Doc 0000151762

19 1959 ~y 67·A 1-1ee~.nt!y it ha~ besn shcwn.(Hofman.n .!1 n!_, l958a; l~bell, 1959) that <?•?hosphor.f1•4.=hydroxo.t-H•d!met.hyl ~ryptamina referred to a compound isolated (hcre~!ter ~s psila~/bin) 1 fro~ CtZl"taln spcci es of mush'roocs (Hof~a..'1..'1 ,£! nl, 1958b) which are used eerernon!ally by).!e~lcan Ir...dia:13 (Vtanson a.'l'ld ·ao.s~cn, 1957), has ~ychoto~1m~tlc properties very similar to tho3e of LSD-25. / The close rescr.lblar~e o~ t.he pat terns or synpto~3 induced by LSD and psilocybin $Uggested that 'thcss drtlgs cause c psychosis by som~ common bloche~ical or phys!olooLcal m~~~an!~. Slnca Uta or d!miniah rapidly the drug la Diven affect~ L~ 'ih~4 d~ily .(I$bell !i ·nl~ 19$6), 1t was felt that th~ h~~o~~esl~ that tha Lsb and .p silocybin p$ychos~s ere identical could be . . tez;t.ed by daterminfng 1! ero$n•toleranee existed between the two drugsa In other !t the degree of tho ~~~ds, r~actlon or fnd.uced by a given dcsa ps11oeyb1n V1"a.S 31gnl/!cantly les~ !n a per3on to eros$ tolerance he snid ~ada tole~ant LSD~ ~~!d to end, th3 reaetlon to a given dose of LSD cxi~t, eonv~rsclyt nhou!d rcC.uesd ln a person tolerant. to psilocybin. In the l~t.t~r c~se~ it !3 !:.1pllcd that t.olcranc~ t.o p3ilo~,/bin would develop .. e) f!E"nlODS Suht~et:~. F1va mala for=.ttr opiat3 ndd!ct.s who were serving sentences !or violat!on·or the U. s. narcotic la~ volunteered tor th~ e~p3r1~~ntse Their ages var!ed botwean . . All healthy none presented ~ere physic~lly ~~d any ~vidence of the major psych~s~. All had received LSD-25 Genernl Conditions. subjects 1n a special Th~ ~re hou~ed ward to resaarch. Temperatures respiratory d~~ot~d el~n!ca! 1 rates blood pressures were measured times daily w~ thre~ aftc~ L~e p~tients h~d r~s~~d q~!etly in hed during days in which spscial not being ::tada. The patients ,_-ar.e ~casure1:1ents ~re arug-induccd ehenges ln behavior. det~e~tng DM!S~• r.~e design o! the experiment is s~ar!2cd tn Table 1. LSD and psilocybin vmre given 1n 30 ee of cherry s~u? at. B a.m. t'.lith tha pa-tients fasting. All doses 'tf¢t"9 calculated on a busts. Control were carried out, usinn me9f~g exp~r!ments 1.5 mcg~\g or LSD, 150 meg/kg or psilocybin and a placebo~ .btc:fOf'O' the first period of ehronle !ntox!cation 2..o"ld after- th~ or period medication prior to tha saeond period ot plac~~o !nto:dcat!on. Control tests with LSD and psilocybin \'1Ct"~ /3~2.t:3 /- .r') a .. conducted a.t. ftve days apart tn order to prevent. the lco.~t or of The order of d~lo~~ent tole~s.~ce. admln1~trat1on pl This page features an image of a vault door, likely symbolic of a secure archive, on the left. To the right of the vault, white text on a black background states that the document was obtained from "The Black Vault," an online database of declassified government documents. It specifies that this particular record is part of the "MKULTRA/Mind Control Collection," containing over 20,000 declassified pages from the Central Intelligence Agency (CIA). The text concludes with a website address for accessing the collection. period of ehronle !ntox!cation 2..o"ld after- th~ or period medication prior to tha saeond period ot plac~~o !nto:dcat!on. Control tests with LSD and psilocybin \'1Ct"~ /3~2.t:3 /- .r') a .. conducted a.t. ftve days apart tn order to prevent. the lco.~t or of The order of d~lo~~ent tole~s.~ce. admln1~trat1on pl aeeboz,. LSD a.ttd palloC'1Jb1n was· randomfzed !n both contro 1 p!3'riotls. or Th~r~ vrere tvro pr:rl.o ds ,chronic dru;;; a~l.n!strntion -- , ona with LSD and cn'2 wi t:h p~llo~Jhln. Ths order in ~J.ch the " . . . ~ patients ~ecaivcd t;'le:· drttg-s chronleafly (first. or second} with 3 recQlvlng LSD first 2 receiving w~s randamlz~d~ ~~d / p!l11oeybln first. P..!t.cr tha nece$3nry m.easurements had been obta!nad, LSD or ps!1ocyh!n was replaced ror nt w1~~ pl~e~os laas~ 3ev.zn days, att~r w~iclt tho ~~corA controls \'.'"ate obta!n.ed. this placcho pcr!od,those pnt!cnts received Foll~ng ~~¢had LSD received psilocybin chronteally, and vleg versa. e~ron!ca!Iy ~. 