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Neural mechanisms mediating appetitive regulation and smoking in nicotine addiction

University of Utah Principal Investigator (PI) / Project Lead:


Prime/Overall Principal Investigator (PI) / Project Lead:

Froeliger, Brett, PhD, at University of Missouri-Columbia

Funding Organization:

National Institutes of Health, National Institute on Drug Abuse

RFP / FOA Number:


Award Number:


Funding Period:

6/1/2019 – 3/31/2024

Total Funding:


Project Status:



Project Description:

Nicotine addiction is a chronic, relapsing brain disorder and although it is the leading cause of preventable premature death in the US, ~20% of adults smoke and among those that try to quit, the majority relapse. Preclinical and Human models suggest that nicotine addiction disrupts neural function in a corticostriatal network involved in motivation and reward. The overarching goal of this proposal is to utilize clinical neuroscience to investigate the effects of Mindfulness Oriented Recovery Enhancement (MORE) on corticostriatal circuitry function, regulation of appetitive processes and determine the value of this cognitive training for treating nicotine addiction.



Nicotine addiction is a manifold process involving dysregulated brain circuitry subserving reward and motivation (i.e. corticostriatal). Despite extant cross-species models in the literature, there is a gap in the human literature concerning the role of corticostriatal pathways that regulate appetitive processes, whether cognitive training may restructure circuitry function, and whether neuroplasticity in self-regulatory mechanisms alter appetitive behaviors, in particular cigarette smoking. Preliminary data from our laboratory provide initial support for our published model positing that cognitive control training via Mindfulness Oriented Recovery Enhancement (MORE), to enhance valuation of non-drug related reward relative to drug reward may remediate maladaptive appetitive behaviors, craving, and affective deficits by restructuring reward processing. The goal of this proposal is to examine the effects of MORE on corticostriatal mediated regulation of appetitive responding and smoking. Smokers (N=100) will be randomized to 4-weeks of MORE or CBT, undergo fMRI pre/post training, complete a laboratory-based smoking relapse analog task, and be followed for 2-weeks to assess relations between neural function, lab behavior and real-world smoking.



  1. Upton S, Brown AA, Ithman M, Newman-Norlund R, Sahlem G, Prisciandaro JJ, McClure EA, Froeliger B. Effects of Hyperdirect Pathway Theta-Burst Transcranial Magnetic Stimulation on Inhibitory Control, Craving, and Smoking in Adults with Nicotine Dependence: A Double-Blind Randomized Crossover Trial. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Aug 9:S2451-9022(23)00196-9. doi: 10.1016/j.bpsc.2023.07.014. Epub ahead of print. PMID: 37567363.
  2. Brown AA, Upton S, Craig S, Froeliger B. Associations between right inferior frontal gyrus morphometry and inhibitory control in individuals with nicotine dependence. Drug Alcohol Depend. 2023 Mar 1;244:109766. doi: 10.1016/j.drugalcdep.2023.109766. Epub 2023 Jan 8. PMID: 36640686; PMCID: PMC9974751.
  3. Redwine LS, Schwartz ER, Garland EL. Mindfulness Promotes Positive Health Behaviors by Enhancing Self-Regulation, Motivation, and Learning: Perspectives from Research and Clinical Care. J Integr Complement Med. 2022 Nov;28(11):847-850. doi: 10.1089/jicm.2022.0761. Epub 2022 Nov 4. PMID: 36342808; PMCID: PMC9839340.
  4. Hudak J, Bernat EM, Fix ST, Prince KC, Froeliger B, Garland EL. Neurophysiological Deficits During Reappraisal of Negative Emotional Stimuli in Opioid Misuse. Biol Psychiatry. 2022 Jun 15;91(12):1070-1078. doi: 10.1016/j.biopsych.2022.01.019. Epub 2022 Feb 7. PMID: 35393080; PMCID: PMC9167218.
  5. Parisi A, Landicho HL, Hudak J, Leknes S, Froeliger B, Garland EL. Emotional distress and pain catastrophizing predict cue-elicited opioid craving among chronic pain patients on long-term opioid therapy. Drug Alcohol Depend. 2022 Apr 1;233:109361. doi: 10.1016/j.drugalcdep.2022.109361. Epub 2022 Feb 24. PMID: 35278786; PMCID: PMC9466292.
  6. Parikh A, Moeller SJ, Garland EL. Simulated opioid choice linked to opioid use disorder severity among veterans with chronic pain: initial validation of a novel paradigm. Am J Drug Alcohol Abuse. 2022 Jul 4;48(4):403-412. doi: 10.1080/00952990.2021.2007258. Epub 2022 Jan 31. PMID: 35100056; PMCID: PMC9339010.
  7. Garland EL. Mindful Positive Emotion Regulation as a Treatment for Addiction: From Hedonic Pleasure to Self-Transcendent Meaning. Curr Opin Behav Sci. 2021 Jun;39:168-177. doi: 10.1016/j.cobeha.2021.03.019. Epub 2021 Apr 24. PMID: 34084873; PMCID: PMC8168946.
  8. Fisher ML, Pauly JR, Froeliger B, Turner JR. Translational Research in Nicotine Addiction. Cold Spring Harb Perspect Med. 2020 Jun 8:a039776. doi: 10.1101/cshperspect.a039776.  PMID: 32513669; PMCID: PMC8168530.

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Last Updated: 4/25/24