Pain management is a critical part of healthcare, but relying on opioid painkillers carries significant risks like addiction and overdose. In recent decades, the United States has faced an opioid epidemic, urging medical professionals to seek safer alternatives. [1] Non-opioid pain management options are more important than ever, as they can provide effective relief for many conditions without the same level of risk.
- There are many ways to relieve pain without opioids – from over-the-counter and prescription medications (like acetaminophen or ibuprofen) to nondrug therapies such as CBT and acupuncture.
- Non-opioid treatments can be as effective as opioids for many common types of pain, and they do not carry the same risk of addiction or overdose.
- The FDA has approved new powerful non-opioid pain medications (e.g., suzetrigine, brand name Journavx™) for severe pain, expanding alternatives to opioid painkillers.
The importance of non-opioid medications
Opioid drugs (like morphine or oxycodone) are used for pain, but their potential for dependence and life-threatening overdose has led to a shift in pain management. Healthcare providers now try to use non-opioid medications and therapies as first-line treatments whenever possible. [2]
Using alternative pain medications helps patients avoid the well-known risks of opioids while still addressing pain and improving function. CDC clinical guidance released in January 2025 states that non-opioid medicines and non-drug therapies “are at least as effective as opioids” for common short-term pains such as dental work, sprains, and minor surgery. [2]
A tailored, multimodal approach, combining medications like anti-inflammatories with physical therapy and other methods, is considered essential to safely manage pain without relying too much on opioids. [1] By reducing opioid use/intake, patients can achieve relief with fewer side effects and a much lower chance of developing dependence or an opioid use disorder.
Types of non-opioid pain relief
Non-opioid pain management options fall into two main groups: medications (non-opioid drugs) and non-medication therapies (physical or behavioral treatments). Both types can be combined to reduce pain effectively.
FDA approved non opioid pain medication
Non-opioid pain medications include many familiar drugs that help with pain. Over-the-counter examples are acetaminophen (Tylenol) and what doctors call nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen. [3] These can handle mild to moderate pain quite effectively.
Doctors also use other non-opioid prescription medications for pain. Certain antidepressants (like amitriptyline, doxepin, and nortriptyline) or anti-seizure drugs (like gabapentin and pregabalin) can relieve nerve pain (neuropathic pain), and local anesthetics (like a lidocaine patch) can numb pain in a region. [4]
A 2024 meta-analysis of ten randomized controlled studies found that a fixed-dose ibuprofen + acetaminophen tablet matched or beat single-agent opioids for moderate post-operative pain, while causing fewer side effects. [5]
In hospital settings, even an anesthetic like ketamine (a non-opioid) is sometimes used at low doses to control severe pain without opioids. [6]
Non-FDA-approved pain relief
While FDA approved for sedation during procedures, dexmedetomidine (Precedex) can be used off-label for intraoperative pain relief, particularly as part of a multimodal analgesia approach. It's a sedative and anxiolytic with analgesic properties that can reduce pain scores, opioid consumption, and improve patient satisfaction. [7]
For example, the 2024 adult and paediatric enhanced recovery after surgery (ERAS) updates list intraoperative dexmedetomidine (Precedex) as a standard opioid-sparing measure.
Outside the hospital setting, people also try alternative pain remedies like medical marijuana or CBD products. Some consumers report pain relief from cannabis, but these substances are not approved by the FDA and lack regulated quality. [8]
Experts warn that marijuana and cannabinoids may not be safer than conventional medicines and can have side effects. [3] Likewise, various herbal supplements are used for pain but have unproven benefits. Always consult a doctor before using unregulated products for pain – “natural” doesn’t automatically mean “safe.”
Non-medication pain relief
Non-drug therapies can play a critical role in pain management, especially when used alongside non-opioid medications. These approaches include physical treatments, procedures, and mind-body strategies:
- Physical treatments include: Physical therapy and expert-guided exercise programs; Massage, acupuncture, and dry needling; and Transcutaneous Electrical Nerve Stimulation (TENS), which delivers mild electrical impulses through the skin to interfere with pain signals, is sometimes used for back pain, arthritis, or joint issues. A 2024 systematic review found that high-intensity TENS used during physical activity provided meaningful pain relief, while low-intensity or passive TENS offered little benefit. [9]
- Procedural options such as targeted nerve blocks or localized injections are sometimes used to interrupt pain pathways. [3]
- Mind-body approaches, like cognitive-behavioral therapy (CBT), relaxation techniques, and biofeedback, help many people manage the emotional and psychological aspects of chronic pain. [10]
These methods are usually combined for a personalized, multimodal pain management plan.
Can they be as effective as opioid painkillers?
