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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether buspirone, a medication often used for anxiety, can help individuals with opioid use disorder manage withdrawal symptoms and cravings during detox. Participants will be divided into three groups to receive either buspirone, a placebo, or another medication called lofexidine as part of a step-by-step reduction of opioid use. It targets individuals who have used opioids heavily, have a positive opioid urine test, and wish to undergo detox. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that buspirone is generally safe for use. Studies have found it carries a low risk of side effects and does not cause addiction or withdrawal symptoms, so people usually don't feel unwell when they stop taking it.

Buspirone is already used to treat anxiety, indicating its safety for that purpose. Some common side effects might include dizziness, headaches, or nausea, but these are usually mild for most people. Overall, buspirone works as well as other treatments like methadone for easing opioid withdrawal symptoms, without the risk of addiction. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about buspirone for opioid withdrawal because it offers a different approach from the usual treatments like methadone or buprenorphine. Unlike these opioid-based options, buspirone is a non-opioid medication that primarily targets serotonin receptors, potentially reducing withdrawal symptoms without the risk of addiction. This unique mechanism of action might offer a safer alternative for individuals seeking to overcome opioid dependence.

What evidence suggests that buspirone might be an effective treatment for opioid withdrawal?

Research has shown that buspirone, which participants in this trial may receive, can help reduce symptoms of opioid withdrawal. Studies have found that buspirone eases these symptoms when used during a supervised reduction of opioid use. In one study, patients taking buspirone with methadone experienced significantly fewer withdrawal symptoms than those who did not. Additionally, buspirone is safe and does not cause addiction or withdrawal problems itself. These findings suggest that buspirone could be a useful option for people going through opioid withdrawal. ^{1 2 5 6 7}

Who Is on the Research Team?

Cecilia Bergeria, Ph.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35266779/

A double-blind, randomized, placebo-controlled, pilot clinical ... This study provides further support that buspirone can help mitigate opioid withdrawal during a supervised opioid taper.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03521960

NCT03521960 | Buspirone for Opioid Tapering Buspirone (Buspar) has shown initial efficacy in reducing symptoms of opioid withdrawal in animal studies and in human patients undergoing a methadone taper.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11000212/

A Double-Blind, Randomized, Placebo-Controlled, Pilot ... These studies demonstrated significant, large effect decreases in opioid withdrawal symptoms occurred in persons receiving methadone + buspirone compared to ...

4. semanticscholar.org semanticscholar.org/paper/Efficacy-of-Buspirone-in-the-Treatment-of-Opioid-Buydens-Branchey-Branchey/74238c4ca71cd456dddffd9ca7625216062cf38f

Efficacy of Buspirone in the Treatment of Opioid Withdrawal Buspirone, a nonopiate drug with no abuse potential, a safe side effect profile and no withdrawal symptoms, was as effective as a methadone taper in ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05511909/evaluating-buspirone-to-treat-opioid-withdrawal

Evaluating Buspirone to Treat Opioid Withdrawal The investigators hypothesize that the opioid taper + buspirone and opioid taper + lofexidine will significantly decrease withdrawal (SOWS, COWS) ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/buspirone-oral-route/description/drg-20062457

Buspirone (oral route) - Side effects & dosage Buspirone is used to treat certain anxiety disorders or to relieve the symptoms of anxiety. However, buspirone usually is not used for anxiety or tension ...

7. pdf.hres.ca pdf.hres.ca/dpd_pm/00066194.PDF

APO-BUSPIRONE tablets (Buspirone Hydrochloride) 1.2. Geriatrics. Geriatrics: Buspirone has not been systematically evaluated in geriatric patients. Although it would.