Doc 0000151528

N.I,'WH Addict ion Res e·a r ch -..enter Since my last I~Her of 14 july 1954 I have compl~ted a con- siderable amount more wod: which is sumrnarfz.:d below. TOLERANCE TO LSD. These expertm~nts, which were described in my I e t t e r of 14 .J u I y, have been c ornp I e ted and the ddt a h a v e ;8 . n o w be e n a n a I y z My co. n c I u s 1o n s we r e n o t a I t e r e d by t h e '/ ~-- statistical analysis, a~~d are as follo·Ns: I. Once tolerance to LSD h·asbei_n wzl de.,elo;::>ed, it requires four to five ttmes thte 8ose to which the pdrier.r is / tcl"rant to~restore ~he LSD-reaction to its original irdensir'!; evu1 then the duration of action is refctiv,!ly short. 2. Tol~ranc.z to LSD is not overcor.H: C'f administ..zrlng 3. Tolerence to LSD ts lost in rhr.ze days follcwln:; dis- C 0 n t i n U c t i 0 n 0 f t h •Z d r t.: (~ • 4. N) un}cward te;xic effects ~·~~re obs.zrved, .::vv.n thousr. t Lr·, e p c t t -7. i; L1 s c o n s v mv . a• a s m u c h a . s I f m g • o f I- ~ " D d u. r . 1 n 8 .•1 ..' , ~ c o u r s e 0 f fn e e X p e r i rn Z n t . d high srad~ of tolcrence was d~veloped, no abstinenc~ symptoms were cbs~rved on withdrewal cf thz dru~. . ,,1 / ·...-.... / -· /~ -/ ANT ;DOTES FOR LSD •. I. Corynanthin.z. Results with corynanthine ·have been In 10 pati~nts no antidotal results we.re seen disappointing. -when IS mg. corynantbine were ~dminist~red 30 minutes before --- . In a second experiment, IS mg. corynanthine 40 mcgrm. of LSD. were administered 30 minutes before, 2 hours after, and 4 hours a Her .t!Q mcgrm.· of LSD, us ~ng 9 SL'bjects. Controls included three placebo capsules with 40 mcgrm. LSD, and fhree placebo capsules with a pt~·cebo drink. The t tming of the placebo capsule was the same as that used when corynanthine was administered wl The image displays a stylized graphic representing a vault door with intricate mechanical details and blue lighting accents, accompanying text that announces "THE BLACK VAULT." The text further explains that the document was acquired from The Black Vault, an online repository of declassified government documents, specifically mentioning the MKULTRA/Mind Control Collection. It highlights that this collection contains over 20,000 pages declassified by the CIA and provides a URL for downloading the entire collection. There are no photographs, handwritten annotations, official stamps, forms, diagrams, tables, redacted content, or visual evidence of experimental procedures or facilities. The document is a typewritten letter with handwritten annotations. At the top right, there is a circled number "43". In the center of the page, a handwritten note "(6) (3)" appears in blue ink. Towards the bottom right, another handwritten annotation "A-15" is visible in blue ink. The document appears to be a formal letter from the Public Health Service in Lexington, Kentucky, dated September 15, 1954, addressed to the NIMH Addiction Research Center. While the content discusses experiments related to LSD tolerance, there are no visual elements depicting actual experimental procedures, equipment, or facilities. hours after, and 4 hours a Her .t!Q mcgrm.· of LSD, us ~ng 9 SL'bjects. Controls included three placebo capsules with 40 mcgrm. LSD, and fhree placebo capsules with a pt~·cebo drink. The t tming of the placebo capsule was the same as that used when corynanthine was administered wl · t h l SD • " k' ' 1easure: •: m · en . t s ·t nc l u d ·Z.u-~ pupt· I- .!·o ··F ·Y S.I.