Doc 0000151531

uF· AGSTPA~T n~SUt~ a. Sfne~ StJrf of PrnJ~et: Tht3 porfl6n of thz su~mery eov~rs the ·pcrtod ·(r·om t July !"951 to 3J D:e~nber 1954. As stated .ebove, the obJective of fbe proJect Is to ftn~ a synthcfic drug would be as effective and as safe from w~lch r the po i n t s of' v I c of human to x I e I y a n d a cl d t c t to n I I ab I I J t y '.:f as Is Although lynthetlc substitutes for eodeln~. ad~quate morph lne arc ava flab le,, such e aub•tanee h needed b.zcau~e no ;ueh drug of the codeine-type ls kno~n. Sev~nty-llv~ per cent of needs for narcotics are for eodclne th~ r~th2r than rnorphln~. Thlt means that the Unfted States ~usr conttnu: to l§pott and stockpile unttl en adequate optu~ ~ynHttJtlc S1 Jbstitu·t-e :for eocfcinz has bec:l dev~lop;:!·u. 1'he •J role of the NI~H Add~~tlon Rese~reh ~enter In thi• Jnvestl- gation cons!~ts of·th3 dctcrm~natlcn.of the addictive properties Qf new drugs. The ton of the anaiaeslc ~valuat and ~ntftusstv~ effect~ nuat ncccssartfy b~ m4de elsewhere. The used for studytnc the 4ddlcttcn llabtll•izs ~cthods . to be ;tudtcd as synthetic for codetnc substtt~tcs ~re . ~ ' r,.,..,..;,..,....,~, .. ~ .... ,...f ... ~ '"'·---~'•1,....., h,. J.\., -~r--·~!-!.,,,. . _ .. f"':rn~ ··'-~J,.·'·J·)- v..--4.; ...... ,.,..6 ..... ~ ... ..,..; t.JI ·-··•i~ II;..J .~; ,,, .. ., \....'.' •. ;r., i •""~ VH ~ ._.,;\.) 1\~V "-' · H and t:arcor ic;; of thz Nat lona t :~csecrch Cou:oct I. '::'hzn such the ph2roacoiogy of the ts by hu~an co~?ounds studi~d vJrfous doses on blood prcss~re, • ,- -~·.,· ... '~-- respfratory minute body temperature, pupillary v~fume 6 s I zz , ~d c • Fo l I o"Y! i n g .c o mp 1e t f on o f t h ~ b 4 s I c: ph o r rna co logt~al work, effects of the drugl on the behavlor or addlcts ev31uated by Gdmlnlsterlng fo~m¢r m~r9h!nc ~re . r... .. them In doses ba!ed on the results obtaln~d/fhe phar~"co- loglcal exp~rtrnznts. If .the drug Induces behavior~! effect: those seen administration of morphine or r~sernbflng aft~r codeine, It Is very likely to possess~ddlctton liability .. The ability of the drug to relfeve or to prevent the •.. of of abstinence from morphine ts next app~arance The image displays the title "THE BLACK VAULT" in a stylized font, reminiscent of a password-protected vault. To the left, a metallic vault door with intricate locking mechanisms and glowing blue highlights dominates the frame. The text explains that the document was obtained from The Black Vault, an online database of declassified government documents. The visible content is primarily text-based, with no photographs, handwritten annotations, official stamps, forms, diagrams, tables, or redactions. The visual elements, namely the vault door, serve as a thematic representation of the nature of the information being presented, implying it is sensitive and secured. The document is a typed page of text with a handwritten annotation in the top right corner. The annotation consists of a circled Arabic numeral "46". In the bottom right corner, there is a handwritten annotation that appears to be a signature or initials, "A-126". The document is a section of "ABSTRACT OF RESULTS" concerning synthetic drugs and their addiction liability, with a specific focus on codeine substitutes. There is no visual evidence of experimental procedures, equipment, or facilities. on