'nte doses o£ t.SD and psilocybin on first. day or th~ ehronie 1ntoxlcat!o.il were 0.25 :neg/kg ·and. 2S meg/kg rcsp{!;ctivaly. The30 doses were Increased ty OG25 mcg/}~g (LSD) or 25 meg/kg (ps.t!ocybln) on ~~ch succeeding day until 1.$ meg/kg ct LSD or 1~0 ccg/l:g ot ps11ccyb!n ~re being given on the s!~th dny. On or ninth day of chronic edainistratlon detailed ~~e aigh~~ measurecGilt.s WQre rnede after ad!!l!nis~rat!on of ths druo w.h!ch patient had bean Thia a th~ ree~!ving ~~ron!cally. aer~cd a~ ... ·test ot nd!reet" toler-a.n,ce to that. drug. On t..l-tc subsequent dnyt the patient ~3 nehall~4gqdn w!th. the 4rug (1.$ meg ot LSD or 1.50 !!leg of ps1locyb!n) th:lt. ha h~d not heen reca1ving. The patients placed on placebos for days ~r~ th~n 7~10 attcr which they 'Kcra tzsted a'onln ..n. th placebo, 1.5 mcg/ltg or LS~, snd 150 meg/kg of.ps!locybin. T~ese "a~eond controlsn were obtained to determine !f toleranca hnd been lost. Tha were then to chronic pa~l~nts return~d ~d1eat!on following the described those petientn schcdul~ ahov~, ~th who rcc~ived LSD 111 th~- fir!lt. period ot chronic ad:ninistra.tion r.ow being gi va.n ps 11oeybin, and vle~Z ver:s:1. Th~ pat! c.n ts ~re t.hen chs.11 enged with L.SD o..'"ld p3iloC1Jbln in t.ha manner <ie.scr!bed abcve. Oh~e~~t1on·s. Dur!ng ea.ch day ot the control pe.r!oat) and the perleds of chronic drug during which the a~~lnlstrntion placebo, LSD or patient~ ~re "cho1lcng~dn ~th p~ilocybin the following oh$ervetions ware ~~de at hourly lnte~~als twice &'d elght aftsr administration of The page is a declassified CIA document that contains typewritten text and some handwritten annotations. There is a circled handwritten notation in the upper right corner containing the numbers "3" and "164". Along the bottom right, there is a handwritten annotation that reads "B-264". The document appears to be a research paper or report, with a title "CROSS TOLERANCE BETWEEN LSD-25 AND PSILOCYBIN." and a date "19 May 1959". There are no photographs, diagrams, stamps, or redacted information visible on this page. The page consists of typewritten text. There are no photographs, diagrams, forms, or stamps. There are some handwritten annotations on the right side of the page, including "B-263". The text describes a study involving former opiate addicts in an experimental setting, detailing subjects, conditions, and drug administration. There is no visual evidence of experimental procedures or facilities. enged with L.SD o..'"ld p3iloC1Jbln in t.ha manner <ie.scr!bed abcve. Oh~e~~t1on·s. Dur!ng ea.ch day ot the control pe.r!oat) and the perleds of chronic drug during which the a~~lnlstrntion placebo, LSD or patient~ ~re "cho1lcng~dn ~th p~ilocybin the following oh$ervetions ware ~~de at hourly lnte~~als twice &'d elght aftsr administration of the befor~ t!~cs dru~s; rectal te.:1perat.ure, pulsa rata, systolic blood pressure, or pupillary size. and threshold for e!1cltat1on tha k.""lt:eJer~~. ·• iha.met~ods used ~~re ~hose previously de~erlbed (!$bell ~ ~, -- 19$6; I!:bell ct. nl,- 1959; Isbell. 1959)• In add1tton tha . patl~t.s cor:pleted, with the help o! an a!da, a special (itleStioluJ.aire l\t hourly intervals from 7::30 a.m. to 3:J0 p.m. or Clinical gr~de~ ,or. the tnten~! ty the reaction wera assigned on t.he l:/nsle or th~ syst'Ct.l of l3b~lt ~-.2!. {1956). . .A..n. n!c!