Clinical trial NCT06485817: How Stress Alters Opioid Drug Effects
Official title: How Distress Alters Opioid Drug Effects and Abuse Liability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Motivation
Drug Effect
Stress Reaction
Misuse, Opioid
Lead sponsor: University of Oslo
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
name: Linkoeping University
First posted: 2024-07-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Cross-over 2\*2 design Drug (i.v. oxycodone/placebo) State induction (stress/control)
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Amount of oxycodone self-administered in the behavioral drug wanting task relative to the first sampling dose (0-125%).
timeFrame: Single measure: final task result ~22 minutes after sampling dose
measure: Self-report of oxycodone wanting relative to the first sampling dose (0-125 %)
timeFrame: Single measure: ~20 minutes after sampling dose
measure: Self-reported drug wanting from "drug effects questionnaire".
timeFrame: From the drug administration until the start of the self-administration task (~15 minutes)
Secondary outcomes:
measure: Stress response 1: increase in self-reported stress to the primary stress induction and subsequent stress reinstatement (as compared to control tasks).
timeFrame: From the measure before state induction until the end of the state induction (~20 minutes).
measure: Stress response 2: increase in physiological stress measured by heart rate (beats per minute: BMP) induced by the primary stress induction.
timeFrame: Data from 20 minutes before to 20 minutes after the middle of the stress induction were used to estimate the heart rate increase
measure: Stress response 3: change in endocrine stress response measured by cortisol induced by the primary stress induction.
timeFrame: Throughout the experiment session (~3 hours, 6 samples)
measure: Changes in positive and negative affect after the state manipulations (induction and reinstatement) and drug administrations
timeFrame: From immediately before to immediately after the state induction (~20 minutes)
measure: Drug effects questionnaire (DEQ)
timeFrame: From the drug administration until the start of the self-administration task (~15 minutes)
measure: Side effects
timeFrame: From the drug administration until the start of the self-administration task (~15 minutes)
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: University of Oslo
Study officials:
affiliation: University of Oslo
name: Siri Leknes, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oslo
name: Marie Eikemo, PhD
role: PRINCIPAL_INVESTIGATOR
References: