Effect of Nicotine on Brain Reward Pathways

The investigators will determine whether an acute dose of nicotine, in the form of the nicotine lozenge, impacts brain and behavioral measures of mood and reward responsiveness in individuals with major depressive disorder.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder
• Intervention / Treatment: Drug: Nicotine polacrilex

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for subjects with Major Depressive Disorder:

1. Provide written informed consent;
2. Both genders and all ethnic origins, age between 18 and 45;
3. Meet DSM-IV diagnostic criteria for MDD (diagnosed with the use of the SCID);
4. A baseline HAM-D score of 16 or greater;
5. Absence of pregnancy;

6. Absence of any psychotropic medication for at least 2 weeks:

   1. 6 weeks for fluoxetine
   2. 6 months for neuroleptics
   3. 2 weeks for benzodiazepines
   4. 2 weeks for any other antidepressants

Inclusion Criteria for Healthy Controls

1. Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse); as assessed by subject history and a structured clinical interview (SCID);
2. Provide written informed consent;
3. Both genders and all ethnic origins, age between 18 and 45;
4. Absence of any medications for at least 3 weeks;
5. Absence of pregnancy.

Exclusion Criteria:

1. Subjects with suicidal ideation where outpatient treatment is determined unsafe. These patients will be immediately referred to a licensed psychologist or psychiatrist to determine the appropriate clinical treatment;
2. Serious or unstable medical illness
3. Lifetime history of seizure disorder;
4. Lifetime history or current diagnosis of any of the following DSM-IV psychiatric illnesses: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, ADHD, patients with mood congruent or mood incongruent psychotic features; simple phobia, social anxiety disorder and generalized anxiety disorders will be allowed only if secondary to MDD;
5. Patients with a lifetime history of electroconvulsive therapy (ECT);
6. Failure to meet standard MRI safety requirements;
7. May not have used any nicotine product in the past year; must report fewer than 20 lifetime uses of nicotine
8. Must have an expired carbon monoxide level of less than or equal to 10 ppm.
9. Use of anticholinergic drugs in the past week
10. Any past or present history of cardiac problems including known arrhythmias, acute coronary syndrome, or ischemic heart disease
11. Uncontrolled hypertension
12. History of substance abuse in the past 6 months (other than caffeine), self-reported use of marijuana in past month, or history of treatment with methadone
13. Heavy caffeine users (consume greater than 500 mg on a regular or daily basis)
14. Subjects that cannot speak English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo comparator	Drug: Nicotine polacrilex; Single Acute dose; Other Names: Nicotine lozenge
Experimental: Nicotine; 2mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time. 4mg of nicotine in the form of a nicotine polacrilex lozenge will be administered orally, one time.	Drug: Nicotine polacrilex; Single Acute dose; Other Names: Nicotine lozenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Placebo in functional magnetic resonance imaging (fMRI) BOLD Response	Nicotine will enhance the fMRI BOLD response to monetary reinforcers relative to placebo administration	Participants will be assessed during 2 fMRI scanning sessions, an expected average of 2 weeks.

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Amy Janes, Ph.D, McLean Hospital

Publications and helpful links

General Publications

• Wang KS, Brown K, Frederick BB, Moran LV, Olson D, Pizzagalli DA, Kaiser RH, Janes AC. Nicotine acutely alters temporal properties of resting brain states. Drug Alcohol Depend. 2021 Sep 1;226:108846. doi: 10.1016/j.drugalcdep.2021.108846. Epub 2021 Jun 24.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: January 14, 2015
• First Submitted That Met QC Criteria: January 20, 2015
• First Posted (Estimate): January 27, 2015

Study Record Updates

• Last Update Posted (Actual): March 22, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Depression; Nicotine
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 2014P002495-01; 5K01DA029645-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No