Doc 0000153378

c.• 'f~'-.;,-,· -"?'<'-'7•0' .,-,_ > _,,, i . ~ 21~ January 1952 .. ------ '• OROMORAN P R 0 J E C T .. ... ----- .. Q\IR 44 t :FH:l :op NR 113-149 s~r. 3t__540 ., - .. .. ·. -. · - ·. . . p - . . --~-·-_-;f .. . ..· : .. . .-· -: c 0 p y - Oeciassified by ....___187475-- d ate 4 ,F.'. E"~ 6 " .J -. 1 . . . .; : 1 : -~, . (!) ·• • .. ( .. ~-. . . ~ ("-/".,_~ . ···-. . ~ ~ - / ... _ ·.· ~ l _,. '~ ... ... ~ ._ ..., , . . , . l I .. WOKK ACCQAPL ISHEO TO ~.T~ . · Th c recru ltm~n t and q.~ 1-tl-I-.af1,·.o.f.:. pu.aonne 1 began In July. ""' -...,,. .. I ''f.Hl.iiL;hllliaf The trafntn~?f p~~~onn~l was completed tn l•te September aRd an additional r~search ward was opened In October 1951. The work, on th~ .human pharmacology and tox tel ty of 3-rnethoxy-n-. · mcthvlmorphinan as well as the work on the detection of euphoria, 1 was completed during the s~arjtmer. Work on the relief of absttnP.:nee and subst ttut ion of th ts compound for morphIne was completed in .. Dccembe r 1951. T h c res u rt s to . d a t e c a n be s um m·a. r i zed a s f o I f ow s : 0 o s e s of less than 30 ~g. dl-methoxy-n-methylmorphtnan produced no untoward toxtc effects in former morphine addicts. Doses of 20 to 30 mg. ctfher hypodermic~(ly or orally, Induced euphoria 1 ~ s Jmt lar to and equ_dl In ,intensity to .that seen after the adminis- tration of 30 mg. morphl~~. Othe~ morp~fne-lik~ effects, such as navs~a, vomiting, mlos.Is and r~sp.tratory depre~slon, were observed / with the larger doses. The compound was found to Induce tts effects more quickly when administered orally as compared with hypodermic ~dmJnistratioa. It reltzved ab$tlnence from morph~ne and could be substituted for morphTne Tn addt=ted p~rsons. , . Substitution was comp-lete as contrasted with _codein-t.,···wni=h will not _s-upport-.phys icat depende_nce on moroh ine comp.le.tely. FoUow tng wtth~rawal of 3-methoxy-o-methyl~orpblnan after substitution for morphine, a typical morphtne:-Jlke abstinence syndrome appeared. For further deta rls of these studies se~ the r~ports 'to The image displays a graphic promoting "The Black Vault," an online database of declassified government documents, specifically mentioning the MKULTRA/Mind Control Collection. Visually, the page features a stylized illustration of a bank vault door on the left side, rendered in metallic grays and blues with glowing accents. On the right, white text details the origin and content of the database, including a prominent yellow hyperlink to the website. There are no photographs, handwritten annotations, official stamps, forms, diagrams, tables, redactions, or any visual evidence of experimental procedures or facilities. This is a declassified document with a dark header line across the top, partially obscured by dark smudges. Text in the upper right corner reads "21 January 1952". The document title, "DROMORAN PROJECT", is centered in the upper half of the page. There are several dark, scribbled redactions in the upper and lower portions of the page. A handwritten annotation "A-8" appears on the right side of the document. In the bottom right corner, there is a circular stamp marked with a "1" and a form indicating "Declassified by 187475" with a date of "4 FEB 1974". substituted for morphTne Tn addt=ted p~rsons. , . Substitution was comp-lete as contrasted with _codein-t.,···wni=h will not _s-upport-.phys icat depende_nce on moroh ine comp.le.tely. FoUow tng wtth~rawal of 3-methoxy-o-methyl~orpblnan after substitution for morphine, a typical morphtne:-Jlke abstinence syndrome appeared. For further deta rls of these studies se~ the r~ports 'to tht _Drug Addiction Commfttee, National Research Cou~ctl, wfiicfl are attached. A-~ -·- -· -- -· -- ·-· ------- ---- -- .... ' . i ...i ,. .. ·-·. ···.t::})'·. ". ~ ... . ADDICTICN;~--;Jt;fl"HETIC ANALGESICS w.J:i ICH MIGHT ·sERVE AS SUBSTITUTES FOR CCOE I NE. BACKGROUND INFO~tATION .. In lat~ June of 1951 $30,000 was made ~vail~ble by the Department of Defense for determfntng the addiction liiblltty of dl-3-methoxy-n-rne.t. hy[~orphlnan Cmethoxy-dromor~n} In the hope ·that this drug might r~present an adeq~ate synthetic sobstltvte for codeine. Thts grant was made fo(lowlng the submission of a·project description entitled "The Determination a.