Doc 0000151883

The image is a digital representation of a document's header or landing page. The top of the image features a stylized, glowing title that reads "THE BLACK VAULT". Below this title, white text provides information about the document's origin, stating it was obtained from "The Black Vault, an online database of declassified government documents." It specifies that this particular record is part of the "MKULTRA/Mind Control Collection," comprising over 20,000 declassified pages from the Central Intelligence Agency (CIA). The text concludes with a URL for the collection: "http://mkultra.theblackvault.com", displayed in yellow. To the left, a graphic depicts a portion of a bank vault door, complete with a large wheel mechanism and multiple locking components, rendered in metallic tones with a blue glow. A~~.::--:1.;.-w·.- ..· t·A. l l I t I l H. and .... Harris IsZ>~ll 'l j ·-~ l ·I i I ! l ' ' .. -- . ... i ·' :_ J j --0 - ~~--- ·. ./ · " '·' ·. ... . ~: .. . lt. 1!1 al~OSt -~~OSSibla to !$\L"!"~:~rl~e l!HJ ._ork Of th.:! Nl!---"H Add!c:tion Pcsearch tor a. year ln a a,"tort preee.n-· ~ntcr tat1on,· and this. Is beco~lnr; stea<itly InOr~ dttt!ci.l.lt ~a our .. '--· en(:o~as~4!3 \..'O ..l \ 1n clln!cnl pha.rrr.a~loay ot analgcelc~,.< coloc1cal Jnv~s~!gatlcns. blcch2:'llc::.-l ~j(~(';r!~entS" ranstna frOm Cl1nlcal enc..o<:rlnoLogy to <lrt.tg r~talK:l_i~~,_ ce;::nt-~~ . ·-- or Si\~:tchlly en !! few or thG hlthl h1hts- tm;-~{ wt-ttt ~-!'ltc11 l . 1(~ have. bacn direct.. ly tn.volv~d <.\nd •which. ! hope, -w!ll b~ cr -.:.· . -- ------· . --·- --~ -- -·-·-- -- ---· - ---· -. --·· ~-~----·- A-JO/ ' ..'.#. }· ... \ .. i l ,· -. or · ...... tatcr~in!n~ A~df~t!v~ness An~11CS1Cs~ ::.-.:::..;;.::.....;;...;:_.;:..;.~~~........... .. you knew, r:r. round that &ubstitution or ~$ rra~cr ~~s - . new anal~'i!S!c!l tor r:orp!t!ne in add!ct~!d patients for a ;Jt::ricd -ot 24 bou~s ts a s~nstt1vc.2nc useful lr:st. of tht.! a!>ility or:'~­ .. " a dr~s t~- ~t;ppr.is5. a;b:tl~~-~~-~ !.'rur.t IWrp~1ln~. · Sc!l!lt.itut Ion tor' 24 hours has scV.l:ral a~vu.ntag<.~~: Only ;;-;inimal a:~'!vt:nts of n~w . . ! ... ' ~ 1 l because of the sho~t per to d. of.. :n;hs.t..lt..ut..lon. Pat.t.c.nts do r.ot ! ' ! i ~ i I r~!lected relatively 'M;?ll tlw T'!:lults witZ1 the classic 10-cay l l . aubzt1tut1cn nc.t.hod. Tha ;:4-!icur procccurt.i eoes not, o!'. cour~a, reflect lhc Intensity ot ahst!nence toliowln~ ~ithdra~al of ( 1' l t - j - l '! I l .. ....#. -· ) ·. ·. £urlnr; thoa tr. Fraser t•as collected hourly :t~ar-- ~e1nt. .so, ~qs. obterin-td' cur!.n-q·· wb::t.ltutlon at lGO • ~·20, 10 nnd 0 cnnt ot · U \e . I . or 1n a p<~!r p~~tlant.s a.cc:ustcs~ea. dos~. ~r~h.tna 24 hour p~riod. Th« procecure us~d ~~s es !ollcwss Fnl!cnt3 or \te·re stahl l17!ed on ~ tlg. rnorph!na .rour tl~s dally; at 4 p.n. on cl3y prior to the test., the last regular do.sc of· Jt?rph lne ~-as aivcn; a~ .10 p.m. ot the ua~ n! {;!1t., 6 a.r.. u:nd . or 10 a.m. the tollowlng morning patient received a subcutanuou~ or CoS~ an "l.:n}'JlCa"'n" medtcatlon (actually rnorph!na .rour tl~s dally; at 4 p.n. on cl3y prior to the test., the last regular do.sc of· Jt?rph lne ~-as aivcn; a~ .10 p.m. ot the ua~ n! {;!1t., 6 a.r.. u:nd . or 10 a.m. the tollowlng morning patient received a subcutanuou~ or CoS~ an "l.:n}'JlCa"'n" medtcatlon (actually :..orphin.a in CO!A~S ~£' 60, 30• 12, 6 rl~·· or a. placebo). Usual ob:~.;rvations fer tto:st c!ny ( lf,th to t~e 24th hot.:r ot a.bstlncnc•l), an.d. t~ki1:. ho~;r J..y point scoras calculated accorcHng to tln: Hin'X:"~le!Y~c!l sy~t~:'l (l). end Fl~ta~(J.r (2). thus c~:-nv~rt.!ng all the data on a p~r-tlc..!l~r­ patlcnt tor a to one r1Gure, called "point-hours." partic~lar ~ay In nll,. '..1:'-a h~ve cellect~d datn on .39 pnf.I~nts after sub:.st.itt~tie:n Ob"tilously the data for-m a ver-y prc:.