Oxytocin + Oxycodone for Pain

Overseen By Lauren Nieder

Age: 18 - 65

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)

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

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 explores whether combining oxytocin with oxycodone, an opioid pain medication, can reduce misuse while effectively easing pain. Participants will try various combinations of these drugs to assess their effects on pain, emotions, and decision-making. Individuals who use opioids recreationally and do not have chronic pain might be suitable candidates. The trial includes multiple sessions to test different drug combinations. As an Early Phase 1 trial, this research aims to understand 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. However, it does mention that participants should not have any significant physical diseases or major psychiatric disorders, which might imply some restrictions on medications. It's best to discuss your specific medications with the trial coordinators.

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

Research has shown that oxycodone effectively relieves pain but carries risks. It can cause side effects and may lead to addiction if not used carefully. In some studies, individuals taking oxycodone experienced unwanted effects, particularly if they were not accustomed to strong pain medications.

Oxytocin, in contrast, is usually well-tolerated and often used safely in medical settings, such as during childbirth. However, high doses of oxytocin have been linked to risks like increased bleeding after childbirth.

Combining oxytocin with oxycodone might reduce the risk of drug abuse and enhance pain relief. Some studies suggest this combination could be safer than using oxycodone alone. However, as these findings come from early research, more studies are needed to understand the safety of this combination.

Since this trial is in an early phase, safety information remains limited. Early-phase trials typically focus on safety, so participation might help gather more information on how well the treatment is tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of oxycodone and oxytocin for pain management because it offers a potentially new way to enhance pain relief while addressing opioid abuse concerns. Unlike traditional opioids that primarily target the brain's pain receptors, adding oxytocin—an intranasal hormone known for its role in social bonding—might reduce the amount of oxycodone needed for effective pain control. This combination could potentially lower the risk of addiction and side effects associated with higher doses of oxycodone. By exploring the synergistic effects of these two substances, scientists hope to develop a more balanced approach to pain relief.

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

Research has shown that oxycodone effectively relieves pain. In studies, it provided better pain relief than a placebo, significantly reducing pain levels. However, oxycodone carries a risk of addiction. Oxytocin, often called the "cuddle hormone," has shown mixed results in managing pain. Some studies suggest it can reduce pain sensitivity and help decrease opioid use. In this trial, participants will receive either oxycodone alone, oxytocin alone, or a combination of both. The combination of oxytocin and oxycodone might offer better pain relief and a lower risk of addiction, but further research is needed to confirm these effects. ^{1 2 6 7 8}

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 individuals who occasionally use opioids recreationally, have normal blood pressure and heart rate, a clean EKG, are within 20% of ideal body weight, and don't suffer from chronic pain. Pregnant or nursing women, those with significant diseases or metal implants that affect MRI safety, or people seeking drug abuse treatment cannot participate.

Inclusion Criteria

I have not had chronic pain in the last 3 months.

My heart's electrical activity is normal and my blood tests show no major health issues.

Have a systolic blood pressure of <=140 and diastolic blood pressure of <= 90, and a heart rate <= 90 beats per minute.

Exclusion Criteria

You are not currently seeking treatment for drug abuse.

You have a problem with using illegal drugs or are currently experiencing withdrawal symptoms from any abused drug (excluding nicotine and caffeine).

Any conditions that preclude safety in the MRI scanner, such as: implanted electrical devices (e.g., cardiac pacemaker, neurostimulator); implanted metallic clips or pins (e.g., aneurysm clip); a history of working with metal (unless able to demonstrate participant is MRI safe), and claustrophobia.

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 oxycodone and oxytocin (combined and separately) across 6 sessions to evaluate effects on pain and abuse liability

6 weeks

6 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

• oxycodone
• oxytocin

Trial Overview The study examines if combining oxytocin nasal spray with oxycodone tablets can reduce the potential for abuse while effectively managing pain. Participants will undergo six sessions where they'll receive different combinations of these drugs (including placebos) to assess their impact on pain perception and brain activity.

How Is the Trial Designed?

Group I: oxytocin+placebo 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 II: 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 III: 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 IV: oxycodone (5mg) + intranasal oxytocin (48 IU) Active Control 2 Interventions

Combined effects of oxycodone and oxytocin

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

Combined effects of oxycodone and oxytocin

Group VI: placebo+placebo Placebo Group 2 Interventions

Serves as the control

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

Approved in United States as OxyContin for:

• Severe pain
• Chronic pain

Approved in Canada as OxyContin for:

• Severe pain
• Chronic pain

Approved in European Union as OxyContin for:

• Severe pain
• Chronic 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

In a study using paclitaxel to induce chemotherapy-induced neuropathic pain (CINP) in mice, it was found that the expression of oxytocin receptors (OXTR) in dorsal root ganglia (DRG) neurons increased significantly, suggesting a role for OXTR in pain modulation.

Activation of OXTR led to antinociceptive effects by reducing the excitability of DRG neurons and impairing the function of the sodium channel NaV 1.7, which is crucial in CINP, indicating that targeting OXTR could be a promising therapeutic approach for managing CINP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Up-regulation of oxytocin receptors on peripheral sensory neurons mediates analgesia in chemotherapy-induced neuropathic pain. Li, L., Li, P., Guo, J., et al.[2023]

A study analyzing 104 reports of adverse drug events (ADEs) for tapentadol and 249 for oxycodone/naloxone revealed that tapentadol is associated with a high incidence of nervous system disorders, with 23.2% of these cases linked to serotonin syndrome, particularly when combined with other serotonergic medications.

Oxycodone/naloxone reports showed significant psychiatric and gastrointestinal ADEs, with 16% of cases indicating withdrawal syndrome, suggesting that caution is needed when transitioning patients from other opioids to this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneously reported adverse drug events related to tapentadol and oxycodone/naloxone in Australia. Abeyaratne, C., Lalic, S., Bell, JS., et al.[2022]

This trial aims to evaluate the efficacy of intranasal oxytocin as a non-addictive treatment for chronic pain, involving adults with various pain conditions across three Canadian provinces, using a placebo-controlled, triple-blind design.

Participants will self-administer different doses of oxytocin nasal spray over two weeks, with primary outcomes focused on pain relief and secondary outcomes including emotional function and sleep disturbance, providing a comprehensive assessment of oxytocin's potential analgesic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the efficacy of intranasal oxytocin on pain and function among individuals who experience chronic pain: a protocol for a multisite, placebo-controlled, blinded, sequential, within-subjects crossover trial. Rash, JA., Campbell, TS., Cooper, L., et al.[2022]

A low-dose combination of oxycodone (average 8.68 mg) and acetaminophen (325 mg) effectively reduced moderate pain from an average score of 5.68 to 2.49 over approximately 21.6 days in a study of 491 patients.

Nearly 97% of patients experienced pain relief with just 5 mg doses of oxycodone combined with acetaminophen, suggesting this combination may minimize the risk of adverse reactions and dependence associated with higher opioid doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Evaluation of a Fixed-Dose Combination of Oxycodone and Acetaminophen to Manage Moderate Pain: The Lower the Better. Natoli, S., Lazzari, M., Carpenedo, R., et al.[2018]

Oxycodone is an effective opioid analgesic for severe pain, particularly in patients who have not responded to weaker opioids, due to its strong affinity for μ and κ opioid receptors and its ability to cross the blood-brain barrier quickly.

Recent formulations, including controlled-release oxycodone and a combination of prolonged-release oxycodone with naloxone, aim to improve pain management while minimizing adverse effects, such as constipation, which is common with opioid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of oxycodone and oxycodone/naloxone in cancer pain management. Leppert, W.[2022]

In a study of 194 patients using tapentadol (TAP) and 175 using oxycodone/naloxone (OXN), TAP provided better tolerability with fewer adverse events compared to OXN, which had a higher morphine equivalent daily dose but also greater pain relief.

Patients using OXN experienced more side effects, particularly COMT-AA homozygotes, indicating that genetic factors and sex may influence the safety profile of OXN, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxycodone/naloxone versus tapentadol in real-world chronic non-cancer pain management: an observational and pharmacogenetic study. Barrachina, J., Margarit, C., Muriel, J., et al.[2022]

Intrathecal administration of oxytocin (OXY) significantly reduces pain responses to noxious visceral stimulation in female rats, with a dose-dependent inhibition of visceromotor reflexes by up to 68%.

