Opioid AbusePhase 2MAPNCT05006079
Opioid/Benzodiazepine Polydrug Abuse: Aim 3
A Phase 2 study testing Morphine and Alprazolam in people with Opioid Abuse and Benzodiazepine Abuse, run by Wayne State University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Abuse, Benzodiazepine Abuse, Polysubstance Abuse
- What is being tested?
- Morphine and Alprazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2024to Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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);
- neurological, cardiovascular, pulmonary, or systemic diseases (see specific exclusionary conditions under Protection of Human Subjects);
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Tolan Park Medical Building
Detroit, Michigan, 48201
Mark Greenwald, PhD, 313-993-3965, mgreen@med.wayne.edu
About this study
Official title: Opioid/Benzodiazepine Polydrug Abuse: Integrating Research on Mechanisms, Treatment and Policies - Study 3
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.
Read the detailed description
The investigators propose that benzodiazepine/opioid polysubstance abuse is perpetuated by a dual-deficit in affective/hedonic regulation (difficulties modulating emotional reactions relative to the context and the person's long-term goals). Furthermore, the investigators propose that this dual-deficit biases neurocognition (interferes with executive function) and behaviors (guided by negative reinforcement processes such that polysubstance use acutely blunts aversive states and directs actions away from natural rewards). The scientific premise for this project builds on George Koob's foundational concept that addiction is a 'reward-deficit/stress-surfeit disorder'. There is an urgent need to obtain clinical pharmacology and mechanistic data to test this hypothesis of dual-deficit in affective/hedonic regulation. This study will use human laboratory methods to test affective, neurocognitive and behavioral mechanisms that maintain benzodiazepine/opioid polysubstance abuse.
The screening phase of this human laboratory study will include measures of affective dysregulation related to benzodiazepine/opioid polysubstance use behaviors. These include distress tolerance, pain sensitivity and nocebo responding, and biomarkers (e.g. plasma cortisol). Also, the investigators will include behavioral measures of drug and non-drug reinforcement (e.g. economic simulations of price elasticity of alprazolam and morphine) and neurocognition (e.g. drug attentional bias, response inhibition, cognitive flexibility).
During the pharmacology study the investigators will administer oral placebo, morphine alone and alprazolam doses alone, as well as morphine and alprazolam sequentially (in counterbalanced order) and simultaneously. Following each drug administration, the investigators will measure responses in affective (e.g. anxiety levels, distress tolerance), neurocognitive (e.g. executive function, learning) and behavioral domains (e.g. impulsivity, psychomotor function, reinforcer preferences). The lab study is highly significant because we lack prospective, controlled, dose-response studies that identify whether opioids, benzodiazepines, and their combination modulate core phenotypes that underlie this harmful polysubstance abuse. Testing effects of both sequential and simultaneous benzodiazepine/opioid administration within the same individuals will establish a firm foundation for understanding which phenotypes are sensitive to disruption and may respond to treatment.
Findings from this study will help to focus clinical assessment and identify mechanisms that maintain benzodiazepine/opioid polysubstance abuse, toward the development of novel medication-assisted, evidence-based psychosocial interventions.
- Conditions
- Opioid Abuse, Benzodiazepine Abuse, Polysubstance Abuse
- Being tested
- Morphine, Alprazolam, Placebo
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
immediate release oral 15mg dose
AlprazolamDrug
oral 0.25mg dose
PlaceboDrug
Lactose
| Study group | Role | What they receive |
|---|---|---|
| Placebo drug | Placebo comparator | Lactose, administered both at 9:30 am and 12:00 pm Receives: Drug: Placebo |
| Morphine alone | Active comparator | 15mg immediate-release oral morphine, administered both at 9:30 am and 12:00 pm Receives: Drug: Morphine |
| Alprazolam alone | Active comparator | 0.25mg oral alprazolam, administered at both 9:30 am and 12:00 pm Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Morphine; Drug: Alprazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
State anxiety
State Trait Anxiety Inventory - state anxiety scale total score
Measured: 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
Measured: 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
Measured: 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
Digit Symbol Substitution Task (DSST) symbol matching total score
Measured: 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
Go/No task percentage of trials correct
Measured: 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
Wisconsin Card Sorting Task (WCST) percentage of trials correct
Measured: 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
Addiction Stroop Task, reaction time to drug vs. neutral words presented in different colors
Measured: 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
Psychomotor Vigilance Task (PVT) average reaction time
Measured: 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
Hypothetical drug purchasing questionnaire
Intensity and elasticity of drug demand. This is measured by having the participant make a series of independent choices as to how many drug units s/he will purchase across a range of (low to high) unit prices. Demand intensity is the drug purchase amount at the lowest non-zero price. Demand intensity is the calculated point on the price/purchasing curve where the slope (in log/log space) equals -1 (i.e. 'tipping point' where purchasing decreases more rapidly than the rate of increase in drug price).
Measured: 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
Preference for natural reinforcement choice procedure
Number of choices for money vs. avoiding listening to soundtrack of crying babies
Measured: 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
Monetary delay discounting questionnaire
Participants are asked to make a series of independent choices (preferences) for delayed larger amounts of money vs. smaller immediate amounts of money. The outcome is the rate at which future choice value is discounted, measured by area under the time-delay curve
Measured: 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
Respiration rate
Breaths per minute, measured by behavioral observation
Measured: 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
Oxygen saturation
Percentage oxygen saturation, measured by photoplethysmograph
Measured: 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
Heart rate
Pulse rate (beats per minute), measured by photoplethysmograph
Measured: 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
Blood pressure
Systolic and diastolic blood pressure (mm Hg)
Measured: 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
Pupil diameter
Pupil size (mm), measured by digital photography
Measured: 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
Drug effect visual analog scale (VAS) ratings
0-100 scale ratings of alert, difficulty concentrating, clumsy, confused, forgetful, blurred vision, dizzy, heaviness in limbs, mellow, yawning, stimulated, sedated, sleepy, tired, energetic, self-confident, dreamy, floating, sluggish, tingling, high, liking, good drug effect, bad drug effect
Measured: 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
Drug craving visual analog scale (VAS) ratings
0-100 scale rating of "want to take drug again", "desire to use", and "craving" for opioids, sedatives, alcohol, cigarettes, marihuana, and cocaine
Measured: 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
Sleep efficiency
Percentage of sleep time (time asleep divided by time in bed), measured using WatchPat device
Measured: difference from placebo condition, measured on an outpatient basis during the evening after each laboratory drug administration; measured after each of the 6 laboratory sessions over about 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2021
- Study start13 Mar 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid AbuseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Repeated measures, placebo-controlled, randomized crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- Henry Ford Health System
- Responsible party
- Principal investigator, Mark Greenwald, PhD, Wayne State University
- Investigators
- Mark K Greenwald, PhD, Principal investigator, Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05006079
- Sponsor's protocol ID
- IRB-21-07-3844
- Acronym
- MAP
- Status last verified
- Dec 2025
- First submitted
- 4 Aug 2021
- Last updated
- 30 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared.