Page 2
obtained from Eli Lilly and Company) in which the acid
amide group of LSD has been replaced with the methyl and
a hydroxyl>1p, has also sedative rather than psychotomimetic
properties. I am go>2ping to try agrocl>1p,av>1pine and the Lilly
compound as possible blockers of LSD.
I will be leaving June >1p5>1pt>1ph for an ext ended trip to
the We2st coast and will not return to Lexington until
the middle of July.
With kindest personal-regards,,
Sincerely yours.,
sbell>2pv M.D.
Director
>2pH>2pl>2p:>2pl>2pw
Enclosures
_>2pP>2pcs>2pi>2pg A randomized, double-blind design >2p.>2p.>2pias used in
both e>2pxp>2peri>2p7>2pr>2p.ents>2p. In both., t>2pi>1p->2pio dr>2pu>2pg co>2pr>2pibinations >2pi>1p->2piere us>1p-ed>1p:
>2pBO>2pL plus LSD, and >2pn>1p->2pO>1pL placebo plus 'SD. T>2phe co>2pr>2pibinations of
>1p->2pR>2pCL p>2pl>2paceb>2po plus LSD placebo and of >2p&>2p)>2pL>1p; plus placebo were
not done because p>2p.>1p-ev>2p;>2p.ous d>2pa>2pta 2indicate t>2phere >2pi>2p.>2p,>2pj>2p->2p-s no chan>2p-ce of
significa>2p.>2pn>2pi>2p'>1p. degree after eit>2pher combination.
"--,ea sur>2pa>2p:>2p.>2p7>2p.e>2prt s>1p. >2pS>2pys>1p-tolic blood pressur>2pc>1p, >2pDu>2pDillary size >2pe>2pnd
threshold for >2p'>2pI>2pr>2pc>1p-neejer>2pi>2p@>2prs wer>2pe deter>2pr>2p.>2p,>2p->2p,ined twic>2p,>2p->2p>>2p- >2pb>2pe>2pf>1pore
and at
hourly inte>2prvals for eight hours >2pa>2pfte>2pr L>2p3>2p7>2p, >2pb>2p->2p@>22p,>1pr i>2pr>2p,>2p.>2p:>2pat>2p.>2p->2p,ods
previo>2p-L>2pisl>2pi>2pf
described. A >2pr>2pnodification o>2pL>2p' t>2pn>2p-e Jarvil>1pt>2p->2p.>2p@>2pf>2p@>2p,ra>2p,>2p->2p,son
questi>2ponn>2p;>2p->2p;ir>2pe
>2pwas given twice before and 1>1p/2>2p, >1p1>2p-1>1p/2>2p, 2>2p->2p.1>1p/2>2p.>2p,
>1p5>2p->2p-1>1p/2>2pj 6>1p->2p1>1p/2 and 7>1p-1>1p/2 hours after LSD. Short >2pr>2pi>2pental status
examinations >2pi>2pqere conducted a>2pt t>2p.>2p->2p.ese t>2pi>2pi>22pi>2p->2p.es>1p, in order to assig>2pr>2p,
a >2pl>2piclinical grade>1pl>2pt to the re>2paction>1p.
>2pP>2p.nalysis of Data,. >1p.>2p1>2p1>2p%>1p.reas representing>1p.change fro>2pm predrug
controls were c>2pilculated for data on>1p'blood pressure>1p,>2p.patellar
reflex and pupillary size. The number of questions scored
posit>2pively after LSD >2pi>2p->2ptere counted, eli>2pminatin>2pg any w>2phich >2pl>2pl>2pere
also scored positi1vely before LSD. Grades >2px>2piere assigned
according to the system previously described. The usual s>2pj>2pt>2p->2p.atis>1p-
tical treatments were performed on>1p.the data. The t>1p-test for
paired observations and non>1p-pa>1ptametric tests >2p(>2p@>2p.>2p->2plilcoxon>1p) wer>2pp>2p,
used in eva>2pl>2puating the sinnificance of results.
!II-:, >2pS>2pL>1pT>1pL TS
zx>2pperi>2pment The results of this ex>2pneri>2pment are
sho>2pw>2pn in tables >2p@6>1p->2p,>2p:>2p)l and >2pc>2p@6>1p->2pD2>1p. All aspects of the LSD
reaction >2pi>2p->2pfere reduced but not to a statistically si>2pgnifican>2pt
degree, This result is si>2pm>2pilar t>2po>1p.that observed in our firs>2pt
e>2p,>2p/>2p,>2p,>1pperii>2pp>2p.>2p,>2pint 2in >2pw>2phich a larger dos>2p->2p@ cf L>2pS>2pL >2pi>2pi>2pz>2p;>2p.s used..
>2pr>2p-x>2pper >2pr>2pient T>2phe results are sho>2p@>2p.>2p,>2p,>2pr>1p. in>2p,tables 56>1p->2pc>1p->2pI
through Significant reductions >1p(t>1p-test>1p' >2pw>2pere observed
,.in every aspect of the LSD reaction exce>2p->2p.>2p:>2p)>2p">2p->2p,>2p. for th>2pz>2p'>2ppatellar
reflex. The non-parametric tests were also sign>2p'>2plficant for
every aspect e2xcept the clinical Grade. T>2pi>2pme course of the
LSD reac>2ption (table >2pwas >2pnot greatly altered b>2p->2p%>2p,>2p- >2pZOL>1p.>1p,
des>2pdite the evide>2pi>2prt atten>2pi>2p->2p,>2pP>2p,tion>1p.>2p.
