Doc 0000151884

?t!CJE.CT DESCRl?TlCN THE LlABJtlTY Cf SUnSTlTUTE~ S ~iDl~TIG~ SY~~HET1C . ~eqoe't for r~ne~dl of N~ 113-149 '· a,ci:C'lround tnformdtlon Since July 1951 project, designed to 4 de~~lc? ~ sy~~hctt~ drug ~hlch ~ould be a'~s•f~ 4S cod~tnc frorn the potnts ot view of toxlc~logy, 4ntltuss1v~ 4ctfv1ty ~nd 4ddletlon llabtltry ~sis code1n~, h.as b~~n carrl~d en ·Nithtn Ha N~tional ln~tltut\1: of Viental H~a!th Addlctton. Reszarci Center, 1-'ubtt: Hzalth Service Ho;ptt"l, lexlnsfon, ~P.tdud:y. Office of Rasearch. th~ ~Jv~l A 3ynthttlc ~ub~tltute for codeine is badty n~~ded op!um, cr from oplum, ccn:tJtute$ the slnc~ morphtn~ dertv~d on1v source of codc!nt. Thts means. that, _unlc~$ a synthetic ts tha States must conttnue to devcJop~d, Un1t~d :tockp!i~ A--J;y . ·.;... . , rhls I$ In the Annual 'cnt su~arlzed lrogr~ss K~~ort to Or. f. H. ~ul~by 1 He~d of th~ ?hyslolosv Sranch, Offlcc of Naval Resc.lrch, ·tn J4nuc~ry l9S4. The most drug yet In the promlsin~ dcv¢lo~ed pro~rd~ ts th~ de-xtrorotatory 3-mcthyJ~thcr of N-m~thylmorphtnJn. Tht1 compound ls c~~pl~tely d«veld of dddietion li4bllttr and lt of sufficiently low toxicity to b~ safe for hu~an us~. Jn has antitussive activity experlment~l anlm~ts t~ consld~rabte and for trl~l antltusslv~ c~tlvtly und~P c~~••c~J ~oodttlona Is now underw4y. result$ wtth this drug in~ ootain~d ~s ~ cllnic"l antihnstvcz ~r~~: stltt confltctinc ar.d it ts n~t yet c~rtatn wh~ther Jt uovld be ~n cclcquat~ substltut~ for codctn~ for thls pvrpost:J. lt h .:Jlio kno·..-n thl!t the drug ls com:.d~detv as an would not subatitute ineff~etlve an~lg~slc ~nd serv~ ~:a for for this cod~~~~ pvrpos~. ]:.h,... .. ,.,;-,t'to-~ ... I :t..:...} ~ .,. •.J ~ "!.. J- A-J/3 '· ·- ;; . ·. -· Thh. I$ $Umr:'!Jriz~d ln th~ A~rHJtll "rogr<.:ss Re~1crt t.cr.t Pr. to f. H. ~ulmby 1 Hz~J-of th: ?hy,tolotv Br4nch, 0fflcc of Naval Research, in 1954. J~nuary The mo$! promls.ins drug tn prorram y~t dcvclop~d th~ 1s th~ dextrorotatory 3-methyfethcr of t~ethylrnorphlna~. ·rhts co:npound ls t":cmpl~tcJy devoid of 4ddtctton lt~5bl1Hv 4nd :r.. and trlal for flntitu~'l!lv~ 4Ctlvity under c:Jtnicdl r;onditlons li now und¢rway. The obtaln(d with thlt drvs r~sults ~t ~ clintc~l ~otltusslv~ c1r~ stttl confltctl~~ and lt ts not yet for thl3 purpos~. lt ls dlso known that the dru; ls c~mplcteiy for code l Ail .;. ;.. ?r·- ... ...... ... ~, ~.r~:- j-JIZ ... D-2,N-dtmethyl-hydroxy-morphlnan Is co~plehdy Jn-~rt· tn m~n and devoid of addiction (J~btllty. The lcvorotdtory c (or. m o f ·· t h h d On the left side of this page, there is a graphic of an open bank vault door with a central dial and multiple gears and levers. The vault is illuminated by a blue light, casting a glow on the metallic surfaces. To the right of the vault graphic is large, stylized white text that reads "THE BLACK VAULT". Below this title, there is a block of white text on a black background that describes the origin of the document. The text explains that the document was obtained from The Black Vault, an online database of declassified government documents, specifically from the MKULTRA/Mind Control Collection. It further states that the collection contains over 20,000 declassified pages from the Central Intelligence Agency (CIA) and provides a website address for downloading the entire collection. The bottom of the page displays a yellow hyperlink to the website: "http://mkultra.theblackvault.com". There are no photographs, handwritten annotations, official stamps, forms, diagrams, tables, redactions, or evidence of experimental procedures visible on this page. This page contains a typed document with several handwritten annotations. At the top right, there is a circled "8.5" and in the bottom right, "A-314" is written. The document itself is titled "PROJECT DESCRIPTION" and discusses "THE ADDICTION LIABILITY OF SYNTHETIC SUBSTITUTES FOR CODEINE," including a request for renewal of N№ 113-149. It details a project focused on developing a synthetic drug substitute for codeine, its funding sources, and its importance to national defense. There are no