Udo Bonnet - Academia.edu (original) (raw)

Papers by Udo Bonnet

Cannabis: Potenzial und Risiko, 2019

Zur gezielten Aufnahme, Verarbeitung und Speicherung der komplexen sensorischen Informationen uns... more Zur gezielten Aufnahme, Verarbeitung und Speicherung der komplexen sensorischen Informationen unserer Umwelt benotigen wir kognitive Fahigkeiten. Unter „Kognition” versteht man dabei eine Vielzahl bewusster sowie unbewusster neuronaler Prozesse des Gehirns, die bei der Verarbeitung externer und interner Informationen ablaufen.

Annals of Pharmacotherapy, 2016

We read with deep interest the article by Mersfelder and Nichols, who provided a precise clinical... more We read with deep interest the article by Mersfelder and Nichols, who provided a precise clinical overview of gabapentin’s potency to be addictive in humans. All identified cases with gabapentin addiction had another current or previous substance use disorder (SUD) involving alcohol, cocaine, or opioids. Most often, gabapentin misuse was identified in association with opiate addiction. An amplification of a desired opioid high and relief of anxiety symptoms during opiate withdrawal might be factors promoting this misuse. Although prescribed several million times since its introduction to the market in 1997, there is no convincing evidence of gabapentin misuse in patients without another past or current SUD. The authors are familiar with gabapentin prescriptions since the late 1990s and have used gabapentin also “off-label” temporarily and beneficially more than a thousand times (1) as an adjunct in the treatment of withdrawal symptoms of alcohol, benzodiazepines, cannabis, and opioids or (2) in the treatment of anxiety or agitation in anxiety and affective disorders or dementia. We remember no patient seeking treatment of gabapentin abuse or who showed a gabapentin-seeking behavior. Among the patients without a history of SUD, there were 6 cases (4 women) of middle-aged adults and elderly people who developed a withdrawal syndrome after several weeks of treatment with gabapentin. These patients had been diagnosed with generalized anxiety disorder or anxious depression and had stopped gabapentin treatment (1200-3200 mg gabapentin/d) erroneously in an abrupt manner. The withdrawal symptoms resembled those of selective serotonin reuptake inhibitors and benzodiazepines. The larger the gabapentin doses had been prior to abrupt quitting, the stronger was the withdrawal syndrome, which could be well mitigated by reinstating gabapentin, which was thereafter gradually tapered in the following few weeks without problems. With the exception of this withdrawal syndrome and some tolerance to gabapentin’s intended beneficial action on agitation and anxiety, there were no further core symptoms of SUD in these patients, especially no craving or drug-seeking behavior. Gabapentin might belong to the class of psychoactive drugs, such as antidepressants (eg, tranylcypromine, tianeptine, bupropion), which themselves have no relevant specific addiction potency (sui generis) but could become addictive in patients with another SUD, who look for various options to induce euphoria or improve their affected stress reactivity that occur following substance addiction. Unlike nicotine, alcohol, or benzodiazepines, there is no evidence that prescription of gabapentin would ease the misuse of other drugs in patients without a history of SUD; thus, no gateway effect has been observed so far. In rats, gabapentin had no effect on conditioned place preference, which is commonly used to find evidence of a drug’s rewarding property. We are aware of no animal experiments conclusively demonstrating rewarding or reinforcing properties of gabapentin. Non–treatment-seeking cocaine abusers did not alter their choice to self-administer cocaine while on gabapentin maintenance (up to 3200 mg/d). Therefore, we support the view that the addiction risk of gabapentin is negligible in patients without a history of SUD. Nevertheless, a larger systematic clinical trial investigating the addictive risk of gabapentin in patients with and without a relation to another SUD is warranted.

Journal of Clinical Psychopharmacology, 2003

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Fortschritte der Neurologie · Psychiatrie, 2006

