Exercise Facilitation of Adolescent Fear Extinction, Frontolimbic Circuitry, and Endocannabinoids

NCT06297278 | Recruiting

• 2 other identifiers: IRB-23-01-5444R01MH132830
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

Anxiety disorders commonly begin during adolescence, and are characterized by deficits in the ability to inhibit or extinguish pathological fear. Recent research has provided new understanding of how fear is learned and can be regulated in the adolescent brain, and how the endocannabinoid system shapes these processes; however, these advances have not yet translated into improved therapeutic outcomes for adolescents with anxiety. This study will test whether a behavioral intervention, acute exercise, can help to improve fear regulation by enhancing brain activity and endocannabinoid signaling. This line of research may ultimately lead to more effect treatments for adolescent anxiety, and to new preventive strategies for at-risk youth.

Conditions

Adolescence

Keywords

anxiety; exercise; fear

Outcome Measures

Primary Outcomes (4)

• Skin Conductance Responding (SCR)

  To compare the effects of acute moderate-intensity exercise (vs. sedentary control) on extinction recall, the investigators will place three electrodes on participant's left hand to acquire SCR data using a BIOPAC MP160 Data Acquisition System (BIOPAC Systems, Inc.).

  Throughout study completion (3 days)

• Unconditioned Stimulus (US) Expectancy Ratings

  US Expectancy Ratings will be measured during fear learning, extinction, and recall tasks

  Throughout study completion (3 days)

• Fear extinction neural circuitry: Functional activation and coupling

  MRI eligible only: fMRI blood-oxygen-level-dependent (BOLD) response will be measured across the entire brain during a test of extinction recall. The investigators will focus on response in the hippocampus and ventromedial prefrontal cortex activation and coupling (gPPI) during recall (CS+E\>CS+U).

  Neuroimaging will occur during the fear extinction recall phase on Day 3

• Endocannabinoid (eCB) Concentrations

  Plasma and saliva samples will be collected immediately before and after exercise or sedentary control condition. Samples will be analyzed using liquid chromatography-mass spectrometry to quantify concentrations of eCBs.

  eCB concentrations will be measured in plasma and saliva immediately before and after the exercise or control condition on Day 2

Secondary Outcomes (3)

• Fear Ratings

  Throughout study completion (3 days)

• Approach/Avoidance Behavior

  Throughout study completion (3 days)

• Amygdala response during extinction recall

  Neuroimaging will occur during the fear extinction recall phase on Day 3

Study Arms (2)

Moderate Intensity Exercise

EXPERIMENTAL

Behavioral: Moderate Intensity Exercise

Control (Coloring)

NO INTERVENTION

Interventions

Moderate Intensity Exercise BEHAVIORAL

Participants randomized to the active (moderate intensity) exercise condition will complete a 3-minute warm-up at low speed on a treadmill. Speed and incline will be increased in 3-minute increments until moderate-intensity exercise, defined as participants staying within a zone of 60-80% AAMHR with the target being to attain and maintain 70-75% AAMHR while briskly walking and/or jogging depending on current fitness status, is reached for a total of 30 min.

Moderate Intensity Exercise

Eligibility Criteria

• Age: 14 Years - 17 Years
• Gender Eligibility Details: Females must not be pregnant, breastfeeding, or postpartum less than 6 months
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and available for the duration of the study
• years of age upon enrollment
• Right-handed
• In good general health as evidenced by medical history
• Adolescent and parent/guardian are English-speaking, as study assessments are in English
• Availability of a parent or legal guardian who is willing to provide consent and attend all study visits

You may not qualify if:

• Traumatic brain injury with ongoing symptoms
• Sensory (e.g., hearing) or physical (e.g., motor, balance) impairment or significant developmental delay
• MRI participants: MRI contraindication (e.g., braces, implants, claustrophobia)
• Any condition that would contraindicate blood draws (e.g., hemophilia, sickle cell)
• Past or current diagnosis or presence of likely neurological disorder (e.g., epilepsy), psychotic disorder (e.g., schizophrenia, schizoaffective disorder), or bipolar disorder
• Severe/unstable medical condition (e.g., diabetes, rheumatoid arthritis)
• Current (past 1-month) use of cannabis or cannabinoid products including CBD unless willing to stop for at least 4 weeks prior to entering the study
• Currently pregnant, lactating, or positive pregnancy test at screening visit
• Current homicidal thoughts or suicide attempt in the past year
• Current suicidal thoughts requiring immediate intervention
• Concurrent use (past 6 weeks) of oral contraceptives
• Diagnosed or probable substance use disorder (past 1-month)
• Positive drug test at baseline visit (e.g., THC, cocaine)
• Moderate/severe drug or alcohol use in the past 8 weeks
• Current or recent (past 1-month) COVID-19 diagnosis or febrile illness

Sponsors & Collaborators

• Wayne State University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Tolan Park Medical Building

Detroit, Michigan, 48201, United States

RECRUITING

MeSH Terms

Conditions

Anxiety Disorders; Motor Activity

Condition Hierarchy (Ancestors)

Mental Disorders; Behavior

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: March 7, 2024
• Study Start: May 17, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)