· . ";, of t h e Add I c t ion L i a b I I i t y . of S y n t he t t c . An a I g e s i c s o f t he . ~ Codetae Type." "The proj~ct wa.~ suppor~ed for the f~llowlttg ~- r~~sons: •J .. D'Uc to the curr_i.ntly dhturbed ·International sttvatton, It was poss tble that the United States might be cut off from / alf Its usual sources of opt~m. SyRthettc analgesics ar~ available which are entirely adequate for the replac.ement of morphine. How~ver, none of the available synthetic analges icJ a r e a s s a f e f o r g e n e r a I u ~ e a s h c '=l d e t n ?. • M~ !"' z t h ! ~ ~ C p .-; r c e n } .. of the Armed Forces' r~qutrements. for narc~tics is· for codetne ra_ther" th·a.o for morphine. : F tnding a synthet tc· subst ltute for codetne Is, rh~refore, of considerabh: importa11ce and it was hoped that methylation of 3-hydroxy-n~~et~yl~orphinan, a synthetic drug of morphi~e-Jike structure, would produce such a _compound. The facr!tttzs of the Addiction Center Researc~ wer~ aot suff£cient to carry out the work unless ddditional funds could be obtain~d. A-7 - ----- --- ---------- -----· '· .. .• . .. . Declassified by -137475--··-.·• n:s date 4 l9t7 . '-.a . >• . ' The page contains typewritten text and handwritten marginalia. There are two instances of blacked-out text, one near the top of the page labeled "INFORMATION" and another larger, darker redaction covering a section of text near the bottom. Handwritten annotations include a "Page 2" at the top right and an "A-6" in the bottom right corner. There is also a "DECLASSIFIED BY" form with a handwritten entry for the date "4 FEB 1977." The document appears to be a report detailing research on a compound related to morphine, with experimental details about dosages, effects, and substitution for morphine in addicts. There are no visible photographs, diagrams, or specific visual evidence of experimental procedures, equipment, or facilities. produce such a _compound. The facr!tttzs of the Addiction Center Researc~ wer~ aot suff£cient to carry out the work unless ddditional funds could be obtain~d. A-7 - ----- --- ---------- -----· '· .. .• . .. . Declassified by -137475--··-.·• n:s date 4 l9t7 . '-.a . >• . ' ~. ·· .. It ls obv lous bas a-ddtc:tton and for tbf~ r~ason, cannot b~ r~garded as being as saf~ as codeine for general u~e. We, th~refore, have n;t earrt~d oyt Part Ftye of . ' - owr ortgln41 experimental procedur~ w~lch deals with direct former addiction .of/morphine addlets to the new drug. It was f e l t that the ttme would b~ better spent tn screening a number of oth~r compouads In the hope of fln·ding·· a drug wh tch gave promtse of being mor~ codetne-ltke than is dl-3-methoxy-n-methylmorphlnan. Work along thes~ ltAes Is now going oA with the dextrorotatory ·. - • ai aad l~vorot3tory Isomers of methoxy-dro~o~an and wtth some v~lerat~s In the ~ethadone sertes. The Isomers of 3-methoxy- '/ R-methylmorphtnan ar~ betng studied because the dextrorotatory "J Isomer ts said to be an e.xcellent antttu,sstve agent tn dogs ras judged by a newly ~eveloped technic) and probably will hdv~ very low addictJon ltabtltty. Later, It ts hoped that additional d~rlvatives of dromoran wtth substttuents other than methyl in position Number 3 will be studied. The reason for Investigating these additional druo .. s .. . tn the dromoran sert~s is that the .. activity of dromoran was altered tn the proper direct·tqn by . methyla.tfon_, ...b ut the .a~~-tction l_iabiltty of the d-erivative was .. aot redut:·ed s.uffictently f~r tt .to be re.Carded as being tnnoc•J·~~s as codetn~. Substitution of ethyl_, propyl or other groups in po~ition 3 might yield a RW~ drug w~th sufficient reduction in addiction liability. A-) - r .