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g ,. 0 STlD l ES CN TI-iE D I ETHYLN.H D£ GF LYSERGIC ACID. Ill. EFFECT GF PHENGXYBENZA'vilNE CN LSD-REACT I Q\1 IN lvtAN. By Harris tsbel I, M.D. C. R. -logan and E. J. Miner From the U~ S. Department of Health; Education, and W~tfare Pub! ic Hea I th Service Nat-ion a I I n s t it u t e of Men t a I He a I t h Addiction Research Center Lexington, Kentucky • -·--- --·· ------------------------- ---------- . ----- -- ------ ----- .. ._. . - ·4--. ----------. ·. ....,.,...-.~~-···· .;~~ _.;.-._-.~---- \ i ·' STlDIES CN THE DIETHYLAMIDE OF LYSERGIC ACID • . ....... l II. EFFECT OF PHENJXYBENZAMINE ON LSD-REACTION IN WAN. -- A number of the signs and symptoms observed after administration of LSD-- pupillary dilatation, elevation of blood pressure, gooseflesh, anxiety, sense of gastrointestinal oppression, etc. --suggest hyperactivity of the sympathetic (adrenergic) ner~ous system. Roth I rn and coworkers fl) have postulated that LSD has central vegetative Cautonomicl effects. Chlorpromazine partially ameliorates the· LSD ·reaction {2;3,41, and since chlorpromazine is a peripheral (5) and possibly a c~ntral (6) adrenergic blocker, one might hy~otheslze that ameliorates the LSD reaction by virtue of chlorpromazin~ central adrenergic effects. bloc~ing !.ill· !.±. !.!..• ~ecentty Elder (7) and Gogerty Cg) have presented some interesting f'iodings in ex::'er!m~nta! anir::a!s. Pretreatment with chlorpromazin~ reduces LSD-induced hyp~rtherm.ia . . . . . in rabbits ·and nfe.l ine-man ian in· cats.. If l.SD is given to. rabbits within two hours after reser;>ine, hyperthermia is accentuated. At this particular release of norepinephrine tim~, ( 9 ) a n d s c r o t on i n ( I 0 l f r o.":l b r a i n i s o c c u r r i n g • t f LSD i s g i v en .. ' ."'".~~-· . ..·. 'J • .... .. -- . --- . - ·.·' '~) \ ten hours after reserpine (when norepinephrine and serotonin ,· have·been depleted) LSD effects are attenuated. Most important, ) ' phen~xybenzamine (dibenzylineJ, an adrenergt~ blocker with no known central effec~s, attenuated t1fel ine-manian induced by LSD. Since very large doses of LSD are required to induce definite behavioral changes i~ animals, and since the relation ship of any behavioral change induced in animals to psychotic symptoms tn humans is always doubtful, tt seemed The image displays a portion of a document with a prominent graphical banner at the top, featuring the words "THE BLACK VAULT" in a stylized font against a dark, possibly blue-tinted background. To the left of the text is an illustration of a vault door, complete with a complex locking mechanism and circular dials, rendered in shades of grey and highlighted with blue light. The main body of the image contains a block of white text that explains the origin of the document as being from "The Black Vault," an online database of declassified government documents, specifically referring to the "MKULTRA/Mind Control Collection" and its relation to the Central Intelligence Agency (CIA). Below this explanatory text, a bright yellow hyperlink is presented: "http://mkultra.theblackvault.com". There are no photographs of people or locations, handwritten annotations, official stamps, forms, diagrams, tables, or evidence of experimental procedures visible in this segment of the document. The content is purely textual and graphical in nature, serving as an informational header and source attribution. This page is a typescript document with handwritten annotations. The typed text details a study on the effect of phenoxybenzamine on LSD reactions in humans. There are two instances of handwritten notations: a circled "110" in the upper right corner