Dextromethorphan abuse among opioid-dependent patients

Background: Among opioid-dependent patients on maintenance therapy, concomitant drug abuse is a serious problem. Dextromethorphan, an over-the-counter antitussive agent that can be purchased without prescription, is a drug with a high potential for misuse, especially when consumed in high doses.The objective of this study was to investigate possible abuse of dextromethorphan among substituted opioid-dependent patients and comparison of subjective and objective findings.Due to its ability to increase serotonin levels, opioid-dependent patients may be particularly susceptible to dextromethorphan misuse. Dextromethorphan misuse may have side effects, including psychiatric symptoms and serotonin syndrome, and may induce assault, suicide, or homicide. Methods: A total of 104 opioid-dependent patients in maintenance treatment were included in this cross-sectional study conducted in the outpatient department of the Psychiatric Hospital, University of Zurich. Study participants were divided into 2 groups based on laboratory results: dextromethorphan abusers (n = 12) and nonabusers (n = 92). The objective use and concentrations of dextromethorphan was detected using 3-month hair toxicology analysis.Statistical analysis was performed by using χ test, Student t test, Mann-Whitney U test, and Barnard exact test. Results: Dextromethorphan was abused by 12 (11.5%) patients, 11 (91.7%) of whom did not report concomitant abuse of dextromethorphan but were identified through hair analysis. In general, there were significant differences among patients abusing dextromethorphan compared with nondextromethorphan consumers in terms of trauma due to sexual maltreatment/violence, multiple traumas, or harmful use of hallucinogenic drugs. Conclusions: Further studies are necessary to examine dextromethorphan and its impact on patients with psychiatric comorbidities and psychiatric medication. According to literature, there is a significant drug interaction risk due to the impact of dextromethorphan misuse on serotonin syndrome and psychiatric symptoms. We recommend active inquiry into and testing for concomitant drug abuse among substituted opioid-dependent patients to reduce the risk of drug interactions and side effects in this especially vulnerable group of patients

Disentangling craving‐ and valence‐related brain responses to smoking cues in individuals with nicotine use disorder

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments. Keywords: craving; cue-reactivity; functional Magnetic Resonance Imaging; neuroimaging; nicotine use disorder; smoking

Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33; controls: N=43). In an additional analysis using$^{11}$C-ABP688 positron emission tomography (PET) in a male subsample (CU: N=18; controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence

Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N = 103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N = 92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N = 33; controls: N = 43). In an additional analysis using $^{11}$C-ABP688 positron emission tomography (PET) in a male subsample (CU: N = 18; controls: N = 16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence

Stable self-serving personality traits in recreational and dependent cocaine users

Chronic cocaine use has been associated with impairments in social cognition, self-serving and antisocial behavior, and socially relevant personality disorders (PD). Despite the apparent relationship between Machiavellianism and stimulant use, no study has explicitly examined this personality concept in cocaine users so far. In the frame of the longitudinal Zurich Cocaine Cognition Study, the Machiavellianism Questionnaire (MACH-IV) was assessed in 68 recreational and 30 dependent cocaine users as well as in 68 psychostimulant-naïve controls at baseline. Additionally, three closely related personality dimensions from the Temperament and Character Inventory (TCI)-cooperativeness, (social) reward dependence, and self-directedness-and the screening questionnaire of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) were acquired. At the one-year follow-up, 57 cocaine users and 48 controls were reassessed with the MACH-IV. Finally, MACH-IV scores were correlated with measures of social cognition and interaction (cognitive/emotional empathy, Theory-of-Mind, prosocial behavior) and with SCID-II PD scores assessed at baseline. Both recreational and dependent cocaine users showed significantly higher Machiavellianism than controls, while dependent cocaine users additionally displayed significantly lower levels of TCI cooperativeness and self-directedness. During the one-year interval, MACH-IV scores showed high test-retest reliability and also the significant gap between cocaine users and controls remained. Moreover, in cocaine users, higher Machiavellianism correlated significantly with lower levels of cooperativeness and self-directedness, with less prosocial behavior, and with higher cluster B PD scores. However, Machiavellianism was not correlated with measures of cocaine use severity (r<-.15). Both recreational and dependent cocaine users display pronounced and stable Machiavellian personality traits. The lack of correlations with severity of cocaine use and its temporal stability indicates that a Machiavellian personality trait might represent a predisposition for cocaine use that potentially serves as a predictor for stimulant addiction