--·,.to -... 'A - 1874'10--- oeclassitied by - - . date- 4 FEB 1977 "r---.---., ) ' ' ~. .C~c·• t{~Jamtnderof lh• ll<n<'·avallab(e under lh< ·current • g • rla •• n • t ~ • r ••• om the Dt~ • :i '· t:_c " t,w! • I 1 J • J~ • ] iltifs c m~s • t be spe·n t- • fn· screening, It Is hoped that an _additional graat can be obtained f o r co n t i n u ~ t ·r o n of t h The document is a declassified CIA report, evident from the text at the bottom stating "Declassified by - 137475 - date - 4 FEB 1977". There are no photographs, diagrams, or tables present. Handwritten annotations include the designation "A-7" in the bottom right corner. There is a large, dark redacted area near the bottom of the page in the form of a dense, irregular shape, obscuring some text. The document itself appears to be a typed report with the title "ADDICTIONS CLASSIFICATION OF SYNTHETIC ANALGESICS WHICH MIGHT SERVE AS SUBSTITUTES FOR CODEINE." '· t:_c " t,w! • I 1 J • J~ • ] iltifs c m~s • t be spe·n t- • fn· screening, It Is hoped that an _additional graat can be obtained f o r co n t i n u ~ t ·r o n of t h e work d u r I n 9 t he f Is c a I yea r I 9 53 • I f a promising drug Is revealed by the· screening test, tntcns tve wor~ ·with it wt II begin as soon as poss lble during ftsca I year . 1953. If so such drug 11 found, screening should continue. I II. EXPER IMENfAL PROCEDURES Drugs beiQg screcn~d wlll.be $ubjected to ·the following types of Investigation: A. Human.Pharmacology and Tox~ctty. Thts Involves tbe admt~istratton of progressively tncr~asJrig doses of the drug onder study to hu~an volunteers, chiefly former morphine addicts. ,,. Observations on respiratory min~"te volume, pupillary size, 'I blood pr~ssure and pulse r·a t e, etc.:; a re'Jild de following frC.e a dm I n i s t r a t to n of the drug .. s .. . . B. Ad ml -n is t r a t t o n to Human Volunteers of Stngle Doses ~f the Drugs Being Screened for the Detection of Euoho~Ta. This espertment ts conducted In exactly the same way as the studies on human pharmacology,_ except ltflat det~tled obse:-v.st ioils 'on the physiological effects of the drug are not mad~, _beca·use . ' t~king of observations tends _to n~gate the plea~~rable effects ~-' •• • • 4 of th-~ dr"ugs.- T'.»'o methods· are. used for sauging the "euphortd" induced by the drugs. These are, 11 unobtrusive clinical ' ' observations for the appzarance of behavior rzsembling that seen· after the administration of morphine, and 2J the admi·ntstratfon of projective psych61ogtcal tests. ----·------- -- -- . . .... ~ _187475- 0eclassl1f t•e <\ E,. .~"'"""' _ -----~~~~~~·~l;u.t~'------­ ·date- · . ..... :_ _ ·. ··- ·- .· c. oF Dr os~s th~ s r 't e n-t·s h 0 w n ns·of Moder~t~ to Mar~ed Abstinence from Ootates. Any drug·.whtch, on the basts of the scr~entng test, appear~ to be promising as a potential substtt~t~ for codeine wtll be subjected to additional studies: I) ~~bstttutton of the drug for morphine in strongly addicted persons, followed by abru~wlthdrawal of the new drug, This page contains typed text, a handwritten annotation "A-5" in the top right corner, and a declassification stamp in the bottom right corner indicating it was "Declassified by 187475" on "4 FEB 1977". There are also several black scribbled redactions at the top and a few scattered dots that appear to be from the scanning process. The text discusses drug research related to addiction liability and potential antitussive agents. ns·of Moder~t~ to Mar~ed Abstinence from Ootates. Any drug·.whtch, on the basts of the scr~entng test, appear~ to be promising as a potential substtt~t~ for codeine wtll be subjected to additional studies: I) ~~bstttutton of the drug for morphine in strongly addicted persons, followed by abru~wlthdrawal of the new drug, 2) dt~ect addtctton of fb~mer morpbtne addict volunteers, undcr.two conditions, (a) htgb-dose levels, such as would ~ery be expected tn -~naturalu addtctton under conditions of abuse, a.