Frontiers in Psychiatry, Apr 23, 2021

Background: In response to the COVID-19-pandemic, a lockdown was established in the middle of Mar... more Background: In response to the COVID-19-pandemic, a lockdown was established in the middle of March 2020 by the German Federal Government resulting in drastic reduction of private and professional traveling in and out of Germany with a reduction of social contacts in public areas. Research Questions: We seek evidence on whether the lockdown has led to a reduced availability of illegal drugs and whether subjects with substance-related problems tried to cope with possible drug availability issues by increasingly obtaining drugs via the internet, replacing their preferred illegal drug with novel psychoactive substances, including new synthetic opioids (NSO), and/or by seeking drug treatment. Methods: A questionnaire was anonymously filled in by subjects with substance-related disorders, typically attending low-threshold settings, drug consumption facilities, and inpatient detoxification wards from a range of locations in the Western part of Germany. Participants had to both identify their main drug of abuse and to answer questions regarding its availability, price, quality, and routes of acquisition. Results: Data were obtained from 362 participants. The most frequent main substances of abuse were cannabis (n = 109), heroin (n = 103), and cocaine (n = 75). A minority of participants reported decreased availability (8.4%), increased price (14.4%), or decreased quality (28.3%) of their main drug. About 81% reported no change in their drug consumption due to the COVID-19 pandemic and the lockdown. A shift to the use of novel psychoactive substances including NSO were reported only by single subjects. Only 1-2% of the participants obtained their main drug via the web. Scherbaum et al. Drug Availability During COVID-19 Pandemic Discussion: Present findings may suggest that recent pandemic-related imposed restrictions may have not been able to substantially influence either acquisition or consumption of drugs within the context of polydrug users (including opiates) attending a range of addiction services in Germany.

Medical Principles and Practice

Fortschritte der Neurologie · Psychiatrie, 2017

ZusammenfassungDie Verschreibungshäufigkeit der Gabapentinoide Gabapentin und Pregabalin hat in d... more ZusammenfassungDie Verschreibungshäufigkeit der Gabapentinoide Gabapentin und Pregabalin hat in den letzten 10 Jahren auch in Deutschland stark zugenommen. Insbesondere Warnungen aus mehreren nationalen und internationalen Pharmakovigilanz-Registern sowie der Handel von Gabapentoiden auf Schwarzmärkten und im Internet haben zu einer anhaltenden Debatte über das Gefährdungs- und Abhängigkeitsrisiko dieser Substanzen geführt. Da klinische Zulassungsstudien bisher keine bedeutsamen Hinweise auf eine Abhängigkeitsentwicklung zeigten, haben wir systematisch in PubMed und Scopus nach Kasuistiken und klinischen Studien zu Missbrauch und Abhängigkeit von Gabapentin und Pregabalin gesucht. Wir fanden 14 klinisch-epidemiologische Studien und 38 Kasuistiken. Diese wurden durchsucht nach Hinweisen auf i) erfüllte Abhängigkeitskriterien nach ICD-10, ii) nicht-medizinische Einnahmen und deren Dauer, iii) Rückfälle, iv) soziale Folgeschäden und v) Fälle mit Behandlung wegen eines nicht-medizinisch...

GeroPsych, 2016

. There is a lack of studies using a structured face-to-face interview focusing on the full spect... more . There is a lack of studies using a structured face-to-face interview focusing on the full spectrum of substance addictions according to ICD or DSM classification systems in older patients. We therefore examined a cohort of 400 randomly selected, at least 65-year-old inpatients of a general hospital concerning addictive disorders using a well-tested structured clinical interview (DSM-IV-TR-based SKID-I). Nearly one third of this cohort was substance dependent: The 12-month prevalence rate for nicotine was 10.3% and for alcohol dependence 3%, with 24.4% and 66.7%, respectively, being severely dependent. These rates were similar to those found in the general German population of persons under 65 year of age. A fifth of the cohort was (mostly mildly) dependent on prescription drugs, remarkably including nonopioid analgesics. One case with a previous dependence on gabapentin was identified. Identification and management of addiction disorders should be considered as part of the basic geriatric assessment.

Alcohol and Alcoholism, 2010

Aims: To compare two inpatient symptom-triggered pharmacological treatments of acute alcohol with... more Aims: To compare two inpatient symptom-triggered pharmacological treatments of acute alcohol withdrawal (AWS) (clomethiazole vs. clonazepam). Methods: Prospective observational comparison within a quality improvement project. Because of a need for extra precautions against complications such as seizures and severe respiratory complaints, patients with a history of withdrawal seizures or complications with clomethiazole in their history were automatically assigned to the clonazepam group. The remaining patients were alternately assigned either to the clonazepam group (n = 38 altogether) or the clomethiazole group (n = 36). Rescue medication could consist of adding either extra clonazepam or clomethiazole. Effectiveness was measured by Clinical Global Impression Scale, Revised Clinical Institute Withdrawal Assessment for Alcohol Scale, Mainz Alcohol Withdrawal Scale, Essen Self-Assessment-Alcohol Withdrawal and attrition rate. Safety and tolerability was estimated from adverse clinical events. Secondary outcome values were heart rate, blood and pulse pressure. Results: There were no significant differences between the treatments with respect to primary and secondary effectiveness measures, safety or tolerability or duration of medication treatment. Both reduced the severity of initial withdrawal symptoms below 20% up to the ending of withdrawal medications. No withdrawal seizure or delirium occurred. Conclusion: Both score-driven treatments were equally effective, safe and well tolerated in this setting. This is the first study demonstrating the utility of clonazepam in the treatment of AWS syndrome.

