[PAGE 1]
un56t0 31 lu157. Ep
Balasce onthnd ide 6 15713
1 p57to 31t 1953 576871
1Sept53/0311959 Epense 117220
1Sept59 to tel1960 Eype 1548601
He 6o to 3 Me 0 Efp 1102571
13130651
TOTAL ElpRROs
Refundid 13 pnany 1961
131744
30103001550323 15713
1056-31/151
Sep 7-31/5/58 3533000-39568.81 10515
1Se58:31/3/59 53922004972209
1Sep59-29/2/60 1548607
1a60-3112160 17940001102511
Refcead

[PAGE 3]
Whao 1esh 1956 Est cot 14eas 5040000 1216.00 376160 TeTAt Est:Cot

#2 Wiheno:25lpu1957 &t Ct 1ar \*3933000 151320 4% u 4090520 TOTHL

\# 3 llms: 17pt 1958 Cnt 1Yas 5392200 1%u 215538 5607888 TOTH

1 Mmo: 9Mach 1960 E4Ct1w 1194000 71760 4%pe 1865760 TOTAK 1412556

HEURCLOGIST 4000.00

141,592.00
137. 592.00 fardugrepotil ly prjecd A.000.0.0

[PAGE 4]
This Filc\_was\_reviewed on

1 5 JUN 1977 for Drug/Behavior Modification material\_responsive to FOIA requests.

/7 Nothing-responsive was found.

considered-responsive and sanitized för release or released-unsanitized.

1. MFRt, 1 Mar'6

25tpr57

17 dipt'58

q Iar'6o

[PAGE 6]
2 9: Doct Nber 1, 190

[PAGE 7]
lov. Desesk to de Gredit of (one et) wih eeeka ete s yoee ceoviedged nnd retored o at da,ota Lo zegciercá snat oy. Ooo s

\+ Prre nceie excedy as sseoust is

[PAGE 8]
OFFICE OF CONTROLLER

April.29, 1960

We are onclosing our-financial.statement covering. the for the period Soptember 1, 1959 to Fobruary 29, 1960.

Sincerely yours,

[PAGE 9]
UTIVERSITY

Financial Statement

September 1, 1959 to February-29,1960

Balance August 31, 1959.

\$15,015.00

Salaries \$7;475:00

Equipment 5,423.40

Supplies. 2,587.67

Balance February 29, 1960

(Deficit)\$(471.07)

i bave examined "and approved the subaitted expenditure..

Maton 27 Jiena

56-4

TSS/Chenlcal Division

[PAGE 10]
We are enclosing our financial.statement covering for the year ended August 31, 1959.

November i1, 1959

[PAGE 11]
Financial:Statement-September 1, 1958 to August 31, 1959

Balance Auguet 31, 1958 Funds Received

I b.vo exapined enl npo tte outaitted oxpenditures.

\$10,815.09 53,922.00 64,737.09

131/elu ieni Evstea

[PAGE 12]
Dr of our Clinical Staff hs inforned ne that your office has never received a financial stctement for the yeer 1957-58, covering expenditures on the which was at-that tine under. the direction of the

We are enclosing a copy of that-financial-statement which our records show was forwarded on-April-13,-1959.

If we can be of further assistance, please ¿o not hesftate to cell on vs.

3537
4114.230

CO

April 28, 1961

[PAGE 13]
Financial Stete:ent September 1, 1957 to ugust 31; 1958

Balence Auust 31, 1957 unds Received

I have examined and approved the subaitto4 expenditures.

Dater /+/61

COPY

Sle-te

\$15,053.90 35,330.00 50,383.90

[PAGE 14]
27 December 1960

Will you please send us a copy of the financial statenent

7 of the covering the poriod-1-September-1957 to 31 August 1958.

In check through our project: files we find the above accountis miesing.

Sincerely yours,

M. D.

[PAGE 15]
We are.enclosing our finsncial statenent covering the for the perioà June 1, 1956 to August 31, 1957.Liquidation of outstanding cormituents will-be reported at August 31, 1958.

February 3, 1958

[PAGE 16]
Financial Statement June 1, 1956\_to Avgust 31, 1957

.Balance.June 1, 1956 Funds received

Total expenditures

Total commitments

Uncoamitted balance August 3l, 1957

I have examined and approved the submitted expenditurcs,

et 10/59

57--

TSS/Choaical Division

[PAGE 17]
Your rescarch proposal on metabolism on ethanol at the has been approved by our Board of Directors.A check for-\$17,940.00-payable to is forwarded horewith.

The above monies aro in support of your alcohol metabolism studies and are for a period of one ycar.

It is requosted that a summary accounting be rendered ewhich was extended until the residual balance vas expsndeù on the rosearch in progresa.

It is further understood-that-previoug agrcemcnta relating to exponditnres and summary accountings as well as tho returo of any unoxpended funds romaining at tho terminatione aplyto

5-9

6 Aprit 1960

[PAGE 18]
RECEIPT

I hereby acknowledge receipt of the following checks:

Caehier'a Check No. A239594, dated April 5, 1960, drawn

on the in the.

amount of \$17,940.00, made payable to the

Official Check of the No, G40663,

dated April 6, 1960, in the amount of \$717.60, payable to the

[PAGE 20]
MEMORANDUM FOR: CHEF, FINANCE DIVISION

VIA

: TSD/3udget Offlcer

SUBJECT

: Project MKULTRA, Sabproject 56, Invoice 66 Allotoent 0522-1002-4202-

1.. Invcico 26 covoring tho ebove subproject is attached. Payraent shodid be roada aa foilowa:

Casbier'a check-la the emouct of \$17, 940. C0 payablo, to
dsavn on agbaok.

Ceshicr'g check in- tho amount of \$717, ó0 payable Co 1 Grava cn at bank.

2. Please forward the checks to Chief, TSo/Chsmical Branch through TS/Budget Cfütcer. by H April 1960. .

3, Thla Is a foal iavolce, However, aince it is-enticipated that addltional fuads will bo abligated for-taio-projact, tha fles should not be closoá.

TSD/Chomical Brench

Attachmente: lavolce & Ceztifcationo

Dictribction: Grig & 2 - Addresnee

LCERTEY TAT FUTDS ANE AVATA3LEAR 1910

56-12

20 March 1960

[PAGE 21]
CERTIFICATIONS

(l) It is horeby cortificd that this is invoice g6 applylng to Subproject 56 of MkULTRA, that periormance is saticfactory, that services are being accompllshed ia accordaaco with mutual agreemonto, that a detailed agenda of the payments and recsipts is flod in TSD/CB, that this bill is joot and correct ani that paymont thercof has not yot been made.

Chief, TSD/Chemical-Branch-

Date:

(2) It is hazeby certified that this invoice appliea to Subprojoct 56 under MiKULTRA wiich was duly approved and that the project ia beiug carried out ia accordance -with the meroorandum dated 13 April 1953 from tha DCI to tho DD/A, and tho extonsion of this authority in subscquout merooranda.

Rosearch Lirector:

Dato:

52-17

INVOICE

\$18,657:60

[PAGE 22]
No. -- 1910

Cost Account 0525- 1008- 490.2

Object Class

5613

[PAGE 23]
-MAMORANDUM FCR:COMPTROLLER

ATTENTION : Flcaace Diviçioa.

SUEJECT : MKULTRA, SubprojeCt No. 56

Additional-Authorisatlon No. 4

Uader tho authority grauteá ia tho Momorandun.dated

13 Ayelt 1953 om the ECI to tho DD/A. .ead the extonsloa of

thia autkority iu aubeequert memoranda. Sabpzroject S6 has beea

appzoved and \$18, 637. 60 of the over-all Project MkULTRA. fupds.

havo besn cbliçatod to.cavar the.subproject'a espeases and ahoulo

be cbargs4 to Alletaont 0525-1009-2902.