~ls of rata. Alter drti"g adrJ.inlstratlon the change , "' ln rectal temp~ra~ure, pul~e and respir~tory_rates. pup111ury or s!za, blood prass~re ~~d thrs$hold !o~ ellcit~tion ths lm4~Jer1{S were calculated by subtracting the avet'ag9 of the t~ pre•drug obs3rv~tions from the values obtained nt vdr!cus hcur3. !hG Qre~ undsr the time-action curves to~ aaeh or partt~1ar :ea~ui"ement composed these f'1g-..tres ware caleul~tcd by the me~~od ct Winter ~~ Flataker {1950). thus converting all the data on a part!cula~ subJeet, a part1~~lar dr~g ~~d a pnrt.l~.ll;J.l' dey to onE: .!f\T.li"S tar.m0d Hc!egr~e-hours" ( t.e;-nperature), ttbca~-hcurs~ (pulse rate), etc. The total w~~cr of positive respcnse3 on ~~e que~tlOl~~!rQ ware cottnled over the entire period~ ~11mlnat1ng answer$ ~lch were also scored positively ctllculnted according to sto.ndard st.atistieo.t t~chniqu~s. Tha diftarGnees in various after placabo, ~;c mea~ure~onts 1.5 meg/kg of LSD~ and 150 me~/ko of psilo~Jbin in the first -~-~ ~econd cont~e1 periods ~re ¢Valcated by a t•tast for pair~d or ohse~ations (Zdw~ds, 1946). S!nce none thG differences , statistically in the of ~re 5ig~lflcant t~~ ~ets cont~ols1 th~/ W(Jra avet"aged and th~ a.~nirages';'used in aval u~t!ng the prcsanc~ I and degree of tolera.."lcEf, a.'1d cross•tole~a.."lce. The differQnce~-1n the effe~t or LSD ~~d p~lloeybin after ehron!c o£ LSD nnd then admin!~tratlon psllo~/hln ~rc ev~luatcd by the ~~ne stat!~tlcal tec?L~!qua for di!f~rance~ in pnired observations. Four lTSre (l) response to LSD eompar!~ons m~de: a.fter chr-on!c admln!strnt!cn of LS.O (d!rect tolerance to LSD}; I (2} response to psiloeyb!n a:ter ch~onle ad~!n1stration or LSD (cross tolerance LSD and psilocybin); {3) response to psilocybin . ~ or a:!"tcr ch:-or.!e ndl!l!n.t.utration psllo.cy.bf.n "(direct tolcre.. i di!f~rance~ in pnired observations. Four lTSre (l) response to LSD eompar!~ons m~de: a.fter chr-on!c admln!strnt!cn of LS.O (d!rect tolerance to LSD}; I (2} response to psiloeyb!n a:ter ch~onle ad~!n1stration or LSD (cross tolerance LSD and psilocybin); {3) response to psilocybin . ~ or a:!"tcr ch:-or.!e ndl!l!n.t.utration psllo.cy.bf.n "(direct tolcre.. i 1.Ce to p~!locybin); nrA (4) raspons~ to LSD after chronic ucminl$tratlcn cf psi1ccyb1n (cross tolerance psilo~Jbln and LSD). TI1a signs ot th~ di!terencea wgra $0 ar~~~gcd that a ml~Js (-} slgn 1rAicated a decrease in the men~r~ent at'~ar chronic !ntoxicatlon tUJ CO;::lpared with control.t a.."ld n plu3 (+) sign fndic:ated an RESULTS The di!tarences the tlrst second controls are bet~en ar~ shown in Table 2. None or the d-!ffcrences are stat1st1ca.lly . slgni:tieont, aa _indicated by the large st~"l.dard errors. The~c dld to be a for of pulse rete, see~ tenden~ ~he mea~u~ements blood pras$ure a.'\d threshold for the kneE:j~rk to decreasa on 1 or the scc~nd control. ,A slight d~creaaQ .in the n~~er positive . res~on$eS on the second cen . tro! also oc~~rrad with both LSD arA ~ p$lloe"..rbin. Thc~e -decreases ~ay possibly tndlcats thnt some degree of tolerance and cross tolerance was present ~es!du~l even aft.Gr avreek's t1oe. or ntter_ehroriic adm1n!str3tlon e!ther drug are !n Table 3. ~h~qn !he the to LSD a!ter chronie fl~at coluon.sh~ respons~ ' or ~dl:lin1strat!on lSD and rta!lects direct tolartlnce to LSD. 1 The second column tho respcnse to after chronic sho~~ ps11o~Jbin . t~~atmeJlt. v;i th LSD,. ~'1!1 t"sflects "'cross" tolera.'lce betw~an LSD The third eolHmq shows tha to LSD after ~~ p31lo~;bin. respoP~s or chronic ed~1n!str~t!on o~ psilocybin, ~~d is 3·C2tt$ure cro$~ tolcr~~c2 ~et~een LSD and psilocybin. TilQ last (fourth) colvnn -- showrs the r~spons e to ps 11oC~;b!n. nfter chronic trsatr:lcnt ~!. th psilocybin, and is n t:lo~~ura c!' d!r€ct tolere:'1ce to psilcC"/bln .. ./. .n.; a Inspact!on ot tha