1954_rinkel_1532_2.pdf

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_I ISD No. 67 (§102a)
M
M
M
J
L
L
377 psychotic effect
M 409 psychologicaltests
500properties
F 17 urine
analysis;
249 lobotomy
ACTH (§407f)stimulation
20 carbohydrate metabolism
lll.4 autonomic drug tests
115.5 adrenaline cycle
RINKEL, M., HYDE, R.W., SOLOMON, H.C. (Dept.of Psychiatry, Harvard Med.School &
Boston Psychopath.Hosp., Boston; Dr.H.C. Solomon)
_erimental
psychiatry. III. A chemical' concept of psychosis.
--
J.Nerv.Syst. 15, 259 (1954).
The effects of LSD on normal subjects, schizophrenic patients and patients
with affective disorders: clinical manifestations;
psychological tests; biochemical
studies; ANS phenomena; pharmacodynamic studies. An attempt to develop a chemical
concept of psychosis.
M_THOD and DOSAGE: O.12pg/kg - 2.0pg/kg (usually l.O/_g/kg) LSD orally at 8 a.m.
Subjects under observation throughout the day. Control studies: I) pre-experimental
evaluation of subject's personality and motivation (which allowed prediction of
reactions) ; 2) Placebos (water); 3) Observer kept ignorant of whether LSD or
placebo was administered; 4) Series of 7 experiments on one subject at one-week
intervals, neither the subject nor the observer knowing whether LSD or placebo was
administered.
MATERIAL: Personal experiments, studies on mor_ than 100 normal volunteers, ll
Schizophrenics
and 4 patients with affective disorders.
E_SULTS :
i.) Clinical manifestations: depended on dosage; doses of lpg/kg and above
caused phenomena of the schizophrenic turmoil types; doses below lj_g/kg more often
induced affective reactions. As the usual dose was l p_kg,
the clinical
manifestations were predominantly characterized by a syndrome similar to a moderately
acute schizophrenic upheaval of the turmoil or the schizo-affective type with or
without catatonic features. Disturbances of thought processes and distortions of
perception were quite c6mmon; other manifestations were related to behaviour,
affect and mood. Hallucinations,
illusions and delusions occurred occasionally.
DepersonalizatiOn,
suspiciousness and paranoid reactions were frequent. Hostility,
often associated with extra-punitive or intra-punitive anger, was noted - when the
subject was hostile, he tended to devaluate the object, "a diabolical face"bUt When
the subject's attitude was affiliative, he tended to overvaluate the object, "big,
my very Rock of Gibraltar." Psychological tests (Rorschach, Wechsler-Bellevue,
Draw-a-Person,
Thematic Apperception) tended to corroborate clinical observations
and uncovered new phenomena, such as the subject's reduction in organization and
integration , loss of emotional control and decrease in orientation to past and
future. Anxiety and tension were increased in some subjects and decreased in others.
The subjects were aware that the LSD experience was temporary; insight remained
pres a_rved.
2.) Biochemical studies: One day devoted to controls, one day to LSD. Urine samples
taken at 9 a.m., 3 p.m. and 6 p.m. 0.5 _g/kg LSD given at 9 a.m. 25 rag.ACTH given
i.m. at 3 p.m. Urine samples analyzea for rates of excretion of urine, creatinine,
17-ketosteroids, sodium, potassium, phosphates and uric acid. LSD appeared to
stimulate the pitiutary-adrenal axis, probably in the manner of a non-specific
stressor. LSD seemed to render the adrenals somewhat unresponsive to ACTH stimulation,
a similarity to findings in schizophre__ia.LSD depressed the urinary phosphate output
but increased it under the additional stimulation of ACTH (a similar pattern seen
in schizophrenics).
3.) ANS Dhenomena were present in all instances and always preceded the mental
phenomena. The subjective autoncmic experiences manifested
themselves as dysfunctions
of the different organ systems. On objectD_e examination (clinical observation,
polygraphic recordings and pharmacodynamic_methods),
the pupils gradually dilated
after LSD from 3 ram. to 5.25 ram. within 2_ hours. Control studies demonstrated
convincingly _that psychodynamic interviews
did not influence the phenomenom. B.P.
was slightly lower after LSD; however, with LSD, B.P. became
somewhat higher after
psychodynamic interview (average 132/94 ram.Hg) and someWhat lower on control days
(average 125/99 mm. Hg). Heart rate was higher than normal under the influence of
LSD and was more stable. Respiration during LSD studies was faster and showed a
greater variabilltyin
length and depth.
4.) Pharmacod_namic studies (ll schizophrenics and 4 cases of affective disorders):
0.025 mg. nor-adrenallne i.v., 0.025 mg. adrenaline i.v. and 2.5 mg mecholyl i.m.
were used to test autonomic reactivity after 0.5_g/k_ LSD orally. Under LSD, the
systolic B.P. response to nor-adrenaline (61.5 mm.Hg ) was not significantly
different from the controls (68.2 mm.Hg ), but the response to adrenaline was
significantly lower after LSD (57.6 mm.Hg) than in controls (85.4 mm. Hg ). After
the effect of LSD had become manifest there was only a slight response to meCholyl.
More pronounced responses to adrenaline and mecholyl were observed in a successfully
lobotomized patient.
Under LSD this patient relapsed into the pre-lobotomy physical
and mental state of agitation, but the effect subsided within a few hours.
5.) Chemical concept of psychosis: In analyzing their observations and those reported
in the literature_ the authors were led to assume that LSD may interfere with a
major enzyme system° The most outstanding phenomena seemed to implicate the
adrenaline system (dilatation of pupils, changes in B.P., increase in respiratory
rate, varied responses to adrenaline and nor-adrenaline, mild response to mecholyl,
manifestations of hostility with associated anger). Moreover, the study by WITT
(LSD No. 8) suggests that the adrenaline supply of the spider becomes exhausted.
These phenomena suggest that the enzyme system of the adrenaline cycle may be
involved. MAYER-GROSS et al. (LSD Nos l0 and 15) reported that LSD interfered with
the carbohydrate cycle at the hexosemonophosphate
level. The authors of the present
paper could not confirm this in normal subjects.
It is possible that adrenoxine (a break-down product of adrenaline), in
addition to its LSD-like physiological effects, may also have mental effects similar
to those caused by LSD interference with the adrenaline cycle. If this assumption
proves correct_ the inevitable conclusion will be that adrenoxine is operative in
psychosis.
COMMENT:
Further evidence is required to substantiate the assumption that LSD inter-
feres with the adrenaline cycle in the manner outlined. The effects of LSD on a
lobotomized patient are of particular interest. No details
are
given of the studies
which resulted in non-confirmation of the findings of _&YER-GROSS et alo
(Experimentelle
Psychiatrie.
III_ Eine chemische
Theorie
der Psychosen)
Die Wirkung yon iSD bei Gesunden (in klinischer Beobachtung und gelegentlich
psychologischer
Teste) entsprachen den bereits in der Literatur berichteteno
Nach den Ergebnissen biochemischer Untersuchungen
scheint LSD die Hypophyse-
Nebennieren-Achse
zu aktivieren. Wie bei Schizophrenen ist die Ansprechbarkeit
der Nebennieren auf ACTH nach LSD herabgesetzt und auch die renale Phosphat-
ausscheidun_ ist in _hnlicher Weise ver_ndert. Die BD-Reaktion auf Adrenalin
war nach LSD imVergleich
zu Kontrollversuchen
signifikant abgeschw_cht. Unter
LSD trat bel einem lobotomierten Patienten die gleiche psychomotorische Erregung
auf, wie sie vor dem Eingriff bestanden hatte. Auf Grund dieser und der in der
Literatu_ berichteten Ergebnissen nehmen die Autoren an, dass LSD in den Adrenalin-
abbau eingreift und dass Adrenoxin (einAbbauprodukt
des Adrenalin) bei der Ent-
steh_mg der Psychose eine Rolle spiele.
/Or.Sp
bp/255
(ED 71%2) w@_

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