Stimulant-dependent Individuals Research Articles

Childhood abuse and craving in methamphetamine-dependent individuals: the mediating role of alexithymia.

Individuals with a history of childhood abuse (CA,including neglect and abuse by caregivers before the age of 18years) have more severe substance dependence problems than those without a history of childhood abuse. However, whether a history of CA exacerbates craving and the mechanism of this effect remain largely unknown. The aim of this study was to explore the role of alexithymia in the effects of CA on craving in a large sample of methamphetamine-dependent individuals based on latent vulnerability theory. A total of 324 methamphetamine-dependent individuals who met DSM-5 criteria for substance use disorder were recruited. CA, alexithymia, and craving data were collected from the Childhood Trauma Questionnaire, the Toronto Alexithymia Scale-20, and the Obsessive Compulsive Drug Use Scale, respectively. t tests and ANCOVA were conducted to compare variables between the CA and non-CA groups, while partial correlation and mediation analyses were conducted to examine the potential mediating role of alexithymia in the relationship between CA and craving. Abused methamphetamine-dependent individuals reported higher levels of craving and higher levels of alexithymia than those of non-abused methamphetamine-dependent individuals. Alexithymia partially mediated the link between CA and craving, especially the effect of CA on craving frequency was fully mediated by alexithymia. Our findings reveal that a history of childhood abuse has a lasting effect on craving in stimulant-dependent individuals, and alexithymia contributes to some extent to the severity of substance abuse problems in abused methamphetamine-dependent individuals.

Time perception in stimulant-dependent participants undergoing repetitive transcranial magnetic stimulation

BackgroundThe dopaminergic (DA) system is an important neural system for the modulation of time perception and the timing of motor actions. Dysregulation of the DA system is related to chronic use of stimulant drugs, which lead, among others, to executive dysfunctions. Little is known instead about the potential deficiencies in temporal processing of stimulant-dependent individuals. The present study aimed to investigate temporal processing using a time bisection task with different temporal intervals in chronic cocaine users undergoing repetitive transcranial magnetic stimulation (rTMS). MethodStudy 1: A time bisection task with short temporal intervals range (480/1920 ms) was administered to 18 cocaine use disorder (CocUD) patients and 20 healthy control before and after the intensive phase of rTMS treatment (5 days apart). Study 2: 22 CocUD participants and 23 control participants completed two temporal tasks (time bisection and time reproduction) with long temporal intervals range (1200/2640 ms) at baseline and immediately after the intensive phase of rTMS treatment. ResultsStudy 1: A shift in the psychometric function consistent with temporal overestimation in CocUD patients compared to controls was observed. However, no temporal impairment in CocUD patients at test session was found. Study 2: The analysis of temporal variability indices showed a significant difference between groups at baseline but not at Day 5 due to a significant difference between time points only in the CocUD group. ConclusionsThis study report a temporal overestimation in CocUD patients and a temporal variability reduction after an rTMS protocol in CocUD patients.

Prevalence of obesity among U.S. population with substance dependence

AimTo investigate associations between substance dependence and obesity. MethodsObesity (body mass index ≥ 30 kg/m2) status and the status of dependence on heroin, stimulant, marijuana, nicotine and alcohol (past-month status for nicotine and past-year status for all others) were identified from the U.S. National Survey on Drug Use and Health (NSDUH, 2015–2017) datasets. SAS Surveylogistic regression was used to estimate adjusted odds ratio (AOR) for the association between each substance dependence and obesity, adjusting for potentially confounding effects of sociodemographic factors and health condition. ResultsIt was estimated that 10.6 % of noninstitutional U.S. residents aged 12 years or older were nicotine-dependent, 3.0 % alcohol-dependent, 1.0 % marijuana-dependent, 0.6 % stimulant-dependent, and 0.2 % heroin-dependent. Heroin-dependent individuals had 59 % lower odds of obesity relative to their non-dependent counterparts (AOR = 0.41; 95 % CI: 0.28−0.60; p < 0.0001). Lower odds of obesity were also noted for marijuana-dependent (AOR = 0.64; 95 % CI: 0.56−0.73; p < 0.0001), nicotine-dependent (AOR = 0.68; 95 % CI: 0.64−0.72; p < 0.0001) and alcohol-dependent (AOR = 0.77, 95 % CI: 0.69−0.84; p < 0.0001) individuals, but not statistically significant for stimulant-dependent individuals (AOR = 0.84; 95 % CI: 0.68−1.02; p = 0.0825). ConclusionsHeroin, marijuana, nicotine and alcohol dependence were associated with lower odds of obesity than their non-dependence counterparts. Main findings based on 2015–2017 NSDUH are consistent with findings from our prior report based on clinical trials data from National Institute on Drug Abuse Clinical Trials Network, and other epidemiological evidence in the literature. These findings can alert substance abuse treatment professionals to monitor weight change, especially among weight-concerned substance abusers.

