Oxytocin + Oxycodone for Opioid Use Disorder

Overseen By Lauren E Nieder, MSPH

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Florida

Disqualifiers: Physical disease, Psychiatric disorder, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether combining oxytocin, a hormone administered as a nasal spray, with oxycodone, an opioid pain medication, can lower the risk of abuse while still managing pain effectively. Participants will take oxycodone and oxytocin, either together or separately, to assess how these combinations affect pain and decision-making. The trial seeks individuals who have tried opioids at least once, are not experiencing chronic pain, and have stable heart health. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

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

Research shows that using oxytocin with oxycodone might help lower the risk of opioid misuse and improve pain relief. Oxycodone effectively manages severe pain when used properly, but it can lead to dependence and addiction if misused. Oxytocin, often called the "cuddle hormone," has been studied for its ability to ease pain and reduce withdrawal symptoms from opioids. One study found that a single dose of oxytocin, given as a nasal spray, was generally well-tolerated by patients with opioid use disorder, with no major side effects reported.

Although this trial is in the early stages, it builds on the idea that oxytocin could lessen the harmful effects of opioids like oxycodone. Overall, both treatments have shown promise in studies for managing pain and reducing opioid misuse, but the safety of using them together remains under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the oxytocin and oxycodone combination treatment for opioid use disorder because it explores a novel approach by combining a hormone with an opioid. Unlike standard treatments like methadone or buprenorphine, which primarily focus on reducing cravings and withdrawal symptoms, this treatment aims to address the condition by potentially enhancing the social and emotional processing effects of oxytocin. Oxytocin, administered as a nasal spray, could complement the effects of oxycodone, offering a unique mechanism that might improve treatment outcomes by addressing the psychological aspects of addiction. This innovative pairing opens up new possibilities for managing opioid use disorder in a more holistic manner.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

This trial will evaluate the effects of combining oxytocin with oxycodone for opioid use disorder. Studies have shown that this combination might reduce misuse risk and improve pain relief. Oxytocin, often called the "cuddle hormone," has been linked to easing withdrawal symptoms in those stopping opioid use. Research suggests that oxytocin can reduce harmful opioid use and provide pain relief. Early findings indicate that oxytocin may decrease opioid tolerance, potentially requiring less of the drug over time. Overall, combining oxytocin with oxycodone could make pain treatment safer and more effective. Participants in this trial will join different treatment arms to assess these potential benefits. ^{1 2 3 5 6}

Who Is on the Research Team?

Meredith S Berry, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for English-speaking adults who have used opioids at least once, with normal blood pressure, heart rate, EKG, and bloodwork. They should be near their ideal body weight and not in chronic pain. Excluded are those with severe diseases or psychiatric disorders, pregnant or nursing women, individuals seeking drug abuse treatment, or those with substance use disorders other than nicotine or caffeine.

Inclusion Criteria

My weight is close to what is considered ideal for my height.

Must report some experience with opioids (e.g., oxycodone, defined as use at least once in the subject's lifetime)

Individuals fluent in English will participate

Exclusion Criteria

I am not pregnant or nursing.

No self-reported current interest in drug abuse treatment

I do not have a severe drug use problem or withdrawal symptoms, except for nicotine or caffeine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive intranasal oxytocin and oral oxycodone or placebo across 6 sessions with a one-week washout period between each session

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• OxyCODONE 2.5 mg Oral Tablet
• OxyCODONE 5 mg Oral Tablet
• Oxytocin Nasal Spray (48 IU)
• Placebo oxyCODONE Oral Tablet
• Placebo Oxytocin Nasal Spray

Trial Overview

The study tests if oxytocin nasal spray can reduce the addictive potential of oxycodone and enhance its pain relief effects. Participants will undergo six sessions where they'll receive combinations of oxycodone (5 mg or 2.5 mg), placebo tablets, oxytocin spray (48 IU), and placebo sprays to assess their impact on pain response and decision-making.

How Is the Trial Designed?

