Attitudes of Swiss psychiatrists towards cannabis regulation and medical use in psychiatry: a cross-sectional study.

BACKGROUND: Changes in regulation for cannabis for nonmedical use (CNMU) are underway worldwide. Switzerland amended the law in 2021 allowing pilot trials evaluating regulative models for cannabis production and distribution. Simultaneously, cannabis for medical use (CMU) in psychiatry is a growing issue, asked for by patients and being discussed by medical professionals. METHODS: From December 2021 to February 2022, we conducted an online survey of psychiatrists in Switzerland. The survey comprised questions on attitudes towards regulative models for CNMU and towards prescribing CMU for mental disorders. RESULTS: We contacted 2010 psychiatrists in Switzerland. A total of 274 (14%) participated in the survey. Sixty-four percent agreed to a regulated legalization of CNMU, and 89% would welcome pilot trials in Switzerland assessing models for regulating CNMU with those from a French-speaking region being more skeptical. Forty-nine percent of psychiatrists agree that CMU might have a therapeutic effect in mental disorders, but 50% agree that there is not enough scientific evidence yet. Participants working in an inpatient setting or in a French-speaking region as well as those with a longer duration of practice were more skeptical on CMU for mental health. CONCLUSIONS: Most surveyed Swiss psychiatrists favor the regulation of CNMU and the conduct of pilot trials. Despite little evidence and potential negative consequences, many participating Swiss psychiatrists agreed that cannabis could be efficacious in the treatment of some mental disorders advocating for more research in this topic.

Levomethadone Therapeutic Drug Monitoring to Aid Opioid Withdrawal Therapy: A Short Communication.

BACKGROUND: Therapeutic drug monitoring (TDM) is recommended for opioid maintenance therapy with levomethadone. However, TDM has not yet been applied to monitor opioid withdrawal therapy clinically, although tools to improve it are required. METHODS: In this observational cohort study, repeated TDM with levomethadone was performed according to a prospective opioid withdrawal study protocol. Objective and subjective opioid withdrawal symptoms were measured using validated rating scales and correlated to levomethadone plasma concentrations. Plasma levels were measured using high-pressure liquid chromatography with column switching and spectroscopic detection of methadone and its major metabolite. RESULTS: This study included 31 opioid-dependent patients who participated in standardized opioid withdrawal therapy. The serum levels of levomethadone were found to be highly variable and below the recommended therapeutic reference range of 250 ng/mL for maintenance therapy. These serum levels were positively correlated with dosage (r = 0.632; P < 0.001) and inversely correlated with subjective (r = -0.29; P = 0.011) and objective (r = -0.28; P = 0.014) withdrawal symptoms. CONCLUSIONS: The evidence provided sheds light on how to improve levomethadone withdrawal therapy in patients with opioid dependence. It seems likely that higher initial doses at the beginning and lower dose reductions would have been advantageous. TDM can enhance the safety of opioid withdrawal therapies, minimize withdrawal symptoms, and reduce dropout rates.

Evaluation of Phosphatidylethanol Elimination in Alcohol Use Disorder Patients Undergoing Withdrawal Treatment.

AIMS: Phosphatidylethanol (PEth) is used to monitor alcohol consumption in alcohol use disorder (AUD). In this study, we aim to evaluate the elimination time of PEth with regard to the clinically established 200 and 20 ng/ml cutoffs for PEth 16:0/18:1. METHODS: Data from 49 patients undergoing treatment for AUD were evaluated. PEth concentrations were measured at the beginning and repeatedly during the treatment period of up to 12 weeks to monitor the elimination of PEth. We evaluated the time in weeks until the cutoff concentrations of <200 and <20 ng/ml were achieved. The correlation between the initial PEth concentration and the number of days until the PEth concentration had dropped below 200 and 20 ng/ml was assessed by calculating Pearson's correlation coefficients. RESULTS: The initial PEth concentrations ranged from <20 to >2500 ng/ml. In 31 patients, the time until the cutoff values were reached could be documented. Even after 6 weeks of abstinence, PEth concentrations above the cutoff of 200 ng/ml could still be detected in two patients. A strong significant positive correlation was found between the initial PEth concentration and the time required to drop below the two cutoffs. CONCLUSION: A waiting period of more than 6 weeks after declared abstinence should be granted for individuals with AUD before using only one single PEth concentration to assess the consumption behavior. However, we recommend to always use at least two PEth concentrations for the evaluation of alcohol-drinking behaviors in AUD patients.

