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F M Leweke

Publications and source records attributed to F M Leweke.

16 recordsLinked to original sources

[Efficacy and tolerability of quetiapine in hospitalised schizophrenic patients during the acute treatment phase: a PMS study].

We performed a post marketing surveillance study (PMS study) to reveal the efficacy and tolerability of orally administered quetiapine in the treatment of acute psychosis over a period of up to three weeks. 398 respective inpatients were assessed in 88 psychiatric departments in Germany by use of the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS) as well as the clinical impression of psychiatric raters. Safety and tolerability were assessed by vital parameters such as blood pressure, hearth rate and weight as well as the clinical impression of the psychiatric raters. In addition, dosing, concomitant and/or previous pharmacotherapies as well as certain aspects of psychiatric and medical history were documented. A significant reduction of psychopathology was found during three weeks of drug treatment. Daily dosages of quetiapine between 400 and 1200 mg were well tolerated with a limited number of adverse and no serious adverse events. Noteworthy, more than 35 % of all patients received and tolerated excellently more than 800 mg of quetiapine per day under naturalistic treatment conditions, well above the approved maximum daily dosage. This study reflects the clinical efficacy and good tolerability of quetiapine under real world treatment conditions and is in line with the results of the controlled clinical trials of phase II and III.

Acute Disease↗

Systems-theory of psychosis--the relevance of "internal censorship".

The different aspects of the neurobiology of psychotic disorders are presently discussed under the perspective of Arvid Calssons neurochemical theory of mesolimbic/cortico-thalamic loops. In this regard the question as to whether--neuropsychologically--a "filter-defect" or a disturbance of "internal censorship" is causative for psychoses. This topic is discussed in the present paper.

Adult↗

[AWMF-guideline: disorders related to cannabis].

Actually, guidelines for treatment of substance-related disorders were written under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines is the description of the current scientifically proven and evidence-based medicine in addiction to derive recommendations to therapy. In this context, the guideline for treatment of cannabis-related disorders is introduced.

Cannabis↗

Reduced binocular depth inversion in schizophrenic patients.

Binocular depth inversion represents an illusion of visual perception, serving to invert the perception of implausible hollow objects, e.g. a hollow face into a normal face. Such inversion occurs frequently, especially when objects with a high degree of familiarity (e.g. photographs of faces) are displayed. Under normal conditions, cognitive factors apparently override the binocular disparity cues of stereopsis. This internal mechanism--a kind of "censorship" of perception balancing "top-down" and "bottom-up" processes of perception--appears to be disturbed in psychotic states. The clinical and neuropsychological performance of schizophrenic patients was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive And Negative Symptoms Scale (PANSS), the Clinical Global Impression Scale (CGI), the Mehrfach-Wahlwortschatz Intelligence Test (MWT-B) and the binocular depth inversion test (BDIT) using pictures with a high degree of familiarity. In schizophrenic patients, the performance in the BDIT differed significantly from healthy controls and from patients with major depression. The schizophrenic patients were more veridical in their judgements in the BDIT. During antipsychotic treatment, BPRS and PANSS scores improved and the inversed faces were seen as more illusionary, driven by an increase in top-down processing. At the end of treatment, there was no significant difference between the patient group and the healthy controls in the score of binocular depth inversion. These findings suggest that testing of binocular depth inversion can detect specific dysfunctions in visual perception and might be useful as a state-marker for psychotic states.

Adult↗

Different effects of nabilone and cannabidiol on binocular depth inversion in Man.

The physiological and pathophysiological roles of the central nervous endogenous cannabinoid system are not completely understood, but still represent a challenge in basic neurobiological, cognitive, and psychiatric research. The system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, provides a model of impaired perception during psychotic states. Using this model the effects of nabilone, a psychoactive synthetic 9-trans-ketocannabinoid, and of cannabidiol, the main natural component of herbal cannabis, and a combined application of both substances on binocular depth inversion and behavioural states were investigated in nine healthy male volunteers. The time course of the effects of both substances on binocular depth inversion was analysed after oral administration using three different groups of natural stimuli. A significant impairment of binocular depth perception was found when nabilone was administered, but combined application with cannabidiol revealed somewhat reduced effects on binocular depth inversion. The influence of psychoactive cannabinoids on this perceptual model and the role of the endogenous cannabinoid system in visual information processing are discussed.

Adult↗

Elevated endogenous cannabinoids in schizophrenia.

Evidence suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/mass-spectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls (p < 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The findings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.

Adult↗

Effects of synthetic delta9-tetrahydrocannabinol on binocular depth inversion of natural and artificial objects in man.

Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic delta9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The timecourse of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.

Adult↗

Treatment of alcohol withdrawal syndrome with gabapentin.

Four in-patients with moderate alcohol-withdrawal syndromes benefited from treatment with gabapentin administered in an add-on fashion to clomethiazole. In comparison with the amount of clomethiazole required as estimated using a specially developed score during previous detoxifications of these patients at our hospital, gabapentin (400 mg q.i.d.) clearly reduced the amount of clomethiazole needed now Gabapentin, an anticonvulsant with favorable pharmacokinetic properties and tolerability, and with no known risk of dependence, may therefore be a useful new drug in the treatment of alcohol withdrawal. We believe that the potential value of gabapentin in alcohol withdrawal deserves further controlled studies.

Acetates↗

Carbamazepine as an adjunct in the treatment of schizophrenia-like psychosis related to cannabis abuse.

The efficacy of an adjuvant application of carbamazepine in cannabis-related schizophrenia-like psychosis not responsive to neuroleptic treatment is reported for the first time. In two patients, psychotic states occurred after continuous cannabis consumption over a period of 8 and 18 months, respectively, which were mainly characterized by severe thought disorders, disturbances of perception, delusions and weak affect. Both patients were admitted to hospital with no previous clinical history of psychotic episodes. After nonresponsive treatment with neuroleptics over several weeks, they both rapidly responded to additional medication with carbamazepine within a week after onset with a marked reduction in clinical signs and symptoms.

