Opioid Use DisorderPhase 2NCT05511909
Evaluating Buspirone to Treat Opioid Withdrawal
A Phase 2 study testing Buspirone and Lofexidine in people with Opioid Use Disorder and Opioid Withdrawal, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
The investigators propose a rigorous, Phase II, three-group, placebo-controlled double-blind randomized controlled trial (RCT) to evaluate the efficacy of buspirone for both withdrawal and craving among individuals with opioid use disorder (OUD) undergoing a standardized stepwise taper. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Opioid Use Disorder, Opioid Withdrawal, Opioid Craving
- What is being tested?
- Buspirone and Lofexidine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2022to 31 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-75
- Opioid positive urine sample
- Current moderate-severe opioid use disorder with evidence of physical dependence
- Interested in undergoing opioid detoxification
Who cannot join
- Being pregnant or breastfeeding
- Enrolled in methadone or buprenorphine maintenance treatment
- Allergic to study medication or taking medications that are contraindicated with study medication (e.g., CYP3A4 inhibitors or inducers and/or monoamine oxidase (MAO) inhibitors)
- Significant mental health or physical disorder, or life circumstance, that is expected to interfere with study participation (detailed further in protection of human subjects form).
- Hypotension and/or prolonged QTc interval
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
Kahlert Institute for Addictino Medicin
Baltimore, Maryland, 21224
Cecilia Bergeria, Ph.D., 410-550-1979, cberge21@jhmi.edu
Cecilia Bergeria, Ph.D.
About this study
Official title: Evaluating a Mechanistically-Supported Pharmacotherapy to Treat Opioid Withdrawal
The investigators propose a rigorous, Phase II, three-group, placebo-controlled double-blind randomized controlled trial (RCT) to evaluate the efficacy of buspirone for both withdrawal and craving among individuals with opioid use disorder (OUD) undergoing a standardized stepwise taper. During this 10 to 12-day residential study, participants with OUD will be enrolled, stabilized on a short-acting opioid, undergo an opioid stepwise taper, and complete a post-taper observation period where participants will have the opportunity to initiate long-term buprenorphine or extended-release naltrexone.
Read the detailed description
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.
- Conditions
- Opioid Use Disorder, Opioid Withdrawal, Opioid Craving, Anxiety
- Being tested
- Buspirone, Lofexidine, Placebo
- Medical subject headings
- Opioid-Related Disorders, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuspironeDrug
Buspirone administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7).
LofexidineDrug
Lofexidine administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7).
PlaceboDrug
Participants administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7).
| Study group | Role | What they receive |
|---|---|---|
| opioid stepwise taper + buspirone | Experimental | up to 45mg/day buspirone during the opioid stepwise taper Receives: Drug: Buspirone |
| opioid stepwise taper + lofexidine | Active comparator | up to 2.16mg/day lofexidine during the opioid stepwise taper Receives: Drug: Lofexidine |
| opioid stepwise taper + placebo | Placebo comparator | placebo during the opioid stepwise taper Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Opioid Withdrawal as assessed by the Subjective Opiate Withdrawal Scale (SOWS)
Opioid withdrawal severity will be measured with the Subjective Opiate Withdrawal Scale (SOWS) and will be computed as a daily peak total SOWS score for study days -2 to 8. The SOWS consists of 16 opioid withdrawal symptoms that are assessed for severity on a scale from 0-4 ("Not at all" to "Extremely"). Total scores range from 0-64 where a score between 0-10 is considered mild, between 11-20 is considered moderate, and greater than 21 is considered severe.
Measured: Days -2 to 8
Secondary outcomes (6)
Change in tonic craving scores
Craving will be measured by tonic craving will be computed as daily peak total craving scores. The tonic craving assessment consists of 5 items related to craving that are completed on a visual analog scale (VAS) where 0 = not at all and 100 = A lot.
Measured: Days -2 to 8
Change in cue-induced craving scores
Cue-induced craving will be computed as total craving scores before and after the craving task. The craving assessment consists of 5 items related to craving that are completed on a visual analog scale (VAS) where 0 = not at all and 100 = A lot.
Measured: Days -2 to 8
Change in stress-induced craving scores
Stress-induced craving will be computed as total craving scores before and after stress/craving task. The craving assessment consists of 5 items related to craving that are completed on a visual analog scale (VAS) where 0 = not at all and 100 = A lot.