- Z.G.,. '" 'ne.e. J· -Cr.'r-;.s, '/ systolic blood pressure, lSD questionnaire, and estirration of . ., t he c f t n i c a I g r a de of men i: a I c f f e c t :. Res. u t t s a r e s u mm a r l zed l n t:-te table. These resufts were obt-s"in~d by plctting the data on pup i I 1a r y s_l -£e, knee jerk , and b I o o d pres s v r e , a n d me as u r In g . . are~ under the curve over a 7-hour period. The quest lonna ire was evaluated by counting the numb-zr of posttive answers (checks i:l questions not mark~d· prior to administration <Jf LSDl. Clinicai Placebo effects Gr a d e s w~ r e a :; s i g n e d a s i n p r e v i c u s \'• o r k • ~ere eliminated by subtrac~ion of the proper control. Statist-ical an a I y s i s ·, was· done by· the 11 t tt t e s t d s a pp I i e d to d i f f e r en c e s i n p a 1 r e d o b s e r ., a t i o n s • A s l a n c e a t t h e t a b I e s h o s t h e r e i s n o \'t significant chanse in any of the rn·zasvrerr.ents, indicating no signiflcan7 ontidot-"a! effect of corynanthine against LSD. I should I ike io learn if you wish t:;e io try larger doses o f c o r 'I r. a n t h i n e • ' . 2. Sa n·.t.h in chanse in any of the rn·zasvrerr.ents, indicating no signiflcan7 ontidot-"a! effect of corynanthine against LSD. I should I ike io learn if you wish t:;e io try larger doses o f c o r 'I r. a n t h i n e • ' . 2. Sa n·.t.h in e. Ban.th ine a lone had no ,zffect on LSD reuct ton, netther did a comblnatton of banthtne plus corynanthln,z. Experi- m e n t s , h o we v c r , a r e s t i I t t o o f e '" t o p e r m t t s t a t t s t 1c a I a n d I y s i s • 3. Chlorpro:naztne. lr. contrast, e~~~rtments with chlorpro- mazine are at least promis lng. Two sets of experiments have been completed. t n o n e s e t , 5 0 mg • o f c h I o r prom a z t n e o r a I I y w a s followed in 30 minutes by 40 mcgrm. of LSD orally. tn the other set of experir<;ents, 75 mg. chlorpromazine oral tv was followed by 40mq;rm. LSD orally. Contrqls have included {all tests being done in a randcmize_d order)· placebo followed by placebo; placebo -:- followed by LSD;~ ch lorprqmaz In~ followed by a placebo. The ~.. .. measurements ma-:le_ and Fl)ethod of analysis are the sume as those described abo•:e. Inspection of fhe tables shows a sisnifica:1t reduct ion in the intensity of rne.nta I response (number of quesi lens / and clinicat grade} after 50 mg. ~hlorpromazinz ~s compared with the response after placebo plus LSD. Diminution in blood pressure and pupillary responses were almost significant, and very t ikely would be with a ierger number of subjects. After 75 mg. chlorpromazine, signific,H.t reductions in all responses, -to except puiJi t !ary s iz~, were observed. Fa i I uFe obra in d s isr• i fican~ rzdL•ct ion in pupi llarv respon:;e was due ro an ab2rr.:1~ r reaction in one of the 7 patients. The trend, however, is toward reduct ion of tl-te p'.lpi llary response. The ant idota I effects of chlorpromazine persisr aboc..:t eig~t hours; aHer this time LSD reaction may reappear. /. -;e;; ../ / . . ~;~· . I _,-, ,r ·--·.I ··.1:.1· The image displays a page of typed text with a handwritten annotation in the bottom right corner, appearing to be "A-150". The text discusses the antidotal effects of corynanthine against LSD, detailing experimental procedures such as administering dosages and measurements taken. There are no photographs, official stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures. The focus is entirely on the typed content and the single handwritten mark. reaction in one of the 7 patients. The trend, however, is toward reduct ion of tl-te p'.lpi llary response. The ant idota I effects of chlorpromazine persisr aboc..:t eig~t hours; aHer this time LSD reaction may reappear. /. -;e;; ../ / . . ~;~· . I _,-, ,r ·--·.I ··.1:.1· ~ ... i\'t~ "'\'111~~1 ···l~ N o s • 1 gn · ' . f . · t .ca f w .~~ · l f.t · -~c t s were o b serve d w tL , h~·so m · g . o f chlorpromazine alone. After 75 mg., d~ftnite drowsiness ensued· which, however, ·was not accompan icd by confusion and arax ia, as is the case with barbiturates. t t seems to me that these observations need ex tens ion in the following ways: I. Confirmation in other laboratories. 2 • Ex t e n s i on of my own s e r t e s t o a I a r g e r n um be r o f subjects. 