Doc 0000151772

.· 25 January 1960 Dr. Rudolf Blrc~er Sandoz Pharmaceuticals Sundcz, lnc. ,. New Jersey l~nover, Dear B1rc..i,er: L~. :t . We h~ve finally compl~e ted our study ~n tolerance to psilocybin and LSD-25 and cross-tolerance.bct\::een these <!rugs in five subjects, the earlier· study of Dr. lsbell on supplc~enting five otl1er subjects. The tables enclosed represent the data on all ten subjects • cor~ined. .t\s you t..ri ll note in Table 3, there· is no doubt that our subjects clcve lo9ed tolcrunce to LSD-25 ( l.S ncg/1\g}, and after they became tolerant to this drug, they exhibited cross toleranc.z .to psilocybin (l.SO r.:cg/kg), w!t..'-1 respect to all ceasures except possibly tl1e temperature-elevating effect of t.!'lc drun. .on t:1e otl1er hand, the for deve 1att~r evidenc~ lop~cnt of tolerance to p·silocybin is not so cor.:plete {alt.houghly strongly and on several measures {tereperature, susg~stive), blood pressure and knee jerk), the subjects reactive re~ined to LSD-25, chronic of psilocybin for aft~r a~~inistration seven days. - One possible reason for the failure to dewonstrate tolc~ancc to psiloc:,rbin and cross-tolernncc to LSD-25 on all ~casurcs. is suggested by the data in Table 1 Which indicate at t~at~ least with respect to their effects on pupillary size nnd responses to quest lonna ire, the doses of LSD-25 and r.a;·d~l psi!ccybin He used ~verc not equipotent-- i.e., LSD-25 (l.~ meg/kg) procuccd greater effects than psilocybin { 150 mco/kg), ar:d/or, the period of C:1ronic aC.."':l.lnistro.tlon of psilocybin l-.:ts too short. -- -· -) r· ·-.., . ' \ Since the ~~ention of t~lerance and cross-tolcr~ncc in ra93rd to psilocybin LSD-2,:, is o.f considezoable th.coretical ~nd s13ni.fiClncc, •r~c arc tl·dnriing rJr Going unothcr study~ with -larger dosas of psllocy.>in (possibly up to 250 ~cg/l~g, ;;1axir.al \.lose) and lona,zr cu:'a tlon or c!u·onic intoxication ( lJ.t days). To do thin !n the few months l still have remaining before my sabbatical to use pros~cct!vc ~ar·abroad, ~~will hav~ ten ne~·.' subjects un<.i begin t:te stu.uy Hi-thin ti:.lo \·Jee~ at tlv~ lu t~nt. Also, w"C ha·ve cu lc.J.la tee that in a d~i t ion to 'H~1n t. \;c lmve lf.:.ft of the su~ply of psilocybin you no 1dndly furnis:1;;:d a fe11t1 nonths ago, t.rc ~ould rc~!\.!.iro cbout 2.0 g1·un3 fo-. completion of cxper · t!1~ !m~nt. :t. r Ur-•.f crtxnate 1~··, \N <..:enr..o't bL!sin t:"!c £':pt.:r !ncnt unt l \Ye have the conplete supply,of on sincz do psilc~jbin h~nd3 ~a mu~t some The image is a web page with a black background adorned with a graphic of a vault door on the left and the text "THE BLACK VAULT" in stylized white lettering at the top. Below this, white text explains that the document was obtained from "The Black Vault," an online database of declassified government documents. It specifically mentions the "MKULTRA/Mind Control Collection" containing over 20,000 declassified CIA pages and provides a URL for download. The overall presentation is that of a digital portal or header for declassified information, using a vault motif to symbolize access to secret records. The document is a typewritten letter dated January 25, 1960, addressed to Dr. Rudolf Bircher at Sandoz Pharmaceuticals. In the upper left quadrant, a handwritten annotation in black ink circles the numeral "174". Towards the bottom right, there are two handwritten marks: a looping line above the letters "e" and "p", and below that, the designation "B-306". No other visual elements such as photographs, stamps, forms, diagrams, tables, or redactions are present. su~ply of psilocybin you no 1dndly furnis:1;;:d a fe11t1 nonths ago, t.rc ~ould rc~!