Doc 0000151801

-/ ') . Psychophamta('ologia 2, 147-150 (1061) From the )io.tiono.l Institute of )[ental Hcn!th Addiction Research Center, U.S. Public Hea.Ith Service Hospital, Lexington, Kentucky Cross Tolerance Between LSD awl Psilocyh.in By .-''".! lL\RRIS IsnET. . L, •. \.. n. "~OLDJ.CII, .\. ,,. . II~LElt uncl E. ,J. )ltXER ,;{Recci!·ed Decemba 10,1960) Recently it has been ~hown (HOF:O.L\~ ef al., Hl;jSa.; DEL\.Y et al., 1958; IsBELL, r~50) that 0-Phosphoryl-4:-hydrox~·-::\-dimethyl tryptamine (hereafter referred to as psilocybin), =~J. compound isolated (Honus et al., 1958b) from certain species of mushrooms that are used ceremonially by )Iexicnn Indians (\\.~so~ and \\. lSSO~, Hl.3i), has psyc-hototnimetic properties similar to those of the diethylamide of lysergic add (LSD-::!5). The close resemblance of the patterns of symptoms induced by LSD a.nd psilocybin suggested that 'these dn1gs produce mental aberrations by some common action or by affecting different mechanisms sharing a common final pathway. Since the effects of LSD diminish rapidly when the drug is ginn daily (ISBELL et al., 19.36), it was felt that if the LSD and psilocybin syndromes haYe a common mechanism, this hy·po thesis could be further tested by determining if "cross tolerance" between the two drugs e::cisted. In other words, if the degree of the reaction induced by a given close of psilocybin was significantly less in a. person tolerant to LSD, cross tolerance would be said to exist; and, conversely, the reaction to a. ginn dose of LSD should be reduced in a. person tolerant to psilocybin. In the latter case it is implied that "direct" tolerance to • psilocybin can be de...-eloped. :\Icthods Experiments. Two experiments were performed at different times. Experiment II was carried out to determine if administration of a larger doso of ·psilocybin gi>en o>er a. longer period o£ time than in Experi ment I would create a. greater degree of tolerance· :md cross tolerance. A "cross-o>er" design using each patient as his own control was employed in both experiments and is. summarized in Table 1. Both experiments consisted of seven periods: (l) first control, in which measurements were obtained after the test closes of psilocybin and LSD, (:!) first chronic administration, in which patients received either psilocybin or LSD once daily in doses increasing to the test leYcl over <1. period of G--12 days, (3) first test of tolerance and cross tolerance, in which pntit'nts were "cbnllcnged" with the dmg they had bet'll taking ?-·· .. . \ The image is a graphic featuring a stylized vault door on the left and text on the right. The vault door appears to be a digital illustration with metallic textures and a blue glow emanating from the right side. The text is white and appears to be a disclaimer about the origin of the document, stating it was obtained from "The Black Vault," an online database of declassified government documents. It also mentions that the specific record is housed in the MKULTRA/Mind Control Collection and provides a URL for download. There are no photographs, handwritten annotations, signatures, official stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures visible in this graphic. The page is a scan of a research paper, with a handwritten annotation "206" in the top right corner, circled once. Another handwritten notation "B-375" appears in the bottom right corner, underlined. There is a dark circular stamp near the top center of the page, and what appears to be a partial circular stamp to its left. The text is primarily typed, with some faint vertical lines suggesting it was a physical document. No photographs, diagrams, or forms with filled-in fields are visible. There are no official stamps other than what appears to be marginalia. first chronic administration, in which patients received either psilocybin or LSD once daily in doses increasing to the test leYcl over <1. period of G--12 days, (3) first test of tolerance and cross tolerance, in which pntit'nts were "cbnllcnged" with the dmg they had bet'll taking ?