How Stress Alters Opioid Drug Effects

Not Applicable

Completed

• Conditions: Motivation; Drug Effect; Stress Reaction; Misuse, Opioid
• Interventions: Drug: Placebo; Drug: Oxycodone; Behavioral: Control State Induction; Behavioral: Stress State Induction

• Registration Number: NCT06485817
• Lead Sponsor: University of Oslo

Brief Summary

The main objective of the study is to test the hypothesis that opioid drug effects vary as a function of pre-drug affective state. Specifically, it is hypothesized that social stress induction enhances opioid drug wanting compared a non-stress control condition.

Detailed Description

Healthy participants complete four experiment sessions in a placebo-controlled, double-blind, randomized repeated-measures psychopharmacological study. Participants completed four combinations of pre-drug state induction (social stress or no-stress) and drug (intravenous oxycodone or saline).

Temporary and reversible social stress is induced using the Repeatable Social Stress Test (ReSST) which enables repeated administrations of stress-inductions. Across four sessions participants experience two carefully tailored tasks to provoke the experience of social evaluative threat and two non-stressful control tasks.

After each state inductions, participants receive an injection of opioid drug or saline. After a drug absorption phase and viewing of a state reinstatement video designed to evoke a mild form of social evaluative threat participants perform a drug-self-administration test to determine the potency of a second dose.

Self-reported affect, mental and physiological state and drug effects are assessed throughout the session.

Study Timeline

• Study Start: 2021-11-15
• Primary Completion: 2022-04-28
• Study Completion: 2022-04-28
• Study First Submitted: 2024-06-07
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-01
• Last Update Submitted: 2024-07-02
• Study First Posted: 2024-07-03
• Last Update Posted: 2024-07-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Mentally and physically healthy
• Body mass index (BMI) in the healthy range (18.5 < BMI < 30)
• Normal or corrected vision
• Had received an opioid drug at least once in their lifetime (to ensure no severe adverse or allergic reactions).

Exclusion Criteria

• Any significant physical health problem (e.g., heart, lung, kidney, liver, and other conditions)
• Current or past substance use problems
• Current mental health problems
• Past mental health problems beyond mild episodic anxiety or depression
• Social anxiety or fear of public speaking
• Past or current chronic pain
• Pregnancy or breastfeeding
• Recent use of any contraindicating medications
• Prior difficulty in providing blood samples.

All exclusion criteria required a 'yes' or 'no' response from participants. Participants were also asked to report any illnesses or medical conditions that were not covered by the questions in the clinical interview. Mental health and substance use were assessed during the clinical interview using the Mini-International Neuropsychiatric Interview (MINI). The interview required binary responses to questions regarding a wide range of psychological symptoms relevant for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) and ICD-10 (International Classification of Diseases) psychiatric disorders. Interviewers then used the pre-defined cut offs relevant to the severity of symptoms for each psychiatric disorder to assist the clinical judgement.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo_Control	Placebo	Control state induction: Participants answer simple questions about their color or music preferences in a hybrid (zoom-lab) session with a friendly experimenter (The Repeatable Social Stress Test (ReSST) control conditions). Drug administration: A sampling dose of intravenous (i.v.) saline administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of saline (0-100% of the initial sampling dose) determined by a behavioral self-administration task.
Placebo_Control	Control State Induction	Control state induction: Participants answer simple questions about their color or music preferences in a hybrid (zoom-lab) session with a friendly experimenter (The Repeatable Social Stress Test (ReSST) control conditions). Drug administration: A sampling dose of intravenous (i.v.) saline administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of saline (0-100% of the initial sampling dose) determined by a behavioral self-administration task.
Oxycodone_Control	Control State Induction	Control state induction: Participants answer simple questions about their color or music preferences in a hybrid (zoom-lab) session with a friendly experimenter. (The Repeatable Social Stress Test (ReSST) control conditions). Drug administration: A sampling dose of i.v. oxycodone administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of oxycodone (0-100% of the initial sampling dose) determined by a behavioral self-administration task.
Placebo_Stress	Placebo	State induction: Stress The Repeatable Social Stress Test (ReSST) was used to induce psychosocial stress (mock job talk in stress session 1 and singing task in stress session 2). Drug administration: A sampling dose of i.v. saline administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of saline (0-100% of the initial sampling dose) determined by a behavioral self-administration task.
Placebo_Stress	Stress State Induction	State induction: Stress The Repeatable Social Stress Test (ReSST) was used to induce psychosocial stress (mock job talk in stress session 1 and singing task in stress session 2). Drug administration: A sampling dose of i.v. saline administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of saline (0-100% of the initial sampling dose) determined by a behavioral self-administration task.
Oxycodone_Stress	Stress State Induction	State induction: Stress ReSST was used to induce psychosocial stress (mock job talk in stress session 1 and singing task in stress session 2). Drug administration: A sampling dose of i.v. oxycodone administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of oxycodone (0-100% of the initial sampling dose) determined by a behavioral self-administration task.
Oxycodone_Control	Oxycodone	Control state induction: Participants answer simple questions about their color or music preferences in a hybrid (zoom-lab) session with a friendly experimenter. (The Repeatable Social Stress Test (ReSST) control conditions). Drug administration: A sampling dose of i.v. oxycodone administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of oxycodone (0-100% of the initial sampling dose) determined by a behavioral self-administration task.
Oxycodone_Stress	Oxycodone	State induction: Stress ReSST was used to induce psychosocial stress (mock job talk in stress session 1 and singing task in stress session 2). Drug administration: A sampling dose of i.v. oxycodone administered over 15 seconds through a venous catheter after the state induction. 45 minutes later participants receive the second dose of oxycodone (0-100% of the initial sampling dose) determined by a behavioral self-administration task.

