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Biomedical subjects

Udo Schneider

Publications and source records attributed to Udo Schneider.

At least 19 recordsLinked to original sources
PubMed2006

Disturbances of visual information processing in early states of psychosis and experimental delta-9-tetrahydrocannabinol altered states of consciousness.

Recent data on alterations of the endogenous cannabinoid system in schizophrenia have raised the question of its functional role in this disease. The psychoactive compound of Cannabis sativa, delta-9-tetrahydrocannabinol (Delta9-THC), has been shown to induce psychotic symptoms, but it is unknown to what extend prodromal states of psychoses are reflected by these experimental approaches. This study compares four groups of subjects: antipsychotic-naïve patients suffering from acute paranoid schizophrenic or schizophreniform psychosis (SZ), patients in the prodromal state (IPS), healthy controls without any pharmacological intervention (HC) and a second group of healthy volunteers who were orally administered synthetic Delta9-THC (Dronabinol) (HC-THC). Neither SZ and IPS nor HC received the experimental drug. All subjects were assessed using the Brief Psychiatric Rating Scale (BPRS) and the Binocular Depth Inversion Illusion Test (BDII). The latter represents a sensitive measure of impaired visual information processing that manifests in various experimental and naturally occurring psychotic states. BDII values were well comparable in SZ, IPS and HC-THC, and all groups differed significantly to HC. The BPRS revealed no significant difference between HC-THC and IPS while both were significantly different from SZ and HC, respectively. Our results suggest that Delta9-THC-induced altered states of consciousness may serve as a useful tool for modeling psychotic disorders, particularly their prodromal states. Furthermore, they provide insight into the perceptual and psychopathological alterations induced by Delta9-THC, which is essential for the understanding of the pro-psychotic effects of herbal cannabis preparations with highly enriched Delta9-THC content.

Acute Disease↗
PubMed2006

Membrane glucocorticoid receptor expression on peripheral blood mononuclear cells in patients with ankylosing spondylitis.

OBJECTIVE: To investigate the expression of membrane glucocorticoid receptors (mGCR) on peripheral blood mononuclear cells (PBMC) in patients with ankylosing spondylitis (AS). METHODS: We used high sensitivity immunofluorescence with magnetofluorescent liposomes for the detection of mGCR on PBMC from patients with AS (n = 26) and healthy controls (n = 11). RESULTS: The frequency of mGCR+ monocytes and B lymphocytes was significantly higher in patients with AS than in controls (monocytes 12.5 +/- 9.9% vs 4.8 +/- 1.4%, B lymphocytes 8.7 +/- 6.3% vs 4.4 +/- 3.6%). We did not find mGCR on T lymphocytes. The frequency of mGCR+ cells did not correlate with variables of AS disease activity [C-reactive protein, erythrocyte sedimentation rate, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI 6, or numerical rating scales]. CONCLUSION: mGCR are upregulated in monocytes and B lymphocytes of patients with AS. This upregulation does not correlate with the humoral or overall disease activity. mGCR are not present on T lymphocytes. Our findings may be related to the limited benefit of low-dose and the efficacy of high-dose (intravenous pulse or intraarticular) glucocorticoid treatment in AS. Drugs binding selectively to mGCR may be a new therapeutic option for AS.

Adult↗
PubMed2006

Feasibility of central cannabinoid CB1 receptor imaging with [124I]AM281 PET demonstrated in a schizophrenic patient.

We studied central cannabinoid CB1 receptors in a schizophrenic patient using the pyrazole derivative AM281 labelled with the positron-emitting nuclide iodine-124. A dynamic positron emission tomography (PET) acquisition with simultaneous blood sampling was performed up to 1.5 h post-injection. The classical Logan plot analysis was applied to generate a three-dimensional map of distribution volume (DV). The map was spatially normalised into the Montreal Neurological Institute stereotactic space. Using a volume of interest (VOI) template, mean values of DV were extracted from multiple grey matter regions and white matter (as a reference). As a measure of regional receptor availability, ratios of DV in grey matter to DV in white matter minus one (DVR-1) were calculated. The highest receptor binding was observed in the striatum and the pallidum (DVR-1: 0.35-0.37). Binding in basal ganglia regions was lower on the left than the right side. Moderately high binding was seen in the frontal cortex (0.22), the temporal cortex (0.18) and the cerebellum (0.15). In conclusion, 124I-AM281 PET can be used to reveal areas with prominent CB1 receptor binding. Nevertheless, limited image contrast and relatively high radiation exposure (physical half-life of 124I: 4 days) have to be taken into account. Asymmetric receptor binding may possibly reflect pathologic changes in schizophrenia.

