Doc 0000151824

DEPARTMENT OF HEALTH, EDUCATION. AND WELFARE PUBLIC HEALTH SERVICE 26 May 1958 Na&itlul lutltQItet •-I •We lll&l Heal~ Acl4ictloa Ceater u.s. hbllc K~ Sema KoePtw Lez!apa, ~aaaackr \ t . II i ' ~ ! ____ .. ... -·. ......... --~_---P.·-·· ~- ·-···--~---;-~ .. -.:...·--..-4-· ~ - -· The National Institute of Mental Health (Mr. Gordon Klovdahl) has informed me that he has asked the NIH budget office to forward the request for renewal of ·the synthetic substitutes for codeine project to the Office of Naval Research. The amounts requested will be identical with those given in the budget that 1 left. with you. The Institute has requested an increase in their appropriation in the hope of being able to take over some of the personnel assigned to this project, but this matter cannot be settled until the budget for fiscal 1959 is known exactly. In case they do take over any of the personnel then arrangements will be made to return whatever part of the funds that will not be required. Please let me know if this meets with your approval. 1 am enclosing a print of the slide that 1 used in a Seminar at Bethesda. Although of not great interest, it does show the comparative psychotomimetic potencies of all the compounds I have tested for the Sandoz Company. I currently have been working with the Japanese compounds from the Taked~Company {agroclavine and dihydroagroclavine). Neither compound has shown any psychotomimetic potency in doses ranging up to . 50 mcg./kg. of body weight. On the contrary, agro clavine may have sedative properties. Another compound ·------·--··--· --- ~-CbJC~! Page 2 obtained from Eli Lilly and Company, in which the acid ~ · amide group of tSD has been replaced with the methyl and a hydroxyl, has also sedative rather than psychotomimetic properties.. 1 am going to try a.grocl,avine and the Lilly compound as possible blockers of LSD. 1 will be leaving June 5th for an extended trip to the West coast and will not return to Lexington until the middle of July. With kindest personal- regards, Sincerely yours, M.D. Hl :lw Enclosures {3-3J' Design.· A randomized, double-blind design ·Has used in both ex?erir::ents. In both, t".·/O drug combinations \·!ere uszd: BOL plus LSD, and BOL placebo plus LSD. The combinations of BOL placebo plus LSD placebo a!ld of EOI: plus LS:; pl2.cebo \·Jc:re not done because previous data indicate there The image presents a stylized graphic with text overlay. On the left, a large, metallic vault door is depicted, featuring intricate mechanical details like dials, levers, and what appear to be multiple locking mechanisms. The vault has a cool, blue-toned illumination, suggesting a modern or digital representation rather than a physical one. To the right of the vault image, large, stylized white text reads "THE BLACK VAULT". Below this title, smaller white text provides information about the document's origin from "The Black Vault," an online database of declassified government documents, specifically mentioning the "MKULTRA/Mind Control Collection" and its source as the CIA. The text concludes with a website address in yellow: "http://mkultra.theblackvault.com". There are no photographs of people, locations, equipment, or subjects, nor any handwritten annotations, signatures, official stamps, forms, diagrams, schematics, organizational charts, tables, structured data, or redactions. The visual elements primarily serve to brand the document's source and highlight its connection to sensitive historical information. The document is a typed letter with handwritten annotations. At the top, there are handwritten numbers "132" circled and "(6x3)" also circled. The letter is dated "26 May 1958" and appears to be from the "DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE". There is a seal visible on the left side, and text below it identifies the sender as the "National Institute of Mental Health". The main body of the document is typed, discussing requests for budget renewal and research findings. In the bottom left corner, there is a handwritten notation "C-733", and in the bottom right, "B-30" is written. There are no photographs, diagrams, or visual evidence of experimental procedures. :lw Enclosures {3-3J' Design.