TOD/Chemical 2zaoch-

APPROVED FOR OBLIGATION

CF PUNDS: 15

I CIDPY TPAT RNCS AR AVARATS 910 QUSARON PENTNO Ra.

Ciatributicot Crig l 4 = Addreasoe

5

5-13

9 March 1960

[PAGE 24]
SUBJECT : MKULTRA, Subproject No. 56

The purpose of this project is to provide funds to continue 1 a research program Thie program is designed to exploit all the knowledge and facilitiea available at the in providing information of direct interest to the Agency in the area of alcohol intoxication. Specifically, basic information required to provide practical answers will be developed. A proposal for an extension of the work during the coming year has been submittcd and ia attached herewith.

Executive of the Department of Neurology at the was the principal investigator on this project. the direction of the research-in the hands of the Acting Executive of the Department of Neurology, It has beeq deterrnined that the researchiprogram to be pursued under the budget proposed herewith will be pursued in a diligent and fruitful manner.

3. The funds for this project will be traneferred using the as cutout in the usual manner.

Q

naed to: nt y atxcity of: cte: Jun 1977

52-14

LOATEEL: CLBY

DRAFT 9 March 1960

MEMORANDUM FOR: THE RECORD

56-4

[PAGE 25]
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 centmaking a total amcunt of \$18, 657.60. fce to

Charges should be made against Allotment..0525-1009-4902. 5. . ue has requested a

to submit to them a summary accoupting on an annual basis of all monies received from Aoy unexpended funds remaining at termination will be returned to the

6. The requirement for a six mouths' informal accounting on the part

of the principal investigator is waived.

Title to any pormanent equipment purchased by funds granted
7.
15 shall be retaincd in lieu of higher overhcad

8. In connection with travel under this project, it ia agreed that the Agency will accept the travel documentation and accounting which conform with the practiccs

9. It is agreed that technical reports reflecting the progress of the research program shall be submitted at mutually acceptable,intervals. 13

10. The project is unclagsified after it lcaves

APPROVED FOR OBLIGATION OF FUNDS:

Chief TSD/Chemical Branch

57-14

Attachment: Proposal & Budget

Reasarch Director

Distrihmtlor: Original only.

[PAGE 26]
We are desirous of continuing our reaearch activities on measures aimed at permitting consumption of larger amounts of ethanol without an increase in overall nervous system depression..Our research to -date (sce technical reporte) has brought us to à better understanding of the intermediary metaboliam of ethanol, As previously reported, it appears that the limiting factor\_in the rate of disappearance of ethanol from the body is due to the relative rate.of conversion of ethanol to acetaldehyde.Any measurea that can increase the rate of this reaction would certainly reduce the overall effecte of ethanol\_upon the nervous . system,

Currently, we have\_established a coordinated clinical program of investigation with human volunteer subjects in thel and affiliated A This, of course, would open up many new vistas and avenues of approach and investigation.

Therefore, it is our.proposal to continueto conduct our research activities as follows:.

1.

The continuing program of work will be biologically and enzymologically oriented to.determine the stepa involved in the intermediary metabolism of alcohol.

A. A comparison of the incorporation of acetate 1-Cl4 and ethanol i-Cl4 ia fat fractions will be made to determine whether the pathway of ethanol metaboliom enters.the acetate stage.

B. In view of the fact that large doses of ethanol will inhibit methanol metabolism, atteropts will also be made to compare the pathways of methanol vs. ethanol metabolism. The infiuence and effects of catalase, both in vivo and in vitro, upon methanol and/or ethanol mctabolism will be investigated.

C. The role of alcohol dehydrogenase in reducing glyceraldehyde to glycerol and its relationship to the effects of fructose in increasing the rate of ethanol metabolism will also be investigated. The implications in this specific instance hold great promise towards devising an antagonist against the depressant effects of ethanol.

O

O0

PROPOSAL

WARNING NOTICE

SENSITIVE INTELERSNCE SURCES AND METHODS ETRLVED

[PAGE 27]
BUDGET

I. PERSONNEL

Neurologist (M, D.) 1/4 time Neurophysiclogist (M.D.) 1/4 time Enzymologist (Ph, D.) full time Research Aesistant, full time

Subtotal \$ 12,800

Chemicals, glassware;-etc \$ 2,000

III. Experimental Animals (emall) 800

Univeraity overhead 15%

WARNING NOTICE SENGUIVE INTSACENCE

5X-14

[PAGE 28]
has in a sense "left the ship without a rudder". I have been appointed Acting Ezecutive of the Department of Neurclogy in his place. Urgent-reorganization and unavoidable confusion within the Departient has resulted in my delay in proparing the attached research proposals.

preyions oxcired on Septomber 30, 1959. It was pointed out to mio that commibects for. both rescarch space and personnel had been made ram for sn additional year subject to your final approval.There is still a residual balance of last year's available to mcet ur current cbligutioas,-Therefore, I would appreciate your grant ing us an estonsion or last year'smm árd authorising oxpenditures from the residual Lalance uctil the new arr can be iosued.

Due to the coasolidation of the and the continuance of cur oricical activities inD I am herevith enclosing two .separate recearch proposals for your perucal.Within our activities, we have cocoblished a coordinated clinical progran of investigation that is rosearch orieated.

Your previcus support of  has been greatly.approciatod. We hepe we will bo able to justify your continning support and continue to perform in a manner and fachion cstablished

Very truly yours,

Acting Dxecutive Division of Neurology

9

27 November 1959

[PAGE 29]
-MEMORANDUM FOR: THE RECORD

SUBJECT : Extension of er

Subproject #56, expiring 30 September 1959, is extended without additiooal funds for.a period not to exceed eight months or until the balance as of August 31, 1959 ie expended.

30 September 1959

[PAGE 30]
RECEIPT

I hereby acknowledge receipt of the follcwing two checks:

Cashier's Check No. A202870, dated October 2, 1958, drawn in the on the amount of \$53,922, made payable to the

Official Check of the , No. 209-345465, ,dated September 30, 1958, in the amount of \$2,156,88, payable to

Q 56-17

[PAGE 31]
FICOO3 2

Tra/oaloov.crrteea

G. 423 : 4 Lavolca \$5, Allov2nt 2F 1

l. Invotco to. 5 ia etlell eoveoica tha stovo aborojeotr fayrtat stouad ba rade es follorat

Crohior'a chaos 1a 1ta czzns sf \$53.922.00, drawn

Catter's choce 1n tho szt of s,15€ 0, érova 三

t A i TEs/cheatco1 品 11 to lates

1 i.veics 73 Rothot-54 :411 站 4 45 L小

er6/creale.l Divialcn

Te0/er  (2 Soptonkor 1953)

515

22 Soptober 1953

[PAGE 32]
CXNTIFICATIONS

(1) It is heroby certisied that-thio-is-Invoico No.5 epplying to Subproject 56 of Eala, thot porforvenco. io. satisfactory, that services ere being cccoaaliehed in cccortance vith mytunal agreements; that a detailed tgorãa of tho payuents end recolpts is on filo in Tos/cd, that this bill io just snd correct and that payment thoroof has not yet been mado.

Chicr, 12S/Chonicnl Divisiou

Date:

(2) It is hereby cortificd that thio invoiçe epplios to Subproject 56 of NulA vich vas duly aparoved, cnd that the project is being carried cut in cccorcance vith tho Easorcndua dated 13 Aprir 1953 from the DCT to the to/a, ená the oxtonsioa o2 this authority in subsequent temorenda.

