Examining the impact of circulating endocannabinoid levels on neurocognition, mood, and early cannabis use in youth enrolled in the ABCD Study

检查循环内源性大麻素水平对参加 ABCD 研究的青少年的神经认知、情绪和早期大麻使用的影响

• 批准号: 9916212
• 负责人: Cecilia J Hillard
• 金额: $ 28.02万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9916212
• 关键词: 2-arachidonylglycerol; Address; Adolescence; Adolescent; Adolescent Development; Adult; Affective; Age; Age of Onset; Alcohol or Other Drugs use; Animals; Anxiety; Behavioral inhibition; Biological Assay; Blood; Brain; Brain region; CNR1 gene; CNR2 gene; Cannabis; Cognitive; Corpus striatum structure; Data; Development; Diagnosis; Emotional; Endocannabinoids; Enrollment; Female; Future; Geography; Health Campaign; Human; Knowledge; Ligands; Link; Measures; Mediating; Mental Depression; Mental Health; Moods; National Institute of Mental Health; Neurocognition; Neurocognitive; Neurons; Outcome; Parietal; Pattern; Peripheral; Play; Policies; Positron-Emission Tomography; Psychopathology; Research; Rewards; Risk; Role; Sampling; Scientist; Serum; Sex Differences; Short-Term Memory; Signal Transduction; Site; Statistical Data Interpretation; Stress; Structure; Symptoms; System; Techniques; Testing; Time; Youth; aged; anandamide; anxiety symptoms; biological adaptation to stress; brain abnormalities; cognitive development; cognitive function; data archive; depressive symptoms; early onset; endocannabinoid signaling; endogenous cannabinoid system; executive function; male; marijuana use; mood symptom; negative affect; neurodevelopment; neuron development; neurotransmission; pre-clinical; response; sex; white matter

PROJECT SUMMARY  The  endogenous  endocannabinoid  (eCB)  system  includes  cannabinoid  receptor  1  (CB1R),  CB2R,  and  two  endogenous  ligands  (N-­arachidonoylethanolamine;;  AEA  and  2-­arachidonoylglycerol,  2AG).  Animal  findings  demonstrate  that  the  eCB  system  undergoes  dynamic  changes  during  adolescence  and  suggest  a  significant  role  in  neurodevelopment,  especially  in  CB1R-­dense  prefrontal,  parietal,  striatal  and  limbic  brain  regions.  Research  in  adults  have  found  that  eCB  system  signaling  modulates  executive  functioning,  reward  response,  and  stress  and  affective  processing.  Thus,  there  is  strong  preclinical  evidence  that  the  eCB  system  plays  a  substantial  role  in  neuronal  activity  and  neurodevelopment  and  disruption  of  or  reduced  eCB  signaling  during  adolescence may result in abnormal neurocognitive development, risk for psychopathology, and increased risk  for  substance  use,  especially  cannabis  (CAN)  use.  Despite  this  evidence,  no  study  to  date  has  examined  the  role  of  the  eCB  system  on  neurocognition,  mood,  or  early  onset  cannabis  use  and  early  cannabis  subjective  effects  ex  vivo  in  human  youth  due  to  the  inherent  challenges  in  employing  invasive  techniques  [i.e.,  PET  studies  or  collecting  CSF].  However,  there  is  now  an  available  bioassay  to  measure  circulating  AEA  and  2AG  in  serum  collected  from  blood,  that  can  be  measured  ex  vivo  in  humans.  Serum  AEA  and  2AG  levels  reflect  both  peripheral  system  synthesis  and  overflow  from  the  brain and  animal  evidence  has  shown  that  circulating  and  brain  eCB  concentrations  are  robustly  and  significantly  correlated.  Further,  adult  studies  have  found  significant  associations  between  circulating  serum  eCBs  and  executive  functioning,  stress  response,  reward  signaling,  affective  processing,  mood  and  anxiety  symptoms  and  regular  CAN  use.  Notably,  studies  relating  serum eCB levels and neurocognitive, psychopathology, and CAN use outcomes have not yet been conducted  in  youth-­  despite  convincing  preclinical  evidence  that  the  impact  may  be  greater  during  these  critical  neurodevelopmental years. Thus, this R21 project will be the first to establish the link between circulating eCB  levels and neurocognitive, psychopathology, and early CAN use outcomes in a subset of 2000 youth aged 11-­ 14  who  are  already  enrolled  in  the  longitudinal  Adolescent  Brain  Cognitive  Development  (ABCD)  Study  (at  8  geographically-­diverse  research  sites).  We  will  also  examine  sex  differences  in  these  effects.  Ultimately,  this  project  will  inform  policy  and  health  campaigns  regarding  the  role  of  the  eCB  system  in  adolescent  development and provide mechanistic information regarding the long-­term impact of CAN exposure in youth.

项目总结