Alcohol Biomarker Phosphatidylethanol as a Predictor of the Severity of Alcohol Withdrawal Syndrome.

AIMS: to investigate the relationship between phosphatidylethanol (PEth) and withdrawal severity in patients with alcohol use disorder (AUD). METHODS: in 34 patients with AUD admitted for treatment of acute alcohol withdrawal, data were available for initial blood PEth concentrations and scores throughout detoxification of symptoms of withdrawal assessed by trained medical staff using the alcohol withdrawal syndrome (AWS)-scale, a validated scale consisting of 11 items in the alcohol withdrawal syndrome (two subscales with seven physiological and five psychological symptoms). RESULTS: a significant positive correlation between PEth and the severity of alcohol withdrawal was found. When the sample was divided into two groups, according to whether or not AWS score at some point in the treatment reached 6 or more, the median PEth score was higher in those whose peak score had been 6 or more (score of 6 being the suggested cutoff to start medicating the withdrawal syndrome). Although there was a trend for some aspects of the clinical history to be more 'severe' in those with higher AWS, no differences reached significance. CONCLUSION: blood PEth on admission could have a role in identifying patients at risk of more severe AWS.

Prefrontal and striatal dopamine D2/D3 receptors correlate with fMRI BOLD activation during stopping.

D2-like dopamine receptors in animals and humans have been shown to be linked to impulsive behaviors that are highly relevant for several psychiatric disorders. Here, we investigate the relationship between the fronto-striatal D2/D3 dopamine receptor availability and response inhibition in a selected population of healthy OPRM1 G-allele carriers. Twenty-two participants successively underwent blood-oxygen level dependent functional magnetic resonance imaging (fMRI) while performing a stop-signal task and a separate positron emission tomography (PET) scan. Striatal and extrastriatal D2/D3 dopamine receptor availability was measured using the radiotracer [18F]fallypride. Caudate D2/D3 dopamine receptor availability positively correlated with stopping-related fronto-striatal fMRI activation. In addition, right prefrontal D2/D3 dopamine receptor availability correlated positively with stopping-related striatal fMRI BOLD signal. Our study partially replicates previous findings on correlations between striatal D2/D3 dopamine receptor availability and response inhibition in a population selected for its genetic determination of dopamine response to alcohol and as a modulator of impulse control via the endogenous opioid system. We confirm the important role of D2/D3 dopamine receptor availability in the fronto-striatal neural circuit for response inhibition. Moreover, we extend previous findings suggesting that dopamine receptor availability in the right inferior frontal cortex, a crucial region of the stopping network, is also strongly associated with stopping-related striatal fMRI activity in healthy OPRM1 G-allele carriers.

A Nationwide Study of Inpatient Case Rate Incidence of Cannabis-Related Diagnoses in Switzerland.

Objectives: Cannabis is the most commonly used illicit substance and has been associated with mental health issues. In this study, we examined trends in hospitalizations due to cannabis use. Methods: Data were obtained from the Swiss Federal Statistics Office and comprised hospital main diagnoses, gender, age group and region of all psychiatric inpatient cases in Switzerland from 1998 to 2020. We performed trend analyses of annual case rates with cannabinoid-related diagnoses and compared them to trend analyses of alcohol-related and psychotic disorders. Results: Case rates of CRDs significantly increased in the observed time period. From all psychiatric main diagnoses, CRDs were overrepresented in the age groups of 15-24 and 25-44 years. Conclusion: We found a sharp increase in hospitalizations for CRD. Future studies should test whether changes in the upcoming cannabis regulation, which can facilitate the implementation of interventions to address mental health among users, impact future hospitalization rates of CRD.

Neurophysiological correlates of alcohol-specific inhibition in alcohol use disorder and its association with craving and relapse.