DISC>2pL>2pJSSION
T>2phe results show that pretreatment with >1pB>2pOL for five days
does reduce t>2phe intensity of the reaction induced by
>2p1 >2pi>2pt>2pi>2pc>2pg>2pm>2p.>1p/kg>1p. of LSD. 2The results strongly suggest that the
longer ROL is administered the greater is t>2phe reduction in
intensity of the reaction. Such resultz are >2p->2p.>2p.>2prore co>2pr>2pi>2p->2p.pat>2pi>2p.ble
with the development of some decree of cross-tolerance between
>2pBOL and LSD than with direct co>2pmpetition of these drugs for
receptor sites. The degree of cross tolerance to LSD conferred
by pretreat>2pment with SOL is, ho>2pt>2pv>2ppver>13p, not co>2pm>2pi>2pct>2pe>1p. Even after
son-
C\i
0 0
-01 co
re)
0 0 C\i 'IO
.,@ 0 0
4j 20
0 0
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0
4-)
(d
0 @4
4-)
CA)
4J 5 4-)
tn .4j
>1pT>1pA>2pj>2pB>2pL>2pr>2p.>2p. 56>1p-D2>1p.
,Number o>2pf >2p'>2p,>2pDati>2pents in >2pl>2p@>2pl>2p'>2p.>2pI>2piich Change
>2p,>2p4>2p,fter >2p3>2p0>1pL Placebo >2p!>2p,>2p->2p,>2pr>2pas Greater Than After 3>2p.>2pnL>1p.
C>1pH>2pA>1p2>2p.>2p!>2pG>2pE >2pG>2p.>1p7>2p1>2p->2p,>2pkT>2p7>2p->2p'>2p:>2p?
>2pi>2p,>2p;>2pZ>1pA>2pS>2pU>22pP>2p:>2pi
>2pK>1pne e j e r>2p'>2pX>2p'>2p->1p. >1p0
pupillary Size >2p5 >1p0
Systolic Blood Pressure 6 2 >1p0
Number of Questions 7 >1p1 >1p0
Grade >1p5 >1p1 6 2
>2pl>2p@>2plumber of Patients in >2p@>2p,>2p,>2p,hich Chance fter
>2pBOL Placebo >2p'>2p@>2p->2p2>2p1>2p->2pas Greater than >2pAfter >2pBCL>1p.
>2pKneejer>2pl>2p[>2pt >2p0
Pupillary Size 2 >1p0
Systolic Blood Pressure 2 >1p0
>2pl>2p,>2plumbe1r of Questions 2 >1p0
>2pC>2pTrade
>2p56>1p-E3>2p.
T>2pi>2pm>1pe Course of LSD >2pi>2pl>2p.eaction after Pretreatment with >2pK>2p@>2p.>2pdL or
>2pBOL Placebo A-or Fiv>2pa>1p-
Pupillary Size
Hours after 2 LSD
Treatment >2pc >1p1 2 3 >2p4 >1p5 6 7
>1p8
4>1p.2 >1p->1p.6
>2pDOL 5>2p.7 >2pg>2p@>1p.8 >2p- >1p.>2p1>2p@>2p,
>2p.>2p1>2p@>1p.3 5>1p.2
B>2pOL Placebo >2pL>2p@>1p.2 >2p1>2p0>2p.>2pi 2 6>1p.>2p8 6>1p.8 6>1p.6
6>1p.>2p1>2p@ 6>1p.1 6>1p.1 5>2p.>2p4>2p-
Systolic Blood Pres>1p,su>2pL>1p-e
>2pBOL 106 ill ill >2pi>2pl>2pl l>2pi>2p@>2p. 112 >1p1
>2p1>2p;>2p2 ill,, l>2pi>2p@
BOL Placebo 104 116_ 117 >1pll>2p'>2p-2>2pv >1p1>1p1>1p0>2p/ 119
>2p1>1p1>2p8 li>2p@ 116
>2pl>2p,>2plu>2pr>2p@>2p,ber of Questions
Hours a>1p->2pL>1p-ter
1>1p/2 1>1p-1>1p/2 2>1p-1>1p/2 >2p->2p@>1p->2p.>1p1>2p,>2p@2
>2pL>2p@>1p->2pI>1pL2 >1p1>1p2/2 7>1p-1>1p/2
ROL >1p0 2>2p.7 5>2p-4 6>1p.>1p- >2p11>1p.9 2>2p.7
2>1p.1 0>2p.7
B>2pOL Placebo >1p0 >2p.7>2p.9 16>1p.9 17>2p.>2p0 12>2p.>2p,>2p,>2p->2p) 6>1p.7
3>2p->1p->2p@ >1p1>1p.>1p0 0>2p.>2p->2p->2p@
Figures are ave>2prages of results on >1p1>1p0 3patients.
BOL dos>2page was I >2pmg>1p. orally three ti>2pr>2pies daily for f>2pl>2p-ve da>2prs
>2p->2pi>1p-ior
to LSD plus >1p1 mg. two hours prior to LSD.
LSD dosage >2pwas >1p1 mcgm>1p.>1p/kg>1p.
C Control >1p(>2ppredrug>1p) >1p->2p,>2pieasure>2p,>2p->2p,>2p,>2p-ent>1p.