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VI
ISD Nr. 15
Translation
of
Germ-n
original
_-C_OSS,
W.,
_kLADAM,
W., _UXER,
J.
(From the
Department
of
Clinical
Research)Crichton
Royal, _meries)
4-Lvser_ic Acid
Di_lamide
(LSD
25)
_
Carbohydrate
MetabQ1 _-m_.Prel 4m_
,._
Onm,,,n4
ation.
c
Nervemarzt 23j 3_ (1952)
The interest in the
newly discovered
substance
d-lysergic
acid
diethylamide
(LSD 25) can be explained by the fact that
it is effective in
dosage
of 0.01 rag.when given
orally
and
t can be considered as a substance capable of producing an
acute psychotic condition of the "exogenic reaction" type
(STOLL 19/.7).
The tremendous activity of
this
product suggests
that
the
intoxicative symptom-
might
be caused by an antienzymatic
mechanism
on
cerebral cellular metabolism. Since
normally
glucose is the
most
important and perhaps the
only
substance
required by the
nerve
cells (SOSKIN
and
LEVINE 1946), it seem-
ed
logic
to
analyze
the influence of the
drug on human
carbo-
hydrate
metabolism.
Experiments were made
on 2_
persons,
physicians
-_d
other
employees of our research
department
who received
in
the
morning before breakfast
0.0_
to 0.07
rag. of ISD
25
depending
on
their body weights. Prior to the experiment, these persons
spent 30 minutes in supine position completely relaxed after
which time the first blood sample was taken. Additional
blood s-mples were taken one and two
hours
after _n4stra-
tion
of LSD. On the following
day,
under the same conditions,
ontrol
experiments _ere made on 19 persons, 15 of which were
identical with the ones who had already received
ISD
and
others
(A-D in table). Since ISD solution is without color,
taste or smell, water was administered during the control
experiment without knowledge of the
persons.
The blood s_mples were tested for the following sub-
stances and according to the
methods mentioned
hereafter:
glucose (KING et
el.
1937), alkali reserve (HAWK et el. 1917),
lactic acid (BARKER and SUMMERSON 1941), pyruvic acid
(FRIEDEMANN and HAUGHEN 1943), inorganic phosphates (FISKE
and
SUBARROW
1925), acid soluble phosphates, adenosintri-
phosphate,
lipCidphosphate (GOTTFRIED end WILLNER
19_9),
hexose
monophosphate (CCBI and 00RI 1931). _
:__
-2-
The
results
of the I_D
group
-_ control
group
were
identical with the exception
of hexosemonophosphate
a_
glucose values
(see
table).
In
the
LgD
group
he_osGmono-
phosphate
increased
on
an average
of
1.7 mg./lO0
ml.
after
the
first
hour
while
in the eontrol experiment the values
decreased on
an average
of
2.3
and
2_
mg./lO0 ml. The
carbo-
hydrate values,
which only
showed
minor
changes in the con_
trols,
increased during
experiments
by 9
mg./lOO ml.
after
the first hour and by ii mg./lOO
ml. after
the second hour.
_raen fasting and
during pbysical
inactivity which were
maintained as
much
as possible
during
all experiments,
glycogen is the
most
essential carbohydrate reserve.
Hexose-
monophosphate
is the first step in the
breakdown of
glycogen,
During inactivity the carbohydrate reserve is consumed only
to
a
limited extent and therefore
we
expect the hexosemono-
phosphate content
of
the blood to
decrease. This
real_
happened
during
the control
experiments. The
increase in
hexosemonophosphate
or
the lack
of
decrease
which was observ-
ed
in 22
of
the 24
I_D
experiments suggests a greater
demand
on
glycogen.
However,
the increased carbohydrate
metabolism
did
not
coincide with an increase in
pyruvic
acid and lactic
acid levels
which
would have
been expected. In addition,
minor but m,_ked_y increased carbohydrate values in the blood
(adrenergic effect
?)
were noticed, which
also indicate
a
need
for carbohydrate.