· A randomized, double-blind design ·Has used in both ex?erir::ents. In both, t".·/O drug combinations \·!ere uszd: BOL plus LSD, and BOL placebo plus LSD. The combinations of BOL placebo plus LSD placebo a!ld of EOI: plus LS:; pl2.cebo \·Jc:re not done because previous data indicate there 1.1as no change of significant degree after either combination. r-:easurements. Sys.tolic blood pressu~~J pupillary siZf:! Z:n:d threshold for l<.neej·~rl{s ..,Jere determined twice before and at hourly intervals for eight hours after LSD by methods previously described. A modification of the Jarvil~-..-".bra:n.son questionnaire 1.:.-l/2, .... ras given t\·lice before and 1/2, 1-l/2, 2-1/2, 3-1/2, 5-1/2, 6-1/2 and 7-1/2 hours after LSD. Short mental status examinations ,.,ere conducted at these times, in order to assign a "clinical grade" to the reaction. P.nalysis of Data. Areas representing.change from preclrug controls were cal~ulated for data on"blood pressure,.patellar reflex and pupillary size. The number of questions scored positively after LSD '\·rere counted, eliminating any which vLere also scored positively before LSD. Grades ~rere assigned according to the system previously described. The usual statis tical treatments were performed on .the data. The t-test for paired observations and non-parametric tests (Wilcoxon) were used in evaluating the sionificance of results. [J -J .,...._- . RESULTS 56:JQ· ~xperiment The results of this experiment are sho\·m in tables 56-0l and 56-D2. All aspects of the LSD reaction \•tere reduced but not to a statistically significant degree. This result is similar to that. observed in our first experim~nt in \•Ihich a larger dos~ cf LSD 1:1~.s used. ~xneriment 56-'3.. The results are shot:tn in. tables .56-El through .56-~3. Significant reductio~s (t-test) vrere observed· , in every aspect of the LSD reaction except for the-patellar refle;<. The non-parametric tests \vere also significant for every aspect except the clinical grade. Time course of the LSD reaction (table 56-~3) \-laS not greatly altered by BOL, despite the attenu?tion. eviden~ DISOJSSION The results show that pretreatment with BOL for five days does reduce the intensity of the reaction induced by 1 mcgm./kg. of LSD. The results strongly suggest that the longer BOL is-administered the greater is the reduction in intensity of the reaction. Such result.s are more compatible \'ii th the development of sone degree of cross ·tolerance between BOL and LSD than with direct comp~tition of these drugs for receptor sites. The degree of cross tolerance to LSD conferred by pretreatment Hith BOL is, is the reduction in intensity of the reaction. Such result.s are more compatible \'ii th the development of sone degree of cross ·tolerance between BOL and LSD than with direct comp~tition of these drugs for receptor sites. The degree of cross tolerance to LSD conferred by pretreatment Hith BOL is, ho1....rever, not complete. S:ven after • five days pretreatment \vith BOL significant changes over control occurred in blood pressure, pupillary size, and mental responses. There \·ras arso .a marked variation bet\veen indivi- duals. In several patients cross tolerance appeared to be al1r.ost co1:1plete; in others, only partial tolerance \-Jas observed. CONCLUSION Pretreatment \vith 1 r.1g. of BOL threz times daily for five 'days causes a significant reduction in intensity of the reaction induced by 1 mcgm./kg. of LSD, "'·''"'L'=' C6 Dl .L.M..O .... :;; - • Attempted Bloc1{ing of· Reaction Induced by 1 mcgm. of LSD By of 1 mg. of BOL t.i.d. for Tv;o Ddys. A~~inistration FZASURE BOL AND LSD EOL PL-A-C·3-B-O- . . . A . I' , 'rD _ .L.S_D- Patellar Reflex 5.2 ± 1.38 5 .c / :t 1. 