This R01 will conduct a rigorous and appropriately powered randomized clinical trial to
evaluate the efficacy of buspirone to decrease opioid withdrawal and craving, improve
treatment retention and decrease rates of relapse. The use of buspirone for opioid use
disorder (OUD) is mechanistically-supported and has demonstrated initial efficacy in
small clinical trials including mostly male samples. Since the latest promising results
were published 15 years ago, buspirone has yet to be evaluated in a rigorous and
appropriately representative and powered randomized clinical trial. Buspirone stands to
provide immediate aid to unmet treatment needs among individuals with OUD because it is
FDA-approved and generically available. The investigators have designed a Phase-II,
three-group, double-blind, placebo controlled evaluation of buspirone for opioid
withdrawal and craving during a residential stepwise opioid taper. The study will take
place in a clinical research unit over 10-12 days where participants will undergo a
short-term stabilization period, an opioid taper, and a post-taper observation period
where participants will initiate extended release naltrexone (XR-NTX) or buprenorphine or
will receive a referral to a treatment program of the participants' choice. One hundred
participants with OUD and interested in completing a residential opioid taper will be
enrolled and randomized to one of three conditions: (1) an opioid stepwise taper with
placebo (control), (2) an opioid stepwise taper with lofexidine (positive control), and
(3) an opioid stepwise taper with buspirone (experimental). Based on previous retention
rates, the investigators anticipate completing 90 participants (n=30/condition).
Withdrawal and tonic craving will be collected daily throughout the course of the study
using standardized questionnaires. Acute craving will be assessed in a cue-induced
craving task, which was developed by Co-I Huhn, once during the residential phase and
once during the outpatient phase. Finally, the safety and acceptability by the study
participants will be assessed through Adverse Events (AEs), abnormal ECGs, acceptability
scores, and negative comments.
The Primary Aim will compare the changes in opioid withdrawal across the three
conditions. The investigators hypothesize that the opioid taper + buspirone and opioid
taper + lofexidine will significantly decrease withdrawal (SOWS, COWS) relative to opioid
taper alone.
Secondary Aim 1 will compare changes in craving across the three conditions. The
investigators hypothesize that individuals will have significantly lower tonic and
cue-induced craving scores when the individuals are actively receiving opioid taper +
buspirone relative to opioid taper alone and opioid taper + buspirone. Individuals who
receive opioid taper + lofexidine will have significantly lower craving following
cue-induced craving + stress tasks compared to opioid taper alone and opioid taper +
buspirone conditions. Secondary Aim 2 will compare the safety and acceptability by the
participants in the three conditions. The investigators hypothesize that buspirone will
produce the fewest adverse events and instances of negative qualitative feedback and the
greatest acceptability scores, followed by opioid taper + lofexidine. Opioid taper alone
is expected to produce the highest number of adverse events and the lowest acceptability.
The Exploratory Aim will compare the changes in anxiety and acute stress response across
the three conditions. The investigators offer no hypothesis on this aim.
This study will determine whether buspirone is an effective medication for treating
opioid withdrawal and craving. This study will demonstrate the utility of using
mechanistically supported medications to treat opioid withdrawal symptoms. If proven to
have a positive impact on OUD and related sequelae, these data would support additional
research evaluating the benefits of buspirone in other short -and long-term treatment
settings for opioid use disorder. Further, this medication should be evaluated among
chronic pain patients interested in tapering off of opioids but requiring additional
therapeutic support to address acute and protracted withdrawal. The re-purposing of
buspirone to treat OUD could occur rapidly and offers a safe pharmacotherapy for
individuals requiring additional support for OUD.