Brain↗
PubMed2006

Endocrine alterations during a detoxification treatment with carbamazepine in male alcoholics.

This study aimed to evaluate the prevalence and time-course of endocrine alterations in male alcohol addicts during a detoxification treatment and to examine a possible relation between endocrine alterations and depressive symptoms and overall mental distress. Blood samples were drawn in 54 male alcohol addicts on admission, at day 7 of treatment and at day 14 on discharge. Endocrine analysis was performed for cortisol, luteinizing hormone, prolactin, androgens, free testosterone and 17beta-estradiol. Psychometric measures (Beck's depression inventory and the symptom checklist-90-R) were taken on admission and on discharge and were correlated with endocrine measures. Cortisol plasma levels were substantially increased at the beginning of the detoxification, whereas all other endocrine parameters were within the normal range. Although subjects depicted mild to moderate levels of depressive symptoms and mental distress, there were no correlations with endocrine variables. Further analysis revealed a high variation in sex steroid levels with approximately 55% of participants showing initial (n = 19) or developing (n = 11) hypogonadal values during detoxification. In conclusion, chronic alcohol consumption induces disturbances of gonadal function which are reversible in the majority of cases. However, few patients develop a hypogonadal state during detoxification. Initially increased cortisol levels indicate a bodily stress response with the onset of alcohol withdrawal but are not related to mental disturbances.

Adult↗
PubMed2006

Cytochrome P-450 2D6 and 2C19 polymorphisms and length of hospitalization in psychiatry.

We evaluated whether cytochrome P450 (CYP) poor metabolizer polymorphisms of CYP2D6 and CYP2C19 are relevant for the outcome (measured by length of hospitalization) during treatment with psychotropic medications in patients with depression or schizophrenia. 229 patients were genotyped by real-time PCR hybridization probe melting curve technique for CYP2C19*2, CYP2D6*3, *4, and *6, respectively. The gene deletion CYP2D6*5 was analyzed by a long PCR method. Detailed clinical information was obtained from 53 subjects. Patients genotyped homozygous or heterozygous for those CYP2D6 and CYP2C19 poor metabolizer alleles were treated for a longer time in hospital (median 57.5 vs. 40.0 days). Psychiatric patients might benefit from CYP genotyping, the duration of stay as inpatient might be reduced by a priori selection of the appropriate drug for the individual patient.

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

Effects of different subanesthetic doses of (S)-ketamine on neuropsychology, psychopathology, and state of consciousness in man.

This is the first neuropsychological study using the S-enantiomer of the noncompetitive N-methyl-D-aspartate antagonist ketamine. In 2 randomized placebo-controlled trials we studied effects of two different doses of (S)-ketamine (low dose/high dose) on neuropsychological functions and psychopathology in 12 healthy male volunteers. Impairment was measured via standardized neuropsychological tests. Results indicate that both subanaesthetic doses produce only nonsignificant impairment in most of the tasks. Tasks involving divided and sustained attention as well as scores for objective and subjective psychopathology show significant impairment in a dose-dependent manner. Implications of these findings for the neuropsychology of attention and schizophrenia are discussed.

Adult↗
PubMed2005

N-terminal fragment of B-type natriuretic peptide (NT-proBNP), a marker of cardiac safety during antipsychotic treatment.

