43-Y
                    d-Dihydro-lyser,gic acid diethylamide (V-A-24,).
                'These experiments were carried out to determine If d-dihydro-
            lysergic acid diethylamide (V-A-241) has psychotomimetic properties,
            and to assess roughly its potency in.this respect as compared
            with LSD-25.  V-A-2Jl Is known, to be about one-half a2s potent as
            LSD in blocking serotonin-induced contractions of the isolated
            uteririe muscle of the rat.  No previous human trials were knoum.
                                       METF-ODS
                 Subjects.  All the subjects were nontolerant former
            Lriorphine addicts .vhb were serving sentences for violation of the
            Federal narcotic la@irs. All were physically healthy and 9 none
            pre!@.ented any of the major psychoses.
                '-Gen.eral CQnditions. Subjects entered a special ward  on
            the night before experiments were conducted.  During the exder-
            lmental day they could-remain in their own rooms or  mix  with
            other patients in a common day room'.
                                                                         x@5 --I

                                                                     Page
                       'd D
               Drugs.      ihydro4ysergic acid  diethylamide'was  given  in
           solution at 8 a.m. with the patients fasting.  Preliminary
           experiments were conducted in which single patients received
           V-A-24 in doses Increasing from 0.5 to'5.0 mcg/'.kg.  The  proper
    2       dose range was found to be 3.0-5.0 mcg/kg, so that ill
           12 patients were given these doses in a randomized balanced
           order.  Placebos were not done.  For comdarison, data on
           9 patients who  receiveId 1.0 and 1.5 mc-g/kg of LSD-25 In another
           experiment are Included.
                Observations, Observations were  made  at  hourly  intervals
           once before and eight times after administra2tion  of  the  drug.
           The standard routine.of the Addiction Research Cente.r for drugs
           of the LSD type was used.  The  observations  included  systolic
           blood pressure,,pupillary diameter, and threshold for the
           knee erk. The change after drug  was  calculated  by  subtracting
               J,
           the average of the pre-drug observations from the values at each
           hour after drug.  The areas under the time-action3 curve composed
           of these areas was calculated by the method of Winter and
           Flataker (1).  The number of responses on the questionnaire
          @which were not scored positively before the  drug  were  counted.
           "Clinical gradeslt were assigned by.the system of Isbell et al (2),
           and were based on short psychiatric  examinations  performed  at
           intervals after the drug.

                                      RESULTS
                The results-are tabulated in Table 1.  They show that
           V-A-2L induces'a pattern of change similar to that caused by
           LSD; but is,, of-course, less potent.  From the data, it appears
           that V-A-24 is roughly slightly less than one-third as potent
           as LSD.
                The mental phenomena after!V-A-2L were similar to those
           reported aft8er LSD and included nervousness, anxiety, a sense
           of strangenerss-, haptic sensations, visual perceptual distortion,
           and, in sensitive patients, visual-hallucl-nations.
                                      SUPIAARY
                1.  d-Dihydro-lysergic acid diethylamide is a psychotomimetic
           drug.  It is about one-third as potent as LSD.

                                                                    P a,, 3 e
                                    REFERENCES
                1.  WINTE.R, C. A.- and FLATAKER, L.:  Studies on-Heptazone
           (6-Morpholino-LL  -dipheriyl  -heptanone hydrochloride) in
                         .,4         -3
           Comparison with Other@Analgesic Agents.  J. Pharmacol. & Exper.
   2        Therap., 98: 305-317 (i4arch) 191:@0.
                2.  ISSELLJ H., BELLEVILLE, R. E.j FRASER$ H. F.t WIKLER, A.,
           and LOOAIN. C. R.:- Studies on Lysergic Acid Diethylan-ide.
           1.  Effects in Former Morphine Addicts and D-evelopment of Tolerance
           During Chronic Intoxicatior,,.. A.M.A. Arch. Neurol.8 & Psychiat.
           76: 468-LI,78 (Nov.) 1956.

                                                                                                                                             
@y
                                                                         Table 1.
                               Comparison of the Effects of d-Dlhydro-lysergic acid diethylamide and LSD-25.
                   tIrASURE                                                         DRUG AND-DOSE_(mcg/2lig)
                                                     Placebo'           LSL)-25          LSD-25'*          V-A-24             V-A-2,1@
                                                                          I.o                1.5              3.0                5.0
                   fli.tpillary Size                    0.2 ±    l@4      10.2 ±   1.18  +15.20      2.  1  +  8.0      1.7    +12.1   t   1.7
                   blood Pressure                      15.6  ±  13.5   +611..8 ± 10.9    +94.6       17.5  +  69.1     21@. 1  8@.6  ±   12.1
                   F'ntellar Reflex                  +20.7      II.I.-   -50.9   31      -72.9       21.7    -68.7    15-4       91.1    22.9
                2   l@,iiimber of Positive
                   Pr@r,ponses on Questionnaire         0.1     0.3     57    ± 23.2      98    ±    26.6     15.5     6.4       38.7 ±   15.6
                   f-:Ilnical Grade                     0    + .0          2.2 ±  0.38       2.8 ±  0.17..    0.63     0.27       1.5 ±  0-h-8
                                      1.  F0igures  are  means   ±   stan4ard   errors   of observations   on 9 subjects.
                                     2.    Figures  are  means  ±   standird   errors   of observations   on 12 subjects.