photographs, diagrams, stamps, forms, or evidence of experimental procedures visible. yet for thl3 purpos~. lt ls dlso known that the dru; ls c~mplcteiy for code l Ail .;. ;.. ?r·- ... ...... ... ~, ~.r~:- j-JIZ ... D-2,N-dtmethyl-hydroxy-morphlnan Is co~plehdy Jn-~rt· tn m~n and devoid of addiction (J~btllty. The lcvorotdtory c (or. m o f ·· t h h d rug ha s m J I d mo r ph i n e -I H. e { f ~ c t s on d p tl r t Ja ll y luporessrs ebstlncnce from mor;)hJnc. Its addJctlon lisblltty Is probably ~omewhat gr~atcr th4n that of codtlne and, on th~ other hand, ts far less than that of morphin~. Oepandlng on the ovi~omc- of cl ii'llc:aJ. trl4h with ·the d-meth\'lether of Oro,-:1~ran, .. a· tn~ Ccmpcund mtgh t b.:- cons tder'!d as potent 145 I. sub$ t ltute for cod~tnc. ft has one adv~~tage o~er d-m«thyl Drcmoran In that It will probably be~ mlld 4ntlsestc: drug stmitar to codein«. . -· . ~or~ ':1rth ~h~s~ e;,mpovnds h still continulns-. 4-4-diph¢nyJ-6-dim€thyl~;;;fno-hex"non€'-J,_ a m~mb~r of tha meth~dcnG ;ro~p, ~fji 4p~~r~ntly hdva dddfctlon ll4blltty cf a low order. Thts cc~pound Is in usc ln G~rmdny 4s an I I f • on~ of th~se so far Is In clirdcaJ trl41. and lt h unkncwn ,.r.,.,,.,,.r ·,.,,II cL_,..., .... .. f .,.. ........ ,.._. . ,;,.,.,.., ......... ~., .. ~ .. "~ •,..,.,,. . ,.: t!.1,;s L.,. th~ ~ ~ •···-· .,. ...... , .• ,... ... ._ .. _ ........ , ... ,_ Ft:.•..,;, • "" ~ ... ~ .. ,.. • ~... .. IJto>tSI;.;·. ... ... .1--3/j .... .1 ) IV. ~~rk Proo~s~d Ourtng the p~rlod July l954 to July 1955 we ho~c tQ .. ne-3. .' on 4-4-d 1p heny l-6-d 1m~ thy t 4m t no-hcxano In ~dd 1 t l on to thts, we ho~e to ~xamtne the potentialities of the myrlstyl cat~r of morphine: end of' 3-hydroxy-N-m:thylmorphlnan. Two new appro~ch~s to the problem will be ~xptorcd. One of thcs¢ consl$tS of 4tt¢m?ts to attcnuat~'the pot~ncy -'4nd .tddlc:tlon llc1btllty of the synthetic: drucs math4don~ and "" ... .... . Dromoran by mtxlng th(..-n wtth ap~clfie antagoni5ts, N-t1\lyCnor- ,... morpbJne 4nd N-altvlnordro~oran, 4nd su~& other anf~goutsts as mdy be rccommend._:d by lh'l O.rug Addt-cti.o~ Cor::~ul-t-ie¢. of t~-e N4tlon41 Rc~~areh Counc11. ln this connect•on it m~y be '· The folto~tnu anh2f;onlsts wlll be examlnlld:- tt )· N--1)'}1-.,..J·Rcr di4c~tvl~orphln~, t2) N-propyl-di~ydronormorph1ne, £3J d~xtro- by mtxlng th(..-n wtth ap~clfie antagoni5ts, N-t1\lyCnor- ,... morpbJne 4nd N-altvlnordro~oran, 4nd su~& other anf~goutsts as mdy be rccommend._:d by lh'l O.rug Addt-cti.o~ Cor::~ul-t-ie¢. of t~-e N4tlon41 Rc~~areh Counc11. ln this connect•on it m~y be '· The folto~tnu anh2f;onlsts wlll be examlnlld:- tt )· N--1)'}1-.,..J·Rcr di4c~tvl~orphln~, t2) N-propyl-di~ydronormorph1ne, £3J d~xtro- vo 4 nd l c vo r c ~ ~ f o ry -:--.l.-4 I 1 y l r:c r d rom!'> ran , ( 4 l t ~ rot a tory -3 -.";·, ~ thy I - no rdro::'\o r ~ n, and ( 6 l l e vorc hd o ry-3-.J CO! r owt-N-d 1 1v l nord ra:1~~r~ ~. . . . . . ... 'of \txi~Zndlns.r th'.: 5vp;::,!y of cccie:in;e t)y -cor.,tJ.;Iling }r ~eiit~ .a r:1c:r~~::l :·,: ;f-]1/}. .. . ...... .... . • .. ) . been report~d to tncr-:as.: the )'ot~ncy .snd lcnsth o( a~t r.-,n ,· V •.. Methods ·The methods to bt us~d ~rc the standard dddtctlcn l lablll ty test Jng ~~thod$ of th~ NH•H Addict lon Resedr:h Center. ·rhcse have been described In dettll In pr~vlous. proJ~ct dcscrtpti~ns aad Jn pr~vtovs Annu41 Reports. For details these should be consulted. .. VI. of EvaJu~t1nn D~td The evaluation of dahs haw c1lso b-rt!lT d'f~~us~ed tn which pr~vtous d~scriptfons sh~uld b~ consult~d. ,)::~ntucky. This lnstHution provide$ the t~o nccessliry faef 1 it i.:s fer th:! type of 'Atork. to be <Jndertuk<':t'!! t r J 4 pool of ~utient! ~ho wll l ~otun!eer fer tha ~x~zrs~cnts ~ith control_ ~htch ~~~~-~t: # . tntroductJen of druss than th~ oth~r t n t o t h ~ t :c ;) e r i ~ ~ n t ·i I s t t u d r i :·:.:: • . #.. .... l". v Exoertm~ntal P~rsonnel The ~rk ~111 ba Curr;~d our under the directtqn of ·- Harris Isbell, M.D., Dtr~ctor of Rc:serJrch. Nlt.r:H-Addtction Rctcarch Center. Thts lnv¢stlg~tor has hod ten year' of ¢xoerJ enc~ tn re.se4reh tn n~rcotlc