Emerging adults ages 18-22 show the highest rates of heavy marijuana (MJ) use. Heavy MJ use during this age range is associated with poorer social, academic, and occupational functioning. Importantly, this period is also characterized by continued brain maturation. Importantly, regions involved in long-term memory, such as prefrontal cortex and hippocampus, develop relatively late and also have high densities of cannabinoid receptors, the primary targets for the psychoactive components of MJ. Thus, given that these sensitive brain regions and corresponding cognitive processes are still developing during the typical age of peak MJ use, it is critical to investigate the impact of heavy MJ use on the structure and function of these regions. Recent work suggests that adolescent and emerging adult heavy MJ users demonstrate poorer memory performance, as well as abnormal functional magnetic resonance imaging (fMRI) brain response patterns on working memory and long-term memory tasks. However, these fMRI response patterns may be better understood when examined in conjunction with additional imaging methods. Notably, magnetic resonance spectroscopy (MRS) can measure specific neurochemicals that reflect cellular integrity and energetics, and could therefore provide critical insight into the neurochemical mechanisms of functional and cognitive abnormalities in MJ users. To this end, the proposed study will integrate MRS and fMRI to better understand the neurobiological correlates of altered memory processing in emerging adult MJ users. We will assess both fMRI and MRS in the same imaging session in order to characterize the function and neurochemistry of two brain regions known to be involved in memory and thought to be particularly impacted by heavy MJ use: dorsolateral prefrontal cortex (DLPFC) and hippocampus. fMRI data will be collected during the performance of a Figural Memory task, which ascertains brain response during the encoding and subsequent recognition of abstract visual stimuli, and typically activates DLPFC and hippocampus. Proton MRS data will be acquired in the right DLPFC and right hippocampus to measure brain metabolites in these regions. This concomitant measurement of neurochemicals and memory-related brain response will allow the direct investigation of the associations between neuronal integrity and function during the period of typical heaviest MJ use and continued brain maturation. The results of this study will have significant relevance to public health by identifyig cognitive and neurobiological correlates of heavy MJ use, which may better inform treatment and prevention efforts, as well as provide a model for studying the neurobiological outcomes of treatment programs. Overall, the proposed training and research plan will provide exceptional training and opportunities in the theory and implementation of multiple neuroimaging techniques, as well as pave the way towards an independent research career conducting future studies aimed at delineating the multifaceted neurocognitive implications of substance use.

Public Health Relevance

The proposed study aims to better characterize the multifaceted impact of heavy marijuana (MJ) use on memory by innovatively integrating functional magnetic resonance aiming (fMRI) and magnetic resonance spectroscopy (MRS). Heavy MJ use in this age range has been linked to poorer social, academic, and occupational functioning and this study may provide some insight into the neurobiological correlates of heavy MJ use. This work will establish a new paradigm that could provide a foundation for future studies examining the neurobiological impact of various treatment approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA038207-02
Application #
9110238
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Sirocco, Karen
Project Start
2015-07-15
Project End
2019-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
Dager, Alecia D; Tice, Madelynn R; Book, Gregory A et al. (2018) Relationship between fMRI response during a nonverbal memory task and marijuana use in college students. Drug Alcohol Depend 188:71-78
Silveri, Marisa M; Dager, Alecia D; Cohen-Gilbert, Julia E et al. (2016) Neurobiological signatures associated with alcohol and drug use in the human adolescent brain. Neurosci Biobehav Rev 70:244-259