Opioid/Benzodiazepine Polydrug Abuse

NCT03696017 | Recruiting

• 1 other identifier: Polydrug Aim 2
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Benzodiazepine (BZD)/opioid polysubstance abuse (PSA) dramatically increases risks of overdose, disability and death; however, little is known about phenotypes that could be targeted to decrease this use and these associated risks. The opioid abuse epidemic is generating unprecedented numbers of overdoses (OD) and deaths from prescribed and illegal sources (e.g. fentanyl combined with, or sold as, heroin). Yet, medical and epidemiological data suggest these adverse outcomes are not solely due to over-consumption of opioids.The FDA recognizes the health danger of BZD/opioid PSA, and issued labeling changes for prescribing BZDs and opioids. Impact of these changes is unclear and could be minimal if people obtain these substances illegally. BZD abuse can be harmful alone or combined with opioids, as BZDs: (a) contribute to OD/death e.g. 31% of opioid OD-related deaths from 1999 to 2011 were related to coincident BZD use, BZD co-use is dose-dependently related to mortality and rates of BZD OD deaths have sharply increased. (b) exacerbate progression and adverse outcomes of opioid abuse. and (c) worsen behavioral impairment from opioids, increase rates of falls and fractures, motor vehicle accidents, and sleep-disordered breathing. There has been limited systematic research of BZD/opioid PSA. This is a major gap because BZD are often co-prescribed with opioids (in 33 to 50% of cases) and are easily obtained illegally. In response to these problems, there is an urgent need to obtain population-level, clinical pharmacology, and mechanistic data to test our unified hypothesis of dual-deficit in affective/hedonic regulation.

Conditions

Polysubstance Abuse

Keywords

Opioid Abuse; Benzodiazepine abuse

Outcome Measures

Primary Outcomes (25)

• Psychopathology

  Semi-Structured Clinical Interview for DSM (Face-to-face interview) Evaluates lifetime and current psychiatric and substance use disorders.

  Administered once during the baseline clinical assessment.

• Beck Depression Inventory-II

  Questionnaire measure of current depression symptoms

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Snaith-Hamilton Pleasure Scale

  Questionnaire 14-item scale that measures anhedonia, the inability to experience pleasure. The items cover the domains of: social interaction, food and drink, sensory experience, and interest/pastimes. A score of 2 or less constitutes a "normal" score, while an "abnormal" score is defined as 3 or more. Each item has four possible responses: strongly disagree, disagree, agree, or strongly agree. Either of the "disagree" responses score one point, and either of the "agree" responses score 0 points.

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Perceived Stress Scale

  Questionnaire that measures the degree to which situations in one's life are appraised as stressful. Items were designed to assess how unpredictable, uncontrollable, and overloaded respondents find their lives to be. The scale also includes a number of direct queries about current levels of experienced stress.

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• State-Trait Anxiety Inventory

  Questionnaire that differentiates state anxiety from chronic trait anxiety symptoms.

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Difficulties with Emotion Regulation Scale

  36-item questionnaire measure of six facets of emotion regulation. Items are rated on a scale of 1 ("almost never \[0-10%\]") to 5 ("almost always \[91-100%\]"). Higher scores indicate more difficulty in emotion regulation. measures 6 empirically valid constructs related to emotion dysregulation: Non-acceptance of emotional responses, Difficulties in engaging in goal-directed behavior, Impulse control difficulties, Lack of emotional awareness, Limited access to emotion regulation strategies, and Lack of emotional clarity.

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Alcohol and Drug Use Self-Efficacy Scale

  Questionnaire assesses self-efficacy and responses to high-risk situations that can trigger substance use.Items are grouped into negative affect, social positive withdrawal/urges, and physical/other concerns; subjects indicate how "tempted" and "confident" they would be in each situation.

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Distress Tolerance Scale

  Questionnaire measure of emotional distress tolerance

  Administered once during the clinical assessment.

• Positive and Negative Affect Schedule-Short Form: Positive Affect

  Questionnaire: 10-item measure of Positive Affect

  Administered once during the baseline clinical assessment.

• Positive and Negative Affect Schedule-Short Form: Negative Affect

  Questionnaire: 10-item measure of Negative Affect

  Administered once during the baseline clinical assessment.

• Paced Auditory Serial Addition Task

  mental arithmetic task with 3 trial blocks of increasing difficulty. Subjects can escape the task during block 3; latency (sec) to task termination is a primary outcome.

  Administered once during the baseline clinical assessment.

• Brief Pain Inventory-Short Form

  Questionnaire measures pain severity (0=no pain; 10=pain as bad as you can imagine) and its functional impact (0=no interference; 10= interferes completely).

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Current Opioid Misuse Measure

  Questionnaire measures risk of opioid misuse

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Insomnia Severity Index

  Questionnaire asks about problem severity of sleep-onset, sleep-maintenance, early morning awakening, sleep satisfaction, interference with daily function, perceived impairment, and level of distress from insomnia. It has good internal consistency and concurrent validity (with polysomnography, sleep diaries, and clinician or significant-other reports), making it a valid and reliable measure of perceived sleep disturbance.

