Clonidine Improved Laboratory-Measured Decision-Making Performance in Abstinent Heroin Addicts

BACKGROUND: Impulsivity refers to a wide spectrum of actions characterized by quick and nonplanned reactions to external and internal stimuli, without taking into account the possible negative consequences for the individual or others, and decision-making is one of the biologically dissociated impulsive behaviors. Changes in impulsivity may be associated with norepinephrine. Various populations of drug addicts all performed impulsive decision making, which is a key risk factor in drug dependence and relapse. The present study investigated the effects of clonidine, which decreased norepinephrine release through presynaptic alpha-2 receptor activation, on the impaired decision-making performance in abstinent heroin addicts. METHODOLOGY/PRINCIPAL FINDINGS: Decision-making performance was assessed using the original version of Iowa Gambling Task (IGT). Both heroin addicts and normal controls were randomly assigned to three groups receiving clonidine, 0, 75 µg or 150 µg orally under double blind conditions. Psychiatric symptoms, including anxiety, depression and impulsivity, were rated on standardized scales. Heroin addicts reported higher scores on the Barratt Impulsiveness Scale and exhibited impaired decision-making on the IGT. A single high-dose of clonidine improved the decision-making performance in heroin addicts. CONCLUSIONS/SIGNIFICANCE: Our results suggest clonidine may have a potential therapeutic role in heroin addicts by improving the impaired impulsive decision-making. The current findings have important implications for behavioral and pharmacological interventions targeting decision-making in heroin addiction

Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches

Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with internet gaming disorder (IGD), which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs) without IGD were recruited, and the balloon analog risk task (BART) was used in a functional magnetic resonance imaging experiment to evaluate the modulation of the risk level (the probability of balloon explosion) on brain activity during risky decision making in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC) during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11) scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents

The role of the cerebellum in drug-cue associative memory: functional interactions with the medial prefrontal cortex

Drug-induced Pavlovian memories are thought to be crucial for drug addiction because they guide behaviour towards environments with drug availability. Drug-related memory depends on persistent changes in dopamine-glutamate interactions in the medial pre- frontal cortex (mPFC), basolateral amygdala, nucleus accumbens core and hippocampus. Recent evidence from our laboratory indi- cated that the cerebellum is also a relevant node for drug-cue associations. In the present study, we tested the role that specific regions of the cerebellum and mPFC play in the acquisition of cocaine-induced preference conditioning. Quinolinic acid was used to manage a permanent deactivation of lobule VIII in the vermis prior to conditioning. Additionally, lidocaine was infused into the prelim- bic and infralimbic (IL) cortices for reversible deactivation before every training session. The present findings show, for the first time, that the cerebellum and mPFC might act together in order to acquire drug-cue Pavlovian associations. Either a dorsal lesion in lobule VIII or an IL deactivation encouraged cocaine-induced preference conditioning. Moreover, simultaneous IL-cerebellar deactivation prevented the effect of either of the separate deactivations. Therefore, similar to the IL cortex, neural activity in the cerebellum may be crucial for ensuring inhibitory control of the expression of cocaine-related memories

Behavioral Risk Elicits Selective Activation of the Executive System in Adolescents: Clinical Implications

We investigated adolescent brain processing of decisions under conditions of varying risk, reward, and uncertainty. Adolescents (n = 31) preformed a Decision–Reward Uncertainty task that separates decision uncertainty into behavioral and reward risk, while they were scanned using functional magnetic resonance imaging. Behavioral risk trials involved uncertainty about which action to perform to earn a fixed monetary reward. In contrast, during reward risk the decision that might lead to a reward was known, but the likelihood of earning a reward was probabilistically determined. Behavioral risk trials evoked greater activation than the reward risk and no risk conditions in the anterior cingulate, medial frontal gyrus, bilateral frontal poles, bilateral inferior parietal lobe, precuneus, bilateral superior-middle frontal gyrus, inferior frontal gyrus, and insula. Our results were similar to those of young adults using the same task (Huettel, 2006) except that adolescents did not show significant activation in the posterior supramarginal gyrus during behavioral risk. During the behavioral risk condition regardless of reward outcome, overall mean frontal pole activity showed a positive correlation with age during the behavioral and reward risk conditions suggesting a developmental difference of this region of interest. Additionally, reward response to the Decision–Reward Uncertainty task in adolescents was similar to that seen in young adults (Huettel, 2006). Our data did not show a correlation between age and mean ventral striatum activity during the three conditions. While our results came from a healthy high functioning non-maltreated sample of adolescents, this method can be used to address types of risks and reward processing in children and adolescents with predisposing vulnerabilities and add to the paucity of imaging studies of risk and reward processing during adolescence

Decision-making in Adolescents: Performance under Different Conditions of Information and Alcohol Intoxication