OBJECTIVE: This study investigates neurophysiological correlates of general and alcohol-specific inhibitory control in patients with Alcohol Use Disorder (AUD), focusing on its association with individual craving levels and with relapse at three-month follow-up. METHODS: 59 abstinent AUD patients and 20 healthy controls performed a Go/NoGo task incorporating alcohol-related and neutral stimuli during 64-channel electroencephalography (EEG) recording, yielding four event-related potentials (ERP) per participant (NoGo-Alcohol, Go-Alcohol, NoGo-Neutral, Go-Neutral). Whole-scalp randomization-based statistics assessed effects of the factors group (patients/controls or relapsers/abstainers), craving level, response type (NoGo/Go) and picture type (alcohol/neutral) on topography and signal strength of the ERP components N2 and P3. RESULTS: No differences on group level were observed between patients and controls. However, analyses incorporating individual craving indicated that the topographic difference between alcohol-related and neutral NoGo-N2 components increased with craving. Moreover, topographic differences in the alcohol-related and neutral NoGo-P3 component allowed for differentiation between relapsers and abstainers. CONCLUSIONS: In alcohol-related contexts, the response inhibition conflict reflected in the NoGo-N2 seems enhanced in patients with high craving. The inhibition-sensitive NoGo-P3 varies in relapsers but not in abstainers between neutral and alcohol-related contexts. SIGNIFICANCE: In AUD patients, neurophysiological correlates of inhibition vary with alcohol-related contexts and craving, and might be indicative of relapse risk.

Characteristics of Suicides and Toxicology in a Cohort of Individuals With Opioid Use Disorder.

Suicide in patients with opioid use disorder (OUD) is a complex issue. In addition to accidental intoxications, a higher prevalence of fatal suicides in patients with OUD can be found compared to the general population. In this study, suicides with a diagnosis of OUD documented in the project "Suicides, A National Survey" were extracted from our data bank. Individuals with a diagnosis of OUD in their medical history were compared to other suicides. The analyses included clinical and demographic factors as well as an investigation of suicide methods and toxicology of psychotropic drugs. For the statistical analyses, we applied chi-square tests and calculated odds ratios. Out of 6,495 suicide cases in Switzerland between 2000 and 2010, 215 individuals with a medical history of OUD could be identified. Persons in OUD cases were significantly younger than in other suicide cases (p < .001) and had more frequently a positive history for suicide attempts (p = .02). In addition, persons in OUD cases were more often female (p = .076). Intentional self-poisoning with medication was applied more often in individuals with OUD compared to other suicide methods (p < .001). When self-poisoning with drugs was compared to violent suicide methods, a combination of benzodiazepines with antidepressants was predominantly found. Our study yielded significant characteristics and risk factors for suicides in individuals with OUD. The predominant method of suicide in individuals with OUD was intended self-poisoning by medication. This knowledge is of clinical importance for the monitoring of at-risk individuals with OUD as well as for suicide prevention in this patient group.

The Neurophysiology of Implicit Alcohol Associations in Recently Abstinent Patients With Alcohol Use Disorder: An Event-Related Potential Study Considering Gender Effects.

BACKGROUND: Neuroscientific models of alcohol use disorders (AUDs) postulate an imbalance between automatic, implicit, and controlled (conscious) processes. Implicit associations towards alcohol indicate the automatically attributed appeal of alcohol-related stimuli. First, behavioral studies indicate that negative alcohol associations are less pronounced in patients compared to controls, but potential neurophysiological differences remain unexplored. This study investigates neurophysiological correlates of implicit alcohol associations in recently abstinent patients with AUD for the first time, including possible gender effects. METHODS: A total of 62 patients (40 males and 22 females) and 21 controls performed an alcohol valence Implicit Association Test, combining alcohol-related pictures with positive (incongruent condition) or negative (congruent condition) words, while brain activity was recorded using 64-channel electroencephalography. Event-related potentials (ERPs) for alcohol-negative and alcohol-positive trials were computed. Microstate analyses investigated the effects of group (patients, controls) and condition (incongruent, congruent); furthermore, possible gender effects in patients were analyzed. Significant effects were localized with standardized low-resolution brain electromagnetic topography analysis. RESULTS: Although no behavioral group differences were found, ERPs of patients and controls were characterized by distinct microstates from 320 ms onwards. ERPs between conditions differed only in patients with higher signal strength during incongruent trials. Around 600 ms, controls displayed higher signal strength than patients. A gender effect mirrored this pattern with enhanced signal strength in females as opposed to male patients. Around 690 ms, a group-by-valence interaction indicated enhanced signal strength in congruent compared to incongruent trials, which was more pronounced in controls. CONCLUSIONS: For patients with AUD, the pattern, timing, and source localization of effects suggest greater effort regarding semantic and self-relevant integration around 400 ms during incongruent trials and attenuated emotional processing during the late positive potential timeframe. Interestingly, this emotional attenuation seemed reduced in female patients, thus corroborating the importance of gender-sensitive research and potential treatment of AUD.