Datet

Eoecarch Direotor

36-18

IIVOICE

\$56,078.88

[PAGE 33]
MEMORANDUM FOR: THE RECORD

SUBJECT : MaULTRA Subproject No. 56

1. The purpose of this project is to provide funds to continue the research progrum conducted by rat ihie program 1s designed to exploit all the knovledge-and-facilitiee available to.its director in providing answers to specific queettons of direct interest to the Agency in the area of alcohol intoxication. In addition, those areas of basic knowledge required to provido these practical answers will te developed.

2.  has submttted the attached progress report and a proposal for an extension of the work during the coming year,It should be noted that three publicationa based on the material covered in the short progress report arepresently in pross.Included as a -pert of this project is a proposal from who is working in  leboratory a work will make available a much better indicator of alcoholic intoxication than is now available.Prcsumably it will wake possible an absolute measure:cf physiological impairwent due to alcohol which will in tura materially aid in the final phases of the

56.19

17 September 1958

bongraded to: by wority of: date: June:1077 E2 TRFOET; Ch B

[PAGE 34]
3. The funds for this project will be transferred using the as cutout in the

usval manner.

4.. Costs for this program for a period of one year beginning August 31, 1958 are estinated to be \$53,922.00 to which must be added 1: a four percent (4%) fee to the (\$2,156.88), making the total amount \$56,078.88. Charges should be made egainst Allotment 9-2502-15-902. )

5. has requested to submit to then a pummary accounting on an annuel basis of all monies\_received from . Also, it has been requested that any unexpended funds be returned at the close of the  year.

6. The requirement for a-six-months'-informal accounting on the part of-the principal investigator is waived.i

7. Title to eny rermanent equipment purchased by funds granted 1 shall te retained by in lieu of higher overhead rates.

8.. In-connection with travel under this project, it is agreed that the Agency will accept the travel docuventation and accounting vbich t.1 conforn with the practices of i

9. It is agreed that technical reports reflecting the progresa of the research program-shall-be-cubmitted at mutually acceptable intervals.

2

E2 CUFDET; CL BT SPEO

by authrit of: to cate: Jon  1977 12 IMSET; CL BY RUON

[PAGE 35]
10.  is cleared through TOP SECRET and 1s aware

of the true purposes of the progran. He has also agreed to comply

with the requiremente of the Hemorandum of Agreement.

Chief TSS/Chemical Diviaion

APPROVED FOR OBLIGATION OF FUNDS:

Research Director

SEP Date: 19,858

Attachment: Progress Report and Proposal

Distribution: Original only.

Downyeied to: d iy otyof: Cat01 J21977 BY

5e-19

[PAGE 36]
PROGRESS REPORT

Researchon Antagonists to the Depressant Effect of Ethyl Alcohol

As an informal interir progress report, the following research for this year has been completed and is in preparation for publication.

1, Tri-iodothyronine

The prominence attributed to the use of tri-iodothyronine as an agent for rapid "sobering up" has not been substantiated in our laboratories. The dosageof tri-iodothyroninc used experimontally in our dogs were astronomical in relation to the usual therapeutic dose in man. Amazingly, the dogs tolerated the high dosage quite well and manifested only a rise in body temperature and increased panting. The cffcct of tri-iodothyronine on the rate of alcohol oxidation was neglegible and certainly not, more than that normally caused by the increase in body temperature.

2. Pyridoxine

The effectiveness of pyridoxine or vitamin B6 is essentially. the same.. as that of tri-iodothyronine. It is difficult to accouat for the reputation recentiy gained by both pyridoxine and tri-iodothyronine in the press without the support of critical experimental data.

Perhaps this can be accounted for by.the.fact that the effect of a rising conccntration of alcohol in the blood does not have a linear relationship to nervous system depression, but rather a logarithmic one, Therefore, there is a critical concentration below which the individual may appear relatively sober and above which, by a very small margin, a few milligrams/100ec, a considerable demonstrable degree of intoxication is present. Therefore, any agent, with or wihout any appreciable effects on the rate of alcohol metabolism and/or concentration, given at this critical level, may give a spurious impression of being an excellent alcohol antagonist.

WARNINGNOTICE SCNSITIVAINTELLANCNCE VRCES AND RTHODSUVOLVED

[PAGE 37]
3. Alcohol metabolism in mice

The effects of glucose, fructose, pyruvate, alanine, glycine, glutamine, glutamic acid and aspartic acid on the rate of ethanol mctabolism in vivo were studied in mice with equivocal results.Data obtained were extremely variable from mouse to mouse, as well as from weck to week, in spite of the large number of animals used.There is strong indication that the mouse may possess mctabolic pathways for ethanol that are unique to that specie.

4. Alcohol metabolisın-in-dogs

Various compounds studied showed a definite cffect in promoting an. increase in the rate.of alcohol\_mctabolism.\_Glycine\_ showed an increase of 25-50%; alanine 25-60%; and fructosc, which gavc an increase of about 25%. Glucose, pyruvate, tri-iodothyronine-and pyridoxine showed no increase.. In the case of acetate, the converse, a slowing of alçohol metabolism scened to result.

5. In viro studies on rat and mouse liver slides

Experiments with liver slices showed that liver from a fasting aninal metabolizes alcohol about one half as rapidly as that from normal animals.

Stcps were initiated to-determine where the block in alcohol mctabolism by liver slices from fasting rats may occur. The most likely starting place secmcd to be the first step in oxidation, the conversion of alcohol to acetaldehyde. Since the necessary coenzyme of the énžyme mediating this step is diphosphopyridine nucleotide, or DPN,the first experiments were designed to determinc whether the coenzyme is deficient in tl;e livers of fasting animals. Our experimental mcasurements showed that DPN was not deficient in the livers of fasting animals.

Attention was next directed to the enzyme itself, alcohol dehydrogenase. Livers wcre assayed for total content of alcohol dehydrogenase and it was determined that fasting animals had a higher concentration of the enzyme.

Sinçe the equilibrium constant for alcobol dehydrogenase is far to the left in favor of alcohol, it would appear tbat if the concentration of acetaldehyde rises, the rate of alcohol oxidation would be slowed. Therofore, semicarbazide, which couples with acetaldehýde, was added to the incubating medium. Our data shows that the addition of semicarbazide did not change the rate of oxidation. Moreover, the addition of either acetaldehyde or acetate did not change the relationship. Thus it-would seem that the accunulation of acetaldehyde did not influence the rate of alcohol metabolism.

O0

S6-10

WARNING NOTICE SENSITIVE INTELNGENCE SOURCES AND METHOD INVOLVED

-2-

[PAGE 38]
The poşsibility that the rate of oxidation and reduction od DPN may have a direct rclationship 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 ethanol, Three compounds capable of reoxidizing any DPNH which might accumulate were tested : methylene blue which acts as a short circuit betwcen the flavin system and oxygen ; ferricyanide\_which directy links DPNH and oxygen ; and pyruvate, which in the process of being enzymatically reduced to lactate oxidizes DPNH. Experiments show that pyruvate increascd the rate of metabolism in both the fed and fasting animal livers. Methylene blue and ferricyanide raised the rate in the fasted animal livers, but not in the fed. Fröm the promising leads above, investigation of the actual state of oxidation and reduction of the DPN in liver was undertaken and is now in progress.

5. Radioactive alcohol and acetate

The deposition of radioactive carbon in the tissues of mice fed radioactive alcohol or radioactive acctate indicate that the metabolic pathways for both alcohol and acetate were very sinilar.