and "A-391" in the lower right corner. There are no photographs, stamps, forms, diagrams, tables, or redacted content visible on this page. adrenergt~ blocker with no known central effec~s, attenuated t1fel ine-manian induced by LSD. Since very large doses of LSD are required to induce definite behavioral changes i~ animals, and since the relation ship of any behavioral change induced in animals to psychotic symptoms tn humans is always doubtful, tt seemed important to study the effect of phenoxybenzamtne on the LSD psychosis in a ma n • The pur p os e of t h e pres en t ·report i s t o pres en t · d t a showing that pretreatment with phenoxybenzamine did not alter significantly the mental symptoms produced by LSD in human subjects, de~pite d~finite evidence of peripheral adrenergic blockade. GENERAL METriO')S Subjects. All were former ~orphine addicts serving sentences for violation of narcotic laws who volunteered for the ex~eriments. All were physically healthy adult Negro males who presen-ted no evidence of ·p·sychosis on ·psychiatric examination. - ' •. .. .... .. - -------~-- .. ' · Druqs. ·LSD tartrate and LSD placebo administered w~re orally ln solution to patients in the fasting state. Phenoxy- and phenoxybenzamine placebo were given in capsules. ben~amlne L-Epinephrine HCL and epinephrine placebo were administered subcutaneously. Specific details on dosage are gtven under the particul•r experiments. Experiments were "double-blind"-- neither the patients nor the ~bservers knew what drugs had been given. In evaluating the effect of phenoxybenzamine on the LSD reaction the following combinations of drugs were administered at intervals of seven ddys in randcm b~lanced or~er: LSD placebo plus phenoxybenzarnine LSD phenoxybenzamine placebo, LSD plus ~lacebo, ~Ius phenoxybenzamine, and LSD placebo plus phenoxybenzarnine. Methods of Measure~ent. Intensity of the LSD reaction was assessed by methods previously described t111. The following observations were obtalhed at intervals twice before and h~urly eight times after administratJcn of LSD, or LSD placebo: pupillary slze, threshold fqr kneejerk, systolic blood pressurz, number of positive answers on a modification the o~ qu~stionnalre de'lised ·by Abramson ll_ 21_ ... {12),_ dnd the clinical grade, based ·on a-short me:1tal status exa;nination {11). Areas under tlme- action curves were calculated by the method of Winter and Flataker C!31 and resu+ts express.cd as mm. hours <pupilsl, ·- ' - mm. hours (blood pressure), and degree-hours In {kne~jcrkJ. .. addition, rest1ng pulse rates, resting systolic blood pressures, and pulse rates and systol lc·p~essure aft~r standing for one minute were determined and time-action areas calculated. These .~ latter measurements could not The document is a typed page of scientific text with a handwritten annotation in the bottom right corner, "A-390". There are no photographs, forms, diagrams, tables, stamps, or redactions visible on the page. The text appears to be research notes or experimental findings related to the effects of Lysergic Acid Diethylamide (LSD). There is no visual evidence of experimental procedures or facilities. and resu+ts express.cd as mm. hours <pupilsl, ·- ' - mm. hours (blood pressure), and degree-hours In {kne~jcrkJ. .. addition, rest1ng pulse rates, resting systolic blood pressures, and pulse rates and systol lc·p~essure aft~r standing for one minute were determined and time-action areas calculated. These .