclijiical services Technician, laboratory 4, 800. 00 Secretary 4,200.00 LaL)orator2y, an.iii-tal I-ee-pe:r 2,000.00 - IH Clinical subjects 1,500.00 1V Eq-aipmcnt and apparatus 1,200.00 V Supplies, expenda",)Ie ( radioactive alcohol, eto) 2 2,000.00 'VI Larp animals ( iriel upkoep 1,500.00 VII Travel ( alcohol nic-,etings 1,000.00 Sub total 38,900.00 Univer2sity overheid 14% S, 446. 00 Total 44,346.00 -3- @VARN l'ICC- -S C t., -Z I T I V E '-NCE 0 @IVOI@VEI) The research proposal and budget for nd his added researcii activ-lties are attached. His proposed re-search-wotild certainly yield invalu.able data specially suited foryour purposes. We are extremely grateful for your Wnerosity in supporting us an wprc,, it 2not for the extraordinary opportunity of liaving p=W with us, , we -)Iemental MIANK. At this time however, would most certainly not request a stipi we feel that this opportunity should be exploited to the fullest.- Your immediate attention and consideration would be greatly2 appreciated. Sincerely yours, Professor of Medicine Neurology -4- SEt4SIIIVL EI.LI L%,CE t @tt tr's@"C C I@ tri t, ED @D CA 2 CO,u KI; 7 C)rn % t PROPOSAL To determine whether or not tranquilizers exert a synergistic --------and/or supplexi-iciital action upon the usual rate and degree of alcohol intoxication. INTRODUCTION The present day definitions of anxiety and stress remain in dis2t3ute.---However, anxiety can be considered essentially a human function because it is associated with the cal@tacity for delayed re- action, setf reflection of motivation and the capacity for projection of the individual into the future. The concept of stres@!i'@-e'volves around the arousal of anxieties. In general, anxiety may be aroused -by any conditio2n which threatens the integrity of the organism. Therefor e. any stiiyiullis nity, in principle, -arouse an dnxiety res - ponse because of the particular i-iieaniiig of threat it may have for that particular individual. Ho%vever, we can distinguish a class of stii-riuli which will invariably produce disturbarces in-rnost in- dividual2s. The term "stress" can be-applied to this class of conditions. Acute stresses and anxieties with in our social patterns of - behavior necessitates the use of tranquilizers on the part of many persons to adequately meet and cope with these problems. Often titi-ies people will partake-of-",%-few tranquilizers" prior to going----- o2ut for an evenin--of-social-drinki-ig and partying-. Ilow does the combination of tranquilizers and alcohol affect the motor skills, sensory processes and ciritical judgements which are not normally affected by either tranquilizers-or-alcohol taken separately? Therefore.- the following coiirse -of investigation is proposed:-- To2 determine whether or not tranquilizers exert a syn- ergistic and/or- s-,ii.)plexllental action upon the usual rate degree of alcohol intoxication. 1. Desitn and test methods involving clinical subjects which will-descrit-iiinate betnveen norn-iill tranquilizedi- 2 alcoholic, and tr;inquilized-alcobolic states; and for particular and spcc-i,fic-states-or effects which can eventx,-ally be related, to overt behavioral responses of a sort whicii entail soi-i-ie possiL)i,li.ty of practi.ca,l exploitation. Z. Valida2te the above methods and effects in normal Iiiii-riaiis and relate them to alterations in 1-nood and behavior in as objective a fashion as possible. The above rnethodolooy will involve the use of a Nystagixiograph, electroencephalograph (Lead 11), Breathalyzer, Polygraph, and Drive_U er. Biocher,,-i2ical rnethods include enzyri-atic and bio- chemical d'eteri-iiiiiations of ilcohol levels in blood, urine, and saliva. It is envis;oiied that at ilie end of a iiinety days study, some -ive dat-i., will be obtained. 