3. Study of a wider range of doses; first, us tng more chlorpromazine, and fi'nally rnore LSD. 4. Admini • . • -str·ation of chlorprcmazin,e.. d.ft.~r: LS.D. •. / 5. Administratiory of ch~orprorr.aztne parenferally rather than orally •. · ., It ~hould be emph~~ized that:chlo~promazlne is not a perfect ' antidote for LSD, at least in the dose combinai·icns studied. It does not compl"'etelv obliterate the response in all subjects. The effect is ant idota I rather than competitive. With the larger doses of chlorpromazine,_ drowsiness b~comes d definite drawback, eve:'l t~.o:...o~h patlenb hav~ rec.ziv.zd LSD. Th~i:re is, however, n.:) ccnfus ion or motor inccord inat ion as is the case wr+h doses of barbit-urcdes sufficientlv Jarse to alleviare.anxi~ty caused by LSD. CA-iOI. Results with this. interesting compound wos pd.dly summarized in my letter of 14 July 1954, and since that time measurements of the b:ood pressure response on stclnding, before L-lt;J--' , i I . .. --"" , Results show that this compound induces profound postural hypotension in doses of only 2 mg. Furth~r work wi~h CA-101 has been deferred in order to con c en t r a t e on b u f o t e n i n e • Howe v e r , CA- I 0 I · a p pea r s wo r t h y of further The document page contains typed text detailing experimental results related to drug interactions, specifically with LSD, banthine, and chlorpromazine. There are no photographs, diagrams, or tables visible. A handwritten annotation "A-149" is present in the bottom right corner. No official stamps or redactions are apparent on this particular page. The document is a typed report with handwritten annotations and a stamp. It features a handwritten signature or identifier, "A-148," in the lower right corner. There is a black redacted or obscured area near the bottom of the page, obscuring text related to discussions. Another small, vertical black mark is visible near the top of the page, potentially obscuring content. The text discusses effects of chlorpromazine and LSD, referencing experimental observations and a letter dated July 14, 1954. There are no photographs, diagrams, tables, or forms visible. wi~h CA-101 has been deferred in order to con c en t r a t e on b u f o t e n i n e • Howe v e r , CA- I 0 I · a p pea r s wo r t h y of further study. Closer evaluation of mental effects utilizing a v a r i e t y of de f i n i t ~ psycho I o g i c a f t e s t s i n a· I a r g e r n um be r of lndividuats might be .illuminating. A more detatled study of the c a r d i ova s c u I a r res po n s e is a I so i n d i c a t e d t n t he hope of elucidating t~e mechanism. An antidote for drugs of this .... sort may also be needed. BUfOTENINE.~ ~'fh. now have carried out over one-hundred •r p r e I i m i n a r y t r i a I s w l t h: t h i s /u b s t a n c e • T h i s w a s d -~ n e i n a n effort tc locate a dose-range and to obtain some idea of the e f f e c t s i n d IJ c e d • T he d 0 s e h d s . b-e e n g r a d u d I I y e I e v a t e d f r em 5 mcgrm. totaf dose to 500 mcsrm. todal dose. With doses of less than 250 mcsrm. neither subjective nor objective effects were observed. Between 250 to 500 mcgrm., we have had scat~ered . . r.c:ports of dizziness, confusion and siight nervousness lastina fer only an hour or two. As yet no cons is tent effzcts on t~fl blood~pr·zssure, knee jerk, pupi I :ary s !ze, pulse r~de, ctc. 1 hdve b~en ocserved. intend to keep elevatinG th~ dose, following my retvrn from Europe. As far as the work has gonz, hcYI>\:ver, results with this CCi.!pound are not prcmisir,~. H a r r i s I s be I I , lv\ • U • HI: r n E.FFECIS OF 15 i-.:'GM. ocserved. intend to keep elevatinG th~ dose, following my retvrn from Europe. As far as the work has gonz, hcYI>\:ver, results with this CCi.!pound are not prcmisir,~. H a r r i s I s be I I , lv\ • U • HI: r n E.FFECIS OF 15 i-.:'GM. CCRYi'-JAJ"iTH INE CCC-I. J GIVEN BEFORE AND 2 HCURS AND 4 HOURS AFTER LSD-25 PI d ce co.;:, 1 "t" 0 f 1 Significance + LSD 1 D iff. D iff. of Diff. > Knee Jerk I • 78 I • 5 I 0.27 0.3 0.5 Pup i Is 3. 08 2.84 0 •. 24 0.57 ~ 0.5 Blood Pressure I. 94 2.38 -0.44 0.94 >0.5 ·Qu~stions 62.5 66.1 3. 6 . 0.49 - 0.5 ! Grade I • I I I • I I 0 0 I .0 A ~- V a I u e s a r e me an s o 9 s u b j e c _t s a n d a r e cor r e c t e d for p I d"c e-b o res pons e s • .. ·_- A--1~£ ·' ' ·so Of lv'GVt. 01LORPRQ.Al\Z lf'.t GJVE.N 30 :~HNUTES BEFORE 40 MCGRM. LSD I -.,- Placebo CPM ·. . - rrru of Significdnce + LSD + LSD D iff .. D iff. 1ofDiff. Knee Jed: s I. 33 I. 31 0.02 0.209 > 0.5 i'upillarv Size 4.00 2.93 I .07 I • 71 >C. I Blood Pressure 2.09 0.77 I. 32 I • 4 I >O.l Questions 77 44 33 3.72 < 0.05 .-A, ·· :;.· Grade I. 3 3 0.66 0.67 2.68- <0.05 ~ ... > ... w-Means per cent on 6 patlent~; Val~es corr~cted for plac~bo effzct • . Under knee jeri::, pupi-ls and..biood pre.ssur.z, figures represent sq•Je:-e inches under curve. ' ' Gu~srions- Number of positive answers on Guestionnair.z. Grade- Cl.,inical_ grade. EFFECT OF 75 iv~GM. OF CHLORPROVAZ IN£ GIVEN 30 MIN. BEFORE 40 MCGRM. LSD PI ace bo·~· CPM -~~- "t" of Significdnce + LSD + LSD D iff. l D iff. of Difference Knee Jerk + 0.64 0.83 1.47 2.98 .( 0. OS ..., 7 ~; Pupillary Size + 3.50 + 2. 14 I. 36 1.52 > 0. I Blood Pressure + 2 •. 31 + 1.06 I .25 2. 14 > 0.05 7 Gues~ions 91 35 56 2.35 < o.os T"' Gr-a-de 1;.71 The document is a typed page with handwritten annotations. The main text concerns an experimental drug, CA-101, and its effects on subjects. There are no photographs, diagrams, or forms. There are two handwritten annotations: a mark next to "BUFOTENINE" and a signature "Harris Isbell, M.D." at the bottom right, accompanied by a handwritten alphanumeric code "A-147". The content is solely textual information, with no visual elements that depict experimental procedures, equipment, or facilities. Jerk + 0.64 0.83 1.47 2.98 .( 0. OS ..., 7 ~; Pupillary Size + 3.50 + 2. 14 I. 36 1.52 > 0. I Blood Pressure + 2 •. 31 + 1.06 I .25 2. 14 > 0.05 7 Gues~ions 91 35 56 2.35 < o.os T"' Gr-a-de 1;.71 o. 86 0.85 3-•. co~ <O. 05 ··:~· ~'/ * Values are means on 7 patfznts and are correct~d for pldcebo effect. / Ur.d~r kn<Ge jerk, puplls,arid blood pressure, figure:. represzr.t squ-3re inches under curve. Guestions - Numblr of positive answers o~ ~uestionnaire. Grade- Clinicol grede. f . '-r ._.i. -· .. : r. - · ...1. ·- ;;..- . ,- j't -- -. -·- I ----... -- -------- -- --~----- I 1 I -=-1 ;.,. ... L _ i , ! . --· .. ··: -·-- -- ----- i '--' -.- lt / / I I l I -" ! -r I .;;... --!-------/- . I ..... I rI ---1- 1 I ! •J 2.52 t -/ :~ "· ,: · , ' 5 \ J I I . . 7-0 ..... /. / ,._·· ..... A __ _ ________ ,. - ............__---,!-/-' ·-·-~----- ~ .J -,._· c..· ) I . i I I I ~· I;J ! I·- j ' . . _, r· '6- ~ -t - ._) 't~ _v ' f' 'I' ,~ I 3 I .... -~0,30 " '\ "· z ' i' J . ::. ~- ! j ' \ ~lp /i-~·.:_~~·~-; (; I ( ( v -.--- - . '- - ;r,. './ / . 1 ~ i I ! · .~. / .· ~ . .. . . f·)~ f ! · / ' / i f f i . . ! i I ~ .. '.. f . . /. J 'f ) ) ' I It'" I I - , 4-l~; , i I I ' ..:.;l r- .... 6.J! /'- ..;. '(.;I ~- - . . i-.5/) ~ ;-j- "'f J ~ . ... ./. ~;· tJ) (/ q. .._/) - ... & . - I ~ ---r--------- ----·--------------------- ---·------·------·- --·-- ------------------· ---· -~ I I - I - . . ~- -~----·---- --·------1 --- ---- ----_E .. -___ ·__ -----. ---·· ------.- I . ,-p/f. ... s ~ - ; < ::- -- __ .j ~ ! . . ·.'-. ~ - __ r - ·· ~ ~~~;~~------~-----~~'~r~----------- The document is a scanned page containing a table summarizing the effects of corynanthine and LSD on various physiological and subjective measures. The table presents data under headings such as "Placebo + LSD," "CC-1 + LSD," "Diff.," "th of Diff.," and "Significance of Diff.," with rows for "Knee Jerk," "Pupils," "Blood Pressure," "Questions," and "Grade." At the bottom, there is a footnote clarifying that "* Values are means of nine subjects and are corrected for placebo responses." A handwritten annotation, "A-146," is present in the bottom right corner, and there are a few small ink marks and smudges throughout the page. There are no photographs, stamps, forms, or diagrams visible. The page displays a typed table with handwritten annotations above and below. The table presents data categorized by "Knee Jerks," "Pupillary Size," "Blood Pressure," "Questions," and "Grade," with columns for "Placebo + LSD," "CPM + LSD," "Diff.," "t" of Diff.," and "Significance of Diff." Handwritten notes below the table define the asterisked entries and explain the units for certain measurements. A handwritten number "A-145" is present in the bottom right corner, and some faint vertical lines of text are visible in the top margin. ---·------·------·- --·-- ------------------· ---· -~ I I - I - . . ~- -~----·---- --·------1 --- ---- ----_E .. -___ ·__ -----. ---·· ------.- I . ,-p/f. ... s ~ - ; < ::- -- __ .j ~ ! . . ·.'-. ~ - __ r - ·· ~ ~~~;~~------~-----~~'~r~----------- i . I I - . I I I I I I I I ! ! i l I I " "' ' .. I ' . - {w/..'_ I; .. . : '· / ( ;\, I ;A._/~~Jl /. 7 LL /)0~ \ I \ · I I . ! . -- I ----~- i ... .. -~~: . I ; \ t i \ l I I . .II \ \ - ltD t · · - J t I I /4, This document appears to be a page from a scientific report, likely detailing experimental results. It contains a table with header rows stating "Placebo + LSD", "CPM + LSD", "Diff.", "t'' of Diff.", and "Significance of Difference". The table lists measurements for "Knee Jerk", "Pupillary Size", "Blood Pressure", "Questions", and "Grade". Below the table are several explanatory notes. Handwritten annotations are present in the bottom right corner, appearing to be a number or code ("A-144"). There are no photographs, official stamps, or diagrams visible on this page. The page contains three line graphs, each plotted on a grid. Data points are marked with dots and connected by straight lines. To the right of each graph is a handwritten number: 1.85, 2.52, and 5.46. Handwritten text at the top of the page includes a date, "9-7-84," and other illegible or partially legible notes. The y-axis of the middle graph is labeled "PIES". A handwritten "A-443" appears in the bottom right corner. There are no photographs, stamps, forms, or diagrams of experimental procedures visible on this page. The image displays a handwritten graph with plotted data points, indicating experimental results. The Y-axis is labeled with numerical values and appears to represent different measurements, while the X-axis is also numerically labeled, likely representing time or trials. Several handwritten annotations provide context, including numerical values associated with the plotted lines and what appears to be a date (8-24-54) and identifiers like "Q=" and "G=". There are also some faint, unidentifiable printed marks in the upper right and lower right corners, the latter of which may be a document identifier. The overall impression is of a technical document analyzing experimental data. The document contains three line graphs, each with a y-axis labeled with numbers and seemingly representing quantities or scores. The first graph ranges from approximately 2 to 4, with notable downward spikes and subsequent rises. The second graph is scaled from 4 to 6 and shows a more consistent fluctuation pattern. The third graph, labeled with "ST" and numbers like 100 and 120 on its y-axis, displays a wave-like trend with a significant dip. Handwritten notations appear throughout, including what looks like a date ("8-31-04"), experimental codes ("CAP-0601", "LSD-25"), and numerical results ("-0.28", "0.88", "1.74"). A faint, vertical line on the right edge suggests some form of official stamp or marking.