tabla that all tha signs minus sho~ ~ra or signa, which s1:.gga~ts tba presence tolerance ancl cross tolerance to both ,.druG~• In tha casa ot -direct ·tolerance {first to LSD, tha highly significant statistically colur~~> ~~ng$s ~re (P <0.01) on thre·a measure~ {blood pressur~., pupillary ·size, and clinical grade) and st~'~ficant (P ~-0~) en one m~asure (puls~ rote) L'l ths casa of d_i'rect tolarallca =~o psilocybin (fourth 9 co!ucn}J hlghly significant decreases ~~r$ obsar~ed in threshold tor the I~"le~j.er"k, and on e1inics1 grade. A sign!f !cant change or in This page is a typed document with a heading "Page 3" in the top right corner. There are no photographs, diagrams, forms, or tables. There are no official stamps present. In the bottom right corner, there is a handwritten annotation "B-262". There are no redactions or obscured content. The page is densely packed with text discussing an experiment involving LSD and psilocybin administration over multiple days, detailing dosages and schedules. The page contains typed text and handwritten annotations in the top right and bottom right corners. There are no photographs, stamps, forms, diagrams, tables, or redacted content visible on this page. The handwritten annotation in the top right corner appears to indicate "Page", and the annotation in the bottom right corner is "B-261". The text discusses experimental procedures involving drug administration and observations of patient physiological responses. on thre·a measure~ {blood pressur~., pupillary ·size, and clinical grade) and st~'~ficant (P ~-0~) en one m~asure (puls~ rote) L'l ths casa of d_i'rect tolarallca =~o psilocybin (fourth 9 co!ucn}J hlghly significant decreases ~~r$ obsar~ed in threshold tor the I~"le~j.er"k, and on e1inics1 grade. A sign!f !cant change or in the pulse rate also seen.. In casQ cross toleranca lr.la~ t.~c LSD and psi"l' o?yhin, a highly sign!f1C3nt dacreasa betv~en ~~s - th3 for and s!gnirlcant observ~d 1~ thre~~old th~ ~~~eja~k~ ssen on blood pressure, pupillary oiu and d~crcases \":~ro Tha resulta nrc not clear in case c£ cross cl!nic~l grad~. a$ toleranea and LSD the bat\~en p~ilocyh!n (col~~~). Al~~ough responses 1~r0 less on all me~su~as~ ~~e changg3 ~ra s!gn!r- only ln tha cases ot the blood and clinical ic~nt p~cssuro grade. or Tha 4ata doubt t.f!..at. a graat. deal direct le~a littl~ tclerunce to tSD ~us 1nducadt and that~ •mila the patients ners tolerant to LSD eros3 tolorcnca to psilocybin cons!cl~rabla ~s 6 prGsent.. In the of direct .. to psilocybin, ~sa tole~nce 1nte' rp£"et.aticn !s not as ea::sy. Al U1ou~l1 a11 tha changes w0s-e or in tha·prcper directioA, In the caso ot tho ar~, t~~ or tha the decrease measurc~ent~, h!~1ly s!gn!fic~~t, ~agn!tude in the respo~ses was less th~~ ~th dir~ct tolerance to LSD. Thcs~ facts $ugges t.. that~ sl though toler~"'lce to pailocyh!!l does develop, it. dav~lops mo~a· elowly or 1e less complete thEl.J."'l is tolerance to LSD.· For ~ . h !9 rea$oz:t,, the rc!~tivcly s.::lall (thou~h • . is not surprising. treatc~nt wlt~psilo~;b1n 7he fail~re to· reach stgntf!c~~eg ln the decreasa 1n res~;nses on th~ ~estlonna.i ra Wtf.S due in ever"-.{ case to one ln~iv!dual 'Who ~~s very sensl tivo to both d!"1l9S whlla r.ot. tolerant. He scored over 200 rssponses LSD.r over 90 a!tc~ ~ responses ~ftar pa!loeybln !n l;),)th the !ir~t. a.'1d second cantrols. ' The of response$ on challengQ wlth LSD or nu-~er e!the~ p~!lo• cybin a!ter ehren!e ct vnr1cd ad~1ni$tration e!the~ a~~g bst~ean 10 and 30. The daerease tn of po$it1va responses ~~a n~er was, thcret.. ore, V(lr::/ great. and lnd!cntive of a h!