\.!.iro cbout 2.0 g1·un3 fo-. completion of cxper · t!1~ !m~nt. :t. r Ur-•.f crtxnate 1~··, \N <..:enr..o't bL!sin t:"!c £':pt.:r !ncnt unt l \Ye have the conplete supply,of on sincz do psilc~jbin h~nd3 ~a mu~t some prr~l ir::ir:ary ~ssay~ of re ln.ti ve pot~r:.cy before car. . !!.li tt !ng oursGlves tc such a lcmr; anc. CC.j;~plicatccl <:;;q;~rlr;leHlal d~sigt .. Therefore, ~ tr!e d~c1 slon \;Jhct~'~r or not. to UI"ldcrtal-re th'3 neH study depends on ~~e possibility of J~ur being able to send us 2.0 r:rans of pslloc~'bin 'ltJi thin t.t!c. next t1.::o \-.'{;eks • l realize that this is an extraordinary request and that you may not hav~ th-:J.t :r:u_c.'l psilocybir. on. ~..a.nd. Ho'!,o.'-V~r# 1 shall be very grateful if you ~rill let ~c lmcu a!'l soan as possible tho prospects are. ~t Wt th r:1uny thar.l~:: for your ass! stance. past. &nd present., and resnrdo w1~~~cordia1 1 S1nc:?rc ly, Abraha:n ~:f.il~ler, !t..:J. Acting Director Enclosures \ - Table 1 Dlf!erences in Response to Control Doses of LSD and Psilocybin MEA SiRE DlFFE'RE.i~CZ IN RESPONSE Temperature / - 0.31 t 0.48 Pulse Rate +27.55 ± 13.52 Blood Pre/ ssure +34. 15 ± 16.23 Pupillary Size + 4.-54: 1.o3·:Hr:} ... Knee Jerk + 8.4.7 : 22.1.~0 Responses on Questionnaire +39.25 ± 12.30~~· Clinical Grade + 0.35 ± 0.2.5 Figures represent mean differences ± standard errors of the differences bet,JJeen means· of responses to ~ control doses of LSD-25 (1.5 meg/kg) and mean~ of responses to~ control doses of Psi 1 ocyb in (150 meg/kg). Note: ~~- : p < .02 {.'-1.!~5- : p < • 0 1 +, indicates LSD-25 stronger in effect than Psilocybin -, indicates Psilocybin stronger ln effect than LSD-25 -- .. . . . .... Table 2 . Differences in Responses to Placebo, 1.5 meg/kg or LSD-25, . and 150 mcg/k~ of Psilocybin on first and second controls. ,._ DRUG -~ l'vffi.l\SUR E Placebo ~-- LSD•25 Pslloevbin Temperature + o. 98 : _ - ·o • 63 + ~ 0.42 ·± 0.64 - 1.24 ± o.53·:s- ; Pulse Rate -11.53 ± 13.30 •12.62 ± 18.40 •19.60 ± 9.30 / Blood Pressure ~ - 1.10: 15.70 - 1.35 ± 12.70 -2.5.40 ± 11.60 Pupillary Size - 0.29 :f: . 1. 65 + 0.-52 ± 1.18 + 0.10 % 0.83 Knee Jerk ·12.56 ~ - 1.24 ± o.53·:s- ; Pulse Rate -11.53 ± 13.30 •12.62 ± 18.40 •19.60 ± 9.30 / Blood Pressure ~ - 1.10: 15.70 - 1.35 ± 12.70 -2.5.40 ± 11.60 Pupillary Size - 0.29 :f: . 1. 65 + 0.-52 ± 1.18 + 0.10 % 0.83 Knee Jerk ·12.56 ~ 11.90 -14.83 ± 21. 7.5 •17.88 t 18.70 Responses on Questionnaire + 0. 90 :f: 1.31 + o.6o ± 6.10 + 4.90 ± 9.65 Clinical 6rade + 0.10 ± 0.10 - 0.,30 t 0.20 + 0.20·± 0.41 #, Figures represent the mean differences ± standard errors of the differences between measurements on the first and second controls in 10 subjects. None of the differences except that for temperature change after psilocybin were slgnif!cant. . +' Indicates that the average measurement was increased on the second control, Indicates that it was decreased. • 1 * = p < .0$ /.J-·)cJ) ·~ J ,',I t.' Table 3 A) 'J Differences between Control Response to LSD-25 and Psilocybin and ";) flcsponse after Chronic Admlnlstratlon of either Drug. ~ ______________________ ____ e ._ ~~--------•- -~----------------------------·------------~----~------------~----------.-------.----------------------------~ After LSD. Chronlc~1.1y_ . After Psilocybin Cr1ronlcnl~.~v-------- t LSD J Psilocybin Psilocybin LSD "_To r.1eo.sure ( "Dl rect" To 1 era nee} ("Cross 1 era nee} I(''Dl rect Tol era nee) ("Cross" Tolerance) H It)- 'erature - 1. • 93 ± 0.79* 1) - 1.85 t o.6tiHJ 1.87 ± o.l~7*-"H!-f- o.5o t o.$9 2) - 0.62 :t o.67 P-> - o.63 1 o.lt-7 Pulse Rate 1-47.70 t 8.1~5-~*l" .. '., -11.05 ± 16.60 •22.20 :t 11. 