-·· .. . \ ej '\ .,!-.. '•. ... . ' ~ ...... ~ 'fablo 1. Sununary oJ experimeutal dui!JIII Jor Experimerll• I an1l II No. of nrus:• and ))oge~ \. ' . ltomarka rcrlod ]!lxJ•t. })ay¥ lluhjocta x• Suhjoc;ta y • I. }'irut control . . • . • • • • I 1 I 7 8- - U 8 J L ,S S J D )3 1 1 .5 .6 , : 1 · '1 p , p I , ' l 1 l ~ 1 2 1 1 l 0 li O. I I '1 'l 1 l 3 2 I w fil , l ; 1 ' 1 1 ' , 1 . v u m m I.a ' O l'o rd o e b r t o a f i n t e b s n t 1 s :1 a r l a d tu n l t o n m . ized. .. At leullt 5 t.lny:~ bctwcon 1't~ nrul LSD 2. Fir11t. chronic ndministro.tion • I 6-7 J.f;J) inCJ'Cilllillg (~) 1.5 1111 incrcnsiug 1-o 150 'J'o develop t.olcrnnco ]J 12 LSD incrcauing to 1.6 l'u incn•nsing to !HO 3. F cr i o r ~ l! ~ t ~ . : t ~ c - 1 t 1 . t o l o c f m n t c o o lc . n m • co • a . m . i • • 1 I 1 2 2 V L H H) > ) 1 1 . . 6 5 , , l J> ' 1 u 1 2 Jf 1 iO 0 1 l' • 1 1 1 1 ! I . f !J il O l, , u L: m ·m 1 u . 5 'l'cllt t . u o le f r t u u n l c u o rn nco nnd crollll -' 4. Withdmwnl pcl'iod ..... l 7~-10 l'l 1'1 'J'o lo:~u tolcmnco ll 1:1 Nouu Nuno 5. Second control . • • • . • • 1 l 1 8 7- - H 9 1 1 ' r t u u n l c u o rn nco nnd crollll -' 4. Withdmwnl pcl'iod ..... l 7~-10 l'l 1'1 'J'o lo:~u tolcmnco ll 1:1 Nouu Nuno 5. Second control . • • • . • • 1 l 1 8 7- - H 9 1 1 ' ' 1 1 , , l 1' ' 1 s 1 2 )1 1 )1 0 ) , , u u; m u l 1 . . f r i . ] u ,H m U L U l i i , , 1 1 ' ' 1 1 , , l l ' ' 1 1 1 1 2 ll 1 iO 0 ' ' J J ' ' o o r t c c p :; l t i e l 1 o 1 :~ t s o o c f o t n o t l r c o m l d n u c t o o . '--...~- 1.1. Sccontl chronic admini1:1tro.tion 1 i 1 1. 1 1 2 -7 1 l' '1 l 1 i i i a n w c r r · e c a u s ll i i n n g g t t o o 2 1 1 5 0 0 L u S m )) i i n n c cr rc on n : ! ~ li i n u g g t t o o 1 l. . 5 5 "C t r o o l ! c ll m l·o n v co cr " to de . velop • 7. H cr c o c ~ o t~ m -L l o t l c c s r L u n o c f e . t o . lc • m n . ce • a . nd • • 1 I 1 2 2 1 l ' ' 1 s 1 2 lf 1 iO 0 , , L L S ~ D D 1 1 . . 5 5 u J. m ~D 1 1 . . 5 5 , , l 1 '1 '1 1 1 1 21 li 1 O 1 'l'(l t ! u !t l c o • f rn ( n . c o o lc ro.nco and crow • 1'\uhjecbt "K" a·cedvnd J,S)) 1:hwuieuUy, fir11t. . 2 Huhjt·ctll "y" r·ct:eiHd p11ii01:,1'!Jiu chl'tlllicully, find .. a This declassified document page from the MKUltra collection contains a table summarizing experimental designs for Experiments I and II. The table is titled "Table 1. Summary of experimental designs for Experiments I and II" and includes columns for Period, Expt., No. of Days, Drugs and Doses (with sub-columns for Subjects x and Subjects y), and Remarks. The table details different experimental periods, drug administrations, and their purposes, such as obtaining basal data, developing tolerance, and testing tolerance and cross-tolerance. There are no photographs, handwritten annotations, official stamps, or diagrams present. A single large redaction obscures a portion of the right side of the page, and another redaction is present at the bottom of the page. This page contains typed text with some faint handwritten marks. At the top center, there are two circular ink marks, one hollow and one filled, and a curved line. There are also scattered small ink dots and smudges throughout the page, potentially from the printing or handling process. A page number "149" is visible in the upper right corner. In the lower right corner, there is a lightly printed "11*" and a horizontal line which might represent a torn edge. There are no photographs, stamps, forms, diagrams, tables, redacted content, or visual evidence of experimental procedures. l 1 '1 '1 1 1 1 21 li 1 O 1 'l'(l t ! u !t l c o • f rn ( n . c o o lc ro.nco and crow • 1'\uhjecbt "K" a·cedvnd J,S)) 1:hwuieuUy, fir11t. . 