Network failures: When incentives trigger impulsive responses.

Adequate control of impulsive urges to act is demanded in everyday life but is impaired in neuropsychiatric conditions such as stimulant use disorder. Despite intensive research it remains unclear whether failures in impulse control are caused by impaired suppression of behavior or by the over invigoration of behavior by stimuli associated with salient incentives such as drugs, food, and money. We investigated failures in impulse control using functional magnetic resonance imaging (fMRI) to map the neural correlates of premature (impulsive) responses during the anticipation phase of the Monetary Incentive Delay (MID) task in healthy controls (HC), stimulant‐dependent individuals (SDIs), and their unaffected first‐degree siblings (SIB). We combined task‐based fMRI analyses with dynamic causal modeling to show that failures of impulse control were associated with interactions between cingulo‐opercular and dorsal striatal networks regardless of group status and incentive type. We further report that group‐specific incentive salience plays a critical role in modulating impulsivity in SDIs since drug‐related incentives specifically increased premature responding and shifted task modulation away from the dorsal striatal network to the cingulo‐opercular network. Our findings thus indicate that impulsive actions are elicited by salient personally‐relevant incentive stimuli and those such slips of action recruit a distinct fronto‐striatal network.

F272. Psychiatric and Impulsivity Dimensions as Common and Specific Candidate Endophenotypes for Heroin and Amphetamine Dependence

Research reveals distinct psychiatric profiles and substance-specific manifestations of impulsivity among opiate and stimulant dependent individuals. However, findings have been inconclusive, due in part to the high rates of polysubstance dependence, which limit investigations of the common vs. specific effects of different drug classes. The aim of the present study is to examine sibling correlations on psychiatric symptoms and dimensions of impulsivity among individuals with ‘pure’ heroin and amphetamine dependence in Bulgaria, in order to explore their utility as common vs. specific endophenotypes for opiate and stimulant dependence.

Psychometrics of the Self-Report Concise Associated Symptoms Tracking Scale (CAST-SR): Results From the STRIDE (CTN-0037) Study.

The self-report Concise Associated Symptoms Tracking Scale (CAST-SR) was developed to track mania, irritability, anxiety, panic, and insomnia symptoms among depressed outpatients receiving antidepressant medication. Given the overlap between these domains, depression, and stimulant use disorders, we reexamined CAST-SR psychometrics in a novel sample: individuals with stimulant use disorder receiving aerobic exercise or health education interventions. Using the subsample of stimulant-dependent (following DSM-IV criteria) individuals prescribed antidepressants (N = 124) from the multisite Stimulant Reduction Intervention Using Dosed Exercise (CTN-0037) trial (total sample N = 302), conducted July 2010 to February 2013, we analyzed CAST-SR data collected at the first assessment after participant's discharge from residential treatment. We also evaluated the convergent/discriminant validity of the CAST-SR with several self-report questionnaires. Confirmatory factor analysis revealed a 12-item measure composed of 4 factors: irritability, anxiety, panic, and insomnia. This factor structure loaded only in participants prescribed antidepressant medication, not in those who were not prescribed antidepressants. These results replicate the original CAST-SR factor structure, except for the mania factor, which failed to load. Internal consistency was high (α = 0.92 for total scale and α = 0.78-0.89 for the 4 factors), and convergent validity was established, especially for the insomnia and irritability factors, alongside the total score with depressive symptoms, insomnia, quality of life, suicide risk, and physical health measures. These results demonstrate the factor structure, reliability, and validity of the CAST-SR in a novel population of only individuals with stimulant use disorders receiving both exercise/health education interventions and antidepressant medication. ClinicalTrials.gov identifier: NCT01141608.

