HEALTH, EDUCATION, AND lvvELF/
                                                                  PuaLIC HEALTH SERVICE
                                                                    LEXINGTON. KENTUCKY
                                                                     t6 September  1953'
            PusLic HeAt.Tm SERvict HosriikL
         NIMH      A2ddictio@,          Res ea re.h       Ceii te
                           Ycu.may  be          interes-fed   In  the  pr,,)cress  of                     our                exoerimen@s
                           with-  LSD  f'o  date.    Originallywe  had'planned                                    to  determine
                           the  @hreshcld            ddse  for  each2  oati.ent                   individually,  and  this
                           was  atteinoted           e-3cly  in  Augus't,  usin                               ty  of  LSD  which
                                                                                              9  a  s u-.,)p
                           was      more       thcin.,@two       years       old.
                                                2                                                                                              
3W
                           Negative  sub;ective  reports  were  obtained                                    with  doses  of
                           20       to       70       micrc-crams.       Finally,       patients        were        given        100       
micro-
                           grams   in  divlded  doses,  with  marked  subjective2  effects   (as
                           well      as      oblei@tivel      appearin-C,      in       all       5       patients'.       We       then
                           a t fzmo fed  t,-@  t i t ra t e, t h e  e-l@-Tec f s   1 n           each         pati.-.nf,         gi,ting
                           doses     of      80      to.      90      micro!Crams2     V z r:y_   little  effect  was.  observzd.
                           Thesz     doses  werz  adr-.lnlst-@red  on  the  day  following  the   IC'-,@ micro-
                           cram,dose.    These  doses  were  r'aised:.progressively  until   120-tc
                           130      microcrars      were      beinc      civen      to      4      of'the       sub       ects       and
    2                       90 microgra.ms   to  the  other,  wlfhoull                            any  sicnificant  effects
                           of  any  kind.     It  was  found  that  the                          time     of      day      did      not     
alter
                           the  lack-of  effects  a@ndl  also,,  that                            a  fresh  supply  of  LSD
                           produccd  no  c2han--,e   tn  the  effects,  or  lack  of  therri.
                           Since      the      lack      of       effects       nic?ht       be       due       to       tolerance,      
adminis-
                           tr      ation      of      the      drug      was      @4is@ontinued      and      after      five       lays      
was
                           acain                        2         wtih  m,@rkp,4-  subie-cf tv,--'                         MbTv.,cf-lvo.,
                           chances  ai:Deeri--,  with  doses  of  90  to                                    micr.:)c-,rams.               a n -
                           'Wh I I e    tests     of     the      drur-      in      indi,viduals 2     'W,@o      had      not      been
                                              tt  h,4d      s-ho win   i t r
                           receicinc                                            n a  0 c s     i v e  r    i u I t s      The            
findincs
                           --w@e r.! %se ry  @st.#-ces  iy            T  r .;a  !'c@4  dz v  2      m
                                                                                           elc@z,  e,-4@  of folerarce.
                           It  -'was$     therefore             necessary  fc  obta in  neasuremen@s  af'ler
                                                            .1
                           single       doses  at  widely  scattered  intervals.    As   Iona  as   t@@z
                          0 intervai'vias            as  much  as  3  days,   flizrc  wa-s  no  notice@ble
                                                            D-eci.a@3i4lied  bY   4-7e@,l    87475
                                                            date

              decrease   In  effect,  but there may  be some  decrease  -in effect
                -f the -dru@ig Is' admtnlstered everyl third day..
              -Whe-n §Ive; at proper in terva Is   LSD I ndtices,. ver@' def in I te
              blood  pressure  rise, poolildry    dilatation, Increase in deep
              tendon  reflexes,  and  diminution  in   superficial   skin   reflexe2s.
              T@e puoillary.effects and blood      pressure'effects appear to
              be suitable for measurements of      tolerance.
              LSD  aopears to' fac,ifitate  synchro'm-'tzation of the efectro-
              encepha.locram  by  photic-  stimulation.   Photic   stimulation   also
              seems to' ienhance, the percept !on o f e I emet,2 ta ry ha I I uc Ina f ions .
              Apparently the supply@of,LSD is quite limited and we         may be
              unable to obtain sufficien-t amounts of the drug to carry out
              the study as art'ginally planned.  However, we believe we
                                                      lish the fol tcwing:
              have sufficient material to accomp
              11 Effects of l2arger doses  in non-tolerant patients.;
              21  Determination  of  whether  tolerance  occurs  after   one   single
                  dose of LS;O;
              31  Controllecf@studies   -of  toterance.develoorent  in  5   patients-
              4 1 Comparison of         I f h L,2(E
                                       -Sincerely  yours,
                                        Harris  Isbell   m2.D.
                                        Director  of  Research
                                     t)eclassified by 18747Z-
                                      date