~ latter measurements could not always be obtained (experiment 4) due to postural hypotensicn·with resultant faintlns on standing. Effects.of epinephrine were assessed by measuring pulse rate and_systolic and diastolic blood pressure at the fol-lo'wlng interv~ls: 10 minutes before, and immediately before subcutaneous injection of epinephrfne or epinephrine placebo; 5, 10, 15 20, 1 30, -40,·. and 60 minutes after injection of epinephrine ·or placebo. Ttrne-action areas were also calculated for these measurements. Ex per i men t I • E f f e c t of I m 9 ./kg. c f ? he-n ox v benz am i n e Reaction lnduced by 0.5-J.O mcom./kg. of LSD. Phenoxybenzamine or phenoxybenzaminc placebo was admi_nistzred orally in capsules .. . ~ at 6 a.m., and LSD or LSD placebo orally in solution at 8 a.m., thus allowing three to four for adrenergic blockade to h~urs develop prior to expected pe~k of LSD effects. Four p~tien7s . . '' ' r e c e i v e d c or.1 b i n a t i on s of I • 0 mc sr;, • of ph e n ox y b en z a i':'l i n e Q r phenoxyb~nzanlne pla6ebo with ~.5 ~cgm./kg. of LSD.or LSD placebo.· Since the number of subjects was s:nall, and since the resul b ct were. similar ~o the group that receiv~d 1.0 mc~m./kg·. LSD, the results will not be prese1ifej in detail. ------- --- -------·---- -- ------------- ------ -~ 4-J!-7 •. ,.-· .... f Six patients received co:nbinarions of 1.0 mg./kg. of phenoxybenzamine or p:henoxybenzamine pl~cebo with. 1.0 mcg.n./ks. of LSD or LSD placebo. Resul·ts· are presented in table f. Both ------ · the number of answers and the cl lnica I grade were less after the combinalion of LSD plus phenoxybenzamine, as compared with LSD alone. The differences.,- however, were not s_tat.tstically signi~icant. PhenoAybenzamine dtd reduce pupillary dil~tation significantly ~fter LSD, but had no effect en the LSD-induced r i s e i n res t t n g s y s t o l i c b I o ad pres. s u r e o.r This document is a scanned page of typewritten text, likely a research report. There are no photographs, diagrams, or forms visible. The page contains some handwritten marginalia, most notably a designation "A-389" in the lower right corner. There are also a few small black dots, which could be ink smudges or marks from the scanning process. The text itself discusses the effects of LSD and phenoxybenzamine on human subjects, detailing experimental design and findings. There are no official stamps or redactions visible on this particular page. differences.,- however, were not s_tat.tstically signi~icant. PhenoAybenzamine dtd reduce pupillary dil~tation significantly ~fter LSD, but had no effect en the LSD-induced r i s e i n res t t n g s y s t o l i c b I o ad pres. s u r e o.r on t he dec rea s e d threshold for the kneej2rk. Mtbsis, postural hypotension, and postural tachycardia indicated that some degree of peripheral adr~n~rgic blcckade hdd occurred after phenoxy~enzamine alone. LSD was an effective antidote for the postural hypotension after this dose of phenoxybenzamine. f. Experim~n_u. Blocking of Epinephrine by J.O mg./kp.·cf Phenoxybenzamine. Since ·no definite attenuation of the LSD reaction was observed in the p~evicus experiment, it seemed wise to determine whether the.dose of phenoxybcnzamine u~ed would significantly alter the response to epinephrine. Four pa_tients .,.,;er~ "challeng~J" with 0.4 to 0.6 mg./70 kg. of eptn~phrine ·s~b~utaneously before and three hours after ingestion of 1.0 mg./kg. of phenoxybenzam.ine. R~sults were controlled by placebo injections before and aftir phenoxybenzamine. rA v' •easure- ments ·wer~ those described above under _ge~er~(_methods. .. ' .... ..i. --~- Results are shown in table 2. As expected, no blocking ,. of the, increase in pulse rate. induced by epinephrine was !i .. observed after phenoxybenzamine. Ri~e in svstol ic blood j l pressure after epinephrine was reduced by phenoxybenzamine, but the reduction was not significant statistically