DACC response to presentation of negative feedback predicts stimulant dependence diagnosis and stimulant use severity.

Error-monitoring abnormalities in stimulant-dependent individuals (SDIs) may be due to reduced awareness of committed errors, or to reduced sensitivity upon such awareness. The distinction between these alternatives remains largely undifferentiated, but may have substantial clinical relevance. We sought to better characterize the nature, and clinical relevance, of SDIs' error-monitoring processes by comparing carefully isolated neural responses during the presentation of negative feedback to a) stimulant dependence status and b) lifetime stimulant use. Forty-eight SDIs and twenty-three non-SDIs performed an fMRI-based time-estimation task specifically designed to isolate neural responses associated with the presentation (versus expectation) of contingent negative feedback. SDIs showed reduced dACC response compared to non-SDIs following the presentation of negative feedback, but only when error expectancies were controlled. Moreover, lifetime stimulant use correlated negatively with magnitude of expectancy-controlled dACC attenuation. While this finding was minimized after controlling for age, these results suggest that SDIs may be characterized by a core reduction in neural activity following error feedback, in the context of intact feedback expectancies. Correlations with lifetime stimulant use suggest that this neural attenuation may hold clinical significance.

The comparison of impulsivity and craving in stimulant-dependent, opiate-dependent and normal individuals

ABSTRACTThe aim of this study was to compare the severity of impulsivity and craving among stimulant-dependent (e.g. methamphetamine and crack) and opiate-dependent (e.g. opium and heroin) patients as well as normal subjects. Forty stimulant-dependent patients, 40 opiate-dependent patients, and 40 normal controls completed the Barratt impulsiveness scale-II (BIS-II) and the craving beliefs questionnaire (CBQ). The results showed that there were significant differences concerning the impulsivity and craving among the three groups. Stimulant-dependent and opiate-dependent patients had more impulsivity and craving than normal controls. Stimulant-dependent patients exceeded opiate-dependent ones on total impulsivity and its subscales except for cognitive impulsivity as well as craving. These findings indicated that increased impulsivity and craving in substance-dependent patients compared with normal community suggest the role of cognitive impairments in substance dependency. Also, impulsivity and craving may be more vulnerable factors to depend on stimulant than opiate substances.

P.6.d.009 - Altered grey matter co-variance in stimulant-dependent individuals: a graph-theory analysis

P.6.d.009 - Altered grey matter co-variance in stimulant-dependent individuals: a graph-theory analysis

Time perception deficits in impulsivity disorders: A systematic review

Abstract This systematic review aims to identify evidences of distortions in time perception (TP) in people with impulsivity disorders or other conditions having impulsivity traits, namely traumatic brain injuries, certain personality disorders, addictive behavior disorders, and pathological gambling. Studies related to TP deficits and impulsivity disorders were retrieved from multiple literature databases, through predefined inclusion and exclusion criteria. From the 197 obtained documents, 47 were selected for analysis, and a final set of 15 studies was retrieved for this review. Regardless of some conflicting findings, the available results suggest that patients with orbitofrontal lesions produce and reproduce significantly less time and estimate time periods significantly longer than healthy subjects. Patients with borderline personality disorder show decreased time perception and patients with antisocial personality disorder seem to execute more premature responses during time estimation tasks. Stimulant dependent individuals also tend to overestimate the time intervals, and pathological gamblers demonstrate shorter time horizons than social gamblers. Taken together, the available data suggest that impulsive individuals tend to overestimate the passage of time and to execute more premature responses, producing and reproducing less time, but more research is necessary to increase the strength of the evidences on this issue. This systematic review updates evidences of distortions in TP in impulsivity, improving the understanding of the relations between these two variables.