~h degrf;t'3 o£ or and T.ha large size dtftgronca, toler~~ea ero~s to!cran~a. th~ · for the group as a Hholc ho~~er, 3k~~d the distribution of the data/and ~cde the sign!!icnnt result. . Since tha exper!m~nt.was not ~1t1rcly eoneluslve 1 and since the failure ta reaeh a co~l~taly conclusive The page contains typed text and handwritten annotations. A handwritten identifier "B-260" is present in the bottom right corner. There are also faint dots and smudges scattered across the page, consistent with aging paper or the original duplication process. No photographs, forms, diagrams, tables, or official stamps are visible. There is no visible evidence of experimental procedures, equipment, or facilities. of a h!~h degrf;t'3 o£ or and T.ha large size dtftgronca, toler~~ea ero~s to!cran~a. th~ · for the group as a Hholc ho~~er, 3k~~d the distribution of the data/and ~cde the sign!!icnnt result. . Since tha exper!m~nt.was not ~1t1rcly eoneluslve 1 and since the failure ta reaeh a co~l~taly conclusive result might be dua to the s~all na~b~r or subj~cts, It should be repeated using the sa.'ile d~Zsi gn in the hope that the lt?-rge nur~er of subjects will rerluca the· varlanc~. lt 1~ also "' possible that the fnilur~ to re~ch statlst!c~l slunific~ce .I or was due to a relatively low degre2 tole~ance to psilocybin. ln th~ latter case, th~ p~riod of.. chronic treat~ent wlth p~!loeybln s~onld be extended ~~d, perhaps the pstto~;b1n doaa~e shculd bQ increased to 200 ~g/kg. Although not conclusive, results ara ~~tlrely th~ su!flclently suggeGtivc to support rathar st~ongly the notion that LSD a."ld psilocybin induce t1 p:~yehosis by seine cc:mr~n b1oc..~e21cnl ot" physiological m~chenism. 1. Cross tolcranc:a··bc"tweein LSD-2.5 and pniloeybln \'Ia$ t.e~t.cd cy t'challcng!ngn 5 men. with 150 m.cg/!tg of pa!lo~.!bln after th~ had ~Qce!ved LSD-25 onca daily fo~ 7-8 days (25 meo/Kg increasing to 150 meg/Itg)~ ~--- . _J..., A r"'). ./ 2. A high degree of "direc~n tolerance developed to LSD after ·chronic a~~~nistratl~n for 7-8 days. The development of ., ndtrectn toler~~ea to ps!loeybln ~~s not proved conclus1vely, althou~h tho re~ults are ~trongly sugg~stlve that partial 3· n~'Sp!):lses to P:silocyb!n ai"ter chronie a~inist.rat!on or . .J LSD a~~ highly sugg~tive of cross tolerance bctwe~n LSD ~~ J ' • : p3llocyb!n. D1r.tlnution tn the- r~~sponses to LSD aft.cr chro!llc treatl2ant. wittl psilocybin. ~~tla suggs=tive,.were not :su:f£1eie:tt!y between psilceyb!n acd LSD. 4• The experiment ~hould he extcnd~d to Include at least S other suhJ!:~t~ and, 1f' tha re~ult,s are at111 inconc1us1ve,. LSD ana psl!o~Jbin shoutd be e~t~nded for Q longar period of ~. t1ms and higher glvcn. dose~ -zo-;· B- ! _ _.. REFERENCES EDUk1DS A. L.1 Stati~tical Analysis tor Student~ ln 1 Psyeho1cgy end Edac:1t 1on~ 1. Ne'.il York: Rhinehart. an? Co., 19h.6. ,,. '; Psllo~fbin1 cin. p:s~rchot~opar Wlrkstn..ff and d~ Mexik~.,.i~'len (Easel) Rauschp 11 z s ... -;xpt Kor.~tltuticnsaufltl T a t rung t:nd Synthese von Psilocyb1n. ~~n~rlentln (Ba3cll lht 397 (l958b). Isnm.L, H. 1 Co~pa.rison. of t.ha reactions induced by tn P~vchcnhar~necloni~J ~ress -.a - y ( 1959)·. and LOOAJ~. C~ R.: studies on lys~rgic aeid diethylamide (LSD•2.5). !. Mexik~.,.i~'len (Easel) Rauschp 11 z s ... -;xpt Kor.~tltuticnsaufltl T a t rung t:nd Synthese von Psilocyb1n. ~~n~rlentln (Ba3cll lht 397 (l958b). Isnm.L, H. 1 Co~pa.rison. of t.ha reactions induced by tn P~vchcnhar~necloni~J ~ress -.a - y ( 1959)·. and LOOAJ~. C~ R.: studies on lys~rgic aeid diethylamide (LSD•2.5). !. :erfcetn ln tcr'r.ler ~ ..p hlne addicts ~t.d dw-elop• ment. of to!er~.nce during chronic !nt.oxlcat.!on. A.r.1.A. Arch. lSBEl.L, H., !..OOt.Jit C. R., or~ MINER, E. J.