56-141

3

WARNING NOTICE SNSITIVE IATELLGENCE WUTS AND MENODSUINVGLVED

[PAGE 39]
We are desirous of continuing our work further on measures aimed at permitting consumption of.larger amounts of ethanol without an increase in nervous system depression.\_Considerable progress has been made in our research program since September 1;-1957;

The attached progress report summarizes our research completed to . date. In the past year, -we have made tremendous strides towards a beteer understanding of the intermediary netabolism of cthanol. It appears that the limiting factor in the rate of disappcarance of ethanol from the body is duc to the rate of conversion of ethanol to-acetaldehyde, Any measures that can increase the rate of this reaction would reduce the overall effects of ethanol on nervous system depression.

Moreover, we are now in the position of being able to conduct clinical experiments with human volunteer subjects. This, of course, opens up mauy new avenucs of approach and investigation.

Provided we are able to obtain a supplemental for the coming ycar, who is at can conduct a series of experiments to dtermine whether or not tranquilizers exert à synergistic and/or supplemental effeet or action upon the usual rate and degree of alcqhol intoxication,

52-4

August 22, 1958

Gentlemen :

SENSITIVLNTELATENCE SOURCES AND MBINOOSONVOLVED

[PAGE 40]
Therefore, it is our proposal to continue to couduct our next year's Investigation alorg the following lines :

1. Expedite the removal of alcohol from the blood stream through selective metabolic pathways.

Preliminary.studies indicate that glycine, alaninc and fructose will increase the rate of alcohol mctabolism. We plan to determine whether or not these\_effects are. statistically. significant.

We also intend to continue studies on the intermediary metabolism of alcohol. Experiments have been formultted to determine the effects of lactate on the specd óf alcohol metabolism; the effects of pyruvate on the DPN/DPNII ratio and the use of another enzyme system, such as the oxalo-acctate-malatc onc, to reoxidize the DPN coenzyme so necessary to convert alcohol to acetaldehyde.

The use.of radioactive alcohol will be continued in the study of intermediary metabolismi pathways. After ingestion of radioactive alcohol, varicus tissues and fractions, including the water soluble : fraction, phospholipids, non-saponifiable fraction 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.

Preliminary work demonstrated that fat will delay the absorption of alcohol from the gastrointestinal tract. We intend to initiate clinical studics on the various types of fat in this respect:-Expressed fats and oils, theobroma, butter, suet, lanolin, kaolin and gastric mucin will be investigated.

The effects of wine buffers on the ratc of absorption will also be investigated clinically.

56-19

WARNAG NOTICE SENSITIVE TELLGENCE SOURCES AND MEHODSIHVOLVED

·2

[PAGE 41]
—3.-Determine the effectiveness of sympathomimetic drugs in delaying the absórption of alcohol from the gastrointestinal tract.

\- Since the aboorption of alcohol from the gastrointestinal tract is related to the emptying time of the stomach, the effectivcness of various sympathomimetic drugs, such as nalline, Bonamine, ephédrine and others, will be investigated.

The folfowing is the proposed yearly budget:

I Professional services. Neprologist (MD) half time \$5,000.00 Fellow, neurophysiologist (MD) 2/3 time 7,200.00 Enzymologist (PhD) full time 8,500.00

II Technical services Technician, laboratory 4,800.00- 4,200.00 Sccretary 2,000.00 Laboratory, animal keeper

I Clinical subjects 1,500.00

IV Equipment and apparatus 1,200.00

V Supplies, expendable (radioactive alcohol, etc)2, 000.00

VI Large animals ( inel upkecp ) 1,500.00

VII Travel ( alcohol mectings ) 1,000.00

Sub total 38,900.00

University overhead 14% 5,446.00
Total 44,346,00

8

8

56.-141

·3

WARNNG NOTICE

SOURCES AND MATIOCAINVOLVED

[PAGE 42]
The research proposal and budget for and his added research activities are attached.  His proposed research would certainly yield invaluable data specially suited foryour purposes.

We are extremely grateful for your generosity in supporting us and were it not for the extraordinary opportunity of liaving  with us, we would most certainly not request a supplemental  At this time, however, we feel that this opportunity should be exploited to the fullest.→

Your immediate attention and consideration would be greatly appreciated.

Sincerely yours,

Professor of Medicine (Neurology)

WARNING WOTICE

SENSITIVE INTELLIGANCE

56e-19

-4-

CORDOTS ANn EFTSDS EOLVED

[PAGE 43]
9.3502:75:.962 5C

[PAGE 44]
To determine whether or not tranquilizers exert a synergistic :and/or suppleinental action upon the usual rate and degrce of alcohol intoxication.

INTRODUCTION

The present day definitions of anxiety and stress remain in dispute.--However, anxiety can be considered essentially a human function because it is associated with the capacity for delayed reaction, self reflection of motivation and the capacity for projection of the individual into the future. The concept of stress revolves around the arousal of anxietics, In general, anxiety may be aroused -by any condition which threatens the integrity.of the organism. Therefore, any stimulus may, in principle,-arouse an anxiety response because of the particular meaning of threat it may have for that particular individual. However, we can distinguish a class of stimuli which will invariably produce disturbances in most in-- dividuals. 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 tranquilizcrs on the part of many persons to.adequately meet and cope with these problems...Often times people will partake-of-"a-few tranquilizers" prior to going out for an evening of-social-drinking and partying. How does the combination of tranquilizers and alcohol affect-the motor skills, sensory processes and critical judgements which are not normally affected by cither tranquilizcrs-or-alcohol taken scparately?-

Therefore, the following course of investigation is proposed: To determine whether or ņot tranquilizers exert a synergistic and/or-supplemental action upon the usual rate.. degree of alcohol intoxication.

1. Design and test methods involving clinical subjects which will-descriminate between normal, tranquilized; alcoholic, and tranquilized-alcoholic states; and for particular and specific-states-or effects which can eventually be related to overt behavioral responses of a sort which entail sone possibility of practical exploitation.

2. Validate the above methods and effects in normal hunans and relate them to alterations in mood and behavior in as objective a fashion as possible.

The above methodology will involve the use of a Nystagrnograph,
electroencephalograph (Lead II), Breathalyzer, Polygraph, and
Drive-U-Meter. Biochemical methods include enzymatic and bio
chemical determinations of alcohol levels in blood, urine, and saliva. It is envisioned that at the end of a nincty days study, some
definitive answers, substantiatcd by objective data, will be obtained.

CO

PROPOSAL

Q0

≤6.-19

WARN NGNOTICE SENSITIVEETITELCENCE rrre spe

OURCES AND MECHODNRIVOLVED

[PAGE 45]
BUDGET

\*This budget has since been extended to one year without change in funds.

[PAGE 46]
NEORMEL POS: COUTROLIER

: Fizcaco Division.

MuiTaA, G.bpvojeet 56.Additioual intaorisation No. 3

Urder Uha auttority creatal in Uhe osoracdw datoù

13 Apell ly53. croa the BoI to tho Do/A rod the extesoion of

thia snzority la cuboeqent oenornsda, Gotprojoet 5o ves

reoviooly eprovesd. Gucer Ute sao authority an cdaitoual

cus of \$56,073.G3 hao been muthorieed-to cover-tho anbprojoot's

exporreo (doroby brirging to a total oe Q€,C73.33 taãs

cbltgated duriog F 90), to do chunad to Allotoent 9-8500-15-90a.

