Doc 0000151882

n1E ADDICT ION l L-\ SIll N OF s•tNTHE TIC SUSS T I TUT~ S FOil CLuE JNE __ CProJ:ct D~•crtptlonJ -· Requctt' to. the OFf lee of N.sva I ~~search for Rotnc wa I of @ Contr<1et 113-149 N~ Serial 18249 Naonr lSI-53 I. Baeknroun~ fnlormatforr ..... ------------·--------·~ SJnce J~ly 1951 a project dc1lgned to develop a synthetic drug which would be as safe aa codeine with respect to toxfelty, antltu,slv~ activity, and addl~tfon ltabll lty hat b~~n earrftd on within the National Institute of Mental Health *ddfefton ~cS~.!rch Center, PHS Hosplt~l, lex fngton, l<~ntuelo:y .. T-h.l$ proJect has b~en fl~anced tn large part by funds from the Office of Navll ~esear~h and this description constttures a requ!st f'or renewal "' the project for thf: period- I Jutv t957 to 30 June 1958. A synthetic $Ubstrtute for Is badly since codeln~ ne~ded optum or r.~rphin~ dr.rlv~d fr~m ~plum ecn!tlt~te "h ,. .......... J .. • ... w ~ •• , source of eod~lne. Unless a synthetic substltut~ For codetn~ Jn order to provtdz adequJte su~~Jtes of ccd~lne f~r b~th The fa c ; I l t ie s of t h ~ N I::,Y .~ d d I c t 1o n · R\ !sea r c h C en h: r a r ~ nc t sufficient fo csrry out thls work, in addition to drua tzsting • . · . . ~ .. . -· rc-qufrcd' for the ev.a.fuatlon of alf n~w anafgcslca. uftlesJ ..CcHI"·lorta-f· ,.U1fd$ ar« suppl.led by the Oep.srtmcnt bt Deien1e. 2. Jiorf: Aeeomol hh~td to Date- Pr~vlous work has been summarl%ed In the cnnual progress rcporta lent to Capt. F. H. Quimby and Capt. T. K. Ruebush of the Physiology Branch, Office of Naval Resear' ch. T~ drugs ha~~ beeD developed whJeh are promising potenttaf substitutes for codeine for relief of cough. These drugs are CIJ dextromethorphan and t2) narcotfnt. 1 ~~~her drug posaessea any addJetton !!ability and both have re·lattvely fo~1 toxlefty. The :tudtes reported at t-h~ meeting o~ Commit tee· on Dr-vg Addfef Jon and Narc:ot Jes of' the Nat iona t Retearch Ccune: I, In January 1957, eont fnue to fndJcate that the drugs arC! ac effcetlv~ os eodefn~ ro·r reti~f o1 cough. lr seems almost certain~ therefore, that the antffusstve Although the antltussJve probl~m ts no longer a; pre~3fng l: n-o wn t o be a s c f f' The image displays a digital graphic that serves as a cover page or introductory screen for a declassified document. On the left, a stylized illustration of a bank vault door is visible, complete with complex locking mechanisms and a glowing blue accent. To the right of the vault, text informs the viewer that the document comes from "The Black Vault," an online database of declassified government documents, specifically housing a collection of over 20,000 pages related to the CIA's MKULTRA/Mind Control program. The text also provides a URL for downloading the collection. There are no photographs of people, locations, equipment, or subjects. No handwritten annotations, signatures, or marginalia are present. There are no official stamps, forms, diagrams, schematics, organizational charts, tables, or structured data. Additionally, there are no visible redactions or obscured content, nor is there any visual evidence of experimental procedures, equipment, or facilities. Retearch Ccune: I, In January 1957, eont fnue to fndJcate that the drugs arC! ac effcetlv~ os eodefn~ ro·r reti~f o1 cough. lr seems almost certain~ therefore, that the antffusstve Although the antltussJve probl~m ts no longer a; pre~3fng l: n-o wn t o be a s c f f' e c t J va : a n d s a f ~Z a s eo de l ne 1 o r r e J ! e f o t m tt d grad;! s or p<l J J • U.o r e th a n 3 5 ma r e r J a I s h a v-=: no w be c n $Cr?..er.zd for thIs perpos~. The outstt'lndlng substances wh kh hat been developed Js ~-aJpha-4-dJm~thytamrno-1,2-dfphenyl- •. "# .. ·? •.. -, -,. 