78 Pup i 11ary Size 14.6 ± l. .56 18!5 ± 2.12 -- Systolic Blood Pressure 77·4 ::::: 16.7 109.3 -.- 12.2 Questions .53 ± 17.6 9.3 - 24 .• 9 Grade 2.0 ± 0.4 2.9 :::': : 0.3 -- (3-<. - TABLE 56-02. Number of Fatiznts in Hhich Change A.fter BOL Placebo Greater Than After BOL. 1:[ci.S Kneejer}~ 5 3 0 Pupillary Size 3 0 . Systolic Blood Pressure 6 2 0 Number of Questions 7 1 0 Grade 5 1 2 - Pag~ c ·TABU: $6-Ei. Attempted B1oc}~ing of Reaction Induc~d by 1 mcgm./kg. of LSD By Five Days Pretreatment 1 mg. of BOL t.i.d. ~rtth - BOL PJ!D LSD BOL P.LAC3BO AN-D LSD Patellar Reflex 5.08 ± 1. 7~- 6-.6 ± 1.}3 . . Pupillary Size 0. ,.;,..;.:..). ::::: 1.65 15.97 ::: 1.78 S~stolic Blood Pressure .~, 0 • 3 ~ . - . = :. - 11.8 C ~ C ' ) . v C ± 17.1 NU!"lber of Questions 28 ± 1 ;, 66 ± 13 -r Cl inica 1 Grade 0.9 ± 0.45 2.0 ± 0.36 . (J-2.( 9 ?as~ T.ABLE 56-:2. Number of Patients in Change After ~'lhich BOL Placebo !/las Greater than ;...rter BCL. I·';"':'J\.SUR3 Kn eeJ . er z , t 8 2 0 Pupillary Size 8 2 The page appears to be a single-spaced typed document with handwritten annotations. Visually, there are two circular ink marks near the top, one black and one slightly faded. To the left of the text, there is a handwritten annotation enclosed in parentheses, "(6)3)". On the right side, the page number "Page 2" is typed. Further down, a handwritten signature is visible, followed by "Harris Isbell, M.D." and "Director". The bottom right corner of the page has a handwritten mark, "B-38", and a small section of the bottom edge is obscured by a black bar. ;, 66 ± 13 -r Cl inica 1 Grade 0.9 ± 0.45 2.0 ± 0.36 . (J-2.( 9 ?as~ T.ABLE 56-:2. Number of Patients in Change After ~'lhich BOL Placebo !/las Greater than ;...rter BCL. I·';"':'J\.SUR3 Kn eeJ . er z , t 8 2 0 Pupillary Size 8 2 0 Systolic Blood Pressure 8 2 0 Number of Questions 8 --2 0 Grade 6 1 - -; - - - ..; .. .,L .... !:.:6 '""'3 T 1--...u -~ ;,.,J - c., • ~ Time Course of LSD Reaction after Pretreatment vii th BOL or BOL Placebo for Five ILys. Size Pupi~lary Hours after LSD Treatment c 1 2 3 4 5 6 7 8 BOL 4-2 5-7 $.8 5.8. 5.6 5-4 5.3 5.2 . .5.2 BOL Placebo 6.1 6.8 6.8 6.6 6. 1 6.1 5.9· ~-· 2 Systolic Blood Pre~sure BOL 106 111 111 111 114 112 112 114 11.5 EOL Placebo 104 116 117 115 119 119 118 114 116 Number of Questions Hours after LSD .5-!LU_-..... 112 1-1/2 2-112 3-1/2 4.-112 1/'--2_ __7_-_ 1-'-/_2 , BQL 0 5.4 Oo. .. ) .. 2.1 0.7 BOL Placebo 0 . 7.9 16.9 17 = . = 0 = == 1 = 2 = . = 2 = ===6=.=~= ====r.= 3 = - = 3 = === 1 = . : 0 == ==-== 0 == .5 == Figures are of results on 10 patients. ave~ages BOL dosage was 1 mg. orally three times daily for five days prior to LSD plus 1 mg. two hours prior to LSD. LSD dosage \'lias 1 mcgm./kg. C ~ Control (predrug) measurement. {J-2. <; This page is a typed document with a simple black-and-white presentation. There are no images, photographs, or diagrams present. Handwritten annotations appear in the bottom right corner, reading "B-3". A faint horizontal line is visible near the top of the page, and a circular ink mark is present near the top center. The text describes research methodology, including experimental design, measurements, and data analysis, suggesting a scientific or experimental context. The document is a typed page, appearing to be part of a scientific report or research document. There are no photographs or images of people, locations, equipment, or facilities. The primary visual content consists of text organized into sections labeled "RESULTS" and "DISCUSSION." There are some handwritten annotations, most notably a diagonal line and what appears to be "B-3" at the bottom right, as well as a horizontal line and what looks like a "+ " symbol near the top right. A faded circular stamp or mark is visible near the top center. No official stamps or redacted content are immediately apparent. The visible content of the document is mainly text, suggesting it's a report or findings derived from an experiment. There is no photographic imagery of people, locations, equipment, or subjects. The page contains a handwritten annotation in the bottom right corner, reading "B-20", which may be a document identifier or subject code. There are no official stamps or seals visible. The page appears to be a typed document with a "Page 5" designation at the top right. There are no forms, diagrams, schematics, organizational charts, tables, or structured data visible, nor are there any redactions or obscured content. No visual evidence of experimental procedures, equipment, or facilities is present. The image displays a typed table with the heading "TABLE 56-D1." The table presents data categorized by "MEASURE," "BOL AND LSD," and "BOL PLACEBO AND LSD," with rows for "Patellar Reflex," "Pupillary Size," "Systolic Blood Pressure," "Questions," and "Grade." Each measurement includes a numerical value and a standard deviation. Handwritten text "B-2" appears in the bottom right corner. The text is mostly clear, with no visible photographs, stamps, or diagrams. The image displays a declassified document from the MKUltra collection. The page features a table titled "TABLE 56-D2," which presents data categorized by "MEASURE" and then by "CHANGE GREATER," "CHANGE SHALLER," and "NO CHANGE," with numerical entries for each. There are no photographs, stamps, signatures, or handwritten annotations visible, nor are there any redactions or obscured content. The layout suggests a formal report or data compilation characteristic of scientific or administrative documentation. The document presents a table detailing the results of a study titled "Attempted Blocking of Reaction Induced by 1 mcg/kg of LSD by Five Days Pretreatment with 1 mg of BOL t.i.d." The table includes measures such as Patellar Reflex, Pupillary Size, Systolic Blood Pressure, Number of Questions, and Clinical Grade. Data is presented for two groups: "BOL AND LSD" and "BOL PLACEBO AND LSD," with numerical values and standard deviations listed for each measure. Handwritten annotations are visible in the bottom right corner, including "B-20," and there is a single black dot, possibly a hole punch mark, near the top center. The page is also marked as "Page 6." The document is a single page with a title "TABLE 56-32." and a subtitle "Number of Patients in Which Change After BOL Placebo Was Greater than After BCL." It contains a table with columns for "MEASURE," "CHANGE GREATER," "CHANGE SMALLER," and "NO CHANGE." The rows list "Kneejerk," "Pupillary Size," "Systolic Blood Pressure," "Number of Questions," and "Grade," with corresponding numerical data in the columns. A handwritten annotation "B–25" appears in the bottom right corner. There are no photographs, stamps, diagrams, or redacted content visible. The document contains a single page of text, primarily consisting of a data table. The table is titled "TABLE 56-B3" and presents research data on the "Time Course of LSD Reaction after Pretreatment with BOL or BOL Placebo for Five Days." It includes rows for "BOL" and "BOL Placebo" treatments, with columns for "Pupillary Size" and "Systolic Blood Pressure" measured at various hours after LSD administration, and a section for "Number of Questions." Below the table, there are notes explaining the dosage and a definition for "C: Control (predrug) measurement." A handwritten annotation, "B-24", appears in the lower right corner of the page.