Primary Outcome Measures

Name	Time	Method
Amount of oxycodone self-administered in the behavioral drug wanting task relative to the first sampling dose (0-125%).	Single measure: final task result ~22 minutes after sampling dose	The number corresponds to the achieved cursor placement on a vertical electronic scale indicated desired effect intensity from second dose relative to the first (sampling) dose. Cursor placement depends on the amount of effort exerted (keyboard presses) and the task difficulty adapted to performance. The task ended abruptly after 2 minutes.
Self-reported drug wanting from "drug effects questionnaire".	From the drug administration until the start of the self-administration task (~15 minutes)	Drug effects questionnaire (DEQ) take again item indicated on a 0-100 electronic Visual analogue scale (VAS) at two survey timepoints after the drug administration. Anchors were 'neutral' and 'very much'. Average rating was used.
Self-report of oxycodone wanting relative to the first sampling dose (0-125 %)	Single measure: ~20 minutes after sampling dose	Self-reported target effect intensity was indicated on a vertical scale at the onset of the behavioral drug wanting task before the effortful part of the task.; Anchors visible to to participants were: "no effect/drug", "half the effect", "same effect", "a little stronger effect than the first drug dose". Numerically the scale anchors were 0-125 (VAS) where 100 corresponded to the "same effect".

Secondary Outcome Measures

Name	Time	Method
Stress response 1: increase in self-reported stress to the primary stress induction and subsequent stress reinstatement (as compared to control tasks).	From the measure before state induction until the end of the state induction (~20 minutes).	Change in ratings on the item "feeling stressed" measured on a 0-100 Visual Analogue Scale (VAS) The following items were collected to assess stress effects: anxious, self-conscious, embarrassed, vulnerable, happy, relaxed, irritable, confident, shaky, distressed, flushed face, heart palpitations, stomach discomfort, dizzy (to stress on a 0-100 VAS) and report this in the supplementary materials.
Stress response 2: increase in physiological stress measured by heart rate (beats per minute: BMP) induced by the primary stress induction.	Data from 20 minutes before to 20 minutes after the middle of the stress induction were used to estimate the heart rate increase	Heart rate change during the state induction compared to the time period before state induction.
Stress response 3: change in endocrine stress response measured by cortisol induced by the primary stress induction.	Throughout the experiment session (~3 hours, 6 samples)	Estimates of plasma cortisol levels changes from the baseline (2 blood samples) to the samples after the state induction (4 blood samples).
Changes in positive and negative affect after the state manipulations (induction and reinstatement) and drug administrations	From immediately before to immediately after the state induction (~20 minutes)	Select items from the PANAS based on pilot data. Baseline measures are collected several times before the state induction. Items were rated on a 0-100 Visual Analogue Scale (VAS).; Negative affect (mood) items = "distressed", "anxious", "vulnerable", "irritable" Positive affect (mood) items = "good", "happy", "confident", "safe", "relaxed"; Composite ratings from all measures collected throughout each session (k=11 measures) will be reported as descriptive information.
Drug effects questionnaire (DEQ)	From the drug administration until the start of the self-administration task (~15 minutes)	Drug effect, liking and disliking was measured using items from the Drug Effects Questionnaire (DEQ; 'Feel effect', 'Like effect', 'Dislike effect') measured on an electronic 0-100 VAS, anchors 'neutral' and 'very much'.
Side effects	From the drug administration until the start of the self-administration task (~15 minutes)	To assess the overall drug- and side effects, the following items were collected on a 0-100 electronic VAS: feeling high, blunted and dizzy.; Additional items will be explored and reported where relevant and in the supplementary materials (feeling good, euphoric, indifferent, safe, dry mouth, nauseous, "not like myself").

Trial Locations

Locations (1)

University of Oslo; 🇳🇴 Oslo, Norway