BACKGROUND: The potential cardiotoxicity of antipsychotic drugs is well known. The N-terminal fragment of B-type natriuretic peptide (NT-proBNP) is considered to be a possible biomarker in clinical practice for the diagnosis and prognosis in patients with suspected heart failure. This pilot evaluation tests the influence of antipsychotic drugs on NT-proBNP concentration in view of the hypothesis that NT-proBNP could be used as marker for the tolerability and safety of antipsychotic medications. METHODS: On a routine basis, patient's blood samples were examined for NT-proBNP on days 0, 7 and 21 after initiation of a new antipsychotic monotherapy. All plasma samples were analysed for NT-proBNP using an electrochemiluminiscence immunoassay "ECLIA" (proBNP kit, Roche Diagnostics, Mannheim, Germany) on an Elecsys 2010 analyser. RESULTS: A difference was found in NT-proBNP values at day 0 between patients younger versus older than 40 years. Also women had comparatively lower NTproBNP on days 7 and 21. Smokers' levels of NT-proBNP values decreased more from day 0 to day 7. CONCLUSION: Our results suggest that antipsychotic medication influences the plasma concentration of NT-proBNP, suggesting a possible method to identify high-risk-patients for cardiovascular adverse effects due to antipsychotic medication. Larger studies should further test this hypothesis.

Journal Article↗
PubMed2005

Determination of ajulemic acid and its glucuronide in human plasma by gas chromatography-mass spectrometry.

A method using gas chromatography-mass spectrometry (GC-MS) and solid-phase extraction (SPE) was developed for the determination of ajulemic acid (AJA), a non-psychoactive synthetic cannabinoid with interesting therapeutic potential, in human plasma. When using two calibration graphs, the assay linearity ranged from 10 to 750 ng/ml, and 750 to 3000 ng/ml AJA. The intra- and inter-day precision (R.S.D., %), assessed across the linear ranges of the assay, was between 1.5 and 7.0, and 3.6 and 7.9, respectively. The limit of quantitation (LOQ) was 10 ng/ml. The amount of AJA glucuronide was determined by calculating the difference in the AJA concentration before ("free AJA") and after enzymatic hydrolysis ("total AJA"). The present method was used within a clinical study on 21 patients suffering from neuropathic pain with hyperalgesia and allodynia. For example, plasma levels of 599.4+/-37.2 ng/ml (mean+/-R.S.D., n=9) AJA were obtained for samples taken 2 h after the administration of an oral dose of 20 mg AJA. The mean AJA glucuronide concentration at 2h was 63.8+/-127.9 ng/ml.

Adult↗
PubMed2005

Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT).

OBJECTIVE: To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA). METHODS: One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score. RESULTS: The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of >/=2.5 at baseline, 68% of infliximab-treated patients achieved improvement of >/=75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups. CONCLUSION: Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.

Adult↗
PubMed2005

Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion.

Methylenedioxymethamphetamine (MDMA or "Ecstasy") is a major stimulant drug of abuse worldwide. MDMA produces euphoria, enhances interpersonal communication and feelings of closeness with others. In contrast to the induced emotions of affection and sensual enhancement, clinical studies show that it impairs sexual drive and functioning. In drug-free humans, sexual stimulation with orgasm induces a pronounced secretion of prolactin, which may mediate the post-orgasmic state. The phenomenological features of the psychological state induced by MDMA show some similarities with features of the post-orgasmic state. In addition, MDMA also induces a prominent increase of prolactin plasma levels with a similar time kinetic compared to the post-orgasmic prolactin increase. Here, we present the hypothesis that the impairment of sexual parameters after MDMA may be mediated by increased prolactin.

N-Methyl-3,4-methylenedioxyamphetamine↗
PubMed2005

Pain measurements and side effect profile of the novel cannabinoid ajulemic acid.