2 Huhjt·ctll "y" r·ct:eiHd p11ii01:,1'!Jiu chl'tlllicully, find .. a L:-;1>,, tlidhylumitlc of ly11m·gic at:icl; J>J ,,, Jlllwt:huj 1'11 ~- p11ilcu:yhiu. 'J'ho unl~:~· of nclminiHtmtiun of tlw •lmg in c·•u:h IM'rimlls I hulit'llll·•l l1y the •mlcr in which tlu•y nppeur in tho l:lecLiuu of tim tnltlt1 fm· thut.I•~'riod. 'Jt'il-(111'1'11 ufh:r tlw 11ytnhul:• fur llll' drngt~ huli•·nto t th(,l, clo~c: iu nwgfk!l· I• ...... , ) e / _) 149 (test of· "direct tolerance") and on the ;ubscquent day with the drug they had not been taking (test of "eros~" tolerance), (4) a withdrawal or "washout" period, in which the patients rce<-in•d placebos (Exneriment I) or no dntg (Experiment II) in order to lose tolerance, (5) a seco·11d ~:_co1ttrol period, in which the test doses of LSD and psilocybin were "!epeated, in order to replicate the <'Ontrol data obtained in the first control pcripd ·and to cktcrmine i£ tol<'rancc hacl been completely lost, (6_) second c]ironic admini~tration, in whic·h the patients rece-i,·ccl daily doses of the- altemate dntg that they had not taken in the first period of chronic administration f''cross-ov:~r"), and (j) finally, the .second challenae, ,\ith test doses of LSD and psilocybin as in period 3. Drugs and Doses. LSD imd psilocybin 1 wel'E~ given in 30 cc of cherry syrup at S a.m. with the patients fasting. The syrup, which ·was used to mask the bitter taste of the psilocybin, scr...-ed as the placebo. In the first and second control periods the patients receh-ed in randomized order 1.5 mcg.kg of LSD, placebo, and 150 mcgjkg (E:s:pcriment I) or 210 mcgfkg of psilocybin (Experiment II) b<'fore chronic administration of the drugs was begun. Detailed observations· were made on these test days. These. control experiments were conducted at inter;als of at least five <:lays in order that any tolerance conferred by the first cln1g would be lost. During the first n.nd second periods of chronic administration the patients in Experiment I received 0.:25 mcgikg of LSD or :23 meg/kg of psilocybin on the first day. These doses were increased 0.:25 m<'g}kg (LSD) or 25 mcgjkg (p..-.ilocybiu) daily until the patients were receiving 1.5 mt'gjkg of LSD or 150 mcgfl~g of The document page contains only printed text without any images, stamps, handwritten annotations, or forms. The text describes details of a drug experiment, including the methodology, subjects, and observations. There are no visual elements to convey information about experimental procedures, equipment, or facilities beyond what is described in the text. n.nd second periods of chronic administration the patients in Experiment I received 0.:25 mcgikg of LSD or :23 meg/kg of psilocybin on the first day. These doses were increased 0.:25 m<'g}kg (LSD) or 25 mcgjkg (p..-.ilocybiu) daily until the patients were receiving 1.5 mt'gjkg of LSD or 150 mcgfl~g of psilocybin on the sixth day. These doses were maintained until the tests of tolt.