Disrupted homeostasis during chronic ethanol consumption associated with specific mechanism of endogenous neurosteroids activity

IntroductionNeurobiological research describes one of mechanisms overlap in the Cortico-Striatal-Limbic Circuit (CSLC), which can be disrupted due to chronic stress and alcohol abuse that primarily modulated by the hypothalamic-pituitary-adrenal (HPA) axis, from which cortisol is an end-product.ObjectivesTo investigate the effects of chronic stimulant abuse on the CSLC. This was examined by relating cortisol levels with grey matter volume in brain structures associated with addiction and stress.AimsWe hypothesized that stimulant-dependent individuals show increased cortisol levels and abnormalities in the CSLC. We further hypothesized relationships between altered grey matter volume and increased cortisol levels in the patients.MethodsTwenty-two alcohol-dependent individuals, men only and 21 healthy volunteers (matched for age and gender) underwent an assessment session. Cortisol, DHEA and DHEA-S was assessed in blood plasma. Mood, impulsivity and compulsivity were measured by clinical instruments.ResultsAlcohol-dependent individuals showed higher levels of cortisol in blood plasma, and decreased levels of progesterone and its metabolites DHEA and DHEA-S, which were associated with distinct expression in impulsivity and compulsivity in alcoholic patients. Indices of these steroids were changed compared with healthy persons. Plasma cortisol was positively correlated with the duration of alcohol use. The relationships observed between cortisol, progesterone and its metabolites: DHEA and DHEA-S may be explained by abnormal functioning of HPA axis.ConclusionsOptimizing of disrupted homeostasis during chronic ethanol consumption being provided with specific mechanism by manipulation of endogenous neurosteroids activity may prove a beneficial pharmacotherapeutic strategy in the intervention of alcohol abuse.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Hyperactivation to pleasant interoceptive stimuli characterizes the transition to stimulant addiction

AimsAltered interoception, how the brain processes afferents from the body, may contribute to the urge to take drugs, and subsequently, the development of addiction. Although chronic stimulant dependent individuals exhibit attenuated brain responses to pleasant interoceptive stimuli, it is unclear whether this deficit exists early-on in the process of transition to stimulant addiction. MethodsTo this end, we compared problem stimulant users (PSU; n=18), desisted stimulant users (DSU; n=15), and stimulant naïve comparison subjects (CTL; n=15) during functional magnetic resonance imaging (fMRI) while they anticipated and experienced pleasant soft touch (slow brushstroke to the palm and forearm). ResultsGroups did not differ in behavioral performance or visual analog scale ratings of soft touch stimuli. fMRI results indicated that PSU exhibited greater right anterior insula, left inferior frontal gyrus, and right superior frontal gyrus activation than DSU and CTL during the anticipation and experience of soft touch. Moreover, during the experience of soft touch, PSU demonstrated higher bilateral precentral gyrus/middle insula and right posterior temporal gyrus activation than DSU and CTL. ConclusionsIn contrast to chronic stimulant dependence, individuals who have recently developed stimulant use disorders show exaggerated neural processing of pleasant interoceptive stimuli. Thus, increased processing of body-relevant information signaling pleasant touch in those individuals who develop problem use may be a predictive interoceptive biomarker. However, future investigations will need to determine whether the combination of probing pleasant interoception using neuroimaging is sufficiently sensitive and specific to help identify individuals at high risk for future problem use.

Attenuated insular and frontocingulate decision-making related activation during an aversive interoceptive state in methamphetamine-dependent individuals