the results obtaln~d/fhe phar~"co- loglcal exp~rtrnznts. If .the drug Induces behavior~! effect: those seen administration of morphine or r~sernbflng aft~r codeine, It Is very likely to possess~ddlctton liability .. The ability of the drug to relfeve or to prevent the •.. of of abstinence from morphine ts next app~arance sy~ptoms studied tn pJtlc~ts strongly addicted to corphtne. If the .r . ~':, ~rug u~der test relieves or !uppre3ses ~bstlncne•r tt ts i ~.. .... io have ftablJtty. In such judg~d ~cldic~fon exp~cl~cnts, ro ·th~ c·~S(! cf the drug .. under test" wh tch Is required re l levc or su~~rcss the sy~~toms of ab~t!nence and the degree of / reJfcf or·supprcsston of are lndlce: for ccrnparfsou ~bsttnenee the standJrd drug, codeine. ~lrh When an especially promtstno drug becomes avatl~bic, lt l3 ~ivdled b'l th~ direct addiction technlc. ThJs lnvolvcs ·1 ' i the of Jsccndlng doses to addict c2~fnfzfrctt~n for~zr .-i ~olbn~eers over perfod~ of tine ranging b~tw~en 30 to 130 t 1 carrted out to dzt~ct and ev~luate th! development of tolerance. 1 I l . r .. • n ~t't c - 'r. .. , .. ... ,. wlfhdra~n abruptly~ and obs:rv~tin~: for (I • , , c.; " th~ dcvclopi:1en{· of Jb:dtncnce syn;:>tcm.s m<lde. - 1 · ~ ;c c • r uGs s ·, r uc • t e d o • ur t ng the period I july 19Si to j 31 1954 drc tabufated below: Dcce~ber 1 l -- _____ ! ... ...,._. ·-·- ,; f• f.,~ I 1: ·-~, ,.~ 'r ~ ADDICT leN liA£.1 ll tTY TUX IC JTY !'USS In lE UTILITY ORU) CRelat1ve to Coc!cln,::J (Rclc!\•lvc i·o <>:d'!lnel .. ......-........ .. .. _----~-------.----------~-------------- ----------~~----._--~~--~~~--~~--------~------~--------.--.._~ .. --.~ ~. l: ··orphr.t n Much hlgh~ .. Greater . t r:J IIC C! ··Dromoran) 3 : ;~dhyt q;ther of Levorphan H1gher Grc.Jter lf needed, tould be l• !l c d for m I 1d pa In , ( . , thy 1r nc thy llHn 1n o-1 :I ( 2 t Higher. Higher t·hn~ L-ti : h 1 € n ·tl ) But -1-~ n e 2-·'I c thy 111m f no-I :I t 2' Htoher Gre~ter t<one ttihlenyl) But-l-en~. Dr :: t r-:>pha n Lower lowiZr· t :) nc \ · , • ··~. r . -1r !"riO ran ) ~. .. \ . Qr~tromelhorphan (3-Mcthvl tower lower V-:ry prc'~~11s ino for The page contains typed text describing a pharmacological study on drug addiction and abstinence. There are no photographs, diagrams, or forms visible. The only handwritten annotations are a checkmark and a number "2" in the margins, along with a signature or stamp in the bottom right corner that appears to read "AY165". There are no visible official stamps or redactions. The text discusses experimental procedures like administering drugs, evaluating behavioral effects, and monitoring withdrawal symptoms. -1-~ n e 2-·'I c thy 111m f no-I :I t 2' Htoher Gre~ter t<one ttihlenyl) But-l-en~. Dr :: t r-:>pha n Lower lowiZr· t :) nc \ · , • ··~. r . -1r !"riO ran ) ~. .. \ . Qr~tromelhorphan (3-Mcthvl tower lower V-:ry prc'~~11s ino for c I i·.zr of D,.:xt·ro,Jh~n J c n IJCi h ~ .... (!I 2 :2-D lphe H'/ J- 4 dImethyl- Higher :- ~ Somcwhe t h s s S t I 0 h t pr·, s s I b! 1 H I c ~ ~·;lnoethyl Villcrate f r ptl J n r c 1 l c f f) ~ 2:2-Dtphcnyl-4 dimethyl HlghP.r ." About equal Slight pn$slbllftlc~ ( "i1noethyl Valer"~e for pa1u relief ··,'t"~ I ~:2-Dtphcnvl-4 d1mcthvl Higher ' So me wrud h s s _ S I 1o h t p j s s 1b l I It k s "ii:.1noethyl ValenHe ~ . for p~ln relief '/' ,/ll ethyl 2:~-Diphenyl-4 ... Htgh~tr Som.:wh!lt lets Sttnht pc:.