~!sinq ~J.) ~~~ .... ctt-.:c t. curve. . ' ....., ... It. 1s our.l1op~ tbact. th!s c:urva c~n be t!cfl~_~d so ~c-1 t· '[}y _ a(!dlng other- pat1t~nts at the points rllrcady _Gtud!ad, by ntudy- · · lng ,ether aoscs. and determining ll::n!ts ot vartat!ons for or sroups can reasonably accurate dlrt~rent ~n. tt~t ~~ ~ka ~st.lmations of tho cow· or new analgesles _.h!e!l "-''uld nc· · equivalent to a atanttard anount or .e~rph!nu 'tn 3Upprt3~~1t•!J - a:;,:~t1ntnca. \Ja will t.ave to study t!H! $upprcss1v.-: potency ct effect curv.:s so ·obtained with the n\lw wlth that of th(! ~ru.g a \-:roeit and ror a li:tit~d nu.~bQ~ of trluls. th1s is ohvic'.:sly Only those drucs We also hope to a qunntitatlvc d~velcp syst~~ fo~ . . .. '.1, !- , ·a ~-. adc!!ctlon" procedure ln tht.l. 1ntcns1 ty. of c;,stlnii!n1:c C:.~t:!rm1nina aJ"tt:r c1r~c·t vlthcrawal. Patients wlll r~celve tho n~w crl.:.:; tor a per .tod of cays v1 th L,_e dose !no eleva led 19-~J b~ c.~ r.:ap!dly tolerance per::llts and ooscrvat.lons tor intensity.· ~s or· absllnanca carr:!Qd out tor 10 · G-3}.'? ~rter abrupt. d.1 scont in uatlon ot the DCUtcat'.lor.. Cllct:.lat.l~ns t'"or'''1ntcnn!t.y c.f . ! .' I this case) end coop<ircd \11th th~ tntansU.y art.er u:orphine or ar~ being studied by thls r.~thoc • .. -SCl th.-:lt no f!r..:!l CVCJ.luatlon o! Any cf the~e drUGS !S possU:le. or HotTevar, sor~ oC the results are con31dara!lley !nt.:.!r-est sa . -··. . .4. .. .. _-·. -i·rl_··· -~-- . -~--.-•- ,. ";~· . .· .: ..: .,/>··. •.· .'.Ltt!tl:J.l-i:2!i~'lz1•1.(3;-(Ehen;:,lnmtpo) -~r~pyll-!t=-2fpcr1uin~. ~rb.s;<Y.: ,j I NlU-7590 1s app,rox!:::ately tv1c~ as. . af:t.ive as r:-.orphine: a::. an • .{: This page is a title page for an "ANNUAL PROGRESS REPORT" titled "APPENDIX". The report is authored by H. F. Fraser and Harris Isbell and is from the NINH Addiction Research Center at PRR Hospital in Lexington, Kentucky. There are no photographs or diagrams present. A handwritten annotation "#4" is visible in the upper right quadrant, near the authors' names, and another handwritten notation "A-302" appears in the lower right corner. There are also some small, unidentifiable handwritten marks along the top edge of the page, and what appears to be two official stamps partially visible at the very top. No experimental procedures, equipment, or facilities are visually represented. This image is a scanned document with a lot of noise, making certain details difficult to discern. There are no photographs, diagrams, tables, or forms visible. The page contains a typed text, and in the bottom right corner, a handwritten notation, "A-301," is present. The text discusses the work of the NIMH Addiction Research Center and hints at the broad scope of research conducted. The overall appearance suggests a scanned document with significant degradation and some annotation. drUGS !S possU:le. or HotTevar, sor~ oC the results are con31dara!lley !nt.:.!r-est sa . -··. . .4. .. .. _-·. -i·rl_··· -~-- . -~--.-•- ,. ";~· . .· .: ..: .,/>··. •.· .'.Ltt!tl:J.l-i:2!i~'lz1•1.(3;-(Ehen;:,lnmtpo) -~r~pyll-!t=-2fpcr1uin~. ~rb.s;<Y.: ,j I NlU-7590 1s app,rox!:::ately tv1c~ as. . af:t.ive as r:-.orphine: a::. an • .{: •• • > ~ ·a• :. ! · '*en~lgt;sle .. ln ~teo... It.· ls- about. ~C t1.ro-<~:oJ .as pot.~nt. ;norp!r!n~ . ln suppressing nbst.1n~nc:Uc 1n th11 t:onkcy. ThCil drug !a e.n ...__ . __ ei'f1l-ct.1vl! ana1g-:s1c ln. l!lan• and Ja probably a!l potent atJ ~J.Vr;H1inu -1!:) to 20 I!tJ• of irl!{•7.S90 ln~UC!l.\.t. ~u.bJcl'>~t.iva< efi',.~!~U !n 10 nontolQrant- torr~r a<Jd1cts · 'Wt1lc.'1 \i.;:r-e 1c::::nt1!'1c\i as rc$;-.:::.b- fcur pat1-ents ~H). w;z:r~ actively ada..tcted to ant! sta~il!