4c definitive answers, substantiated by 7objec"6 @v IT t@ C F@ BUDCTET 11 ing is the proposed ninety days budget:* -The 0 ow 1. Professional services -- - -a. Neurophysiologist (MD) $Z400 (Full tirric) --- b. Neurophysiologist (MDI'., (Half tii-ne) c. Neurologist (MD) 1050 (.I.=,falf time) 11. -1 echnical -services b. ici -Bio-Chei-i-iical 2 -- a. Tec n an, 1200 b. Technician,-Neurophysiologicat--@@ 1050 c. Electroencephaloa rapher d. Secretary II I. Subjects, Clinical----- .1500 IV. Supplies,, Expendable 2 300 V. Equipnient and Apparatus------ 900 Sub-to tal-- 8.400 1176------ ",,VI. --Woverhead (14%) 3 957 Total T7 6 *'Phir. bu(ir,,,et has since been extend6d to one year without cha)i@@,e in funla. CD 22 1958 o i3 the above a!,-* follows,., in c@f $53,cl-'?P--00.2, dmvn r. a ior a in iYLe of- 1.5ri .&3, d rawn checi@,@3 td to Clileft Div', !,.'Otiday, 6 it N;ill 'fe@a [7@ NW--A& zi!, t:; u 0 2 Kim I I'l Igo rxECEIIIT tho folloving tvo.obeelti3:- I haro'by eclcnOvlcd.,t-oO receipt Of on the W,22o.oo.. ma2de )t, 0-ato& April n-tbe Lcp 6562 CeLshierle-Chock 110- t of $1,048.80, drava-on amoun 4@ payable to 3 -IN a Da 0,., f i 'c r - - In tlie of :2.-,o oo clc-..,,@ck ii the of 5%@l dr.-@"4n 2 Ikii--- ei-le,@ks to re o@ r,nt!3 t"la tO',t',l -"'t JS 6 -IV @xt c-A pro-ject, 1-hA3 ---Now r IC) - - - - - - - - - - W 40 t c,6 c@@ t,: L-4 riot Y-_t 2 Cal 1:ivicl(--..,t to Ir-6 ":,45 3 vo Da RECFIIPT ipt of the following two checks. 1,,creby acknowledge rer-o d,,ted August Z3, 1957, drawn hieriq check No. A176790, -Cas 2 in on the the arnount of $13* Treasurers Check No. 68094 ---..'aated August Z3. 1957, draxvn on in the aixiount the of $5Z4.40. DATIE@; 4.@ f; Lt A @N v 1.1 Ti 3 II..voice viiii It i3 of 0(2- d --awn 1', L- rscheck iii tlio zi oltia $"?,4-40, dravin o4 -o to ttic Chief, 2 h I-at@@r tiian lpvoic,@ @-!xd Certitic.-itio-is i'@ it t"t i o -1,@ t r r TSS/FASB '6SS/CD $13,634.40 For oer%,ices .............. ------------------------------------- ------------------ is It -Ivoice tNo. 3 @p! iviii2i to Subp,-oject i.-, b @-,U LT c-atic-Caelory. cervices are beirifr f.) r r@ L-i @iccord,,.P-.co thi,t a cletai2let.'l agondv of tz,-o T,)'/'D, I!apt this. bill in ji-idt and and is c)ti i @"> %@, ha$ r;o'.' bCC-.'l 2 'i@ ',i/C on-kical I)ivioion p@ ate-. (2) !:, is 'tiereby certified '&'tiia-irivoico aro bproject @-l.6 of lies to St, v@,hici-i wtta d@tly @i@6-proveeA, .,rid t-he @ir iict is carri.@,e@ in d-tcd 13 April 1953 froa:.n o@;le DCI Lo DD/A. ind oi t'@iis w,,ttliority in rtibsequcnt D t APR V'N ",/,;I L.;-A4 t.@-to extension of t,tis s,-ino atitli-,,ri v an adf@iiticri@Al &ujai o r ztut'iorizi,-d to cover tlii! @t tol-ki. C-f (:7;@te!j .1 ti r i.-I 'i@;y i?) !3 i- ".IC% AI 7 4i 57) t F T / Aki' ff" pril 195'i@ @7, ME,rvioliANDUI,l r-OH: THE RECORD MKULTRA Subproject No. 56 SUBJECT: 1. The purpose of this project is to provide fund continue at NOW$" the research program conducted by ..... This -pr6gran,@ is designed to explo or in providin@t 11 the knowledge and fatilitie.5 availa2ble to its direct a answers to specific questions of direct interest to the Agency in the area of alcohol intoxication. In addition, tho*e areas of basic knowl-- swers Will be developed.---' edge required to provide these practical an It sholild be noted that although the attached proposal describ2es the facilities which will be used in the study. the program itself was deliberately described in-generil terms in order to comply with its unclassified status. 