Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions

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Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation.

ObjectiveProton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence.MethodsSingle-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions.ResultsCompared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits.ConclusionThe anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment

Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings

Background: The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods: Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results: One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. Limitations: However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Conclusion: Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives

Cannabis-Using Youth Demonstrated Blunted Rostral Anterior Cingulate Cortex Activation, but Normal Functional Connectivity, During an Emotional Go/No-Go Task

Cannabis use has been associated with deficits in self-regulation, including inhibitory control. Cannabis users have previously exhibited both structural and functional deficits in the rostral anterior cingulate cortex (rACC), a region involved in self-regulation of emotional response and inhibitory control. The present study aimed to examine whether abstinent cannabis users demonstrated abnormal functional activation and connectivity of the bilateral rACC during an emotional inhibitory processing task, and whether gender moderated these relationships. The study also aimed to examine whether bilateral rACC activation and connectivity in cannabis users was related to perceived stress. It was hypothesized that cannabis users would exhibit hypoactivation and hyperconnectivity of the rACC with the rest of the brain during emotional inhibitory processing. Further, it was predicted that female cannabis users would exhibit the most pronounced activation and connectivity abnormalities. It was also expected that abnormal functional activation and connectivity would be related to increased perceived stress. In the current study, cannabis users ages 16-25 underwent fMRI scanning while completing a Go/No-go task using fearful and calm emotional faces as non-targets. Participants were excluded for psychiatric disorders, major medical conditions, and excessive other drug use. Multiple linear regression and ANCOVA were used to determine (1) if cannabis group status was related to rACC activation and functional connectivity after controlling for alcohol and nicotine use and (2) whether gender moderated these relationships. Functional connectivity analysis included linear modeling consistent with psychophysiological interaction (PPI) analysis. Subsequently, Pearson correlations were conducted to investigate whether significant activation and functional connectivity were associated with perceived stress. Results showed blunted bilateral rACC activation in cannabis users during fearful response inhibition. Male, relative to female, cannabis users had greater right rACC connectivity with the right cerebellum during calm response inhibition (marginal finding; cannabis x gender interaction did not reach significance). Further, across the entire sample, males, relative to females, had enhanced right rACC and precuneus/posterior cingulate connectivity during calm response inhibition, which was related to gender differences in perceived stress. These results suggest that chronic cannabis use may disrupt typical rACC development, conferring risk for later development of mood disorders

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

Intrinsic Frontolimbic Connectivity and Associated Patterns on Reported Mood Symptoms in Young Adult Cannabis Users

Introduction: Recent legislation changes regarding cannabis in the United States highlights the importance of investigating the impact of regular cannabis use on populations, such as emerging adults, that will likely drive the market given their greater daily use (see Johnston et al., 2014). The endocannbinoid system plays a role in neurodevelopment (see Bossong & Niesink, 2010) and has been implicated in behavioral and emotional processing (see Moreira & Lutz, 2008; see Solinas et al., 2008; see Covey et al., 2014). The current study utilized a multisite functional magnetic resonance imaging (fMRI) dataset of intrinsic (a.k.a. no task/resting state) frontolimbic connectivity among healthy emerging adults. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Methods: Participants included consortium data totaling 79 cannabis users (average of 58 past month joints) and 80 controls (0 past month joints & no history of regular use) emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Exclusion criteria included history of medical/neurological illness or injury, independent DSM-IV-TR axis I disorders, and inability to maintain monitored abstinence. Structural and functional neuroimages were preprocessed and analyzed using CPAC software. Regions of interest included: anterior cingulate (rostral and caudal subdivisions), amygdala, insula, and ventral medial prefrontal cortex. Behavioral measurements included the Beck Depression Inventory-II, Beck Anxiety Scale, and the State Trait Anxiety Inventory-Y1. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Pearson r correlations were run to examine the relationship between group differences in connectivity and self-reported depression and anxiety total scores. Results: On self-reported measures, cannabis users reported significantly more total depression (p=.02) and anxiety (p=.04) symptoms. After controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: left amygdala (p=.03; corrected p=.47; ƒ2 = .17), left insula (p=.03; corrected p=.47; ƒ2 = .16), and right rACC (p=.001; corrected p=.05; ƒ2 =.55). Among cannabis users, greater bilateral rACC connectivity was associated with significantly greater total depressive scores (p=.02). Discussion: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls with no recent or regular cannabis use. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with higher levels of depression symptoms. Current findings suggest that regular cannabis use during neurodevelopmental periods may alter intrinsic brain characteristics involved in cognitive control and emotion regulation, and this finding should be considered when designing clinical interventions for this population. Future research may investigate the mechanisms underlying altered rACC connectivity, such as GABA and GLUT signaling, and the impact on mood in young cannabis users

Neuroimagen y adicción II: Correlatos neuroanatómicos y funcionales de la administración aguda, el craving y el consumo crónico de opiáceos, alcohol y cannabis

En las últimas décadas las técnicas de neuroimagen han contribuido en gran medida al estudio in vivo de los efectos neurobiológicos del consumo agudo y crónico de sustancias de abuso. El incremento en los últimos años del consumo de alcohol y cannabis, así como las graves consecuencias asociadas al consumo de opiáceos han contribuido al aumento del interés por estudiar los efectos de estas sustancias en el sistema nervioso central. Los objetivos de esta revisión son: (1) presentar los hallazgos más actualizados de neuroimagen en el estudio de los correlatos cerebrales del consumo de opiáceos, alcohol y cannabis, teniendo en cuenta: (i) la administración aguda de estas sustancias, (ii) el craving, y (iii) los efectos asociados al consumo crónico (2) discutir las implicaciones de estos hallazgos para una mejor comprensión de los procesos adictivos y su tratamiento. Los resultados sugieren que el consumo de estas tres drogas está asociado con alteraciones estructurales y funcionales en varias regiones del córtex frontal y el sistema límbico, con sutiles diferencias en la intensidad y extensión de estas alteraciones. A su vez, estas regiones muestran una mayor activación durante la inducción de estados de craving, y muestran alteraciones durante la neuroactivación mediante tareas cognitivas. Las alteraciones cerebrales observadas se han relacionado con síntomas clínicos, como la co-ocurrencia de trastornos psquiátricos, la intensidad del craving en condiciones naturales, o la probabilidad de recaídas. Por tanto, el uso de técnicas basadas en la modulación del funcionamiento cerebral puede contribuir a mejorar el tratamiento de estas adicciones

Neuroimaging in cannabis use: a systematic review of the literature

Background We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug. Method We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy. Results Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls. Conclusions Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reporte