in this small sroup. Th~ decrease in diastot lc pressure after ~pinephrine was enhanced after phenoxyb•nz~mine. These results indicated that some degree of adrenergic blockade was present. Experiment 3. Blocking of Epinephrine by 2.5 mg./kg. of r.o Phenoxybenzamine~ Eight patie~ts received 0.5, 1.0 and mg./kg. [total of 2.5 mg./kg.l of phenoxybenzamine at 26, 13, and 3 hours prior to challenge with 0.6 mg./79 kg. cf epinephrine. A second test with epinephrine was carried out. five hours after .the last dose of pher.oxybenzamine. The resul-ts are shown in . table 3. A definite diminution in the rise in systol tc pressure after epinephrine was observed five hours after the last dose of phenoxybenzamlne·-as well as a marked enhancement of the decline in diastolic blood pressure aft~r both test ·doses cf epinephrine. ln addition, alI patients were unable . . . to ·stan~ quiitly for ~ore than~- minute wltho~t becoming dizzy or f~intlng. Since these findings were compatible with a ·considerable degree of adrenergic blockade, this dosage of dibenzyl ine was decline in diastolic blood pressure aft~r both test ·doses cf epinephrine. ln addition, alI patients were unable . . . to ·stan~ quiitly for ~ore than~- minute wltho~t becoming dizzy or f~intlng. Since these findings were compatible with a ·considerable degree of adrenergic blockade, this dosage of dibenzyl ine was used in experiment 4. -, . ..... Exoertment 4. Effect of 2.5 mg./kg. of Phenoxybenzamine (Dtvtded Doses 1 on the LSD-Reaction. Ten patienfs received <I 0.5~ 1.0 and 1~0 mg./kg. of phenoxybenzamine (Dr phenoxybenza- . mine placebo) 24 II, and 2 hours prior to 1.0 mcgrn./kg. of LSD. 6 Results are shown in table 4. Although the effects of phenoxybenzamlne were so pronounced that 5 of the patients fainted on standing for less than minute, there was no on~ reduction in the number of symptoms reported or in the intensity (cl tnical grade) of the reaction after phenoxybenzamine combined with LSD. A significant reducfion in pupillary diameter was noted but the other indicators of LSD effect, including the rise in systolic blood pressure, were unaffected. LSD tended to antagonize the effect of phenoxybenzamine on the pulse rate when standing. '· DISCUSS ICN No definite evidence of .a}tentJation of the. LSD-induced mental symptoms by phenoxybe~zamine was observed in the experiments described above. l t hardly see;ns I ikely that this ·could be due to tnddequate dosage of phencxybenzamine, since signs of a considerable desree of adrenergic blockade were present after phenoxybenzamine lmiosis, attenuation of parti~l . .. • j - ; the epinephrine-induced rlse in systolic blood pressure, accentuation of epineph~ine-Jnduced drop in di~stol ic pressu~e, and marked postural hypotension and.tachycardial •. ,. c:ven though the adrenergic blockade may not have been complete, the doses of LSD used were small, so some evidence of attenuation of the mental symptoms should have been detected. Failure of phenoxybenzamine to block the mental changes ~aused by LSD might indicate that the LSD reaction is not mediated adrenergically, or that phenoxybenzamine lacks centrat adrenergic blocking actrons. ·Stnce r61~ of epinephrine and/or as norepinephrine central synaptic transmitters is strrr speculative, these alternatives cannot be assessed at the present time. Failure to confirm amelioration of the LSD•reJction 'observed in animals after phenoxybenzamtne emphasizes that care t s n e c e s s a r y i n ex t r a p o I a t i n g be h a v i or a The document is a typed page of text with some handwritten annotations. The text describes a scientific experiment involving LSD and phenoxybenzamine, detailing the