FFEAOED TCR COLIGATTOL OP FURAE

Dle ribeticot Cig 00- Idaressee

56-20

17 Ceptecber 1920

[PAGE 47]
MEMCRNTUM FOR: CHIEF, FITANOA DIVISION

: qes/bodget Officer

SURJCOT

A, Bubproject 56, Invoice \$5, A11ctrent 9-2502-25-902

1. Invoice No. 5 is ettaohed covering the above subproject. Peyuent should be rade as follows:

Cashier's check: in the enount of \$53,922.00, drawa a

Cashior's chock in the aoount of \$2,156.88, drawn CC. C 2

Each check should to nade payable-to

2. The checka should be forworãed to Chief, Tss/Chemical Divioion, through Tes/Dudcat Officer, no later then Konday, 6 Ootober 1958.

3. This invoice ropresents-tho-total-anouns currently duthor ized wndor Suborojoet 56. hovever, since 1t is ensioipated that edaitional Suás vill be obligated sor this projeet, the files chould ECK FA not o closed.T DF 929 %9 MOUNT OF GZOZS RECEP... 1156 19c.

Chief TSS/Cherical Divisica

Attaahsents: Tevoice and Certirieatiora

Dlateibutlont Oda 0 2 - Adircceaa

56-21

290

22 September 1958

07589

[PAGE 48]
I hereby acknowledge receipt of the following two.checks:

Cashier'a Check No, A193o44, dated Hay 1, 1958, drawn on the in thə emount of \$26,220.00, made payable to

Cashior's Chock Ho. ICP 65624, dated Apr11 30, 1958, in the amount of \$1,048.60, dravn on ths payable to

5…22

RECEIPT

[PAGE 49]
: MOLTA, Subproject 56, -Involee §4, A11ot:ent 7-2502-10-C01

l. Invotco Ko. h is attachod covering the above subproject. Payuent should be node as follovs:

Cashier'a check 1n the azount of \$26,220.00, drawa on a E

Cashier's check in thp naount of §1,013.80, drawn. C. E

-Foch check should be rado payablā to the B

2. The checks should be forvarded to Guiet, T8s/Choaical Division, through Sss/Budget Officor, no later than Mondey, 12 May 1956.

C 3, Tis iavoice ropresents the total exopmt currently authorisel weor Dutorcjzot 56.-However, sineo it is snticipated thet sdaittonal foãs vill te obllgoted for\_this project, ths filzaltold cot bo.clooed. -ir PSWE AMOUNT OF S/

Chtof-TSs/Cbenical Diviston

Attechronts: Involce and Certifteations

Liotributico:

1C 2 10.CV1
S. 7

2 M hesce? 2. ASB 2 v T8D

TE3/cD(21 Apr 1958)

ÉVEJEOT

56.23

21 Apri1 1958

MESAORANDUM FOR: CHIEP, FINNCE DIVTSION

T3s/Budget\_officer

[PAGE 50]
CETTPTCATIOSA

(1) It ao heredy coxtifled that this io Invoico No. 4 applying to Subcrofeet 56 of ltaA, that perioiuance is saticisstory, that sorvicod are doing accouplisced in accordanco with ratual agreecent9.. that a detailsd cçonda of tho paçasaty and recsipto is on file in Eeo/cb, that thio bill is just ana correct aod that payuent thereor hes not yot been nodo.

212 /Chenical Divisica

fater

(2) It io horeby cortifici that this invoice spplies to Subpvoject 56 of Narra wuca vas doly epproved, and taat tas project is being eerrisi cut in aocetdance sith te osooranáua dated 13 April. l953 Tron the I to the Do/A, end the entersion or this. autority in suboequent re0eroda.

56-33

For porvices

LIVOICE

\$27,263.80

[PAGE 51]
I hereby acknowledge receipt of the following two checks:

-Cashier's check No. A176790, dated August 23, 1957, drawn 警in
on theeks
the amount of \$13, 110.00
Treasurers Check No, 68094,dated August 23, 1957, drawn on in the amount
the
of \$524.40.

DATE: 38 auy 57

56-24

RECEIPT

Sapuriet56

[PAGE 52]
-MEMORANDUM FOR: CHIEE, FINANCE DIVISION

VIA

+4 TSS. Budget Clficer

SUBJECT

MKUI.TRA, Subaroject 56, Invoice 93
Allotroent 7-2502-10-001

1. lnvoice i3 covering tho above sabproject is attached.L. Other iovoicos will follow. It is requested thet payment de maue \_as folkowst

Cashier's chcck in tho araount of \$13,110. 00; drawa on a E

Caahier's check ia the amount of \$524.40, dravn on E

Each check should be made payable to the B

IE Z. The checks should be forwarded to Chief, TSs/Chemical Divisioa, throvgh TaS.Budget Officer, no later than Tuesday,= 20 Augxst 1937....02%/0

12m.

Actiag chief Tss/Chomical Diviaioa

Attachn onte: Invoice and Certifications

Pistribetioa:

Grig f Z• Addvoosce

2766 725026

1 - Corptrollor

Lf- TSS/FASB 2 - TSS/CD

56-25

5 August 1957

[PAGE 53]
CERTIFICATIONS

(1) l is hereby certified that this is Invoice No. 3 applying to Subproject 56 el NKULTRA, that periormance ia satistactory. that serviceo are being accomplished in accordance with rautual agreemente, that a detatled agonda of the paymente and receipts is on file in TSS/CD, that this bill is just and correct and that payment thoreof has not yet boea made.

Actirg Chief, TSS/Chemical Division

Date:

(2) Re is heroby certified that this invoico applies to Subproject &56.of MKULTRA which was duly aoproved, and that the project is being carried out in accordance vith the memorandum dated 13 April 1953 from the DCI to the DD/A, and the extenaion of this authority in subsequent mcinoranda.

Roeearch Director

Dato:

56-25

For services

INVOICE

\$13,634.40

[PAGE 54]
0 56-26

[PAGE 55]
MEAORANGUMTORCOMPAOLLEA

ATTERTRON

F inanco vision

SUEJECT:

AlULTAA, Subproject Sa, Additioaal Authorization No. 1

Under the authocity graated in the nencrandum dated

-13 Aprii 1353, frvãa the DCI 1o the 00/à aad the extension of this

authoruly in subsequent memornada, Subproject 56 waa previousty

apiroved. Uoder tho sun:e authority an additioaal sum of S40, 903.20

has been authorized to cover the subpccject's expenses (thereby

pringiag to a total cf s10, 003.20 tunds ooligated during FY 57),

to be ebarged to Allotment 7-2302-10-001.

SIDNEY GOTTLIEB Chief Tss/Chemteal Oivision

APPRUVLD FCS COLIGATION OF FUARS

Date: MAY 3

Ofstriaution:

$$
\sin \frac { \pi } { 2 } = \frac { 1 } { 2 } \sin \frac { \pi } { 4 } + \frac { 5 } { 2 } \sin \frac { \pi } { 4 } \sin \frac { \pi } { 4 } \sin \frac { \pi } { 4 } \sin \frac { \pi } { 4 } \sin \frac { \pi } { 4 } \sin \frac { \pi } { 4 }
$$

$$
1  \Gamma S S / ( \mathrm { C L }
$$

$$
\sin ^ { 2 } + \pi = \pi + \sin ^ { 2 } \alpha + \sin \alpha + 3
$$

2 - TSs/Cv

PSS/C(1 ay 57)

50-27

1 kay 1957

[PAGE 56]
SUBJECT:

MKULTRA Subproject No. 56

1. The purpose of this project is to provide fundsto continue the research program conducted by at mneewe This program is designed to exploit all the knowledge and facilities available to its director in providing answèrs to specific questions of direct interest to the Agency in the area of alcohol intoxication. In addition, those areas of basic knowledge required to provide these practical answers wili be developed. It should be noted that although the attached proposal describes the facilities which will be used in the study, the program itself was deliberately described in general terms in order to comply with its unclassified status.