· (b) condtttons of low-dosage, such as would be expected during long eo~trnued c'lntca! admintstratton of the drug. ~/ 0. Evaluation ."of Data. The drttg w~ are seek-tng should have thefollo!'lng chara~tertstlcs: 11 It should be / a weak analgesic, judged by experimentation; ~s ·~ntmaJ 2) Tbe ratto'of toxicity to therapeutic effect sho~ld be favorable In both animals ~nd man; 3} It should be a good antttusstve agent; 4) should relizve abstinence from morphine only parttatly; Sl should not substitute for morphine completeiy; 6) should only a mltd grade of physical dependence In lnd~ce -i.~· .·.. ·. ... · ~ .· : d ~ ·r.e ~,t .~.a~d J e·t t o.~n . ).~_ s·.f.~-:--u~-~ ~-:r.:::-~·P ~ ~-1 t .-t~c? i: _:.of."~. ~t.".-g ;-.- do s .s 9e . •· -. • .....· .i ~ •. "'! ·~ e• -~ -~~· ~~ )=;·-:.~· .. •-.: -~:::~·e.".:.:.~~-:~~=-- ..- -_ e.~.:.. ~- ~e • ~~ •• .• ..• 0 •" - ....." • lnforrria~fon submitted_to the Drug Addiction Committee by the pharmaceutical companies and universities wTII be sufficient to evaluate the actions of t-he drug- l·n an·tmals • . -- ---· ---- -------- . ..• -~------ ' . 4' -- ...... f .. :.-.~ '( Information on the Studies on add tox teo I og y*· ph ac:ology and euphoric potency of the drug la maa aad on Its ability to produce ~nd s~pport physical dependence. From these data a sattsfactorv. eval.uation of fhe addtctton ltabiltty of the compound can be made. E. Location of the ProJect. The experiments described above wtll be carried out tn the Addtc:tlon Research Cente~~ U.S. Public: Health Se'rvtce H'Osp.ttal, lexington, Kentucky. Thts hospital ts devoted enttrely to the treatment and study of drog addiction and Is the only place In· the world where "'' a study such as those desc:rtbed above can be satisfactorily .tt. carried out •.! The tnstttuttoo provided the two necessary / fact II ties for-th ts t_ype Thts hospital ts devoted enttrely to the treatment and study of drog addiction and Is the only place In· the world where "'' a study such as those desc:rtbed above can be satisfactorily .tt. carried out •.! The tnstttuttoo provided the two necessary / fact II ties for-th ts t_ype of work: I) 6" targe- pool of pat te~t yolunteers, . 21 strtef/ environm : e ntal ... ~ ontrol which prevents / ' the Introduction of drugs oth~r than those under study tnto / the situation. F. Exoertmental Personnel. The work will be carrted out uader the direction of Harris Isbell, M.D., Director of tbe Addtction Research Center. This tnvestigator has had almost etght years experience tn narc:-o+lc dr11g- addrctton and . .. . . . _.:_: __· - .. : -~,-~·--.·. -~ ~- .· ..... 'r.····. :;-~ ~--~·----~_·;.': -~··.:··-~ .. -:'>·. ·. . ·. . : •. ' ·;_. -~ . :-; .-··: ::·h:~ s ,;mart~-p_u~I'i•=-~-·.='-orr5·:·t;r:-~.:n fs:·_~-I::.-1-d •" · .Re·.-Vi·r-l.t- b~ ass 1 st~d by • -··-~· ·• --~ ·. ·'. .- :.·:~-~.·-_.;.._ ..· -- · .•• -· ·:- -:..-~·· .•. -:. ... ~ 7"---~- . ·. :- -.~ ... - .... :. ·. two othe.r experienced Medical Offtc:ers, Dr. H. F. Frase-r and Or. Abraham Wikler, both of whom have had extensive experi~nce ln research In addiction and have many pu·blt-c:attorrs in this field. A-2 ~ ...... ------- --- -------- - --- - . ·-. -· ------ --- ... - ··- . ~- '· .. . ~ - ... d b 18747S--- Declz.ssl~~s Y - . _ da~e 4 FE~ i~f1 -·. ... ·· .. ·.. ... - _....:- .. -'···-·. -.: ,_.. ·a-_varlable. Sub-proT'esstonal personnel tn.elude ·s Psychiatric a Medical Technician, BtologicaJ Atdes~ Atd~, Se~urlty At~~· . and Clerk-Stenographer. ·A special ward for condocttng the$e studies has already been set up and ts In operatio..n ~ G.