•ss 1bll rt lc:s \:. _ 3 lr~~~ th ylam lno butyrate . .. , , for pa t n r e I 1e f I .. \ I; ;. h ~~~ 'r ~ ADDICT ICN liA131 L ITY iOX IC 1TY POSS IB tE Vr It lTV DRtG (Relative to Codeine) to (Rcl~tlvc Cod~ln~) .\ Jp lta-1-Mc t hado I Higher 1-flgher r k>nc ( " ') - . r da-d 1-Mc t hado 1'1 ;. Higher .. lower Unl~nown 3. r ·-~2, N-D I me tf1 yl-3-h ydrox v Hlohcr less Unl:.nc\'m : · 'r ph In a n~:· . ' • t . r~2, N-Dinethyl-3-hydroxy~ t-lrgher So me 'II h Q ~ h f (I h c r Possible for relief· , · , r o h I n a n -:;. ' ', \. of polo - i'txturcs Cl-IO, 1-5, 1-3) .. Higher About cqua 1 Very I lmtted ). ,. i' f·!J lorph Inc and f,brph lne·..-. passlbllltles .. ,. ~ ) ~-4~Dipheoyl-dlmeth~lamfno-- Higher Sorn~Zwhot. h 3rher .· V<!tY dcflnlt.z f'·~anone-3 {'r · p•JS s J b I I f t 1i.: s f ·~ r cough.Md p11!n relief .,,, .... ~ ~ ' -::1 M~rl not entirely completed during p~rlod 1~1~53 to 1-1-54 . tc L~low for further detail~~~ . . ' .· ··--. '' ' r ~·i"'~ · ~ · \ : i · . .:f The image is a scanned page from a declassified document, likely a table, with handwritten annotations and some smudged text. The visible content is primarily a table with columns labeled "DRUG," "ADDICTION LIABILITY (Relative to Codeine)," "TOXICITY (Relative to Codeine)," and "POSSIBLE UTILITY." The table lists various drugs and their relative addiction liability, toxicity, and potential uses. There are no photographs, diagrams, or stamps visible. Handwritten marginalia, including a date or identifier "A-164," is present in the upper right corner. Some text within the table is partially obscured or smudged, making it difficult to read certain entries. I f t 1i.: s f ·~ r cough.Md p11!n relief .,,, .... ~ ~ ' -::1 M~rl not entirely completed during p~rlod 1~1~53 to 1-1-54 . tc L~low for further detail~~~ . . ' .· ··--. '' ' r ~·i"'~ · ~ · \ : i · . .:f ?i ~,' b. 2esultsflrl"" C••rr·'"f Rcnortln'] Pe•hd: The v~ ~~" ~~ add let I pro;>u el oh t drugc :·tor clusu d' c!r ug: I were evafvat·ed 'W'L...;IIy or {i} ·part dut_fng th~ eurr.cnt repcrttn.~ period.. Results arc $OOWLl bclo·.v under tn~ lndtvtdual he4dlngs. lnvestfgatton of these two compound$ was p4rtlally eomplet~d during the precedlng reporting period (See Numbers 13 and 14 In Table above). The results previously obt~Jned werq or eonftrmed. The dextro form the- compound was COi::;:>letel't -· Inert, devoid of addiction 1tabtllty; and probably devord of any lr.1~ortant therapeuttc prope.rtle$. For thJs latter reason, I t t s no t prom t$ f n.g a s a s yn t h e t r e s u b s t tt u t e f' o r eo de t n e • J The levorotatory form ~t' the eru.g, on the other hu.n-d.~ ~rf tu t l y au;')pressed abstln • cnce· 'I in patlcnt_s who were strongly a:ddfch:d / . hours were s~ff!eleilr f'or this ptJrpose. The l~vo Isomer, therefore, ba$ htgh«r addfctton,lfdblllty then that of ~odeine# but tess tha~ that of rnorphfn~. Although thf3 drug Js not . 2. 4-4-Diohcnvl-6-dirnethyf~~lno-hexanone-f {See i·t.,. 16 fn Tab J:z ob:)VC i. lr; dosc;J,ot 60 to 73 r::c;. every fr::.:..:r of abstfncncc In 5 patients who wzrc strongly fro~ morphia~ addicted to f·hat drua. Its addiction lldbifify, therci'ot·.:, is A-It~ .. ,~, i~i' ccm~ound rcprcJ~nts ~~other possfbl~ J1J b' t ft u t e for eo de Jn e s Jn c e t t J $ l a a c t i ve • u; e I n G? r r:ta n y as ~_cough .