3 . -/'~ .... - ·· ~ .~.-< j 1 · / • but unconfirmed -ork lndfeat~: th4t thl1 compound ts •• czftectlve as eod~tnc a& an analgesic In clinical praetl.e~·. · Extensive work ha& &ho\'ln that, although the compound poste's~a addlettvc pot~nthlfttea, the overall addiction liability h considerably less ·than that of codeine. This drug, ther~fore, f& quite promtstng, but ffnal evaluation muat walt completion ,.· or of extensive clinical trial for reltef paln. 3. Need for Continuation of the Project The chief need for continuation of project Js th~ ref~ted to uncert~lnty eonc~rnfng the analgesic potency of ~-Pro­ poxyphene. If c I tn lea I tr h h show that· th Js drua ft ~s effective as eodtlne then all aspects of our original problem would bE completely solved. Since, however, we cannot be - certain at this tJme that d-Propoxyphen~ wlll replace codelne r'n ellnical u.se, tt li .still essential· l·bat the search for a,ynthetJc: substitutes must be eont Jnued since rhe larger the number of compounds greater ehance ot finding t~sted th~ th~ completely substitutes. ~d~quate 4. ~!orl: Proooscd During th~ p~rfod from Jull( 1957 fo 30 Jun~ 1959 w~- propbze to test the addictive properties of D-3-methoxy~~- , morphtnan, phen~thyt D-3-hydroxy~~-phen~thyf rnerphinen~ and N-al coC:elnone • Norm-;)rphln~, N_,rcod~lne, Jyldihydrohydro~-Y- .. • -· .... .~ IB addition, studfea of other substances rtferrcd by the res or. . ComntHtee on Drug Addict lon and Narcot the Nat lonal Research Council will be carrled on. 5• M~thods The mcthoda to be used arc the standard addiction IJablllty testtng methods of the Nih~ Addletton The document is a typed report with handwritten annotations. A blue circle contains the handwritten number "83". In the lower right corner, the handwritten text "A-307" is visible. The page also shows a few smudged markings, common in older documents. There are no photographs, diagrams, tables, official stamps, or redacted content. This page is text-heavy, consisting of typed content and a handwritten annotation. A header at the top indicates "Page 2" and the main body comprises several paragraphs of technical text discussing research into analgesics and antitussive drugs. A handwritten annotation in the lower right corner reads "A-306," possibly a document identifier or accession number. There are no images, stamps, forms, diagrams, or redactions visible on this page. The visual presentation is solely focused on conveying textual information. • -· .... .~ IB addition, studfea of other substances rtferrcd by the res or. . ComntHtee on Drug Addict lon and Narcot the Nat lonal Research Council will be carrled on. 5• M~thods The mcthoda to be used arc the standard addiction IJablllty testtng methods of the Nih~ Addletton 2e$e~rch Center. These met n .o d s a r c a c c c p t c d a s s t a n dar d by the Co mm It t c e on ·or ug Addict ton ancf Nareot lcs and hevc been deser lb-~d Jn prevlous proJect deserlptJons, whleh should be consulted for details. or 6. Ev~luatlon Data The evaluation of data obtained In th~ addteflon i;&~fl lty rn program has also been discussed previous proJect ~escrfpt:onJ. 7~ ~~atton of ProJect "-'ori. will be carried out at the Nll\-H·Addtctfon Research Cent'~r, ?Hs Hospital, lexington, Ke:ntt-oety. Thts Institution provfdes the two necessary factfltles for the typ~ of work to ~xperlments with drugs, and (2) strict envlronme~t~l control whfch prevents the tntroduction of drug$ other th~n those und~r study into the ex?zriment~f situat to~. 