An interventional study of Morphine and Placebo in Stress, Early Life Stress and Sex Differences, sponsored by Sara L. Kroll. Recruiting at 1 site in Switzerland. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Sara L. Kroll · Not applicable, Interventional, and Basic science
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.
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.
844 studies on the registry are indexed under Stress, Psychological; 136 are open to participants now.
This study's planned enrollment of 72 is below the median of 84 across 688 interventional studies indexed under Stress, Psychological.
Browse Stress, Psychological studies →This is the only study on the registry with Sara L. Kroll as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive the active drug (morphine) on Visit 1or Visit 2.
Drug: Morphine
Participants receive the non-active comparator (placebo) on Visit 1 or Visit 2.
Drug: Placebo
Sevredol 10mg, oral single-dose administration
identical in appearance to active drug, containing no active substance (mannitol), oral one-time administration
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.
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 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"
Time frame: 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.
Time frame: ~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.
Time frame: 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.
Time frame: Prior to enrollment
Subjective differences in experiencing social interaction
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.
Time frame: During the experimental tasks
Behavioural differences of social approach and avoidance
Sex-specific differences in morphine effects on behavioural measures (measured by number of button presses) during the social approach/avoidance task.
Time frame: During the experimental task
Psychophysiological cardiac markers of social interaction measured by heart rate using electrocardiogram
Sex-specific differences in morphine effects on heart rate (beats per minute) during the social approach/avoidance task and the affective touch task.
Time frame: During the experimental tasks
Psychophysiological cardiac markers of social interaction measured by heart rate variability using electrocardiogram
Sex-specific differences in morphine effects on heart rate variability during the social approach/avoidance task and the affective touch task.
Time frame: During the experimental tasks
Psychophysiological measure of sympathetic activity during social interaction
Sex-specific differences in morphine effects on skin conductance response (SCR) during the social approach/avoidance task and the affective touch task.
Time frame: During the experimental tasks.
State anxiety over time
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
Time frame: 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)
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".
Time frame: Throughout the experimental sessions (immediately after drug administration until approx. 3 hours after study medication administration, 7 times).
Drug concentration
Differences in concentration of the study drug in blood between the two test sessions.
Time frame: 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
Sex-specific differences in morphine effects on oxytocin levels measured in saliva.
Time frame: 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
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.
Time frame: Prior to enrollment
Hair concentrations of chronic stress markers
Modulation of tonic endocannabinoid (2-AG, AEA, OEA, PEA, SEA) and glucocorticoid (cortisol, cortisone, ACTH) concentrations in hair on primary and secondary outcomes.
Time frame: At screening
Personality traits
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.
Time frame: Single measure, during experimental session
Trait assessment of loneliness
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.
Time frame: Single measure, during experimental session
Rosenberg Self Esteem Scale
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.
Time frame: Single measure, during experimental session.
Brief Resilience Scale
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.
Time frame: Single measure, during experimental session.
Becker Depression Inventory
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.
Time frame: Single measure, during experimental session.
Trait anxiety level
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.
Time frame: Single measure, during experimental session.
Snaith Hamilton Anhedonia Pleasure Scale
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.
Time frame: Single measure, during experimental session.
Relationship Structures Questionnaire
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.
Time frame: Single measure, during experimental session.
Socioeconomic status ladder
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.
Time frame: Single measure, during experimental session.
Sex hormone concentration
Modulation of baseline concentrations of steroid sex hormones (testosterone, progesterone, estradiol) in plasma on primary and secondary outcomes.
Time frame: Single measure at both experimental sessions.
Started Sep 2026 (actual). Primary completion is estimated for Dec 2026, 3 months after the start.
Of 457 non-industry interventional studies with no phase under Stress, Psychological, half reached primary completion within 13 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 26. This study's planned 3 months is below that.
Counting every sponsor, half of 470 studies reached it within 13 months; a quarter within 5 and three quarters within 26.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Morphine