Group I: Oral oxycodone (5mg) + intranasal oxytocin (48 IU) Active Control 2 Interventions

Combined effects of oxycodone and oxytocin.

Group II: Oral oxycodone (2.5mg) + intranasal oxytocin (48 IU) Active Control 2 Interventions

Combined effects of oxycodone and oxytocin.

Group III: Oral placebo + intranasal oxytocin (48 IU) Active Control 2 Interventions

Separate effects of oxytocin. As is standard methodology in abuse liability and pain assessments, a placebo condition will be included for each drug in order to compare the abuse liability and pain assessments change from placebo.

Group IV: Oral oxycodone (5mg) + intranasal placebo Active Control 2 Interventions

Separate effects of oxycodone. As is standard methodology in abuse liability and pain assessments, a placebo condition will be included for each drug in order to compare the abuse liability and pain assessments change from placebo.

Group V: Oral oxycodone (2.5mg) + intranasal placebo Active Control 2 Interventions

Separate effects of oxycodone. As is standard methodology in abuse liability and pain assessments, a placebo condition will be included for each drug in order to compare the abuse liability and pain assessments change from placebo.

Group VI: Oral placebo + intranasal placebo Placebo Group 2 Interventions

Serves as the control.

OxyCODONE 2.5 mg Oral Tablet is already approved in United States, European Union, Canada for the following indications:

Approved in United States as OxyContin for:

• Moderate to severe pain
• Chronic pain

Approved in European Union as OxyNorm for:

• Severe pain
• Chronic pain

Approved in Canada as Roxicodone for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The study involving 27 healthy adult recreational opioid users found that intranasally administered reformulated OxyContin® (ORF) resulted in lower and delayed peak plasma concentrations of oxycodone compared to the original OxyContin® (OC) and oxycodone powder, suggesting a reduced potential for abuse.

Pharmacodynamic measures, such as Overall Drug Liking and Take Drug Again scores, were significantly lower for ORF, indicating that the reformulated version may be less appealing for misuse, while no significant safety concerns were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users. Harris, SC., Perrino, PJ., Smith, I., et al.[2022]

In a study involving 40 nondependent recreational opioid users, the new formulation of immediate release oxycodone (IRO-A) resulted in significantly lower subjective ratings of 'drug liking' and 'overall drug liking' compared to the standard immediate release oxycodone (IRO) when both were crushed and administered intranasally.

While both formulations caused common opioid-related side effects, IRO-A was associated with more nasal-related symptoms, suggesting that although it may be less appealing for recreational use, it still carries risks of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing subjective and physiologic effects following intranasal administration of a new formulation of immediate release oxycodone HCl (Oxecta™) tablets in nondependent recreational opioid users. Schoedel, KA., Rolleri, RL., Faulknor, JY., et al.[2019]

Oxycodone, particularly in its slow-release form OxyContin, has been widely prescribed for chronic pain, leading to significant misuse and overdose cases across the United States, with 6.9 million prescriptions written in just one year.

The study aims to identify and characterize potential metabolites of oxycodone that appear in drug tests, suggesting that there may be additional metabolic pathways for oxycodone that have not been fully documented in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tentative identification of novel oxycodone metabolites in human urine. Moore, KA., Ramcharitar, V., Levine, B., et al.[2019]

A study involving 22 individuals receiving methadone for opioid use disorder showed that intranasal oxytocin significantly reduced cocaine craving after two weeks, indicating its potential as an adjunctive treatment for co-occurring cocaine use disorder.

The study demonstrated high retention rates and no adverse events related to oxytocin, suggesting it is safe and well-tolerated, which supports the need for larger trials to further explore its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A two-week pilot study of intranasal oxytocin for cocaine-dependent individuals receiving methadone maintenance treatment for opioid use disorder. Stauffer, CS., Musinipally, V., Suen, A., et al.[2020]

Oxytocin (OT) has poor permeability across the blood-brain barrier, similar to sucrose, which suggests limited direct access to the central nervous system when administered systemically.