8. Exper-Imental Personnel '\-~ork will be carried ouf under the. dlrectfon of H~·rr·Js Isbell, .. .. ' . .~~ . ... --.-- ·- -..... . .. ~.~ --=~~. Dfrcetor, NlkH Addlctlon Rese~H·ch Center. Thts lnvestlo... 1rcr.' _. h~s had thirteen years of ~xpcrrenec In research tn narcotic drug addict ion and has pub I I shed m~ny ~apers ln t·he f leI d. He wtlf b~ ·assisted by tw other ex;>~rle.'lc~d phystcl~ns, . Or. H. F. Fras~r ~nd Or. Abraham Wfkler, both of whom hav~ had extensive i~perfence tn rese6rch· In addtctJon, with m~nv pubflcartons. In addition to th$!Se medtcaf pcrsonnef the part-tlmz S¢rvtce$ of a bfoch~mtst and research psychologist will be made avalfable. A speetu l ward for the_ conduct of··_ these studies fs currently In operatlon. 9. E:fftntded Cost ~0. The amount of money requested has b·zen hefd/the r s~m~ Jgure 41 cus available Jn fiscal year 1957o r. ?ersonn~l 6 Psyehlatrtc Atd~s GS-5 ($4345. p.a.J I Ph ys leal ~c i e nc~ -At de GS-5 2 •. ·V.eser.v·z- for Premium Pe~y (NIGht differentIa J, ~¢I ide.y, Overt lme) 3. Tr~v::: 4. Mlsc~lfaneous E~pense (Drug~, ehemlc~ls, glassware~­ phctographle su~pfi~s, efc)- .. J . ' ~ t.:_~.- , k . ·.l/ ;( \ - · . . / • 1 .., ~· The page is a typescript document with numbered sections, likely an internal report or proposal. Handwritten annotations are present: a section symbol and "A" are written to the right of section "3", and "A-305" is written in the lower right corner. There are also several small, dark circular marks scattered across the page, possibly ink blots or minor damage. The text discusses the effectiveness and addictive potential of certain compounds, including codeine and d-propoxyphene, and proposes further testing. There are no photographs, official stamps, forms, diagrams, tables, or redactions visible on this page. e nc~ -At de GS-5 2 •. ·V.eser.v·z- for Premium Pe~y (NIGht differentIa J, ~¢I ide.y, Overt lme) 3. Tr~v::: 4. Mlsc~lfaneous E~pense (Drug~, ehemlc~ls, glassware~­ phctographle su~pfi~s, efc)- .. J . ' ~ t.:_~.- , k . ·.l/ ;( \ - · . . / • 1 .., ~· . ; · ..' . ·,_ ,: - , ·v ., . 1 . - ,.. ' _ , ·. _ ; J l · ,.-; :: ._ .. >" . i ~-- .-:>/ .4 - . ' : '· .·:,~.: -:• • / • .v. ;.-1 ·.· . .< q ' .. r,., .. '"~l"tl M .. D. ' J._ f ,..., .. ..,-~ •• ~ ~,., Dir:cror Hi :1'11 .. -- - ~ ... / The page from the declassified CIA document contains typed text detailing research procedures and personnel. There is a handwritten annotation "A-304" in the bottom right corner. The document appears to be a continuation of a report, indicated by the page number "g 4" at the top. There are no photographs, diagrams, tables, or forms visible on this particular page, nor are there any official stamps or redactions. The content describes the methods, evaluation of data, project location, and experimental personnel for a research study. The declassified document features a typewritten report from the NIMH Addiction Research Center, dated February 18, 1957. Handwritten annotations appear in the top right corner, one of which looks like a signature. There are several scribbled lines and markings in redacting boxes, obscuring portions of the document's content. The text discusses personnel, estimated costs, and other expenses for research studies. Finally, at the bottom right, there is a handwritten alphanumeric identifier "A-303."