- Esttmate of Co$t. 2. lese~v~ for night dtfferentral and overtigre pay, wlthin.:-g';-ade ratses,. ~tc: ~~2;.~ _ ... . .. .. _ ... .... _ ' ,., __ 3. Miscellaneous e~penses ~ - .. It should be.noted thpt personnel cost for the ftsc~l J.· ye r 1953 wtll be higher due to ttie recent salary tnerease g~anted government· employees. Item T'or mtscet·laneous expenSe$· l~elude~ money·for t~e purc~ase.of drugs. chemtcals,-gfa~sware~ :. :.~-;~7:::. e J-e~ t r~~~-c,~p:~_a t·.dg ~-~-~h-;l-~:-~ ~-f1.d: _photog t:.a~h. ~~: .P~P~:i:, _e·t c ~-;· ~-. . . . · This page from a declassified CIA document contains typed text with some handwritten marginalia and official stamps. Notably, there are two prominent black redaction marks near the bottom of the page, obscuring some content. In the bottom right corner, there is a stamp indicating "Declassified by _ 187475- date _ 4 FEB 1977". Additionally, a handwritten annotation "A-4" appears on the right side of the page. The text discusses experimental procedures for drug screening, including human pharmacology and toxicity studies. There are no photographs, diagrams, or other visual depictions of experimental procedures, equipment, facilities, or individuals. The page is a typed document with handwritten annotations. There are several dark, smudged redactions spread across the upper portion of the page, obscuring content. In the lower right corner, there is a "Declassified by" form with "187475" and "4 FE 1977" filled in. A handwritten annotation "A-3" is present on the right side of the page. The text describes a drug study and its evaluation criteria, alongside information about the drug addiction committee. for the ftsc~l J.· ye r 1953 wtll be higher due to ttie recent salary tnerease g~anted government· employees. Item T'or mtscet·laneous expenSe$· l~elude~ money·for t~e purc~ase.of drugs. chemtcals,-gfa~sware~ :. :.~-;~7:::. e J-e~ t r~~~-c,~p:~_a t·.dg ~-~-~h-;l-~:-~ ~-f1.d: _photog t:.a~h. ~~: .P~P~:i:, _e·t c ~-;· ~-. . . . · \ .. ':.:_\ .. ·_ :: ·. ": . ·. . -. --. ,. . :,~: :·,~~ -~~~~~<::~ ·i~~>~:::-~~:;~~:;:~~:~~~~ ~ ~~-i;;=:~~Y."=~~~f~,-~~~~:·:.-~~~~":f·;. ~ ~/._,. :~~~ _~:::-;~-~~-~~~~ -~ .-.....: :-,_ ·,. ;:.~:r. Isbell, M.D. Ha~ri~ t. Dfrectar· of Research HI :rn Attachments 2 4 January 1952 A;_f . .· - - r· .. ,. #=' . .. ""1: t • .... t I ' .. __. .,-~-"" · Declassified by -137475- ----r-=--:-:=:::::;:--- . ~ate 4 FEB 1977 ~ ·.: -:~~-~ ..- . .. The page contains typed text from a declassified CIA document, discussing studies on drug addiction and experimental procedures, including the location and personnel involved. A handwritten annotation "A-2" is present in the lower right corner. At the bottom, a "Declassified by" stamp with the number "187475" and the date "4 FEB 1977" is visible. There are also some faint charcoal-like smudges near the center of the page, and a black and white photograph of what appears to be stacked boxes or materials in the lower center. The document is a typed memo with handwritten annotations. It contains a list of personnel with their corresponding pay grades and a section detailing miscellaneous expenses, including purchases for drugs, chemicals, glassware, and photographic paper. There are no images of people, locations, or experimental procedures. Handwritten marginalia include a circled "#1" and the notation "A-1". Official stamp markings are minimal, but a "Declassified by" and "Date" form is filled out with "137475" and "4 FEB 1977". There is some smudged or obscured content in the upper right portion of the document, and a few areas of what appear to be redactions or markings that obscure underlying text.