Doc 0000151543

. "..: THE ADDfCTlON Ll A tTY OF SYNTHET tC Sl.SST ITufES F02 CCOE INE (Pro jcc: t · O~ser Jpt I on l or 2~quest to the Off' Ice of Nava f l?ese~rch for ~cncwa f Co D t r a c: t N,~ I f 3-f 4 9 Ser Ia I f 8249 Naonr lSI-53 , I. fnf'orrnatton Suc:~sround Since ·July 19~1, a project designed to develop a ayofbctrc drug which would be as safe as cod~lne wtth respect to toxtctty, ..... antitussive ac:tlv_tty, and addtctlon llabtl_fty has. been carrted ~) on wtthtn the Nafional Institute-/of' Meofaf Hcafth Addictton • .r .. :. Research Center, PHS Hos~ltal, lexington, Kenfucky. This / project has been rtnan~ed to tarse part by funds from the Office of' Navaf R~fsearch and tbts de,crtptlon constitutes a / or request f'or renewal tbe project for the period I July 1956 to 30 June 1957. A :ynthetic substrtut~ for coderne ts badly needed stnce • • on1 • y source rn~ of codelne. Unless a synthetrc substttut~ for codefce f$ d~'lefoped. th~ Unrted Sra~es-.must.eor:tfnu¢. to stocS:plle o~lum fn order to provide adequatz svp~fies of ccdclne for both t~e elvrflan and mtllfary po;:>ula.t lons In the event of war. The facJitttes of th~ NI~H Addict ron Research Center are nof sufficient to carry on thIs work In add!t lo.n.: to drug: t.::·~.t lng , . ·--r- /""":'~ ) ·-,_- or •• , rcqurr~d for the l_uatroo stew aoafgeslc:s- unless addlttonal funds ~ svppl led by the D_~partmcAt o.f o~f'e&U:t:. 2. Aeeomoftshed to Date 1br~ Previous work has beco summ4rlzed In the annual progress reports sent to Capt. F. H. Gutmbv, Head of the Physiology Branch, Off'tce of Naval Research. Two drugs ha.vc bceo devcroped whtcb are promfslng poh!attal subst Uuh:s for codctRc for rei ter of cougb. These d-rugs ar~ ttl and C2J narcotine. Neither drug possesses dexfrometborphan~ anv addtc:t Jon lli,bll tty a ad both have ref at lvefv. tow tox le tty • .- . tussive effect. / Although two very-p~omtslng_4_ntttus.$1ve sub$tltufes fo~ codeine h4V~ b~en found~ oo compound is yet available.wb.feh Ia as cf(ecrlve codeine for the reltef of mild grades of parn 4S and which Is as safe as codeine wlth respect to botb to~lcify aad addlc:t ton I tabt I lty. Wore rhao 25 C:Ofl1pounds bav~ been $t.U~ Q 1 . 8 .. - . ( J ] f • . The image displays a graphic representation of a secure vault door, symbolizing "The Black Vault," an online repository for declassified government documents. Text overlayed on the dark background clarifies that this specific document originates from the MKULTRA/Mind Control Collection, a compilation of over 20,000 declassified pages from the CIA. The text also provides a URL for accessing the full collection online. No photographs, handwritten annotations, official stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures are present on this page. The page is a scanned document with handwritten annotations, including a circled "66" in the upper right corner and a longer alphanumeric string "A-230" at the bottom right. The document appears to be a formal report or request. There are no photographs, diagrams, or experimental procedures visible. The text itself is mostly legible, with some minor smudging or bleed-through from the original paper. There are no official stamps indicating classification or distribution. cf(ecrlve codeine for the reltef of mild grades of parn 4S and which Is as safe as codeine wlth respect to botb to~lcify aad addlc:t ton I tabt I lty. Wore rhao 25 C:Ofl1pounds bav~ been $t.U~ Q 1 . 