Alprazolam + Oxycodone for Drug Interaction

Overseen By Paul A Nuzzo

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shanna Babalonis, PhD

Must be taking: Opioids, Sedatives

Must not be taking: CYP inhibitors/inducers

Disqualifiers: Alcohol dependence, Hypertension, Diabetes, Bipolar, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6.5 hours per session

25 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those with chronic medical problems requiring daily medication. It also excludes recent use of certain long-acting drugs that affect liver enzymes, which might suggest some medications need to be stopped.

Is the combination of alprazolam and oxycodone safe for humans?

Combining alprazolam (a type of sedative) with oxycodone (a painkiller) can be dangerous because it may cause severe breathing problems and increase the risk of overdose. Studies show that using these drugs together has led to many unintentional overdose deaths. ^{1 2 3 4 5}

How does the drug combination of alprazolam and oxycodone differ from other treatments?

The combination of alprazolam (a benzodiazepine) and oxycodone (an opioid) is unique because it involves two drugs that can significantly increase the risk of respiratory depression when used together, which is not typically seen with other treatments. This combination is often associated with higher risks of overdose and fatalities compared to using either drug alone. ^{1 2 3 5 6}

What is the purpose of this trial?

This study will examine the effects of doses of opioid/placebo and doses of alprazolam/placebo, alone and in combination. The primary outcomes are pharmacodynamic measures (subjective ratings of drug liking and other abuse-related effects; physiological outcomes) and pharmacokinetic outcomes (from blood samples) to determine the interaction effects of these compounds.

Research Team

Shanna Babalonis, PhD

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for individuals who can safely take opioids and benzodiazepines, specifically oxycodone and alprazolam. Participants should be interested in how these drugs interact with each other. The study excludes those with allergies to the drugs being tested, current drug abuse issues, or any health conditions that might interfere with the study's safety or outcomes.

Inclusion Criteria

Self-reported opioid use

English-speaking and literate participants, able to understand and sign Informed Consent Document

Self-reported sedative-like drug use

Exclusion Criteria

Clinically significant abnormal ECG (as determined by study physician/cardiologist)

I have a chronic condition like high blood pressure or diabetes that needs daily medication.

I need medical help to manage my addiction to alcohol or drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various combinations of alprazolam and oxycodone, or placebo, to assess pharmacodynamic and pharmacokinetic interactions

6.5 hours per session

Multiple sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Opioid Drug Interaction Study

Trial Overview The study is testing how oxycodone (an opioid) interacts with alprazolam (a benzodiazepine). Some participants will receive the actual drugs while others will get a placebo. Researchers are looking at both subjective effects like drug liking and objective measures from blood tests to understand this interaction.

Participant Groups

Group I: Placebo / Oxycodone low oral dose (Percocet, Roxicodone) Experimental Treatment 2 Interventions

Participants will receive 2 drug administrations, one dose oral placebo and one low dose oral oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group II: Placebo / Oxycodone high oral dose (Percocet, Roxicodone) Experimental Treatment 2 Interventions

Participants will receive 2 drug administrations, one dose oral placebo and one high dose oral oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group III: Alprazolam low oral dose (Xanax) / Placebo Experimental Treatment 2 Interventions

Participants will receive 2 drug administrations, one dose oral placebo and one low dose oral alprazolam. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group IV: Alprazolam low oral dose (Xanax) / Oxycodone low oral dose (Percocet, Roxicodone) Experimental Treatment 2 Interventions

Participants will receive 2 non-therapeutic oral drug administrations, one low dose alprazolam, and one low dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group V: Alprazolam low oral dose (Xanax) / Oxycodone high oral dose (Percocet, Roxicodone) Experimental Treatment 2 Interventions

Participants will receive 2 non-therapeutic oral drug administrations, one low dose alprazolam, and one high dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group VI: Alprazolam high oral dose (Xanax) / Placebo Experimental Treatment 2 Interventions

Participants will receive 2 drug administrations, one dose oral placebo and one high dose oral alprazolam. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group VII: Alprazolam high oral dose (Xanax) / Oxycodone low oral dose (Percocet, Roxicodone) Experimental Treatment 2 Interventions

Participants will receive 2 non-therapeutic oral drug administrations, one high dose alprazolam, and one low dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group VIII: Alprazolam high oral dose (Xanax) / Oxycodone high oral dose (Percocet, Roxicodone) Experimental Treatment 2 Interventions

Participants will receive 2 non-therapeutic oral drug administrations, one high dose alprazolam, and one high dose oxycodone. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Group IX: Placebo / Placebo Placebo Group 1 Intervention

Participants will receive 2 drug administrations, neither will be active. The experimental sessions are designed to capture the time-action curves for the test drugs (Tmax for both alprazolam and oxycodone ≈ 1.5 hr).

Who Is Running the Clinical Trial?

Shanna Babalonis, PhD

Lead Sponsor

Trials

5

Recruited

140+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

A study analyzing 1.3 million drug tests found that the combination of opiates and benzodiazepines in patients decreased from 2016 to 2019, suggesting a positive impact of the 2016 CDC prescribing guidelines on reducing polypharmacy.

Despite variability in the use of different opiate pairs, the overall trend indicates fewer patients were using both opiates and benzodiazepines together, which may enhance patient safety by reducing the risk of adverse drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of Drug-Drug Interaction Risk; CDC Guidelines Influence on Opiate Benzodiazepine Prescribing. Pesce, A., Thomas, R., Krock, K., et al.[2021]

References

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

Benzodiazepines: a major component in unintentional prescription drug overdoses with opioid analgesics. [2022]

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

One hundred seventy two deaths involving the use of oxycodone in Palm Beach County. [2013]

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

Reduction of Drug-Drug Interaction Risk; CDC Guidelines Influence on Opiate Benzodiazepine Prescribing. [2021]

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

Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat. [2022]

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

A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats. [2022]

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

Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations. [2018]