•r:mce and <'ross· tolerance were perfonned. In Experiment II the patients received 0.15 meg/kg of LSD or :21 meg/kg of psilocybin on the first day of chronic administra tion, increasing by 0.15 meg/kg of LSD or :21 m.cg;kg of psilocybin daily until the patients were receiving 1.5 m<'gfl.:g of LSD Ol' :210 meg/kg of psilocybin on the tenth day. These dos~-s were maintained through the twelfth day. The order in which the pati<>nts received the dntgs in the first and second periods of chronic administr:.1tion was randomized in both Experiments I and II. During these periods of t'hronic ,\Clmin.istra tion, detailed obscn·ntions were not made. On the first day after completion of the period of chronic administra tion the patients were "chall<'ngcd" with the dow of dntg they had been r<'cciYing (test o£ direct tolerance). On the second Jay, they were 1 \Ve are indebted to Dr::o. It. HmCHER tmd C. Jh::sz~; of Sandoz Pharmaceuticals. of Hano,·cr. Xt•W .Tcrscy, for supplies psilocybin t\1111 diethylamide of lysergic acid t:ntrntc ( L::5D-:!5). n• -) I 150 .. \ . I challenged with the test dose of the nltcrnntc dntg (test of cross tolcrruH·e). On both of these days dctnilcd measurements W('re made. Th:e patients then recci\·cd placebos for i-10 days (Experiment I) l .· or no drug for 13 days (Experiment II). It was presumed that the patients would lo~e any tolcrnn.cc the~· had de\·cloped, since in prc,·ious ! experiments (IsBELL et al., 195G) tolerance wns largt:lY dis~ipnted ·within ~ three dnys after discontinuation of LSD. Following this withdra\\al period, second control measurements were ~ obtained aft~r the patients had receh·cd in randomized order pbccbo ~ (E~eriments I:and II), L3 meg, kg o£ LSD (Experiments I and II) nnd I ~ 159 meg/kg (E~-pcriment I) or :!10 meg: kg of psilocybin (Experimem II), ~ 1 witha.t least fh-e days intcn·ening between adruinstration of LSD and i psilocybin. · The patients then again rccch·ed the drugs chronicnll~-. those patients i 1 who had taken LSD in the first period of I ~ 159 meg/kg (E~-pcriment I) or :!10 meg: kg of psilocybin (Experimem II), ~ 1 witha.t least fh-e days intcn·ening between adruinstration of LSD and i psilocybin. · The patients then again rccch·ed the drugs chronicnll~-. those patients i 1 who had taken LSD in the first period of chronic administration were i l given psilocybin according to the schedules described abo'e and vice t t versa.. They were then "challenged" with LSD and psiloc)·bin in the ' t manner described abo,e. Preliminary •. \.ssay. E:t;periment II. Since the test dose of psilocybin (150 meg/kg) had a. lesser degree of effect than the test dose of LSD (1.5 mcgjkg), a preliminary assay was carried out prior to Esperiment II. The dose-response curres obtained by !snELL (1959) were extended and 210 mcgikg of psilocybin were estimated to be equnl to 1.5 mcg,kg of LSD. .Accordingly, the abo\e doses of LSD and psilocybin were ad minis~red on two occasions at interr~ls of sen•n du.ys in random order to 10 subjects. Statistical analyses (see bclo"t for method) re,ealed no significant differences in any of the compari~ons made (Table 5, -~ssa.y ~. Study). Subjcets. The subjects who volunteered for both experiments were former opiate addicts who were ser\·ing sentences fOl· violation of the United States narcotic la'vs. Their ages ,-aried between !!5 to 35 years, all were physically healthy males, and none presented any eYidence of the major psychoses. .