Buspirone for Opioid Withdrawal

Overseen By Cecilia Bergeria, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must be taking: Opioids

Must not be taking: CYP3A4 inhibitors, MAO inhibitors

Disqualifiers: Pregnancy, Methadone, Buprenorphine, Hypotension, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking medications that interact negatively with the study drug, such as certain enzyme inhibitors or MAO inhibitors.

What data supports the effectiveness of the drug buspirone for opioid withdrawal?

Research shows that buspirone can help reduce withdrawal symptoms in people stopping opioid use, as it was found to lower scores on withdrawal symptom scales compared to a placebo. It was as effective as methadone in alleviating withdrawal symptoms in heroin addicts, and it also improved sleep during withdrawal. ^{1 2 3 4 5}

How is the drug buspirone unique in treating opioid withdrawal?

Buspirone is unique in treating opioid withdrawal because it is a non-opiate drug that interacts with the serotonergic system, helping to alleviate withdrawal symptoms without the risk of abuse or withdrawal symptoms itself. It has been shown to be as effective as methadone in reducing withdrawal symptoms, making it a potentially safer option for outpatient settings. ^{1 2 3 4 6}

Research Team

Cecilia Bergeria, Ph.D.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-75 with opioid use disorder who are physically dependent on opioids and want to detox. They must have a positive urine test for opioids but can't be pregnant, breastfeeding, or have low blood pressure or heart issues. People taking certain other meds or with serious mental/physical health problems that could affect their participation are also excluded.

Inclusion Criteria

Opioid positive urine sample

You want to stop using opioids and need help to do so.

You currently have a serious problem with using opioids and are physically dependent on them.

Exclusion Criteria

Being pregnant or breastfeeding

Enrolled in methadone or buprenorphine maintenance treatment

You have a mental or physical condition that may make it difficult for you to take part in the study. This will be explained in a separate form that protects your privacy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Stabilization

Participants are stabilized on a short-acting opioid

2 days

Opioid Taper

Participants undergo a stepwise opioid taper with either placebo, lofexidine, or buspirone

8 days

Daily monitoring

Post-taper Observation

Participants complete a post-taper observation period and may initiate long-term buprenorphine or extended-release naltrexone

2 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Buspirone
• Lofexidine
• Placebo

Trial Overview The study tests the effectiveness of Buspirone in managing withdrawal symptoms and cravings during opioid detoxification compared to Lofexidine and a placebo. Participants will undergo a controlled tapering off opioids over 10-12 days in a residential setting, followed by an observation period where they may start long-term addiction treatments.

Participant Groups

Group I: opioid stepwise taper + buspirone Experimental Treatment 1 Intervention

up to 45mg/day buspirone during the opioid stepwise taper

Group II: opioid stepwise taper + lofexidine Active Control 1 Intervention

up to 2.16mg/day lofexidine during the opioid stepwise taper

Group III: opioid stepwise taper + placebo Placebo Group 1 Intervention

placebo during the opioid stepwise taper

Buspirone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Buspar for:

• Generalized anxiety disorder

Approved in European Union as Buspirone for:

• Generalized anxiety disorder

Approved in Canada as Buspirone for:

• Generalized anxiety disorder

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Findings from Research

In a study involving 20 male chronic opiate users, buspirone significantly reduced withdrawal symptoms compared to a placebo, as measured by both the Objective Opiate Withdrawal Scale (OOWS) and the Subjective Opiate Withdrawal Scale (SOWS).

Buspirone treatment led to lower withdrawal scores on multiple days, indicating its effectiveness in managing symptoms following the cessation of heroin or methadone use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of buspirone in withdrawal from opiates. Rose, JS., Branchey, M., Wallach, L., et al.[2016]

In a clinical trial with 15 participants undergoing opioid withdrawal, buspirone (45 mg/day) significantly reduced withdrawal symptoms compared to placebo, particularly during the second week of treatment.

Buspirone also improved sleep outcomes, leading to longer sleep duration and quicker sleep onset, suggesting it may be beneficial for managing both withdrawal symptoms and sleep disturbances during opioid tapering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled, pilot clinical trial examining buspirone as an adjunctive medication during buprenorphine-assisted supervised opioid withdrawal. Bergeria, CL., Tan, H., Antoine, D., et al.[2023]

In a study involving 29 hospitalized heroin addicts, buspirone was found to be as effective as methadone in alleviating withdrawal symptoms, demonstrating its potential as a safe and non-addictive alternative for detoxification.

Buspirone, with doses of 30 mg and 45 mg, showed a favorable safety profile with no abuse potential or withdrawal symptoms, making it particularly suitable for outpatient detoxification settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of buspirone in the treatment of opioid withdrawal. Buydens-Branchey, L., Branchey, M., Reel-Brander, C.[2019]

In a study involving 15 patients with extensive benzodiazepine use, switching to buspirone did not alleviate withdrawal symptoms, indicating that buspirone may not effectively manage benzodiazepine withdrawal.

The results align with preclinical studies suggesting that buspirone does not significantly interact with benzodiazepine receptors, which may explain its limited efficacy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of buspirone to manage benzodiazepine withdrawal. Schweizer, E., Rickels, K.[2013]

In a 12-week study involving 36 opioid-dependent individuals receiving methadone, buspirone did not significantly reduce anxiety symptoms compared to placebo.

However, buspirone showed potential benefits by trending towards reduced depression scores and a slower return to substance use, suggesting it may have some positive effects in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled trial of buspirone for the treatment of anxiety in opioid-dependent individuals. McRae, AL., Sonne, SC., Brady, KT., et al.[2019]

In a study involving 24 outpatients on long-term benzodiazepine treatment, buspirone was tested as a potential aid for withdrawal, but only 5 out of 13 patients on buspirone successfully completed the withdrawal compared to 6 out of 11 on placebo.

The study found that buspirone did not demonstrate cross-tolerance with benzodiazepines and was not effective in alleviating withdrawal symptoms, indicating it may not be a suitable option for patients trying to discontinue benzodiazepines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of buspirone and placebo in relieving benzodiazepine withdrawal symptoms. Lader, M., Olajide, D.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of buspirone in withdrawal from opiates. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled, pilot clinical trial examining buspirone as an adjunctive medication during buprenorphine-assisted supervised opioid withdrawal. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of buspirone in the treatment of opioid withdrawal. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Failure of buspirone to manage benzodiazepine withdrawal. [2013]

5. England pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled trial of buspirone for the treatment of anxiety in opioid-dependent individuals. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

A comparison of buspirone and placebo in relieving benzodiazepine withdrawal symptoms. [2013]