~ Studies on. II!. attenuate Att~pts ~o lysergic acid diethylam!d~ (LSD-25). /J-263 ·J a.s WASSOi~, V. P. and ~ASSC.Ut R. Mushroo:ns1 Russia a.r'ld H!stoty. liaw. York: Panth<:on Book$, 1957. W!N1ER, c. A• and F'LATr~.ltER1 L.: St.udice on Hept.a~one ( 6-Mor pho 1 ir.o-4, 4-d 1p henyl•3 •h ep t an.cna hyd roch! or 1d e) in ) / -. "? .. : .· FOO'TNOTE 1 • Footnota 1. We .are !ndcbted to Drs. R. Btrche1'" and c .. Henze of Sandoz. ~h:u-m.ac~t:. ticals, Han.ovet* U. J. for 1 supp1!ez of ps1lo~Jb1n ~d LSD. I 1 ,., .: \' l ,',I ; ·•·. -........ r-~ t. Tnhlc 1. "J N I E;r.pcrlr:H~ntal De~lua f()f Te5linn Cros3.-Tolcrnnce ~ De tween LS0-25 and P~llocyhln (V-C-5). • ftoy or , - . 2 l .. " . - <: r J o~! f>n c r l m~n t ~.u b t cct~ \ l '.... . $ . u h kc t.,n.;.....::Y:.-_-____. .;..R.;-.;';.;.:~.;;;::·o~r;;...k;..;.'.:;;.~---------------- ... ~ .........--.~ ~----- '>~u trot 1; 2 or 3 LSD, l.S ~cg~tU v-c~5, 150 mcg~tg To obtnln bu~al dnta t l h, ~ or 6 Placebo Plncebo Order bf tests rnndo~iz~d f)t 9. to·or ll v-c ... 5, 150 mcg/J·qJ LSD, 1.5 mcg/lqJ At lcnnt flvu d:.1ys hctw.::~:n tents •' wlth t.sn ~ncJ v-e-t) I ..,.._._...... • ".....,. ••w , ... p t ., •• ••• ~···-· •• ......... .. ••• • ·;frog • ...,. ,.,, .....~ . • • ..... ~ .. ••• .., ............. •• ..:: -.-..~• ....,..........,_~ n~t·onlc 12 or 1) to LSD, l1,1cren~lng v .... c ... S, J.ncrco~lno To develop tolcrnncc ''·!rt~nis- 19 or 20 t.o 1~5· rncg/itg to 150 mcg/l\g tratlon 20 or 21 LSD, 1~5 'rncg/~f.... V-c.-S, 150 mcg/l~g Test of "direct" tolernn::~ l'J. ~~ or 2..? ....... ~~-C.:2.. tr;u mco Jm LSD t .~:) mc~L!~!l ~ctl_t. . or_ "cr2!if" ~~)ltP.!ftr~.~...... __ r r'n=~bo or 22 or 23 t~ lacebo '. Plec.:tbo 1'o 1o sc tol crnnce ~n The page contains typed text detailing experimental findings, possibly from a scientific report or study. There is a handwritten annotation in the bottom right corner, "B-259," and a small horizontal line above it. The top right corner has a handwritten notation, "Page 6." The text discusses measurements related to LSD and psilocybin administration and their effects, including concepts like tolerance and cross-tolerance. There are no photographs, diagrams, stamps, forms, or redactions visible on this page. mcg/l\g tratlon 20 or 21 LSD, 1~5 'rncg/~f.... V-c.-S, 150 mcg/l~g Test of "direct" tolernn::~ l'J. ~~ or 2..? ....... ~~-C.:2.. tr;u mco Jm LSD t .~:) mc~L!~!l ~ctl_t. . or_ "cr2!if" ~~)ltP.!ftr~.~...... __ r r'n=~bo or 22 or 23 t~ lacebo '. Plec.:tbo 1'o 1o sc tol crnnce ~n U'drnt;ol 29 or 31 ,'. ~· - I · ' - ' · < .... ..........~.. ...r.· :·. ~. -----------------------~:-----~·------------------------- 1.' r·!_t :r., , · C!'nt.rcl J 1 , or )2 'Plac<tho LSD To prove los~ of tol~r~ncv , .. so '•~: 3~, ~1~., 35, v;.c.~;; 1 mcg/hg Placebo To replicate ba~nl dut~ .,.. ~ · ~, 1," 7 , .~:·),v or "~" 9 LSD, 1 • .5 mag/kg V-:aC-5, 150 mcg/l~g Or(!cr raadomlzcd at lc~.1t flve __ dnyg between te~t~ with LSD ..t..-....----------- ' ' end p~ 11 ocv.•t~n • \ • Tf.D • a 1 k f ..... Jl 1 ................ ,... I Q d • f flll'l U ff 4i011 Chrcnlc .:-19 or li.O to ·- V-C-~)~ lw.!t\_cnstng LSD, lncrca!llng "Cros:l ... Ov~r" ,.- r• . ;·~:r:d_~- · !16 or h7 to ISO mco/hg to 1.5 r.lcg/1-to To cnv;:~lop toleranr:e ( •t·•·.t.l·:Hl h7 or h'·~ v-c-:;, t;)o mc':)/Hg I.SD, t.~ rncg/l~g Test "direct" tnlcrnnce .:' I ~.9 cr (~() L$D. t.t; r~t~n/luT v-c-~~ 1.50 !':'!C.. Tc:.c;t. tlcro'l~" tol~r-::>l~f':e .,.,. . .,... "• .......... •11 -- ... I 1 ......... ._ ti• f~ _ ................ ...__ ____ . ' t. SubJe:cts "l.tr first received LSI> chronically. 2. Subjects "Y" r~celvud psllocybln first. Table 2. Dtf£erences in R~spon~e3 to Placebo, 1.5 mcg/J~g of LSD-25 1 a..-w 150 mca/ltQ of Psi locybln on First and Second Control~. ~Rln MEAStffiE Placebo LSD-25 Psi locy~l;t - + 1.!.