What are safe alternatives to synthetic opioids for non-medical use?

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Last updated: June 3, 2025View editorial policy

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From the Guidelines

There are no safe alternatives to synthetic opioids for non-medical use, and using any opioid without medical supervision is dangerous and potentially life-threatening. Instead, if you're experiencing pain, consider evidence-based non-opioid approaches such as acetaminophen (Tylenol) or NSAIDs like ibuprofen (Advil, Motrin) for mild to moderate pain, following package directions 1. For emotional or psychological issues that might lead to substance use, healthier alternatives include exercise, which releases natural endorphins; mindfulness meditation; cognitive behavioral therapy; and professional counseling. If you're struggling with substance use disorder, please seek help from a healthcare provider, call SAMHSA's helpline (1-800-662-4357), or find local support groups. These approaches address underlying issues without the serious risks of opioid use, which include addiction, respiratory depression, overdose, and death. No recreational use of opioids, synthetic or otherwise, can be considered safe.

Some key points to consider:

  • Opioid use disorder is a leading cause of morbidity and mortality among US youth, and effective treatments are available but underused 1.
  • Methadone is a synthetic, long-acting, Schedule II opioid used to treat opioid use disorder, but its administration to alleviate acute opioid withdrawal is not common in many emergency departments due to its long duration of action and potential to interfere with ongoing opioid treatment program adherence 1.
  • Buprenorphine has a role in the analgesic therapy of patients with renal impairment undergoing hemodialysis treatment, but dose conversion from other opioids to buprenorphine can be complex and requires palliative care advice 1.
  • Fentanyl and buprenorphine are the safest opioids in patients with chronic kidney disease stages 4 or 5, but opioid switching should be done with caution and under the guidance of experienced professionals 1.
  • Non-opioid approaches, such as non-steroidal anti-inflammatory drugs, gabapentinoids, acetaminophen, regional analgesic techniques, and non-pharmacological adjuncts, are recommended as part of a larger multimodal approach to manage pain and sedation in the intensive care unit 1.

From the Research

Synthetic Opioids and Toxicology Screens

  • There is no direct evidence to suggest that synthetic opioids won't show up on a toxicology screen 2, 3, 4, 5, 6.
  • However, it's essential to note that toxicology screens may not detect all types of synthetic opioids, especially new or emerging substances.

Safe Alternatives to Synthetic Opioids

  • Medications like methadone, buprenorphine, and naltrexone are effective treatments for opioid use disorder (OUD) and can be considered safe alternatives to synthetic opioids 2, 3, 4.
  • These medications can help reduce opioid cravings, increase treatment retention, and decrease illicit opioid use 3, 4.
  • Buprenorphine and methadone are first-line treatment options for OUD, and they have been shown to reduce fatal and nonfatal opioid overdose and infectious complications of OUD 4.

Comparison of Medications for OUD

  • A study comparing methadone, buprenorphine, and naltrexone found that methadone was associated with a higher risk of cardiac arrhythmias, long QT syndrome, and death compared to buprenorphine and naltrexone 5.
  • Another study found that fentanyl exposure was associated with reduced likelihood of treatment initiation and shorter median times in assigned and overall MOUD discontinuation, but the negative effects were no longer statistically significant in adjusted models 6.

Treatment Considerations

  • Interdisciplinary office-based addiction treatment programs can support high-quality OUD care 4.
  • Take-home naloxone programs can help prevent fatal overdose by providing an opioid antagonist to reverse opioid overdose 2.
  • Expanding access to approved treatments like methadone, buprenorphine, and naltrexone may be the most useful approach to addressing the opioid epidemic 2, 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Medication Treatment of Opioid Use Disorder.

Biological psychiatry, 2020

Research

Medications for management of opioid use disorder.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2019

Research

Opioid Use Disorder.

Annals of internal medicine, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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