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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)

2026年8月19日 更新者：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.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

72

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人

接受健康志愿者

是的

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：基础科学
  • 分配：随机化
  • 介入模型：交叉作业
  • 屏蔽：双倍的

武器和干预

参与者组/臂
干预/治疗
有源比较器：Morphine
Participants receive the active drug (morphine) on Visit 1or Visit 2.
药品：Morphine
Sevredol 10mg, oral single-dose administration
安慰剂比较：Placebo
Participants receive the non-active comparator (placebo) on Visit 1 or Visit 2.
药品：Placebo
identical in appearance to active drug, containing no active substance (mannitol), oral one-time administration

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Self-report of subjective stress during stress exposure
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：~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
大体时间：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
大体时间：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

次要结果测量

结果测量
措施说明
大体时间
Subjective differences in experiencing social interaction
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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)
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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.

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Sara L. Kroll

调查人员

  • 首席研究员：Sara L Kroll, Dr.、Psychiatric University Hospital, Zurich

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年9月1日

初级完成 (估计的)

2026年12月1日

研究完成 (估计的)

2028年3月1日

研究注册日期

首次提交

2026年8月5日

首先提交符合 QC 标准的

2026年8月19日

首次发布 (实际的)

2026年8月21日

研究记录更新

最后更新发布 (实际的)

2026年8月21日

上次提交的符合 QC 标准的更新

2026年8月19日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 2026-00586
  • PZ00P1_208759 (其他赠款/资助编号：Swiss National Science Foundation)

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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