~ ~ 0.93 0.2 ± 1.1 + 0.7 ± 0.57 -10.8 t 1 3.1 -24.8 :t 23.2 -16.1 -± l '·.1 ~ Slood Pressure •22.2 :i ~5- ,," ' -16.6 ± 22 -20.3 ± 9 • M ~ - - Pupillary Size + 0.2 t I ·2.3 0.02:: 1.3 0.3 t l.J2 .. - / .... +25.5 1" _, K.neejerk ).6 t '1•.) .-2!).9 ± 21 ± !') • .:.• - - Re Q sp u; o ;s n ses on . a 0 4 •- 31 8~8 ! l"' . > . ;eU q ti~J-n.nair - Cl !nical Gracie 0 0 .. 2" t 0.37 0 rieur~~ represent the me~~ dlff~rences : ntancia~d c~~o~s The page contains typewritten text and a handwritten annotation. The text is a section titled "RESULTS" discussing experimental findings related to drug administration and tolerance, referencing tables and measurements of physiological responses. Near the bottom right corner, there is a handwritten annotation "B-258". No photographs, official stamps, forms, diagrams, or visual evidence of experimental procedures are present on this page. This page contains typed text that discusses the results of drug tolerance experiments, mentioning LSD and psilocybin. There are no photographs, forms, diagrams, or tables visible. Handwritten marginalia appears at the bottom right corner with the text "B-257". There are also a few dark circular marks near the top, potentially from a physical scanner or binder. The document appears to be a printed page from a report, but no official stamps or redactions are present. 21 ± !') • .:.• - - Re Q sp u; o ;s n ses on . a 0 4 •- 31 8~8 ! l"' . > . ;eU q ti~J-n.nair - Cl !nical Gracie 0 0 .. 2" t 0.37 0 rieur~~ represent the me~~ dlff~rences : ntancia~d c~~o~s of t.he differences between measurements· on the first and :;ec•:Hld. contr-ols ln 5 au·bjects. Uonc ef tha dlffci"e.i1Ce~ are significant. •• lrtdicate3 that the average measurement ~~s increased on the s<lcom! contro.l J -. Indicates th3t lt decreased. ! ,',I !·' ;.1 :~ e J. 'I t_~ L.. Tahlc .3 .. ,).. \'{ rs I Di ffcnmcc!J I?.ct.t•rccn Contro 1 Hezponse to LSD·2S and 11 ocybl n, ~ and ncsJ:onscg oftcr Chronlc Ad!nlnlstr~tlon of Either Drug. --- ,. --------------------------~~----------~~------------- A l"'T.f:71 lS D CHf\0i:U C.'\ Lt. V ----:..-.;,;.,.;. , tsn ...P a • , ....." ""............... ......... Psllc''='Ybln l.SD ("Direct" T'>lernnce) (11Cro5st'· Tc-lcrtlnce) f"Crons'' Toleran(';~) J.~r·:l\ SU'i E ------------------ •• •• •• ,.. 1 ... o.•n s • •• tr•• · r • , - 0 P:.,. . .. , 7 .. • o.J ----. 0.99 t 0.9} ! T(;•1nerature l.h ! o. 711 - t.l t X -t.s.a te .. 7 -)).2± 11 .. 2 .... o Y . · -12.5 t 10.) t fnlse Rate ~~~- t ll~.o :X -35-1 ,; ..:ton.?i 17.1 .. ·. -33-~. . 1; 9.01 -1.2. 7 ± 1). 7 ~ J::!.() 0 h:u-,d Pre!:sure l'nplllary Size .. 11~.0 Y .X t 2.1~ - 8.2)-J, X t 2.2 - ).1 :1: 2 •.3 7 - f 2.0 t 1.2 \ rA~e ·-\erk - .2B.7 t 1$.1+ .. . ' -h.2. 7 X ~ t 0.6 - 6.9 :t 6.7 -Jo.av - v · ! 7-2 ~, \ -67.0 )8.6 -18.0 f 15.6 -22.h. t '10. 3 t i., r nponses on - 77.2 t JS.~ Cu•.z~ t l oanal re o.s ,. l~ - ~~. 1 s·x o .I.J.!> 1.8 X :t ~ 1.1 :t 0.2·1 •:llntca.l Grade 2.3 t ..0 ~b~(l - • t Wi \ ,l'!'lg,Jtt:s repre~cnt th~ mean tUfferrJnce!l t.. ntandarrl errors hct·Meen the svcrn.Qc of the t1.;.•o control!\ and t.he vn.tu~·!l 'found 'V.-t'l(?:\ th~ pc.tlct\l v::.:l.~ tcstc:!t1 with LSD or pallocyb1n after rcc~lvlng either dru~1 chronically. •( -, lndlcatc~ n d~cranse ' in the responsa nfter chronlc drug admlnlstratlon ("t.e>lcrnncen) a~ co~1lpat'cd with c<.,ntrol (nontol~rnnt). '•, xx, Dlffcrcnclli': nl·galflcanl. at The document is a typed page with handwritten annotations. There are no photographs, diagrams, or forms present. Near the top right corner, there is a handwritten notation "Page 9" and a handwritten number "B-256" at the bottom right. There are also a few small dots which may be ink smudges. errors hct·Meen the svcrn.Qc of the t1.;.•o control!\ and t.he vn.tu~·!l 'found 'V.-t'l(?:\ th~ pc.tlct\l v::.:l.