OT demonstrated dose-dependent analgesic effects in a nociception test, and its pain-relieving properties were not influenced by naloxone, indicating that OT may modulate pain through mechanisms distinct from the opioid system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain uptake and the analgesic effect of oxytocin--its usefulness as an analgesic agent. Kang, YS., Park, JH.[2019]

The new oxycodone 10-mg/acetaminophen 325-mg formulation (Percocet) was found to be more effective than a higher dose of oxycodone alone in managing acute pain after oral surgery, based on a study of 141 patients.

This combination not only provided faster pain relief but also resulted in fewer treatment-related side effects, highlighting its potential as a safer alternative for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. Gammaitoni, AR., Galer, BS., Bulloch, S., et al.[2019]

In a study of 463 patients with chronic low back pain, oxycodone combined with naloxone in a prolonged release formulation significantly increased the time to pain events compared to placebo, reducing the risk of inadequate pain relief by 42%.

The combination of oxycodone PR and naloxone PR not only maintained the analgesic efficacy of oxycodone alone but also improved bowel function, addressing a common side effect of opioid treatment and enhancing the overall tolerability of long-term opioid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain. Vondrackova, D., Leyendecker, P., Meissner, W., et al.[2022]

Oxytocin (OT) has shown promise in preclinical studies for reducing the development of opioid use disorders, suggesting it could be an effective treatment option for managing opioid-related behaviors.

OT may help address behavioral, cognitive, and emotional deficits linked to substance use, potentially aiding in relapse prevention and improving treatment outcomes for individuals with opioid use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioids and the hormone oxytocin. Kovatsi, L., Nikolaou, K.[2020]

In a 3-week Phase II clinical trial involving patients with moderate to severe osteoarthritis pain, Oxytrex (combining oxycodone with ultralow-dose naltrexone) showed a 39% reduction in pain intensity, significantly outperforming placebo and standard oxycodone treatment.

Oxytrex administered twice a day provided better pain relief and quality of analgesia compared to oxycodone taken four times a day, while maintaining a similar incidence of side effects, suggesting a more convenient and effective dosing option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex. Chindalore, VL., Craven, RA., Yu, KP., et al.[2013]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05761860

The Potential of Oxytocin to Reduce Opioid Abuse Liability ...

Oral oxycodone (2.5mg) + intranasal oxytocin (48 IU). Combined effects of oxycodone and oxytocin. Intervention/Treatment, Drug : OxyCODONE 2.5 mg Oral Tablet.

2.

hhp.ufl.edu

hhp.ufl.edu/cuddle-hormone-oxytocin-may-provide-pain-relief-and-help-curb-harmful-opioid-use/

Cuddle hormone oxytocin may provide pain relief and help ...

“Cuddle hormone” oxytocin may provide pain relief and help curb harmful opioid use. 2024. A two-year interdisciplinary study at UF examines synthetic oxytocin's ...

3.

nida.nih.gov

nida.nih.gov/publications/drugfacts/prescription-opioids

Prescription Opioids DrugFacts | National Institute on Drug ...

Medications for opioid use disorders are safe, effective, and save lives. These medicines interact with the same opioid receptors in the brain ...

4.

fda.gov

fda.gov/drugs/food-and-drug-administration-overdose-prevention-framework/timeline-selected-fda-activities-and-significant-events-addressing-substance-use-and-overdose

Overdose Prevention Activities Timeline

OxyContin (oxycodone controlled-release) approved; first formulation of oxycodone that allowed dosing every 12 hours instead of every 4 to 6 hours.

5.

mayoclinic.org

mayoclinic.org/diseases-conditions/prescription-drug-abuse/in-depth/tapering-off-opioids-when-and-how/art-20386036

Tapering off opioids: When and how

Tapering means slowly lowering over time the amount of opioid medicine you take until you stop completely.

6.

mayoclinic.org

mayoclinic.org/drugs-supplements/oxycodone-oral-route/description/drg-20074193

Oxycodone (oral route) - Side effects & dosage

Oxycodone is used to relieve pain severe enough to require opioid treatment and when other pain medicines did not work well enough or cannot be tolerated.