=cd ' ! on 24';) t~g. ot" morphln..; eul!at.<l · cai ly: r~c~ Iv~d .tU:I-159\) 1-Q t~rtle 24-hour- ti.:sts f•"Jt: -aupl)resslon of. ah:!ttncnca. ln t.h3 first. tG~t ! --------------------·---- -----------~-------------·----- ··------ -- ------------ ·--- .. ,. • . _ · __ j \ · · . \ ) ..... Y• . . / :.J ' ... thrca -:. ho . urs ~ . . .. . . wa . '· ~ 79 "polnt-l".o_urs;•_ t:t.: avern\Ja score \-11th tS· ;;lg. or • HlH-759-J cv~ry three hours \.a3 ,S5 "point-hours," Which or seen G!ter of 50 per c:cnt. the su!lstit~tion c.ccusto:r;~:..i ~os~. ,.., . J o r !t:erp .• ~ne. l l ! j t.M stat!st1eal ca1C"~l3tlrJn:; lor·sco;>e. pant~le113!!1,· !S.nd .. cor.1para tlvt: p-~te1ne1~s on thc$-ii: curves.. . This \Will be collC \lt.l..:n r• .. Zl..tOJ"C data hav~ he~n ttceut\ulated. A~ l'\lU sec 1n •". < ;J : ;Ur . . . .. . . , 2 w~ ~~vc drn\..'l"l t!l1! ·- ~ .. \ ~ o!T <! l -. ~ . , ! ' € for NI?!-7590 throu~h th~ two P ,· , O ·"·" ' " , .i . . ·t . - J 1 i!41 l fh,~ rea~on !$ t!mt ln th>t: first t~st. ( 12 :-;g. 0-vcr;; stx hours) i was lt. ~Vlde~t. tro;;t tnspection of L~a cata th#lt. :-tl!i-759·') \i~S . 1 ,.,! ' l \. l -·. .. .:. ~.. .. .... .. ,.. .... ~ ... ""'./ c ..... 1G very etfcctiva lri suppressing ab~tln~nc~ L. j ; i ' ... -· I ) ~ant tt is appro x1ma t.a 1 y .30 t.l""" s "a po a a '"'C rpll l l \. l -·. .. .:. ~.. .. .... .. ,.. .... ~ ... ""'./ c ..... 1G very etfcctiva lri suppressing ab~tln~nc~ L. j ; i ' ... -· I ) ~ant tt is appro x1ma t.a 1 y .30 t.l""" s "a po a a '"'C rpll l ne ln ana l fi<'Sl c ·aa tests 1n mice:• .tt .ts only on~-r.trL.,_ pot;;nt. an Q)rph1ne ln_.,. -' . It, therefore,. S:?;c;!ed possl~le- eon~1d~ra!Jle f.as~cc:t~tton bclw~cn a~lgestc tlla:t a ett'ect Qnd. o.blll. ty t.o sup~:-e-ss a1ist. in~nc~ ~~l~ht have b~cn __ ln 7 non tolerant. .fo~er Cdi}ict-s·r co~s of" z.· ""r 3· ::g. cr t!t~es ~rpl1lnc ·eup~lor!ant•- 5-10 as potent as. as nn --- .,). : I 2~0 ~g. or morph1~ sulfate dally racc1v~d .3 ng. (ona patient, j i ; total dost: 9 r.:a.} or 5 m~. (2 'pat.i'::Jnts, tot~1l a-os~ !S ng.) cr '1 i 'I I test. Sub~t!tut!on I l l i j - --- -·- -- --------- - -- ----- l "'i .. ·- ., - -..... ·: _;:' .. - a.crough-op~-el!r.tlr.ar.J estl:,. :at..a, · UIH-7525 Sile~s to ~ 7•'E.~ ih~s- a ·. ·. ->"~ .._ ; as;~e!!"ct'tv~' a lilOrl)hln,;, !n suppre-ss1ng abst 1n~nce In r.i.::.n. . .. . - . Fur,thcr tast& cu·c ~urrently U.."ld·2T'\,Jay tn oracr to dcter:1ina ... -.··.-.. Su~press!ve pot~ncy ~ore c~~ctly. One :hort a.Gd1c:t1on bus ccrr:;plctcd. · c:tir~ct. t~st b~cn On~ nontclerant former Zl".orpblne e.d,:tict. received lilJl-·/52$ In dos~,s ' ·. ., :.~ 1ner~as1ng !r?*1: . !, l ~!l• t.;t 7 !i·J· subeuto.n~ously QV$r the coursa -.- .. :.·: ,:..-··-. :·. .... d<t;)~~~~lon of ·resp1r"t.ory rate, na~sca, Elnd vo::~t.tlns. The pat:Cent hn".l t~x.!c frf!t!cts 'Wtt.h -!oo;-ctl of 5 r.'lg_. fQt.:.r t:t·r.-'\!_, ~J;s tly. en t~1' 17th c.hy of nddlctl~n., S m3. <lf' nalor,h!nV> ~t~b~tu~ol!sly ap,.zar~d on t!1e th! rd t.iay end p'!:!'t:l ~ted thr~ugh the· fl_..-:v~:snth day. 1'!'1~ r~s·~lt~ ~r.:: ~c!.f'lclt>nt for Q tcntottv<i: st-=t-sr;t!"nt t~1nt. .. ... .."."..J...;.. . -. .~., 4- ··£···:• .:_ . '.,.,-~ .: .. - . --~- ' ./ ·. Th!s cor:1pound !s one ot a nev scr1cs prepared by I . . ~ ·. Dt. tvcr~tt r··ay a.t '!Hll "nd :ltud!.:d by Dr. !-lathan D. Eddy. It. 1s nearly 10 as cttectlve as tnOf1'h1ne as an-analgesic-. j t.lm~s l l _, .. ,· l' ln mlce. -- C~!lp1tt3 thls, it. !a :2UC!l le·s~ ett'cctlvc than IT:Crph!ne ~ _ l I in suppressing a.bst.1ncnc~ 'in This page contains mostly typed text, likely a research paper or report, with a handwritten annotation in the lower right corner reading "A-300". The document appears to be printed on aged, slightly yellowed paper with some visible speckling and a few faint lines consistent with an older printing or scanning process. There are no photographs, stamps, diagrams, tables, filled-in forms, or redactions visible on this page. The overall visual impression is of a single-page document with standard text formatting and a single handwritten identifier. Dt. tvcr~tt r··ay a.t '!Hll "nd :ltud!.:d by Dr. !