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How Does the Opioid System Shape Stress and Social Behaviour in Men and Women and What Role Does Childhood Unpredictability Play? (MOR-SAFE)

19. srpna 2026 aktualizováno: Sara L. Kroll

Randomized, Double-blind, Placebo-controlled, Crossover Study Investigating Sex-specific Effects of Mu-opioid Receptor Activation on Stress and Social Interaction and Its Modulation by Early Life Stress

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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

While opioid use disorder presents a rising public health concern, the underlying neurobiological mechanisms of substance use are not well understood. In animal studies, activation of the Mu Opioid Receptor (MOR) system has been shown to have stress-buffering effects and to decrease affiliative behaviour, which is in line with addiction models postulating impaired stress response and poor social interactions to be risk indicators for addiction pathogenesis. In humans however, this has not been consistently found. Importantly, behavioural pharmacology studies have often been restricted to male test subjects or have been underpowered. Therefore, a significant knowledge gap remains regarding sex-specific differences in MOR activation. The additional impact of chronic stress in the form of early life stress significantly affects brain development, in turn shaping stress reactivity and affiliative behaviour in later life. This forms the basis of the research question of the present study, whether sex and childhood unpredictability modulate the effects of MOR activation on stress response and social interaction behaviour.

The prototypical opioid morphine will be used to activate the MOR. Participants will receive the study medication on two separate visits in a randomised, counterbalanced order. Afterwards, participants will conduct computer-based stress and social interaction tasks.

Learning more about individual differences in MOR activation and its effects on stress and social behaviour can help to uncover vulnerability and risk factors for opioid use disorder and improve personalised treatment opportunities.

Typ studie

Intervenční

Zápis (Odhadovaný)

72

Fáze

  • Nelze použít

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní záloha kontaktů

Studijní místa

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý

Přijímá zdravé dobrovolníky

Ano

Popis

Inclusion Criteria:

  • 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.
  • Females must have a negative urine pregnancy test (hCG) at inclusion and at the start of each study session. Females of childbearing potential who are sexually active and have not been surgically sterilized must agree to use an adequate method of birth control during the study.
  • 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

Exclusion Criteria:

  • 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
  • Daily cannabis consumption in the past three months
  • Use of psychotropic medication within the last 7 days
  • Participation in other pharmacological studies within the last 2 months
  • Alcohol use within the last 24 hours controlled by breathalyzer
  • Unable to provide a negative urine drug screen (cannabinoids, amphetamines, opiates and opioids, benzodiazepines, and cocaine).
  • Positive pregnancy test or nursing (self-report)
  • For women: irregular menstrual cycle or menopause

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Základní věda
  • Přidělení: Randomizované
  • Intervenční model: Crossover Assignment
  • Maskování: Dvojnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Aktivní komparátor: Morphine
Participants receive the active drug (morphine) on Visit 1or Visit 2.
Sevredol 10mg, oral single-dose administration
Komparátor placeba: Placebo
Participants receive the non-active comparator (placebo) on Visit 1 or Visit 2.
identical in appearance to active drug, containing no active substance (mannitol), oral one-time administration

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Self-report of subjective stress during stress exposure
Časové okno: During the experimental stress task
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
Časové okno: Throughout the experiment sessions (baseline and approx. 10, 20, 30, 60 and 105 minutes after stress onset, 6 samples).
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
Časové okno: During the experimental stress task
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
Časové okno: During the experimental stress task
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
Časové okno: During the experimental stress task
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
Časové okno: Throughout the experimental sessions (from before stress induction to 10, 20, 30, 60 and 105 minutes after stress onset, 7 times).

