Stress Test for Substance Addiction

(APSU Trial)

Overseen By Aysenil Belger, PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Beta blockers, Antipsychotics

Disqualifiers: Psychosis, Severe emotional disturbance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how changes during adolescence affect brain connections, stress responses, and the link between anxiety and the risk of substance use. Participants will undergo the Trier Social Stress Test, which includes storytelling and math tasks to measure stress responses. The trial seeks children aged 12-14 who feel anxious and have not used substances like alcohol or tobacco more than a few times. The findings could enhance understanding of how anxiety leads to substance use, potentially guiding future treatments. As an unphased trial, this study offers participants a unique opportunity to contribute to groundbreaking research that could shape future interventions for anxiety and substance use.

Will I have to stop taking my current medications?

If you are taking medications that directly affect heart function, like beta blockers, you cannot participate in this trial. Otherwise, the trial does not specify if you need to stop other medications.

What prior data suggests that the Trier Social Stress Test is safe for children?

Research has shown that the Trier Social Stress Test (TSST) is generally safe for use in studies. It creates a controlled stress environment by having participants perform tasks such as storytelling and solving math problems in front of neutral judges. Studies have found that the TSST affects stress-related hormones, like salivary cortisol, indicating it successfully induces stress without causing harm.

Reports do not mention any serious negative effects from using the TSST. Researchers widely use it to study the body's response to stress. No evidence of long-term negative effects exists, making it a well-tolerated method for inducing stress in a controlled setting. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Trier Social Stress Test (TSST) is unique because it offers a new way to understand and measure stress responses in individuals with substance addiction. Unlike traditional treatments that focus on medication or therapy to manage addiction, the TSST provides a controlled environment to observe how stress impacts someone physiologically and psychologically. Researchers are excited about this approach because it could help identify specific stress-related triggers for addiction, potentially leading to more targeted and effective intervention strategies.

What evidence suggests that the Trier Social Stress Test is effective for studying stress responses in adolescents?

Research has shown that the Trier Social Stress Test (TSST), which participants in this trial will undergo, is a common method for studying stress responses. It effectively activates the body's stress systems, including the part controlling the 'fight or flight' response. Studies have found that responses to stress during the TSST can predict cravings for substances like alcohol and opioids. Individuals with stronger stress reactions often experience higher cravings and may relapse more easily. This makes the TSST a valuable tool for understanding how stress might lead to substance use, particularly in individuals with anxiety. ^{2 6 7 8 9}

Who Is on the Research Team?

Aysenil Belger, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for children aged 12-14 who show symptoms of anxiety. They must be accompanied by a legal caregiver and are willing to undergo questionnaires, interviews, neuroimaging during cognitive tasks, and physiological monitoring under mild stress.

Inclusion Criteria

Understands and signs an assent, and parents will sign a permission and a consent document in English

Meets study hearing and vision requirements

Substance use naïve

Exclusion Criteria

Has been diagnosed with psychosis or a severe emotional disturbance

Has any foreign metal objects or implants as determined by the safety questionnaires (e.g., bone screws, shunts or body piercing that can't be removed, etc.)

Has used alcohol, tobacco, or marijuana more than 3 times

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including neuroimaging, cognitive tasks, and physiological stress response measurements

4 weeks

1 visit (in-person)

Longitudinal Data Collection

Participants are assessed at 12-month intervals with neuroimaging, cognitive tasks, and physiological stress response measurements

24 months

3 visits (in-person) at baseline, 12 months, and 24 months

Follow-up

Participants complete a final online exit survey to evaluate clinical symptoms and end-point APSU

4 weeks

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Trier Social Stress Test

Trial Overview The study aims to understand how changes in the brain and body's response to stress during adolescence can lead to substance use due to anxiety. It involves non-invasive procedures like questionnaires, neuroimaging, heart rate and skin conductance monitoring.

How Is the Trial Designed?

Group I: Trier Social Stress Test (TSST) Experimental Treatment 1 Intervention

The Trier Social Stress Test for Children (TSST-C) is a social stressor involving story telling in front of two neutral judges, preparation time and a cognitive stressor involving mental arithmetic-counting backward from 1023 by 13s. It is used to elicit physiological stress responses. The TSST-C is administered in 4 parts: an anticipatory stress phase (5 min to prepare the speech); the speech task (5 min), the arithmetic task (5 min), and the recovery phase (up through 40 min post-task).

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

RTI International

Collaborator

Trials

201

Recruited

942,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7739033/

A systematic review of the Trier Social Stress Test methodology The Trier Social Stress Test (TSST) has been used widely as a psychosocial stress paradigm to activate the sympathetic nervous system and hypothalamic- ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871621002507

Laboratory-induced stress and craving predict opioid use ... Additionally, there was a significant interaction between randomization to the TSST, stress reactivity, and amount of opioids used. Conclusions.

3. nature.com nature.com/articles/s41398-025-03447-8

Individual stress reactivity predicts alcohol craving and ... Our results highlight the impact of psychosocial stress on cue-induced craving and subjective and neuroendocrine stress responses.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2815094/

Reactivity to Laboratory Stress Provocation Predicts Relapse ... The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving ...

5. frontiersin.org frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2015.00014/full

The Trier Social Stress Test as a paradigm to study how ... The Trier Social Stress Test (TSST) is a well-established paradigm in biopsychology that induces social-evaluative threat in the laboratory.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5895062/

The Trier Social Stress Test and the ... The TSST and the TSST-G lead to effects on different physiological and psychological markers, such as salivary cortisol, anxiety, and emotional ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5645206/

A paradigm for examining stress effects on alcohol ... The Trier Social Stress Test increased alcohol craving and rate of responding and decreased the number of changeovers between alcohol versus money reinforcers ...

8. cmhsrp.uic.edu cmhsrp.uic.edu/download/Brady_2-15_Presentation.pdf

Relationship Between Stress and Substance Use Disorders Interaction of Social Support and. Oxytocin on Stress Response. • 37 healthy males. • Trier Social Stress Test. • Social support from friend during preparation.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871624002710

The importance of community engagement in experimental ... CEnR can improve experimental stress and substance use research by engaging applicable communities in research design, recruitment, data interpretation, and ...