Adult↗

Cannabinoid/anandamide system and schizophrenia: is there evidence for association?

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also to be due to an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes. Here, the perceptual abnormalities induced by psychotogenic agents play a major role as tools for understanding model psychoses. The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulation system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses. The present paper discusses the possible associations between the endogenous anandamide/cannabinoid system and schizophrenic psychoses. Neuropsychological experiments with the 3-D inversion paradigm were performed in healthy volunteers intoxicated with delta9-Tetrahydrocannabinol (delta9-THC). The 3-D inversion paradigm represents a visual illusion of binocular depth perception. Such an inversion occurs in many cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. It is assumed that cognitive factors override the binocular disparity cues of stereopsis. We tested the hypothesis that, during psychotic and related prepsychotic states, the human CNS is unable to correct implausible perceptual hypotheses. Our study provides evidence of strong similarities between data acquired from patients, suffering from productive schizophrenic psychoses and delta9-THC-intoxicated healthy volunteers, as concerns disturbances in the internal regulation of perceptual processes.

Arachidonic Acids↗

[Pro-psychotic change of binocular depth inversion by sleep deprivation].

Binocular depth inversion represents an illusion of visual perception. Such inversion does not occur in all cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. We tested the hypothesis that during sleep deprivation the human CNS is unable to correct the implausible perceptual information. Measurements of binocular depth inversion in perception of 3D objects were taken in sleep-deprived medical staff and healthy volunteers. The binocular depth inversion scores were highly elevated in the sleep-deprived group in comparison to the healthy volunteers. The data demonstrate a strong impairment of binocular depth inversion after sleep deprivation and support the view that sleep deprivation may be accompanied by a disorganisation of the interaction between sensory input and generation of perceptual hypotheses.

Adult↗

Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system.

Cognitive impairments during psychotic episodes are assumed to be caused not only by one single putative classical neurotransmitter dysfunction but also by an impaired equilibrium of the interaction between different neurobiological generators of cognitive processes. Herein, the perceptual abnormalities induced by psychotogenic agents play a major role as tools for the understanding of model psychoses. The recently discovered cannabinoid receptor system with its endogenous ligand anandamide can be regarded as an extremely relevant regulator system, a dysfunctionality of which may explain at least one subtype of endogenous psychoses. Neuropsychological results (three-dimensional inversion illusion) in delta 9-tetrahydrocannabinol-intoxicated normal volunteers exhibit strong similarities with data acquired from patients suffering from productive schizophrenic psychoses, regarding disturbances in internal regulation of perceptual processes. The relevance of this finding to a general cognitive dysfunction concept of schizophrenic psychosis is discussed.

Adult↗

Visual 3D illusion: a systems-theoretical approach to psychosis.

Binocular depth inversion represents an illusion of visual perception. Such an inversion does not occur in all cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. We tested the hypothesis that during psychotic and similar states the human CNS is unable to correct the implausible perceptual hypothesis. Measurements of binocular depth inversion in perception of 3D objects were performed in schizophrenic patients (n = 13), in patients with alcohol withdrawal (n = 10), in sleep-deprived medical staff (n = 10) and in healthy volunteers (n = 41). The binocular depth inversion scores were highly elevated in the patient group and in the sleep-deprivated medical staff in comparison with healthy volunteers. The data demonstrate that impairment of binocular depth inversion reflects a common final pathway, characterized by an impairment of adaptive systems regulating perception.

Adult↗

Effects of pentetrazol on neuronal activity and on extracellular calcium concentration in rat hippocampal slices.

Effects of pentetrazol (PTZ) were studied on neuronal responses in dentate granule cells and area CA1 hippocampal pyramidal cells with intra- and extracellular recording techniques. PTZ induced spontaneous epileptiform field potential transients in areas CA3 and CA1, but not in the dentate gyrus. The concentration optimum for induction of spontaneous epileptiform activity was 2 mM. The epileptiform activity compared in many respects to that induced by GABA antagonists such as picrotoxin, bicuculline and penicillin. Paired pulse stimulus induced responses were affected by concentrations of 0.5 mM. In the concentration range 0.5-2 mM mostly disinhibitory effects were noted. Stimulus induced Ca2+ concentration changes were found to be maximally augmented at concentrations of 2-5 mM. In this range, intracellular studies revealed a block of frequency habituation and an increase in input resistance. The convulsant action of PTZ decreased at concentrations above 5 mM, probably due to a decrease of inward currents. We suggest that the action of PTZ in screening studies for anticonvulsants is mostly due to a decrease of GABAA-receptor mediated IPSPs.

Action Potentials↗

Impaired binocular depth inversion in patients with alcohol withdrawal.

Binocular depth inversion represents an illusion of visual perception. Such inversion does not occur in all cases, especially when objects with a higher degree of familiarity (e.g. photographs of faces) are displayed. Cognitive factors are assumed to override the binocular disparity cues of stereopsis. We tested the hypothesis that during alcohol withdrawal the human CNS is unable to correct the implausible perceptual hypothesis. Measurements of binocular depth inversion in perception of 3D objects were performed in 10 patients with mild alcohol withdrawal and in 11 healthy volunteers. The binocular depth inversion scores were highly elevated in the patients group in comparison to the healthy volunteers. The data demonstrates a strong impairment of binocular depth inversion in alcohol withdrawal and support the view that alcohol withdrawal may be accompanied by a disorganization of the interaction between sensory input and generation of perceptual hypotheses.

Adult↗