Frontiers in Psychiatry

BackgroundThere is a lack of benefit/harm assessments of illicit and licit psychoactive substance... more BackgroundThere is a lack of benefit/harm assessments of illicit and licit psychoactive substances performed by substance-dependent users in comparison to addiction medicine experts.MethodsWe extended the analyses of substance harm/benefit assessments of German addiction medicine experts (N = 101), in parts reported recently in this journal [doi.org/10.3389/fpsyt.2020.59219], by the perspectives of substance-addicted persons. The same questionnaire as used for the abovementioned “experts-study” was handed out to inpatient detoxification or rehab treatment seeking German substance-dependent adults (N = 117) for a subsequent structured interview about harms and benefits of 33 new and traditional psychoactive substances comprising also prescription drugs.Results and discussionBoth, users and experts, ranked the traditional illicit psychoactive substances heroin, cocaine and amphetamines within the top overall harm level group. Synthetic cannabinoids, alcohol and benzodiazepine were in ...

Journal of Clinical Psychopharmacology

Purpose/Background: Studies for repurposed drugs in severe acute respiratory syndrome coronavirus... more Purpose/Background: Studies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2-infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19. Methods/Procedures: We conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19. Finding/Results: As of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19-related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate. Implications/Conclusions: At present, the best evidence of an "anti-COVID-19" potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute "dark zones" in COVID-19 research. Further controlled studies testing the effectiveness/ efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.

Frontiers in Psychiatry, 2020

BackgroundAbout 15 years ago, a diverse group of new recreational psychotropic substances began t... more BackgroundAbout 15 years ago, a diverse group of new recreational psychotropic substances began to emerge, which were marketed for example as “legal highs,” “research chemicals,” or “designer drugs.” These substances were later subsumed under the label “Novel Psychoactive Substances” (NPS). Important NPS classes are cathinones, synthetic cannabimimetics, phenethylamines, and herbal drugs. The health care system for psychotropic substance use disorders (SUDs) traditionally focused on a few substances, such as alcohol, heroin, cocaine, amphetamines, or cannabis. Users of illicit substances often engage in polydrug use. However little is known about the prevalence of NPS use within the group of “classical” illicit substance users.ObjectiveWe investigated lifetime and recent use of NPS and other drugs in patients who underwent in-patient detoxification treatment from illicit drugs in Germany.MethodsIn a multicenter study with eight participating facilities, patients admitted to treatmen...

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2009

The intensity of withdrawal in opiate dependence shows a high inter-individual variability. The 8... more The intensity of withdrawal in opiate dependence shows a high inter-individual variability. The 825CNT polymorphism (rs5443) of the G-protein beta 3 (GNB3) subunit gene has a strong influence on clinical signs of sympathetic activity in cardiac research. This study was carried out in order to test the hypothesis that carriers of the T allele have an increased sympathetic activity in opiate withdrawal. Methods: Thirty-nine monovalent opiate addicted patients consecutively admitted to a detoxification ward were investigated. The main parameter for sympathetic activity was the pulse rate in the first 3 days after the regular end of gradual methadone reduction. Results: Thirty-three out of 39 patients achieved a drug-free state: 22 carried a T allele (TT, CT), 11 belonged to the CC genotype group. The pulse rate was significantly (p b 0.05) raised in the T allele group compared to the CC genotype group on the first 2 days after stopping methadone administration. In addition, about a third of the T allele carriers needed clonidine treatment on the respective days, but only one patient among the 11 CC homozygotes. There was no significant difference between groups in systolic and diastolic blood pressures as well as in subjective withdrawal ratings. Conclusion: A group difference regarding pulse rate could be observed in a small sample and despite a higher degree of concomitant clonidine medication in T allele carriers. The failure to detect group differences in blood pressure and self-rated withdrawal symptoms may be attributed to the more complex regulation of blood pressure and the known weak correlation between objective and subjective withdrawal symptoms.

