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Dr. R. C. Pogge Director of Medlcal Research The Wm. S. Merrell Company Cincinnatl 15, Ohlo

Dear Dr. Pogge:

We have completed the effort to reverse. the LSD reactlon with Frenquel, except for checklng the statistical constants. I am enclosing tables which show the results.

The methods used were the same as those described in the report on the "blocking" experlment, wlth one exception - the kneejerk. This was measured by deternining the angle throuch which a callbrated hamper must fall In order to eliclt a detectable kneejcrk. Puptls were measured by comparing thelr dlameter with those of circles on a cárd lara dark room under conditions.of constant light. Blood pressure was determlned by the euscultatory method after l0 minutés rest in bed. The mental effecis of LSD zre assessed by administratlon of our version of the Abranson-Jarvik questlonnalre for two hours before and elght hours after admlnlstration of LSD and by a short psychlatric examlnatlon in whlch particular attentlon was paid to anxlety, apprehension, perceptual distortion, hallucinations, and insight was done hourly, and also wlthin a few minutes after administratlon of Frenquel.

You will recalt that in this system Grade I consisfed of nervousness, anxiety and epprehenslon onlv. Crade 2, Bervousness, anxtety, apprehenslon, and visual distortlon. Grade 3. anxiety, apprehenslon, visual distortlon, end hailucinatlons with malntenancs of lnsiyht. Grade 4, same as Grade 3, but with insicht lost.

These observations were all carried out for twg hours before and elcht hours after LSo. The mcasurable of "nonmental" effests of lsD are evalustod by plotting tha data on craoh paser and measuring the eres undtr tha time-actlon curve vith & pianinetzr. Positive answsrs on questlonnolre ware counted hourly and totaled for the entire day. Guestions ahlch were scored posltiyely prior to LSD were ellminated. Clinlcal grades were zvatuatad houriy and for the total dey accordlng to the sysfem described above.

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lakmation copy

13 January 1950

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Individual analysls of the records from a qualitative polnt of vley hour-by-hour also showed no dlfference. Halluclnatlons and perceptual distortlon continued to be present after the Frenquel and dcélined at the usual rate. Thls polnt Is best exempllfied by cose report on the paflent whom Dr. Allin saw during his vislt here.

LJU December 9, 1955. 150 mcgm/11.5 mcg/kgl at 8 a.m. At 9.o1clock, nervous. confused, nouseated,  body is expanding and contracting, hands and feet look big, eyes are biurred, oblects are changing size and shape, skln melts off hands leaving only bones., insects are crawllng under his stin, colors on wall runnlng tocether Ilke melted wax and forming plctures of people and ghosts. Pictures are horrible but not dlsturbing, because he knows they are due to LSD. l0 o'clock sxax, nervous and aporehensive, confused, feels as if in a nightmare, has been floating in the air, people and objects are changing sizs, shape and color. He can see biood vessels under the skin, things ere crawling under the skin, heed is. drled up and shrunken, and plctures on the walls are parts of people, animols, devils, ond so on. Insight maintainzd. Af 10 a.m. recelved 60 mg. Frenqucl Intravenously. After lajeciion, patlent reported to the Aide that all LSD effects had disaopeared. Dr.Allin and  immedlately went to see about this and on detalled questloning found the patlent still had marked visual distortlon, hallucinations of the fype dessrlbed above, but stlll maintalned Inslght. At Il e.m. patlent received 40 mg. frenquel intravenously. He reported nervousness was less, but stilt was obylousiy confused, visual distortlons in size shape and color were still present, flesh stlll mzltd off hands and he could sce blood vesscls and bones, 1 looked very small, very small, and very horrible. Insight was stlll present.

twslve to 4 g.a. symptoms graduaiiy decreased. At 4 p.m. was still seeing colored lights which. however, formed no deflnite pictures, continued tense and strange until 2 a.m., after which he went to stzep.

Deczmber 30. 1935. At 8 a.n., patlent glven 150.mcg L5D (l.5 mcg/zg). At 9 a.m. nervousness, walls are scen through a fog, many llghts and colors seen with eyes closed, feet and hands seem to melt, look old and sklnny, felt strance, confused and lost. At iO a.n, stlll confused, feels strance end lost, orlentatlon Is mdinralned, very nervous, people and objects are changlng size shape and color. Hils hands and- my hands

A-2151

Dr. zonges

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decay and. turn tnto anlmal clows. walls are covered wlth plctures resembllng melted wax, pictures are of ghosts, pretty women and so on, his body has dlsappeared from the chest down. l0 o.m., given Frsnquel placebo. After this, reported he was much more relaxed:and LSD effects were less. He was obviously stlll confused and on looking at the walls still saw the plctures, hands,still decay, stomach Is gone, effects are due to LSD.ll a.m, frenquel placebo was repeated. Plctures still on wall, sees llchts and colors with eyes closed, people and objects are very distorted, Inslght malntained. 12 M to 4 p.m. Effects, whlch persisied throughout this time, gradually became weoker. At 4 a.me, still saw llghts with eyes closed, and nervousness and hallucinatlons continued until about 2 a.m.

I would be pleased to have your reactlon to this. l can conclude only that, in the doses used, Frenquel had no slgnificant" effect on the LSD reactlon:

I belleve that i have told you Reserpine makes the L5D reactlon worse, rather than amelloratlná lt. Thls means that the effects of a drug on the LSD reaction cannot be used to predict Its possible clinlcal usefulness es a quleting agent In the "ndtural" psychoses. Our experiments, thorefore, have no bearing on the polentialifies cf Frenquel in these condttlons.

I was very interested In Hemwlchts report of Its use in schizophrenics. lf thls le confirmed, there caa be ao doubt that Frenquel would be a very useful agent because of lts extremely low toxlclty.

With kindest personel regords.

Or. Poeio

Poge4

Sincerely yours,

Hhrrls Isbeli, M.D. Director

Hitrn

Attachmeais 3

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TOTCOURSE CF THE LSD REACTION

Figures are means of valves oa ll sublecis. None of the dliierences betreen LSD ↓ Frenquet placebo or LSD ↓ Frenquel are signlficant.

l. Expressed as square Inches under effect curve, S a.o. - 4 p.m.

2. Number of aasmers on questlcanalres, exciuding any that were also scored positively before LSD.

3. Based oa scele of l-4 (sen texi).

0 Dose 1.5 - 3.0 nco/kg. Average 2.4.

s Dose G0 mc. l.v. 2 hours and 40 mg. 1.v. 3 hours aftar LSD.

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Figures are means on ll patlents. Nean dose of LSD 2.4 meg/kg. Dose three hours of frenquel 60 mg. i.v. 2 hours and 40 mg. l.v./after LSD.

IN CHANGINGLSD REACTION HOUR-BYHCUR

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SPERG:ECUS CONENTS ON FRENCUEL