ELYMOCLAVINE (43-Y).

• Document Type: SPECIALCOLLECTION
• Collection: General CIA Records
• Document Number (FOIA) /ESDN (CREST): 00151761
• Release Decision: RIPPUB
• Original Classification: U
• Document Page Count: 7
• Document Creation Date: January 21, 2025
• Document Release Date: September 8, 1976
• Publication Date: May 13, 1959

Page P
METHODS
Subjects,. NOntolerant former opiate addicts who were
serving sentences for violating the Federal narcotic laws
volunteered for these experiments. All were healthy males
between 21 and 40 years.of age who presented no evidence of
any of the major psychoses on mental status examinations. All
had experienced the effects of LSD-25 in previous experiments.
General Conditions. The experiments were conducted in a
special ward. Patients entered this ward on the night before
experiments were conducted, and were observed hourly by
specially trained attendants. Between observations the patients
were free to remain in their own rooms, to sleep or to socialize
with other patients in a common day room.
"Druos�. Elymoclavine was given orally in solution at 8 a.m.
The taste was masked with cherry syrup.
In preliminary experiments, the dose of elymoclavine was
cautiously elevated from 1 mcg/kg to 7.5 mcg/kg. No psycho-
somimetic effects were observed, and with the larger doses
patients began to report headaches and drowsiness. Accordingly
Page L.
V-A-22 did, however, induce symptoms differing from those
of LSD. The most. commonly reported symptoms were sleepiness
and relaxation .(Table 2).
DISCUSSION
Like agroclavine and Lill' 23194, elymoclavine had sedative
effect, rather than ps'ychosomimetic effects in man. Whether
such sedation could-be exploited therapeutically remains to be
determined. /
In further woi-k, the sleep-inducing properties of elymoclavine
should be compared with those of a barbiturate.
13 May 1959
ELYMOCLAVINE (43-Y
Elymoclavine (J-A-22) is a material isolated fro.m a cultured
saprophytic fungus by the Research Laboratories of Takeda
Pharmaceutical Industr:ies in Japan. It is related to agro-
clavine (f-A-18) and to dihydroagroclavine, both of which have
sedative and hypnotic effects 1.n man, although they are
primarily exitant in animals. All these drugs are related to
the ergot group. In elymoclavine the acid amide group of LSD
has been replaced with a hydrogen and a CH20H group.
According to Yui and Takeo (1) agroclavine and elymoclavinc
cause a syndrome of "central sympathetic excitation" in mice,
rabbits, cats and dogs manifested by mydriasis, tachypnea,
convulsions, hyperactivity, etc; whereas dihydroagroclavine,
dihydroergokryptine, etc., cause sedation. Elymoclavine and
agroclavine had analeptic effects in reserpine sedated mice.
Because of discrepancy in the effects of agroclavine (in
animals, excitation and in man, sedation) a preliminary study
of elymoclavine was thought to be of interest. The study was
designed to determine the effective dose range in man, and to
�
determine if LSD-like (psychosomimetic) effects were induced.
(N(
Table 1.
Comparison of the Effects of Elymoclavine (V-A-22) with those of LSD-25.
DRUG AND DOSE (mcg/kg)'
MEA0URE
Placebo'
Pupillary Size
Blood Pressure
Threshold for
knee jerk
ILSD-251
1.0
1.1..11101.4*.moloom.00�11.40����������������������
0.2 � 1.4
+15.6 � 13.5
+20.7 � 11
Tctal positive
rcsponses on
Olestionnaire 0.1 � 0.3
Clinical Grade ,0 � 0
ELYMOCLAVINE
10
20
25
+10.2� 1.2
64.8 � 10.9
-50.9 � 31
57-* � 23.2
2.2 � 0.4 ,
- 0.4 � 1.3
+25 4 11
- 7.6 � 1.
5 � 1.3
0 � 0
I....." .111.411.4 1.0.4 �
1.2 � 1.3
+43 � 14
8 � 1.
7.3 � 1.9
0� 0
3.0 � 2.2
-16.7 �
5.2 � 3.2
0� 0
- 1.9 � 2.5
.494.5 � 8.7
+10 � 9
1. Figures are means � standard errors of observations on 9 subjects in the
6.5 � 3.9
0�0
case of placebo and 1 mcg/kg of LSD; 12 subjects in case of 10 and 15 mcg/kg
of V-A-22; 5 subjects in case of 20 mcg/kg of V-A-22; and 4 subjects in case
of 25 mcg/kg of V-A-22.
Page 7
Table 2. Incidence.of Certain Symptoms after Elymoclavine,
10
,
SYMPTOMS
12
Sleepiness
/
9
Relaxed -
7
Headache
2
Nausea
3
Dizziness
0
Feel "different"
7
DOSE (mcg/kg)
15 20 25
Number of Subjects
12
9
4
4
0
8
5
a
3
2
3
2
2
0
2
2
1
0
2
2
Page 3
more formal experiments were carried out in which 12 patients
received on two separate occasions 10 and 15 mcg/kg of V-A-22.
In addition, 5 patients received 20 mcg/kg and L. received
25 mcg/kg.
Observations. The following observations were made at �
hourly intervals twice before7and eight times after adminis-
tration of V-A-22: pupillary size, systolic blood pressure,
and threshold for eliciting the kneejerk. In addition patients
completed a questionnaire hourly, with the help of an aide, and
short mental status examinations were made at appropriate
intervals. The methods of making the observations and analyzing
the data were described by Isbell et al (2,3). For comparative
purposes, data on 9 other subjects who received a placebo and
1.0 mcg/kg of LSD in other experiments are included.
� RESULTS
The combined data are presented in Table 1 which shows that,
as compared with LSD-, elymoclavine had relatively minor effects
on pupillary diameter, threshold for kneejerk, and blood
pressure (except at-the 25 mcg/kg level). The table also shows
the lack of any psychosomimetic effect, even with 25 mcg/kg.
Positive responses on the questionnaire after elymoclavine were
usually to such items as: "I feel sleepy," "I am nauseated," etc.
B
Page 5
REFERENCES .
1. YUI, T. and TAKEO, Y.: Neuropharmacologica,1 studies
on a new series of ergot alkaloids. Elymoclavine as. a potent
analeptic on reserpind sedation. Japanese J. Pharmacol.,
157-161 (March) 1958.
2. ISBELL, H.,' BELLEVILLE). R. E., FRASER, H. F., WIKLER, A.,
and LOGAN,,C% R.: Studies on lysergic acid diethylamide.
I. Effects in former morphine addicts and development of
tolerance during chronic intoxication. A.M.A. Arch. Neurol.
& Psychiat., 76. 468-478 (Nov.) 1956.
3. ISBELL, H., LOGAN, C. R., and MINER, E. J.: Studies
on lysergic acid diethylamide (LSD-25). III. Attempts to
attenuate the LSD-reaction in man by pretreatment with neuro-
humoral blocking agents. A.M.A. Arch. Neurol. & Psychiat.,
81: 20-27 (Jan.) 1959,