Objective: Phencyclidine (PCP, “angel dust”) induces a psychotomimetic state that closely resembles schizophrenia. As opposed to amphetamine-induced psychosis, PCP-induced psychosis incorporates both positive (e.g., hallucinations, paranoia) and negative (e.g., emotional withdrawal, motor retardation) schizophrenic symptoms. PCP-induced psychosis also uniquely incorporates the formal thought disorder and neuropsychological deficits associated with schizophrenia. The purpose of the present paper is to review recent advances in the study of the molecular mechanisms of PCP action and to describe their implications for the understanding ofschizophrenic pathophysiology. Methoc�: Twenty-five papers were identified that described the clinicaldose and serum and CSF levelsat which PCP induces its psychotomimetic effects. The dose range ofPCP-induced effects were compared to the dose range at which PCP interacts with specific molecular targets and affects neurotransmission. Results: It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP. At these concentrations PCP interacts selectively with a specific binding site (PCP receptor) that is associated with the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. Occupation ofits receptor by PCP induces noncompetitive inhibition of NMDA receptor-mediated neurotransmission. Other NMDA antagonists such as the dissociative anesthetic ketamine induce PCP-like neurobehavioral effects in proportion to their potency in binding to the PCP receptor and inducing NMDA receptor inhibition. Conclusions: These findings suggestthat endogenous dysfunction ofNMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizophrenia. The relative implications of the PCP and amphetamine models ofschizophrenia are discussedin relationship to the diagnosis and etiology of schizophrenia. (Am J Psychiatry1991;148:1301-1308)

Recent advances in the phencyclidine model of schizophrenia.

In this article, we advance a unified hypothesis pertaining to combined dysfunction of dopamine andN-methyl-D-aspartate glutamate receptors that highlights N-methyl-D-aspartate receptor hypofunction as a key mechanism that can help explain major clinical and pathophysiological aspects of schizophrenia. The following fundamental features of schizophrenia are accommodated by this hypothesis: (1) the occurrence of structural brain changes during early development that have the potential for producing subsequent clinical manifestations of schizophrenia, (2) a quiescent period in infancy and adolescence before clinical manifestations are expressed, (3) onset in early adulthood of psychotic symptoms, (4) involvement of dopamine (D2) receptors in some cases but not others that would explain why some but not all patients are responsive to typical neuroleptic therapy, and (5) ongoing neurodegenerative changes and cognitive deterioration in some patients. We propose that since N-methyl-D-aspartate receptor hypofunction can cause psychosis in humans and corticolimbic neurodegenerative changes in the rat brain, and since these changes are prevented by certain antipsychotic drugs, including atypical neuroleptic agents (clozapine, olanzapine, fluperlapine), a better understanding of the N-methyl-D-aspartate receptor hypofunction mechanism and ways of preventing its neurodegenerative consequences in the rat brain may lead to improved pharmacotherapy in schizophrenia.

Glutamate receptor dysfunction and schizophrenia.

Subanesthetic doses of ketamine stimulate psychosis in schizophrenia

Dual diagnosis: a review of etiological theories.

Ketamine-Induced NMDA Receptor Hypofunction as a Model of Memory Impairment and Psychosis

(1980). The PCP Psychosis: Prolonged Intoxication or Drug-Precipitated Functional Illness? Journal of Psychedelic Drugs: Vol. 12, PCP: Problems and Prevention. Selected Proceedings of the National PCP Conference 1979+K2, pp. 235-251.

The PCP Psychosis: Prolonged Intoxication or Drug-Precipitated Functional Illness?

Deinstitutionalization of the chronically mentally ill does not mean they no longer need social support, protection, and relief from the pressures of life--in other words, asylum and sanctuary The authors address the questions of why asylum should be provided, for what patients, the relationship between asylum and rehabilitation, and the implications for mental health professionals They point out that while many chronic patients eventually attain high levels of social and vocational functioning, many cannot meet simple demands of living, even with long-term rehabilitative help Many consciously limit their exposure to stimuli and pressure not from laziness but from a well-founded fear of failure Professionals must realize that whatever degree of rehabilitation is possible for each patient cannot take place unless support and protection--whether from family, treatment program, board-and-care home, or public hospital--are provided at the same time

The need for continuing asylum and sanctuary.

Phencyclidine (PCP) Abuse: An Appraisal. NIDA Research Monograph 21

The authors studied case records of 27 men who had been diagnosed as having hysterical personality, although they note that the current literature assumes that the diagnosis of hysterical personality applies predominantly to women. They believe that not recognizing the hysterical personality in men is not only a common diagnostic error but antitherapeutic and counterproductive as well.

Roger Peele

Papers

The PCP Psychosis: Prolonged Intoxication or Drug-Precipitated Functional Illness?

The need for continuing asylum and sanctuary.

Phencyclidine (PCP) Abuse: An Appraisal. NIDA Research Monograph 21

The hysterical personality in men.

Classifying Psychopathology: Mental Kinds and Natural Kinds