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
Časové okno: ~10 minutes after stress onset
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
Časové okno: Throughout the experimental sessions (from before stress induction to 10, 30, 60 and 105 minutes after stress onset, 6 times).
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
Časové okno: Prior to enrollment
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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Subjective differences in experiencing social interaction
Časové okno: During the experimental tasks
Sex-specific differences in morphine effects on subjective pleasantness ratings measured by VAS scales (1-100) during the social approach/avoidance task and affective touch task with higher ratings indicating more pleasantness.
During the experimental tasks
Behavioural differences of social approach and avoidance
Časové okno: During the experimental task
Sex-specific differences in morphine effects on behavioural measures (measured by number of button presses) during the social approach/avoidance task.
During the experimental task
Psychophysiological cardiac markers of social interaction measured by heart rate using electrocardiogram
Časové okno: During the experimental tasks
Sex-specific differences in morphine effects on heart rate (beats per minute) during the social approach/avoidance task and the affective touch task.
During the experimental tasks
Psychophysiological cardiac markers of social interaction measured by heart rate variability using electrocardiogram
Časové okno: During the experimental tasks
Sex-specific differences in morphine effects on heart rate variability during the social approach/avoidance task and the affective touch task.
During the experimental tasks
Psychophysiological measure of sympathetic activity during social interaction
Časové okno: During the experimental tasks.
Sex-specific differences in morphine effects on skin conductance response (SCR) during the social approach/avoidance task and the affective touch task.
During the experimental tasks.
State anxiety over time
Časové okno: Throughout the experimental sessions (from before stress induction to approx. 10, 30, 60, and 105 minutes after stress onset, 6 times).
Sex-specific differences in morphine effects on changes in state anxiety measured by the State-Trait Anxiety Inventory (STAI) score. Scores can range from 20 -80 with higher scores indicating greater anxiety
Throughout the experimental sessions (from before stress induction to approx. 10, 30, 60, and 105 minutes after stress onset, 6 times).
Drug Effects Questionnaire (DEQ)
Časové okno: Throughout the experimental sessions (immediately after drug administration until approx. 3 hours after study medication administration, 7 times).
Sex-specific differences in drug effects will be measured using the Drug Effects Questionnaire (DEQ; subjective experiences are reported of "feeling the drug", "feeling high", "drug liking" and "disliking", and "desire to take the drug again") measured on an electronic 0-100 VAS, anchors "not at all" and "extremely".
Throughout the experimental sessions (immediately after drug administration until approx. 3 hours after study medication administration, 7 times).
Drug concentration
Časové okno: Throughout the experimental sessions (from 1 hour after drug administration until approx. 3 hours after study medication administration, 4 samples).
Differences in concentration of the study drug in blood between the two test sessions.
Throughout the experimental sessions (from 1 hour after drug administration until approx. 3 hours after study medication administration, 4 samples).
Changes in oxytocin over time
Časové okno: Throughout the experimental sessions (from before stress induction to approx. 10, 20, 30, 60 and 105 minutes after stress onset, 6 samples).
Sex-specific differences in morphine effects on oxytocin levels measured in saliva.
Throughout the experimental sessions (from before stress induction to approx. 10, 20, 30, 60 and 105 minutes after stress onset, 6 samples).
Early life stress
Časové okno: Prior to enrollment
Modulation of the Questionnaire of Unpredictability in Childhood (QUIC) sum score on differences in secondary outcomes. Scores range from 0-38 with higher scores indicating greater exposure to instability and unpredictability during childhood.
Prior to enrollment
Hair concentrations of chronic stress markers
Časové okno: At screening
Modulation of tonic endocannabinoid (2-AG, AEA, OEA, PEA, SEA) and glucocorticoid (cortisol, cortisone, ACTH) concentrations in hair on primary and secondary outcomes.
At screening
Personality traits
Časové okno: Single measure, during experimental session
Modulation of personality traits measured by the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) on primary and secondary outcomes. Scores range from 0-48 per subscale. Higher scores indicate higher expression of the trait.
Single measure, during experimental session
Trait assessment of loneliness
Časové okno: Single measure, during experimental session
Modulation of loneliness measured by the German version of the UCLA loneliness scale on primary and secondary outcomes. Scores can range from 20-80 with higher scores indicating greater feelings of loneliness.
Single measure, during experimental session
Rosenberg Self Esteem Scale
Časové okno: Single measure, during experimental session.
Modulation of self-esteem measured by the Rosenberg Self Esteem Scale (RSES) on primary and secondary outcomes. Scores range from 0 -30 with scores below 15 suggesting low self-esteem, 15 to 25 reflecting a normal or average range, and 26 to 30 indicating high self-esteem.
Single measure, during experimental session.
Brief Resilience Scale
Časové okno: Single measure, during experimental session.
Modulation of resilience measured by the Brief Resilience Scale (BRS) on primary and secondary outcomes. Scores range from 1-5 with a higher score indicating a better ability to bounce back after stress.
Single measure, during experimental session.
Becker Depression Inventory
Časové okno: Single measure, during experimental session.
Modulation of depression measured by the Becker Depression Inventory (BDI-II) on primary and secondary outcomes. Scores range from 0-63 with higher scores indicating more severe depressive symptoms.
Single measure, during experimental session.
Trait anxiety level
Časové okno: Single measure, during experimental session.
Modulation of anxiety measured by the State Trait Anxiety Inventory (STAI) on primary and secondary outcomes. Scores range from 20-80 per subscale, with higher scores indicating higher levels of trait anxiety.
Single measure, during experimental session.
Snaith Hamilton Anhedonia Pleasure Scale
Časové okno: Single measure, during experimental session.
Modulation of anhedonia measured by the Snaith Hamilton Anhedonia Pleasure Scale (SHAPS) on primary and secondary outcomes. Scores range from 0-14 with higher scores indicating less ability to feel pleasure.
Single measure, during experimental session.
Relationship Structures Questionnaire
Časové okno: Single measure, during experimental session.
Modulation of attachment style measured by the Experiences in Close Relationship Structures Questionnaire (ECR-RS) on primary and secondary outcomes. Two scores, one for attachment-related avoidance and the other for attachment-related anxiety, are computed for different interpersonal targets. The avoidance score can be computed by averaging items 1 - 6 and the anxiety score by averaging items 7 - 9, respectively.
Single measure, during experimental session.
Socioeconomic status ladder
Časové okno: Single measure, during experimental session.
Modulation of socioeconomic status (SES) measured by the MacArthur SES ladder on primary and secondary outcomes. Participants rate their perceived socioeconomic status and social standing using two ladder scales ranging from 1-10: one relative to people in Switzerland and one relative to people in their community. Higher scores indicate higher perceived socioeconomic status or social standing.
Single measure, during experimental session.
Sex hormone concentration
Časové okno: Single measure at both experimental sessions.
Modulation of baseline concentrations of steroid sex hormones (testosterone, progesterone, estradiol) in plasma on primary and secondary outcomes.
Single measure at both experimental sessions.

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Vyšetřovatelé

  • Vrchní vyšetřovatel: Sara L Kroll, Dr., Psychiatric University Hospital, Zurich

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

1. září 2026

Primární dokončení (Odhadovaný)

1. prosince 2026

Dokončení studie (Odhadovaný)

1. března 2028

Termíny zápisu do studia

První předloženo

5. srpna 2026

První předloženo, které splnilo kritéria kontroly kvality

19. srpna 2026

První zveřejněno (Aktuální)

21. srpna 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

21. srpna 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

19. srpna 2026

Naposledy ověřeno

1. srpna 2026

Více informací

Termíny související s touto studií

Další identifikační čísla studie

  • 2026-00586
  • PZ00P1_208759 (Jiné číslo grantu/financování: Swiss National Science Foundation)

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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