title: Functional connectivity alterations in brain networks relevant to self-awareness in chronic cannabis users.
abstract: BACKGROUND
  Recreational drugs are generally used to intentionally alter conscious experience. Long-lasting cannabis users frequently seek this effect as a means to relieve negative affect states. As with conventional anxiolytic drugs, however, changes in subjective feelings may be associated with memory impairment. We have tested whether the use of cannabis, as a psychoactive compound, is associated with alterations in spontaneous activity in brain networks relevant to self-awareness, and whether such potential changes are related to perceived anxiety and memory performance.
  
  
  METHODS
  Functional connectivity was assessed in the Default and Insula networks during resting state using fMRI in 28 heavy cannabis users and 29 control subjects. Imaging assessments were conducted during cannabis use in the unintoxicated state and repeated after one month of controlled abstinence.
  
  
  RESULTS
  Cannabis users showed increased functional connectivity in the core of the Default and Insula networks and selective enhancement of functional anticorrelation between both. Reduced functional connectivity was observed in areas overlapping with other brain networks. Observed alterations were associated with behavioral measurements in a direction suggesting anxiety score reduction and interference with memory performance. Alterations were also related to the amount of cannabis used and partially persisted after one month of abstinence.
  
  
  CONCLUSIONS
  Chronic cannabis use was associated with significant effects on the tuning and coupling of brain networks relevant to self-awareness, which in turn are integrated into brain systems supporting the storage of personal experience and motivated behavior. The results suggest potential mechanisms for recreational drugs to interfere with higher-order network interactions generating conscious experience.
authors.affiliation: MRI Research Unit, CRC Mar, Hospital del Mar, Barcelona, Spain. Electronic address: jpujol@crccorp.es.
authors.forename: Jesus
authors.initials: J
authors.lastname: Pujol
authors.affiliation: MRI Research Unit, CRC Mar, Hospital del Mar, Barcelona, Spain; Human Pharmacology and Neurosciences, Institute of Neuropsychiatry and Addiction, Hospital del Mar Research Institute, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Blanco-Hinojo
authors.affiliation: Clinical Institute of Neuroscience, Hospital Clínic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Batalla
authors.affiliation: MRI Research Unit, CRC Mar, Hospital del Mar, Barcelona, Spain; Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: López-Solà
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Harrison
authors.affiliation: Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain; Carlos III Health Institute, Ministry of Science and Innovation, CIBERSAM, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Soriano-Mas
authors.affiliation: Department of Neuroscience and Behavior, RibeirãoPreto Medical School, University of São Paulo, Brazil; INCT Translational Medicine (CNPq), Brazil.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Human Pharmacology and Neurosciences, Institute of Neuropsychiatry and Addiction, Hospital del Mar Research Institute, Barcelona, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Fagundo
authors.affiliation: MRI Research Unit, CRC Mar, Hospital del Mar, Barcelona, Spain; Department of Clinical and Health Psychology, Autonomous University of Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Deus
authors.affiliation: Human Pharmacology and Neurosciences, Institute of Neuropsychiatry and Addiction, Hospital del Mar Research Institute, Barcelona, Spain; Red-Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.affiliation: Section of Clinical Toxicology, Emergency Service, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Nogué
authors.affiliation: Human Pharmacology and Neurosciences, Institute of Neuropsychiatry and Addiction, Hospital del Mar Research Institute, Barcelona, Spain; School of Medicine, Autonomous University of Barcelona, Red de Trastornos Adictivos (RETIC), Barcelona, Spain.
authors.forename: Magí
authors.initials: M
authors.lastname: Farré
authors.affiliation: Human Pharmacology and Neurosciences, Institute of Neuropsychiatry and Addiction, Hospital del Mar Research Institute, Barcelona, Spain; School of Medicine, Autonomous University of Barcelona, Red de Trastornos Adictivos (RETIC), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Torrens
authors.affiliation: Clinical Institute of Neuroscience, Hospital Clínic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain; INCT Translational Medicine (CNPq), Brazil.
authors.forename: Rocío
authors.initials: R
authors.lastname: Martín-Santos
mesh_terms: D001007:Anxiety / Q000209:etiology; D001364:Awareness / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D002189:Marijuana Abuse / Q000150:complications / Q000473:pathology / Q000523:psychology; D008569:Memory Disorders / Q000209:etiology; D009434:Neural Pathways / Q000098:blood supply* / Q000473:pathology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Anxiety; Cannabis; Memory; Resting state; Self-awareness; fMRI