A common and pressing question is whether non-opioid treatments can control pain as well as opioids do, especially for severe pain. The good news is that yes, they often can. As mentioned, the CDC reports that non-opioid therapies are at least as effective as opioids for many common types of acute pain. [2]
Injuries like sprains, dental extractions, or many cases of back pain can be managed successfully with NSAIDs, acetaminophen, and other methods, achieving similar pain relief without needing opioids. [2] Even in chronic pain conditions, studies have found that opioids are not significantly more effective than non-opioid medications in the long term, but opioids carry far more side effects. [1]
Patients might also wonder what the most potent non opioid painkiller is, since opioids are known for treating severe pain. In medical practice, certain non-opioid drugs can be highly potent. For instance, ketamine is a dissociative anesthetic that doctors use at low doses to treat intense acute pain; it is considered one of the most powerful non-opioid painkillers and can provide rapid relief even for severe post-surgical pain. [6]
Additionally, new medications like suzetrigine (Journavx™) have shown that non-opioids can rival opioids in pain-relieving strength. [11] Once again, by using combinations of non-opioid strategies, for example, combining an NSAID with acetaminophen, or pairing medication with a nerve block, healthcare providers can match opioid-level pain control more safely.
Risks of non-opioid pain relief
Choosing non-opioid options avoids the addiction and overdose risks of opioids, but it does not mean zero risk. Any medication or treatment can have side effects or downsides.
- Long-term or high-dose NSAID use irritates the stomach lining, leading to ulcers or bleeding, and can also impair kidney function. [12]
- Acetaminophen is much safer for the stomach, but can cause severe liver damage if too much is taken. [12]
- Other prescription non-opioids (like antidepressants or anticonvulsants used for pain) have their side effects, such as drowsiness or dizziness.
- “Natural” remedies can also be risky; certain herbal supplements could interfere with other medications or cause unexpected reactions.
People who should not use non-opioid painkillers
Although non-opioid painkillers are generally safe for most people, certain individuals need to avoid specific kinds of these medications. NSAIDs are not suitable for some patients: [12]
- People with advanced kidney disease
- People with active stomach ulcers or a history of severe gastrointestinal bleeding
- People with heart failure
- People currently treated with anticoagulants (blood thinners)
NSAIDs can also trigger asthma flare-ups in a subset of patients with asthma, and they are usually avoided in late pregnancy.
Acetaminophen should be avoided by: [12]
- People with severe liver disease
- People who struggle with active alcohol abuse
In all such cases, doctors can recommend alternative pain treatments that bypass these risks.
Research and new pain relief options
Researchers are continually developing new non-opioid pain medications to improve pain management without opioids. A major recent breakthrough is the FDA’s approval of suzetrigine (Journavx™) in early 2025; this is a first-in-class non-opioid analgesic for moderate to severe acute pain. [11]
Suzetrigine blocks specific sodium channels in nerves, preventing pain signals from reaching the brain. Its approval was hailed as a milestone, as it offers a new option to treat severe pain while mitigating the risks associated with opioids. [11] Two phase-3 randomized trials (874 adults after bunionectomy or abdominoplasty) showed that a single oral dose cut pain scores for 24 hours and lowered rescue ibuprofen use by ~35 % versus placebo. [11]
Journavx™, however, is just one example of innovation in this field. Other pharmaceutical companies are testing novel painkillers that do not rely on opioid receptors. However, access to new medications like suzetrigine may be limited in low-resource or underserved regions, highlighting persistent global disparities in pain care.
In 2025, Tris Pharma announced successful phase 3 trial results for cebranopadol, a non-opioid medication for severe pain. [13] In addition, another experimental drug, AP-325, has shown promising results in early studies for neuropathic pain. [13]
Practicing safe opioid use for pain relief
Sometimes opioid painkillers might be needed to control severe pain, potentially after major surgery or for specific acute injuries. Thus, you must know how to use them safely. Safe opioid use means:
- Taking opioids exactly as prescribed by a doctor and only for the shortest duration necessary
- Taking the lowest effective dose
- Avoid combining opioids with alcohol or sedative drugs (like benzodiazepines) unless specifically instructed by their doctor, as such combinations heighten the risk of overdose
- Not to share opioid medications with others
- Store them securely out of reach of others (especially children or those who might misuse them).
Opioids are generally safe when taken for a brief period under medical supervision. Still, misuse, such as taking higher doses or using someone else’s prescription (diversion), increases risks of addiction and overdose. [14] Patients can minimize risks by closely following the doctor’s guidelines and tracking how much they use. [14]
When to seek help
People must seek help if they find themselves struggling with uncontrolled pain or with any medication use or misuse, especially opioid medication. If severe pain is not improving despite non-opioid treatments, consult a healthcare provider. You may need a re-evaluation of your pain management plan. [14]
Equally crucial, be alert for warning signs of opioid dependence or addiction if you are using opioid painkillers. Signs of trouble include: [14]
- Needing higher doses to get the same relief
- Feeling unable to cut back on the opioid
- Using it for reasons other than pain (such as to feel good)
- Taking more than prescribed
If you notice any of these red flags in yourself or a loved one, seek professional help immediately. Talk to your doctor about your concerns; they can adjust your treatment and provide resources. You can also contact addiction support services, for example, the SAMHSA National Helpline (1-800-662-4357 in the U.S.) is a confidential service that can guide you to appropriate help.
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