~uppre'ssant• Furthermor~, it sho•Jfd be a ml fd ~natg~stc and ts easfly Aynthe~ized. a. 8enzylmorphli~C ~~1yrtstyl Ester. This drug, which \7a: d~velopzd tn France, is .Insoluble In w~ter a,nd , 1 • (,!. . irl,...· ~:·~-t~ can be InJected only as oral ~uspensJon. For thrs reason, 1'1 a J f work carr Jed out wtth the drug has been by the ora I route. Doses ranglng up to 600 mg. ora I tn France, is .Insoluble In w~ter a,nd , 1 • (,!. . irl,...· ~:·~-t~ can be InJected only as oral ~uspensJon. For thrs reason, 1'1 a J f work carr Jed out wtth the drug has been by the ora I route. Doses ranglng up to 600 mg. ora I Jy dld not Induce any 4--- . deffnit4! r.tO:-phfne-ll~e effects. tn !'l'-'ntoler~nt addtcts. Transient skin eruptions conslstlog of blotchy erythema and urttcarfaJ whc~ls wer= observed ln both of the patlen+s . ~ who received the farg~st dose~. .s . The d·rug was COI:'I()f.:~ely . .,. ineffective in su~pr~lslng abstinence tro~ corphfn~. a ,,e drug Is not regJ:-de/d ~sa pror:1i~Jng :.obstftute $lnce tt Js not a true synthetic, has too hlgh toxicity, and Is probably / ther~pcufl~ally ine~t •... , 4. BetJ-£1.-t.iethadot. In doses r~ngJng betw~cn 30 to iOO mn. orally or subeuta~eously, beta-dl-mefhadol did not '-1 • ~ . f ron.r.;erp,h ' t nC t n · =: • r ronJ I '! u " " .J ; . J J J · ~ • , .~ · . ~ . a ' pu.. t·.·~• n:.• . - . • It Js, th~rcforc, juc • ~ ca ' i•·: :> • n Jv~ no a a•( :1 i c.~~· '• . ~. . . .., I . L . : - .t~""' ·, I t• ~~ \t• • --·~ t• ,,, .-... "'- l,. h" ~. :- -c I s n ·' cllnical duta avaJI, ab1; : on lt. 1• 1~ poss·•a t o ' .c value of beta-cll- a s a n an -; I ~ us s J -.·c ' " - ' : - ;,; . . . . . , .. ' . " i ' . ' ! : J •l ~ ' . - ~ ; r" . ' I l .v- . ~ " ~ "" •J ! v - . '1 II t { • - t f - "' S 1--1£! .. . ··.· . · present c: h ~m t.:: a l I y • tn~ a drug wtth very htgh conv~rttble a.c:fd'fc:t !on I tab If 1t y. For thts r~as~n~ tt Is ucrltkelv th~f It would be regard~d as betng a safe substitute for codeine. 5. Addiction IJabtllty of Natorphlne-r.brphlne Cl-10) Mixture. ln previous rc~ort! It wa~ sho~n that mixturzs of Nalorphine and morphine ~~re not lt~ely to The document is a declassified CIA study related to drugs, detailing their addiction liability, toxicity, and possible utility. The content is primarily presented in a table format, listing various drugs with their associated properties. There are handwritten annotations at the top right corner of the page that include the number "A-163" and the word "Page". There are no images of people, locations, equipment, or experimental procedures visible; the document consists solely of text and a table. This document is a typed report with some handwritten marginalia. The text discusses the addictive properties of different drugs, reporting on experimental findings. There are no photographs, diagrams, or forms visible on this page. A handwritten annotation "A162" appears in the bottom right corner. There is also a stamp in the upper right corner which is partially obscured but appears to be a classification marking. htgh conv~rttble a.c:fd'fc:t !on I tab If 1t y. For thts r~as~n~ tt Is ucrltkelv th~f It would be regard~d as betng a safe substitute for codeine. 