The explanation
suggests itself that
the carbohydrate
metabolism
in the
presence of LSD
is inter-
rupted
and
cannot pass beyond the stage
of
hexosemonophos-
phate. These
results are
presented
in the following:
G_ycggen
hexose-l-_phosphate
locked by
I_D 25
>
h_se-6-phosphate
f
glucose
hexose-1:6
_phosphate
3-gly ceralde_ _de-phosphate
i :3-phosphogl
'cerinic
acid
J
3-phosphogl',
_cerinic acid
phosphop_
A
_vic acid
pyruvlc acid.
v
_ lactic
acid
÷%
0
•
_
_'_
3
_o
-- _
--_
"[_
-£-
-4-
Up to
now
we have
not been
able to prove clearly a cor-
relation between the strength and duration of the symptoms
caused by oral e_m4n4etration of
LSD
25 which
differ_
widely
from case to case and the chemical findings in the blood
ssmp_les. Though the hexosemonophosphate content of the blood
decreased
in two persons, they showed only
minor
psychic effects.
The effect on 22 persons in which an increase of hexosemono-
phosphate or at least
no decrease
was
noted,
varied from slight
mood changes to severe
disturbances
of perception, ideation_
consciousness and psyche.
If the theory is adopted that LSD 25 blocks the break-
_own of hexosemonophosphate and furthermore this blocking
action is held responsible for the psychic symptoms, then the
direct intake of carbohydrate, which can be utilized without
detour via hexosemonophosphate, should influence the c14-ical
picture of the intoxication. As yet we have
not made
enough
experiments to arrive at a
definite
conclusion.
Yet
it is
evident that the symptomatology (optical illusions, alienation
of perception, lack of concentration power, euphoria, etc.)
were
modified
and partly
disappeared
after intravenous admi-
nistration
of 33% glucose solution.
Dur4ng and after the injection of glucose, the blood
glucose was
determined
at brief intervals (approx4_tely
I minute). When the experiments were
made,
one of our co-
workers recorded accurately the general reaction and appear-
ance of symptoms. The effect was
not manifested
_,_diate_7
and only lasted from 3 to 5 m4nutes and coincided with a blood
sugar level of 200--300mg./IO0
ml.
Control experiments with
inJections of saline solution on the same persons did
not
result in any clinical change.
The connection between psychic effects and chemical
changes in the blood produced by ISD 25 is probably
not
a
simple
nor
a
direct
one. The aforementioned experiments
would suggest that the effects of the
drug
_nd the chan£es
in blood chemistry are hardly coincidental.
Sandoz was kind enough to supply us the agents
necessary
to conduct these experiments. We
are
especial/y grateful to
Prof.Dr.E. ROTHLIN, head of the Pharmacology Laboratory.
-5-
BIBLIOGRAP_
BARKER, A., SUMMERSON, T.:
CORI, G.T., CORI, C.F.:
J .biol.Chem. _8,
535 (1941)
J .biol.Chem. 94, 561 (1931)
FISKE, C.H., SUBARRGg, Y. : J.biol.Chem. 66, 375 (1925)
FRIEDEMANN,
T.E., KAUGHEN, G.H.:
J.biol.Chem.
147, 415 (1943)
GOTTFRIED, S.P., WIILNER, H.H.:
Arch.Neur.(Am.) 62, 809 (1949)
KAWK_ P.B., OSER, B.L., SUMMERSON, W.H.: Practical Physiologic-
al Chemistry,
London,
Churchill 1947
KING, EeJ., KASLE_4OOD,G.A.D., DELORY, G.E.:
Lancet 2_2,
886 (1937)
MAYER-GR0SS, _.,
McADAM,
W., WALKER, J.W.:
827 (1951)
Nature 168,
SOSKIN, S., IEVlNE, R. :
Carbohydrate
Metabolism,
Univ. of
Chicago Press, Chicago
1946
STOLL, W.A. :
Schweiz.Arch.Neur. 60,
I
(1947)

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