How Stress Alters Opioid Drug Effects

NCT06485817 | Completed DMC

• 2 other identifiers: 802885https://osf.io/bcxv8
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Motivation; Drug Effect; Stress Reaction; Misuse, Opioid

Outcome Measures

Primary Outcomes (3)

• Amount of oxycodone self-administered in the behavioral drug wanting task relative to the first sampling dose (0-125%).

  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.

  Single measure: final task result ~22 minutes after sampling dose

• Self-report of oxycodone wanting relative to the first sampling dose (0-125 %)

  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".

  Single measure: ~20 minutes after sampling dose

• Self-reported drug wanting from "drug effects questionnaire".

  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.

  From the drug administration until the start of the self-administration task (~15 minutes)

Secondary Outcomes (6)

• 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).

• 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

• 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)

• 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)

• Drug effects questionnaire (DEQ)

  From the drug administration until the start of the self-administration task (~15 minutes)

Study Arms (4)

Placebo_Control

PLACEBO COMPARATOR

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.

Drug: Placebo; Behavioral: Control State Induction

Oxycodone_Control

ACTIVE COMPARATOR

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.

Drug: Oxycodone; Behavioral: Control State Induction

Placebo_Stress

ACTIVE COMPARATOR

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.

Drug: Placebo; Behavioral: Stress State Induction

Oxycodone_Stress

EXPERIMENTAL

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.

Drug: Oxycodone; Behavioral: Stress State Induction

Interventions

Oxycodone DRUG

3.1mg oxycodone/70 kg body weight was administered as the main drug intervention. Based on body weight, the study nurse/anesthetist adjusted the (unknown) content in two syringes by removing enough fluid to reach a volume that would result in a dose equivalent of 3.1mg/70kg (0,043 mg/ml pr kg) should the syringes contain oxycodone. The first dose was administered 5 minutes after the state induction task. The second dose was adjusted according to the performance on the self-administration task (but maximum 100% of the first dose) and administered 45 later.

Oxycodone_Control; Oxycodone_Stress

Placebo DRUG

Pure saline was administered as the placebo condition. Based on body weight, the study nurse/anesthetist adjusted the (unknown) content in two syringes by removing enough fluid to reach a volume that would result in a dose equivalent of 3.1mg/70kg (0,043 mg/ml pr kg) should the syringes contain oxycodone. The first dose was administered 5 minutes after the state induction task. The second dose was adjusted according to the performance on the self-administration task (but maximum 100% of the first dose) and administered 45 later.

Also known as: Saline

Placebo_Control; Placebo_Stress

Stress State Induction BEHAVIORAL

ReSST is an in-house hybrid online-lab implementation of two stress induction paradigms based on the Trier Social stress test (TSST) and Iowa Social Singing Stress Test (I-SSST). The set-up was tailored to allow repeated stress induction without diminishing effects that allowed for an online experiment panel. Stress and control state inductions were administered every-other session. The singing version of the stress test was always administered last as it was deemed more stressful during piloting.

Also known as: ReSST (Repeatable Social Stress Test): Stress

Oxycodone_Stress; Placebo_Stress

Control State Induction BEHAVIORAL

Two different control tasks matched to the stress conditions on key parameters outlined in the protocol.

Also known as: ReSST (Repeatable Social Stress Test): Control

Oxycodone_Control; Placebo_Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oslo: lead
• Oslo University Hospital: collaborator
• Linkoeping University: collaborator

Study Sites (1)

University of Oslo

Oslo, 0317, Norway

Location

Related Links

• Time locked preregistration prior to data collection

MeSH Terms

Conditions

Fractures, Stress; Opioid-Related Disorders

Interventions

Oxycodone; Sodium Chloride

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Siri Leknes, PhD

  University of Oslo

  PRINCIPAL INVESTIGATOR

• Marie Eikemo, PhD

  University of Oslo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Experimenters, care providers (nurses/physicians) and participants were blinded to both the stress induction condition and the drug in all sessions.
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator

Model Details: Cross-over 2\*2 design Drug (i.v. oxycodone/placebo) State induction (stress/control)

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: July 3, 2024
• Study Start: November 15, 2021
• Primary Completion: April 28, 2022
• Study Completion: April 28, 2022
• Last Updated: July 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: The data will be released with the publication. The code, protocol, and supplementary materials have been released in the project repository.
• Access Criteria: none. For conditional access to health/sensitive data following publication contact the corresponding author (marie.eikemo@psykologi.uio.no) A data use agreement may also be required.

Locations

NO (1)