naloxone and Schizophrenia

Current treatments for the symptoms of schizophrenia are only effective for positive symptoms in some individuals, and have considerable side effects that impact compliance. Thus, there is a need to investigate the efficacy of other compounds in treating both positive and negative symptoms. We conducted a meta-analysis of English language placebo-controlled clinical trials of naloxone, naltrexone, nalmefene, and buprenorphine in patients with schizophrenia to determine whether opioid antagonists have therapeutic efficacy on positive, negative, total, or general symptoms. We searched online databases Ovid Medline and PsychINFO, PubMed, EMBASE, Scopus, Cochrane library/CENTRAL, Web of Science, and Google Scholar from 1970 through February 2019. Following PRISMA guidelines, Hedges g was calculated for each study. Primary study outcomes were the within-subject change on any symptom assessment scale for positive, negative, total, or general symptoms of schizophrenia between active drug and placebo conditions. Thirty studies were included with 434 total patients. We found a significant effect of all drugs on all scales combined with both a standard random effects model: (g = 0.26; P = 0.02; k = 22; CI = 0.03-0.49) and a more inclusive bootstrap model: (g = 0.26; P = 0.0002; k = 30; CI = 0.11-0.51) and a significant effect on total scales with the bootstrap model (g = 0.25288; P = 0.015; k = 19; CI = 0.04-0.35). We also observed a significant effect of all drugs on all positive scales combined with both the random effects (g = 0.33; P = 0.015; k = 17; CI = 0.07-0.60) and bootstrap models (g = 0.32; P < 0.0001; k = 21; CI = 0.13-1.38). This evidence provides support for further testing in randomized clinical trials of a new class of non-D2-receptor drugs, based on opioid mechanisms, for the treatment of positive and negative symptoms of schizophrenia.

Topics: Buprenorphine; Humans; Naloxone; Narcotic Antagonists; Schizophrenia

The authors seek to extend understanding and treatment of hospitalized schizophrenics presenting with complications of polydipsia and dilutional hyponatremia. Attending physicians may ask the consultation/liaison psychiatrist to see schizophrenics with hyponatremically-induced delirium or other psychiatric syndromes. The referring physician may or may not have identified polydipsia and dilutional hyponatremia and their complications. This article will help the consultation/liaison psychiatrist recognize early evidence of water imbalance, describe evaluation, and provide somatic and behavioral treatment approaches to this life-threatening syndrome.. Over the past ten years, the authors have treated more than 100 patients with the polydipsia-hyponatremia syndrome. The authors discuss their and others' experience with drugs that help and hinder patients suffering from dilutional hyponatremia. They review current key articles from the polydipsia-hyponatremia syndrome literature including articles identified via Medline search 1985-94.. Schizophrenics with the polydipsia-hyponatremia syndrome most commonly present with polydipsia, polyuria, urinary incontinence, cognitive, affective, and behavioral changes, seizures, or coma. Quantitating polydipsia, hyponatremia, and diurnal changes in body weight facilitate therapeutic interventions. Treatment include patient and caregiver education, drug therapies to better treat psychosis and better treat osmotic dysregulation, behavioral interventions to interdict polydipsia, and diurnal weight monitoring.. Once recognized, acute, subacute, and chronic complications of the polydipsia-hyponatremia syndrome are readily treatable. Besides treating the patient, consultation/liaison psychiatrists can teach their medical colleagues about this syndrome. In so doing, they will enhance the quality of their patients' lives and help the internist and surgeon feel more comfortable when working with schizophrenics.

Topics: Angiotensin II; Anti-Inflammatory Agents, Non-Steroidal; Antipsychotic Agents; Carbamazepine; Cognition Disorders; Demeclocycline; Drinking Behavior; Electroconvulsive Therapy; Humans; Hyponatremia; Lithium; Mood Disorders; Naloxone; Phenytoin; Polyuria; Propranolol; Psychiatry; Psychotherapy; Schizophrenia; Sodium Chloride; Syndrome; Water Intoxication; Workforce

Numerous studies suggest that opiate antagonists may have antipsychotic properties. A review of the literature describing the use of naloxone to treat schizophrenic patients has shown mixed results. The three studies on naltrexone have found no benefit in controlling auditory hallucinations. We present a synopsis of these studies.

Topics: Hallucinations; Humans; Naloxone; Naltrexone; Schizophrenia

It is suggested that the antipsychotic efficacy of opioids in patients suffering from schizophrenia may result from an interaction of opioids with the dopaminergic system. The modulatory effect of opioids on dopaminergic functions has already been demonstrated in basic experiments: Anatomical and biochemical data reveal an interaction between opioid receptors and dopamine (DA) actions on dopaminergic nerve terminals, cell bodies, and afferent nerve endings. Endogenous enkephalin levels correlate well with the endogenous dopamine content in various brain areas. Systemic or iontophoretic administration of morphine alters the spontaneous activity of ventral tegmental dopaminergic neurons. Morphine and enkephalin effectively enhance pituitary prolactin release, whereas dopamine inhibits it. Opioid agonists effectively alter DA release, DA reuptake, and DA metabolism in the striatum and substantia nigra. In reverse, chronic neuroleptic treatment enhances the synthesis and release of pituitary beta-endorphin. Opioids affect contralateral rotation elicited by dopamine agonists in animals with unilateral lesions of the nigrostriatal pathway. Phencyclidine, a psychotropic drug that shares certain pharmacological characteristics with the putative sigma-opioid receptor ligand SKF 10,047, indirectly mimics the effects of dopamine agonists on prolactin release, release of acetylcholine, etc. It is suggested that an imbalance of opiate-DA interaction might be involved in the pathogenesis of schizophrenia. Consequently, clinical studies on the effects of opioids on psychotic symptoms should also examine opioid influence on dopaminergic functions in these patients.

Topics: Brain; Corpus Striatum; Dopamine; Dyskinesia, Drug-Induced; Endorphins; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Morphine; Naloxone; Phencyclidine; Prolactin; Receptors, Dopamine; Receptors, Opioid; Schizophrenia; Substantia Nigra; Synaptic Transmission

Topics: Animals; Anticonvulsants; Antipsychotic Agents; Depressive Disorder; Drug Therapy, Combination; Endorphins; Enkephalins; Humans; Mental Disorders; Naloxone; Naltrexone; Nerve Tissue Proteins; Pituitary Hormones; Psychotropic Drugs; Schizophrenia; Substance-Related Disorders; Vasopressins

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

Topics: Affective Disorders, Psychotic; Animals; beta-Endorphin; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Endorphins; Growth Hormone; Humans; Hydrocortisone; Methylphenidate; Models, Psychological; Naloxone; Prolactin; Schizophrenia

Endorphinergic neurons certainly play a role in the brain's processing of painful stimuli. Endorphins act to alter pain appreciation at many levels within the central nervous system including spinal cord, midbrain, thalamus, and cortex. The activity of this pain-suppressing system may play a role in individual differences in the experience of pain. Endorphinergic mechanisms play a major role in analgesia associated with stress and acupuncture, and perhaps mediate placebo-induced analgesia. Chronic pain influences endorphinergic function perhaps depleting endorphinergic neurons of their neurotransmitters. Endorphin function and pain sensibility are prominently affected in affective illness and schizophrenia. It may be that endorphinergic neurons play a fundamental role in selective attention--a kind of sensory filtering of information flow--in somatosensory and other sensory modalities.

Topics: Analgesia; Analgesics; Animals; Antidepressive Agents; Attention; Central Nervous System; Circadian Rhythm; Depressive Disorder; Endorphins; Humans; Mice; Naloxone; Neural Pathways; Pain; Schizophrenia; Stress, Physiological; Synaptic Transmission

Topics: Animals; Behavior; Behavior, Animal; Drug Tolerance; Endorphins; Enkephalins; Euphoria; Humans; Learning; Memory; Mood Disorders; Naloxone; Opioid-Related Disorders; Rats; Schizophrenia

Topics: Adult; Affective Disorders, Psychotic; Bipolar Disorder; Depressive Disorder; Endorphins; Humans; Hydrocortisone; Male; Methadone; Middle Aged; Naloxone; Narcotics; Prolactin; Schizophrenia

Topics: Animals; Behavior, Animal; Bipolar Disorder; Brain; Depression; Endorphins; Humans; Naloxone; Pituitary Gland; Pituitary Hormones, Anterior; Pro-Opiomelanocortin; Protein Precursors; Receptors, Opioid; Schizophrenia

More than a decade of scientific inquiry into the biochemistry of schizophrenia has been organized by the dopamine hypothesis. The evidence that neuroleptics reduce brain dopamine activity is compelling and derives from both human and animal studies. In addition, agents which enhance brain dopamine activity, such as amphetamine or cocaine, can cause a syndrome that can be indistinguishable from acute paranoid schizophrenia. However, a major problem with the dopamine hypothesis is the lack of strong direct evidence of altered dopamine concentrations or metabolism when measured in large groups of schizophrenic subjects. The idea that schizophrenia is more than one illness is an old concept, but it finds increasing support in new studies of the clinical phenomenology, genetics, and biochemistry of schizophrenic patients. The revival of the concept of multiple forms of schizophrenia, in turn, has fostered the development of new biochemical hypotheses of the disorder. These hypotheses propose that neurotransmitters, other than dopamine, may be involved in schizophrenic symptoms. Reports of elevated concentrations of norepinephrine is specific areas of the brain and in the spinal fluid have led to the hypothesis that norepinephrine may be involved in schizophrenia. At least two groups of investigators have suggested that phenylethylamine might be involved in schizophrenia. In part, this proposal is based on the structural and pharmacological similarities of phenylethylamine and amphetamine. gamma-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter. Evidence for the inhibitory influence of GABA-ergic neurons on dopaminergic neurons has led to the hypothesis that decreased GABA-ergic activity may be involved in producing schizophrenic symptoms. Studies with the reversible acetylcholinesterase inhibitor physostigmine and the dopamine agonist methylphenidate have led to the suggestion that acetylcholine and dopamine imbalance may be involved in schizophrenia. This hypothesis is one example of the idea that altered balance between several neurotransmitters may underlie schizophrenia. The recent discovery of the endorphins has led to speculations about the possible role of these substances in schizophrenia. Both an excess and a deficiency of endorphin activity have been implicated in schizophrenia, and speculative evidence has been used to support both hypotheses. The ultimate aim of the search for biochemical defects in schizophrenia is the developm

Topics: Acetylcholine; Amphetamine; Animals; Brain; Cocaine; Dopamine; Endorphins; gamma-Aminobutyric Acid; Humans; Methylphenidate; Naloxone; Norepinephrine; Phenethylamines; Physostigmine; Schizophrenia; Schizophrenia, Paranoid

It has been suggested that the newly discovered endogenous opiate peptides (called endorphins) might play a role in the symptoms of schizophrenia. The administration of narcotic antagonists provides both a test of the hypothesis and a potential treatment. In this article, we review the methods by which data have been gathered to test endorphin involvement in schizophrenia. Alternative strategies, which hold greater promise of producing conclusive positive or negative evidence, include exploitation of individual differences, use of psychophysiological measures, genetic strategies, and multivariate statistical techniques with larger sample sizes.

Topics: Antipsychotic Agents; Brief Psychiatric Rating Scale; Clinical Trials as Topic; Double-Blind Method; Endorphins; Humans; Individuality; Models, Biological; Naloxone; Narcotic Antagonists; Research Design; Schizophrenia; Statistics as Topic

With the discovery of the opiate peptides, several major avenues of research became apparent. These peptides produced a great deal of focused attention on their anatomy, biochemistry, and physiology. In this article, we present an overview of some of the main research issues and recent findings in the field of opiate peptides. The possible relationship of the opiate peptide neuronal systems to schizophrenia is discussed in light of attempts to alter schizophrenic symptoms with opiate antagonists, beta-endorphin, and dialysis. It is hypothesized that if the opiate peptides are involved in schizophrenia, then their involvement with dopamine systems and/or with stress responses may be critical.

