Neurobehavioral Mechanisms Linking Childhood Adversity to Increased Risk for Smoking

The purpose of this study is to evaluate how certain childhood experiences influences brain function and responses to nicotine exposure in a group of nonsmoking young adults. The investigators assess responses to nicotine exposure by giving participants a small amount of nicotine or placebo, and then asking them to answer questionnaires. The investigational drugs used in this study are a nicotine nasal spray (i.e., Nicotrol) and/or a nasal spray placebo (made of common kitchen ingredients, including a very tiny amount of pepper extract also called capsaicin). The investigators assess brain function through function magnetic resonance imaging (fMRI), which is a noninvasive procedure that uses a magnetic field to take pictures of your brain while you are performing certain tasks. This study will help us to learn more about why some childhood experiences (adverse childhood experiences, or ACEs) contribute to increased risk for smoking and other substance use.

Individuals with a history of adverse childhood experiences (ACEs) are more likely to smoke cigarettes than those without, but little is known about the factors that account for this increased risk. This study will examine brain function in regions related to reward processing and inhibitory control, along with reactions to initial nicotine exposure to help explain why ACEs lead to increased risk for smoking. In this study, young adult non-smokers ages 18-21 (n=150) with a history of exposure to ACEs ranging from 0 to 4 or more will be enrolled to attend 7 visits including an MRI scan and administration of a nicotine nasal spray. Participants will complete an in-person screening visit, followed by a training visit to provide training for the MRI tasks and to acclimate them to the mock MRI scanner. They will then complete a functional neuroimaging scanning session to examine brain reactivity during a monetary reward task, an inhibitory control task, and during rest. Participants will then attend 3 separate visits in which subjective reactions to a nasal spray containing 0, .5, or 1 mg doses of nicotine will be measured. During a final choice session participants will choose to self-administer nicotine or placebo nasal spray. Breath and urine samples will be collected at each visit to test for recent smoking, alcohol use, or illicit drug use. Plasma samples will be collected at each fixed-dose session to assess nicotine and cotinine levels. All nicotine administration will occur during laboratory sessions, and the study physician will be on site or on call during all visits.