The Impact of Methadone Maintenance Therapy on Food Reward Processing in Opioid Dependence

The Impact of Methadone Maintenance Therapy on Food Intake and Food Reward Processing in Opioid Dependence: An Event-related Brain Potential Study

Mid-Atlantic Nutrition Obesity Research Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Methadone maintenance therapy (MMT) has shown clear efficacy for relieving opioid withdrawal symptoms and reducing the morbidity and mortality of opioid dependence. A notable phenomenon associated with MMT is increased food intake, enhanced sweet preferences, and weight gain. The underlying neural mechanisms for opioid-related overconsumption are not well understood but are thought to arise from role in 1) increasing the palatability and hedonic aspects of food and 2) diminishing satiety signaling systems. In the proposed project, the investigators will examine methadone's potential role in opioid-related overconsumption of food. The investigators propose to examine eating behavior, sucrose preferences, and an event-related potential (ERP) component that is induced by appetitive motivation for highly rewarding foods in patients with a history of opioid dependence receiving methadone maintenance therapy (O+MMT) and not receiving opioid agonist therapy (O-MMT). A matched sample of obese and overweight adults without history of opioid use (HOC) will also be examined.

Methadone maintenance therapy (MMT) has shown clear efficacy for relieving opioid withdrawal symptoms and reducing the morbidity and mortality of opioid dependence. A notable phenomenon associated with MMT is increased food intake, enhanced sweet preferences, and weight gain. The underlying neural mechanisms for opioid-related overconsumption are not well understood but are thought to arise from role in 1) increasing the palatability and hedonic aspects of food and 2) diminishing satiety signaling systems. In the proposed project, the investigators will examine methadone's potential role in opioid-related overconsumption of food. The investigators propose to examine eating behavior, sucrose preferences, and an event-related potential (ERP) component that is induced by appetitive motivation for highly rewarding foods in patients with a history of opioid dependence receiving methadone maintenance therapy (O+MMT) and not receiving opioid agonist therapy (O-MMT). A matched sample of obese and overweight adults without history of opioid use (HOC) will also be examined. Specifically, group differences in food intake and eating behaviors in the O+MMT group relative to individuals in the O-MMT and HOC group will be examined. Individuals will complete 24-hour dietary food recalls and inventories to characterize eating behavior and food addiction. Participants will complete psychophysical measures of chemosensory functioning of sucrose preference and pleasantness and identification ratings for odors varying in participants' hedonic characteristics. Individuals will also complete validated computer tasks to assess food preferences. Differences in cortical ERPs for high-reward food relative to low-reward food and non-food items will be examined. Event-related potentials will be recorded as participants view photos of rewarding and non-rewarding food items, as well as non-food items. ERP components that index sustained attentional engagement will be measured and compared.

The investigators will recruit thirty individuals meeting criteria for opioid dependence of which 15 will be receiving MMT (O+MMT) and 15 will be on no opioid agonist therapy (O-MMT). The investigators will attempt to match the O-MMT group to the O+MMT group for clinical characteristics and smoking burden. Fifteen obese/overweight adults without history of opioid/substance use will be matched to the patient groups for age, gender, education, smoking and BMI.

Patients with a history of opioid dependence receiving methadone maintenance therapy will be administered Sniffin' Sticks Odor Identification and Hedonic Scale, Sucrose Taste Preference Assessment, Food Preferences Task, Progressive Ratio Task, Clinical Electrophysiology, and Standardized Meal and Hunger and Satiety Ratings

Patients with a history of opioid dependence not current receiving methadone maintenance therapy will be administered Sniffin' Sticks Odor Identification and Hedonic Scale, Sucrose Taste Preference Assessment, Food Preferences Task, Progressive Ratio Task, Clinical Electrophysiology, and Standardized Meal and Hunger and Satiety Ratings

Healthy controls without history of opioid use will be administered Sniffin' Sticks Odor Identification and Hedonic Scale, Sucrose Taste Preference Assessment, Food Preferences Task, Progressive Ratio Task, Clinical Electrophysiology, and Standardized Meal and Hunger and Satiety Ratings

Participants rate images of various food stimuli. Variables derived include relative preferences and reaction time (in milliseconds).

In the PR task, the subject is required to make an increasing number of operant responses for each successive reward

To examine motivated attention in response to food stimuli, brain electrophysiology via event related potentials (ERPs) will be assessed while participants view and rate images of food and non-food items.

Cortical ERPs for high-reward food relative to low-reward food and non-food items will be measured using a BrainVision actiCHamp system (32-channel amplifier). For each group, the grand averages and standard deviations for the late positive potential will be calculated. Group differences in LPP will be assessed within and between picture categories for each arm of the study.

For the odorants, participants provide a rating of intensity and pleasantness based on a -5 to 5 point scale for each of the 16 markers. Afterwards, averages of all 16 marker scores will be calculated for the mean ratings of intensity and pleasantness. Odor identification accuracy will be assessed for each marker, with the score representing the total items correct out of 16.

Participants are showed images of high fat savory, low fat savory, high fat sweet, and low fat sweet foods. Participants must select one of the two pictures to answer the question "which food item do you most want to eat right now." Selection averages of each category and time for selection, for each arm of the study, are automatically calculated by E-Prime software.

Participants begin with 20 M&Ms and a computer prompt that specifies how many times the mouse must be clicked to earn a piece of candy. Participants can earn as little as desired. The click ratio starts at 10 and geometrically increases in increments of 2 (i.e., 10, 20, 40, 80, etc.). The computer program E-Prime automatically records the participant's work capacity and the administrator records the number of M&Ms left in the cup.

Inclusion criteria: English-speaking individuals Must be between 18 and 60 years of age For the O+MMT group, participants must be receiving MMT for at least 3 months For the O-MMT group, participants must have concluded their MMT (if applicable) at least three months prior to the date of the screening visit. Exclusion criteria: Individuals may not have a history of major neurological disorders No unstable medical issues that would affect appetite or blood glucose No pervasive developmental disorder or intellectual disability No significant visual/auditory impairment No history or current episode of psychosis No current opioid abuse No current antipsychotic medication use No major conditions that affect chemosensory function (e.g., history of nasal fracture or respiratory infection) Individuals with contraindication for the EEG will be excluded Individuals who are current pregnant or breastfeeding will not be enrolled For HOC, individuals with history of opioid dependence or current or past psychiatric disorders will be excluded