Efficacy of Varenicline in Patients With Severe Alcohol Dependence: A Pilot Double-Blind Randomized and Controlled Study.

PURPOSE/BACKGROUND: Varenicline has proven its efficacy in the treatment of nicotine dependence, and there is also evidence that it could be helpful in the treatment of alcohol dependence. In our pilot study, we investigated the feasibility and acceptability of varenicline for the treatment of a population of patients with severe alcohol dependence and multiple somatic comorbidities after alcohol detoxification. METHODS/PROCEDURES: We conducted a phase II, double-blind, placebo-controlled randomized trial of daily oral varenicline versus a placebo in alcohol-dependent men and women after alcohol detoxification (n = 28). Following our study protocol, somatic conditions and adverse events were thoroughly monitored and several study end points were investigated (percentage of abstinent days for both alcohol and nicotine, number of standardized drinks and cigarettes per day, days of heavy drinking). FINDINGS/RESULTS: Compared with the placebo, varenicline did not have more side effects and did not provoke more adverse events. Patients in the varenicline group did not show a significantly higher percentage of alcohol abstinent days or fewer heavy drinking days. A trend significance was found for a reduced number of standard drinks per day (P = 0.06) in the varenicline group. IMPLICATIONS/CONCLUSIONS: In this pilot trial, varenicline was shown to be well tolerated by our study population of severely alcohol-dependent patients with somatic conditions. Varenicline did not sustain alcohol abstinence or reduce the number of heavy drinking days, but it did reduce the daily amount of alcohol consumed.

Effect of fluvoxamine augmentation and smoking on clozapine serum concentrations.

BACKGROUND: Clozapine (CLZ) is metabolized via cytochrome P450 CYP1A2 to N-desmethylclozapine (NCLZ). Smoking induces CYP1A2 thereby increasing clozapine metabolism whereas fluvoxamine inhibits CYP1A2. Studies suggest that the beneficial effect of fluvoxamine augmentation in raising serum clozapine concentrations also occurs when serum concentrations are low due to smoking. Yet, little is known about the influence of fluvoxamine augmentation on clozapine serum concentrations in smoking versus non-smoking patients. METHODS: A TDM database was analyzed. Serum concentrations of CLZ, NCLZ, dose-adjusted serum concentrations (C/D) and metabolite-to-parent ratios (MPR) were compared using non-parametrical tests in four groups: clozapine-monotherapy in non-smokers (VNS, n = 28) and smokers (VS, n = 43); combined treatment with clozapine and fluvoxamine in non-smokers (VNS+F, n = 11) and smokers (VS+F, n = 43). RESULTS: The CLZ monotherapy smoking group showed lower values of C/D CLZ of -38.6% (p < 0.001), C/D NCLZ -35.6% (p < 0.001) and a higher MPR (p = 0.021) than in the non-smoking group. The combination of CLZ and fluvoxamine in non-smoking patients led to higher C/D values: C/D CLZ +117.9% (p < 0.001), C/D NCLZ +60.8% (p = 0.029) while the MPR did not differ between groups (p = 0.089). Changes were comparable to fluvoxamine augmentation in the smoking group with increased C/D CLZ of +120.1% (p < 0.001), C/D NCLZ of +85.8% (p < 0.001) and lower MPR (p = 0.006). CONCLUSIONS: Smoking in clozapine monotherapy reduced median dose-adjusted serum concentrations more than a third. Combined treatment with fluvoxamine and clozapine led to higher median C/D values in both, smokers and non-smokers. The opposing effects of CYP1A2 induction by smoking and inhibition by fluvoxamine on clozapine serum concentrations balanced out.

