ton copy 13 January 1956 Dr. R Co Director of Niedical Research .The Wm.'S. Merrell Company Cincinnati IS$ Ohio Dear 2 Dr. Pogge: 'We have. conplcfed the effort to reverse t.Sc L@D reaction with franquel, except for checking the statistical constants. I am enclosing tables which show the results. The methods usv28 were the same as th-ose described In the report on the "blocking"experinent, *Ith one exception - the kneelerk. This was medsured by dater.-nining the angle throuch which a calibr 'ated hamEt-.er- r-.ust fall In order fo clictf a detectable knecicrk. Puplis were measured L-v thel-r, diameter with those of circles on a cdrd lm;-a dark roc!@--i under conclitions-of constant ITC-ht. Sto,,--@d:presture was deterritned by tSe -uscultator,/ method after 10 r-iinute".3 rest In bed. The rienfal eff'cc4ts of LS:) w-zre assesse2d by ad.,ninlsfratton 'of efur ve,-sion of th,- Abra-,nson. 'I'arvik .-ucsflonnalre fc.- fwe@ bours'b-@-T'ore and elC-,@t hours affer ad.-.iinistration of LZA@D and by a--.short psychiatric exijr2tina,ion in which particular attention was paid to perceptual drstorlion, hailticinations.-and lnslght was 4one hoi.-r 1 an@ also withlr, a ftw minutes after administr-atio.-I of 2 Frgnq@et. You will recall thart In thts systei (;rade I consisf--d of ncryou3- ness., anx.izty and e,,@prehension cily. Grade 2,, nervousncs.,.,#, 2 --anxiety,, apprehension af-,d Y13val d!stortion. Gr,3d.-. 3. anxiely. -inJ @difucinaVions wlih as Si-iiiurii. .arade 4,, ;or-le as C2-7rade 3. but with in$ i-17@ t T-h-,csg'. observations werz all carrica' cut for ty.-o hours bzfore of ncn-licn. a n d e I c @-2. t h,,- u r s a e.- T@i r,-U-asurabl;a -re b-I pt 'ina i;,e da@a on oi@)er aid o f L o i r 2 P f h c a r c a cl 7 r -z o ii u,- ..cat ur I nr@ ?ositive answers on que@itionnalre were counted hourly an-I tofaicd 2 for the entire --;ay. 'u c s t I o n s l@., S I c h v; c r c ; c 0 r d t I -v 1,/ i o r to LSD were eliminafecl. C I I n I c a I c-- r a,.' c a w c r z. c v a @ ii c d c ii r and f,-,r fric total 7 accordin,-, -?o t,'@c- sys44@- -4 d e s c r i d a 1)0@v c cr y, 0 12, -10 0 -0 0, M- r. 10 2 M X ft L@p a-C tr CGo tr ib -ft 2 xCA 0 44 0 cr 2 ,n -4, c cr C -ft ea a af% -*. a - - -v- Z O%0 2 X) I" OA - n Ccr M < Is M -t uO 'I 1.@L 0-,&, a. - -ft 0. 2 00 =. 00 Go n CL 94 C C0 .3 u 00 2 C a 0 :r CO n 2 C CO 14 ob 1* 4, 44 -P z CL t% azzr 000 2 co 0 'a @-. - > " A-I Z'o .C 0O 40 0 a, zr = oo 'U -n C goaDP cr - O :7- f46 2 M CL Co 0-2 40 C) O C AZa C'L x0 0-1 % co 2 O. .1 O 4 0 'I -+@ n:2 I" TJ -C 0 lb :@ @ (X -0 2 M O C 0, cr O O- 40 0 C4 2 .1 tA - 0 no a -4- a (L CL 0 nCC 2 0 et, ME3' 4%0-1 a %V-@ r- " .A0 0 O 2 60 i.- - - tCL -cr 11 00 cr 94 :I n0 0 cr =--.0- op O- 2 ft ui Ii I 0 4% a4% 'O0 -M. 0 0 O'U :r0 @ 0to <0 zi rr M -1 *P0of -" 0 0 'D 'U 0 c 04 tr n 0 C 2 M 40 -1 i3 0 -1 co a C- - 0. 0 tl t% t% &- n:3 cr C Cb 2 n Z % a CLO 0< 10n= -r -" n =r -0C 0lb 0 o 2 CL 0ZI-nto a-.""M M 2; CA M -$ if 0 C: @'U t*0 cr (a Co 0 ;: C)- a. 0 O% 2 1.6 .