8 .. - . ( J ] f • . . . , . 1 . ' J 7." s ' tA ...., • s.., . .. , . . .. . . " ., ' .I : J '_ I- , f . t l - ""t · + ' . ' L ' J · ,~ - 4 ~ ! . ,. _ . , - _ - ,- · . - . 1 ... " _ " ~" - " - "" · • - •· . ~ .. " . A - • "_-."...- , ••...-.... .....,...._..,....,. _. _ tJ _ •' _ -'" _ ••" , " , 1 .. 1 . ; . O$ sub~tJtutes for c:odeln~·for analgcstc: use. The outstanding eompo.un·ds are a Jpha-dl- and illp!la-d-1 ,2-Di?~,enyl-2-~ropioncxy­ di~rbylawlno-3-m~ihyibutane. The d2~trcrora~ory Isomer accounts fer all the analgesic: potency of these particular The drugs are nonroxfc. com~ounds. 7 A-2.2.. . ' . - . ) Js codtdne, suppr: ·abs.tiDcQce fror>~ m~rphlne only slightly,. aDd have ~cd-fo be effect tv~ tn the reI icf of ., eltnfcal pdln, although studtc~ of the analgcsfc: effect arc still Tnadequ4te. 3. Need f' or Con tJ n u a t l on of the P r o) e c: t Although two drugs have ~ea discovered that· have promise as potential antttussivc'substltuteS: for codeine end several. drugs have been d1scovercd whlc:h mtgbt serve as po•stblc -·.· substitutes for codeine for analges1a~ It Is stilt un~nown ... whether any of these drugs wlll be ccmptetcly satt~factory ~~ to· c:llnlc:al use for elthe·r purpo$e. t't is.t therc1ofe.- . / essential to c:ontl3ue t~e seerc:h stnce the larger the number of compounds d~veloped,~ / reafer ts the ~hance of rtndtog a cocpletefy adequ~t~ substitute. / 4. Wcr~ ?roooscd Ourtng tb~ p~riod t july 1956 to 30 lun~ 1957 ~e propo$e · c.ompound3 rr~nt loned ~hove. Thts drug ts $0 promi5lng that dtreef acldtcfton llabl1tty_ studtes are ~~qutred. Such studtes ar~ ~ery tim~ consuPing and wttl require st~ to nJn~ month$ ror complzfion. In addition, ~e Intend to study the addlctton Jtabtlity of N-allyidthydrohydroxycodeinone to everv~te th·z . . , " addfetfon liabfltty The document is a typed report with some handwritten annotations and a stamp. The typed text details work accomplished on new analgesic drugs, specifically mentioning dextromethorphan and narcotine as substitutes for codeine. There is a handwritten annotation "A-229" in the bottom right corner. The text at the top appears to be part of a classification marking, with some characters obscured. The document's content suggests a scientific or research context. rr~nt loned ~hove. Thts drug ts $0 promi5lng that dtreef acldtcfton llabl1tty_ studtes are ~~qutred. Such studtes ar~ ~ery tim~ consuPing and wttl require st~ to nJn~ month$ ror complzfion. In addition, ~e Intend to study the addlctton Jtabtlity of N-allyidthydrohydroxycodeinone to everv~te th·z . . , " addfetfon liabfltty or tb~ dthydroc~d~tnc and_to study sucb other substance~ as !My· be suggested by tbc. Commft.t4!c CD Drug Addlcttoa end Narcorlcs, Nattonal l:!escarch Counc11. M-ethods I -~-- The methods to be used arc tbe st4adard addtcttoa llablltty testing mctbods of the NI~H Addtcrtoa 2esearch Cent~r. The£e . have been described ln prevtou~ project deserfptlons ~nd should be consulted for details • --- .. :.' 6 .. Ev4 fuat ton of Data ~~ Tne eva luat ton of datn ofir~:.t'ned fo fh~ add-ict Too J/~b_Jl tty program has also bezo d·tscuss~d In previous proleer des.crfpttons • - . or 7. loect1cn Prole'ct / Wor~ wl 11 be carried out ar rh¢ NtM-t Addlcr lon e~search Center~ PHS f-'tosplt41, l_extngton.