DEPARTMENT OF-, LEX 'K -77 HEALTH EDUCATIONI, AND ,,,ELF/-, G PUBLIC HEALTH SERVICE LEXINGTON. KENTUCKY I" OMPt;YINC.. ADDRESS THV '29 March 1954 PUBLIC HEALTH SEqltcE HCSPITAL NltVuH Addiction Research Center As you undoubtedly knoi, I had a visit week before last from Mr. Kornelsky. We went over the d.ata obtained so far, and are In the process of,.making duplicates of the graphs In the dose- e f f ect exper imen f Since Mr. Kornetsky has been here, we have completed another 2 tolerance expe'ripent. In this experiment pafients.-were given LSD for eight days i@ doses increasi,ng from 20 mcg. to 75 mcg. oice dall%, at 9 a.m. 0-i the,n'lnth d-ay, the 75-,-ncg. dose w-is reocated. The results aopear in Table 1. J'N-- expected,. a conside2rable d-gree of tolerance was develo'ed to the subjective effects of L5D-25. p Pa,lienfs an avcrag@@ of only IS pos:ifive answers., as comoared to SS positive answers'after three days-'of water. The clinical- a f ter e lgh t days was es f I vii'h 1.7 2 r a d e -na'tzd as 0.625 as compared I after thrce days of weter. In scoring e- number of positive answers and clinical-cirades, the same criteria were used as described in my prior letter. The grade of tolerance, however, taking into account the individuals concerned, does not appear to be any areater than that developzd after three day2a on f-,vo small doses daily (see prior report). Moreover, patients on the eight-day sci%edule reported more side effects as toler,ance was developing,.nore par- ficulariy In the middle part of the sc.@edule. We have some preliminary information on aftc,,-r-pts to-break ihrough th2,- LSD-tolera@ice by Increasing the dos-,. The number of p,iticrfs is not@yef to permit. any conclusions but, ho,.ievzr, @,e 'ion is being sub,,.iitfed I n f o.-rial I- f o r wha t' I f I s -.Yo r ts i n ce i 1i not likely 'chat 1. will be able to do more prior to lihe Federd,'IOP mecting. In one exoerimen'i-, 4 patients were made tolerant by the f.%r@zri-day sche-ju'le (10, 20, and 30 mcg. LSD-2:r) all 9 a.m. and 9 p.m.), the test dose being given oti the fourth day. Two of patients receiv-.d a 100 mcg. test dos e ( i n c r ea s e ,,r -13 pe r cc- -i a n d -'@ r-I cc I v e d 125 mcg. (an increase of 66 per cent). No occt..rred In an@ of these 4 patients. ^9 a r c h 1 @-54 page 2 OL f-,- ".A In another experiment 6-patienfs w2ere Made foleran@t, using a nine- dose sc@iedult' (one dose of LSC)-O@5 daily af 9 a.m., increas';ng frc,-,i I n c 20 to 7'@o mcg. on the.el-ch'h.day). 0 the ninth day., one pafi'nt was tested with ICO mc 'and 5 were tes'ed with.125 mcc,. _a. I j There was rio signi.ficant break-fhrough with either of these 2 doses, although in one patient (DEL) partial break-fhrouch was achieved. These series of experirr@znfs will be completed as soon as posst',-,Ie, after which we will go on to even hieher doses. At the moment, the trend appears2 to Indicate that the dose must be increased more than 66 per cent to res'lore the original effect of LSD-1@)5, once tolerance has been deyeloped. I think If Is. of some int,-,rest and some practical import'ance that we have now tested (nore than 50 forr,.er rrorphine addicts with L'-@D-25 (this number inclvdes the group tested. in 19511. The i-mporfant thing seems to be that the mental effects obs2erved in this population o-re, so far as I can tell from the literature, identical with those obser,.,ed Tr. other popula.ions despite the fact that my _croup differs so greatly.with respect to race, e c 0 n 0 m 1 c a n d e d u c a o n2 a I s t b t u s p e r s o n a t y c h a r a c t e r i s t I c a dnd pr ior drug tfs e I would like your a d v i ciz c on c o u r p I a n s f o r t h imr,,ed i a t e future. I have 8-pattenfs checking info the ward next we2ek. This group is m6de up of-individu.clls Yho havc been In the dose- effec@ experiment ancl tn' the prev'ious +-oier,,nce experiment. Viy objectives are., (1) fo corrobor-& 2 'fe the'resul'l---r obtained wlth questionnaire and clinica, men-'al e;zamination, usipg our objecfi-@e measuremen iIL$,,,(2) to defe;.,rine the break-through dose, 2using these objective me-asurements, (3) to t-est the SKF metabolic blocker for enhan cerren t of t he LSD e f T'e c i . a nd f o r 1 t,@ e f f ect dr-,r tqc tolerance, (4) to deternifne the speed of less oT' folere2i.rce, and (5) l'o obtain da t a on t he ef fect of LSD on t he IV.IVIP I a nd Ro r-. cha ch t es f s The main thinn- Is t ha-t o a t t a I n a + hes @- ob i e,,cf I've-S v!- I I 2 I f o u r c@ o,-, c - a o e i,-,c i-i s ; or !it o @l iit,.r wor@s @liL- &xper i m,@, r i:i will continue until August or September. TFz 2decision .@lliai must be made -is whether these ar@-- the most important things for us to do at-thi@s time. n cc r e I y y@- u r s Ha r'@ I'.. 1 s"b c I I t6vt. D Direcfor of Research H I e n Affacliments cc: Mi- . Kornets@@! TA 2 I TCLER/,PCE LSD-25 -- Eight Day Schedule .7-5. mcg. Test Dose After 3 Days H After 8 Days LSD PATIENT 2( 20 mcc, lncreas i n r, to 75 mcc No. positivi,. 2 No. @Ositive Answers Grade Answers Grade Sim 34 23 DEL 97 3 16 WEI; 167 i 3 38 FO 18 1/2 22 0 3 251 24 GR 0 5 5 0 DO 32 t 31 I AU I C) I 2 4 0 Tota I 2 705 13-1/2 t43 5 Average 88- 1.7 0.625 0 0 HU 0 2 Control not yet obta ined TABLE "BREA,-,-THRCLO-i"- LSD TOLERANCE 3-Day @chedule li After 3 days H 0 After 3 days LSD After 3 days LSD 2 SC Break-flircug@. PATIENT Test Dose 75 mcc. Test Do 2 100 mcg.-Test Dose ii No. pos. Ans. Grade i No& pos. Ans* Gr. No. pos Ans. Ur a c.4 c GR 0 1 o 9 1/2 AU ioi 2 10 o 2 0 125 4 mcg. Test Dose HU* 7 1/2 15 0 32 2 o TAPLE 3 "BR,:&:-AK-THRCGH" - LSD TCLERANf%--E 8-Day Schedule After Days H C After 8 Days LSD Afier 8 Days LSD 2 2 PAT I ENT Test Dose 75 Test Dose-75 Test Dose t4o . Pos. Graoe No. Pos. Grade 1\@o - eos . Grade 2 Answers Answers Answers sm 251 24 0 0 Test Dose 125 2 FO 18 .1/2 2 0 0 SHw 2 0 0 0 BEL 97 3 16 1 4 53 2 5 INI 34 ,+2 3 15 vi'E I 167 3 3 8 1 1 35