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Stefan Bleich - One of the best experts on this subject based on the ideXlab platform.
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Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth Factor-A and Nerve Growth Factor in Opioid-Maintained Patients.
European addiction research, 2017Co-Authors: Adrian Groh, Rilana Schuster, Mariekathrin Rehme, Thomas Hillemacher, Kirsten Jahn, Alexandra Burkert, Alexandra Neyazi, Laura Schares, Eva Janke, Stefan BleichAbstract:AIMS The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis. METHODS We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or Levomethadone (n = 54) and similar levels in a healthy control group (n = 72). RESULTS There was a significantly higher methylation of VEGF-A in opioid-maintained patients with Levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001). CONCLUSIONS The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.
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elevated methylation and decreased serum concentrations of bdnf in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements (r = −0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on Levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. Levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. Levomethadone with heroine co-use: p = 0.043, diamorphine vs. Levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving Levomethadone without heroine co-use (linear mixed model: control vs. Levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. Levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in Levomethadone maintenance treatment.
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Elevated methylation and decreased serum concentrations of BDNF in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone ( n = 55) or diamorphine ( n = 28) with a healthy control group ( n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate ( r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements ( r = −0.177, p
Uwe Verthein - One of the best experts on this subject based on the ideXlab platform.
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Switching opioid-dependent patients in substitution treatment from racemic methadone, Levomethadone and buprenorphine to slow-release oral morphine: Analysis of the switching process in routine care
Journal of pharmacological sciences, 2020Co-Authors: Cinzia Baschirotto, Kirsten Lehmann, Silke Kuhn, Jens Reimer, Uwe VertheinAbstract:Abstract Since 2015 slow-release oral morphine (SROM) is approved for opioid substitution treatment (OST) in Germany. The SROMOS study (efficacy and tolerability of slow-release oral morphine in opioid substitution treatment) evaluates the efficacy and safety of SROM in routine care. This article describes the switching process from racemic methadone, Levomethadone and buprenorphine to SROM. Between July 2016 and November 2017 180 patients in 23 study centers in Germany were included in the prospective, non-interventional, naturalistic observational study. Patients were already in OST and switched from a previous medication to SROM. The switching process was analyzed during a period of fourteen days. Data were available for 169 participants. The switching process had a different progression depending on premedication and pre dosage. On the fourteenth day of SROM treatment patients switched from racemic methadone took an average dosage of 922.2 mg/day, from Levomethadone 801.0 mg/day and from buprenorphine 626.7 mg/day. Average conversion ratio racemic methadone to SROM was 1:11.8, Levomethadone to SROM 1:17.4 and buprenorphine to SROM 1:58.0. This study provides the first data on the switching process from buprenorphine to SROM. Average dose ratio racemic methadone to SROM on the fourteenth day of treatment was considerably higher than recommended in the prescribing information.
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The effects of racemic D,L-methadone and L-methadone in substituted patients--a randomized controlled study.
Drug and alcohol dependence, 2005Co-Authors: Uwe Verthein, Jens Reimer, Rainer Ullmann, Anke Lachmann, Andreas Düring, Barbara Koch, Hans-günter Meyer-thompson, Rolf Schmidt, Christian HaasenAbstract:Abstract Aims: To test the hypothesis that switching from l -methadone to d , l -methadone is associated with more frequent withdrawal symptoms and side-effects than switching from d , l -methadone to l -methadone. Design: Stratified, randomized 2 × 2 crossover study design over a time-period of 8 weeks. At study entry, every second patient was switched from the pre-study substance to the other medication, after 4 weeks all patients were subject to a (re-)switch. Setting: The study was conducted as a multi-centre trial in three methadone maintenance therapy (MMT) clinics. Participants: Seventy-five patients previously treated with either d , l -methadone or l -methadone for at least 1 year took part in the study. Measurements: Intra-individual changes in withdrawal symptoms (Short Opiate Withdrawal Scale, SOWS) and side-effects were defined as primary outcome criteria. Secondary outcome measures included necessity for methadone dose adjustment. Findings: Complete data were available for 68 patients (91%). Sample strata were unbalanced at baseline: 15 patients (22%) were treated with l -methadone and 43 with d , l -methadone (78%). Thirty-five patients were randomized into the group treated with l -methadone and 33 into the group treated with d , l -methadone during the first 4 weeks. There were no significant differences in intra-individual change of withdrawal symptoms and side-effects between groups after crossover. However, patients treated with Levomethadone tended to feel less withdrawal symptoms than patients treated with d , l -methadone. Conclusions: d , l -methadone and l -methadone can safely be replaced by each other on a 2:1 ratio. Withdrawal symptoms or side-effects due to conversion are of transient nature only.
