Defining Neurobiological Links Between Substance Use and Mental Illness
- Conditions
- Substance Use DisorderMajor Depressive DisorderNormal Physiology
- Interventions
- Other: Placebo Nicotine Patch
- Registration Number
- NCT05538910
- Lead Sponsor
- National Institute on Drug Abuse (NIDA)
- Brief Summary
Background:
Nicotine dependence leads to about 480,000 deaths every year in the United States. People with major depressive disorder (MDD) are twice as likely to use nicotine compared to the general population. They have greater withdrawal symptoms and are more likely to relapse after quitting compared with smokers without MDD. More research is needed on how nicotine affects brain function in those with MDD.
Objective:
To understand how nicotine affects symptoms of depression and related brain function.
Eligibility:
People aged 18 to 60 years, at the time of consent, with and without MDD who do not smoke cigarettes or use other nicotine products.
Design:
Participants will have 2 or 3 study visits over 1 year.
Participants will have 2 MRI scans no less than 4 days apart. Each scan visit will last 5 to 7 hours. At each scan, they will have urine and breath tests to screen for recent use of alcohol, nicotine, and illegal drugs.
Before each scan, they will take 1 of 2 medications: nicotine or placebo. Participants will receive each medication once. They will not know which medication they are receiving at each scan.
For each MRI scan, they will lie on a table that slides into a cylinder. Sometimes they will be asked to lie still. Sometimes they will complete tasks on a computer. Tasks may include identifying colors or playing games to win money. Each scan will take about 2 hours.
Participants will answer questions about their thoughts, feelings, and behaviors before and after each scan.
They will have a blood test after each scan.
- Detailed Description
Study Description:
Tobacco smoking leads to 480,000 deaths and a loss of $300 billion a year in the U.S. Individuals with major depressive disorder (MDD) are more vulnerable for experiencing these burdens as they are twice as likely to use nicotine versus the general population. The current work will explain the neurobiological basis of this enhanced risk and will define potential targets for lessening the impact of nicotine on those with MDD. This research plan will take the innovative approach of evaluating nicotine s effects in non-smokers with and without MDD. In contrast to focusing on nicotine dependent individuals, which introduces confounds due to chronic use, this design will directly show the domains in which the neurobiological impact of nicotine is greater in those with MDD, providing a mechanistic framework for enhanced risk.
Objectives:
The primary objective is to determine the differential neurobiological impact of a nicotinic agonist on those with and without current major depressive disorder. Whether such effects are linked with specific symptoms of MDD will be assessed as will the potential modifying influence of biological sex. Those with a lifetime history of MDD will be assessed as well given evidence that reduced reward responsivity is a trait that persists even when one no longer meets current MDD criteria.
Endpoints:
Brain function will be assessed in several ways: 1) Resting-state fMRI will determine pharmacologically mediated group-specific differences in functional brain organization and inherent dynamic functioning 2) Task-based fMRI will determine pharmacologically mediated group-specific differences in reward function, affective processing, and interceptive awareness. These same measures will further be assessed considering specific symptoms of MDD and biological sex.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 420
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2: Nicotine Patch Nicotine Patch Nicotine Patch + Placebo Pill Arm 1: Placebo Placebo Nicotine Patch Placebo patch + Placebo Pill
- Primary Outcome Measures
Name Time Method 4.Nicotine effects and symptoms of MDD At each scan visit Greater expression of MDD symptoms will related to a larger nicotine-induced impact within that domain.
2.Task-fMRI At each scan visit 2. Evaluate nicotine agonism on: 1) different phases of reward processing, 2) brain/behavioral measures of attentional bias using the classic and emotional Stroop task, and 1.3. 3) interoceptive awareness. 4) confidence on value-based decisions, determine the influence of sex in the context of points 1-3.
1.Resting-fMRI At each scan visit 1.Determine the impact of nicotine agonism on the brain s inherent function and organization at rest.
3. Task and Resting State Brain At each scan visit Relate static and temporal dynamic resting state brain function to nicotinic effects.
- Secondary Outcome Measures
Name Time Method Determine the relationship between blood-based biomarkers, such as inflammatory makers/metabolomics and nicotinic effects Ongoing Correlate levels of blood-based biomarkers with brain and behavioral measures and determine whether nicotine...
Trial Locations
- Locations (1)
National Institute on Drug Abuse
🇺🇸Baltimore, Maryland, United States