-lathan D. Eddy. It. 1s nearly 10 as cttectlve as tnOf1'h1ne as an-analgesic-. j t.lm~s l l _, .. ,· l' ln mlce. -- C~!lp1tt3 thls, it. !a :2UC!l le·s~ ett'cctlvc than IT:Crph!ne ~ _ l I in suppressing a.bst.1ncnc~ 'in t;-:Qnkeys n:osa equivalent to .3 mo. ·-·-or ~rphinc !s approx!~tcly 17 r.1o._). Pr~llmlnary l""t:S'trlt.s d1ssoc1at!on b~t\lecn analc~!l...tc and. .. ~.~-t.t~~c~·!J.:t~~ph;.:,ss.J.ve potencies b" pre: sent., t1w::-1n nla~t cxp~r in~nts \t~rc un~~rta}~cn. ln B nontol~rant .forp:;;r ~-.orphlne addicts • .>·4 ng. o£ ''! ·and h<,;!'~vioral e1..:t~cts -~tn 12 l'l tricl~. 11'1e- urug_ is pi"oha~ly .S-lo as potent aa moJ?hl:1.:: as an eui)horiant.. t!::1;2~ 'I- Fcur pat.ientn M'to \ierc a~dicte:d to ~nd stabilized en Z40 ~n~ ot n:.orp!'tln~ sulfate dally rcC:::lv~c.! 2 mg.. ( t.ota l 0.! 6 ~:.-r- .. ln ;_ ' - -e. • . I ·:::- I l ., i I Abstin.;:nce· ~'0~ supprcs~ed v~ry efr-~ctlv~ly l:.y tho;5\J c'~!l~.;.;s. \ \ ' '' ' ' ! . ----- --- -------------- ----- ~------ -- ___ _......_ .. ...,. -------.. - ---- ----·- --- j ·- . __ ,. l I -L -- • J, 4. 1• . . -------. .· ""'· .I "po1nt.•hour_~. scor~ ln.l~ patients r~~~lvlng 2 :";.~· -.*:'~ry six hour~· '.-as 76 .:~. a·.t-cra;-J-'3 "p'lint-nour"· sc:orc 1n T:.'l·l . J patiunt& ·~rt.~r 3 ~· avc:-y s1:t h~urs ·~~ 63. !ll'H-7519 ie 'ro~~~lJ at leaaiS-1) t1~e3 A~ potent ~a ~7.)~h!n~ !n supp;cs~!na 1\:o patients have u.~.jer;one ·sh~rt dir'l':t ad·:llctlon''· exp.er!~nl:s.. n1~ tJo.sa ;;t ~aH·7S19 l.'nS f:l:;:-e3se.i. trom 5 mg. to 24·36 mg~ ·ently over the ccur~r:: or 19 to 24- days. t-..~ I'h:d l 1 i l r.alorphlna prccipltat.cd mld &bstin~ncc in. !Joth 1n~tar.cc3 • . i i I I i -- ... :v· .... ~ t .._-. t 1 : . · . " _ " ,·.,~.-.~.. 1· ... . • . ..-. :-. --""~. • '"'""'~"'"""- \ . or U·'-, - ·.· : .; · :•:\.. - _.~nd ~ ... · ... · .. . w .., ~ ,. ~ ..- -:, - ,. .,. ~ .,. ..... - .... ri-. - .. - '" ~ 'n . t".. · ·, - .~ 1. · -• - ~ ~ r - - · •-• · • - c"· - ·ity ~~ .• a~ ' ~~ j ~~nc~ aft~r t~~zc ""•··r! y·,.. -v,'~-.64. 0.J , .. . • w The document is a typewritten page with handwritten annotations. The text describes an experiment related to morphine and patient abstinence, referencing figures and external sources. In the bottom right corner, there is a handwritten number "A-299." There are no photographs, diagrams, tables, or official stamps visible on this page. There are also no redactions or obscured content. - .... ri-. - .. - '" ~ 'n . t".. · ·, - .~ 1. · -• - ~ ~ r - - · •-• · • - c"· - ·ity ~~ .• a~ ' ~~ j ~~nc~ aft~r t~~zc ""•··r! y·,.. -v,'~-.64. 0.J , .. . • w . 1 .. . . .. " ... ~ .. . •. j - ...~... } - ! l . . :.- :;_: ·~:;~;~~~1~7~~\,~ -~·;: '<. "! ,.,..~;L._:··. ....... .,.~-~~~~<·: ~~.,...· • "\_•,-~ • ·.-·.:.~,;: :.~ ..: :. o •! • ,. You wi~ll .., rcc.1.tl t!"-.at:, tn· cur.~p~t!cnt.s, notnorp!11na is, 1n :1ngle· t!o~c, tas- less potent. than ~ti'lhlnc. Y..:t wh~n s;.:.all doses (10 mg. subcut~n~ously) ara given~ s~c!at..tv~ e!fects of nor:r.orphlne accu::n11ata to such a.~ extent that tho dosane o! •. -~. ... •, ... . ·_:·:_--;'-:t ~-·::·· .. ---c:, no~-rphlni Cl~.liot ~ el..-,:.vat.cd .t.f.3 ra;1ldly cr tOo CS. gr.~at :1 --d-eoree as·_:.:: tJ1e r..asc wlt!l :.-.orph1n~. Following wlthdr~wl ot . nornorphine, abstinence \olaS ~.1ch r:Iil\icr in 1nt~ns"ity Ur.i.l.n w~~ .... ab~t.in~ne-:. !ro~ roerph.!n~. For- thi $ reason, a CQC"ik)O.r .l:$011 or } I frO!:! urlne at pH 9.3 1nto a mixtur~ of 20 per 0'3nt. ar.lyl .J.lcohc1 4 , . · , -i . o · . , t . ·~ ~ , k_ .. : . - H. · . ".' .:.