El objetivo fue evaluar la toma de decisiones en adolescentes. Se utilizó la Iowa Gambling Task (IGT) y la Game of Dice Task (GDT). Se utilizó un diseño experimental con pre y postest donde se manipuló el tratamiento (intoxicado/no intoxicado) y la información recibida (verdadera/falsa). Se evaluaron 77 participantes voluntarios entre 18 y 25 años. Para analizar los datos se utilizaron ANOVAs. Se encontraron diferencias en hombres y mujeres en relación a las distintas puntuaciones de la IGT y GDT. Encontrar efectos relacionados al sexo de los participantes coincide con lo informado en algunos estudios. El mejor rendimiento de las mujeres en la GDT puede explicarse teniendo en cuenta que las funciones ejecutivas están implicadas, lo que daría ventaja a las mujeres. Finalmente, los resultados relacionados a la intoxicación podrían mostrar que el alcohol afecta la calidad de la toma de decisiones.The aim was to assess decision-making in adolescents. To this, we used the Iowa Gambling Task (IGT) and the Game of Dice Task (GDT). We used an experimental design with pre-post-test where we manipulated the treatment (Intoxicated/ Non Intoxicated) and the information received (True/False). 77 volunteers were evaluated between 18 and 25 years old. Data was analyzed using ANOVA. We found differences between men and women in different scores on the IGT and GDT. Sex-related effects of the participants agreed with other studies. The better performance of women on the GDT can be explained taking into account that executive functions are involved in task execution, at which women perform better. Finally, results related to intoxication suggest that alcohol affects the quality of decision making.Fil: Acuña, Hugo Ignacio. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castillo, Daniela Susana. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bechara, Antoine. University of Southern California; Estados UnidosFil: Godoy, Juan Carlos. Universidad Nacional de Córdoba; Argentin

Cannabis use and cognitive functions in at-risk mental state and first episode psychosis

BACKGROUND: Meta-analyses suggest that schizophrenia patients with a history of cannabis use have less impaired cognitive functioning compared to patients without cannabis use. AIMS: The objective of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in at-risk mental state for psychosis (ARMS) and first episode psychosis (FEP) individuals. METHODS: One hundred thirty-six participants completed a cognitive test battery and were assessed for current and past cannabis use. Analyses of covariance models were applied to evaluate the main effects of cannabis use and patient group (ARMS vs. FEP) as well as their interactions on cognitive functioning. RESULTS: No differences were observed in cognitive performance between current, former, and never users, and there were no significant interactions between cannabis use and patient group. Furthermore, within the group of current cannabis users, the frequency of cannabis use was not significantly associated with cognitive functioning. CONCLUSION: The results of the present study do not support the notion that FEP patients and ARMS individuals with a history of cannabis use have less impaired cognitive functioning compared to those without cannabis use

Cannabis use and cognitive functions in at-risk mental state and first episode psychosis

Background: Meta-analyses suggest that schizophrenia patients with a history of cannabis use have less impaired cognitive functioning compared to patients without cannabis use. Aims: The objective of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in at-risk mental state for psychosis (ARMS) and first episode psychosis (FEP) individuals. Methods: One hundred thirty-six participants completed a cognitive test battery and were assessed for current and past cannabis use. Analyses of covariance models were applied to evaluate the main effects of cannabis use and patient group (ARMS vs. FEP) as well as their interactions on cognitive functioning. Results: No differences were observed in cognitive performance between current, former, and never users, and there were no significant interactions between cannabis use and patient group. Furthermore, within the group of current cannabis users, the frequency of cannabis use was not significantly associated with cognitive functioning. Conclusion: The results of the present study do not support the notion that FEP patients and ARMS individuals with a history of cannabis use have less impaired cognitive functioning compared to those without cannabis us

Cannabis use and neurocognitive functioning in a non-clinical sample of users

OBJECTIVE: With the recent debates over marijuana legalization and increases in use, it is critical to examine its role in cognition. While many studies generally support the adverse acute effects of cannabis on neurocognition, the non-acute effects remain less clear. The current study used a cross-sectional design to examine relationships between recent and past cannabis use on neurocognitive functioning in a non-clinical adult sample. METHOD: One hundred and fifty-eight participants were recruited through fliers distributed around local college campuses and the community. All participants completed the Brief Drug Use History Form, the Structured Clinical Interview for DSM-IV Disorders, and neurocognitive assessment, and underwent urine toxicology screening. Participants consisted of recent users (n = 68), past users (n = 41), and non-users (n = 49). RESULTS: Recent users demonstrated significantly (p < .05) worse performance than non-users across cognitive domains of attention/working memory (M = 42.4, SD = 16.1 vs. M = 50.5, SD = 10.2), information processing speed (M = 44.3, SD = 7.3 vs. M = 52.1, SD = 11.0), and executive functioning (M = 43.6, SD = 13.4 vs. M = 48.6, SD = 7.2). There were no statistically significant differences between recent users and past users on neurocognitive performance. Frequency of cannabis use in the last 4 weeks was negatively associated with global neurocognitive performance and all individual cognitive domains. Similarly, amount of daily cannabis use was negatively associated with global neurocognitive performance and individual cognitive domains. CONCLUSIONS: Our results support the widespread adverse effects of cannabis use on neurocognitive functioning. Although some of these adverse effects appear to attenuate with abstinence, past users' neurocognitive functioning was consistently lower than non-users

High times: The effect of medical marijuana laws on student time use

Medical marijuana laws (MMLs) represent a major change of marijuana policy in the U.S. Previous research shows that these laws increase marijuana use among adults. In this paper, we estimate the effects of MMLs on secondary and post-secondary students’ time use using data from the American Time Use Survey. We apply a difference-in-differences research design and estimate flexible fixed effects models that condition on state fixed effects and state-specific time trends. We find no effect of MMLs on secondary students’ time use. However, we find that college students in MML states spend approximately 20% less time on education-related activities and 20% more time on leisure activities than their counterparts in non-MML states. These behavioral responses largely occur during weekends and summer when students have more spare time. Finally, the impacts of MMLs are heterogeneous and stronger among part-time college students, who are more likely to be first-generation college goers and to come from underrepresented racial and ethnic groups