2. Attached is the research proposal submitted by requesting a renewal of the project for another year.-According to his interim progress repor, considerable progress has been accomplished; in a relatively short period of time, to wit: additional laboratory facilities have been equipped and placed int functional state, additional personnel have been recruited and specially trained, and substantive research completed to date and now in progress.

3. In view of the above, it is desired to describe more specifically the various 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 metabolic pathways that will allow the alcohol to be stored rather than completely metabolized.· Studies will be conducted on a number of agents claimed to expedite al-- cohol metabolism (alanine, pyruvate, fructose, alcohol dehydrogenase).

(b) Determine the effectiveness of foodstuffs in delaying the absorption of alcohol from the gastrointestinal tract, Investigations will be conducted on the effects of various fats on the absorption rate of alcohot. The effects of gastric mucin, kaolin and wine buffers will also be determined.

(c) Determine the effectiveness-of sympathomimetric drugs in

DRAFT/25 Aprit 1957

Dounceded to: ty at rty .s Cate: n 1377

560-28

Doneroded to: by ugrity of: e -datet-1377 T2 IPOTCL BY

[PAGE 57]
Dovasoced to: by cutority of:mr cate: Ju 1977

E2 IXFDET; BY de

delaying the absorption of alcohol from the gastrointestinal tract. The effectiveness of various sympathomimetric drugs on the emptying time of the stomach will be investigated on larger animals, (Amphetamine, Nalline, Bonamine)

3. 'The funds for this project will be transferred using the as cutout in the usual manner:

4. Costs for this program for a period of one year beginning August 31, 1957 are estimated to be \$39, 330.00 to which must be B added a four percent (4%) fee to the (\$1,573.20). making the total amount \$40, 903, 20...Charges should be made against Allotment 7-2502=10-001. 2

has requested to submit to them a summary acsounting on-an annual basis of all monies received from @DAlso, it has been requested that any unexpended funds be returned at the ctose of the grant year.

6. The requirement for a six months! informal accounting on the part of the principal investigator is waived.

7.Title to any permanent equipment purchased by. shall be retained by  in licu of higher overhead rates.

8. In connection with travel under this project, it is agreed that the Agency will accept the travel documentation and accounting which confcrm with the practices of

9. It is agreed that technical reports reflecting tho progress of the research program shall be submitted at mutually acceptable intervals.

10. is cleared through TOP SECRET and is aware of the true purposes of the program, He has also agreed to

56-28

[PAGE 58]
comply with the requirements of the Memorandum of Agreement.

Chief, Branch II TSS/Chemical Division

APPROVED FOR OBLIGATIONAPProVed: OF. FUNDS:

Research Director Chief, TSS/Chemical Division

Date:

Attached: Research proposal.

Distribution: Original only

211 raded to: ty ouascrity of: cater J:C 1977 E2 IUPDET CL BY E2 IUPDETACL BY comply

56-28

[PAGE 59]
Gentlemen:

We are desirous of continuing our work further on measures aimed at permitting consumption of larger amounts of ethyl alcohol without an increase in nervous system depression,.. Considerable progress has been made in our research program since l September 1956.

Our laboratories have been equipped and placed into functioning condition since the last visit of your representative, The suite of three rooms in the Nurses' Residence has been converted into a an Enzymology Labora-
Biochemistry Laboratory and an office and machine shop for myself. The
tory ford Enzymology Laboratory is set up for in-vitro work with tissues and enzymes. In addition, a Neurophysiology Laboratory, named for our ad-C jacent to the Animal Surgical Operating Theatre, on the fifth floor of the Medical School Building, has been allotted to the Department of Neurology under me. As a nucleus for expansion, the Neurophysiology Laboratory is alrcady equipped with an 8 channel Grass Model 3 EEG and a Meditron EMG.

As an informal interim progress report, the following research for this year has been completed or is very near completion.

The deposition of carbon derived from the ingestion of radio-A. active alcohel has been published under joint authorship with Mstand aein the sonea

WARNINGWOTICE SENSIOVE ROTEALICENCE :ONRCES ANONETHOL INVCLVED

56-28

1 May 1957

[PAGE 60]
B.A paper on the EEG in acute alcohol intoxication has been submitted for publication to the Quarterly Journal of Studies on Alcohol.

We have completed a paper on the effects of premedication with nicotinamide on the speed of alcohol metabolism,

D. The comparison of the deposition of radioactive carbon in the tissues after continued feeding of alcohol and acetate is being completed by

E. The dehydrogenase method of alcohol determination has been standardized by awhereas continues to refine the dichromate method. With these two micro techniques developed to a satisfactory stage, in vivo studies on mice can be conducted.

It.is\_our\_ proposal to continue to conduct our next year's investigations along the following lines:

(1) Expedite the removal of alcohol from the blood stream by selective metabolic pathways that will allow the alcohol to be stored rather than completely metabolized.

We plan to study the effects of a nurober of agents that are claimed toexpedite alcohol metabolism (alanine, pyruvate, fructose, alcohol dehydrogenase). Preliminary studies indicate that the nutri-. tional state of the animal is very important and if this is maintained at an optimal state, none of the agents show any. striking,-if indeed statistically significant effects.

(2) Determine the effectiveness of foodstuffs in delaying the absorption of alcohol from thegastrointestinal tract.

Preliminary work deroonstrated that neither carbohydrate nor protein can be expected to delay the absorption of alcohol. However, 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, peanut, theobroma; soft animal fats, butter, suet, lanolin.) The effects of gastric mucin and kaolin will also be investigated in this -respect,

560-28

2

WARIING NOTICE SENSITIVALINTLLIGENCE SOURCES AND NETIAOS INVOLVEO

[PAGE 61]
Work on the effects of wine buffers on human subjects is being continued under the auspices of a

(3)Determine the effectiveness of sympathomimetric drugs in delaying the absorption of alcohol from the gastrointestinal tract.

With the addition of the Neurophysiology Laboratory,, we plan to re-enter the field of working with larger animals (dogs, cats), and testing synergism and antagonism between alcohol and other drugs.

Since we are convinced that the effectiveness\_of fat in delay= ing the absorption of alcohol from the gastrointestinal tract is related to the slowing of the emptying time of the stomach, it is desired to investigate the effectiveness of other measures which might have the same effect. The sympathomimetric drugs suggest themselves as likely candidates in this respect, (Amphetamine, Nalline, Bonamine, 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 participation. The follówing is the proposed yearly budget:

Nergs 7,500;00 Fellow, neurophysiologist (Ph.D.) 8.000.00 8,000.0v

Enzymologist-(PhD.) 4.000.00

4.vUv. vv Laboratory, animal keeper Laboratory,auunasvzr 3 500.00 3,500.00

Equipment & apparatus

Supplies (chemicals, radioactive 3,000.00 atcohol, etc.) 1 500 00

Total \$34,500.00
Overhead 14% \$39.330.00 4,830.00

0

ó

26020

3

[PAGE 62]
It is our hope that with our assembled research team, more definitive results will be obtained in the very near future.

Very truly yours,

Professor of Medicine (Neurology)

0

O

56-28

4

[PAGE 63]
56-29

[PAGE 64]
RECEIPT

Receipt of \$3, 028.76 from the  representing

a return to the Agency of surplus funds under contract RD-37 from

Dato: C/4/56

5630 FILE-SUB-S6

[PAGE 65]
RECEIPT

Receipt is hereby acknowledged of the sum of \$2, 360.40 in cash,.

RECEIPT

Reccipt is hereby acknowledged of thē sumof \$2;360,40 in cash.

[PAGE 66]
RECEIPT

Recolpt of S10, 440, 93 from tho representing

a return to the Agency of surplus funds under contract RD-37 from

C

Dator //56131

D

CUB-5650-32

[PAGE 67]
RFOBIPT

I horety aokowlodge rocoipt of tho folloving two checkst

Cashier's check No, DH 35652, dated April 16, 1956, drewa on in the nucunt of s510.67.

official Check No. G 8253, dated April 16, 1956, drawn oa in the asount of E €10,190.48.

856-33

[PAGE 68]
: Tes/cudget Officer

\$ MCLA sroject 56, Iavotco 2.. Al1otment (-25C2-10-001 ∴

l. Invoice 2 for the abova suborojeet ia ettached. Payannt should be code es follova;

shior'a cheok in the anount of è310.67, dro o a E able to the si

Czcdter's cheek in the seount o? ș10,190.k8, drasm on

Osch in the anount of 10,076.19,-in\_denorination of ono hndrèd, fifty, and tuenty dollor bills,

2. Eoth chocka end tho cash shoulal ba Toraded to Chief, Tes/cseriesl Divisten, thrcagh Ges/Eudget Crficer,, :7 vo latee Chon 20 Ayril. 1956. 1

3. Tris in a Tiral invoteo. A total of 831,66.06 ws celigated drring 7Y 5e wrier this saurolect. Esdver, olnee the voas: is rot yot caoploted, tho filos ou Dubprojoot 5G chenld not be olosed.

Actachasntst Zmnotco à Certificationa

bictrdlutien: Osig 6 2 - 7oece 1  Jatotrolter

CERTFET

Chier ao/olonical piviatca

[PAGE 69]
MEIGAEM FOR CHIP, FEAH DIVISIGA

1 To/evdgat orrieer

SURGDTR

1 NavuTa Sutprojoet 5, Iavoleo 2 A11otent C-2502-10-001

l. Lavotee 8 for tho ctovs subproject io attachol. Payzent shculd te eede os folloust

Cachtor's chock in the scount of éöl0.67, draaa ca e E Nable to Eo 4 B

Coaler'3 aheet in the wricut of tlo,J0o.43, drava on 12vcblo to tho mee B

Coah tn the cvant or slo,07.19, 1a doncsinatica o2 one hroi, firty, sna twenty áollor billa.

8. Eoth chocks end the:cah-should-la-forarlol to Ohier, des/herdcel Divisica, Wrovaa Ts/Éuiges onpicer, no lator thuan 20 èpr11 153t.

3. is is a Siral invotce. A totsl of 51,616.00 vs cdilisatct dvzirz s7 sé wder thio eutyrojeot. novezer, oince ta vors is net sot cocpleted, the filss cn dutproject 55 atoula not de clozot.

OILY COPTLAUD Cntet 4

Atioetrnntst Bevolee à Certiclcations

1 CESTIFY THAT FUNDS ARE AVAIRADLS:0n. ORLIGAHON PUEENCE No. 162.2 11CHAGE10 MENN6202--0

1:1 it ri 1.4

36-34

9 Açril A956

[PAGE 70]
CERTTFICATTQRS

(1) It is horeby certified that thio.is Invoice 2 applying to MoaA Suboroject 56, that porfcrneo is catiofeetory, that the servicos are being seccaplished in accordaace with mutupl agreecents, that a dotrilod agenda of the paynonts end recqiyts is on file in TSs/cD, that this bill io just and corect aná that payment thereor has not yet been mode.

Sidney Gotlieb Chief, TSS/Chemicel Division

Chier, Tss/cheaical Divioion.

Date: 915

(2) It is horeby certifieà that thio involce applios to ILA Subprojeet 56, vhich ves duly epproved, and trat the projeet is boirg corriod out in accordance vith the tazmorandum datoa 13 April 1953, Iron the IOI to the ED/A, ed.the oxtension cf this authority in suboeqent comoronãa.

Latet

56-34

INVOICE

For serrices

\$21,077.34

Heoeareh Director

[PAGE 71]
HIXCEIPT

I hereby acknovledge recoipt of.the folloving checkst I hereoy acauv

Cashior's Check M7097 E in the emount of \$3,732.88;

Cashier'a Check fT35633 E in the aoust of șh05.331

both checks payable to

[PAGE 72]
RECORIDCA FORI CATES, FIIAGOE DIVISICA

i Ts/Bodzet offieer

I5FA Subproject 56, Iavoico 1
A11otcent 6-2502-10-001

1. Involce 1 coverlng the ebove suborojoct ia attacbed. Other invoices vill follov later.\_It\_io\_nequgtea that poynont be mle in the rolioving pamer:

Caohicr's check for 3,732.08, @rawa on E

Cashior's check for dho5.33, dravm on both checks tayatle to the

Cash in the caount of £6,h0o.45, in doncairatioa of one honered, fifty, end tueuty dollar bills.

2. The cesh and both checka should bo foriarded to Chief, TSs/chenieel Divioion, through m.s/Doáget Cricer, no later then 20 Apri1 1956.

DASH PAYNENT H AMOUNT DF CGIRS :2APR
RECEIVED. 1953

Attaciyaentot Involce f Certirldations

we/cn (5 Aori1 1956)

STENEY COETLENS Chio2 res/chenleottscloE CHECKIRZ ANTTUNT OE G RECEIVEO.

心

56-36

6 Apeil 1956

[PAGE 73]
CEROTPTCATIONS

(i) It is hereby certified that this io Invoice 1 ayplying to Subproject 56 of MOlA, that porfonmonce is satisTaotory, that tho services are boing eccoanlishoa in acçorusnce vith rutual airecrents, that a detailod açenda of tho yeyaents and receipts is on file.in TS3/cD, that this biil io just and correct snd that poyuont thoreor bos not yet tęen rado.

Dato:

Chiet, TSs/Chenical Division

(2) It is horety cortified that this invoice smplies to Sulprojoot 56 uéer Kolsta waich vns duly aoproved and that the projcot is taing corricl out in cccorionce with the pouoronäñra dated 13 Arr11 1053 froa tha D0r to tho rD/A, and the. extençion of this authority in subsequent uovoraala.

56-36

For services

LIVOTCO

\$10,538.66

Tocenrch pireeter

[PAGE 74]
6.2507.10.051

[PAGE 75]
COPTHER

Franeo Davisien

1 NtT, Cutprojoet SS

oen sard to 10-1X1

Actirg Ctdet /orentcal Divieion

FOR 503 FUET31

LCERTIFY THAT FUNDS AREE RATIO NE

50-38

1 Wrch 1056

tf7566

[PAGE 76]
alcohol research by 1. The purpose of Sübproject-56-is-to continue york on 8

2. The scope of the research program-will be to pursue studies on determining the effectiveness of foodstuffs in delaying absorption\_of alcohol\_fron the gastrointestinal tract; determining the effectiveness of various syapathoniometic drugs in delaying the absorption of alcohol fron the gastrointestinal tract; expediting the removal of alcohol from the blood stream by selective netabolic pathways that will allow the alcohol to be stored rather than completely metabolized, and developing a simple and roliable test of tolerance to alcohol for use in the selection of personncl and prediction:of- behavior.