&.. ~ ~ -~ · . .; . ~ o ·-- . ~ . , ~ .... ; ~ ; - - -~ a ·~ .s. . ~ . • ~ : ~ .. : . ~ - $-- ' ~ ' . . ~ .~ ' ~~ " t " -. ' 2 · - : :; ' . t . . ; .. - > , t: h-; ' . J ·:" < ..1 : ! : . ' ~ - -- f - l -=" ; ~~ ~ ;S t :. l..#,.. . ~ - ;. ' - " ~. .. + ·'t. " ~ ~ " .. - . ... • ('i .• c..._ _e. ...t.. . •+J. -.-.-- . • . . · -· • . () .......... i.. H' ---·"" ·• -~~- "\, -..' "·. . ' or . .: ! . As .ls. true_ trt.orphlna, non~rph.tne ts excrelcd in .t.wo" .. ~· rorm$ --'.'tree" or re::uU ly _cxtracU1ble and. "bounct, or extract- tt ' . ./ ·. .. _a~le. This document is a typed page of text with handwritten annotations. In the top right corner, there are two small circles, one filled black and the other outlined. At the bottom right of the document, there is a handwritten annotation that reads "4-298". There are no photographs, stamps, forms, diagrams, tables, or obvious visual evidence of experimental procedures. The overall appearance of the document suggests it is a page from a report or research paper. The image displays a scanned page of text, likely from a report. At the top right, "Page 5" is visible. There are no photographs, diagrams, forms, or tables. Two small, abstract circular shapes are present near the top, along with a few scattered dots and specks consistent with a scanned document. The bottom right corner features a handwritten annotation that reads "4-297". No official stamps or redactions are apparent on this page. . · -· • . () .......... i.. H' ---·"" ·• -~~- "\, -..' "·. . ' or . .: ! . As .ls. true_ trt.orphlna, non~rph.tne ts excrelcd in .t.wo" .. ~· rorm$ --'.'tree" or re::uU ly _cxtracU1ble and. "bounct, or extract- tt ' . ./ ·. .. _a~le. enly after app11cat1on ~r- so~ hydrolytlc proe::dure such <;-.·j -~~-r -. J : -a~ hc~ting viti\ &trong at:ld or lnct:batlncr with bc~-alucuranh. . il~c. j 'l'here Is. ho\lrevcr, a ::arkcd cU!!cr~ncu- 1n the d£sree o! "b1nti1n;J" or as not::i0rph1ne OJt<!parct1 wlth ~rphlne. You w111 not lee ln- the _ f'ollowing -slid~ {Table 1) t..~at "!rc~" rnorp!'dna acc.Ounte;.! tor only . - . )· . . . . 11.4 pi::r cent. O! tha tot.ill t'"'.Orphlna rcCOV~f'ti!Jla. !C'O!'il tlH! ur-in,:: · o! .3 ·pattcnt: 70 ng. ot th,;: dTug, ~~o recslve~ \Jh;;r~s "fr~~" accounted for 51 per ol:' tn..r ta-ta-z norn~rphinc ~nt· ~;terctea. 'j' • •. .. . i - ··!~) , . ··.·. ·. mlne.tha nature· ~t "bounu" nornorpatn:~ nne. to. 1;olat.a lt • . -.. ~- ~ . -· . . · The- :::1cantng o~ thc$e d1ffcrt:~ci:_$ bct.w~cn the r.~taboll ~;} or .·_ ~·- :. ··~· -y . . :.--:.:· morphine and norr:-;orp!l1nc 6t'\l still o!lscl!re. Gn.: h~'Ot!H.:S!S m1~'lt w trar.~d as rollo'WsJ 'Tho. "tre.::tt rorw$ ct norn--.orph1n~ .. or and ~;erphina ars the Act1ve tor~s th~se arugs; nor!"':t;.~r?hing· is lrtitct•ently a \IP..;;aii.ar drug than !~orph!M; t.mdcr:· con-dlt..lons .. ot c..lotranlc ao1n!st.r~t1on, ·less norMrphlne Is· bound· so t.'lat JtOre tree and,. pl"CS~"'.13bly, a ctivc eruo nccu.r-..;ula tas In .broln than is t.he ~sa. \>:lth t;!Jrvh!nc. O~Viou.sly t!llS lij?vth~Si!l eiri only bz t<~tileu !n unl~.ill~ sr.:d; !.>cf{'Jffi l;;; ccn f.Bsf.. _ft_, t.-c . \. \ f . -- ~ -- ...... -. . . ~ -· . -··.. - . ·- - .. I I . 'l ; ' - . -.. ·-' .tie an. interested· 1n cn\1 have carr led out a lnt:;;rc~t in u.~.sc co::poun.Jti $b:n4, !n pur t, rr..:n 1 1 -... ~ .:, : ~ 'A""~C t ~· ... a ,. ~ "·~ v·--. .... 1:' .. • ' - .. '-I-~ • ·-- ... I _, _;, \ ~ j ' ,_ ."\ ~crotcn!n-!nd~~~d contr;;J.-::t.!on5. ls co:-rp~1r.ed: li!th. th::·f'r- p5ychoto \ \ I f.ai th. e.n·t.i !n ~croton l ---------------.- l j I ' .. - /). ts r~t ais':- a pCJt:ttt :iat.ls"'"&otnnfn. ";::usf;u ~\.