Opioid/Benzodiazepine Polydrug Abuse: Aim 3

NCT05006079 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB-21-07-3844
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators will measure affective, neurocognitive and behavioral outcomes related to chronic use of opioids and benzodiazepines (screening phase), and in response to the administration of the opioid morphine, the benzodiazepine alprazolam, morphine then alprazolam, alprazolam then morphine, morphine+alprazolam simultaneously, and placebo (laboratory pharmacology experiment). The latter will enable the investigators to assess the effects of an opioid alone, benzodiazepine alone, concurrent and simultaneous administration of opioid+benzodiazepine, relative to a placebo control.

Conditions

Opioid Abuse; Benzodiazepine Abuse; Polysubstance Abuse

Outcome Measures

Primary Outcomes (3)

• State anxiety

  State Trait Anxiety Inventory - state anxiety scale total score

  within-session peak change from pre-drug baseline to 15-120 min post-drug 1 and 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

• Positive affect

  Positive and Negative Affect Scale-Short Form (PANAS-SF) positive affect scale score

  within-session peak change from baseline to 15-120 min post-drug 1 and 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

• Negative affect

  Positive and Negative Affect Scale-Short Form (PANAS-SF) negative affect scale score

  within-session peak change from baseline to 15-120 min post-drug 1 and 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

Secondary Outcomes (16)

• Symbol matching performance task

  difference from placebo condition, measured within each session at 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

• Impulsivity performance task accuracy

  difference from placebo condition, measured within each session at 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

• Cognitive flexibility performance task

  difference from placebo condition, measured within each session at 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

• Cognitive inhibition performance task

  difference from placebo condition, measured within each session at 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

• Vigilance performance task

  difference from placebo condition, measured within each session at 15-240 min post-drug 2 administration; measured in each of the 6 laboratory sessions over about 3 weeks

Study Arms (6)

Placebo drug

PLACEBO COMPARATOR

Lactose, administered both at 9:30 am and 12:00 pm

Drug: Placebo

Morphine alone

ACTIVE COMPARATOR

15mg immediate-release oral morphine, administered both at 9:30 am and 12:00 pm

Drug: Morphine

Alprazolam alone

ACTIVE COMPARATOR

0.25mg oral alprazolam, administered at both 9:30 am and 12:00 pm

Drug: Alprazolam

Morphine then alprazolam

ACTIVE COMPARATOR

15mg oral morphine administered at 9:30 am, then 0.25mg oral alprazolam administered at 12:00 pm

Drug: Morphine; Drug: Alprazolam

Alprazolam then morphine

ACTIVE COMPARATOR

0.25mg oral alprazolam administered at 9:30 am, then 15mg oral morphine administered at 12:00 pm

Drug: Morphine; Drug: Alprazolam

Morphine+alprazolam simultaneously

ACTIVE COMPARATOR

morphine 15mg + 0.25mg alprazolam at 9:30 am, then morphine 15mg + 0.25mg alprazolam at 12:00 pm

Drug: Morphine; Drug: Alprazolam

Interventions

Morphine DRUG

immediate release oral 15mg dose

Alprazolam then morphine; Morphine alone; Morphine then alprazolam; Morphine+alprazolam simultaneously

Alprazolam DRUG

oral 0.25mg dose

Alprazolam alone; Alprazolam then morphine; Morphine then alprazolam; Morphine+alprazolam simultaneously

Placebo DRUG

Lactose

Placebo drug

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• must self-report past 10-year experience taking opioid and sedative drugs (for therapeutic or non-therapeutic reasons), but not necessarily at the same time. As an alternative to the sedative drug exposure requirement, participants must have used alcohol on at least 3 separate days during the past month. Participants may have current mild- or moderate-severity Opioid Use Disorder or current mild- or moderate-severity Sedative Use Disorder;
• must not be seeking treatment for their substance use problems;
• must be in current good overall health

You may not qualify if:

• meet DSM-5 criteria for current psychosis, bipolar disorder, or severe depression (i.e. severe psychiatric disorder);
• meet DSM-5 criteria for severe substance use disorder for any substance (e.g. Sedative, Opioid, Alcohol);
• past-month benzodiazepine or opioid prescription (which would suggest daily use, tolerance, or withdrawal upon cessation);
• report of past-year any-drug overdose or suicide attempt/ideation;
• exhibit cognitive impairment (IQ \< 80 on the Shipley Institute of Living Scale);
• body mass index \> 38 kg/m2;
• females who are pregnant (urine), lactating or heterosexually active (self-report) and not using medically approved birth control;
• treatment with methadone, buprenorphine or naltrexone;
• past 30-day use of contraindicated medications;
• alcohol-positive breath sample (\>.02% breath alcohol concentration);
• urine sample positive for methadone, cocaine, amphetamines, or barbiturates (\<300 ng/ml)
• intolerance of lactose

Sponsors & Collaborators

• Wayne State University: lead
• Henry Ford Health System: collaborator

Study Sites (1)

Tolan Park Medical Building

Detroit, Michigan, 48201, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Morphine; Alprazolam

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring

Study Officials

• Mark K Greenwald, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark K Greenwald, PhD

CONTACT

313-993-3965; mgreen@med.wayne.edu

Heidi Aguas

CONTACT

313-993-3960; gh7962@wayne.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: drug doses will be encapsulated, and placebo is included in the design
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division

Model Details: Repeated measures, placebo-controlled, randomized crossover

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: August 16, 2021
• Study Start: March 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)