2. Attached is the research proposal submitteci oy requestina a renewal of the project for another ye'ar.-Accord- ing to his interim progre2ss repor.,__consi_derable progress h-as been accomplished; in a relatively short to wit: additional -period of time, laboratory facilities have been equipped and placed itil-6,functional state, additional personnel have been recruited and specially trained, and subst2antive research completed to date and now in progress. 3. In view of the above, it is desired to describe more specifically the vaeious phases of the general program to be initiated or continued as an extension of research activities now in progress. (a) Expedite the removal of'alcohol from the blood stream by selective Ynetabo2lic pathways that will allow the alcohol to be stored rather than completely metglbolized. , Studies will be conducted on a number of agents ciainied to expedite al--- cohol metabolism (at,,-titine, pyruvate, fructose, alcohol de- hydrogenase). (b) Determine the effectiveness of foodstuffs in delaying the -absorption of alcohol from the gastrointestinal tract. In- vestif!atioiis will b@@-tWucted-on the effects of various fats on the absorption rate of alcohol. The effects of gastric m@icin, kaolin and wine buffers will also be determined1. (c) Determine the effi@ttivetwss-of syiiipathon)iziietric drugs in "LIlwi jjei to; "low I ty It,, Ity of, ROW* 1,477 CL I a to,. 'tY Of:- -*wow b-f P--,! ri 2 1-977 eate: j 13Y the absorption Of alcohol from the gastrointestiiial delaying tract. The effectiveness of various syn-,pathoit)iinetric drugs on the emptying time of tiie stomach will be investigated on larger animals. (Aml)li-.-tamitie, Nalline, Bonamine) 3. The funds for this pr I be transferred using the ut in 2 as cuto the usual iiianner.--- 4. Costs for this program for a period of one year beginning A ugust 31,-1957 are estimated to be $39.530. 00 to wi-ticti must be added a four percent (4,lo) fee to the ($Ijl2 57 3. 2 0 Charges should be niad e ag n-jal-ing the total -amount $40, 903. 20. a@-nst Allotir.ent 7-2502-10 has requested to submit to them a su2mmary acro unting on-an anntial basis of all mon-t@s received from Iso, it has been requested that any urex ended funds be returned at the close of the--- grant year. 6. The reouireroent for a six i2(ionths' inforii-jal accounting on the part of the principal investigator is waived. '7. y -Title to any permanent equipr-ncnt purcliised b M@m A whall-be r-e-tained by our iff I i &a---Of - - ----- higher overhead rates. 8. In connection with travel under this project, it is agreed that the Agency will accept- the travel doctimentition and -Accounting which conform with the practices of 9. It is agree@l that technical reports reflect-ing the progrc.,ss 5 of the research prograt'n sliall be subm itted at muttially acceptable intervals. 10 is 6tii@ed-tlifd"h TOP SECRE@t' and is aware of the true- purposes of the program. Ile has ilso agreed to Downg@ (I to. I.y of: VON* rity 3 -iorandlim of Agreement. com ply with the requirements of the l@ien ciiief, Branch II TSS/Cliemical Divi2sion APPROVED FOR OBLIGATION7--@pProv0d'. OF FUNDS: ]Researeli Director /Cheniica Di ision Date: Attached: Research propqq@@l - Distribution: Original only 4 ed to: by au I ty of: awl* I May 1957 Gentlemen: We are desiroos of continuing our work further on measures yl alcohol amounts of eth,__ aimed at perniittind consumption of larger 2 0 St on. - Consideritble without an increase in nervous-sy en-i depressi am since I September progress has been made in our research- pro r 1956. 