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Methadone Therapy in Hamburg
European Addiction Research, 1995Co-Authors: Uwe Verthein, Peter Raschke, Jens KalkeAbstract:Methadone treatment for opiate addicts as a structured form of therapy has been introduced in Hamburg in the summer of 1988. The number of patients in substitution has been increasing ever since. Since 1991 scientific follow-up research has been done. The following presents a number of selected results, which show the overall positive effects of methadone therapy. The retention rate is 91.3%, which is extremely high. The dose of methadone (10 ml Levomethadone in general) depends primarily on the dose of heroin a patient was using before the beginning of substitution. The additional use of heroin, cocaine or cannabis does not have any influence on the dosage of methadone. On the whole, we can see positive developments: the patients’ health improved substantially, social reintegration started, the additional use of drugs was given up or decreased. Furthermore the conditions of substitution allow an intensive psycho– and sociotherapy. Both therapists and patients consider such additional therapies effective. Not only do they report an improvement of general well-being but also progress in psychic development as well as progress and changes in social behavior.
Rilana Schuster - One of the best experts on this subject based on the ideXlab platform.
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Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth Factor-A and Nerve Growth Factor in Opioid-Maintained Patients.
European addiction research, 2017Co-Authors: Adrian Groh, Rilana Schuster, Mariekathrin Rehme, Thomas Hillemacher, Kirsten Jahn, Alexandra Burkert, Alexandra Neyazi, Laura Schares, Eva Janke, Stefan BleichAbstract:AIMS The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis. METHODS We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or Levomethadone (n = 54) and similar levels in a healthy control group (n = 72). RESULTS There was a significantly higher methylation of VEGF-A in opioid-maintained patients with Levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001). CONCLUSIONS The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.
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elevated methylation and decreased serum concentrations of bdnf in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements (r = −0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on Levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. Levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. Levomethadone with heroine co-use: p = 0.043, diamorphine vs. Levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving Levomethadone without heroine co-use (linear mixed model: control vs. Levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. Levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in Levomethadone maintenance treatment.
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Elevated methylation and decreased serum concentrations of BDNF in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone ( n = 55) or diamorphine ( n = 28) with a healthy control group ( n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate ( r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements ( r = −0.177, p
Adrian Groh - One of the best experts on this subject based on the ideXlab platform.
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Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth Factor-A and Nerve Growth Factor in Opioid-Maintained Patients.
European addiction research, 2017Co-Authors: Adrian Groh, Rilana Schuster, Mariekathrin Rehme, Thomas Hillemacher, Kirsten Jahn, Alexandra Burkert, Alexandra Neyazi, Laura Schares, Eva Janke, Stefan BleichAbstract:AIMS The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis. METHODS We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or Levomethadone (n = 54) and similar levels in a healthy control group (n = 72). RESULTS There was a significantly higher methylation of VEGF-A in opioid-maintained patients with Levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001). CONCLUSIONS The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.
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elevated methylation and decreased serum concentrations of bdnf in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements (r = −0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on Levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. Levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. Levomethadone with heroine co-use: p = 0.043, diamorphine vs. Levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving Levomethadone without heroine co-use (linear mixed model: control vs. Levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. Levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in Levomethadone maintenance treatment.
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Elevated methylation and decreased serum concentrations of BDNF in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone ( n = 55) or diamorphine ( n = 28) with a healthy control group ( n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate ( r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements ( r = −0.177, p
Thomas Hillemacher - One of the best experts on this subject based on the ideXlab platform.
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Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth Factor-A and Nerve Growth Factor in Opioid-Maintained Patients.
European addiction research, 2017Co-Authors: Adrian Groh, Rilana Schuster, Mariekathrin Rehme, Thomas Hillemacher, Kirsten Jahn, Alexandra Burkert, Alexandra Neyazi, Laura Schares, Eva Janke, Stefan BleichAbstract:AIMS The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis. METHODS We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or Levomethadone (n = 54) and similar levels in a healthy control group (n = 72). RESULTS There was a significantly higher methylation of VEGF-A in opioid-maintained patients with Levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001). CONCLUSIONS The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.
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elevated methylation and decreased serum concentrations of bdnf in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements (r = −0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on Levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. Levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. Levomethadone with heroine co-use: p = 0.043, diamorphine vs. Levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving Levomethadone without heroine co-use (linear mixed model: control vs. Levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. Levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in Levomethadone maintenance treatment.
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Elevated methylation and decreased serum concentrations of BDNF in patients in Levomethadone compared to diamorphine maintenance treatment
European Archives of Psychiatry and Clinical Neuroscience, 2017Co-Authors: Rilana Schuster, Mariekathrin Rehme, Leonie Taschner, Alexander Glahn, Adrian Groh, Helge Frieling, Thomas Hillemacher, Ralf Lichtinghagen, A. Kleimann, Stefan BleichAbstract:Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either Levomethadone ( n = 55) or diamorphine ( n = 28) with a healthy control group ( n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate ( r = −0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck’s Depression Inventory measurements ( r = −0.177, p