Measured: Days -2 to 8
Frequency of Adverse Events
Safety will be assessed with the number of adverse events per treatment condition not including unrelated adverse events.
Measured: Up to day 8
Frequency of QTc Interval Prolongation
Corrected QT (QTc) interval prolongation frequency will be compared across conditions. QTc interval is considered prolonged if >440 ms among male participants and >460 ms among female participants.
Measured: Up to day 8
Acceptability of buspirone for opioid withdrawal and craving
Acceptability will be measured by acceptability questionnaires completed at discharge and will be computed as the average acceptability score. Scores range from 0-10, where 0 reflects no acceptability and 10 reflects high acceptability.
Measured: Up to day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2022
- Study start15 Dec 2022
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cecilia Bergeria, Ph.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05511909
- Sponsor's protocol ID
- #HP-00115626
- Status last verified
- Aug 2026
- First submitted
- 18 Aug 2022
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating a Mechanistically-Supported Pharmacotherapy to Treat Opioid Withdrawal
- ClinicalTrials.gov ID
- NCT05511909
- Acronym / sponsor ID
- #HP-00115626
- Conditions
- Opioid Use Disorder, Opioid Withdrawal, Opioid Craving, Anxiety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 15 Dec 2022 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 23 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose a rigorous, Phase II, three-group, placebo-controlled double-blind randomized controlled trial (RCT) to evaluate the efficacy of buspirone for both withdrawal and craving among individuals with opioid use disorder (OUD) undergoing a standardized stepwise taper. During this 10 to 12-day residential study, participants with OUD will be enrolled, stabilized on a short-acting opioid, undergo an opioid stepwise taper, and complete a post-taper observation period where participants will have the opportunity to initiate long-term buprenorphine or extended-release naltrexone.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| opioid stepwise taper + buspirone | Experimental | Drug: Buspironeup to 45mg/day buspirone during the opioid stepwise taper |
| opioid stepwise taper + lofexidine | Active comparator | Drug: Lofexidineup to 2.16mg/day lofexidine during the opioid stepwise taper |
| opioid stepwise taper + placebo | Placebo comparator | Drug: Placeboplacebo during the opioid stepwise taper |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged 18-75
- Opioid positive urine sample
- Current moderate-severe opioid use disorder with evidence of physical dependence
- Interested in undergoing opioid detoxification
Key exclusion criteria (5 listed)
- Being pregnant or breastfeeding
- Enrolled in methadone or buprenorphine maintenance treatment
- Allergic to study medication or taking medications that are contraindicated with study medication (e.g., CYP3A4 inhibitors or inducers and/or monoamine oxidase (MAO) inhibitors)
- Significant mental health or physical disorder, or life circumstance, that is expected to interfere with study participation (detailed further in protection of human subjects form).
- Hypotension and/or prolonged QTc interval
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BuspironeBuspirone administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7). | Drug | opioid stepwise taper + buspirone |
| LofexidineLofexidine administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7). | Drug | opioid stepwise taper + lofexidine |
| PlaceboParticipants administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7). | Drug | opioid stepwise taper + placebo |
Primary outcome
Change in Opioid Withdrawal as assessed by the Subjective Opiate Withdrawal Scale (SOWS)
Time frame: Days -2 to 8
Opioid withdrawal severity will be measured with the Subjective Opiate Withdrawal Scale (SOWS) and will be computed as a daily peak total SOWS score for study days -2 to 8. The SOWS consists of 16 opioid withdrawal symptoms that are assessed for severity on a scale from 0-4 ("Not at all" to "Extremely"). Total scores range from 0-64 where a score between 0-10 is considered mild, between 11-20 is considered moderate, and greater than 21 is considered severe.
6 secondary outcomes
Change in tonic craving scores
Time frame: Days -2 to 8
Change in cue-induced craving scores
Time frame: Days -2 to 8
Change in stress-induced craving scores
Time frame: Days -2 to 8
Frequency of Adverse Events
Time frame: Up to day 8
Frequency of QTc Interval Prolongation
Time frame: Up to day 8
Acceptability of buspirone for opioid withdrawal and craving
Time frame: Up to day 8
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cecilia Bergeria, Ph.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Buspirone and Lofexidine in people with Opioid Use Disorder and Opioid Withdrawal, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cecilia Bergeria, Ph.D. (410-550-1979, cberge21@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Opioid Withdrawal as assessed by the Subjective Opiate Withdrawal Scale (SOWS) (time frame: Days -2 to 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.