The antinociceptive effects of OXY are receptor-specific and involve the inhibition of spinal dorsal horn neurons, suggesting that intrathecal OXY could be a promising treatment for visceral pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal oxytocin inhibits visceromotor reflex and spinal neuronal responses to noxious distention of the rat urinary bladder. Engle, MP., Ness, TJ., Robbins, MT.[2022]

Oxycodone consumption has significantly increased over the past two decades, surpassing morphine in 2008, yet much of its pharmacokinetic data is outdated, primarily from the 1990s.

Recent studies have provided crucial information on oxycodone's effects in special populations (like neonates and the elderly) and highlighted important drug interactions, particularly with CYP450 enzymes, which can affect its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. Kinnunen, M., Piirainen, P., Kokki, H., et al.[2020]

In a study of 75 patients with opioid-induced constipation (OIC) who had not responded to at least two different laxatives, the combination of oxycodone/naloxone prolonged release tablets (OXN PR) significantly improved bowel function, with a mean reduction in the Bowel Function Index score of 21.2.

OXN PR also provided effective pain relief for both cancer-related and non-cancer pain, with 36% of patients able to stop using laxatives during treatment, and no unexpected adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives. Koopmans, G., Simpson, K., De Andrés, J., et al.[2018]

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]

A study found that oxycodone hydrochloride injection is both safe and effective for use in negative pressure aspiration procedures.

Administering a dose of 0.08 mg/kg significantly reduces postoperative uterine contraction pain in patients suffering from dysmenorrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of oxycodone in treating the uterine contraction pain after negative pressure aspiration: A randomized, compared, multicenter clinical study. Wang, YN., Xu, MJ., Feng, Y., et al.[2023]

The combination of oxycodone and paracetamol provides a synergistic effect for treating moderate-to-severe chronic pain, allowing for lower doses of each drug to be used, which can reduce the risk of side effects.

This fixed-dose combination has been shown to be effective and well-tolerated across various clinical settings, including osteoarthritis, chronic musculoskeletal pain, and cancer-related pain, making it a strong candidate for first-line treatment in chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxycodone/paracetamol: a low-dose synergic combination useful in different types of pain. Gatti, A., Sabato, E., Di Paolo, AR., et al.[2021]

A systematic review and meta-analysis of 14 studies involving 1504 participants found that exogenous oxytocin did not significantly reduce pain intensity compared to a placebo, indicating limited efficacy as a pain management option.

However, narrative evidence suggested that oxytocin may reduce pain sensitivity in specific conditions like back pain, abdominal pain, and migraines, highlighting the need for further research to understand individual differences and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the efficacy of oxytocin for pain management: An updated systematic review and meta-analysis of randomized clinical trials and observational studies. Mekhael, AA., Bent, JE., Fawcett, JM., et al.[2023]

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]

Citations

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Oxycodone - StatPearls - NCBI Bookshelf - NIH This drug is beneficial when used judiciously for pain management, yet it carries the risk of inducing physical dependence and addiction. The immediate-release ...

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Oxycodone Compared with placebo, oxycodone resulted in significantly better pain relief (2.9 ± 1.2 vs 1.8 ± 1.1 on a scale from 0 to 5) and significant reductions in ...

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Effectiveness and safety of new oxycodone/acetaminophen ... After 4 weeks, treatment significantly reduced BPI pain intensity and improved pain relief (P < 0.0005), improved Neuropathic Pain Scale 4 score (P =0.007), ...

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Effects of Short-Term Oxycodone Maintenance on ... This article describes experimental pain, subjective and physiological responses during stabilization and after 6 weeks of oxycodone maintenance.

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Around-the-Clock, Controlled-Release Oxycodone ... Results Use of controlled-release oxycodone, 20 mg, was superior (P<.05) to placebo in reducing pain intensity and the interference of pain with mood, sleep, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01428583

Safety Study of Oxycodone Hydrochloride and Naltrexone ... Safety Study of Oxycodone Hydrochloride and Naltrexone Hydrochloride Extended-Release Capsules in Subjects With Moderate to Severe Chronic Noncancer Pain.

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

Oxycodone (oral route) - Side effects & dosage Oxycodone can cause serious unwanted effects if taken by adults who are not used to strong opioid pain medicines, children, or pets. Make sure ...

8. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/776506

The Comparative Safety of Opioids for Nonmalignant Pain ... During the first 30 days of opioid treatment, the risk of fracture was significantly reduced for tramadol users (RR, 0.21; 95% CI, 0.16-0.28) and propoxyphene ...