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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the interaction between alprazolam (a sedative) and oxycodone (a painkiller) when taken together and separately. Researchers aim to understand how these drugs affect feelings of drug liking and other effects related to potential misuse. Participants will receive different combinations of these drugs or placebos to observe their body's reactions over time. This trial may suit individuals who have previously used opioids and sedative-like drugs and do not have major ongoing health issues. As a Phase 1 and Phase 2 trial, it seeks to understand how the treatment works in people and measure its effectiveness in a smaller group, offering participants a chance to contribute to important early-stage research.

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

Research has shown that taking alprazolam (an anxiety medication) with oxycodone (a pain medication) increases certain risks. Both drugs cause drowsiness and slow breathing, and these effects become more pronounced when combined. Studies have found that using them together can lead to serious problems, including a higher risk of overdose. Evidence also indicates that people often misuse these drugs together. Therefore, while each drug is safe when used correctly on its own, combining them requires careful monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Alprazolam and Oxycodone combination study because it explores how these two drugs interact, which is crucial for understanding their combined effects. Unlike standard treatments that typically focus on the individual effects of opioids like Oxycodone, this study looks at how the benzodiazepine Alprazolam might change the way Oxycodone works in the body. This could help refine dosing guidelines and enhance safety for patients who need both types of medication. Understanding these interactions might lead to better pain management strategies and reduce potential risks linked with drug interactions.

What evidence suggests that this trial's treatments could be effective?

Research has shown that taking alprazolam and oxycodone together enhances the effects of both drugs compared to taking them separately. This trial will explore various combinations of alprazolam and oxycodone, including different dosages, to understand their interaction. One study found that this combination can intensify certain feelings, such as those related to drug enjoyment, and prolong them. However, using these drugs together also increases the risk of serious side effects, such as extreme drowsiness or breathing problems. Some reports indicate a higher chance of severe outcomes, like needing emergency room visits, when these medications are mixed. It is important to carefully weigh these potential risks and benefits. ^{2 3 4 5 6}

Who Is on the Research Team?

Shanna Babalonis, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

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.

Seeking treatment for opioid or any other drug use

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3568773/

Separate and combined psychopharmacological effects of ... Some subjective effects of oxycodone appeared to be attenuated by alprazolam, including self-reports of itchy skin, a proxy for pruritis and a prototypic opioid ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871612000403

Separate and combined psychopharmacological effects of ... The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures.

3. go.drugbank.com go.drugbank.com/drugs/DB00497

Oxycodone: Uses, Interactions, Mechanism of Action The risk or severity of adverse effects can be increased when Oxycodone is combined with Alprazolam. The risk or severity of CNS depression can be increased ...

4. fda.gov fda.gov/media/99761/download

FDA warns about serious risks and death when combining ... Health Administration data from 2004-2009 and found the risk of death from drug overdose increased among those with concomitant opioid ...

5. samhsa.gov samhsa.gov/data/sites/default/files/DAWN-SR192-BenzoCombos-2014/DAWN-SR192-BenzoCombos-2014.htm

Greater Risk of More Serious ED Visit Outcomes This report quantifies the increased risk of more serious outcomes such as hospitalization or, rarely, death in the emergency department (ED),

6. nida.nih.gov nida.nih.gov/research-topics/opioids/benzodiazepines-opioids

Benzodiazepines and Opioids | National Institute on Drug Abuse Combining opioids and benzodiazepines can increase risk of overdose because both types of drugs can cause sedation and suppress breathing—the ...