Topics: Administration, Oral; Brain; Double-Blind Method; Endorphins; Forecasting; Humans; Naloxone; Naltrexone; Receptors, Opioid; Renal Dialysis; Schizophrenia

Topics: Anxiety; Bipolar Disorder; Deficiency Diseases; Depression; Endorphins; gamma-Aminobutyric Acid; Humans; Mental Disorders; Naloxone; Schizophrenia

The rate of substance-use disorders in patients with mental illnesses within the psychotic spectrum, such as schizophrenia, schizoaffective disorder, and bipolar disorder, is higher than the rate observed in the general population and is associated with significant morbidity and mortality. Although there are currently 3 medications approved by the Food and Drug Administration for the treatment of alcohol dependence, no medications have been approved for the specific treatment of dually diagnosed patients. A small but growing body of literature supports the use of 2 of these medications, disulfiram and naltrexone, in dually diagnosed individuals. This article outlines a review of the literature about the use of disulfiram and naltrexone for alcoholism and in patients with comorbid mental illness. In addition, results are presented of a 12-week randomized clinical trial of disulfiram and naltrexone alone and in combination for individuals with Axis I disorders and alcohol dependence who were also receiving intensive psychosocial treatment. Individuals with a psychotic spectrum disorder, including schizophrenia, schizoaffective disorder, and bipolar disorder, had worse alcohol outcomes than those without a psychotic spectrum disorder. Individuals with a psychotic spectrum disorder had better alcohol-use outcomes on an active medication compared with placebo, but there was no clear advantage of disulfiram or naltrexone or of the combination. Retention rates and medication compliance in the study were high and exceeded 80%. Pharmacotherapeutic strategies should take into account the advantages and disadvantages of each medication. Future directions of pharmacotherapeutic options are also discussed.

Topics: Adult; Alcohol Deterrents; Alcoholism; Bipolar Disorder; Combined Modality Therapy; Comorbidity; Diagnosis, Dual (Psychiatry); Disulfiram; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Motivation; Naloxone; Narcotic Antagonists; Psychotic Disorders; Schizophrenia; Treatment Outcome; Veterans

Previously we found significant suppression of polydipsia in a schizophrenic patient with PIP syndrome (psychosis, intermittent hyponatremia, and polydipsia). Suppression was obtained with a small dose of naloxone injected once every 2 weeks in long-term repeated studies. We attempted to confirm the effect of naloxone on PIP syndrome by using a double-blind controlled study. The body weights of eight schizophrenic inpatients with PIP syndrome were checked five times daily, and the maximum weight gain during 1 day was chosen as an index of their polydipsia. Naloxone (0.6 mg in three divided doses) or placebo (saline) injection was given once every 2 weeks three times. Assignment to either the naloxone or placebo series was done randomly in a double-blind, crossover design. Naloxone decreased the maximum weight gain per day significantly in five cases. However, naloxone also increased weight gain significantly in three cases. There was no correlation of the weight-increasing effect of naloxone with the duration and intensity of excessive drinking. Our findings showed that the endogenous opioid system might be related to compulsive drinking behavior in the PIP syndrome and that opioid antagonists such as naloxone or naltrexone could be useful in the therapy of PIP syndrome.

Topics: Adult; Aged; Cross-Over Studies; Double-Blind Method; Drinking Behavior; Female; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Opioid Peptides; Schizophrenia; Water Intoxication; Weight Gain

In the context of a previous WHO collaborative study, six research centers reported that naloxone (0.3 mg/kg) produced significant improvement in symptomatology in neuroleptic-treated patients. In the current Phase II WHO study, repeated (4 days) naloxone (0.3 mg/kg) administration was performed in schizophrenic patients (n = 43) from five WHO collaborating centers using a double-blind, placebo-controlled design. Both naloxone and placebo administrations were associated with significant reductions in symptoms. Naloxone, however, was not superior to placebo. These data are discussed in relation to endorphin hypotheses of schizophrenia.

Topics: Adult; Brain; Double-Blind Method; Drug Evaluation; Female; Humans; Infusions, Intravenous; Male; Naloxone; Prospective Studies; Psychiatric Status Rating Scales; Random Allocation; Receptors, Opioid; Schizophrenia; Schizophrenic Psychology; World Health Organization

The biological enigma of schizophrenia has led, on the basis of thin evidence, to widen the field of clinical research to a study of endomorphines in this disease. Too many different methods of measuring the levels of opiate peptides in the CSF have been used so that it is not possible to analyse the results statistically. Clinical trials of agonists and antagonists to the opiate receptors have once again emphasised the biochemical heterogeneity of schizophrenics but have not allowed any confirmation that the endorphinical system plays any part in the genesis or symptomatology of schizophrenia. The presence of sub-groups who respond positively to experimental treatment can lead to the hope, despite the uncertainties of their mode of pharmacological action, to the next advance in the routine treatment of schizophrenia.

Topics: beta-Endorphin; Clinical Trials as Topic; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Humans; Naloxone; Peptide Fragments; Receptors, Opioid; Schizophrenia

Topics: Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Naloxone; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

A double-blind study of repeated subcutaneous administrations of 20 mg naloxone was performed in 10 schizophrenic patients as part of a World Health Organization collaborative project. No clinically obvious treatment effects were observed. None of the analyzed psychopathological symptoms, including hallucinations and unusual thought content, showed a distinct improvement during the 4 consecutive days of naloxone treatment. A slight but statistically significant decrease of symptomatology was found shortly after placebo injection on the first 2 days of treatment. This effect was not present following naloxone treatment. These findings are discussed in view of the hypothesis that increased endorphin activity contributes to the symptomatology of schizophrenic syndromes.

Topics: Adult; Cognition Disorders; Female; Hallucinations; Humans; Injections; Male; Middle Aged; Naloxone; Schizophrenia

Topics: Affective Disorders, Psychotic; Animals; beta-Endorphin; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Endorphins; Growth Hormone; Humans; Hydrocortisone; Methylphenidate; Models, Psychological; Naloxone; Prolactin; Schizophrenia

6 schizophrenic patients were treated in a cross-over design for 4 days each with 20 mg naloxone or placebo. No patient showed a significant change of his or her psychotic behaviour. This result is not in agreement with an antipsychotic action of the opiate antagonist.

Topics: Adult; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Naloxone; Psychiatric Status Rating Scales; Schizophrenia; Time Factors

A double-blind study of the behavioral effects of short-term naloxone hydrochloride administration was performed in 32 schizophrenic and 26 manic patients in a World Health Organization collaborative project. There was a significant naloxone-associated reduction in overall physician-rated symptoms in schizophrenic patients concurrently treated with neuroleptic medication (N = 19) but not in medication-free schizophrenics (N = 13). Physician rating of auditory hallucinations showed significant naloxone-associated improvement for the total schizophrenic population, while self-ratings of auditory hallucinations showed improvement only in neuroleptic-treated schizophrenics. While further studies are needed to delineate these effects as to clinical significance, they may bear etiological implications for the psychobiology of schizophrenia, including the possibility of synergistic effects of dopamine and endorphin blockade. Naloxone produced no significant behavioral effects in manic patients. These findings are discussed with relationship to the hypotheses of endorphin involvement in schizophrenia and mania.

Topics: Adult; Affective Disorders, Psychotic; Aged; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naloxone; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; World Health Organization

Naloxone produced improvement in abnormal thought content in medicated chronic schizophrenic patients, but not in drug-free patients. In contrast, drowsiness and increases in plasma prolactin concentrations were seen only in drug-free schizophrenic patients. Although growth hormone concentrations increased in drug-free and medicated schizophrenic patients, the time course was different in the two groups. Neuroleptics appear to alter naloxone's clinical and neuroendocrine effects in chronic schizophrenic patients.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Growth Hormone; Humans; Infusions, Parenteral; Male; Middle Aged; Naloxone; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Topics: Clinical Trials as Topic; Double-Blind Method; Hallucinations; Humans; Naloxone; Schizophrenia

Topics: beta-Endorphin; Clinical Trials as Topic; Electroencephalography; Endorphins; Humans; Naloxone; Prolactin; Schizophrenia

The subjects were 13 psychiatric inpatients with tardive dyskinesia. Each subject participated in two sessions. Either naloxone (10 mg) or placebo was administered intravenously during each session. In a subset of subjects (n = 7), blood samples for beta-endorphin were drawn before and at 30 and 60 minutes after the injection. The Abnormal Involuntary Movement Scale was administered before and at 10, 20, 40, 60, 120, and 360 minutes after the injection. Double-blind procedures were maintained throughout the experiment. Neither naloxone nor placebo had any appreciable effect on the involuntary movements. Naloxone elicited a significant increase in the plasma beta-endorphin.

Topics: Adult; Affective Disorders, Psychotic; Aged; beta-Endorphin; Dyskinesia, Drug-Induced; Endorphins; Female; Humans; Male; Middle Aged; Naloxone; Psychotic Disorders; Receptors, Dopamine; Schizophrenia

Topics: Animals; Clinical Trials as Topic; Dyskinesia, Drug-Induced; Endorphins; Humans; Mood Disorders; Naloxone; Naltrexone; Rats; Schizophrenia

Schizophrenics treated with high doses of diazepam (150-200 mg/day) showed marked analgesia besides certain antipsychotic effects. Euphoria was noticed in some of the patients. We hypothesized that influence on the endorphin metabolism might contribute to these clinical effects. Therefore, we measured pain threshold by three different methods before and during diazepam treatment. All patients exhibited a 1.5- to 2-fold increase of pain perception. Further, using a double-blind design, the opiate antagonist naloxone (30 mg i.v.) was administered. A significant decrease but not a complete block of the euphoric state and of analgesia was achieved. It is, therefore, concluded that other pharmacological properties of diazepam might be involved in the diazepam-induced euphoria and analgesia in man.

Topics: Adult; Analgesia; Diazepam; Endorphins; Euphoria; Female; Humans; Male; Middle Aged; Naloxone; Pain; Schizophrenia

Topics: Adult; Bipolar Disorder; Brief Psychiatric Rating Scale; Double-Blind Method; Female; Hallucinations; Humans; Injections, Subcutaneous; Male; Middle Aged; Naloxone; Schizophrenia

In a placebo-controlled, double-blind crossover study of 14 male chronic schizophrenic patients, high doses of the opiate antagonist naloxone were given intravenously. Hallucinations measured on a verbal-report scale were significantly decreased after naloxone administration. The authors suggest that this apparent action of naloxone is mediated by central opiate receptors and that it may result from an interaction between central endorphin systems and central catecholaminergic neurons.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Hallucinations; Humans; Male; Middle Aged; Naloxone; Placebos; Random Allocation; Receptors, Opioid; Schizophrenia; Schizophrenia, Paranoid

Topics: Bipolar Disorder; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Naloxone; Naltrexone; Psychotic Disorders; Receptors, Opioid; Schizophrenia

Topics: beta-Endorphin; Clinical Trials as Topic; Double-Blind Method; Endorphins; Humans; Male; Middle Aged; Naloxone; Random Allocation; Receptors, Opioid; Schizophrenia; Schizophrenic Psychology

Naltrexone, a long acting opiate antagonist, and placebo were administered to eight schizophrenics in doses of 200 mg per day for 1 week in a double-blind, crossover design. No improvement was noted, and no side effects resembling the opiate withdrawal syndrome with naltrexone were found. Naltrexone does not appear to alter schizophrenic symptomatology.

Topics: Adult; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Male; Naloxone; Naltrexone; Schizophrenia

Topics: Adult; Aged; Auditory Perception; Clinical Trials as Topic; Double-Blind Method; Hallucinations; Humans; Middle Aged; Naloxone; Placebos; Schizophrenia

Eleven schizophrenic and three manic patients were randomly administered 0.3 mg/Kg b.wt. of naloxone or placebo in a drug-free state using a double blind procedure. BPRS and CGI were employed for making periodic assessment of mental status; the MRS was additionally used for manic patients. The authors discuss their findings, which are essentially negative.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Schizophrenia

A 4-week clinical trial, including a 1-week placebo washout period, assessed the antipsychotic activity of naltrexone in 'newly admitted', actively hallucinating, chronic schizophrenics. Chronic naltrexone administration was found to benefit 2 patients and to be of no value in 3 patients. Responsive patients differed from non-responders by the presence of hallucinations despite adequate neuroleptic maintenance therapy and an appropriate response to pathological hallucinatory experience. On the basis of these findings, the possibility of a naltrexone-responsive schizophrenic subgroup was considered.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Naloxone; Naltrexone; Psychiatric Status Rating Scales; Schizophrenia

It has been suggested that the newly discovered endogenous opiate peptides (called endorphins) might play a role in the symptoms of schizophrenia. The administration of narcotic antagonists provides both a test of the hypothesis and a potential treatment. In this article, we review the methods by which data have been gathered to test endorphin involvement in schizophrenia. Alternative strategies, which hold greater promise of producing conclusive positive or negative evidence, include exploitation of individual differences, use of psychophysiological measures, genetic strategies, and multivariate statistical techniques with larger sample sizes.

Topics: Antipsychotic Agents; Brief Psychiatric Rating Scale; Clinical Trials as Topic; Double-Blind Method; Endorphins; Humans; Individuality; Models, Biological; Naloxone; Narcotic Antagonists; Research Design; Schizophrenia; Statistics as Topic

Topics: Adult; Female; Hallucinations; Humans; Male; Middle Aged; Naloxone; Schizophrenia

The authors conducted single- and double-blind studies of the responses of 7 chronic male schizophrenic patients to 10 mg of naloxone. BPRS ratings were made before and 6 hours after the injection; ACTH blood levels were determined before and 1 1/2 and 6 hours after injection. Statistically significant improvement of psychotic behavior occurred after 6 hours. The greatest improvement occurred in the patient who showed the most pronounced diurnal variation of ACTH levels, and there was no improvement in the patient who had no diurnal changes. Prolactin plasma levels following endorphin injections were apparently dose-dependent and peaked at approximately 30 minutes. The mean half-life of elimination of exogenous beta-endorphin was between 12 and 35 minutes. The authors theorize that positive and negative behavioral responses to naloxone depend--as possibly do many placebo responses in general--on the relative stress produced by experimental or therapeutic interventions.

Topics: Adrenocorticotropic Hormone; Adult; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Endorphins; Half-Life; Humans; Male; Middle Aged; Naloxone; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Stress, Psychological

Topics: Animals; Behavior, Animal; Catatonia; Clinical Trials as Topic; Double-Blind Method; Endorphins; Enkephalins; Humans; Male; Naloxone; Rats; Schizophrenia; Vocalization, Animal

Endogenous opiate-like peptides (endorphins) are putative neuroregulators located throughout the mammalian brainstem. There is some evidence for their role in pain, stress, and affect. We report that the opiate antagonist, naloxone, alters some schizophrenic symptoms. In a double-blind, cross-over study, naloxone produced decreases in auditory hallucinations in some schizophrenic patients. This finding supports the hypothesis that the endorphins may play a roll in modulating hallucinations in a highly selected subgroup of chronically hallucinating schizophrenic patients.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Endorphins; Hallucinations; Humans; Male; Naloxone; Schizophrenia; Schizophrenia, Paranoid; Time Factors

Topics: Adult; Aged; Alcoholic Intoxication; Biogenic Amines; Clinical Trials as Topic; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Naloxone; Schizophrenia

On the basis of the hypothesis that the opiate-like neuropeptides, such as beta-endorphin, may be involved in the etiology of schizophrenic symptoms, naloxone 1,2 mg and placebo were administered intravenously to 8 schizophrenic patients, using a double-blind, crossover design. Naloxone was not found to be different from placebo in effecting schizophrenic symptoms, including hallucinations and delusions.

Topics: Adult; Brief Psychiatric Rating Scale; Clinical Trials as Topic; Double-Blind Method; Hallucinations; Humans; Male; Middle Aged; Naloxone; Placebos; Schizophrenia

In a single-blind pilot study 0.4 mg naloxone i.v. was found temporarily to reduce or abolish auditory hallucinations in four cases of chronic schizophrenia whereas saline was without effect. In one of these patients there was a similar reversal also of her visual hallucinations. Two additional cases who denied hearing voices before the injections, reported no subjective effects.

Topics: Adult; Clinical Trials as Topic; Drug Evaluation; Female; Hallucinations; Humans; Male; Middle Aged; Naloxone; Schizophrenia

Fourteen schizophrenic patients and five patients with affective disorders were given naloxone (0.4 to 10 milligrams) or placebo intravenously in a double-blind fashion. Physicians' ratings of hallucinations, mannerisms and posturing, conceptual disorganization, psychosis, and mood did not change significantly. A single item, unusual thought content, improved significantly on the naloxone day compared to the placebo day. There was no improvement in mood in affectively ill patients rated either by themselves or by physicians. Naloxone did not markedly improve any patient studied, which suggests that the acute blockade of opiate receptors is not associated with global improvement in psychotic symptomatology.

Topics: Adolescent; Adult; Affective Symptoms; Behavior; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Naloxone; Schizophrenia

The authors treated 12 schizophrenic patients who had overt hallucinatory symptoms with intravenously administered naloxone hydrochloride, a narcotic antagonist purported to have antihallucinatory properties. They found no evidence of the effectiveness of naloxone in preventing hallucinations over that of placebo when administered in a randomized, double-blind fashion.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Hallucinations; Humans; Injections, Intravenous; Male; Middle Aged; Naloxone; Pilot Projects; Placebos; Schizophrenia; Schizophrenic Psychology

The specific narcotic antagonist naloxone (0.4 milligram) was given intravenously to seven chronic schizophrenics who reported that they had very frequent auditory hallucinations. Saline solution was used as a placebo. The coded study did not reveal any effect of naloxone on hallucinations or on global psychopathology.

Topics: Adult; Chronic Disease; Female; Hallucinations; Humans; Male; Middle Aged; Naloxone; Schizophrenia

Carfentanil is a synthetic opioid with an estimated potency that is 10,000 times more than that of morphine and 100 times more than that of fentanyl. Although there is a paucity of evidence, when considering the potency of carfentanil, it is reasonable to speculate that larger doses of naloxone may be required to resuscitate patients after carfentanil ingestion. This case report discusses the use of high-dose naloxone in 2 patients with suspected carfentanil overdose presenting to a small community hospital.. Two patients with suspected carfentanil overdose presented to a 30-bed emergency department at a community hospital in New Hampshire. Cyanosis and respiratory distress were noted in both instances, and airway intervention was ultimately deemed necessary. Patient 1 required a total of 12 mg of naloxone to be successfully resuscitated, while patient 2 required a total of 10 mg for resuscitation. Both patients were successfully resuscitated with high doses of naloxone. The use of high-dose naloxone prevented the need for intubation in these patients.. While more robust studies should be considered, emergency personnel should be comfortable using higher-than-standard doses of naloxone in appropriate cases.

Topics: Adult; Analgesics, Opioid; Cardiopulmonary Resuscitation; Cyanosis; Drug Overdose; Female; Fentanyl; Hospitals, Community; Humans; Male; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Schizophrenia; Substance-Related Disorders

RGS proteins are negative regulators of signaling through heterotrimeric G protein-coupled receptors and, as such, are in a position to regulate a plethora of biological phenomena. However, those have just begun to be explored in vivo. Here, we describe a mouse line deficient for Rgs4, a gene normally expressed early on in discrete populations of differentiating neurons and later on at multiple sites of the central nervous system, the cortex in particular, where it is one of the most highly transcribed Rgs genes. Rgs4(lacZ/lacZ) mice had normal neural development and were viable and fertile. Behavioral testing on mutant adults revealed subtle sensorimotor deficits but, so far, supported neither the proposed status of Rgs4 as a schizophrenia susceptibility gene (by showing intact prepulse inhibition in the mutants) nor (unlike another member of the Rgs family, Rgs9) a role of Rgs4 in the acute or chronic response to opioids.

Topics: Animals; Behavior, Animal; Body Temperature; Body Weight; Cell Differentiation; Conditioning, Classical; Fear; Female; Gene Deletion; Male; Mice; Mice, Knockout; Morphine; Naloxone; Narcotics; Neurologic Examination; Neurons; Pain Threshold; Phenotype; Reflex, Startle; RGS Proteins; Schizophrenia; Substance Withdrawal Syndrome

1. The present study was performed to examine the effect of naloxone on drinking behavior in three schizophrenic inpatients with psychosis, intermittent hyponatremia, and polydipsia. 2. Their body weight were checked five times daily and the maximum weight gain during a day was chosen as an index of their polydipsia. 3. After control recording for six weeks, a daily naloxone (0.6 mg) injection series was performed once every two weeks for three series (six weeks). Withdrawal of this drug for six weeks resulted in weight gain recovering to control level. 4. The present study showed that naloxone seems to be a potential treatment for psychiatric patients displaying self-induced water intoxication and that endogenous opioid systems are involved in the compulsive drinking behavior of this syndrome.

Topics: Drinking Behavior; Female; Humans; Male; Middle Aged; Naloxone; Schizophrenia; Schizophrenic Psychology; Water Intoxication; Weight Gain

Topics: Body Weight; Drinking; Drug Administration Schedule; Humans; Naloxone; Schizophrenia; Schizophrenic Psychology

This study was performed to examine the effect of naloxone on drinking behavior in a schizophrenic inpatient with psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome). His body weight was checked five times daily, and the maximum and minimum weight gains during a day were chosen as an index of polydipsia. Both daily (0.6 mg) and repeated (0.6 mg for 6 days) injections of naloxone suppressed his weight gain significantly for 2 weeks. Withdrawal of the drug for 4 weeks resulted in weight gain recovering to control level. Thereafter, a second trial was performed to examine the long-term effect of this treatment. A daily naloxone (0.6 mg) injection series was performed once every 2 weeks for six series (12 weeks). This drug regimen also suppressed his weight gain in a continuous fashion. The study showed that naloxone seems to be a potential treatment for PIP syndrome and that endogenous opioid systems play a part in the compulsive drinking behavior of the PIP syndrome.

Topics: Drinking Behavior; Humans; Male; Middle Aged; Naloxone; Schizophrenia; Schizophrenic Psychology; Water Intoxication

The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL-secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia.

Topics: Adenoma; Adult; Amenorrhea; Antipsychotic Agents; Dopamine Antagonists; Endorphins; Female; Humans; Hyperprolactinemia; Iatrogenic Disease; Luteinizing Hormone; Menopause; Metoclopramide; Naloxone; Pituitary Neoplasms; Schizophrenia

The main achievements in the field of genetics, biochemistry, and immunology of schizophrenia in the laboratories of European research centers are surveyed. Despite the rapid development of scientific research techniques and methodology, the abundant hypotheses on the pathogenesis of schizophrenia are riddled with so many contradictory facts that it is impossible to formulate any concrete model of the disease. One factor impeding the progress of biological research in schizophrenia is the inadequate development of standardized clinical descriptions. This is an obstacle to the study of clinical-biological correlates, which are among the principal criteria used to verify the importance of biological parameters chosen for study in the pathogenesis of the disease. A current strategy in the biology of schizophrenia, which may obviate some of those problems, is the discovery and study of biological markers.

Topics: Brain; Brain Chemistry; Dopamine; Endorphins; Environment; Europe; Genetic Markers; HLA Antigens; Humans; Hydroxyindoleacetic Acid; Male; Models, Genetic; Monoamine Oxidase; Naloxone; Norepinephrine; Prolactin; Psychotic Disorders; Receptors, Dopamine; Schizophrenia

We utilized a naloxone challenge strategy to investigate the functioning of the endogenous opioid system (EOS) in schizophrenia. Patients with schizophrenia, who were on neuroleptic medication or drug-free, demonstrated a significantly larger serum cortisol response to opioid blockade by naloxone than did age- and sex-matched normal controls. Patients, but not normal controls, also demonstrated an inverse relationship between baseline cortisol and the magnitude of the response. This enhanced cortisol response is consistent with tonic hyperactivity of the EOS in schizophrenia.

Topics: Adult; Antipsychotic Agents; Endorphins; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Naloxone; Pituitary-Adrenal System; Schizophrenia

Opioid receptor binding sites were assessed in membrane preparations of caudate nucleus from post-mortem brains of controls and of patients with schizophrenia. There was no difference between the two groups in the total specific binding of 3H-etorphine or in its 'mu' and ('delta + kappa') components. Similarly, the binding of 3H-naloxone did not differ between patients and controls. It is concluded that a previous report of reduced opioid receptors in caudate of schizophrenics is unlikely to prove a consistent finding and that the results of the present study offer no support to the claim that there is a general disturbance in opiate mechanisms in schizophrenia.

Topics: Aged; Caudate Nucleus; Etorphine; Female; Humans; Male; Middle Aged; Morphinans; Naloxone; Receptors, Opioid; Schizophrenia; Tritium

The evidence for stress activation of endorphinergic systems suggests a physiological role in endogenous analgesic and anti-anxiety regulation which would provide a reserve in emergency situations. The possibility of involvement of these systems in psychiatric illness arises from the psychotogenic and anxiolytic properties of some opiates. The endorphin-excess and -deficiency hypotheses of schizophrenia are reviewed in the light of naloxone's small but statistically significant antipsychotic action, and the activation of endorphinergic systems in the course of neuroleptic therapy. The hypothesis that endorphinergic deficiency may be present in endogenous depression is reviewed. Although alterations in beta-endorphin immunoreactivity measured peripherally and in CNS have not been substantiated, therapeutic trials using a mu-receptor agonist have shown promise of a rapidly-acting antidepressant effect. ECT is accompanied by increases in plasma beta-endorphin immunoreactivity.

Topics: Animals; Anorexia Nervosa; Arousal; Brain; Electroconvulsive Therapy; Endorphins; Humans; Mental Disorders; Mood Disorders; Naloxone; Receptors, Opioid; Schizophrenia; Stress, Physiological; Substance-Related Disorders

Topics: Antipsychotic Agents; Drug Therapy, Combination; Endorphins; Humans; Naloxone; Schizophrenia

The effect of naloxone on CSF [Met5]enkephalin level and on the suppression of psychotic symptoms associated with schizophrenia was studied. Seven patients were treated with naloxone at a dose of 0.4 mg/day for seven days and six were treated with saline for the same period. Of the seven patients receiving naloxone, three showed signs of improvement. In the saline group, only one case of obvious improvement was observed. The mean CSF [Met5]enkephalin level before and after treatment in both the naloxone and saline group did not change significantly. However, there was a highly significant correlation (r = -0.73, P less than 0.01) between the increase of [Met5]enkephalin level and the decrease in psychotic symptoms.

Topics: Adult; Aged; Antipsychotic Agents; Enkephalin, Methionine; Female; Humans; Male; Middle Aged; Naloxone; Psychiatric Status Rating Scales; Schizophrenia

Topics: Adult; beta-Endorphin; Double-Blind Method; Endorphins; Humans; Hydrocortisone; Male; Naloxone; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Topics: beta-Endorphin; Depressive Disorder; Double-Blind Method; Endorphins; Humans; Hydrocortisone; Naloxone; Prolactin; Psychotic Disorders; Psychotropic Drugs; Receptors, Opioid; Schizophrenia

A schizophrenic patient was repeatedly treated with intravenous naloxone 0.04 mg or saline in a double-blind design. The Comprehensive Psychopathological Rating Scale was used to quantify the symptoms before and after each injection. Naloxone significantly reduced the symptoms temporarily, whereas saline was without effect.

Topics: Adult; Antipsychotic Agents; Double-Blind Method; Female; Humans; Naloxone; Psychiatric Status Rating Scales; Renal Dialysis; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Atrophy; Brain; Cerebral Ventricles; Chronic Disease; Dopamine; Endorphins; GABA Antagonists; gamma-Aminobutyric Acid; Humans; Monoamine Oxidase; Naloxone; Neurotransmitter Agents; Receptors, Dopamine; Schizophrenia

A serum fraction from schizophrenic patients has been investigated for its effect on opiate receptor sites and on behaviour in rats. Serum from schizophrenic patients was ultrafiltered and fractionated on DEAE-Sephadex A-25. The concentration of peptide material eluting under 0.1 M HCl (fraction I) was further purified on Sephadex-G10 and four major peaks were identified (fractions II to V). When injected intracerebroventricularly in rats, fraction II produced a characteristic behavioural syndrome, which included hyperactivity associated with hyperemotionality. The effects were long lasting, bouts of hyperemotionality accompanied by analgesia were recorded over a two-week period. The same fraction from control non-patients produced a transient and much reduced, but qualitatively similar response. There was evidence that fraction III was also active. An in vitro opiate receptor binding test showed that fraction II from schizophrenic patients inhibited [3H]naloxone binding.

Topics: Adolescent; Adult; Animals; Behavior, Animal; Chromatography, Ion Exchange; Humans; Injections, Intraventricular; Male; Motor Activity; Muridae; Naloxone; Nociceptors; Peptides; Receptors, Opioid; Reflex, Startle; Schizophrenia

Topics: Apomorphine; Dopamine; Humans; Naloxone; Schizophrenia

The effect of native serum samples from schizophrenic and control patients on the electrically induced contractions of the isolated mouse vas deferens (MVD) preparations was investigated. It was demonstrated that only the samples of schizophrenic origin elicited a naloxone dependent inhibition on the contractions of the MVD preparations, while sera from healthy individuals and those from non schizophrenic but mentally ill patients proved to be ineffective in this respect. By using ultrafiltration and gel chromatographic techniques, four fractions disclosing MVD related biological activity could be separated from schizophrenic samples. Chemical analysis revealed an elevated quantity of ninhydrin and Lowry positive materials as well as of unidentified carbohydrate components in the active fractions. Molecular mass of the serum ingredients carrying opioid activity was found to range between 0.5 and 5.0 KD. It is speculated that new appearance or the accumulation in the sera of several, and partly at least, unknown peptides and glycopeptides disclosing opioid activity might be characteristic of schizophrenia.

Topics: Animals; Chromatography, Gel; Chronic Disease; Endorphins; Humans; Male; Mental Disorders; Mice; Naloxone; Schizophrenia; Vas Deferens

Topics: Affective Disorders, Psychotic; Double-Blind Method; Endorphins; Humans; Hydrocortisone; Methadone; Motor Activity; Naloxone; Narcotic Antagonists; Neurotransmitter Agents; Prolactin; Random Allocation; Receptors, Opioid; Schizophrenia

Topics: Attention; Brain; Dopamine; Endorphins; Humans; Naloxone; Radioligand Assay; Receptors, Opioid; Schizophrenia; Schizophrenic Psychology

Since 1975, different morphinomimetic peptides have been isolated from hypophyseal-hypothalamic extracts: the pentapeptides methionine-enkephalin and leucine-enkephalin, and the longer peptides alpha-, beta- and gamma-endorphin. The primary structure of most of these peptides is also present in that of beta-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.

Topics: Affective Disorders, Psychotic; Bipolar Disorder; Double-Blind Method; Endorphins; Hallucinations; Humans; Naloxone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Endorphins; Female; Humans; Male; Middle Aged; Naloxone; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Time Factors

Topics: Brain; Caudate Nucleus; Corpus Striatum; Frontal Lobe; Humans; Naloxone; Putamen; Receptors, Dopamine; Receptors, Opioid; Schizophrenia; Spiperone

Topics: Double-Blind Method; Endorphins; Hallucinations; Humans; Naloxone; Narcotic Antagonists; Schizophrenia

Topics: Humans; Middle Aged; Naloxone; Naltrexone; Schizophrenia

Topics: Adult; Animals; Brain; Chromatography, Gel; Dopamine; Dopamine Antagonists; Drug Tolerance; Female; Haloperidol; Humans; Male; Motor Activity; Naloxone; Peptides; Phenoxybenzamine; Rats; Receptors, Opioid; Schizophrenia; Serotonin; Synaptosomes

Topics: Animals; Avoidance Learning; Behavior, Animal; Chronic Disease; Endorphins; Humans; Mental Disorders; Naloxone; Naltrexone; Rats; Receptors, Opioid; Schizophrenia

Psychophysical pain ratings and somatosensory evoked potentials (EPs) were studied in 17 off-medication patients with schizophrenia and 17 age- and sex-matched normal controls. Five of the 17 schizophrenic patients also participated in a clinical trial of naltrexone. In comparison with normal controls, schizophrenic patients were significantly more insensitive to painful stimulation (based on nonparametric analogues of d'from signal detection analysis) and had significantly smaller somatosensory EPs to painful stimuli. Schizophreniucs treated with naltrexone showed significant increases in EP amplitude at higher stimulus intensities and hyperalgesic effects on pain ratings.

Topics: Adult; Electric Stimulation; Evoked Potentials; Female; Humans; Male; Naloxone; Naltrexone; Pain; Schizophrenia

Naloxone HCl (0.8 mg intravenously; n=9) or levallorphan tartrate (0.25 mg subcutaneously; n=5) had no effect on basal prolactin or growth hormone secretion in normal men. Neither narcotic antagonist inhibited the growth hormone secretory response to apomorphine HCl (0.75 mg subcutaneously). These findings suggest that narcotic antagonists do not block dopamine receptors in the hypothalamic-pituitary axis in man and that if these agents have antischizophrenic properties then these are not mediated by dopamine receptor blockade.

Topics: Apomorphine; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Levallorphan; Male; Naloxone; Prolactin; Receptors, Dopamine; Schizophrenia

Topics: Endorphins; Humans; Naloxone; Naltrexone; Schizophrenia; Substance Withdrawal Syndrome

Topics: Bipolar Disorder; Endorphins; Enkephalins; Humans; Naloxone; Nociceptors; Pain; Schizophrenia

1. The release of endorphins appears to play a role as a reserve-mechanism in stress situations. 2. The application of high doses of the specific opiate antagonist 12-allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-(4aH)-(8,9-c)-iminoethanophenanthro(4,5-b,c,d)furan-5(6H)-one (naloxone) to schizophrenic patients induces a partial reversal of hallucinations and actual delusional experience within 2--7 h after injection. 3. The blockade of opiate receptors by naloxone is possibly also effective against catatonic states of schizophrenia. 4. In affective psychoses no curative action of naloxone could be detected so far.

Topics: Endorphins; Euphoria; Humans; Mental Disorders; Naloxone; Receptors, Opioid; Schizophrenia

Topics: Female; Humans; Male; Naloxone; Naltrexone; Schizophrenia; Substance Withdrawal Syndrome; Time Factors

Topics: Adult; Female; Hallucinations; Hearing; Humans; Naloxone; Schizophrenia

Topics: Adult; Female; Humans; Male; Middle Aged; Naloxone; Schizophrenia

Topics: Animals; Antipsychotic Agents; Apomorphine; Avoidance Learning; Clozapine; Conditioning, Operant; Dextroamphetamine; Dose-Response Relationship, Drug; Haloperidol; Humans; Male; Mice; Naloxone; Rats; Schizophrenia; Species Specificity; Stereotyped Behavior

Topics: Adult; Anxiety; Chronic Disease; Hallucinations; Humans; Injections, Intravenous; Male; Middle Aged; Naloxone; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Tranquilizing Agents

Topics: Cognition; Depression; Drug Evaluation; Endorphins; Euphoria; Humans; Naloxone; Peptides; Radioimmunoassay; Schizophrenia; Time Factors

Topics: Administration, Oral; Adult; Drug Evaluation; Female; Humans; Male; Middle Aged; Naloxone; Naltrexone; Pilot Projects; Schizophrenia