5. Addiction IJabtllty of Natorphlne-r.brphlne Cl-10) Mixture. ln previous rc~ort! It wa~ sho~n that mixturzs of Nalorphine and morphine ~~re not lt~ely to be abused by drug addicts stnce·morphtne-tnduced euphoria ts effectively bloe~ed for 3 hours by the Nalorphine and stnee lnjcc:tion of sueh a mtxture·would preelpltate abstinence tn addic:t~d lndtvtduals. Previous direct addlc:tlon expertments wlth thts mixture lnvolv~d ·admlnlstretion ~~very htgh do~s.. t~""acdlettna dose sc:hedul~"l. ~b tnfor~afton ~os avollabJe on ~d~tntatrati~n .., of "therapeutte dosest!·enronlc:illly. _,For this rea'S"orr, 6 p41'lenf: wer~ gi•t::.:n 10 r.!tJ• rnorphlne ph:s l mg.· t!alorp!llne every four hours for }O'doy~, ~fter tJhieh the drug· ..~ ~s withdrown. The unpleasant stda effects noted wlth "addfcttogu seh~dules did mlld abstl~ence, ho~cv~r, ~?peered Follo~ing wtfhdrae~t of a c!r:: t n l s t r to r 1-::> n 07.. ! 1 u- r;:·J • ln one- sen~c, the addiction tt.ablllty oi the mll!t~.n·e ls ~! r-.t t orp h l '1 - .. : 1 r. { .. . . , r · .. - . ·s - ~ rar'h . , .. . . . r 1. . .. . . c.tr . " . 'ctrve or~~ tv, H ,-~a ne-:":"~rpn ~e 4-IU coc~Zlne. f'.!a Jorph t ne. \"/ork .ts belr:g·undertakcn In the hope_of developing 4 morphfn.a antagonrst which ts orally effectJve. The comblnation of such an antagonist wtth a :ynthetfc such as meth~donc, or Racemorphan, might decrease addiction llabtltty and, therefore, be reg~rded as a po·sstb.l<: 'ubatltute f'or codetne. ':Vork 'llfth four synthetic ant'agonJsb: has been partly completed. ,(al lev"llorphan. Thts fs the levorotatory or M:>rphln~n analogu~ Nat~r!'hfnc. The drug h~s been ~;hown to be an effc~lv~ antagonist to morphine and r!acc:morphe1n, both subcutaneou:ly and oralfy. Th~ anttgontstlc cff~ct' •J 5 mg. Thes~'toxlc effect$ consist of nausc~: vomltlns and pr~cl~it6~s drop•· tn blood.·p~c~$ure. To~l~ tfr~et~ of· the cornpou~d tn doses whlch ~ight be used fn mixture• ar~ not of any i~rtou3 consequence. Stnce thz drug li cffee~iv~ ora tty it offers dcflnttc p~sslbli Jtte~ icr the devcicpm~nt of the .kind ~c~lred. . . , ~ r!:-t-f~'! \.; I wt Yt.j n dc~t·rororutorv iGomer of Levallor~han. At ~xpcch:d, is quite t;;ert and, !-hert?fore 1~ n::if a prc:-:1istno constlh.J·<:nt 1 Cc) _ leva I r..,r.tctnor?han. Tr, ls_ t:ompound Is thCJ 3-rnzthyl The document is a typed page with handwritten annotations and a stamp. The main content is text detailing information on various drugs, likely for research purposes. There are handwritten numbers and letters in the margins, and a stamp at the bottom right corner reads "A-161." All text appears to be clear with no visible redactions. There are no images, forms, diagrams, tables, or other visual elements apart from the text and handwritten notes. it offers dcflnttc p~sslbli Jtte~ icr the devcicpm~nt of the .kind ~c~lred. . . , ~ r!:-t-f~'! \.; I wt Yt.j n dc~t·rororutorv iGomer of Levallor~han. At ~xpcch:d, is quite t;;ert and, !-hert?fore 1~ n::if a prc:-:1istno constlh.J·<:nt 1 Cc) _ leva I r..,r.tctnor?han. Tr, ls_ t:ompound Is thCJ 3-rnzthyl ~th~r of Lcv~iforphan and was found to be effective, either ar~Ir~ or subcut~~i~usly,_ in antagontzJng the wffcctt of r.1orp~ Inc or P.ac:e_'?orphan. Untovmrd sIde effects appeared . - ·with cio:J~s greater th~n 5 rr'G• While a deftntte posslbJIJty ---- as a constituent of an antagonist-analgesic mixture, It posscsse$ no advantas~~ over the parent compound, levallorphan. (d) · 3-Hydroxy-t'I-Propargyi-M:>rph lnai'J. Th ts compound ts of especlaf tnferest since lt produces anatgeste e-ffects tn mlce"·whic:h arc equal to those induced by meperidine. Despite thts, the drug ts an effecttve ~ntagonlst when ~ dm I n Is t ere d s ~p c u t a n eo us I y, but Is fa r I e $ s e f f e c t h• e wh e n aclmlnht~r~d or(;lly. :It has been shown to precipitate· S'/f.1ptoma •J of abstinence from r,or·p-htne tn addlc.t~d. p.a.Jf~nts. an..d,.. lher~fore, - . It ts r:ot tOady tc-'bc abescd.