-ill had psychiatric diagnoses of character or ·personality disorders, and nll had rcceiYcd I .. SD in previous experiments. Ten subjects served iu E"'--perimcnt I. nnd I) in E~pcrimcnt II. General Conditions. Subjects were housed iu a. special ward de,·oted to clinical research. Temperature, respiratory rate and blood pressure 'vere measured three times daily n.ftcr the patients had rested quietly in bed during days on which spccit1l mcasur:emcnts were not being made. The patients >\"ere obscr>cd by specinlly trnincd aides with long ex perience in detecting dn1g-inducod cha.ngcs in beha\·ior. Observations. During each day of the cont1·ol periods and the pc!'iod.:> of chronic dntg ndministrnt.ion during which the p<lth.'llts were "chnl- 151 lcngccl" with pl!lccbo, LSD or P"ilocyhin, the followin~ obscrYation:s w~re made a.t hourly inter,·n.Is, aitrr 10 minutes rt'st in bed, twi<.'c lidorc ..a nd eight times after administration of clt·ugs: rect·nl temp<'raturc, pulse · rn.tc, systolic blood prcssl~rc, pupillar:-: size and thrcshokl for C'lidtatiou of tho knee jerk. The rut>thods used 'were The page is a scanned document page from a declassified CIA file. It contains typewritten text and some visual artifacts suggesting it originated from a physical document. Specifically, there are faint circular shapes and a dark circle at the top, possibly from a scanner or previous document handling. There are also small, dark specks scattered throughout the page, and a faint, straight line with a zig-zag pattern near the bottom right. The text itself is clear and legible, discussing a scientific experiment involving LSD and psilocybin. There are no images of people, locations, equipment, or subjects depicted. The page is a scanned document that appears to be a scientific report, likely related to drug research. It contains two tables presenting numerical data, titled "Table 2. Differences in responses to placebo, LSD-25, and psilocybin..." and "Table 3. Differences in responses to placebo, LSD-25, and psilocybin...". These tables are structured with columns for "Measure", "Placebo", "LSD-25", and "Psilocybin", and rows detailing various physiological and psychological responses. Below the tables, there is explanatory text with footnotes indicating statistical significance. No photographs, handwritten annotations, or official stamps are visible, and there are no obvious redactions or obscured content on this particular page. pl!lccbo, LSD or P"ilocyhin, the followin~ obscrYation:s w~re made a.t hourly inter,·n.Is, aitrr 10 minutes rt'st in bed, twi<.'c lidorc ..a nd eight times after administration of clt·ugs: rect·nl temp<'raturc, pulse · rn.tc, systolic blood prcssl~rc, pupillar:-: size and thrcshokl for C'lidtatiou of tho knee jerk. The rut>thods used 'were those prcdoush· dt'scribed (ISBELL et al., }!);j(i; I:::;uELL et al., HJ.iO; IsnELL, 1!).3!)). In atlclition, the ·: patients (with the help of ·an aide) completed '' special quostionnaire ... {at hourly interYnls from 7:30a.m. to 3:30p.m. At these same times, general no~cs ·on beha-vror wcrc 'nittcn. Clinical grnd<.'s of the intensity of the reaction we1-e assigned on the basis of the system of IsBELL et al. (1956). ., .1nnlysis- ·of Data. The: change;;: in rectal temperntme, pulse and respir~torj· rates, pupillary size, blood pressure, and threshold for elicitation of the knee jet•k aft('r administration of placebo and drugs were calculated by subtracting the an•ruge of the two prt>.clrug obset'\-a- / tions from the \"alues obtained at nwious hours. The areas under the time-action cun·es for en.ch particuh1r mensurcment composed of thc~e figures were calculated by the method of \Y:cs-n:R. and FL.