s / Drug and Alcohol Dependence 146 (2015) e34–e117 e109 Attenuated insular and frontocingulate decision-making related activation during an aversive interoceptive state in methamphetamine-dependent individuals Jennifer L. Stewart1, April C. May1, Natasha Poppa1, Paul W. Davenport2, Susan F. Tapert3,1, Martin P. Paulus3,1 1 Psychiatry, University of California, San Diego, La Jolla, CA, United States 2 Physiological Sciences, University of Florida, Gainesville, FL, United States 3 Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, United States Aims: Stimulant dependent individuals oftenmake drug-taking decisions when they do not feel well. Yet few studies have examined the influence of an aversive state on decision-making relatedneuralprocessing.We investigatebrainactivation toactionoutcome contingencies during an aversive interoceptive challenge in methamphetamine users using functional magnetic resonance imaging (fMRI). Methods: Abstinent methamphetamine dependent inpatients (MD; n=20) and healthy comparison subjects (CTL; n=22) performed a two-choice prediction task at three fixed error rates (20%= reward, 50%=uncertainty, 80%=punishment) while anticipating and experiencing episodes of inspiratory breathing load during fMRI. Participants rated breathing load unpleasantness/intensity using visual analog scales (VAS). Results: MD exhibited lower anterior insula (AI) and inferior frontal gyrus (IFG) activation thanCTLacross trials.MDalso showed lower posterior insula (PI) and anterior cingulate cortex (ACC) activation than CTL during breathing load independent of error rate. For the crucial error rate by interoception interaction, MD displayed lower dorsal ACC activation to punishment than CTL during breathing load. Within MD, higher VAS unpleasantness was linked to lowerdorsalACCactivation topunishmentduring loadedbreathing. Conclusions: AI/IFG attenuations in MD are suggestive of a global decision making deficit, reflecting reduced resources allocated to the processing of action-outcome contingencies. In contrast, PI/ACC reductions in MD appear specific to impairments in registering and evaluating interoceptive experiences. Taken together, inadequate activationof brain areas that are important for regulatinghowone feels during anaversive interoceptive statemay be the neural basis for poor decision-making by MD individuals. Financial support: NIDA 5P20DA027843-04. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.663 Evidence of gender-specific telescoping effects in chronic, regular heroin users Jonathan J. Stoltman, Eric A. Woodcock, Leslie Lundahl, Mark K. Greenwald Psychiatry, Wayne State University, Detroit, MI,

Commentary on Konsteniuset al. (2014): On medication development for stimulant addiction

The effort to identify a medication, any medication, to treat the broad group of individuals who become dependent on stimulants (methamphetamine, amphetamine) is one of the most significant tasks facing addiction research. This situation may make it tempting to over-interpret the generally positive findings in the Konstenius et al. report in this issue 1. Indeed, the results from the trial are impressive. Participants assigned to high-dose extended release methylphenidate condition were significantly more likely than participants assigned to placebo to reduce attention deficit hyperactive disorder (ADHD) symptoms and to provide scheduled urine samples that were negative both for amphetamine and for other drug metabolites. Time to relapse was longer for those in the active medication condition, as was retention in treatment. The size of the effects of the differences between the medication and placebo groups for both ADHD and drug use outcomes were apparent, even without checking the P-values. The authors are to be congratulated for this achievement. Nevertheless, it is the rarity of this positive report that underscores its importance. If the medication evaluated were anything other than a stimulant, these findings would energize replication trials and in broad groups of stimulant-dependent individuals not comorbid with ADHD; but that is not the case. A probably lackluster response among funders and scientists will highlight that the significant effort to develop medications for stimulant addiction is driven as much by politics as by data. None.

Enhanced Orbitofrontal Cortex Function and Lack of Attentional Bias to Cocaine Cues in Recreational Stimulant Users

Although cocaine is known to be a highly addictive drug, there appears to be a select subset of individuals who are able to use the substance recreationally without developing dependence. These individuals do not report experiencing feelings of craving for cocaine, an important distinction from dependent users. However, no prior studies have compared attentional bias with cocaine cues between these groups to confirm this difference. Additionally, previous investigations into cognitive abilities in these individuals have been conflicting, and no research has been conducted on the neurobiological processes underlying cognitive functioning in this group. This study administered the emotional cocaine-word Stroop to 27 recreational cocaine users, 50 stimulant-dependent individuals, and 52 healthy control participants during functional magnetic resonance imaging scanning. Behavioral and functional imaging results were compared between groups to assess attentional bias and cognitive effort to resist salient cocaine stimuli. Recreational users did not exhibit attentional bias to the cocaine words and did not differ from control subjects on task performance. Conversely, stimulant-dependent individuals were significantly more impaired on the task. Recreational participants also displayed a unique pattern of activation during performance, with significant underactivation in the orbitofrontal and anterior cingulate cortices compared with both dependent users and control subjects. The absence of bias to cocaine-related stimuli in recreational users indicates they do not share attentional preference for these words with dependent users. Their distinct pattern of activation suggests a decreased need for cognitive control due to diminished desire for the drug, potentially serving as a resilience factor against dependence.

Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

Prefrontal hypoactivity associated with impaired inhibition in stimulant-dependent individuals but evidence for hyperactivation in their unaffected siblings.

A neurocognitive endophenotype has been proposed for stimulant dependence, based on behavioral measures of inhibitory response control associated with white matter changes in the frontal cortex. This study investigated the functional neuroimaging correlates of inhibitory response control, as functional activity serves as a more dynamic measure than brain structure, allowing refinement of the suggested endophenotype. Stimulant-dependent individuals (SDIs), their unaffected siblings (SIBs), and healthy controls (CTs) performed the stop-signal task, including stop-signal reaction time (SSRT) as a measure of response inhibition, while undergoing functional magnetic resonance imaging. SDIs had impaired response inhibition accompanied by hypoactivation in the ventrolateral prefrontal cortex (PFC). In addition, they demonstrated hypoactivation in the anterior cingulate when failing to stop. In contrast, no hypoactivations were noted in their unaffected SIBs. Rather, they exhibited increased activation in the dorsomedial PFC relative to controls, together with inhibitory performance that was intermediate between that of the stimulant group and the healthy CT group. Such hyperactivations within the neurocircuitry underlying response inhibition and control are suggestive of compensatory mechanisms that could be protective in nature or could reflect coping with a pre-existing vulnerability, thus expressing potential aspects of resilience. The functional activation associated with response inhibition and error monitoring showed differential patterns of results between SDIs and their unaffected first-degree relatives, suggesting that the proposed endophenotype does not generalize to functional brain activity.

Repurposed Medications Show Promise in Stimulant Dependence

Back to table of contents Previous article Next article From the ExpertsFull AccessRepurposed Medications Show Promise in Stimulant DependencePublished Online:4 Jan 2013https://doi.org/10.1176/appi.pn.2013.1a12Stimulant dependence is a substance use disorder (SUD) that continues to affect society on many levels. The economic temptation of producing or bringing stimulants or their precursors (methamphetamine and cocaine) across the U.S. border to sell is continuing as certain South American countries now allow full-fledged coca plant cultivation. Containing the flow of illicit drugs within state lines and across U.S. borders is an insurmountable task for any agency, and demand reduction from effective treatments is desperately needed.Stimulant dependence is a substance use disorder (SUD) that continues to affect society on many levels. The economic temptation of producing or bringing stimulants or their precursors (methamphetamine and cocaine) across the U.S. border to sell is continuing as certain South American countries now allow full-fledged coca plant cultivation. Containing the flow of illicit drugs within state lines and across U.S. borders is an insurmountable task for any agency, and demand reduction from effective treatments is desperately needed.Research for these addiction treatments has benefited greatly from neuroimaging studies and “repurposed” medications. Neuroimaging studies have been essential to understanding central deficits and altered neurotransmission linked to stimulant dependence. For example, recent evidence dispels the widely held misconception that stimulant-dependent individuals are more sensitive to these drugs than the average person, and this is why they become dependent. In fact, the opposite is true. They are less sensitive to the positive euphoric effects of stimulants. This also extends to natural rewards such as food. In contrast, these same individuals are often hypersensitive to stress and overly influenced by environmental cues associated with drug taking that can trigger relapse. Environmental cues that control behavior are influenced by usurped memory circuits. SUDs are often accompanied by comorbid negative mood states that may also contribute to continued drug use through self-medication. Neuroimaging has revealed that abnormally low dopaminergic neurotransmission is paired with orbitofrontal hypoactivation in stimulant dependence and limits impulse control, executive functioning, and working memory. Medications that modulate dopamine, glutamate, and norepinephrine (NE) neurotransmission that show promise for impulse control and enhance cognition may also be used to treat stimulant dependence. Doxazosin is a repurposed NE blocker used for hypertension that Newton et al. (2012) recently found blocks cocaine’s positive subjective effects and the feeling “likely to use cocaine” in cocaine-dependent volunteers after a cocaine infusion. An outpatient clinical trial is presently examining this medication for decreasing cocaine use. Another repurposed medication, the angiotensin-converting enzyme inhibitor and antihypertensive perindopril blocks the cardiovascular and positive subjective effects of methamphetamine. The commonly prescribed antidepressant bupropion has also shown some efficacy in decreasing methamphetamine use in moderate users. Rivastigmine, used in the treatment of dementia, significantly decreased “likely to use methamphetamine” in dependent volunteers. Finally, the atypical stimulant modafinil, used to treat narcolepsy, blocks cocaine’s positive subjective effects and has decreased cocaine use in a select subpopulation.Psychiatric addiction research has benefited from repurposing a wide range of medications. The science behind using these medications is based on understanding from neuroimaging of damaged and reinforcing human neural circuits due to addictive stimulants. For the most part, the development of effective treatments for this pernicious disorder appears promising. ■References are posted at http://www.psychnews.org/update/experts_2_32.html.Thomas Kosten, M.D., is the J.H. Waggoner Professor of Psychiatry, Pharmacology and Neuroscience, vice chair for psychiatry, and codirector of the Institute for Clinical and Translational Research at Baylor College of Medicine. Colin Haile, M.D., Ph.D., is an assistant professor at Baylor College of Medicine, Menninger Department of Psychiatry and Michael E. DeBakey VA Medical Center. He and Kosten are the coauthors of "Cocaine and Methamphetamine Dependence: Advances in Treatment" from American Psychiatric Publishing. APA members may purchase the book at a discount at http://www.appi.org/SearchCenter/Pages/SearchDetail.aspx?ItemId=62407. ISSUES NewArchived