administration of drugs, experimental procedures, and measurement methods. The annotations include a handwritten "A-388" in the lower right corner. There are no photographs, official stamps, forms, diagrams, tables, redactions, or visual evidence of experimental procedures or equipment. The document page contains handwritten text that appears to be scientific notes or research data. There are no photographs, diagrams, or organizational charts visible. The page does include a handwritten annotation in the bottom right corner, "A-387", which could be a document identifier or project code. There is no visible evidence of experimental procedures or equipment as the content is purely text-based. The page also contains a few scattered black dots and smudges, but no official stamps or redactions are apparent. the present time. Failure to confirm amelioration of the LSD•reJction 'observed in animals after phenoxybenzamtne emphasizes that care t s n e c e s s a r y i n ex t r a p o I a t i n g be h a v i or a r c h a n g e s i n a n im a I s t o mental symptoms in man. SU.NA~Y 1.0 mg./kg.· of p·nenoxybenzamine or 2.5 mg-~/k·g. of phenox'/- b e n z a.m Tn e . ( d i v i d e d i n f h r e e c o s e s 1 d i d n o t a t t en u a t e s i Dn i f i c ~ ;: t I 'I mentaf changes induced by 0.5 to 1 •. 0 mcgm./kg. of LSD-25 • .. • • .• . -~-·. ---'\., - ··-" REF EREf\CES ,. I~ Rothlin, E., Cerletti, A., Konzett, H., Schalch, W. R., )_ and Taeschler, M.: Zentrale Vegetative LSb-effekte. Experientia .!,g,: (4} 154, 1956. 2. Hoch, p. H.: Experimental Psychiatry. Am. j. Psychi4t. - Ill: 787-790 CApr.J 1955. 3. Schwarz, B. E., Bickford, R. G., Rome, H. P.: Reversibility of Induced Psychoses with Chlorpromazine. Proc. _ - Staff Meet. Mayo Ctrn. 30: 407-417 lSept. 2} 1955. . 4. Isbell, H., and logan, C. R.: Studies on the Diethylamide of Lysergic Acid. I I. Effects of Chlorpromazine, Azacyclonol and Reserpine on the Intensity of the LSD-~ea~tron. A.M.A. Arch. N~urol. & Psychiat~ 12: 350-358 {Apr. 1 1957. s., 5. Courvoisier, Fournel, J., Ducrot, R.,, Kols~y, :. . t., and Ko~tschet, P.: Prcprietes phcrmacodynarniques du chlorhydrate de cloro-3-(dimethylamlno-3-propyl )-tO-phenothiazine (4.560 R.P. l. Arch. lnternat. de Phermacodyn. et de·therap. 2,1: 305-361, 1953. 0- • Be n v-""' '11 e •. ~ r· • ·, • , -nell , ~ ," ' • "~ .... o...J.~ • u • . , ~ · b ~ · ' • , r ~o : . - :~ •• • Tonus sympathique et acfivite ele~trique corticale~ E'EG C I in • . . i. , G os e r t y, J. H., and Dille, J. M.: Survey of D-Lysergic Actd Diethylamide [LSDJ Anta~onists. federation - ?roc. 16: ~93-294 (jviar. l 1957. .. • . · .... 'i - ·• \ .~. ; ; 8. Gog~rty~ J. H., I in • . . i. , G os e r t y, J. H., and Dille, J. M.: Survey of D-Lysergic Actd Diethylamide [LSDJ Anta~onists. federation - ?roc. 16: ~93-294 (jviar. l 1957. .. • . · .... 'i - ·• \ .~. ; ; 8. Gog~rty~ J. H., Elder, j.·T., and Harita, A.: Modification of Actions of LSD-25 by ~~ser~tn~. federation ~· J..2.: ? roc • 3 00 ( Ma r • ) 19 57 • · . 9. 8 rod i e, · 8. 8. , 0 I t n, J • S., Kuntzman, R. G. and Sh or'!, P. A.: Possible lnterrelationship between ~elzase of Brain Norepinephrfn€ and Serotonin by Res~r~ine. Science -125: 1293- l 2 94 ( J u n • 2 8 ) l 9 S 7 • 10. Pletscher, A., Shore, P. A., and Brodie, B. B.: ai Serotonin a Mediator of Reserpine Action in Brain. J. Phar~acol. and Exper. Therap .. - 116 - : 84-99 Cj an. l !956. I I • lsoell, H., Bel levi lie,. R. E., Fraser, H. F., 'wikler, A I"\ • .t and Legan, C. R.: Studies on Lysergic Acid Diethylamide (LSD-25):· I. Effects in Former ~.ic,;rphine Addi.:t~ and Devl!lopment of Tolerance During Chronic Intoxication. A.M.A. Arch. Neurot. and Psych iat. 76: 468-478 fNov.) 1956. 