~~ \·1hile • ' - .. '-I-~ • ·-- ... I _, _;, \ ~ j ' ,_ ."\ ~crotcn!n-!nd~~~d contr;;J.-::t.!on5. ls co:-rp~1r.ed: li!th. th::·f'r- p5ychoto \ \ I f.ai th. e.n·t.i !n ~croton l ---------------.- l j I ' .. - /). ts r~t ais':- a pCJt:ttt :iat.ls"'"&otnnfn. ";::usf;u ~\.~~ \·1hile n~t ft>_'~'ortng thtl 't;i!~~:stu-n.t~-,~r~rlch:n.cy :·t~~ioi:hc~!s of th.:: LSD ps;·~:!;utois,. · (.;:, n:;,t 61 t.i)rc:v-~ lt. • .. of· pct...;nt. hy.,not.ic in to d:::t~:cf.!vn a;'tcct~ OJ::-?tJtU"I.c;~ ~~lt$-'!;.,.l\l I ~o: •,potm ..! e l-ie '· 1 't.•'"" ~ .... l 1 #J~;., ..... '\:. .. u .. <:.~. 4 ....... lio.,-to'-..... - ·I· . . .. i -~n fi~-~:;ll!l .:.;~--:.r~ il9:-'oc l~l·~ !n 1 j I 'I l I j· \ -·· ..._. . · . . ~ - i ~ - •. •• -.- ···;; - -· - - : · . - .~. ....j . • ,. · ~ ' ·. - .., . • . • . .. .. . t' 4 H . , . ~ . .. . . . . , . . - . -· ----. ,.., ~ -'"'. •. .-.._. ... ~.ll..t. • ' '":. · I I ...... ,.. - l j j 1 l t- ~'' '.-. · : The ~thod u~~d ~n evaltt~ t.lng h:.:t1nosts ·wa~· ail !ollt::iJ!:: en tha !ollotdng r:.orn!no th~y ~ere ~iv.::n, or • . ~ .:.).o '• , . : p .~ ~ . In randomh:t;d .. t!.~u!)l~-111 t:ld" ta:h!on, 2 or !~ ag. V-A-21~ 1{)0 or 200 so olen or a ran .. ~g. o~ sc~ho.r·!lit3.l6. plac~bo. ~ received all !1vu pa~lents lr~4tmvnts. nru~s ~rc oiv~n wi~~- . .· . . ,- th:.t patl~nts f~stln:J anct eortee \:a!l.'.not pcrn1tt.ed. Patiu:r.ts ~t'<l obsGr.vcd.at hnlf-hcur 1ntcrva1s !t"Or;\ B a~n. to t~~p·;-t· t.o··. .... . 'I I l i ~-·-.. e:::L:m.c.:s !t .. ~/~t~.;nlly \ \ '· ....... I! :i < ' ! . ·.·. .... ;. ';·· tlj:Ig tellt.!nQ .nllcut. s.o:ne or CJur pro!Jra~ and no t!1~a l$ latt. t"o~ n d.lscuss1on ·o! t:1;: 1~oi"t.a.'it and lntcr..tstlng .tas.tc ret~~rch~s ear~!eu on by our neurophys1o1oslcal and p$y~ho­ nr. 1 lob!..-.al s~ct.!cna. ! 2'"~3 t!Mlt at. the n~xt me~t.lni] !-/Htha·.c ! .I and tis c~~~to.:.~.kcrs can c:.v~r tn~~o asp:et.a ot our •ork .for, :,.-cu • l .. .I . I ... _:! I l \ . . i ' l j '· l l ~ f j" .- ' t· The document is a typewritten page of text, appearing to be a research paper or report, with a handwritten annotation at the bottom right corner that reads "A-296". There are no photographs, diagrams, tables, or forms visible on the page. The text is primarily concerned with a compound called "NIH-7590" and its effects, particularly in relation to morphine and addiction. There are no official stamps or redactions present. The page appears to be a single sheet of paper with some minor flecks and specks of dirt. lob!..-.al s~ct.!cna. ! 2'"~3 t!Mlt at. the n~xt me~t.lni] !-/Htha·.c ! .I and tis c~~~to.:.~.kcrs can c:.v~r tn~~o asp:et.a ot our •ork .for, :,.-cu • l .. .I . I ... _:! I l \ . . i ' l j '· l l ~ f j" .- ' t· \ ' !,. 1 1- . I I. I ..... ·- ·-; . - ' ! ! (b) D.thycrod.e~oz.;y.~.rph !ne-D ( "r.~s.or:.orp!'lln~ n): ( c} C.!hyuro I I <le:.oxycodeina-n. (nc.es.oco{telr:~-:"); and (c) ~~tthyld1hydro.:n.or- .! ' .......... r ~ .~ t,.i.. -:....·-~~· • j.: .:. .~.'-" :~- .·~:-If·. . •.• 1 '.t.:.i.• I \· ' -------·--- --______ _: _ _______ - . ------------- ... J' · r LEGEND FOH IGUf-c.a: -1. ·~· or n_elat!onshlp or dose r.:.orph1n.t fo IntcnsJ.ty \ \ . l ' ' - -.;.;. -. ' . ' . . -----. ~\.. . "-../ - I \ j . I I I i I- I . - I I A,"•;}' ., 0 I I I· I :.· 5 I I· / / j - N / 0 ~ - • (J1 N ~ "'; ), 0 (X). . N \ - 0 \ . (Jt 1'\) j .' 0 0 l- ~· N o. ' . Itrl o·o ~ ·N l • ·(J1 r---------·- --- ----------,-- i . -------..c-.. ------------ -- -·---------- -· ------ --·--- 1.. '' . --,.--- -- •, .. . . . i i i l ·j - . ._#.,. , ..... I I I \ I 1 i ~ . ~ i "I ! \ ·\ '· \ \ 1 t '' ·l .... \ ' +-·· -_.,..._.. ·.:--...· ·. . ' .. ' J 60 ·; '· ; ~. 1 f . . . r. 1 40 l . ~ i ' 2.5 Mgm 7590:::49 Mqm MORPHINE ~...:-- ' . t · 1 20 I ·l \ I \ ·; ' ~-i I \ \ 20 .. 40 . 60. 