+$ f)0 0 CA 0 - a. Zs Is -I. cr 0 -0 0 2 co -.s n:3 CX :r -.I- % Ln -c o 4m a.0 & 44 2 io 4% of0 CL " M a 'U0 :2 rr - O. O- -3 it 0ccr a 2 0. CC a 0 C 0 0 a aacr 23 00 a& 2 C%. *A & i's -.k. -*- 0CL 00. cr V, W w (A 40 AIC 2 Z' C 010 AP t@ .0C CL0 C4% .1 0. 2 -10 a tr C r.r 11 110 C=r :3 0 & 0M 0oil i% :41 2 -1 0 0 n &) zr n.0 C 10 11 In:3 iu 1% 2 lb0C 6% C4 C -O- '% ;WI00. 2 gb N 40 - O DP n 0 - 2 -." - 14' C4 0 c M a fk ap in 0. cr Is 2 O- 'U CC4 CL (40 44 CAP 'A -,P.0M 4% Cb 40 40 (4u-.*. 3 ;I :3*4-% ft :3 n *Cl. 0 - CL0 C .. o@ Is cil 0 CX et i4 Go M40 0- > 2 <0 A "r- O Pr - n 0) zi 2 ACr OA - :@p ut - 3--" LI. (b 2 Cp -I U- n. in v 0> :r o 2 doa- C (4 (A n i's to -*. 2 el Ci C 0 a O C > C a, O 5 C 94 r P I nd I vldua I -ina lys I s of thi-.-@ f rom a qua Itative point of v lew hour-by-hour a I so showed -no d I f ference Ha I I uc I na t ton s and ogrccptual dl3tortion continued 2 to be present after the frinq.uel and cic,.@lined at the usual rate. This- point is best exemolifted by case report on the patient-whom Dr. Allin saw durtng his visit here. LSD December 9. 1955. 150 mcgm/11.5 mcg/k2q) at 8 a.m. At 9 o'clock.. nervous, confused, nouseatedlbody Is expanding a'nd contracting,, hands and feet look big, eyes are b.lurred objecta- are changing size and sha-p,; k-l,n melts off hands leaving only boncs. Insects are crawling under his 2 skin, colors on wall running t'ocether like melted wax and forming pictures of people and ghosts. Pictures are horr-lble but not di:sturb-ing., because he kno.",they are due to LSD. 10 o clock a2!mx, nervous and ap..;irchensive, confused 2 feels as if in a nighimare, has been floating in the air, people and objr4cts arc changina size., shape and color. He can see blcrd vessels under the skin, thing& are crawling under the sklw- he@ad ls.drlcd uo and shru,2-tken, and oictures on devils Tnd' -Po on. the vialls are narts at peopi4f, anlr..als, .9 Insight :-aintain@id. At 10 a.m.. received 60 mg. @b:rznquci intra. 2 venously. After lnjecilon., patient r-eporied to tl-;,e "Mide that all LSD effects had d-tsa--)z3zared'. Dr.-.All;n and I- tm:rediately went to see about t-his and on.detalle'd questionin!g fou,.I-IA the 2 patient still had .rarked visual distortion, hallucinat'sons of the type descrit',ed zbove, but still maintained lnst-ht. At 11 patient recel..,cd 40 rig. Frenqu'.1 Intravenously. He rcoorted nervousness was less, but still was obviously 2confused, visual distortions In size shape and color were still rresent, fles!.i still met.-.idoff hands a,.id hz co-ild see blood ves:cls. aid boilcs, I looked very S;-,iall very small and very horrible. Insight was still present. 2 4 Graduaily decreased, At 4 p-..-i. was st-ill seel,-ig colored lirht: which.. ho-.ever, for.-,ied no dzflnitz pictures., continuad tense and'strang-e unti-I 2 a..m., a-irter which ,he. vii:nt to si;,.cp. Dec:zm@bcr 30. 19-5. Af I a ;7 patient c,-Tvcn I 5 c @--i LF@', (1.5 MC(2/kg)* i,.4- 9 a.m-. 