How Does the Opioid System Shape Stress and Social Behaviour in Men and Women and What Role Does Childhood Unpredictability Play?

NCT07778511 | Not Yet Recruiting DMC

• 2 other identifiers: 2026-00586PZ00P1_208759
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to investigate sex differences in the effect of mu-opioid receptor (MOR) activation on stress response and social behaviour modulated by early life stress.

Conditions

Stress; Early Life Stress; Sex Differences; Opioid

Keywords

mu opioid receptor; stress; early life stress; social behaviour; affiliative behaviour; sex differences; endocannabinoid system; morphine; opioid use disorder

Outcome Measures

Primary Outcomes (9)

• Self-report of subjective stress during stress exposure

  Sex-specific differences in the stress relieving effects of morphine compared to placebo. Subjective stress response will be measured by differences between self- and other condition in ratings using a 1-7 Visual Analogue Scale (VAS) with the anchors "not at all" (1) to "very much" (7) for the items "How secure do you feel?" and "How stressed do you feel?" throughout the stress task.

  During the experimental stress task

• Endocrinological markers of stress response

  Sex-specific differences in the stress relieving effects of morphine compared to placebo measured by changes in plasma concentrations of cortisol and endocannabinoids (2-AG, AEA, PEA, SEA, OEA).

  Throughout the experiment sessions (baseline and approx. 10, 20, 30, 60 and 105 minutes after stress onset, 6 samples).

• Psychophysiological stress response of heart rate measured by electrocardiogram

  Sex-specific differences in the stress relieving effects of morphine compared to placebo measured by differences between self and other condition in heart rate (beats per minute).

  During the experimental stress task

• Psychophysiological stress response of heart rate variability measured by electrocardiogram

  Sex-specific differences in the stress relieving effects of morphine compared to placebo measured by differences between self and other condition in heart rate variability.

  During the experimental stress task

• Psychophysiological measure of sympathetic activity

  Sex-specific differences in the stress relieving effects of morphine compared to placebo measured by differences between self and other condition in skin conductance response (SCR).

  During the experimental stress task

• Changes in self-reported subjective stress over time

  Sex-specific differences in morphine-mediated stress relief measured by changes in Visual Analogue Scales (VAS), ranging from 0-100 with the anchors " not at all " (0) and "extremely" (100) for the items: "I feel stressed", "I feel safe", "I feel relaxed", "I have a dry mouth", "I feel nauseous", "I feel confident", "I feel ashamed", "I feel vulnerable"

  Throughout the experimental sessions (from before stress induction to 10, 20, 30, 60 and 105 minutes after stress onset, 7 times).

• Self-reported feeling of shame post-stress

  Sex-differences in morphine effects on the Experiential Shame Scale (ESS) score, ranging from 25 -100, with higher values indicating stronger feelings of shame.

  ~10 minutes after stress onset

• Changes in self-reported affect over time

  Sex-specific differences in morphine effects on changes of positive and negative affect measured using the Positive and Negative Affect Schedule (PANAS) scores. Scores for both subscales range from 10 to 50 with higher scores indicating stronger positive or negative affect, respectively.

  Throughout the experimental sessions (from before stress induction to 10, 30, 60 and 105 minutes after stress onset, 6 times).

• Early life stress

  Modulation of the Questionnaire of Unpredictability in Childhood (QUIC) sum score on differences in primary outcomes. Scores range from 0-38 with higher scores indicating greater exposure to instability and unpredictability during childhood.

  Prior to enrollment

Secondary Outcomes (21)

• Subjective differences in experiencing social interaction

  During the experimental tasks

• Behavioural differences of social approach and avoidance

  During the experimental task

• Psychophysiological cardiac markers of social interaction measured by heart rate using electrocardiogram

  During the experimental tasks

• Psychophysiological cardiac markers of social interaction measured by heart rate variability using electrocardiogram

  During the experimental tasks

• Psychophysiological measure of sympathetic activity during social interaction

  During the experimental tasks.

Study Arms (2)

Morphine

ACTIVE COMPARATOR

Participants receive the active drug (morphine) on Visit 1or Visit 2.

Drug: Morphine

Placebo

PLACEBO COMPARATOR

Participants receive the non-active comparator (placebo) on Visit 1 or Visit 2.

Drug: Placebo

Interventions

Morphine DRUG

Sevredol 10mg, oral single-dose administration

Morphine

Placebo DRUG

identical in appearance to active drug, containing no active substance (mannitol), oral one-time administration

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-40 years
• Ability to read, understand, and provide written informed consent in German
• Proficiency in German
• Able to give blood samples (no blood- or needle-related phobia)
• Good health as determined by medical history, ECG, and clinical assessment of lab tests. Lab tests will include potassium, creatinine, hemoglobin, glucose, calcium, BUN, complete blood count, total bilirubin, AST, ALT, and GGT. The final decision will be according to the judgment of the study physician.
• Prior experience with medical opioids (at least one experience with prescription opioids such as oxycodone, morphine, hydromorphone, fentanyl, hydrocodone, codeine, or dihydrocodeine) and paracetamol.
• Body mass index (BMI) between 19 and 30 kg/m2

You may not qualify if:

• Any current instable medical or neurological condition
• Any clinically significant psychiatric disorder (i.e., psychotic and stress-related disorders) including a diagnosis of substance use disorder (defined in DSM-5 terms as Moderate or Severe). Participants will be screened using the Structured Clinical Interview - SCID for DSM-5). If indication is obtained that a clinically significant psychiatric disorder may be present, a full SCID will be carried out by appropriately trained staff.
• Significant adverse reaction to prior opioid or paracetamol exposure
• Reporting any illegal drug use \>15 life-time occasions and regular drug use during the last three months incl. the test period (except for nicotine and alcohol)
• Any current use of CNS-active medications.
• Current use of opioid analgesics, opioid use for \> 6 weeks (lifetime), or within the three months prior to study enrollment.
• Fagerström Test of Nicotine Dependence (FTND) Score \> 5 (strong nicotine dependence)
• Heavy alcohol use based on the Alcohol Use Disorder Identification Test (AUDIT)
• Lifetime diagnosis of cardiac disease.
• Clinically significant laboratory or ECG abnormality that could be a safety issue in the study
• Acute or chronic respiratory issues (e.g., cold, flu, asthma, etc.)
• Lifetime diagnosis of liver or kidney disease including moderate or severe renal impairment (creatinine clearance \< 50 ml/min)
• Lifetime diagnosis of schizophrenia, bipolar disorder, obsessive-compulsive disorder, or autism spectrum disorder according to DSM-5
• Diagnosis of a current episode of depression based on DSM-5 criteria
• Current diagnosis of a moderate or severe substance use disorder according to DSM-5

Sponsors & Collaborators

• Sara L. Kroll: lead

Study Sites (1)

University Hospital of Psychiatry Zurich

Zurich, 8032, Switzerland

Location

MeSH Terms

Conditions

Stress, Psychological; Social Behavior; Opioid-Related Disorders

Interventions

Morphine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Sara L Kroll, Dr.

  Psychiatric University Hospital, Zurich

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara L Kroll, Dr. phil.

CONTACT

+41 (0)58 384 34 13; saraliane.kroll@bli.uzh.ch

Ella L Sommer

CONTACT

+41 (0)58 384 26 01; ella.sommer@bli.uzh.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Randomized, double-blind, placebo-controlled, crossover study

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: August 21, 2026

Record last verified: 2026-08

Locations

CH (1)