N/A
N=58
Mapping Brain Glutamate in Humans: Sex Differences in Cigarette Smokers
Sex · Cigarette Smoking
Bottom Line
View on ClinicalTrials.gov: NCT05279053 ↗Enrolled (actual)
58
Serious AEs
0.0%
Results posted
Mar 2026
Primary outcome: Primary: Glutamate in the Dorsal Anterior Cingulate Cortex — 8.11; 7.05 Institutional Units — p=0.027
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- Abstinence and Smoking (Behavioral)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of California, Los Angeles
- Primary completion
- Mar 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Glutamate in the Dorsal Anterior Cingulate Cortex |
8.11; 7.05 | 0.027 sig |
| PRIMARY Glutamate in the Insula |
7.44; 6.98 | >0.05 |
| PRIMARY Glutamate in Whole Brain (Gray Matter Plus White Matter). |
5.65; 5.53 | >0.05 |
| PRIMARY Serum Estrogen |
92.77 | 0.408 |
Summary
The proposed study evaluated sex differences in 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 was measured in the entire brain with special focus on the dorsal anterior cingulate cortex (dACC), anterior insula, and thalamus, all of which have been implicated in tobacco withdrawal, using an echo-planar spectroscopic imaging (EPSI) variant of magnetic resonance spectroscopy (MRS). Serum ovarian hormones (estrogen and progesterone) were measured for female participants to determine relationships between brain Glu and this hormone. Glu was be measured in smokers after overnight (~12 h) abstinence and after participants smoked the first cigarette of the day.
Eligibility Criteria
Inclusion Criteria
- Self-identified as only male or female
- Age 18-45 years (children 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
- 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)
- Right handedness (evaluated using the Edinburgh Inventory)
- Generally in good health without cardiovascular, hepatic, renal, or autoimmune diseases, diabetes, or cancer
- Must have smoked for ≥1 year
- Must endorse inhaling while smoking
- Must smoke ≥10 cigarettes per day
- Must have expired CO >10 ppm and urinary cotinine ≥100 ng/ml at screening/intake
- Fulfillment of DSM-5 criteria for Tobacco Use Disorder
Exclusion Criteria
- Seeking treatment for nicotine dependence within 3 months of screening
- Medical condition that may compromise safety (based on history, physical exam)
- Neurological disorder that would compromise compliance and/or informed consent
- Major psychiatric disorder (e.g., Major Depression, Schizophrenia, Bipolar Disorder) per DSM-5 MINI
- Current drug use disorders other than Tobacco Use Disorder (as defined in DSM-5)
- Recent use of cocaine, opiates, benzodiazepines, or amphetamines as shown by urine test at the screening or testing sessions
- Smoke marijuana >3X/week (self-report) or positive marijuana urine test on a scan day (positive at screening allowed)
- Use of tobacco in forms other than cigarettes (e.g., snuff, chewing tobacco, e-cigarettes) >10 days in the month before screening
- Preference for menthol cigarettes, given sex differences in the effect of menthol on the rate of nicotine entry into the brain
- Pregnancy or nursing
- Presence in the body of metal that would compromise safety during MRI
- Claustrophobia
- Any other condition that would compromise safety
Data sourced from ClinicalTrials.gov (NCT05279053). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.