~.Y .such· pJflcnts. It offers so:-:;e prcmlse as being e possrb!e substitute for codeine for th~ -- relief of mlld palM. (\!) l-3-Ace tor. y-i\!-~ 11 y 1n ormorpn t nan. Th 'i ~ compound is also an·cffeetTvc antaccnfst when tnjectcd Is npt as pronlsing a constituz~r ' ,., \.-.. I ' .... r -'-. C."- ·r_. t·..; .-.J:•._~ ,.:~ ~ 7. N~rcotine. T~il compound, though nat ehc~ica! ly • - - l I . ' I t Evidence has • " • ' Ot~ • • J " """ " ' . " ... " f - 40, \ . • . • , C - .~ t • t .· ... • _. - ..,. .~ 1 . . . ., , 1 - • ; J • i l . i t t , ~ - ' ! J . ·r'- r H . :! l .z . . . . . .. . '.. , , v .. ~ t l <t . :• . v -~ : ,u, ,"'". TA T ,. " ,.. " , '- . 'I 'I. 1. ~ 1 • .. ·' ·. .• ~-·· - ., : The document page appears to be a typewritten report with some handwritten annotations. There are no photographs or diagrams. A significant portion of the text is blacked out, indicated by the presence of heavily redacted areas. In the bottom right corner, there is a handwritten annotation that reads "A-160" and a stamp-like marking. The overall appearance suggests a declassified government document with sensitive information that has been censored. :! l .z . . . . . .. . '.. , , v .. ~ t l <t . :• . v -~ : ,u, ,"'". TA T ,. " ,.. " , '- . 'I 'I. 1. ~ 1 • .. ·' ·. .• ~-·· - ., : a n t it us ~ I ve I n h.man and anJm~r:. If this Is confl~med, . t h tt drug mIg f1 t a possJble substttute for codeine as an antttusstve and Ynuld, therefor~, have the effect of e:dendJnc "' the: supply.of codeine derived fr~rn oplum. In doses-·t·anging up to 100 mg., etfher orally or subcutaneously, th~ co~~~und does not Induce morphine-like effects In nont~lerant former morphtne addicts. ~b untoward toxic effects were observzd. It appears to be devoid of any ability to suppress total~y symptoms of abstinence from morphine. Thts. compound h, therefore, reg~~ded as b~Jng v~ry promfslng. a. Olhvdrohydrohydroxvmorphtne~ Thts compount .... Is the morphin1! analogu~ of eub)del {dfhydrohydrc>:yeoc!cfnoneJ. . . In do:es of 2 3 subeutaneousJy,. :t tnduecs t~ ~g; ~arked morphine-like effects~ Jncludln6 eup~?rta. tt rcltzvcs a~d su~pl"esses ab~t inen / ce frcra iror~h tne ccnplcte t y. l rs add I c t I o n J t~ b t I ft y a nd t ox t c it y a r e f a r g r c a i· e r t h a n f h o i ~ of codetnone. The drug ts, therefore, not a suft~ble codelnc substitute. ... 0 2-propionoxv-3-i:iethylbutan'"}. 1'!1ts cor.t;Jouncl \'ii!S r~.:-cr.tfy subr:t'ittcd by the Co::1r-1tttee or: Dr-ug Adc;tctic:"' and t~;trcotlc~. i·ndfcate thJt thls have anafgcslc dru~ ~~Y pro~ertlcs 4-;t>( r--... . ..~"" -. ...,_ I for codeine hav: been antitusslvzs rather than anargealcs~ So far, onl.