12. Abramson, H. A., JI a rv t o ~ ,. 1l 1t1 1. E.' Kaufman ,. M. R., .. Kornetsky, C., Levine, a n d \'"~'/ a g n e r , •' •A• . : 1"\ • ' D i e t h y I am i de ( LSD-2 5 ) : I. Ph v s i o l og i c a I a nd Pe r c e ~ t u a I Responses. J. Psycho! • .±.Q.: ·s3, 1955. t c r' .., .13. \•V•I 1• n er, • dnd Flataker, l •.: 'Sfudics on He~tazcn~ . . . ( 6~Tror ~h v ~ in c-4, -~-dip h eny I ~3-he pta n ·Jn e n y .:.l r vc h lor i C: e ) in Comparison with Ofhei Analgesic Agents. j. Ph~n;-..; ,ccl. cl;<l Exper. Therap. 98: 305-317 {j.,iar. l 1950. .... ..# I' o :J·~ I I :e '"'. TABlE I. • Effect of LO lvtg./l(g •. of Phenoxybenzamlne on the l~eact lrJn I h I n d u c e d The document page contains a typed report on the effects of phenoxybenzamine and LSD. Handwritten annotations at the bottom right corner include the alphanumeric code "A-386" and what appears to be a stamp with multiple small dots and possibly a number or symbol. There are no photographs, diagrams, tables, forms, or explicit visual evidence of experimental procedures. The document's content focuses on scientific observations and results. The page contains a typed report with handwritten annotations. There are no photographs, stamps, forms, or diagrams visible. The document's text discusses experimental results related to blocking epinephrine responses and blocking of epinephrine by phenoxybenzamine. A handwritten annotation "A-385" is present in the lower right corner of the page. There is no visual evidence of experimental procedures, equipment, or facilities. ) in Comparison with Ofhei Analgesic Agents. j. Ph~n;-..; ,ccl. cl;<l Exper. Therap. 98: 305-317 {j.,iar. l 1950. .... ..# I' o :J·~ I I :e '"'. TABlE I. • Effect of LO lvtg./l(g •. of Phenoxybenzamlne on the l~eact lrJn I h I n d u c e d by I • 0 Me gm • /K 9 • of l SO I ~ TREATMENT LSD Placebo LSD Plus Plus LSD LSD Placebo Phenoxybenzamine Plus PI us Phenoxybenza~Jne p r Ph en oxv b~~n zarr~_r~ Phenoxvb~nza.ntne I . i I .i'vl"'Jc Rate, ! : ·ecu~bent ~ 31.6! 16.6 ~57 1 14.9 ~ 80.3.t -14. I · . ·~- :;'ulse ·Rate, i ,) tandIng · ""45.7 .:1:. 58.3 ~ 39 ~ 102 .J. 82. I 1 15. I ~ liS l ,39. 3 - :> ( r s t o I I c P r e s s u r e , + ·~ecumbent ~ 29.4"" 11.7 78 ~ 5.0 ~ 100 -.t- 18.5 .J. 52 .1- IS. 2 ·· r s t o I I c P res s u r t , . ' . ,.tanding ~ 2 - 3.6 + 10.2 I .J. 65 .J. 17.8 .J. 68.9 - 1 32.8 53 ! 18.3 Size 3.7 - .J. o.a "" 12.9.! 0.7 ~ 8. I 1 - 1.8 1.2 .1-'4.2 "" ~liar Reflex 2.8 - .J. 0.9 -1- 5.9 .!. 2.0 3.9 -.J. I • 9 . 0.44 .J.' 0.6 "" - :~'"r of AnsW~ 0.33 .,. I • 8 49 -1- 23 19.4 -.J. 6.6 0 -!.'0 ~·.'c:a I Gr~de 0 !. 0 2.2 .J. o.s 1.6 .J. 0.6 0 ±10 ~·· Ftgures are means standard errors of observations on 6 patients. in case of pulse rate, -1- I ' .p~essurt, pupillary ~lameter and patellar reflex, they represent time-action calculation$ i I Jreas I ~nd are expressed as beat-~ours (pul$e rateJ, mm. hours (blood pressure), etc. Number of represents _number of positive responses on questionnaire &fter LSD (or LSD placebo) which ~swers --- ·~re not $cored positively before the drug. Clinical gradP. assigned by rl'lethod oftsbell et al .. . . _..... ) \ l'uue 12 , .. f, '' . ~ TABLE 2. 'I' - Eff~ct of 1.0 Mg./Kg. of Phenoxybenzamlne on Rcspons1. ' ~-t to 0.4 - 0.6 Mg./70 Kg. of Epinephrine. -- .. __ ....,;,. ., ·BEFORE PHENOXYBENZAMINE A FT ! R PH et al .. . . _..... ) \ l'uue 12 , .. f, '' . ~ TABLE 2. 'I' - Eff~ct of 1.0 Mg./Kg. of Phenoxybenzamlne on Rcspons1. ' ~-t to 0.4 - 0.6 Mg./70 Kg. of Epinephrine. -- .. __ ....,;,. ., ·BEFORE PHENOXYBENZAMINE A FT ! R PH EN;:~ BE f' JZI\1\11 NE -·--~-A-S · l · · J · R - E -- Placebo h>i ncph i- t~e ·-- ----E-p- I- n- e- p -h-L J n e · .:::::::1.~ -Pla-c - <d:- - o - 1' ; IJ Is..; Rd t ~ - 331 !. 94 -1- 433 4- IU6 "' 466 .J. 95 - 318 -.J. 46 - -· --- 1 s t o I t c B I o od ! •• ~"~ssure - 187 -.f. ~4 ~~ .J. 453 1 197 -1- 205 .:!:. I 82 - 173 1 97 -...:.- --- i J .•.. . I i d s f u I t c BI o od . ' I rl!ssure "' 142 - ~ 306 - 441 .f. 219 - 657 -~· 340 .J. 208' -"" 71 --------- i Figures are means± standard err~ts of observ~tlons o~ 4 subj~cts. ' ( I,\ - I (..'\ Th~y r~l->r~sent time-action ~alculatJons lareas) expressed as b~at-ntln~t·~s (pulse . . I bnd mm. ·minutes lblood pressure). A poslf. lve figure Indicates an Increase over : . predr_ug measuremenh; a nega.tlve figure, a decrease·. \ .1 .•• ---- :.,.....:_ P.:~t;e I J ,.. ... ' ~\ .. k ,,) I''· " TAI3lE 3. {'-'\ I 'L-· Effect of ~.5 Mg./Kg. (Three Divided Doses) of phe:noxybenzamtne ·..,_ \(. -\ on Response to 0.¢ Mg. Epinephrine /70 Kg. :! - - ·~ '•W ., [:j ... BEFORE PHENOX YBENZAMI NE A f -T E. -P. PH ENC:X YG E NZAiv': I NE , -' nr ( ( I > ~- E.t. JR E PI a cebo Epinephrine Eplne - )J - -htlne Epi - ne - ph · ri - ne -- --- ---··· -· ulse Rate - 273 - "' 57 "' 545 1 122 "' 780 ±.. 144 . "' 684 !. 99 .• .. \' s t cl I c BI o od .. -+ res sure - 129 .! .12 7 "' 459 .:l 126 -1- 299 129 90 --1- 162 . I i a s t c... I I c BI o od The document page is a typed report with some handwritten annotations. At the bottom right, there is a handwritten annotation "A-384". The page itself appears to have been scanned or photographed, with some light scattering and speckling visible, indicating it's a reproduction of an original document. There are no photographs, diagrams, tables, stamps, or forms present on this page. The content of the typed text is a discussion of the effects of phenoxybenzamine and LSD, with a focus on observed symptoms such as fainting and pupillary changes. ±.. 144 . "' 684 !. 99 .• .. \' s t cl I c BI o od .. -+ res sure - 129 .! .12 7 "' 459 .:l 126 -1- 299 129 90 --1- 162 . I i a s t c... I I c BI o od res sure ... 84 .t 74 - 552 .:1:. 91 -I m~2 - + 148 -1206 - .j. 442 ' - - ( (I) Tested two huurs after last dose of phenoxyberizamlne·. • '2 Tested five hours after last dose of J phenoxybe~%amine~ + figures are means ~tand~rd errors of obs~rvatlons on .a ·s u b J e c t s • . \ l'ogc It!. :. .. ..; .,.,~. . '" '.. • "" . TABLE 4. ' ~ Effect of 2.5 Mg./Kg. ( Thret Divided Doses J of Ph~noxybenzamln•'! " on the· Reaction Induced by 1.0 Mg./Kg. of LSD. / ~ e LSD PI acebo II Plus LSD PI us LSD Placebo ' Phenoxybenzamlne Phenoxybenzamlne LSD PI us·. Plus ~ASURE Placebo Placebo Ph e "~ox :t benz om t n e _ Ph en ox~ benz a rn In e / i•.1l I ~- Rate, I I :cuml>cnt ~ ... 20.8 - "' 5.2 + 56 - + 19.7 I + 77.4 -... 13.0. -~. 48.0:!. 10.1 tdse Rate,. II· .... I .. , i·a n d In g 36.3! 18.5 +. 12 . - .J. ~3 .2 I ... 16.0 1 39.8 .· I 4- 157 -J- 45 , ' .. ,. s tv I I c B ood .1, + ~ressure, ~~cumbent II ... 27.0! 25.4 I .J. 69.9 ,J. 9.3 1 "" 75~2 .J. 10.9 I 38.4 .._. 12.8 '. i '-'P t I I a rv S I z e II ... 3.15 + 1.3 I .&. 14.2 _t 1.5 I ... 9.5 ... 0~7 I - 1.4 ... 3.5 dellor Reflex II - s.o ... I. 7 I .J. 6.65 J. 1.2 ... 8. 35 -.J. I . 6 .. I .J. 0.9 ... I • 12 - er ofAns~ 0.2 ...-. o.oa I 33 ±. 12 47 + IS I 0. I .J. 0.9 '"',c a I Grade 0 .:1:. 0 1.65 .l o. 37 I 1.05 + 0.37 I 0 ... 0 Figures are mean_s! standard errors of observations. <>n 10. subjects.' The page contains the text of an experimental report, likely related to drug testing. Visual elements consist of faint horizontal lines from the paper, some speckling from age or damage, and two dark circular marks near the top, possibly from a binding or hole punch. In the lower right corner, there is a handwritten annotation in black ink: "A-383". There are no images, diagrams, tables, stamps, or forms visible on this page. The image shows a declassified CIA document page featuring a list of references. There are no photographs, diagrams, stamps, or filled-in forms. The page contains handwritten marginalia in the bottom right corner, reading "4-382". There are no visible redactions or obscured content, other than the inherent limitations of the aged document's quality. I 33 ±. 