Mapping Brain Glutamate in Humans: Sex Differences in Cigarette Smokers

Completed

• Conditions: Tobacco Dependence; Cigarette Smoking; Sex

• Registration Number: NCT05279053
• Lead Sponsor: University of California, Los Angeles

Brief Summary

The proposed study will evaluate sex differences in whole-brain glutamate (Glu), with a focus on the dorsal anterior cingulate cortex (dACC), anterior insula, and thalamus, as well as how it is influenced by sex (males vs. females), smoking state (overnight abstinent vs. sated), and circulating ovarian hormones (estrogen and progesterone) in women. Glu will be measured in almost the entire brain, with special focus on the dorsal anterior cingulate cortex (dACC), anterior insula, and thalamus, all of which have been implicated in behavioral states linked to tobacco withdrawal, using an echo-planar spectroscopic imaging (EPSI) variant of magnetic resonance spectroscopy (MRS). Serum ovarian hormones (estrogen and progesterone) will be measured for female participants to determine relationships between brain Glu and this hormone. Whole-brain Glu will be measured in 60 smokers (30 men, 30 women) twice, after overnight (\~12 h) abstinence and after participants smoke the first cigarette of the day.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-01
• Study First Submitted: 2022-02-23
• Study First Submitted QC: 2022-03-03
• Study First Posted: 2022-03-15
• Primary Completion: 2023-03-31
• Study Completion: 2023-03-31
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-11
• Last Update Posted: 2023-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. Self-identified as only male or female
2. Age 18-45 years (children <18 years will be excluded due to low prevalence of conventional cigarette smoking; female participants >45 years of age will be excluded to avoid effects of perimenopause and menopause in women; male participants >45 years of age will be excluded as well to ensure that male and female groups are matched on age
3. English fluency demonstrated by verbal skills sufficient to participate in a conversation, including the ability to ask and answer questions at a level that assures adequate understanding of the study (a comprehension quiz will be given)
4. Right handedness (evaluated using the Edinburgh Inventory)
5. Generally in good health without cardiovascular, hepatic, renal, or autoimmune diseases, diabetes, or cancer
6. Must have smoked for ≥1 year
7. Must endorse inhaling while smoking
8. Must smoke ≥10 cigarettes per day
9. Must have expired CO >10 ppm and urinary cotinine ≥100 ng/ml at screening/intake
10. Fulfillment of DSM-5 criteria for Tobacco Use Disorder

Exclusion Criteria

1. Seeking treatment for nicotine dependence within 3 months of screening
2. Medical condition that may compromise safety (based on history, physical exam)
3. Neurological disorder that would compromise compliance and/or informed consent
4. Major psychiatric disorder (e.g., Major Depression, Schizophrenia, Bipolar Disorder) per DSM-5 MINI
5. Current drug use disorders other than Tobacco Use Disorder (as defined in DSM-5)
6. Recent use of cocaine, opiates, benzodiazepines, or amphetamines as shown by urine test at the screening or testing sessions
7. Smoke marijuana >3X/week (self-report) or positive marijuana urine test on a scan day (positive at screening allowed)
8. Use of tobacco in forms other than cigarettes (e.g., snuff, chewing tobacco, e-cigarettes) >10 days in the month before screening
9. Preference for menthol cigarettes, given sex differences in the effect of menthol on the rate of nicotine entry into the brain
10. Pregnancy or nursing
11. Presence in the body of metal that would compromise safety during MRI
12. Claustrophobia
13. Any other condition that would compromise safety

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Circulating Ovarian Hormone: Estrogen - in overnight abstinent smokers	Measured before and after smoking a cigarette across a period of 2 hours	Estrogen assayed via a blood sample
Circulating Ovarian Hormone: Progesterone - in overnight abstinent smokers	Measured before and after smoking a cigarette across a period of 2 hours	Estrogen assayed via a blood sample
Whole Brain Glutamate	Measured before and after smoking a cigarette across a period of 2 hours	Measured by EPSI acquisition in overnight abstinent smokers
Nicotine Metabolite Ratio	Measured before smoking a cigarette at a single timepoint	Measured by blood sample

Secondary Outcome Measures

Name	Time	Method
Urge to Smoke Scale (UTS)	Measured before and after smoking a cigarette across a period of 2 hours	This is a 10-item self-reporting questionnaire that measures cigarette craving
Shiffman-Jarvik Withdrawal Scale (SJWS)	Measured before and after smoking a cigarette across a period of 2 hours	This is a 25-item self-reporting questionnaire that measures psychological withdrawal
Spielberger State-Trait Anxiety (STAI)	Measured before and after smoking a cigarette across a period of 2 hours	This is a 20-item self-reporting questionnaire that measures anxiety
Positive and Negative Affect Schedule (PANAS)	Measured before and after smoking a cigarette across a period of 2 hours	This is a 20-item self-reporting questionnaire that measures positive and negative affect

Trial Locations

Locations (1)

UCLA Semel Institute; 🇺🇸 Los Angeles, California, United States