Use of Naloxone in Schizophrenic Psychoses and Manic Syndromes

Abstract

Since 1975, different morphinomimetic peptides have been isolated from hypophyseal-hypothalamic extracts: the pentapeptides methionine-enkephalin and leucine-enkephalin, and the longer peptides α-, β- and γ-endorphin. The primary structure of most of these peptides is also present in that of β-lipotropin. The morphinomimetic properties of endorphins can be blocked with opiate-antagonists. In rats, moreover, the endorphins influence behavior which cannot be blocked with opiate antagonists. On the basis of the hypothesis that hyperactivity of endorphin systems may be involved in the pathogenesis of schizophrenia and manic syndromes, the effect of opiate antagonists on psychotic and manic symptoms has been examined in a number of clinical studies in the past few years. A transient therapeutic effect has been demonstrated in about 30% of the patients so treated. Our own double-blind controlled study of 5 schizophrenic and 5 manic patients in the context of a World Health Organization project failed to reveal any therapeutic effect after subcutaneous injection of 20 mg naloxone. The possible reasons of the negative results are discussed.

Diurnal rhythm of plasma beta endorphin, cortisol and growth hormone in schizophrenics as compared to control subjects

“…Beta-EP levels have been reported to be increased in the cerebro-spinal fluid or plasma of schizophrenic patients (Terenius etal. 1976;Domschke et al 1979;Emrich et al 1979) and the beta-EP antagonist naloxone was found to reduce auditory hallucinations in some patients (Verhoeven et al 1981). Other reports have suggested a state of beta-EP deficiency in schizophrenia (Kline et al 1977).…”

Repeated High Dosage Naloxone Treatment without Therapeutic Efficacy in Schizophrenic Patients*

“…Since the single-blind study by Gunne et al (1977), in which schizophrenie patients experienced decreased audi• tory hallucinations after naloxone administration, the effects of the opiate antagonist in schizophrenie patients have been investigated in numerous double-blind studies. Some authors have reported that naloxone reduced psycho• tic syndromes (Berger et al, 1981;Emrich et al, 1977;Jorgensen and Cappelen, 1982;Lehmann et al, 1979;Watson et al, 1978), while others found only marginal therapeutic effects (Davis et al, 1977;Kleinman et al, 1982;Pickar et al, 1982) or no placebo-naloxone differences (Janowsky et al, 1977;Kurland et al, 1977;Lipinski et al, 1979;Sethi and Prakash, 1981;Verhoeven et al, 1981, Volavka et al, 1977. These controversial studies differ considerably in patient population, duration of observation and dosage.…”