The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 than HIV/AIDS at the height of that epidemic. Medication assisted treatment, including methadone and buprenorphine, is the standard of care for the treatment of opioid use disorder (OUD). However, chronic pain can reduce treatment efficacy during medication assisted treatment and is associated with illicit substance relapse, dropout, and subsequent overdose. Mechanisms by which chronic pain may influence the impulsive decision making (e.g., drug relapse) in persons with OUD have not been well characterized. A better understanding is needed of decision-making in this population. Two factors that can influence decisions to use drugs are impulsivity and acute opioid withdrawal. This proposal will test how chronic pain is associated with increases in impulsive decision making in OUD, whether impulsive decision making is greater when undergoing opioid withdrawal, and how catastrophizing may modify the association between withdrawal and impulsive decision making in patients with chronic pain and OUD. An ideal population for this developmental research project are methadone maintained patients, who show high treatment attendance rates and will therefore assure study efficiency and reliable completion.
This is an outpatient Phase 1 clinical trial investigating the effect of naloxone precipitated withdrawal on delay discounting. Eligible participants will undergo two experimental sessions presented in random order. One session will involve the measurement of delay discounting 30 minutes after double-blind intramuscular (IM) administration of placebo (normal saline) and the other will have the exact same procedures performed after double-blind IM administration of naloxone (0.1 mg). Injections will occur 2 hours after methadone dosing (peak levels). Study sessions will last 2 hours and involve pain and opioid withdrawal measures assessed at baseline and 15 minute intervals after injections. The participant should be back to baseline and free of withdrawal by the end of the study session. Sessions will occur at least 48 hours apart.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
10
An intramuscular (IM) injection of naloxone will be given.
An IM injection of 0.9% normal saline will be given.
Zuckerberg San Francisco General Hospital
San Francisco, California, United States
Delay Discounting of Money Rate (k)
Delay discounting is the relative preference for smaller sooner over larger later rewards, an aspect of impulsivity. Most individuals would prefer an immediate $100 over $100 delayed by 1 year. However, when faced with the choice between receiving $95 now versus $100 in 1 year, preferences for the delayed reward may increase. By assessing such choices across multiple delays, delay discounting quantifies the devaluation of rewards over time, which allows for an index of overall discounting rate (k). Delay Discounting of money rate has no units and values can go from 0-infinity. A larger discount rate indicates that a future reward is devalued more, and is associated with more impulsive behavior.
Time frame: k will be calculated from the same series of discounting questions that will be asked once each session at approximately 30 minutes after study medication administration.
Study Session Peak Pain Visual Analog Scale (VAS)
Current pain level rated on 0-100 VAS. This is the validated pain scale typically used by clinicians in an outpatient or inpatient clinical visit to represent current level of pain. Higher ratings indicate worse pain severity.
Time frame: Peak Pain VAS will be the highest rating during each 2 hour study session.
Peak Clinical Opiate Withdrawal Scale (COWS) Rating
The COWS is an 11-item validated clinician administered scale that quantifies level of opioid withdrawal. The range of scores is 0-48, with higher scores indicating greater withdrawal severity. The peak COWS rating will be the highest measurement in the session after study drug administration.
Time frame: Peak COWS rating will be the highest rating during each 2 hour study session.
Peak Subjective Opiate Withdrawal Scale (SOWS) Rating
The SOWS is a 16 item validated self-administered scale for grading opioid withdrawal symptoms. The range of scores is 0-64, with higher scores indicating greater withdrawal severity. The peak SOWS rating will be the highest measurement in the session after study drug administration.
Time frame: Peak SOWS rating will be the highest rating during each 2 hour study session.
Peak Increase From Baseline Pupil Diameter
Pupil diameter (mm) will be measured via digital pupillometer in standard room lighting at baseline and then throughout the study session after study drug administration. The peak increase from baseline value will be the largest increase from baseline pupil diameter measured after study drug administration.
Time frame: Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.
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