Doc 0000151541

)partment of HEALTH. EDUCATION. .\lu WELF.ARE • Public Hearth Servi~~ ----------------- NATIONAL INSTITUTE~.r OF HEALTH r!iJ . Ill lti"-TIMO, ADOIIUS Tllll ADDICf!ON RESEARCH C~NTER 24 January 1956 HATIONALIIITITUTCS OP MINTAI. HU~Tit U. I. PUILIC HIAI.Tit SUVICI HOSPITAl. aoazooo blllll9f011, ICIKTUCKY -·-;··-------- ram attachlng fo~ your information copy of a r¢quest to the Offlce of Naval Research for renewal of our project here. In the event the ONR feels the project should b¢ continued I will arrance to have. the business office of the Natrona I .Institutes of Health send;·thts on at the prop~r r.tme, lat¢r in the spring. You will notice that the amount of money requestea is som~wnat greater than t.~ previous years. This is necessar"Y' in order to provid<! funds :to cover the increase in Ci vi I Service pay which we n t I n t o e f f e c t J n M9 r eft I 9 S:-5 • You nave, no doubt, b·y_now received a copy of my letter to Dr. Pogge of The S. Merrt II :compa:ny concerning efforts to ':·~·m. reverse the LSD rea~tlon with Frenqu~l. This experim~nt was ·n> for two reasons: we had rece lved pers is+ent underta~en reports from other laboratories that large doses of Fr~nquel would ameUofate tne LSD reaction,. and (2) because. the company claimed that in our original blocktng experiment the degree of mental effect was not sufficient for the effects of Frenquel to be e v i de n t • As yo u s e e f r om t h e d a t a i n t h e I e t r ?. r , t h i s reversal expe~tment was a complete failure. We were unabfe to distinguish injections from placebo injections. Frenqu~J COMBINAiTIO\JS OF HYOSCINE AND,LSD These ~xoerirrents wC?r~ carried out in an attemot to d~dermine whet h'e r Hy o s c i ne wo u I d a me I i o r a r e or e n h a nc e t h ~ LSD rea c t i ~ n • Two s e r i e s of ex per i men t s were don'! • I n the f r r s t s e r- t e s II negro subjects received in order Hyoscine rando~ized ~lacebo pfus LSD pl3c~bc; Hyoscine placebo plus LSD; 0.42 mg. of . The image displays a graphic with a large, stylized title "THE BLACK VAULT" in white, outlined in blue. To the left is an illustration of a bank vault door with a circular dial and various levers and gears. The text on the right explains that the document is from "The Black Vault," an online database of declassified government documents, specifically mentioning the "MKULTRA/Mind Control Collection" and providing a website address. There are no photographs, handwritten annotations, official stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures present on this page. s e r i e s of ex per i men t s were don'! • I n the f r r s t s e r- t e s II negro subjects received in order Hyoscine rando~ized ~lacebo pfus LSD pl3c~bc; Hyoscine placebo plus LSD; 0.42 mg. of . Hyoscine LSD placebo; 0.42 mg. Hyoscine plus LSD; 0.64 mg. ~Ius Hyoscine plus LSD; 0.85 mg. Hyoscine plus LSD. Both Hyoscine --·- -- --·- ' and LSD were atv orally under nblfnd" condttJons. The dose of LSD was micrograms. Measurements were those described in pre us reports. - · R~sults are shown In left side of tab-le. You ·wfll note th~t 0.64 mg. and 0.84 mg. of Hyoscine Increased pupil Jary . dl(atation seen after LSD, reduced blood pr~ssure response, Increased the number of positive answers, and Increased the c l f n I c a I . grade of react ton, but the I a s t wa s not s t g n if f c a n t ~s compared with Hyoscine placebo and LSD. In the second series of experiments 12. subjects were used and recetved in randomized order: Hyoscine pla~ebo olus LSD placebo; Hyoscine plac~bo plus LSD;· 1.3 mg. Hvos.C:rn~ plus LSD placebo; and 1.3 mg. Hyoscine plus LSD. Results were similar but more· marked with lower doses of Hyoscine than in the first series·. There was marked increase in pupillary dilatation, marked decrease in blood pressure response, marked enhancement In the number of pos tt lve ~uestions, and •n increase in the clinical grade of reaction ,.. . whtch, however, was not srarist.tcally significant. In thts last series of experiments th.e side- e_ffects of Hyoscine v;ere v;_.ery prominent and fricluded sensafi'ons of giddiness and dlzziness-,_ marked blurring of vision, marked d r yn e s s o f mo u t h , a b s e ~ c e of pe r s p i r a t i o n , a n d s I t g h t co n - fusion. It was yerv ~~sy to see that the patients had both tSD and-Hyoscine effects. lmpre.ssfon was that of a combination of drua toxlctrtes ratJier than of any:soecific enhancem;!rd of the LSD reaction. T.he Hyoscine side e-ffects orobably meke use of this combination impracl)cal~ ' / Ql AMPHETAMINE AND LSD These experiments wer~ carried out because Hocn has stated The document page is a typed letter with handwritten annotations. A header indicates it is from the National Institutes of Health, dated January 24, 1956. Handwritten in the top right corner is a circled number "64". There are also two sets of handwritten marks resembling parentheses containing numbers "(b)(3)". The text discusses research on LSD and a drug called Frenquel, and mentions experimental procedures involving subjects and injections. Near the bottom right, a handwritten alphanumeric code "A-224" is visible. No photographs or diagrams are present. The document appears to be a research paper with typewritten text and a handwritten annotation. The text discusses experiments involving LSD and Hyoscine, followed by a section on DL AMPHETAMINE AND LSD. There are no photographs, diagrams, forms, or stamps visible. The only handwritten annotation is a sequence of characters, "-22", in the bottom right corner. The content is otherwise devoid of visual elements beyond the typed text. patients had both tSD and-Hyoscine effects. lmpre.ssfon was that of a combination of drua toxlctrtes ratJier than of any:soecific enhancem;!rd of the LSD reaction. T.he Hyoscine side e-ffects orobably meke use of this combination impracl)cal~ ' / Ql AMPHETAMINE AND LSD These experiments wer~ carried out because Hocn has stated th-a.t r.'le tharnohe tamtne· a.me I iora res the LSD react: Ton and a I so a because of rheorei"icai cons iderat ton advanced by Dr. \•/ikler. Eleven. subjects were ~sed and rece·ived tn randomized order: dl-amphetamine placebo plus LSD placebo; ,.il-arrip!-etamine ol<!!cebo Pfus-LSD;' .i.l_-<'lmphetainine plus LSD placebo; end EJ.-ampnetamine pfus ~LSD. Both drugs wer.z·· given orally. Tr.e dose of amp!-leta:;;i"re was 20 mo. and th~ dose of LSD was 60 mi~rccrams. ~f-arnoh~ta~in~ was· given one hour prior to LSD to provide time fordl-ampheramine effects to develop. R~sults are shown in the table.--rhe only sfgniflcant change with the combination as compared with LSD alone was increase tn the blood.pressure response. Effects wtth this dose of -dl-amphetamine a·.Jone·· in--o-ur si.J'bjects, however, . . .. -_ ----~ -:-----.----:·~ were mlld and the wor~ really needs repetttton, eTther using farge doses of dl..-amphe.tamfne or som.z more potent sympatho mimetic amtn·e, s·uch as dextroamphetamine, in dos.es suffTcT.enr to induce a more definite reaction in our patients. RESERPINE AND LSD The experiments pre~iouslv reported have been amplified using larger amounts of Reserpine. It was felt that this work Js important because of reports by Srodie, Htmvdcn, \~ooley and others on the possible relationships between LSD, Serotonin, and release of Serotonin by Reserpin·e. In these new experiments 12 negro subjects received in random balanced ordeT: Reserpine placebo plus LSD placebo; Reserpine S m~. orally plus LSD placebo; Reserpine placebo plus LSD; Reserpine 5 mg. oral (y plus LSD; Reserpine 7.5 mg. orally plus LSD; Reserpine 6 mg. orally plus LSD; Cosage times are shown in the table. It ts • evident tnat there was no blocldng of. the LSD effect on any of our ~easurements. -':' The most intere:~ttng observation was that the patien·ts seemed to be worse when they recelve~,.7.5 mo. of Reseroine orally or 6 mo. intramuscularly ;Ius LSD. Thewtntensific~tton of the rea w c tion was mosf ~rcm ~ i nent in the group that recel~~d Reserpine Intramuscularly. In b~th these groups, pattents developed trem-::~rs .and ankle cton.us. ~lGntally, nervousn'<:ss, ~on.riJsion, apprehension, ~nd more frequ~nt~~rid more v~vTd halluclna~ions were reported. These changes are The page contains a typewritten document filled with experimental findings related to Reserpine and LSD. There are no photographs, stamps, or forms visible. One handwritten annotation, "4-22-", is located in the bottom right corner. The text itself hints at experimental procedures and observations, describing patient reactions and proposed future studies. There are visible black marks on the page that could be ink spots or minor smudges, appearing randomly and not obscuring any specific content. 6 mo. intramuscularly ;Ius LSD. Thewtntensific~tton of the rea w c tion was mosf ~rcm ~ i nent in the group that recel~~d Reserpine Intramuscularly. In b~th these groups, pattents developed trem-::~rs .and ankle cton.us. ~lGntally, nervousn'<:ss, ~on.riJsion, apprehension, ~nd more frequ~nt~~rid more v~vTd halluclna~ions were reported. These changes are not appar~nt In th~ figures in the tabl2 ~ecaus~ our methods of measurement are not adequate to reveal them. In ratfng knee jerks, ·no+ntng is allowe-d for f·remors or for clonus. In asstgni~g clinical grades, no allowance is made for the intznsit"y of symptoms. Af rhe pr~s~nt ttme we are unable to determine whether the increase represents a specific enh:~ncem<?J'It. of. the LSD react ion by R~s.e~pine~ or ·,.-~r""-',".,·..-~·,.-,·.,. .. .,·.. t-~ ·m,·.,·,-.~·.1-,,·..J -~ .,..." -"'·"·"·'"-"·t,·._·f-tlf·-·t,.-..,·"·' r""'l:'."c' t·-·••·• ~- , . . , .: , _ _ , ' , : ,. : . : . :J. .. 0" " '' '" ,. - . ' . • : ' . 'C _, . : . , . . . ~ , .. We feel that thTs observation has greed. th'~oreticcil· importance and mav ooss ibty have· some orac~ k·a I use. ':ve· clan: (I) to atte.mof 'to est"lbl ish rhe d\~·le·r~rous effect of -Reseroine on the L~D reac~ion fir~ly by stu~ving the effect of R~serp1ne combined with mi,i.ilal doses of LSD, f2) to develop raring systems which will allow for the neurological change~ and a I t e r a t i o n s i n i n t e n s i t y · a n d. qua I i 7 y of s yr:1 p t oms , ( 3 ) i f' we -can, firilly est~blish thar Reserpine makes the LSD reaetion worse, and study the effects of Reserpi.ne on tolera~ce to LSD. BUFOTENINE ~ ~ffects have n observed wrth doses of 10 mg. of thts substance or·a t ly. We have now been g.tving the drug_ intra muscularlY and have gradually increased the dose to 15 mg. be~n _MUd toxic symptoms have obser•ted which include sensations of a nband around the head,' nausea, and persplrar ion. Effects ~re apparent withtn ten minutes ~nd last less than two hours. One of 4·pattcnts reported seeing spots of color on t.he wall. \Y/e are_sttll gradually Increasing the dose. O.IOL !QUI '1/e have been·asked by Doctor Ketv of the National lnstttute of Menta I nea lth to The document is a typed, single-page report with handwritten annotations. At the top, the term "BUFOTENINE" is clearly typed, followed by a description of its effects. Below this section, "OL IOLIQUI" is typed, followed by another experimental description. Centered near the bottom is the heading "NEUROSURGICAL PROJECT AT THE NATIONAL INSTITUTE OF NEUROLOGICAL DISEASES AND BLINDNESS, NIH." Below this is a narrative account of a proposed research project. The document concludes with a handwritten signature "Harris Isbell, M.D. Director" below "Sincerely yours," and "Enclosures: 3 Tables. Copy of Proj. Description f.y. 1957." A handwritten annotation "A-22" appears in the bottom right corner. No photographs, diagrams, or official stamps are visible. and persplrar ion. Effects ~re apparent withtn ten minutes ~nd last less than two hours. One of 4·pattcnts reported seeing spots of color on t.he wall. \Y/e are_sttll gradually Increasing the dose. O.IOL !QUI '1/e have been·asked by Doctor Ketv of the National lnstttute of Menta I nea lth to study the effects of this crude drug. PreliminarY ~xploratton ts now going on. Doses of 0.8 gram of the ground seeds (approximately 20 seeds} caused no d l s c e r n t b 1e e f f e"c t other t h a n s u b j e c t i ve report s of b I u r red vision tn 2 of 4 patients. We are continuing to increase the dose-gradually and will report if any strtkln.g resull's are o·b t a i n e d • NEUROSURG!C6.l PROJECT Af"THE r~T IO~L INSTITUTE OF NEUROL·CGIO;t. DlSE..A.SES AND Blti'IDN~SS, N\H. / I h a ve d i s cussed t h is pro 1e c t w U h Doc tor ·.:~: i k 1e r • 1 t h a s been proposed to study the effects of drugs on perceptual tracts, pathw«ys, and responses using neurosurgical patients c~rrled tn whom cortical exploration and extirpation is out for eolleosv. Both Dr. 'XIikler and myself believe that this a p~oject would. be verY important which would have great t he or~ t i c ·l I s i o rr l f i c a n c z • l t i s c e r t a i n I v wo r t h y of s up p o· r t , b u.t ne it her of us are i n an v oo s it ion- to advise as to wh ~ t h ~ r .... - "'C~ '~ c .... b- .... -o· .... r""·""A r~:.-n.!-' 'y ..,,. h • ,; uu "'".ovr-',v toc;,•.l I IIICIII...IOit e K · S i n c e r. e 1v . your \i o· I ~;/ /vvV~.10 ~.PZ rra;;is· Isbell, M.D. Director Hl:.rn:lw 3 Tables. Enclosures: CopY of ProJ• Description f .y. 1957. --- - - --- - ~ -- .. fj E FF E CT S "Of CCVv\B INA T I CNS OF HYOSC I NE AND LSD -· - ~ sure Placebo- Placebo- 0.42 mg. 0.42 mg. 0.64 mg. O.S5 Hl:.rn:lw 3 Tables. Enclosures: CopY of ProJ• Description f .y. 1957. --- - - --- - ~ -- .. fj E FF E CT S "Of CCVv\B INA T I CNS OF HYOSC I NE AND LSD -· - ~ sure Placebo- Placebo- 0.42 mg. 0.42 mg. 0.64 mg. O.S5 mg. Placebo- PI cebo- 1.3 lffig. I • 3 mg. (1 Plac~bo LSD Hyoscine Hyosclnt Hyoscine Hyoscine PI ace bo · LSD Hyoscine Hyoscine -1- LSD 4- LSD .._ LSD .J. LSD .... c .. , , . .... " rk ... 0.61 ... 2 .59* ... 0.51 ... 2. 73il- ,, ; ... 3. 30~1- . ... 2.46":1- -1- o~.sJ 4. 3.08* .J. I .44 . ... 3 .26~~ \ ' I \ (y .._ I • 1·0 .J. 3.51~ .J. 1.15 .a. 3 • 8 r~' •• " , i ~ 4.36~~- ... 4 .24~til- ... 0.54 ... 3.45{1- ., 2. oo~~- ... 4. 6:> r.: 4 " d r :- Z<! o I t c * * ~to ~:- + + o. .oo ~~- - o. d .J. 1.03 .J. 2.29 ... 0.19 .J. 1.48 .J. 1.37-:H~ I • 19*i!- 73 . .J. 2 51~(-:!· ..& . 0.43~HI- .. .,sure c r of ., ... .. s it i ve 10 sa"~'" .29*. sa-~~- I 06.:B~~-c- 114 {} 10 65{} 42~'" I I 6{ ir 1- ·:r -s w'! r s ~Hf- .. nic.JI 0 I • 22.Jt- 0 I • 22it- 1 . s >~:- :·· I. 6it- o. os{:- I • I{!- 0.4{!- I .s -lt- a de ' ., '\\ ------- -· ---- -- ---- Experiments to left of double . .llne, means of·observatlons on II patients; ~o right·, means of·l2 patients. ·· :-· ', * Significantly different from plac~bo-placebo ~H:· SI-gnificantly different from placcbo-lSD ·...:.' -...~4;'~ \. ( . " ., OL AMPHETA\A,,._ Measure Placebo PI a cebo Placebo- Amphetamine- Placebo LSD _Amphetamlne LSD g Knee Jerk -1--1.21 "' 2.88" + I • I 3 Puptllary Size + 0.48 + 4.20* + l .oo Systol tc Blood + 0.92 + 2.9ai:· "'2.74 + 4. 77~~· Pres su-re Number of P-os·tttve 12 21 Answers ------------------~------------~~----------~------------~-------------~ Clinical· Grade 0.14 0-. l·& 1.1a~· ~~ r A I I f i g u r e s a r e me a n s o n I .s u b j e ~J s • # ~ Knee The image is a scanned document featuring a table with experimental data. The table's title, "EFFECTS OF COMBINATIONS OF HYOSCINE AND LSD," is prominently displayed at the top. It contains numerical data organized into rows and columns, with headings indicating dosages and experimental conditions. Handwritten annotations are present in the top right corner, appearing to be a document identifier like "A-22." Below the table, there is text explaining the data conventions and statistical significance indicators. The document appears to be a formal research or experimental record. The document contains a table with data organized into columns and rows, detailing experimental results under different conditions. The headers and entries suggest a scientific study involving measurements like "Knee Jerk," "Pupillary Size," and "Systolic Blood Pressure." There are also handwritten annotations, including a series of asterisks and a document identifier "A-219" in the lower right corner. The top of the page has some text suggesting the context of the experiment, mentioning "EFFECTS COMBINING 20 mg. DL AMPHETAM" and "TH 60 mcgm. LSD." There are no photographs, official stamps, diagrams, or clear visual evidence of experimental procedures or facilities presented in the image. 4. 77~~· Pres su-re Number of P-os·tttve 12 21 Answers ------------------~------------~~----------~------------~-------------~ Clinical· Grade 0.14 0-. l·& 1.1a~· ~~ r A I I f i g u r e s a r e me a n s o n I .s u b j e ~J s • # ~ Knee jerk, puptllary_stze~and systolic blood pressure expressed a~ area under time-action ~urve durt~g first 8 hours after adminis tration of LSD. Clinical./grades on· bdsis_ of 1- 4. ' * Statistically significant fro~~laccbo-placebd. ;-· Statisttcal-ly stgnif\cant from placebo-LSD. ' ,f EFFECT OF RESERPINE ON INTENSITY OF LSD REACT ION d .. ·· ----- --- - J...:J_ _ a sure Pl~cebo .1. Reserplne4.a. PI ace bo .1. R~serplne 4 R~ s?. r p t ne 6 Reserpine 7 PI ace bo LSD Placebo LSDS 5.0 mg 1'0" 7.5 mg "o"· 6 .o mg I .M. .J. LSD · .J. LSD .J. LSD --- - .. ,. '!\! Jerk I .1-0.27 .1.0.34 .1.0.5 .... 0.36 .&.2.72 -.1.0.53 - .J. - 2.9 - 5 -.&· .0.4 .1.3 .• 47 _!0.33 .J.3.33 .J-0.27 ; -- ! . ~ 1 1. pillarv ' -0. II .&.- o. 4 -0.96 - .a.o. 39 .1.3. 85 - .t.o. 56 .1.3.33 - .J.0.44 '.1.3.92'.-1.0.28 -l-3.35 - .J-0.33 "":~ ---·"" ~---- srollcl • .. . ood e s sur~ . .1.0.91 .±,0.4 · .a.o. 76 -.a.o. 36 .&.2.54 -.J.O.S4 .1.2.07 -.&.0.60 .J.2.15 _!0.36 .l-1.81 .. . .. 1 . .0,49. I --- - - - - - .. . . 2 .-. . rr.bcr ' ::-,,_ s i I· ; Vt! 18 -.1.8 33 -.1.10 121 - .J.20 II 0 -.J.22 120 .1.24 163 -.&.30 S\'1~ZrS - . ·• . .. ,. ' in. I c ~ I 3 .. .' ~ .. - 2s a de 0 0 2. -~.o. 2'8 2.37'-l-0.27 ·2.17 :.1.0,3 2.5 -.&.0.7 - -- . . . l,"i1"; • F tgures t.epresent mean area.!· standard errors t~nder t lme"-act Jon cu1·ve and llr~ means of values on 12 subjects.: . . ' ·. ·. i ~presents means of counts .1. standard errors of number of posttlvrz llnswers after LSD was given. I' , - Rased on ~atlng scale of 0-4. . " 2.5 mg. orally 10 and 2 hours prior to LSD. . I 75 Meg~ orally. t 2.5 mg. o~&lly 22• 10 and 2 hours prior to LSD. 2.0 mg. tntrarnusc~larly 22, 10 and 2 The image is a scanned page containing a table with numerical data and explanatory text below. The table has several columns and rows, with titles like "Measure" and "Placebo + Placebo". The data entries are numerical values followed by a plus sign and another number, likely representing means and standard errors. Handwritten annotations, including checkmarks and numbers, are present in the upper right corner of the image. Below the table, there is explanatory text providing context for the data, including details about the subjects and dosage of LSD. Some parts of the text are difficult to read due to the scan quality. llnswers after LSD was given. I' , - Rased on ~atlng scale of 0-4. . " 2.5 mg. orally 10 and 2 hours prior to LSD. . I 75 Meg~ orally. t 2.5 mg. o~&lly 22• 10 and 2 hours prior to LSD. 2.0 mg. tntrarnusc~larly 22, 10 and 2 hours prior to LSD • . \ .' ' i '