Cognitive Impairment in Cocaine Users is Drug-Induced but Partially Reversible: Evidence from a Longitudinal Study

Cocaine users consistently display cognitive impairments. However, it is still unknown whether these impairments are cocaine-induced and if they are reversible. Therefore, we examined the relation between changing intensity of cocaine use and the development of cognitive functioning within 1 year. The present data were collected as part of the longitudinal Zurich Cocaine Cognition Study (ZuCo(2)St). Forty-eight psychostimulant-naive controls and 57 cocaine users (19 with increased, 19 with decreased, and 19 with unchanged cocaine use) were eligible for analysis. At baseline and after a 1-year follow-up, cognitive performance was measured by a global cognitive index and four neuropsychological domains (attention, working memory, declarative memory, and executive functions), calculated from 13 parameters of a broad neuropsychological test battery. Intensity of cocaine use was objectively determined by quantitative 6-month hair toxicology at both test sessions. Substantially increased cocaine use within 1 year (mean +297%) was associated with reduced cognitive performance primarily in working memory. By contrast, decreased cocaine use (-72%) was linked to small cognitive improvements in all four domains. Importantly, users who ceased taking cocaine seemed to recover completely, attaining a cognitive performance level similar to that of the control group. However, recovery of working memory was correlated with age of onset of cocaine use-early-onset users showed hampered recovery. These longitudinal data suggest that cognitive impairment might be partially cocaine-induced but also reversible within 1 year, at least after moderate exposure. The reversibility indicates that neuroplastic adaptations underlie cognitive changes in cocaine users, which are potentially modifiable in psychotherapeutical or pharmacological interventions

Social and Non-Social Cognitive Enhancement in Cocaine Users—A Closer Look on Enhancement Motives for Cocaine Consumption

Background: Cognitive disturbances of chronic cocaine users (CU) have been repeatedly investigated. However, it is yet unknown how CU using cocaine for cognitive or social enhancement differ from stimulant-naïve controls and CU that do not have these motives. More precisely, we assumed that CU with an enhancement motive self-medicate deficits in specific cognitive abilities, i.e., they use cocaine to enhance their performance in either social (social motive) or non-social cognitive situations (cognitive motive). Methods: Forty-two CU were categorized according to their motives for cocaine consumption into social and non-social motive groups as well as cognitive and non-cognitive motive groups, respectively. Subsequently, CU motive groups were compared to 48 stimulant-naïve controls in their social and non-social cognitive functioning applying a comprehensive neuropsychological test battery. Results: The social motive group showed deficits in cognitive empathy compared to controls (Cohen’s d = 0.65) and the non-social motive group (d = 0.60). No mentionable effects were found for emotional empathy and Theory-of-Mind. Cognitive and non-cognitive motive groups both showed general cognitive deficits but with different patterns of impairments compared to controls: the cognitive motive group had deficits mainly in working memory (d = 0.84) and declarative memory (d = 0.60), whereas the non-cognitive motive group also had deficits in working memory (d = 0.61) but additionally in executive functions (d = 0.67). For the domains declarative memory and executive functions, the respective other CU group displayed intermediate performance. Conclusions: This study demonstrates that cocaine is partially instrumentalized by CU with specific enhancement motives to counteract related cognitive impairments

Cognitive control predicted by color vision, and vice versa

One of the most important functions of cognitive control is to continuously adapt cognitive processes to changing and often conflicting demands of the environment. Dopamine (DA) has been suggested to play a key role in the signaling and resolution of such response conflict. Given that DA is found in high concentration in the retina, color vision discrimination has been suggested as an index of DA functioning and in particular blue-yellow color vision impairment (CVI) has been used to indicate a central hypodopaminergic state. We used color discrimination (indexed by the total color distance score; TCDS) to predict individual differences in the cognitive control of response conflict, as reflected by conflict-resolution efficiency in an auditory Simon task. As expected, participants showing better color discrimination were more efficient in resolving response conflict. Interestingly, participants showing a blue-yellow CVI were associated with less efficiency in handling response conflict. Our findings indicate that color vision discrimination might represent a promising predictor of cognitive controlability in healthy individuals