Monitoring of direct alcohol markers in alcohol use disorder patients during withdrawal treatment and successive rehabilitation.

Direct and indirect biomarkers are widely applied for the determination of alcohol consumption. They help to assess past or present alcohol consumption. Depending on the window of detection and sensitivity of the investigated marker, punctual alcohol consumption may remain undetected. In this study, different sampling strategies for the intermediary long-term marker phosphatidylethanol (PEth) are evaluated and compared to the determination of the short-term markers ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Samples from 19 patients undergoing alcohol use disorder treatment were collected during the withdrawal treatment and successive rehabilitation (33 ± 26 days (range: 3-74 days)). With liquid chromatography-tandem mass spectrometry (LC-MS/MS) EtG and EtS in urine, PEth in blood, PEth in dried blood spot (DBS) from venous blood, and PEth in DBS from capillary blood were quantified and compared. The use of volumetric capillary DBS, prepared from 20 µL of blood, provided the same results as the use of venous DBS (95% ± 10%, R2 0.9899 for PEth 16:0/18:1). Capillary DBS sampling has the advantage that it can be performed without venipuncture. The use of PEth in DBS proved to prevent post-sampling degradation, providing a longer detection in comparison to PEth in liquid blood, which only showed 67% ± 24% of the PEth DBS 16:0/18:1 concentration. When compared with EtG and EtS in urine, PEth monitoring proved to be advantageous for the detection of relapse situations, as the accumulation of PEth in blood prolongs the detectability. In conclusion, volumetric capillary DBS sampling for PEth is a simple and useful tool for compliance monitoring, and avoids hematocrit issues.

Comparing Attitudes to Containment Measures of Patients, Health Care Professionals and Next of Kin.

Background: In clinical psychiatric practice, health care professionals (HCP) must decide in exceptional circumstances after the weighing of interests, which, if any, containment measures including coercion are to be used. Here, the risk for patients, staff, and third parties, in addition to therapeutic considerations, factor into the decision. Patients' preference and the inclusion of relatives in these decisions are important; therefore, an understanding of how patients and next of kin (NOK) experience different coercive measures is crucial for clinical decision making. The aim of this study is to compare how patients, HCP, and NOK assess commonly used coercive measures. Methods: A sample of 435 patients, 372 HCP, and 230 NOK completed the Attitudes to Containment Measures Questionnaire (ACMQ). This standardized self-rating questionnaire assessed the degree of acceptance or rejection of 11 coercive measures. Results: In general, HCPs rated the coercive measures as more acceptable than did NOK and patients. The largest discrepancy in the ratings was found in regard to the application of coercive intramuscular injection of medication (effect size: 1.0 HCP vs. patients). However, the ratings by NOK were significantly closer to the patients' ratings compared to patients and HCP. The only exception was the acceptance of treatment in a closed acute psychiatric ward, which was deemed significantly more acceptable by NOK than by patients. Also, patients who had experienced coercive measures themselves more strongly refused other measures. Conclusion: Patients most firmly rejected intramuscular injections, and the authors agree that these should only be used with reservation considering a high threshold. This knowledge about the discrepancy of the ratings should therefore be incorporated into professional training of HCP.

Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2 /D3 binding potential. Twenty-four healthy male µ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BPND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BPND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BPND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D2 /D3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D2 /D3 receptors may hint at an addiction relevant trait.

Serum concentrations of hydroxybupropion for dose optimization of depressed patients treated with bupropion.