Der Nervenarzt, 2015

Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affe... more Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affected individuals and for a substantial proportion of the overall burden of disease for the community. To date, existing treatment options are either poorly known by doctors or they are not fully applied and only approximately 15 % of potential patients are treated with a mean latent period of 10 years between early symptoms and the first intervention. So-called S3 treatment guidelines were recently developed to close this gap. Representatives of more than 50 learned societies, families and patients were involved. A systematic literature search from 2005 to 2012 was performed and more than 120 recommendations were made. Financing came exclusively from those societies and the academic and treatment institutes involved. This article summarizes the recommendations pertinent for psychiatrists and include early detection and intervention, acute withdrawal and long-term psychotherapy and pharmacotherapy. Classical and new treatment goals are discussed. If the new guidelines were properly applied an increase in patients receiving treatment to 30-40 % could be expected, which would improve the quality of lives of affected persons and their families and in Germany would save several thousand lives per year

Hypercapnia as well as lowered intracellular pH (pHi) increase the bioelectric activity of CO2/H-... more Hypercapnia as well as lowered intracellular pH (pHi) increase the bioelectric activity of CO2/H-sensitive neurones (VLNcs) of the ventrolateral medulla oblongata. Here we describe that immunoreactive Na+/H+ exchanger (NHE3) is present in ventrolateral neurones from medullary organotypic cultures (obex level). To test whether VLNcs can be acidified and thereby activated by inhibition of NHE3, we used the novel high-affinity NHE3-inhibitors S1611 and S3226. Both drugs raised the firing rates of VLNcs to at least 150% of the control values, and depolarized membrane potential by up to 15 mV at concentrations (0.5–1 μmol/l) suitable for selective inhibition of NHE3. The changes in bioelectric activity strongly resembled the responses to hypercapnia (PCO2: 60–100 mmHg). In BCECF-AM-loaded cultures a subfraction of ventrolateral VLNcs was found to be intracellularly acidified by 0.05–0.1 pH units following treatment with S1611; the time course of this acidification was similar to that evo...

Fortschritte der Neurologie · Psychiatrie, 2011

The intracellular pH (pHi) of neurons is tightly regulated, mainly by membrane-bound transporters... more The intracellular pH (pHi) of neurons is tightly regulated, mainly by membrane-bound transporters acting as acid extruders or acid loaders. Regulation of pHi helps to control neuronal excitability, as increased bioelectric activity moderately lowers pHi and, in the sense of a negative feedback loop, intracellular acidosis mostly reduces neuronal excitability. Moreover, a change of pHi widely influences complex cellular functions. With respect to neuropsychopharmaca, little is known about whether or not they may affect neuronal H ( + )-homeostasis. To this aim, we tested several antipsychotics, antidepressants, anticonvulsants, and lithium for effects on neuronal pHi, using guinea pig hippocampal slice preparations in which CA 3 pyramidal neurons were loaded with the pHi-sensitive dye BCECF-AM. All antipsychotics, most antidepressants and about half of the anticonvulsants tested so far elicited reversible changes of neuronal pHi when applied at therapeutic and supratherapeutic concentrations. Although these results await confirmatory in vivo experiments, we believe that the pHi activity of neuropsychopharmaca needs further attention, especially when therapeutic mechanisms or even harmful side effects are discussed.

British Journal of Pharmacology, 2004

Pfl�gers Archiv European Journal of Physiology, 1999

Hypercapnia as well as lowered intracellular pH (pHi) increase the bioelectric activity of CO2/H+... more Hypercapnia as well as lowered intracellular pH (pHi) increase the bioelectric activity of CO2/H+-sensitive neurones (VLNcs) of the ventrolateral medulla oblongata. Here we describe that immunoreactive Na+/H+ exchanger (NHE3) is present in ventrolateral neurones from medullary organotypic cultures (obex level). To test whether VLNcs can be acidified and thereby activated by inhibition of NHE3, we used the novel high-affinity NHE3-inhibitors S1611 and S3226. Both drugs raised the firing rates of VLNcs to at least 150% of the control values, and depolarized membrane potential by up to 15 mV at concentrations (0.5-1 micromol/l) suitable for selective inhibition of NHE3. The changes in bioelectric activity strongly resembled the responses to hypercapnia (PCO2: 60-100 mmHg). In BCECF-AM-loaded cultures a subfraction of ventrolateral VLNcs was found to be intracellularly acidified by 0.05-0.1 pH units following treatment with S1611; the time course of this acidification was similar to that evoked by hypercapnia. All drug effects were sustained and readily reversible upon washing. Non-CO2/H+-responsive medullary neurones as well as hippocampal CA3 neurones were unaffected by up to 20 micromol/l S1611. It is concluded that the selective inhibition of NHE3 acidifies and activates CO2/H+-sensitive neurones within the ventrolateral medulla oblongata.