-\.TXKER (1050), thus conYerting all the data. on a particular subject, n particular dntg. a particular measurt>ment, and a particuhtr dn.y to one figure termed "degree-hours" (temperat1.1re), "rate-honrs" (pulse rate), etc. The total number of posith·e responses on the qucstionnairc were counted o\·er t.he entire period, eliminating answers which were also scored posith·ely before the drug had been gi,en. )Ican:s and standard errors of the means were calculn.tcd according to standard statistical techniques. The difference in the Yarious measurements aftcr placebo, 1.5 meg, kg of LSD, and 150 or 210 meg kg of psilocybin (each indh·idual dn1g .against itself) in tho first and second controls were evaluated by a. f-test fo~ paired obscn·ations (Enw"um:5, 1!)46). In ExpN·iment I the only statistically significant difference found bctwcen t.he two sets of controls was ~ decrease in the pyretogenic effect of psilocybin (Table 2). In Experiment II, significant decreases in tlie number of positiYc responses on the qtt<.'stionMirc occurred in the second control (Table 3) after both LSD and psilocybin. Because of these difft>renccs in the two <:ontrols, the changes in rcspou:;o to the test llOs<'s of psilocybin and LSD after chronic administration of eithcr dnt.!! were evaluatC'd by comparing the effects of LSD and psilocybin nftN the fir~t and S{'cond periods of (Table 3) after both LSD and psilocybin. Because of these difft>renccs in the two <:ontrols, the changes in rcspou:;o to the test llOs<'s of psilocybin and LSD after chronic administration of eithcr dnt.!! were evaluatC'd by comparing the effects of LSD and psilocybin nftN the fir~t and S{'cond periods of chronic drug admini~trn.tion with the eorrcsponding first or S<.'C'ond control. In addition, cak·ulations Wl't'e made using the a\·c1·ngt's of the two controls. The Intt«:'r proL·t•tlure did not alter the significance of the differences greatly, so only the tabll'S showing t.hc differences calculn.tcd with the indivillual first aml :'et·oncl controls a.rc prt'scntcd heroin. ··-~ -) 152 Table 2. Differences it~ responses to placebo, LSD-2-5, and psilocybiu ., on first and .secoud rmdrols in J.::rprrimP.nt 1 l'oilocrllin = Temperature • + O.OS::: O.f..:l + 0.4:! 0.64 -1.24.::: o.,i:l* Pulse rate .• -11.5:l...:...l3.30 -1:!.6:! ~ ll:iAO -Hl.tlO = = n.::o B Pu lo p o i d ll a p r r y e s s s iz u e r e - - 0 1 . . 2 1 9 0 :: ; : 15 1 . .6 7 5 0 - + 1. 0 :1 .5 5 2 :: : ;_ :: ; 1: l ! . . l 7 S 0 - . : + ! 5 ~ . - ~ ~ 0 0 = ll l . ~ l . i ~ l :; ) Knee jerk • . • • . -12.56::11.00 -14-S:J...:... :!!.7;) '1 •. ~8 -l~ .• t) Responses on questionnaire +o.oo= 1.:n ,O.t>lJ;_; 6.11) +4.!l0= !l.H.) = Clinical grade . • • . • +0.10::: 0.10 -0.30 0.:!0 +0.:!0; 0.41 Figures repr~nt the mean diffcrt-nees ::: standard errors of the diffcrcnees between responses to the same dose of the sutue dnl!f (p!,Jceho, 1..3 mcg;kg of I.SD-:?.3 an,Fll50 mcgjkg of psilocybin) on the first and second controls on 10 subjec-ts. Xo ne of the differem:es except that for tenlpt'rnttu·e change after p~ilocybin werc si;nifi- cant. · +Indicates that the average. measurement was increased on the second control. -Indicates tha~ it wns decreased. * = p < .05• . Table 3. Ditferences in responses fo placebo, LSD·25, ami p-1ilocybin 1n first and 8econd control.1 z'11 EJ:periment II l'ln.cebo LSD·:!5 Psilocy\Jin Temperature . • o.o7::: o:;4 -1.31-'- 0.58 -1.36:::=:: 0.6$ + Pu~e rate ... + -9 .72...:... O.Sl -37.61:::17.69 UO l!).JO . Blood pressure • 21.44; 16.4S -1.