2 Our laboratories have been equipped and placed into function- ing condition_since the last visit of your--representative. The suite of three rooms in the-Ni@i@t residence 4as-oeen converted into a III ISOMOMM,.an Enzymology Labor.-t- (@,Bi2ocliemistry Laboratory -m@@4nd an offi itory for cc and-niachin@ shop for myself. Tli@@-- En-@ymology -Laboratory is set up for in -vitro, work with tissues and enzymes, In addit-.on, a N6Ui@@llysiolog -L,aboratorl or our 2 n a Me @d I jacent to the Anitnal Surgical Oper.Atina Theatre, on the fifth floor of the Medical School !3tildi,-ig, hAs been-allotted to the Department of Neurology UTI(ler 2-As- a-n-ucleus fo-.--- expansion, the Neurophysi- ology Laboratory is already equipped---w-i@t-li---a--n' 8 chitinel Grass A4odel 3 EEG and a tieditr(,-,i EMO, As an itiforri)al interim pro-ress report, the follow-ing research 5 for ttis yeir has been completed or is very near completion. A. The depositioii of carbon derived from the ingestion of radio- active alcohf.,l has been published t)nder joint ,tuthorsliip with nd in ttic qjl 2 - B. A paper on the EFG in acute alooliol intoxication has been o the Quarterly Journal of Studies subniitted for publication t on Alcohol. C. We have complete2d a paper on tlip. effects of premedication with nicotitiamide on the speed of alcohol metabolisme D. The conip@-irison of ttie deposition of radioactive-carbon-in---- feedin,,, of alcohol and acetate is the tissues after continued- 2 being completed by E. The dehydrogqnase method of alcohol determination has been standardized by nere inues -With Ahes to refine the dichroinate iiiethoil. etwomicro--- techniques developed to a satisfactory stage, in 2vivo studies on mice can-be conducted. It-isLoor proposal to continue to conduct our next year's in--- - vestigations along the following lines-. (1) Expedite the removal of alcohol from the blood stream by selective metabolic pathway@@_" wilt allow the alcohol to be stored rather than cor2npletely metabolized. We plan to sttidy the effects of a nuri)',ler of igents that are claimed to-excedite alcohbl i-netabolism (alanine, pyruvate, fructose alcohol dehydrogenase).- P"Iiminary studies indi(,,ate that the nutri- tional state of the animal is very In-jport.-,nt and 2if this -is maintained at an optirial state, none of the agents show an y, striking.- if indeed statistically significant effects. (2) Determine the effecti%,etij@ss-of foodstuffs: in delayiny the absorption of alcohol froib-the-g.-Ar@trointestanal tract. Prelinii2n,,Ary work der,.ionstr@ited that neither carbohydrate nor protein can be expected to delay the absorption of alcohol. Ilot-v- ever, fat was found to be effective in an inconsistent way. We intend to continue studies on the effects of various types of fats on the absorption rate of alcohol. (Expressed oils, olive, 4 peanut, theobroma; soft anini,,Al fats, butter, suet, lanolin.) The effects' of gastric i-nuciii and kaolin will also be investigate(I in this respect. %V A SE@41>'11",V N' L.LICENCF- 'NO , ! -@T 3 Work on the effects of wine buffers on hvynan subject.,qis. being coiitinued tinder the auspices Of a &sea* s of sympathomimetric drugs in --DeterminL- the effectivenes (3) inal tract. delaying the absorption of alcohol from the gastrointest gy. Laboratory we plan With the -tddition of the Neurophysiolo -a f i King with larger animals (dogs. - cats), _ and 2 -enter th eld of Nior to re testing synergism atid antagonism between alco'lol and other drugs. Since we are convinced that the effectiveness of &tat in delay ing the absorption of alcohol from i'lie gastroint,,,,Sti@al tract is related to the slowing of the emptying time-o,,P the stomach, it is desired to investigate the effectiveness of other measures. which might have the emselves as---- same effect. The sympathomimetric dr-ugs su&,gest th 2 m' e, Nalline, Bonamine likely can.ditl,-.tes in-this respect. (An)pheta in Ephedrire. In order to utilize to advantage the increased laboratory space now available to me, I plan to increase my research staff and also.