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit.

• Epworth Sleepiness Scale

  Questionnaire measures 'sleep propensity', i.e. recent likelihood of dozing or falling asleep (rather than just feeling tired) in several situations.

  Administered once during the baseline clinical assessment.

• Psychomotor Vigilance Task

  computerized, adaptive task (reaction time to a visual stimulus presented at random inter-trial intervals \[ITI\]) that will be used to assess attentional lapses; this objective, validated measure of sleepiness.

  Administered once during the baseline clinical assessment.

• Go/No-Go Task

  Immediate and Delayed Memory Task assesses response inhibition. Participants are told to press a button to respond to stimulus X or Y presented in an alternating pattern (Go) and to withhold responding when the pattern is broken (No-Go). We will use percentage of correctly inhibited responses for each presentation.

  Administered once during the baseline clinical assessment.

• California Verbal Learning Test-Revised

  Immediate and delayed memory will be assessed.

  Administered once during the baseline clinical assessment.

• Emotional Stroop Task

  reaction time assessment of attentional bias for both emotion-related words

  Administered once during the baseline clinical assessment.

• Wisconsin Card Sort Test

  number of items correct, measuring ability to shift or maintain cognitive set

  Administered once during the baseline clinical assessment.

• Digit Symbol Substitution Test

  Psychomotor processing speed and associative ability will be assessed.

  Administered once during the baseline clinical assessment.

• Drug History Questionnaire

  assesses lifetime substance use (e.g. age of initial and regular use, sequence of use of opioids and BZDs, adverse consequences of use, quit attempts.

  Administered once during the baseline clinical assessment.

• Timeline Followback interview

  Assesses all substance use over the past 30 days; this will generate detailed data on patterns of opioid, BZD and alcohol use (e.g. simultaneous vs. concurrent, including customized queries to determine whether using one drug primes use of another, under what affective conditions (positive, neutral, negative) substances are used together, and number of days since last use (which could influence affective, neurocognitive or behavioral measures).

  Administered during the baseline clinical assessment, and at the 3-month follow-up visit

• Opioid /Benzodiazepine Purchasing Task

  Hypothetical purchasing tasks (economic simulations) will assess drug demand. will be tailored to each subject's preferred opioid (e.g. heroin, oxycodone, hydrocodone) or benzodiazepine based on screening self-report.

  Administered once during the baseline clinical assessment.

• Urinalysis

  One urine sample will be collected and tested for opioids, methadone, cocaine, amphetamines, barbiturates, and cannabinoids using a 6-panel CLIA waived drug test. The urine sample will be collected into multi-test cups with temperature strips (CLIA Waived; temperature must be 92-96º F). Samples will be tested for opioids, methadone, cocaine, amphetamines, barbiturates (negative cutoff \<300 ng/ml), and cannabinoids (negative cutoff \< 50ng/ml).

  At baseline clinical assessment, and at the 3-month follow-up visit

Study Arms (3)

Group 1

Patients either newly admitted to Substance Use Disorder treatment in Wayne County, or in treatment longer but are using opioids (40 patients per group).

Other: Multi-domain assessment battery

Group 2

Patients either newly admitted to Substance Use Disorder treatment in Wayne County, or in treatment longer but are using benzodiazepines (BZD) (40 patients per group).

Other: Multi-domain assessment battery

Group 3

Patients either newly admitted to Substance Use Disorder treatment in Wayne County, or in treatment longer but are using BZD/opioid (40 patients per group).

Other: Multi-domain assessment battery

Interventions

Multi-domain assessment battery OTHER

Assessments of emotion regulation, neurocognitive performance, pain, sleep, and substance use. There is no therapeutic intervention; all participants are already independently in treatment for their substance use disorder and we are simply assessing them at baseline visit and 3-month follow-up.

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will either be newly admitted to Substance Use Disorder treatment, or in treatment longer but still occasionally using substances.

You may qualify if:

• Recently admitted and/or not clinically stable in treatment for Substance Use Disorder (SUD) in Wayne County
• Using opioids, benzodiazepines (BZD), or BZD/opioid.

You may not qualify if:

• Participants with current psychosis, bipolar disorder, or severe depression (i.e. severe psychiatric disorder)
• Individuals with serious neurological disorders, e.g. brain tumor, history of stroke, history of traumatic brain injury w/ loss of consciousness
• Cognitive impairment (IQ\<80)

Sponsors & Collaborators

• Wayne State University: lead

Study Sites (1)

Tolan Park Medical Building

Detroit, Michigan, 48201, United States

RECRUITING

Related Publications (1)

• Greenwald MK, Moses TEH, Lundahl LH, Roehrs TA. Anhedonia modulates benzodiazepine and opioid demand among persons in treatment for opioid use disorder. Front Psychiatry. 2023 Jan 19;14:1103739. doi: 10.3389/fpsyt.2023.1103739. eCollection 2023.

  PMID: 36741122 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

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

Study Officials

• Mark Greenwald, PhD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heidi Aguas

CONTACT

3139933960; gh7962@wayne.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: October 4, 2018
• Study Start: February 8, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

US (1)