80 roo L---~~~E- DU~~I~G-~~-~-?~12"~!I~N _EEB_IQA~-<7? ' .. l -· ------~-· ----.::---·--~------··:··- ------;.·· ··, . . .. '· ... e· - '· Figure .1• '· .. I l .. 1 !,; ; ! I ' I ' ---------· ·----------·-·· ... --~-·-·- --·- -·---------- - ... ' . .... " I. ~ -~ ~- ~' f • . . ~ " .~ :. -:. ..'. {·. ( (~~\ I . . ~ \.._""' .. :.. The document appears to be a typewritten page with some handwritten marginalia. There are no photographs, official stamps, forms, diagrams, charts, or tables. The text discusses the potency of a drug called NIH-7590 compared to morphine, referencing experimental data and statistical calculations. There are no visible redactions or obscured content. The only handwritten addition is a number or code, "A-295", in the bottom right corner of the page. '· .. I l .. 1 !,; ; ! I ' I ' ---------· ·----------·-·· ... --~-·-·- --·- -·---------- - ... ' . .... " I. ~ -~ ~- ~' f • . . ~ " .~ :. -:. ..'. {·. ( (~~\ I . . ~ \.._""' .. :.. ::.:~~\~ I CH3 · HO CH3 ~ •lNtG2H5)2 CH3 I . \~ I i. . ' I !I ... (-,~- i . ~ ..... · .N·CH3· I ! i . • I .. . j ' ! i · ... LILLY L v·sERGIC ACID ·. . . ,_ AGROCLAVINE DIHYDRO~ 23l94 AGROCLAVINE (FTHYLAM . ID E : .· (ARC VA•2tl . . •• i I I I I • I I l , ..... r' I t ,.,, ,. I I ; I ....... ... ·· .I ..... - ! I .. -~---~--··,...,...__...,_... .. --:-. ----~--· -··- --;~ -~~-~---.. ··· ···---·~·-··-L···-···· ...... I --··· --~'···--··-¥---'·~-·-· -~~-~ --~-----.. -,.~~--. ~ . t ; ... both cru:;s. A-27~- • .- i . . '· .... L l:. i •' p. • ' . I . -"\ r--.. j. ('1" . I @. ~ - II' ., PERCENTAGE OF DOS·E EXCRETED. IN 24 HOURS ·., ' MORPHINE . NORMORPHINE .· . .· ·· ' . ' "\ . . 0/o AS . · 0/o AFTER 0/o AFTER 0/o AS · · 0/o AFTER. · .. 0/o AFTER I ' ·,. II FRE E11 . ACID ENZYME 11FREE II ACID · ENZY.M E : i '. ,., .. : ~.. I ., I II. 4 .··· i..'• . . 60.6 54.6 51 73.1 . ·. ' .. · 56.2. '' I. ' • • (8.9-15.1)·· . (55.9-63.3) ( 41.2-62.1) (48.8-53.2) (68.8 .. 77.5l . ('49.8~64.(} .. ' . ' ' .... ,. .. , . . ,• . , /, . :·· ~ . ,.', . - /" . .. .. I i i • . ' ' •• ···~.i> . . ' I ., FIGURES. A'RE AVERAGES OF OAT~ ON THREE SUBJECTS. • .< .I I ' .. II RANGE SHOWN IN .PARENTHESES •. ·. . ' I I .. I '' c····:. ' I • I I ·, I I ..~....· I i I I . I .. i ' i l. •. . j· . i ... 'j I 1.' . •' I' I ! ; i ·; . ·,' /' The page is primarily text-based, appearing to be a typed report or research note. There are no photographs, diagrams, or tables present. The most notable visual elements are two handwritten annotations. On the right side of the page, there is a handwritten number "A-294" in a cursive style. In the upper right corner, a handwritten notation in a different style is partially visible with some dashed lines. The document appears to be a single page with a slightly aged or faded quality, indicated by the paper's texture and some minor spotting. The document is a typewritten report with some handwritten annotations, most notably a number "A-293" in the lower right-hand corner. The text describes a preliminary estimate of the drug NIH-7525's effectiveness and addictive properties, along with details of a short addiction test. There are no photographs, diagrams, official stamps, forms, tables, or redactions visible on this page. The document appears to be a raw, unformatted text document, possibly an excerpt from a larger report, with varying ink density and some faint spotting throughout. •. ·. . ' I I .. I '' c····:. ' I • I I ·, I I ..~....· I i I I . I .. i ' i l. •. . j· . i ... 'j I 1.' . •' I' I ! ; i ·; . ·,' /' i ,, / I , I ·" i .. j/ - ' ; .......L ....... ! . .,..,..~Lj ~.--·- ··~·--··---··· ···---~-------·-'-"'· .... --~ ......... ~ ..... ..... ~,.. .. '" ·~· ~-. ~·------......- -+-'- ..· ~ . ! ·I ! l. 1 ·I { i "··-ir 'j I Table 2. Comp~r1son of psychotp:;tlmu_t~c:. and pnt.l!l~~rotonln potencies of congeners of LSD. r, t I \ \. \ \ \ ·L" --- ·- --------;; 1 ( •. .. .. . - ' ,. . l. ' . . ' It'- DOSE APPROXIMATELY* RELATIVE RELATIVE*'* EQUIVALENT TO PSYCHOTOMIMETIC ANTISEROTONIN I.Omcg/l<g OF LSD-25 ACTIVITY .ACTIVITY · }' .. CODE COMPOUND (LSD25=100) {LSD25=100l \'{. { ' A. STEREOISOMER$ "\~. d-LYSERGIC ACID DIETHYLAMIDE 1.0 100 100 I '' . \ 1. . LYSERGIC ACID DIETHYLAMIDE >70 0 0 I d-ISO-:L YSERGIC ACID >50· 0. 0 \ ' I '' . I I i B. VARIATIONS IN AMIDE GROUP.·· I ! ' d· LYSERGIC ACID DIMETHYLAMIDE . 10 10 .· 23 I I· d-lY SERGIC ACID MONOETHYLAMIDE 20 .5 ; 12 \I I ;, I d· LYSERGIC ACID PYRROLIDIDE 10 10 5 I .. d· LYSERGIC ACID MORPHOLIDE 9 I I 2 I \ I : I. I C. SUBSTITUTIONS IN RING SYSTEM \ .... \ d-I-METHYL LYSERGIC ACID DIETHYLAMIDE 3 33. 370 I .. d·I·ACETYL LYSERGIC ACIO DIETHYLAMIDE I 100 210 l ' ill \ d-2· BROM· LYSERGIC ACID DIETHYLAMIDE > 86 < 2' 103 d-1-METHYL-2-BROM-LYSERGIC ACID DIETHYLAMIDE ;,, > 175. <I .. 533 '\ ·, .•. ·1·""'· ·. -':_, :~~:. D. SUBSTITUTIONS IN RINGS AND VARIATIONS ,..i~~~~·t IN AMIDE . ')~;;j~ ,d)!,<l~it ·.·~LA ( ; 74 d-I-M A E M TH ID Y E L- . L . YSERGIC ACID M . O N ,, O .. · E .·· THY . L ' · " ' 25 4 835 I I ···.-,.-,tl'J , . 1 . : ' .~;J f~ : ~ }1· ; , J, • · . . LA• ;.·~. . . d·l·ACETYL·LYSE:RGIC ACID MONOETHYL· l '< , . . AMIDE.:. 15 7 ·39 I :;:~o~ 75 d·l·MEiHYL-LYSERGIC ACID PYRROLID1DE > 20 The page contains typed text, likely a research report. There are no photographs, diagrams, or stamps present. Handwritten annotations are visible in the top right corner, including a circled mark and what appears to be "A-292". The document exhibits overall good contrast with some minor speckling throughout the paper. There are no visible redactions obscuring any content. The overall visual impression is of a scanned, typed document with minimal additional markings. " ' 25 4 835 I I ···.-,.-,tl'J , . 1 . : ' .~;J f~ : ~ }1· ; , J, • · . . LA• ;.·~. . . d·l·ACETYL·LYSE:RGIC ACID MONOETHYL· l '< , . . AMIDE.:. 15 7 ·39 I :;:~o~ 75 d·l·MEiHYL-LYSERGIC ACID PYRROLID1DE > 20 < 5 130 I I * SEE TEXi FOR MEiHOD. OF .ESTIMATION } ..: ;.x:~· . t ' I l I \ **TAKEN FROM. OATA.OF CERLETTl AND DOEPFNER ' ' -~r-;. ,. . . ~ ~ ·--::-~·--; --:~-; '--~' .. ~I. ., .::-. ,. .. • -·-·· :·:"·' ~ ~ ,'··· \ .. ,-.. .,..,_ .--~~- -i-,,,_ ., ~~ ---- ·-.:·1 '!;:.- ... •• '!; Table 3· Co::;;:ar ls:.;n cf hypnot 1c eff~ct.s o£ V-A·2l and soco~arbital. '· "i I ! ' "t 1 j \ .. ' ~ l I j ': . , -- .. ... . \: .... ., , . .,. .; . it. . t '......._ ['.... .C"' I ~ .. I HOURS DIFFERENCE ·1 SIGNIFICANCE ·oRUG I sLEPT · ± SE FROM PLACEBO OF DIFFERENCE - ;__ I -- i PLACEBO 1.5 * VA-21 2Mg . 2.8 +1.3 ± ± 0.25 < 0.01 * ~ * i. ( ,.\M-12M .. VA-21 4Mg 3.0 +1.5 0.05 - <' 0.01 I ± ' SECONAL IOOMg .· ~.2 +0.7 0.39 N S i SECONAL. 200Mg 2.3 ·. ·:·< +0.83 ± 0 .3 >0~01 < 0.05 * i . .. I ' .. I • l 'PLACEBO I. 5 .. .·. . .. I 0.6 . -0.9 ± 0.55 NS VA-21 2Mg NS· 12:30PM-4PM . VA- 21 4Mg 1.5 0 SECONAL 100 Mg 1.5 0 NS SECONAL 200 Mg 2.2 +0.7± 0.5 N S PLACEBO · 3. .. .. .. I I V A-21 2Mg · ~. 3.4 +0.4±0.64 ~ NS I 4.5 . . +1.5±0.8 >0.05 NS ·. 8AM-4PM VA-21 4Mg . ( I 3.7 +0.7± o/41 Ns· ! ; SECONAL IOOMg * ' + ',<0.05 SECONAL 200 Mg 4.5 1.5±0. 7 I l r·:,' I ). **.HIGHLY SIGNIFICANT I :. * L.· .. SIGNIFICANT · . ) /: -r~/'"l I ·· N S NOt SIGNIFICAN'r . / I /./·· ·I l .; ' ..- · i l I . I .. :~--. ~ ...... ,... ........... ......,..,._..,__....._. .• --- ~··· ·---~-----·~- ..... - .. ~--t------·-·-·--··~----·- --· -·· '~ ·--~__L :,,- :_ _____ J. .,..+~-~~~_.,....__..~-·- "' i ) /: -r~/'"l I ·· N S NOt SIGNIFICAN'r . / I /./·· ·I l .; ' ..- · i l I . I .. :~--. ~ ...... ,... ........... ......,..,._..,__....._. .• --- ~··· ·---~-----·~- ....