90a -33.0$ t lO.ijt** Olood Pressure I -79.80 ± 1.5.75~HH~ I -30.15 :t: 7 • )JiHH1- -)).55 t 10.15**~· -2). 70d: t5. 30 Pupillary Slzel-11.75 ± 1. 6l~HHt - 5.77 ± l.,So{HHt - ).17 ± 1.2o* 1- 4. 72 :1: 1 • J.~s·· - , · -~ t * · . ' Knee Jerlt -71.16 :!: 23.55i~ -67. m~ :!: 16. 97~m ' ·52.69 ± lO.OJ~·:Hfo f-t~l.79 t 19.,Sla l ftcsponscs on -21.85 5.52:: 15 Questionnaire -6).00 :!: 18.1l('~~tl- '. t -1 6 • 9 5 ;t: . 1. 69 b . - 1 • 10 :1: 19 • 20 ' . H . I (. Clinical Grndel-.1.65 ± o. 32"f-** - 1 • 3.5 t · 0 • 17'' ,r .. - o. 95 :t o. 23 -t}Jf->1- - t.l~o ± o. 32 .·~ VJ.~ .... er 1, Indicates· differences obtalnccl, using The document is a typed letter, with the sender's address and recipient's name at the top. There are no photographs, diagrams, or forms visible on the page. The only handwritten annotation is a numerical code, "B-305," located on the bottom right corner. There are no official stamps or redactions present. The page appears to be a standard memo or letter format. 1 • 10 :1: 19 • 20 ' . H . I (. Clinical Grndel-.1.65 ± o. 32"f-** - 1 • 3.5 t · 0 • 17'' ,r .. - o. 95 :t o. 23 -t}Jf->1- - t.l~o ± o. 32 .·~ VJ.~ .... er 1, Indicates· differences obtalnccl, using first control values, 2, Indicates differences obtained, using second control values . (' Figures represent the mean differences t standard errors between the averaoe of the two controls (with the exception of 1 and 2 which were slgnlflcantly·dtfferent) and the values found when patient was tested with LSD-25 or psilocybin after recclvlng either drug chronically . ,, * , = P < .o5 a, : P >= .o5, < .10 ** ' ':. p < • 02 b, • t 2.20 ***•:: p < .01 (at t = 2.26, P : .o5) This document appears to be a page from a scientific report, likely detailing experimental results. It contains **Table 1**, titled "Differences in Response to Control Doses of LSD and Psilocybin," which presents quantitative data on various measures such as Temperature, Pulse Rate, and Blood Pressure, along with corresponding differences and standard errors. Below the table, a **note** explains the statistical significance denoted by asterisks and the direction of the effect indicated by plus and minus signs. There is also a **handwritten annotation** on the bottom right corner, "B-304." No photographs, forms, diagrams, or official stamps are visible on this page, and there are no apparent redactions or obscured content. The document contains a table titled "Table 2" which presents declassified data on differences in responses to placebo, LSD-25, and psilocybin. The table details measurements such as temperature, pulse rate, blood pressure, pupillary size, knee jerk, and responses on a questionnaire, with associated numerical values and standard errors. Below the table, explanatory notes define symbols used to indicate increased or decreased measurements and statistical significance. A handwritten annotation "B-303" is present in the bottom right corner, along with a partial redaction of what appears to be a stamp or marking in the top right. There are no images or diagrams. The page contains "Table 3" which details differences in responses to LSD and psilocybin between control groups and experimental groups. The table presents numerical data, including means and standard errors, for various physiological and psychological measures, indicating statistical significance with asterisks. Handwritten annotations include a numerical code "B-302" in the top right corner, and notations for different levels of statistical significance. There are no images of people or experimental equipment visible. The document appears to be a declassified governmental report, as suggested by the structured format of the table and statistical notations.