~.66::: The document contains two tables presenting data on the equivalence of LSD and psilocybin dosage in experiments. Table 4 details measures like temperature, pulse rate, and blood pressure, with associated numerical values and statistical significance indicators. Table 5, similarly structured, presents data from an "Assay Study" and two control groups for the same measures. Handwritten annotations and symbols, such as asterisks and plus signs, are present within the tables, likely indicating experimental results or statistical significance. A numeric stamp, "153," is visible in the upper right corner. The document prominently features two tables detailing experimental results: Table 6, "Tolerance and cross tolerance, Experiment I," and Table 7, "Tolerance and cross tolerance, Experiment II." Both tables present numerical data on various physiological measures (temperature, pulse rate, blood pressure, etc.) across different experimental conditions and drug treatments (LSD, psilocybin). Handwritten annotations appear adjacent to the tables, appearing to be corrections or supplementary notes. A page number "154" is visible at the top right, and an official stamp with a symbol and text is present near the bottom right of the page. .05• . Table 3. Ditferences in responses fo placebo, LSD·25, ami p-1ilocybin 1n first and 8econd control.1 z'11 EJ:periment II l'ln.cebo LSD·:!5 Psilocy\Jin Temperature . • o.o7::: o:;4 -1.31-'- 0.58 -1.36:::=:: 0.6$ + Pu~e rate ... + -9 .72...:... O.Sl -37.61:::17.69 UO l!).JO . Blood pressure • 21.44; 16.4S -1.~.66::: 1S.13 + 6.:l:~-1S.GS Pupillary change -0.10..:.. U36 7 2.00; 1.8:? 0.43 ; 1.;)1) + Knee jerk ...... . 14.44; 6.65 -7-8.7.3::::-!:U~ -29.16=10.91 Responses to questionnaire 0 -32.00 ~ 1:?.35* I -29.01)- 9.29** Clinical grade • . . • . 0 -o.55; o.~ -o.3S; u.3o Figures represent the mean differences ::.. the standard errors o£ the differe-nces between responses to the snmc doses of the same drug (placebo, 1.5 mcgjkg of LSD, "· and 210 meg/kg of psilocybin) in the fir.>t and second controls on 9 subjects. + Indicates an increased response on second· control. - Indicates a. decrensed response on second control. * Indicates significance < 0.0.5. ** Indicates significance < 0.02. The differences in the effects of th~ two indh·idunl dn1gs (LSD \'S 'psilocybin) were also calculated for both control periods using tlw same statistical technique for paired ob>'crYations (Tablcs 4 and 5). As explained above, the diflcrcnccs in the response after chronic administrn.tion of both LSD and psilocybin were calculated by compttring the responses after first and second chronic allministrations of LSD and(or psilocybin with their rcspcctiYc fii·st and second control:;. Four different comparisons were made: ( l) response to LSD after <'hronic administ.rntion of LSD ("direct" tolerance to LSD), (2) response to psilocybin after chronic administration of LSD ("cros3" tolerance to psilocybin), (3) response to psilocybin after rhronic administration of .) .. 153 ·Table 4. Equit·alence of dMaql! of LSD and psilocybi11 in Erperime71J I )(usure l:'im Control Second Control -1.14_:_ · O.i3 +0.52'::=:: 0 .66 Temperature . + + Pulse rate •. 24.0•=;; I .i.2G 31.00 = 18 .11 + +46.80:::: 15.43** "":: B Pu lo p o i d ll a p r r y e s s s iz u e re . + 2 4 2 . . : 7 ~: 5 3 _:_ 2o 1 . . : : m !4 *** +4.74 = 1 .24*** K Re n s e p e o n je s r e k ;; O .. . n q . ue . stionn . a i .. r -; e : + -6 4 . _:_ 2o 1 . . : : m !4 *** +4.74 = 1 .24*** K Re n s e p e o n je s r e k ;; O .. . n q . ue . stionn . a i .. r -; e : + -6 4 . 1 8 .4 8 0 :: :: : : : : : : 2! 8 > . .: ~ SO .; ·•· + +2 3 5 i .8 .1 2 0 : ::: 1 1 7 6 . . 8 4 1 5 * -Clinical grade . • . . . +0.60~ 0.16*** +0.10= 0.46 Figures .represent mean d~ffl'rences ::;:: standard errors of the diff~rences be tween responses to LSD-25 ( 1.5 meg/kg} .nnd responses to psilocybin ( 150 meg/kg) in 10 subj~ts, on t"·o separate occasions (1st and 2nd controls) . • p < 0.05; •• p < 0.0'2; ••• p < 0.01. + Indicates LSD-25 stronger in effect than psilocybin. / -Indicates psilocybin stronger in effect than LSD-25. Table 5. Equit·alence of dosag~ of LSD and psilocybin in Experiment II ..USIIY 5tudr l:'Jrs; Control Second Control (~- 10) (;s'-9) (~- 9) = = T P B P u e u lo m l p s o i e p d l l e r a p r a r a r t y e t e u s c s r h u . e a r . n e . g . e . . + + - - 0 i - 2 3 . 5 2 5 6 . . . 5 2 6 5 3 3 0 : : : = = = : : : : : 1 2 0 ~ 1 1 . . . . 4 9 2 8 0 S 1 0 + + - + 0 4 6 . 4 1 5 3 . . 4 . 4 8 6 4 5 : 6 _ = = :_ ; 1 2 0 2 1 1 . . . . 2 5 8 6 4 3 4 0 : * * I+ - + : - + - 0 2 2 6 2 . 3 2 . . . 5 4 4 9 6 4 2 = = 1 1 0 3 1 6 . . . . 4 6 3 0 : 6 7 0 j * + -4.i2-2S.53 +3:tHJ..:...2L04 This document page is primarily text-based, with no photographs, diagrams, or handwritten annotations visible. There are some small dark smudges and speckles across the page, but these do not obscure any content. The only visual element of note is the number "155" printed in the top right corner, likely a page number. The majority of the page is filled with dense, typed text, discussing the results of experiments, and there are no visible official stamps or forms. I+ - + : - + - 0 2 2 6 2 . 3 2 . . . 5 4 4 9 6 4 2 = = 1 1 0 3 1 6 . . . . 4 6 3 0 : 6 7 0 j * + -4.i2-2S.53 +3:tHJ..:...2L04 K Re n s e p e o j n e s r e k s to • q . ue . st . io . nn . ah . -e + 2 9 4 .7 .6 0 3 :: ::1 2 0 9 . . 7 ~ 4 6 : + l6.7S ~ = 10 .98 13.78 =~ 8 .9S Clinical grade • . . . . -0.05:::: 0.22 -0.11 0.20 -0.28 0.18 Figures represent the menn difft>rences ::::: the standard errors of the differences betwe<'n responses to single doses of LSD-25 ( Li mcgjk~) and responses to psilo· cybin (210 mcgjkg) on three separate occasions. + Indicates LSD-25 produced a greater response. - Indicntes psilocybin pt·oduced a gr('ateL· response. • Indicates significance < 0.0,). ** Indicates significance < 0.01. psilocybin ("direct" tolerance to psilocybin), and (-!) response to LSD after ehron..ic administration of psilo<·ybin ("cross" tolerance to LSD). The signs of the difft'rcnccs were so nrrangctl that a minus (-} sign indicated a dt'crenso in the mc;lsuremcnts after chronic n<iministrntion as compared with control, and a plus ( +) sign indiC'atccl nn increase. Since psilocybin has a shorter dmation of action than LSD, the dificrence:> (except clinical g:radc) were n.lso cYnluatccl, using ,·nlucs obtained nt the peak of both LSD and p=-ilocybin reactions rather than using the nrcn. (integrated time action curws) ns described n.uoYc. ln addition, the differences were <'"<lluat<'d h~· n. non-pnrnmctriC' rank order test for pairC'd observations (\VrLcoxo::-, 1!1-+fl). The :-i~nificnncc of the diffcrencc:5 by thc:>c :5tatbtical techniques :urn·cd well with thosc obtained by the t-tc·st on the timc-netion (area) figHI't•s, so only the differences obtained by th1.' arc;\ mcti101l an' rC'pmt(•(l in t.hi>l papet·. . .~ ,) e "\ ... ,,,.. .. I. . 'l'aLlo 6. ~J'oleranu awl cro&.s tolcranu, K:A-11crin~elll 1 c~:n • Arter t•»iluo:yi.Jiul:lorunknlly Allor J,HD chronlcully ~ :llfo,,~uro ("Direct J " , S t D ol craucu) ("Cro l' • • K ll " u c l y ol h o l .- n u llt'O) ("J) ' Ir } c 1d c i t i " 0 C l ) The image appears to be a page from a declassified document, likely a research paper or report. There are no photographs, diagrams, or forms visible. The most prominent visual elements are the page number "156" printed at the top, and a significant amount of typed text forming paragraphs and a section heading labeled "Discussion." There are also a few small, scattered handwritten marks or smudges that do not appear to convey substantial information. No official stamps, signatures, or redactions are present on this section of the page. 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