Preclinical findings on ajulemic acid (AJA) showed analgesic and anti-allodynic effects without psychoactive properties making it an appealing substance for the treatment of pain. A recently published randomized double-blind crossover clinical trial described the pain-reducing effects and side effect profile of AJA on 21 patients with chronic neuropathic pain. In this report from this same sample the effects of AJA on the mechanical hypersensitivity, on pain, and on psychological and physical performance were further characterized. During a 5-week study period, patients were divided into two 7-day treatment groups receiving either AJA or placebo capsules first, respectively. All patients received 40 and 80 mg of AJA or placebo daily in each treatment period. Pain measurements included the determination of mechanical hypersensitivity using the von Frey hair method as well as the visual analog scale (VAS), for which the number needed to treat (NNT) was calculated. The side effect profile of the compound was evaluated using psychotropic and physical measurements as well as obtaining reports on possible subjective side effects. The results showed no significant reduction in mechanical hypersensitivity (p=0.052), although a tendency towards pain reduction could be seen. The VAS score showed significant pain reduction (p=0.021) and NNT values for 30% pain relief were 2.14 for the first treatment group and 5.29 for the second treatment group. No significant findings were observed regarding psychotropic or physical measurements. Reported subjective side effects were mainly dry mouth, tiredness and dizziness and did not increase with dose elevation. Overall, these study findings indicate that AJA shows pain-reducing effects on patients with chronic neuropathic pain without clinically relevant psychotropic or physical side effects.

Adult↗
PubMed2005

Oxidative stress during treatment with first- and second-generation antipsychotics.

Neurotoxicity of first-generation antipsychotics (FGAs) may be involved in lipid peroxidation, which is the pathogenesis of extrapyramidal symptoms, including tardive dyskinesia (TD). Blood samples at day 0, 7, and 21 drawn from patients taking antipsychotics were analyzed for malondialdehyde (MDA) in plasma, a marker of lipid peroxidation, by high-performance liquid chromatography. Of 115 patients enrolled, 92 patients completed the study. Most MDA levels were within normal ranges (<1.0 micromol/liter). Malondialdehyde levels in patients receiving clozapine (p = 0.002), quetiapine (p = 0.003), amisulpride (p = 0.008), and risperidone (p = 0.008) were significantly lower than within the first generation antipsychotic group. The authors conclude that lipid peroxidation is significantly higher in treatment with FGAs.

Adolescent↗
PubMed2004

Ajulemic acid: A novel cannabinoid produces analgesia without a "high".

A long-standing goal in cannabinoid research has been the discovery of potent synthetic analogs of the natural substances that might be developed as clinically useful drugs. This requires, among other things, that they be free of the psychotropic effects that characterize the recreational use of Cannabis. An important driving force for this goal is the long history of the use of Cannabis as a medicinal agent especially in the treatment of pain and inflammation. While few compounds appear to have these properties, ajulemic acid (AJA), also known as CT-3 and IP-751, is a potential candidate that could achieve this goal. Its chemical structure was derived from that of the major metabolite of Delta9-THC, the principal psychotropic constituent of Cannabis. In preclinical studies it displayed many of the properties of non-steroidal anti-inflammatory drugs (NSAIDs); however, it seems to be free of undesirable side effects. The initial short-term trials in healthy human subjects, as well as in patients with chronic neuropathic pain, demonstrated a complete absence of psychotropic actions. Moreover, it proved to be more effective than placebo in reducing this type of pain as measured by the visual analog scale. Unlike the narcotic analgesics, signs of dependency were not observed after withdrawal of the drug at the end of the one-week treatment period. Data on its mechanism of action are not yet complete; however, the activation of PPAR-gamma, and regulation of eicosanoid and cytokine production, appear to be important for its potential therapeutic effects.

Analgesics↗
PubMed2004

[123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Delta9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in tourette patients.

BACKGROUND: The cannabinoid CB1 receptor agonist Delta9-THC has been suggested for treatment of Tourette syndrome (TS). Based on animal studies, the CB1 antagonist [123I]AM281 (N-(Morpholin-4-yl)-1-(2,4-dichlorophenyl)-5-(4-[123I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide) has been proposed for single photon emission computed tomography (SPECT) in humans. Our aims were to 1) evaluate specific binding of [123I]AM281 to CB1 receptors in TS patients and 2) assess radiation exposure associated with the use of AM281 labeled with 123I for SPECT and 124I for positron emission tomography. METHODS: We employed [123I]AM281 in six TS patients before and after Delta9-THC treatment. Dynamic SPECT, plasma measurements (including metabolite analysis with thin layer chromatography), and whole-body imaging were performed. Regions of interest derived from magnetic resonance images were used to extract from SPECT uptake in an area with high CB1 density (lentiform nuclei) and reference regions. Specific over nonspecific partition coefficients V3" were calculated. Whole-body images were carried out for dosimetric analysis. Data obtained with [123I]AM281 were used to predict doses from [124I]AM281. RESULTS: Mean V3" ranged from .19 to .31 and did not change significantly after Delta9-THC treatment. Nevertheless, in the only patient with a marked clinical response, V3" clearly declined. Thin layer chromatography revealed biexponential kinetics of tracer metabolism; about 60% remained nonmetabolized after 3 hours. Effective doses of .011 mSv/MBq for [123I]AM281 and .34 for [124I]AM281 were computed. CONCLUSIONS: This study suggests that specific binding of [123I]AM281 to CB1 receptors can be detected in patients using SPECT. Radiation exposure with [123I]AM281 is low; that with [124I]AM281 is higher but acceptable for single investigations.

