How Stress Alters Opioid Drug Effects

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.

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.