- Keotuel:y. Thfs fnstttutron provld~$ the two nece~$ary factltrles for~~ type of ~ork to expertmellrs with drugs,. and (2} sf'ric:t environr.~ntat conh·o! . wtl lc:h p_re\U!l)T$ rhe ·. introducr ton of drugs other Hl4n fhose under ... 4-2~1 /., ... ·· · . . ( ~ ,...., ~~ ' - I ./ . 8 •. Exp~rlment~f Persoan~t . ...... ~ork wtll ·be carried out ~nder the d 1r e e t ! o ~- q f w'"-" .-- t. 1 • - ... - ... ~ ..C - i • t .• I ~ ·. P.:t.D., Otreeror~ NH/H Addtc:tton ~cseorch Center. Thts. lnvesttgatos has had twelve ycors of cxpertenec Jn res~arcn In narcotic drog 4ddtcilon and has pubfish~d rnany papers l~ tbe fteld. ~k wll I be .,:ssJs.ted by two oth~r «xp~rlenced physJcJ~n$, Dr. H. F. Frase\ and Dr. Abraham Wf!der, both of whom have had extentive expe~~teoce tn res~~rch In ·addict ton, ttl tb ~.any pubt tc~t tons. Jn addition to· -these c~dtcal ·p~r$onoel the part-tJme servfc:es of a ·btoc:hemtsf .. and research psyc:h~·logist will b~ .~de avaltable. A speelal ?'- ward for the conduct of th_ese· srudfes Is currently ·rn· oparatJon. · .. Th Js l s necessary in order fo provide fund; for th~ increase in CivTI / Servl ce:· pay wfdch trent tnt o ~ff eet J n· r.U.reh l9SS. I. Pt!rsonnel 6 Psychiatric: Aides GS-5 {$4210. p.a.l l ?bys the conduct of th_ese· srudfes Is currently ·rn· oparatJon. · .. Th Js l s necessary in order fo provide fund; for th~ increase in CivTI / Servl ce:· pay wfdch trent tnt o ~ff eet J n· r.U.reh l9SS. I. Pt!rsonnel 6 Psychiatric: Aides GS-5 {$4210. p.a.l l ?bys lea t Sc: Jeuce AJda GS.~S 2 •. 2cse~ve for _Pr~r.ium ?ay · 1Nish~ d1ff~~entlal, Holtdev, z. Trcvel 4 .. --~ ...· ~-:~~ tzbztl, H~~ris ~.D. C: i r ~ e r oi~ :·H: rn The document is a typed page with some handwritten additions. There are no photographs, diagrams, or tables. A handwritten annotation at the bottom right reads "A-228". There are no official stamps or markings visible, nor are there any redactions or obscured content. The document discusses scientific research related to potential drug substitutes for codeine and proposes further studies on their addiction liability. This page is a typed document with handwritten annotations. There are no photographs, diagrams, or tables. The document includes numbered sections: "5. Methods", "6. Evaluation of Data", and "7. Location of Project". Handwritten marginalia includes a number and symbol above "6. Evaluation of Data", and a handwritten annotation "A-227" in the bottom right corner. There are no official stamps or redactions visible. The text describes the methods, data evaluation, and location of a project related to addiction liability and drug research. The document is a typed page with some handwritten annotations and marginalia. At the top, there are what appear to be two small, circular, lens-like objects that may be part of some optical equipment, though their purpose is unclear. The text details personnel and estimated costs for a research project related to addiction. There are handwritten figures and text in the right margin, including a signature and what seems to be a document identifier or page number. A block of heavily redacted text is present on the right side of the page, obscuring some numerical data. The bottom left corner includes a handwritten date and a location.