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Protocol Details

Defining Neurobiological Links between Substance Use and Mental Illness

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute on Drug Abuse (NIDA)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 60 Years

Referral Letter Required


Population Exclusion(s)

Non-English Speaking;


Reward Function;
Affective Processing;
Interoceptive Awareness

Recruitment Keyword(s)



Major Depressive Disorder;
Substance Use Disorder;
Normal Physiology

Investigational Drug(s)


Investigational Device(s)



Other: Placebo Nicotine Patch
Drug: Nicotine Patch

Supporting Site

National Institute on Drug Abuse


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.


To understand how nicotine affects symptoms of depression and related brain function.


People aged 18 to 60 years with and without MDD who do not smoke cigarettes or use other nicotine products.


Participants will have 2 or 3 study visits over 1 to 3 months.

Participants will have 2 MRI scans at least 1 week 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.

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To be eligible for this study, an individual must meet all the following criteria assessed under the 06-DA-N415 protocol: Evaluation of potential research subjects - screening protocol for clinical studies (here referred to as the NIDA screening protocol). This is a protocol led by the Office of the Clinical Director (OCD) at the National Institute on Drug Abuse Intramural Research Program (NIDA IRP) to assess potential research participants eligibility for entering clinical protocols at the NIDA/IRP. Additional details can be found in the NIDA screening protocol documents. As routinely done at the NIDA IRP, the screening procedures and data collected under the NIDA

screening protocol will capture information above and beyond what is necessary to determine eligibility for this protocol but allows the Investigators to assess the eligibility criteria for this protocol.

In order to be eligible to participate in this study, an individual must meet all of the following


All Participants:

1) Able and willing to provide written informed consent.

2) Both sexes and all ethnic origins, age between 18 and 60: Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals.

3) Be general healthy

4) Absence of pregnancy and breastfeeding. Justification: study procedures and drugs used in the current protocol may complicate pregnancy or be transferred to nursing children. Assessment tool(s): Urine and/or serum pregnancy tests, and clinical interview. Urine pregnancy tests will also be conducted at the beginning of each imaging visit.

5) Have a Breath Alcohol Value of 0 on all study visit days involving scanning. Participant may be rescheduled if this value is greater than 0.

MDD Subjects:

1) Meet DSM-5 diagnostic criteria for current MDD at screening

2) Have a baseline (Hamilton Depression) HAM-D score indicative of current depression

3) Absence of any psychotropic medication for at least 2 weeks except current stable SSRI/SNRI treatment is allowed (no changes in the last 2 months)

Remitted MDD Subjects:

1) Meet DSM-5 diagnostic criteria for remitted MDD (full remission or past depression)

2) HAM-D score indicating no clinically relevant depression

3) Absence of any psychotropic medication for at least 2 weeks prior to scanning except current stable SSRI/SNRI treatment is allowed, provided there are no changes in the 2 months prior to scanning

Control Subjects (without MDD):

1) In addition to the absence of medical, neurological, and psychiatric illness listed above, control participants must not have current/lifetime MDD

2) HAM-D score indicating no clinically-relevant depression

3) Absence of any psychotropic medication for at least 2 weeks prior to scanning except current stable (no dose or medication changes in the last 2 months) SSRI/SNRI treatment is allowed for treatment of disorders other than mood disorders as evaluated by clinical staff.


An individual who meets any of the following criteria will be excluded from participation in this study:

1) Subjects with suicidal ideation where outpatient treatment is determined unsafe.

2) Lifetime history or current diagnosis of any of the following psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, patients with mood congruent or mood incongruent psychotic features. The MAI and/or PI/LI will reserve the right to exclude based psychiatric history not explicitly described in this criterion

a. Within the current/remitted MDD cohorts, simple phobia, social anxiety disorder, ADHD, and generalized anxiety disorders will be allowed cohort only if secondary to MDD;

b. Within the control group, Current/lifetime MDD will be exclusionary for controls. This group can be stable on medication for anxiety disorders without a depressive comorbidity. The MAI will reserve the right to exclude on the basis of psychiatric history not explicitly described in this criterion.

3) Are cognitively impaired or have a learning disability severe enough to have required intervention throughout most or all of K-12 education. The MAI will reserve the right to evaluate if a participant s history of educational placement is likely to represent a learning disability that could significantly impact the data gathered in this study based on the severity and type of learning disability. Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited during laboratory task performance.

4) Heavy caffeine users (consume greater than 500 mg on a regular or daily basis. This is approximately five 8 fl oz cups of coffee). Participants will be asked to not deviate from their typical caffeine use on all scanning days.

5) May not have regularly used any nicotine product in the past year; must report fewer than 20 lifetime uses of nicotine

6) Must have an expired carbon monoxide level of less than or equal to 5 ppm and no detected cotinine

7) History of moderate or severe substance use disorder in the past 6 months (other than caffeine)

8) Current pharmacological treatment for opioid use disorder (i.e., use of methadone)

9) Current use of illegal drugs other than marijuana as measured by urine drug screen Marijuana will not be allowed in the 24 hours prior to scanning based on self-report. Study day can be rescheduled to accommodate.

10) May not use anticholinergic drugs (i.e., scopolamine) in the week prior to any scanning visit. Scanning visit timing can be adjusted to accommodate.

11) May not use drugs that directly enhance dopamine (i.e., methylphenidate) in the week prior to any scanning visit. Scanning visit timing can be adjusted to accommodate.

12) Any past or present significant cardiovascular, cerebrovascular, or respiratory conditions, including arrhythmias, acute coronary syndrome, ischemic heart disease, or, uncontrolled hypertension

13) Body mass index (BMI) lower than 18.5 kg/m2

14) Contraindication to MRI as determined by MRI Safety Screening form

15) Abnormal structural MRI, significant head trauma, current neurological illness including but not limited to frequent migraines, multiple sclerosis, movement disorder

16) Lifetime history of significant seizure disorder

17) Any other serious or unstable medical illness as defined by self-report, the evaluation of vital signs or other observation that in the view of the investigators would compromise the safety of an individual during participation All data collected will be evaluated by members of the study team to decide if there is an existing medical illness that would compromise participation in this research

18) Subjects that cannot speak English. Justification: To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify, given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI procedures. The inability to effectively communicate MRI safety procedures in a language other than English could compromise the safety of non-English speaking participants

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Amy Janes, Ph.D.
National Institute on Drug Abuse (NIDA)
NIDA IRP Office of Human Subjects Research
251 Bayview Blvd, Suite 200
Baltimore, Maryland 21224
(667) 312-5164

Betty Jo Salmeron, M.D.
National Institute on Drug Abuse (NIDA)
(667) 312-5266

Betty Jo Salmeron, M.D.
(667) 312-5266

Clinical Trials Number:


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