A M A Archives of Neurology & Psychiatry
November 1, 1956
Harris Isbell
112 citations
Lysergic acid diethylamide (LSD), in doses of 20 to 120 micrograms, induces a striking mental state marked by anxiety, autonomic dysfunction, visual perceptual distortion, mood changes, synesthesias, depersonalization, and hallucinations. It is described as the most effective and safest agent for producing a reversible, experimental psychosis in nonpsychotic subjects. Interpretations of this state vary: some European authors classify it as a toxic psychosis of the exogenous reaction type or a diencephalosis, citing autonomic signs that suggest hypothalamic involvement, while others emphasize the resemblance of its psychic manifestations to symptoms of major psychoses.
A M A Archives of Neurology & Psychiatry
April 1, 1957
Harris Isbell
50 citations
Chlorpromazine can both prevent and reverse the abnormal mental state induced by LSD-25, while azacyclonol (Frenquel) and reserpine are ineffective. In experiments with adult male drug addicts, chlorpromazine given before LSD prevented the reaction, and given during the reaction it rapidly brought subjects back to normal. Azacyclonol and reserpine did not block or reverse the LSD effects. The LSD reaction is measurable and reproducible, suggesting it could serve as a screen for predicting the clinical value of new tranquilizing drugs and help elucidate mechanisms of action of both tranquilizers and psychotogenic drugs.
A M A Archives of Neurology & Psychiatry
January 1, 1956
Bert E. Schwarz
49 citations
Injecting drugs directly into the brain's ventricles can produce complex behavioral changes in cats, including sleep-like states, muscle weakness, catatonia, and convulsions. This method allows researchers to study how chemicals interact within the central nervous system. Of particular interest is the possible antagonism between lysergic acid diethylamide (LSD) and serotonin, which had previously been shown to affect smooth muscle. This antagonism may be relevant to schizophrenia, as suggested by Woolley and Shaw. Other drugs of behavioral interest include mescaline and adrenochrome.
A M A Archives of Neurology & Psychiatry
February 1, 1958
Theodore Greiner
47 citations
After 14 years of research, the full range of human responses to lysergic acid diethylamide (LSD-25) remains incompletely described. Most attention has focused on dramatic schizophrenic-like symptoms produced by doses of 40μg to 100μg. The threshold for activity is generally accepted as 20μg, but the effects of smaller doses are uncertain due to perfunctory administration. A controversy exists over whether LSD symptoms mimic schizophrenia or represent a toxic organic psychosis. This preliminary note reports that understanding the complete dosage-response relationship could help resolve this debate, though early stages of toxic psychosis have rarely been described in psychopathological terms, while a firmer basis exists for comparison with schizophrenic processes.
A M A Archives of Neurology & Psychiatry
June 1, 1956
Nicholas A. Bercel
35 citations
Experimental psychosis research has a long history, possibly beginning with Cannabis indica administered to ancient Hun warriors. Scientific experimental psychiatry emerged in the late 19th century during the Kraepelinian era, when the organic theory of psychoses was prominent. Beringer's experiments with mescaline marked a milestone, as many induced symptoms closely resembled those of schizophrenia and the drug showed selective affinity for the brain. The discovery of LSD-25 by Stoll and Hoffmann was even more significant because it worked similarly in infinitesimal amounts. Stoll (1947) proposed the pharmacological designation Phantastium for LSD-25 and classified the resulting model psychosis as acute.
A M A Archives of Neurology & Psychiatry
February 1, 1958
H. A. Abramson
31 citations
A compound called 1-methyl-d-lysergic acid diethylamide (MLD-41), chemically similar to LSD-25, produces reactions in both Siamese fighting fish and humans that are indistinguishable from those of LSD-25, but with a higher reaction threshold. In fish, MLD-41 is about one-tenth as effective as LSD-25, while in humans it is about one-third as effective. Prior administration of MLD-41 for several days induces tolerance to LSD-25 in humans, suggesting a different blocking mechanism than that seen with crude beef brain extract.
A M A Archives of Neurology & Psychiatry
May 1, 1958
Robert S. Liebert
30 citations
Lysergic acid diethylamide (LSD-25) alters size perception of one's own body and objects in space in both schizophrenic and normal adults. The study, grounded in sensory-tonic field theory, shows that changes in organismic state from LSD produce corresponding changes in perception, consistent with the theory that perception reflects the relation between organismic state and external stimuli.
A M A Archives of Neurology & Psychiatry
February 1, 1957
Robert S. Liebert
23 citations
A change in the organismic state induced by the drug LSD-25 affects spatial localization. The study was conducted within the sensory-tonic field theory of perception, which holds that perception depends on relations between stimulus conditions and the organism's state, rather than being an isolated event. LSD-25 produces primitive behavior in normal adults, and the experiment examined how this pharmacological agent alters spatial localization.
A M A Archives of Neurology & Psychiatry
September 1, 1957
William K. Boardman
21 citations
A moderate to low dose of LSD alters time perception in healthy subjects, making them overestimate short audible durations, a pattern also seen in schizophrenia. The study used the same method previously applied to schizophrenic patients, who overestimate such durations more than controls. LSD's capacity to produce schizophrenic-like behavioral changes includes shifts in time sense, with experiences of acceleration, slowing, or even nonexistence of time, though true disorientation is absent.
A M A Archives of Neurology & Psychiatry
December 1, 1957
Lincoln D. Clark
19 citations
Recent interest in psychotomimetic drugs has prompted a search for agents that block drug-induced hallucinations and psychological disturbances. Reports conflict: azacyclonol (Frenquel) was said to prevent LSD-25 psychoses, but one author could not confirm this. Chlorpromazine, serotonin, and reserpine have been reported to both ameliorate and intensify LSD-25 effects. Amobarbital sodium and chlorpromazine did not prevent intoxication but had suppressive effects at peak intoxication. The confusion stems from failing to distinguish true pharmacological antagonism (blocking) from suppression.
A M A Archives of Neurology & Psychiatry
September 1, 1958
B Weiss
8 citations
Lysergic acid diethylamide (LSD-25) is known to enter the brain, but how it produces psychotic patterns in humans remains unknown. Experiments on intact animals may help uncover chemical processes related to schizophrenia. Researchers studied the effects of respiration inhibitors such as potassium cyanide, sodium azide, hydrazine, and oxygen lack, as well as oxidation-reduction indicators like methylene blue and Bindschedler's green, on Siamese fighting fish. It was previously shown that small doses of LSD-25 in the surrounding water markedly change the fish's behavior. The current report adds that potassium cyanide and sodium azide also act on the Siamese fighting fish.