~ prenmrna-ry toxicological tnfcr.matlon. t.s avarlable. In doses r'(L"Iglnf) c,~ to 250 mg. orally nc ~·lfclcncc of rr.o r!)h J n~- f He effects or mot;:>h I ne- J ike. e uphor fa h a v~ been o b .s e r ve d f n non to I e r a n t for mer mo r ph I n e add i c t s • r~b. s e r r o us toxle effects have been ob$erved. SUvf. .J ARY. Of the eo':Ilpounds studied so far, two arc regarded as extremely promising as antitussive agent:. These eo~pound3 are Dextromethorphan 4nd Nlrcotine. Cffnlcal evoluatfon of the The image displays a scanned document page with typed text, suggesting it's a scientific or research paper. There are no photographs, diagrams, or official stamps visible. However, there is a handwritten annotation in the bottom right corner, appearing to be a number sequence (possibly "A-159"). Additionally, there is a barely visible image at the top center that appears to be a stylized graphic or logo, with some text within it that is illegible in this scan. The document's content discusses "Morphine Antagonists" and refers to compounds like "Levallorphan" and "Dextronatorphan," indicating a scientific or pharmaceutical context. ph I n e add i c t s • r~b. s e r r o us toxle effects have been ob$erved. SUvf. .J ARY. Of the eo':Ilpounds studied so far, two arc regarded as extremely promising as antitussive agent:. These eo~pound3 are Dextromethorphan 4nd Nlrcotine. Cffnlcal evoluatfon of the ant ituss ive''propert Jes of ~oth are current Jy underway and It seems prob~ble _that both compound~ wlll soon come tnto the .,. mark(!t r.s con:!Htuents of ~Jnt ituss ive mixtures. Thes.e drugs,~ ., :/ however, constitute an.,: ans'4'cr to on-ly h<rl.f ~-h~ probh:h'l. In . addltion to fts use as"/an c:ntftussive '?gent, cocein·~ Is ro; extensively used the r2J tif~cf ~ifder srade: of paln. As yet no d~rtf~ is. avafJable "'hlch Is, r:no.wn. to be as ~ffective ~s eodetn~ for this purpose and which ~a$ as low addiction liability ond as lov toxlcfty. lm~edfate Pfan:i Duri~g f~c coming sfx ~onths wz ho~e These cc~~ounds arc Propoxyphen6ne tSee par~ 9 ~bovel~ three 1'he·~.Azccyc:Johcptanes ar~ f)f great Interest s Jr.ee n::> evidence n of' addlc.t ton__llab lty .to one of these compounds w~s detcctl!d In an experiment u$Jr.g m~nkeys at the Unl'lersrtv· of Michtsan. . . PreiJminary.elJnleal InFormation has already Indicated that these drugs may be effective analaestc:s. If tnts ts true., and lf' the lr addict ton llabll tty ts lo·.w, lU 1ndicat~d by the exp~rlments at Michigan, they_mlght be eFfectively substituted far codeine In reltcvtnq patn. The ~rug Plperyd1rnethadon~. Is also already tn eltnieaf ute In Great Brlt4tn ~nd~ therefore, or ts some fnte~est. ~e also hope to proceed further wJth the development of antagonlst-analgclic mixtures~ vith chief f:mphas J s en le"3' t I orphan. Further studies o! 3-hvd-ro!'t·y N-Propargy!-l/or;.:thin~n. {d!rect';eddic:tlon} are ~lso Jndlc~tcd. an synthettc substitute far unttt or adcquat~ ~odcinc ~drug, drug:~ Js f~::nJ.r.d wh tch are Jud~ed by the Commlttec co Drug Add i c t Ion and Na reo t t c z of t h.;: ~.Ja t i on 3 l 2 c s c a r c: h Co u n c I I fulfil! all the requirements. Only suspension of neccs~JrY prior to the of this £oal. attain~~Gt F!S?O~TS .·\t·!D ?UBLtC.J.TiCN: {During curr~nf r!;J~rr period) "'· .... • ' H .... .., d ~• ._ :.;...., I 1 1- • ' Y •• ·. of Methadone Otrlvotlv~s (Dbstreet}. F~dcratton J1.: ( Proc ., t) :69 H/.Jr.} 1?54. ,-r , f -. prior to the of this £oal. attain~~Gt F!S?O~TS .·\t·!D ?UBLtC.J.TiCN: {During curr~nf r!;J~rr period) "'· .... • ' H .... .., d ~• ._ :.;...., I 1 1- • ' Y •• ·. of Methadone Otrlvotlv~s (Dbstreet}. F~dcratton J1.: ( Proc ., t) :69 H/.Jr.} 1?54. ,-r , f -. 1 ·, ., c- j ../ •._,I . . / .· REPORTS AN:l PUB llO\ T IC.'NS: (Con t t d)· . - G.u., 2. Fras.:r, H.F .,. N.lah, T .L., Van Horn, and hbc-H, H.: Use or"~uottc: Eif"ccts tn Evalu~ttr:g Aoa!aeslc Drugs In Areh. lntcrnat.,dz M~n. pharmaeodyn. et de therap •• E_: (4) 443-45 (Aug.l 1954. 3. Reports to Comr:t1ttee on Drug Addtctlon and Narcotics, National Research Councllt · (cl l Work of' Nlf.'H Add let Jon !<~search Ccnt~r, A.ulu~ J ~'!port, 22-23 January 1954. ContaIns r~port on the a d d i c t ton 1 tub ll Jt ! ~ s of Na I I t n e -mo r ;::> h t n e v·.~lcraf~s; .£! Et·hyl 2,2-Dlphenyi-4-Di7!1cthyfamtno- : / butyrate; 4-4-Diphcnyt~6-Dioethyi~;,Jnc-Hex<lncne- 3; -dl 1-r.~ethyi-4-Carbcthoxy-Azacyc toheptane; .£ N. . Prop~rgy{-Olhyclro-normorphjne; ..L~nd N- allylnormorphtn~; and N-Aityfdiacctvlnormorphine. !b) Addt~tion liabillty of N~rcotloe,. 2 Cc.rob.-~r 195·-~. (cl Acldletlon ltablllty cf 2 1954. ~orphinonc}, Cctob~r Ha r r t : i s b z 1 1 , I· J • D • Director of Rcsz~rch .. Atta:h~ents A--IS"~ The page is a scanned, typed document with several handwritten annotations. The text content discusses various chemical compounds and their properties, likely related to drug research. There are several instances of underlining in the text, which could be for emphasis by the original reader. A handwritten annotation in the bottom right corner appears to be a number, "A-158," possibly a document identifier or page number. There is no other visible handwritten marginalia, stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures or facilities. This page is a typed document with handwritten annotations. The text discusses antitussives and substitutes for codeine, including specific compounds like Dihydrohydrohydroxymorphine and Propoxyphenone. There is a handwritten annotation at the bottom right corner with "A-157". No photographs, diagrams, forms, stamps, or redactions are visible on this page. The document is a single page of typewritten text, appearing to be a report or memorandum. There are no photographs, diagrams, forms, or official stamps visible. The text is dense and spans the entire page, with some handwritten marginalia at the bottom right corner. There is a single, small black speck on the page, potentially a printing defect. No redactions or visual evidence of experimental procedures are present. The document is a single page of typewritten text, appearing to be a research report or summary. There are no photographs, diagrams, forms, or tables present. The only handwritten annotation is a designation in the lower right corner, "4-155". There are no official stamps or seals visible on the page. No redactions are present, and there is no visual evidence related to experimental procedures, equipment, or facilities. This page contains a typed list of reports and publications, likely from a bibliography or research log. There are no photographs, diagrams, or official stamps visible. The only handwritten annotations are the signature "Harris Isbell, M. D. Director of Research" and a smudged annotation "A-154" in the bottom right corner. The content appears to be focused on drug addiction and related research from the 1950s.