Mapping Brain Glutamate in Humans: Sex Differences in Cigarette Smokers

NCT05279053 | Completed Results

• 2 other identifiers: UCLA IRB 17-0003875R03DA052719
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sex; Cigarette Smoking

Outcome Measures

Primary Outcomes (4)

• Glutamate in the Dorsal Anterior Cingulate Cortex

  Glutamate levels, as measured using MRS, in the dorsal anterior cingulate cortex.

  Measured before and after smoking a cigarette by both groups (men and women). Group means below reflect overall group means averaged across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.

• Glutamate in the Insula

  Glutamate levels, as measured using MRS, in the insula.

  Measured before and after smoking a cigarette by both groups (men and women). Group means below reflect overall group means averaged across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.

• Glutamate in Whole Brain (Gray Matter Plus White Matter).

  Glutamate measured using the MRS echoplanar spectroscopic imaging in abstinent smokers.

  Measured before and after smoking a cigarette by both groups (men and women). Group means below reflect overall group means averaged across time points as reported from descriptive statistics in the Generalized Linear Mixed Model.

• Serum Estrogen

  Estrogen concentration measured in serum from blood samples drawn prior to MRS (women only).

  Sampling performed on same day as MRS (before smoking).

Study Arms (2)

Male adults who endorse daily smoking

Participants recruited for this study will be male adults (18-45 years old), who smoke cigarettes daily and are generally in good health. They will have no other drug use, other than occasional marijuana or alcohol use, and no major psychiatric disorders. Urine and breath tested metrics will be used to establish whether participants meet drug use-related criteria.

Behavioral: Abstinence and Smoking

Female adults who endorse daily smoking

Participants recruited for this study will be female adults (18-45 years old), who smoke cigarettes daily and are generally in good health. They will have no other drug use, other than occasional marijuana or alcohol use, and no major psychiatric disorders. Urine and breath tested metrics will be used to establish whether participants meet drug use-related criteria.

Behavioral: Abstinence and Smoking

Interventions

Abstinence and Smoking BEHAVIORAL

Participants came to the lab after overnight abstinence from smoking and smoked their first cigarette of the day.

Female adults who endorse daily smoking; Male adults who endorse daily smoking

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Target recruitment: 60 adult daily smokers (30 men and 30 women; 18-45 years old), who are otherwise in good health. Interested individuals will be invited to participate in the research project regardless of sex, race or ethnicity, although strong efforts will be made to recruit equal numbers of male and female participants. Individuals will not be excluded from study participation based on race/ethnicity.

You may qualify if:

• Self-identified as only male or female
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

UCLA Semel Institute

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Coitus; Cigarette Smoking

Interventions

Smoking Devices

Condition Hierarchy (Ancestors)

Sexual Behavior; Behavior; Tobacco Smoking; Smoking; Tobacco Use

Intervention Hierarchy (Ancestors)

Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Edythe D. London, Ph.D.
• Organization: UCLA David Geffen School of Medicine

elondon@mednet.ucla.edu

3108250606

Study Officials

• Edythe London, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished Professor In Residence

Study Record Dates

• First Submitted: February 23, 2022
• First Posted: March 15, 2022
• Study Start: April 1, 2021
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: March 20, 2026
• Results First Posted: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)