3. The. cost of this.program is estimated to be \$30,400.00 for a poriod of one year. To this sum must be added 1,216.00 representing a four percent service charge-to Therefore, the total cost will not exceed \$31,616.00. Charges should.be made against A1lotrent 6-2502-10-001

has requested to 4. submit to them a surwary accounting of monies received Also, they requested the return of any unexpended funds receivçà recelvuu ^

5. Title to any permanent equipuent purchased shall be retained by them in lieu of higher overhead rates.

6. It was mutually agreed that documentation and accounting for travel expenses which are reimbursable shall conform with the accepted practices of that institution.

to: 1704 city of: datet 1977 EO IVDET L BY

560-39

1 March 1956

MEMORANDUM FOR: THE RECORD.

SUBJECT

:  MKULTRA, Subproject 56

[PAGE 77]
agreed to comply with the requirements of 7. the memorandum of agreement.

APPROVED FOR OBLIGATION OF FUNDS:

Research Director

Dato: Iareh 2, 1916

Attachment: Proposal

5039

Distribution: Original Only

00

[PAGE 78]
Gentlemen:

We are desirous of continuing our work-on-measures-aimed at permitting consumption of larger amounts of ethyl alcchol without inerease in nervous system depression. Progress.in the past year has been slow; this may be attributed largely to the necessity of uy devoting a larger share of uy time to developaent.of a growing Neurological Service in theMedical School. As a result of this effort, has now sccured supoort from

which have made a residency training progran in Neurology possible, with inorcased personnel to put it into effect. Accordingly, I will be able to again devoto a reasonable agount- of-personal time to research in alcohol, and want to take this opportunity to apply
for continuing support.

It is our proposal to conduet our investigations along the following lines:

(1) Determine the effectiveness of foodstuffs in delaying ebsorption of alcohol from the gestrointestinal tract.

Preliminary work relative to determining tha effect of various foodstuffs in slowing the absorption of alcohol has been of more promise, in that, as set forth in the preliminary report forwarded to you previously, the ingestion of reasonable amounts of fats or oils previous to the taking of alechol has been demonstrated to lower significantly the peak value of blood alcohol concentration. We believe that further work along this line is indicated, .to determine the optinal timing of the fat ingestion, and the dogree of unifortity of the effect in different individuals.

10 Febrvary 1956

WARNTECE

[PAGE 79]
(2)Determine the effectiveness of sympathoniometic drugs in delaying the absorption of alcobol from the gastrointestinal tract.

Since we are convinced that tho effectiveness of fat in this regard is related to slowing of thc emptying time of the stomach, it is dcsired to investigate the effectivenoss of other measures which might have the same effect. The sympathominetic-drugs-suggost themselves as.likely candidates; indeed amphetamine vas shovh- rmr to have such an effect. Although such measures cannot be expected to delay indefinitely the absorption of alcohol into the blood, theymay be sufriciently effcctive-to delay absorption until the stomach can be emptied by induced vomiting by some individuals with soue facility in this naneuver. Of course, the ideal-substance vould be a çompound that would combine with the alcohol in a form that would be unabsorbable, and it-is possible\_that sonc.such compound not in itself unduly toxic might be found.

(3) Expedite-the removal of alcoholfrom the bood stream by selective metabolic pathways that will allow the alcohol to be stored-rather-then coapletely metabolized.

Another point of attack on the problem is the search for measures that will expedite the elimination of absorbed alcohol-from the:body.The amount eliminated in the vrine, breath, and sweat is not of sufficient magnitude to be of practical importance even if doubled, and obviously a greater increase than this in volume of any-of these channels would not be practically acceptable-for the purpose-inwhich we are interested. Increased combustion of a\_cohol, especially if coupled\_with slowed-absorption, might be highly effective. If the normal pathway of complete combustion to carbon dioxide and vater alone is considered, one is limited theoretically by the fact that the ordinary rate of cobustion supplies about half the caloric output needed for the boly metabolisu of a sedentary man, and thus any considerable increase would produce an excess of heat. Even so, it is probable that the difference of rate of alcohol metabolism brought about by a diet that will favor the burning of protein rather than fat will be of sufficient magnitude to allow

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alcohol to be absorbed at double the rate without an increase.in\_tho-slopo of\_the blood alcohol curve. Even more effective would be measures aimed at promoting storage of the-alcohol-by utilizing alternative metabolic pathways, so thet combustion would not be couplete, but that the acetate formod from the alcohol might be converted to glycogen or.fat. Work of others with tracer-techniques-using-radioactive carbon incorporated-in alcohol-seems to shcw that a small proportion of the alcohol takes this pathway. It is our desire to-explore-this possibility more fully with-long-term feeding-experinents-in rats and mice.

(4) Develop a simple and reliable-test-of tolerance to alcohol for use in selcction-of personnel and prediction of\_behavior.

We have demonstrated (and indeed"it-is-comron knowledge) that individuals vary greatly in their resistance to the-depressant-effect-of-alcohol Indécd it is because of this difference in tolerarce that. the whole study is necessary. Would it not be profitable to develop a simple end-reliable test of tolerance to alcohol which would be of value in the.selection of-personnel whose mission and job might entail the necessity.of consuming corsiderable quentities of alcohol?—The techniqucs which we have developed-over-the yearsin-this-type.of-research should be valuable in this cornection.

It is our proposal, then, to explore further the effectiveness of foodstuffs and drugs in dclaying absorption of alcohol from the gastrointestinal tract; to investigate by the use of alcohol incorporating radioactive carbon the possibility of expediting the removal of-alcohol-froar the-blood by favoring metabolic pathways that will allow it to be stored rather than completely burned; and finally to develop a simple and reliable test of tolerance to alcohol for possible use in the selection of personnel.

Q

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The experience in this type of research we hàve already gained over a period of sone 25 years in similar.investigations. We also have the facilities for determination of blood alcohol concentration, and apparatus for testing the degree of nervous system-depression produced -by alcohol.My own active participation in the work is reasonably assured by the addition of personnel\_to-the-Modical.School faculty to take over the bulk of the routine teaching and administrative.detail of the Division of Neurology. It will-be necessary to socure additional technical assistance, and if possible a research Fellow trained in neurophysiological techniques to.assume-the burden of-the actual testing of subjects. Funds will also\_be required for reimbursement of subjects for this rather unpleasant and arduous research, and their retention in the hospital under observation during the period that they are intoxicated.

The following is the proposed yearly\_budget:

Neurologist (MD) -9,000
Fellow, neurophysiology (PhD) 6,000
Technician, chenical 3,600
Clerk-secretary 3,000
Laboratory-animal-keeper 1,800
Equipment & Apparatus (Glassware, ctc.) 1,000
Supplies (Chemicals, radioactive carbon, alcohol, etc.) 3,000
Subjects' fees (incl. hospitalization) 3,000 TOTAL \$30,400

Although itis hoped that definitive results might be cbtained in a year's time, it would be highly desirable in assembling such a team to plan for at least a two-year period.

Very truly yours,

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MTA Batrocot5(.

Date of Origiaal Ferica to Allotaont Acount of 2 Man 56Iyeen 6-2502-10.001 31416.00

Aelitiecal Perict Alloteont Axcrnt af taded to #7 51 H4957to 31105587-1502.10-00190.903.20 31uy689-2608-15-90956,078.88 4 Leg. 19272.600525-1009.420218,657.60

Acaunt 1//56 1053866 21072.34 2 4/9/56 21077.34 -0 3 15lug5713,63410 37.268.80 1131065827268.80 nth317pt5856.078.8856,078.88 523.8μ15815607885 Lutt4 18,657.60 t 601281 60118, 657.60

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