- - my own active pai;ticipa'%-Lo2-ti. The following is the proposed yearly budget: Neurologist (kA-.D.)-half time "$4 000 oo%--- Fellow" neurophys-lologist lPh. D-* 7, 5000 00 Ehzymolocfist-(Phi@D.) 8, 000.00 Ti6-thnician--Laboratory------------- 4, 000.00 Laboratory, anii-nal 1,.,^eper------ 2, 000. 00 Equipment & apparatus 3. 2500. 00 Supplies (chei-nicals, radioactive alcohol, etc.) 38000.00 Large atiini-,Als (upkeep,-- etc.) 1, 500.00 Travel 1, 000.00 8 Total $ 34, 50.0.00 Orhec-@d-14!fo 4, 830. 00 $ 39, 330. 00 0 I C E 4 [t is our hope that with our assembled research te.-im, more definitive results will be obtained in the very near future. Very truly yours, Professor of Medicine (Neurology) 1 4 WARN! T I C, NCE VC)LVI?'D Z9 FISCAL, YEAR 1957 to 14 ilecei,)t is ierel@)y ackno,.vlcdoed of the SL'rr, of $2, 360. 40 in cash.. liECEIPT 'teecipt is hereby acknovtlcdged of thO--"M-of $2;@-360 40 iii cash. 6 Dai.e- cl AUCL@'IPT 44tia @3 -fi@@the mnuwmropre6eqtino a retiwii to t'fie AC.-,-t,.cy of surplus funds under contract l'ID-37 4 Dato., ipt ce tt-o followina, two ohec'kul chnak Ilo 195 It di@two on t%C G r,-6, dr7a,.u on th't azlo:ii-it OIA., Dates A or of dolA,,)r 'U' 1 i;A 2 6-S fro 2 tt 04- to' 7 ce des i,-1,3 077 For n,,,; to i;3 !--,crcby lilvc,.tce 2 1,-L2 t at erA rcl@zirt3 is oi fil@.2 in t Wi not rt v-1 (2% I- Ja by certtfic---@ t7@li* li'VO!r-e a@ lics tO a 'L3 calt ill t@Y)ril 1953, til@,-. "-o t.'!Ic or tlie f->Ilviing elwelle cezhie r s *3 WA 'hii-,tls Cbeek i-L-!@1,35633 op 'W5.33;6 both ChOas Pay"ible to 7 .33, to C'@lief no lat,@.,r 1-,,, p T 1" 5R E i@' E I V;-:! L-:! VC# i@lOi538.66 It ir. 1,,r@io'Lly cei,'V-fl,.ed 'C-h'@%t t" to cl-f s awl 2 -!a C. rceeipt3 izi C""-L file I o- tioa not to :C:c, 5 C tl-.,-i r@,11 to In NdV 9 iv (I T I -zo, @ M(--) lj_ 0 0.1i@T, i3 TO 400000 i Direc-"or 0 4 1977 Df@AnAl BY 1 t4arch 1956 Ii.UIORM[TjUI4 FOR2: t,?,ULTRA, cubpro ect 56 SUWECT to- c k on 1. 5be pj-rpos,3 of -alcohol research b 2 be to p rsue 2. The scope-Of the research pro3r, Ss of focdstufl@s in studies on deterc(tining the e@ti'eetivene tract; 2 oi-,I- posorl)tion of alcohol frof de inS tle effectiveness of -various s@@0-AioiTtetic dilist'. detert,@iir tioli of -tlc6lnol fra..@i the g'-IstrOtp-testinal in the absoip al the blood stream tract; e.,-I)editin,, recioval Of _cohol from by relectiv etabolic Vath,;Te@ys that will -,'IlOw the alcohol to 2 e i-i be stored rp-tl,,er -,b,an completely !ietabolizecl,-ancl clBv,?3.opi-iis@l a test of It-loler,,@nce to alcohol -for use in the simple and rel-lieole-I of --bebb@V-ior. sel(.,CtiOn of personnel an -DreaictiOll TtC cost of this prozrc'-im is estirl,,-itecl to be @30, .0 1 !Rl6.oo 2 t be e,(-Ided f or a poriod Of One Year. To this siirl IIIUS i-edresenting a four percent service ch,%rge to --- 494jibb -The're-fore, the total cost will n:j-'G-excepd $31,616-00. 2 tde against Allottrent 6-22vc--J-,@@-001. Charp,es should be im is-da to 4. has requestel2i til-i-t of cic,-n,,ies rec aecoun, submit to them a r t-'! urey,-o.2!ndp-d funds A Ammmk Also, tl!P-Y 2r-2quezted t-h rp-tilri@%of any rece-tvcd taii .Q--rm-inent equil)rient pureli.,idedANdNft() 5. T lieu of 2 'L @shall be r@it'l-t-'ned ',)y t'r.,,-m in overhead rates. tcltion and accoull nf It ,,Is muttiall 2 6. y a@,,r--ea that doe'Lin!