drug. addiction end h4S publ ishc:d m4ny p4p~rs In th~ fteld. He wlll b¢ 4$Slsted .bv two other . . experienced physlclans, Dr. H. F. Fraser Dr. Abraham Wtkler, ~nd both of whom heve,had extenst~~ experience ln rese4rch tn In eddttton to personnel. the addi~tlon. th~se m~d)eal p~rt- ttmc services of a 8tochemtst and Research ?sychotogtst 'Vlll ~ be made- available. ·A sp«cl~l w.1rd for-.corid'ucflng- the· studies. Is The page is a typed document with a few notable visual elements. At the top, there are two circular black marks and a faint drawing that resembles a cloud. Midway down the right side of the page, there is a handwritten annotation in ink: "A-313". The rest of the page is filled with densely packed text, describing various drugs and their properties. There are no photographs, stamps, forms, diagrams, tables, redations, or visual evidence of experimental procedures or facilities. . . experienced physlclans, Dr. H. F. Fraser Dr. Abraham Wtkler, ~nd both of whom heve,had extenst~~ experience ln rese4rch tn In eddttton to personnel. the addi~tlon. th~se m~d)eal p~rt- ttmc services of a 8tochemtst and Research ?sychotogtst 'Vlll ~ be made- available. ·A sp«cl~l w.1rd for-.corid'ucflng- the· studies. Is currently In oper~tlon. tX. Esttm~t~d Co~t l. Pers.on ne l 6 I I 2. Rescrv~ for nlsnt,·hol td~y and -_overtlmc pay 3. Mtsc~lfaneous cx~~nses Toto I . :i ··~::~;.. .=-~./: ~~- lte~ 3, mtscellaneoui exp~ns~si Jnc(~des mone~·for the ~ purch4:~ of drugs, chemtcafs glass~~re,_electroenc~phatc~r~phtc. 1 r. 1: ·. ... , Director of ~~search H l: rn -. - ..;.. . - .. The page is a typed document with several handwritten annotations. There are no photographs, diagrams, or forms. The document consists of typed text in paragraphs. In the bottom right corner, there is a handwritten annotation: "A-312". There are also some small, dark circular marks and smudges throughout the page. No official stamps or redactions are visible. The document is a typed page with handwritten annotations. There are no photographs, stamps, forms, diagrams, or tables present. The handwritten annotations include what appears to be an accession number, "A-311," in the bottom right corner. Black ink marks obscure a small portion of the text near the top of the page. The document discusses drug research, specifically mentioning potential substitutes for codeine and morphine. The page contains heavily annotated typewritten text, suggesting it's a research report or proposal. The text discusses synthetic drugs like methadone and Dromoran, and various antagonists being examined, including specific chemical compounds listed numerically. The bottom right corner features handwritten annotations, notably "A-310". There are no photographs, diagrams, official stamps, or forms visible, nor is there any visual evidence of experimental procedures, equipment, or facilities. The document appears to be a text-heavy, internal working document. This declassified MKUltra document page contains typed text detailing research methods and project location. There are no photographs, stamps, forms, diagrams, tables, or redactions visible on the page. However, there is a handwritten annotation in the top right corner that appears to be a document identifier: "4-309". The text describes "standard addiction liability testing methods" to be conducted at the NIMH Addiction Research Center in Lexington, Kentucky, highlighting patient volunteers and environmental control as key facilities. The document is a typed page with handwritten annotations. A signature, "Harris Isbell, M.D. Director of Research," is present at the bottom, along with a handwritten notation "A-308" in the bottom right corner. There are several dark, irregular redactions covering portions of the text, primarily on the right side of the page. The text details personnel and estimated costs for an "Experimental Personnel" section, including job titles and salary grades. It also seems to list miscellaneous expenses for research materials. No photographs, diagrams, or explicit descriptions of experimental procedures are visible.