12 47 + IS I 0. I .J. 0.9 '"',c a I Grade 0 .:1:. 0 1.65 .l o. 37 I 1.05 + 0.37 I 0 ... 0 Figures are mean_s! standard errors of observations. <>n 10. subjects.' This page contains a portion of a numbered bibliography with a handwritten annotation in English at the bottom right corner. The text appears to be a list of scientific publications, each with author names, titles, and journal information. There are no photographs, stamps, forms, diagrams, tables, or redacted content visible on this page. The image displays a declassified document page containing a table of experimental data. The table, titled "TABLE 1," presents measurements related to the "Effect of 1.0 Mg./Kg. of Phenoxybenzamine on the Reaction Induced by 1.0 Mcgm./Kg. of LSD." The data is organized by "MEASURE" and "TREATMENT," with numerical values and associated standard errors presented in columns. Handwritten text "A-380" is visible in the upper right corner, and a small, circular stamp is present in the lower left corner. Below the table, there is explanatory text detailing the figures and methodology. No photographs, diagrams, or official stamps are clearly discernible beyond the handwritten annotation and the small circular stamp. The document displays a table labeled "TABLE 2" that presents data on the effect of phenoxybenzamine and epinephrine on physiological responses. The table is divided into sections "BEFORE PHENOXYBENZAMINE" and "AFTER PHENOXYBENZAMINE," with columns for "Placebo" and "Epinephrine" in each section. Handwritten annotations, including numbers and a large arrow with "A-379," are present in the upper right and left portions of the page. Text below the table provides a key explaining the data, noting that the figures represent means and standard errors of observations and how positive and negative figures should be interpreted. The overall page appears to be a scanned document with some unevenness and potential for minor image artifacts. The document contains a table labeled "TABLE 3" which presents data on the "Effect of 2.5 Mg./Kg. (Three Divided Doses) of Phenoxybenzamine on Response to 0.6 Mg. Epinephrine /70 Kg." The table has columns for "BEFORE PHENOXYBENZAMINE" (with subcategories "Placebo" and "Epinephrine") and "AFTER PHENOXYBENZAMINE" (with subcategories "(1) Epinephrine" and "(2) Epinephrine"). Below the table, there are numbered notes (1) and (2) providing context for the data. There is also handwritten marginalia in the top right corner that appears to be a string of characters and numbers, possibly a reference code or identifier. The rest of the page is blank, with some scattered dots that appear to be ink specks. The document is a declassified page from a report, identified as "Page 14" and containing "TABLE 4." This table presents structured data in a tabular format, detailing experimental results under different treatment conditions, specifically related to the effects of "Phenoxybenzamine" and "LSD" on various physiological measures. There is a handwritten annotation in the top right corner, appearing to be a code or identifier: "A-377". The page contains no photographs, diagrams, or stamps. The data itself, presented as mean values with standard errors, visually represents the quantitative outcomes of the experiment, providing a clear comparison across treatment groups.