1897 – Overlapping orbitofrontal volume loss involved in stimulant dependence and weight gain

Introduction Stimulant dependence is commonly associated with decreases in cortical volume in inhibitory control regions, such as the orbitofrontal cortex (OFC). Obese individuals similarly show abnormalities in frontal gray matter, with volume reductions correlating with BMI. These structural deficits may contribute to underlying problems with impulsivity or self-control present in both groups. Objectives Shared structural abnormalities relating to over-consumption of food or drugs of abuse could shed light on similar neurocognitive impairments associated with these behaviors (loss of control, poor decision-making), and could provide evidence for the classification of over-eating as an addictive disorder. Aims To identify overlapping regions of gray matter volume loss associated with both stimulant dependence and increased BMI, specifically in the OFC. Methods Structural MRI scans of stimulant dependent and healthy control individuals were compared using voxel based morphometry analysis. OFC volume was correlated with BMI in all participants, as well as years of drug use in stimulant dependent individuals. Results Both stimulant use and BMI negatively correlated with bilateral OFC gray matter volume. Additionally, select OFC regions showed decreases relating to both variables, indicating an overlap between volume loss associated with years of use and BMI in both stimulant dependent and control individuals. Conclusions Overlapping decreases in OFC gray matter volume that correspond to both overeating and drug use severity indicate underlying commonalities between these two behaviors. This suggests there may be shared cognitive deficits maintained in the OFC, such as poor inhibitory control or decision-making abilities, that preclude these types of behaviors.

1623 – Brain abnormalities associated with stimulant dependence - does gender matter?

According to the United Nations, women are less likely to use illicit drugs compared with men. This gender gap is poorly understood, possibly because female drug users are underrepresented in research studies and treatment. We test the hypothesis of gender differences in neural mechanisms mediating addiction. We aimed to explore gender differences in terms of trait-impulsivity, cognitive function, and brain structure in stimulantdependent individuals. We re-analysed exiting neuroimaging and behavioural data on stimulant-dependent individuals ( n =37; 17 females) and healthy controls ( n =40; 20 females), all matched for demographic variables. Male and female substance users were additionally matched for the type, duration and severity of stimulant use. Behavioural measures included substance use variables, impulsivity and depression scores, and measures of visual sustained attention. ANOVAs using planned contrasts, t tests and Chi-square tests were employed to examine group and gender differences. Consistent with previous studies, stimulant-dependent individuals showed significant, widespread reduction in grey matter volume. Gender differences were observed within both stimulant-dependent individuals and healthy controls in the left parahippocampal gyrus: males showed grey matter reduction in this region relative to females. Stimulant-dependent individuals exhibited higher levels of impulsivity compared with healthy controls, but no gender differences were observed here. Aside from response time on the sustained attention task, there were no further group differences in any of the behavioural measures. We found evidence for gender differences in brain structure between stimulant-dependent individuals and healthy controls, which can be statistically controlled for by matching for gender.