2 nervousness., waII3 arc see-,i throuch a fog, many li,,Thfi and colors'seen w es clostd ect @nd ith Cy hands seem to melt look old and skinny', fzit strance, 2 confused and Icst. A ft @,l .i .s i III co -f tised 7'ec Is s tr art r:11, a Id 1--s-f o r I en t a t Ion I S i n-I a I II ed vzry neevous,, pco.,)Ie anL4 objects are changing size,, shaoe and color. His 3 hands and-my-h,-.nes Page 4 dgcay and-turn Into dritiral claws, wall% are covercd with pictures resembling melted wax, pictures are of hosts, pre y s women and so on his body has'disipocared from the chest down. 2 10 a.m.., gfvea frinquet olacebo. After this, reported he was much more relaxed--.and LSD effects were less. He Wd$ Obviously 1% at the wall% still saw the still confused and on.looki.-it, pictures, hands,still decay, stomach Is gone, effects ar2e due to LSD. It a.m. Frenquel placebo was repeited. Pictures St I I I on Va-I Is es llghts-and colors' with eyes cl-osed, people and objects are very d Is for ted,. Insight- -;na tnt a I nedi 12 0 4 m Effects, which c-r3isted throughout this ttinp-,, gradvaiiy P*.2& p Se c@a m @e weaker .At 4 a.m., st III saw II chts tiosed, with eyes and nervousness and hall u cinations continued until about 2 a.m. I would be pleaied to have your 'reaction to this. I can conclude only that 11 In the doses used, fr2enquet had no signlflcant@ effect on the LSD reaction@, I believe that t have told you Reserpine makes the L.'JD r-aacfllon worse m. c LI' f., This n-eans that t,@e ef-ccts 'rather t.@an a ora-f imb -1 of a drug on t',,te Li'D2 r'action caro,,iot bc used to predlct If$ possible clinlcaf U3CfUlnCSS a%% d quiettng a(,,cnt in the I?n4fural' psychoses. Our experim'ents f h f o.- e4ave no be-3r@ing on the po?l@el-itiallfi2es CT@ Fren'quci In thct;e co-nditions. I was very liit.erastcd In ts report of its use In sc'it)zophrenlc"S' .I f t h I s I!i con@f I r.-,ied I t h -..re ca n be no d-oub t that frenquet would be a very useful agent be.-ause of its cxt$-cmcly 10-1 toxicity. With kindest pZrSOndl regir.Ais. Sincor.-@!ly ,ours, -ector Di. Httrn Attach,n%-.nis 3 'E FE C C-;: FP.EjN::Z,..'EL IN T@Lc TC-T, CW@SE Cf LSD 2 E.-kC-t I cti LSD Placebo 'Frenquel LSD Pfaceb@o LSD* L'.easure P14i:CbO 4 Frdnquel-.,@@" Freaquel Placebo 4, FrenqL-c I Knee-Jerk 4. 0.12 1 0.60 4. 1 4 1.47 I pup litarv Size 4. 0.6-9 4 0.69 S.'s I S.31 Systolic Blood Pressure -L 0079 4. 3.25 3.32 2' 2 OTO Os I An twers on Questlonnalro., 6- 7 c7 8 7; 3 Cltnical Grade 1 2.7 Figures are rw-ant of vatfues oij ti zublects. tbn c of the d?"ferences. befteen LSD .3. F r;,,. n q,-, c Iplacebo or L@'-D 4 rri:nquei 10 r-x")rcssed as stu-are Inches undzr &@c- curve, -.jml-cr of a;-.s-,7crs on ques'-I-nralres., excludinc; anv we6re also scored LSD. on sca'a c s Cose (,lose 6,)' 2 hours and 40 I v 3 hours after isr EFFECTS C'sz F fl, c- i'@, IN LSD Ci la4 -a Y-4i -zu-z FkWi. AFTER LSD DRTUS @2 3 4 S 2 7 Frcaqt,,cf.Pliacebo 0 0 0 LSD-placebo -L re nque I 0 0 0 LU LSD 4. Frenque I 2 9 s 4 Pi;dcebo LSD 4. Frenquet I s: la 17 13- a 5 5 LS;",-plact.-bo 4, Frar.,qu--I-Pl2acebo 0!01 "0.1 o.t 0 0 0 0 0 LS..,-olacebo 4 Fren-uel O.t 0.1 0 0 0 2 2 0.2 0 3; LSD I Freaquel Pfaczbo 2@2 2.7 2.8 2.3 I.S 1 0.7 t 7 LSL-) Frenquel e-4 2.7 2.7 2.1, F r c a r c c a n 3 0 rt pa f I is'*" a. n -losc of LSD 2.4 fhrez hours of Frenquel 60 L-n,-- I v. 2 hours a iid 4 0ma. 1.%-./af @e L SD. r 7P fn CL' cr