~ tcstc:!t1 with LSD or pallocyb1n after rcc~lvlng either dru~1 chronically. •( -, lndlcatc~ n d~cranse ' in the responsa nfter chronlc drug admlnlstratlon ("t.e>lcrnncen) a~ co~1lpat'cd with c<.,ntrol (nontol~rnnt). '•, xx, Dlffcrcnclli': nl·galflcanl. at 1~ level (P··< 0.01) :Jt• tltffercnz:c !;Jlgnlflcnnt at 57~ lavr.tl (P<O..OS) .• This document page *is* the visual content. It displays typed text, likely from a report or research document, with handwritten annotations at the top and bottom right. The top of the page has three circular marks that appear to be hole punches, and the handwritten annotation "Page 10" is present near the top right. The bottom right features a handwritten alphanumeric code, "B-255". There are no photographs, stamps, forms, diagrams, tables, or redactions visible on this page. The page is a typed document, likely a report, with numbered points discussing research on LSD and psilocybin tolerance. There are two circular ink marks near the top, one black and one likely a smudge. The text includes the page number "Page 11" in the upper right corner. In the lower right corner, there is a handwritten annotation "B-254". No photographs, stamps, forms, diagrams, tables, or redactions are visible on this page. The image displays a single page of text, a bibliography titled "REFERENCES." The text is typewritten in a serif font and appears to be from an academic paper or report. There are no photographs, diagrams, stamps, forms, or handwritten annotations visible. The page is numbered "12" in the upper right corner. There is a handwritten mark in the lower right corner, "B-263", which appears to be an internal document identifier. The text itself includes bibliographic entries for various scientific articles and publications, likely related to psychology and pharmacology. The page displays typed text from a bibliography, listing two entries. There are two circular stains near the top center of the page and some scattered speckling throughout. Handwritten annotations are present at the top right corner, labeling it "Page 13", and in the bottom right corner, appearing to be a document identifier "B-262" with a hyphen and another character. No other visual elements such as photographs, stamps, forms, diagrams, or evidence of experimental procedures are visible on this page. This page contains typed text, including a main heading, a page number, and a footnote. The footnote thanks Drs. R. Bircher and C. Henze of Sandoz Pharmaceuticals in Hanover, N. J. for supplies of psilocybin and LSD. There is also a handwritten annotation at the bottom right of the page that reads "B-251". The document appears to be a scan with some minor speckled marks, but no other visual elements like photographs, stamps, or diagrams are present. The image displays a scanned document containing a table titled "Table 1. Experimental Design for Testing Cross-Tolerance Between LSD-25 and Psilocybin (V-C-5)". The table is divided into columns for "Period", "Day of Experiment", "Subjects", and "Remarks". Handwritten marginalia, including what appears to be a document identifier "B-250", are present in the upper right corner of the page. The document's visual format is that of a scientific table, suggesting it describes an experimental protocol. There are no photographs, diagrams, stamps, or other visual elements beyond the text and the handwritten annotation. The image displays a declassified CIA document page containing a table labeled "Table 2." The table presents data on "Differences in Responses to Placebo, 1.5 mcg/kg of LSD-25, and 150 mcg/kg of Psilocybin on First and Second Controls," broken down by Measure, Placebo, LSD-25, and Psilocybin. Below the table, explanatory text describes the statistical representation and significance o