CATION, AN6
                                -,F HEALTH, EDU
                                   NATIONAL  INSTITUTES                OF    HEALTH-
                                                    25 April 1957.
         "O MCPLMMIG AGORCSS T149
       "A""AL flel'n?Uft Of "CRTAL NSAL?"
                RaggARC.M ceftyllp
       U.S. ftsuc mcitlrm seltvict HOSPITAL
             P. 0. Dow zooo
           Lui*ol*m. xilmracxy
                   am enclosing copy of proposed budget forlf'scal year
                1958 which has already been sent to Pir. Robert E. motley,
                Administrative2-Assistant for 3asic Research
                                                                    National
                institute of pAe'
                                 rtal. Health.  He will submit 14 shortly
                                                                    c      lette,-
                to the Office of Naval Research.  Also enclos"d Is
                to &ir. flotley asking him to Increase item         under  tra2vel.,,
                The material-I   have been using    Is designaied   as 1-me-thyl-.
                lysergic acid dlethyla,-nide.  it bears the Sane-oz code
                number iviLD-41, Lot No. 060001      271001.
                Ani.,nal pharzr-acology Indicates toxicity is about    equal' to
                that of LS-ri In mice.  The material Is 3.7'tir,-.es   as  active
                as LSD in inhibiting serotonin.  it Is pyrogeric In the
                rabbit, but less so than LSDT  in mice it is said to proditce
                only miiir..al excitation and no mydriasis..    'in the cat..
                effects are a little different tha.,i those     produced   by LSDJ.
                but studies are not complete.
                EVRI.T!a2tion       all&4%. 4@-A W-uviz incomo'iet-es indicates that the-
                material produces effects     In man somet-itl@-at lilte LSDs but
                that hiLD Is-less potent.     tt induces-mydrlasis,    e'levation
                                                           -D
                In blood pressures:facilitation of dee  tendon re2flexes
                                                   LSD-like sub@'ective sy-r,,pto..mS*
                and the usual constellation oL
                The dose recuired to Intl-tz--e a Grade 3 reaction i--tr prc@)a,-,@ly
                .on the order of  Li-6 mcg./K-. as compared with 2 mcg./kg     .
                of LSD.
            0    0 '%,.her rlaterialsilaie are I-acetyl-lysercic aci%Ak
                bitartr,,-tz (;,LD-52) and Pyrrol.idid of d-lyser-ic acid (LPD-821L).
                                               Sincerely   yot, r.s.,
                                                                       left
                 -losures

                                                        ge
        to the Abramson-larvik   questionnairep and   assessment   of
        the degree   of the reaction by  the clinical  gradi-fig system
        previously-described.    Mefhods.of han ling   these data have
        been previously. reported*
              Results.  The results  are  shown  In the   accompanying
        2table and are suggestive of   a   reduction in  the  intensity
        of the..LSD reaction.' They  show a  reduction  in  every  aspect
        of the LSD reaction measured.  The differences bet*een
        the response seen after SOL plus LSD and those seen after
        SOL-placebo plus  LSD  reached  statistical  significance  in
        the case of effects on   the kneelerks  and  on  blood  pressure,
        but were not  significant on 2 measurements  of'  pupillary  size,
        number of questions., and clinical grade.
              The experiment actually was unsatisfactory    for   several
        reasons:  (1) The number of subjects was small because
        Of the shortage of BOL; t2) Six of the subjectt were new,
        and 4 of these proved   to be non-responders (had no mental
        symptoms with the dose of LSD used) with resufflng      skewrt
               2                                                      ess
        in fhz statistics; t3) fhe eesull's of '@"Oinzel andMayer-Gross
        suggest that  cross-tolerance to   LSD It de ve I op I -,ig   which
        likely 'would 'not be complete  i n- 2 da Vs
                    -only 2 ex erien ed    subjec's ava i la-b le., t h e
              In the           p9     c
        LSD reaction was  almost  totally   blocked by   pretreatment
        wlth  SOL.