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

Trial Summary

What is the purpose of this trial?

Some research suggests that administration of oxytocin with oxycodone may reduce its abuse liability and improve its ability to reduce pain. In a 6-session laboratory study, the investigators will be evaluating the effects of oxycodone and oxytocin (combined and separately, across sessions) on experimentally-induced pain, subjective effects, decision-making, and activation of different neural substrates.

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.

What data supports the effectiveness of the drug combination of oxytocin and oxycodone for pain management?

Research shows that oxycodone, when combined with acetaminophen, is effective for managing moderate-to-severe pain due to their complementary actions, which may suggest potential benefits when combined with other agents like oxytocin. Additionally, oxycodone alone has been effective in reducing pain in various settings, including postoperative and cancer-related pain. ^{1 2 3 4 5}

Is the combination of oxytocin and oxycodone generally safe for humans?

Oxycodone has been studied for safety in various conditions, showing it can be used safely for pain relief, but it may cause side effects like constipation and vomiting. There is no specific safety data available for the combination of oxytocin and oxycodone. ^{1 6 7 8 9}

What makes the drug oxytocin + oxycodone unique for pain management?

This drug combination is unique because it combines oxycodone, a common opioid pain reliever, with oxytocin, a hormone that has potential analgesic (pain-relieving) properties and may offer pain relief with fewer side effects. Oxytocin's role in pain management is being explored for its non-addictive nature and ability to modulate pain through different mechanisms than traditional opioids. ^{10 11 12 13 14}

Research Team

Meredith S Berry, PhD

Principal Investigator

University of Florida

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2023]

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

Retrospective Evaluation of a Fixed-Dose Combination of Oxycodone and Acetaminophen to Manage Moderate Pain: The Lower the Better. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Oxycodone/paracetamol: a low-dose synergic combination useful in different types of pain. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Spontaneously reported adverse drug events related to tapentadol and oxycodone/naloxone in Australia. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Oxycodone/naloxone versus tapentadol in real-world chronic non-cancer pain management: an observational and pharmacogenetic study. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. [2020]

9. England 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. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Up-regulation of oxytocin receptors on peripheral sensory neurons mediates analgesia in chemotherapy-induced neuropathic pain. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Intrathecal oxytocin inhibits visceromotor reflex and spinal neuronal responses to noxious distention of the rat urinary bladder. [2022]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Brain uptake and the analgesic effect of oxytocin--its usefulness as an analgesic agent. [2019]

13. England 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. [2022]

14. United States 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. [2023]