Adult↗
PubMed2003

Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial.

CONTEXT: 1',1'dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid (CT-3), a potent analog of THC-11-oic acid, produces marked antiallodynic and analgesic effects in animals without evoking the typical effects described in models of cannabinoids. Therefore, CT-3 may be an effective analgesic for poorly controlled resistant neuropathic pain. OBJECTIVE: To examine the analgesic efficacy and safety of CT-3 in chronic neuropathic pain in humans. DESIGN AND SETTING: Randomized, placebo-controlled, double-blind crossover trial conducted in Germany from May-September 2002. PARTICIPANTS: Twenty-one patients (8 women and 13 men) aged 29 to 65 years (mean, 51 years) who had a clinical presentation and examination consistent with chronic neuropathic pain (for at least 6 months) with hyperalgesia (n = 21) and allodynia (n = 7). INTERVENTIONS: Patients were randomized to two 7-day treatment orders in a crossover design. Two daily doses of CT-3 (four 10-mg capsules per day) or identical placebo capsules were given during the first 4 days and 8 capsules per day were given in 2 daily doses in the following 3 days. After a washout and baseline period of 1 week each, patients crossed over to the second 7-day treatment period. MAIN OUTCOME MEASURES: Visual analog scale (VAS) and verbal rating scale scores for pain; vital sign, hematologic and blood chemistry, and electrocardiogram measurements; scores on the Trail-Making Test and the Addiction Research Center Inventory-Marijuana scale; and adverse effects. RESULTS: The mean differences over time for the VAS values in the CT-3-placebo sequence measured 3 hours after intake of study drug differed significantly from those in the placebo-CT-3 sequence (mean [SD], -11.54 [14.16] vs 9.86 [21.43]; P =.02). Eight hours after intake of the drug, the pain scale differences between groups were less marked. No dose response was observed. Adverse effects, mainly transient dry mouth and tiredness, were reported significantly more often during CT-3 treatment (mean [SD] difference, -0.67 [0.50] for CT-3-placebo sequence vs 0.10 [0.74] for placebo-CT-3 sequence; P =.02). There were no significant differences with respect to vital signs, blood tests, electrocardiogram, Trail-Making Test, and Addiction Research Center Inventory-Marijuana scale. No carryover or period effects were observed except on the Trail-Making Test. CONCLUSIONS: In this preliminary study, CT-3 was effective in reducing chronic neuropathic pain compared with placebo. No major adverse effects were observed.

Adult↗
PubMed2003

Gender differences in the effect of repetitive transcranial magnetic stimulation in schizophrenia.

Repetitive transcranial magnetic stimulation (rTMS) can be beneficial in schizophrenia, possibly through a reversal of pre-treatment hypofrontality. Twelve schizophrenic patients (8 men, 4 women) were treated with high-frequency rTMS of the dominant dorsolateral prefrontal cortex. Their performance of the number-connection test, which assesses cognitive processes related to the frontal lobe, was evaluated before and after rTMS. Women improved markedly on the test after rTMS, whereas men did not show a significant change. There were no corresponding sex differences in clinical measures after rTMS. The preliminary findings of sex differences in the response to rTMS, as reflected by performance on the number-connection test, suggest the need for investigations of a greater number of schizophrenic men and women with a more intensive examination of the effects of rTMS on cognitive functions.

Adult↗