- for travel expenses 14bich are reiniburse-ble t ,he accep,,Od practices 0 tb shall cclr2lfoi-m vii-.I-l ,at institution ,d to: by y acreed to covi@@@th"equirements of of acreement. ti-,e-, Lqc-ii,.orandum udeal ivision APPROVPD FOR OBLIC-IATICkl OF M,,IDS, Date: Attach@ii,,c@iit: Pro-.)Osal Dist-ribLi@%j@Loll: Or-,Lr@a.lial Gnl.y Do -ty 0,\ to 19'77 BY slow%" fA 10 February 1956 Contlemo-n: -ri@-,asures- aimed at permitting We are dssiroxis of continuing our work on constirii-ption of ],,irr-r amounts of ethyl alconol without increa3e-in nervous-sy@@tem depression. proo:ess irt- the_p4;@t_y@@@ has been slo,,t;- this nipy be attributed lareely to the necessity of Liy devoting a larger shaxe of my tirle to d@-,velc@.or,,en-t of a growing NaiLrological Service in the School. As a result-c-,f-this effort, has now secured-sup-.oort--,rrom M wa@ which have P-tade a residency tra-riiiig proe;rai-a in li'eurology L with 2increased personnel to put it into effect. Ace@irdina_ly,------- I will be able to again d--Vote a reasonable tL,-aount-of-personal time to researeli in alcohol, and want to taL'.@:e this opportunity to apply iwm(@i for continxiini,, support. It is O-Ll:r p-opoeal to conduct our i@-ivestigations-along the follcarin-. lines: (1) Deteraine the effectiveness of foodstuffs in delayin- ebsorption of alco7nol from the gastrointestinal tract. Preliminary i!ork relative to deteretil.ni-ng th3 effect 2 of various foodstuffs in slowli,,cr the abso-L-ption of alcohol has been of more ptomise, in that, as set forth in the prelimi-nary report forwarded to you I)re@viously, tha in-estion of reasoneb3.e apiounts of fats or oils previao.s to the 2 of alechol has been ie,.nonstr,-tted to lowp-r significantly the pe,t'..c value of blood a!coiol ccncentration. I-le believe further work along t)ii-s line is iiidicated, to the iiiriiiic, C)f tl)e fat itiL7,estion5, aii(i -the dt-,,@ree of uiii-foi-Ldty of the effect in dif- w Pl@ (2) D--terLqine the effectiveness of synipathotiiometic drugs in delaying the absorption of alcohol from the gastrointestinal tract. Since we are co-@ivinced that the effectiveness of fat- in this regard-is related to sl6iAng 2or the emptying tim.-, of the stomach, it is desired to investirate the her me@-tsures i,,hich ciialit have the effectiveness of ot ry- - same effect. Thli--s motic drugs-sugp"est 2 themaelve,g as likely candidates; indeed anip.@etamine was sh to have such an effect. Although such measur" cati-riot be expected to de3ay indefinitely the absorption of alcohol into -the- blood, they rr,4y be sufficiently effective to delay absorption until the stomach can be ei4ptied by induced vomiting by some individuals with so-,tie facility in this mpri@.-uver. Of course, the ideal-substance would be a compound that wou.@'-d cceibine -with the alcohol in a f o7,-in that would be2 unabsorl,,able, and-it-is possible-that so@,.ic-stich com- pound not in itself unduly toxic might be found. Expedite-the rolnoval of alcobol--frWthe-Ilood streexa by selective metabolic pathways -Vc@%t will allow the alcohol to be sto2red-rat@tier-then coutpletely metabolized. Another point of attack on the problem is the search for uicasuies that will ecpcdi,te the el-iyqination of absorbed alco'.ho'--from the body.-The am,,),Lint eliminated j in the2 urine, breath, and sweat is not of siif f icient magnitud,a to be of practical importance even if doubled, an