BACKGROUND: Bupropion is a dopamine and norepinephrine reuptake inhibitor approved for the treatment of depression and smoking cessation. According to the recently published reviews, it is a candidate for therapeutic drug monitoring (TDM) to improve therapeutic outcomes and reduce risks of intolerability or intoxication. In practice, however, the use of TDM is limited due to the chemical instability of bupropion. This investigation sought to determine if the major, active, and chemically stable metabolite 4-hydroxybupropion is a suitable measure to guide antidepressant drug therapy with bupropion. METHODS: 4-Hydroxybupropion serum levels were measured using a newly developed and validated high-performance liquid chromatography assay with ultraviolet detection. They correlated with therapeutic effects measured by the clinical global impression scale for improvement. RESULTS: The study included 52 patients (50% women). Patients who were markedly improved according to the clinical global impression scale score had significantly (P = 0.042) higher 4-hydroxybupropion serum levels than those with moderate or minimal improvement (mean ± SD, 1113 ± 576, 825 ± 398, and 475 ± 331 ng/mL, respectively). Analysis of receiver operating characteristics revealed significant predictive properties of 4-hydroxybupropion serum levels (P = 0.002) for marked improvement with a lower threshold level of 858 ng/mL. Under similar mean doses (265 ± 107 versus 239 ± 100 mg, respectively), women attained significantly higher serum levels than men (1050 ± 524 versus 589 ± 352 ng/mL, respectively) and exhibited a better therapeutic effect (P = 0.018). CONCLUSIONS: Despite multiple limitations of this naturalistic study, evidence could be given that the measurement of 4-hydroxybupropion in serum is suitable to perform TDM for bupropion. Blood levels should be above 860 ng/mL to attain therapeutic improvement. Potential sex differences in bupropion pharmacokinetics, probably due to differential activities of CYP2B6, should be taken into account when the drug is prescribed.

Broad disruption of brain white matter microstructure and relationship with neuropsychological performance in male patients with severe alcohol dependence.

AIMS: In the last years, refined magnetic resonance diffusion tensor imaging (DTI) methods have become available to study microstructural alterations in the human brain. We investigated to what extent white matter tissue abnormalities are present in male patients after chronic, excessive alcohol consumption and if these alterations are correlated with measures of alcohol consumption and neuropsychological performance. METHODS: Twenty-four detoxified adult male patients with severe alcohol dependence and 23 healthy male control subjects were included in the study. Neuropsychological tests were assessed for executive function, attention, memory and visuospatial function. DTI was acquired and preprocessing of the data was performed using tract-based spatial statistics. Group differences of fractional anisotropy (FA) as well as correlation analyses with neuropsychological measures and drinking history were calculated. RESULTS: Performance in alcoholic patients was significantly poorer in tests of non-verbal reasoning and attention. In detoxified alcoholic patients, lower FA was primarily found in the body of the corpus callosum, but these findings did not correlate directly with behavioral measures. However, executive and psychomotor performance (Trail-Making Test) correlated significantly with FA in right anterior cingulate and left motor areas. CONCLUSION: These findings provide further evidence for reduced integrity of interhemispheric connections in male patients with severe alcohol dependence, and neurocognitive performance was in part correlated with FA.

Impulsiveness and venturesomeness in German smokers.

INTRODUCTION: Cigarette smoking is a behavior, which is influenced by genetic, demographic, and psychological factors. A large body of research has examined the association of cigarette smoking variables with individual differences in personality traits. The aim of the current study was to replicate the findings of higher self-reported impulsivity in smokers compared with never-smokers in a German sample using Eysenck´s construct of impulsivity. Furthermore, it was intended to further the knowledge about associations between different self-reported impulsivity components and different smoking variables. METHODS: We used the Impulsiveness-Venturesomeness-Empathy questionnaire (I7) to measure self-reported impulsiveness and venturesomeness and the Temperament and Character Inventory (TCI) to measure novelty seeking (NS) in a sample of 82 nicotine-dependent smokers and 119 never-smokers. RESULTS: Smokers scored higher on impulsiveness, venturesomeness, and NS than never-smokers independent of age, gender, and years of education. We found a significant association between venturesomeness, impulsiveness and smoking status in daily smokers. CONCLUSIONS: In summary, this study provides evidence that impulsiveness and venturesomeness as well as the novelty-seeking subscale extravagance are significantly associated with smoking status in a German sample of female and male smokers compared with never-smokers.