Opioids are among the most commonly prescribed medicines for pain. Yet there is a puzzle at the heart of how they work: over time, opioids can make the body more sensitive to pain — an effect called opioid-induced hyperalgesia. In theory, this could create a cycle in which higher and higher doses are needed while pain gets worse rather than better. A 2026 review set out to test whether this happens in practice by comparing how well opioids relieve pain over short and long periods.
Key Takeaways:
- What the review looked at. Researchers pooled 27 randomised trials in people with osteoarthritis or chronic low back pain, comparing opioids with placebo or opioid-sparing pain management.
- Helpful in the short term. Opioids provided meaningful pain relief in short-term trials (four weeks or less).
- Little benefit over time. In trials lasting 12 weeks or more, opioids were no more effective than the comparison, and results leaned slightly in favour of non-opioid treatment.
- What it means. Opioids may help short-term pain, but for long-term conditions their benefit appears to fade — so the decision to continue them needs careful, ongoing review.
How do opioids relieve pain?
Opioids are a group of medicines used for moderate to severe pain. Some are natural, such as morphine and codeine; others are made in a laboratory, such as fentanyl and methadone. They work by attaching to opioid receptors in the body, which dampens pain signals.
Opioids can be effective for short-term pain, but they carry well-recognised risks, including tolerance, dependence, addiction, withdrawal and, at high doses, overdose. Over time, the body can also become used to them, so the same dose may bring less relief. These trade-offs are the reason clinicians think carefully before prescribing opioids for long-term pain.
A recent systematic review and meta-analysis aimed to determine whether the effectiveness of opioid pain relief diminishes over time.
What did the researchers do?
The team carried out a systematic review and meta-analysis — a structured way of finding all the relevant trials and combining their results. They included randomised trials in adults with osteoarthritis (OA) or chronic low back pain (CLBP) that compared an opioid with either a placebo (a dummy treatment) or an “opioid-minimised” approach, meaning non-opioid pain relief was used first and opioids only if other options had been exhausted.
Their main measure was whether people reached a clinically meaningful level of pain relief (broadly, a “moderate” improvement or at least 30% less pain). They also looked at reported pain scores on a standard scale. Crucially, they grouped the trials by how long treatment lasted: short-term (four weeks or less), intermediate-term (four to 12 weeks), and long-term (12 weeks or more).
What did the review find?
Twenty-seven trials met the criteria: 13 short-term, 2 intermediate-term and 12 long-term. Most involved people with osteoarthritis, and across all trials participants were, on average, 57 years old and just over half were women. Oxycodone was the most commonly studied opioid, and most trials compared opioids with a placebo.
How pain relief changed with time
The benefit of opioids differed significantly depending on how long treatment lasted:
Short term (≤4 weeks): people taking opioids were more likely to report meaningful pain relief than those in the comparison groups.
Intermediate term (4–12 weeks): there was no clear difference between opioids and the comparison.
Long term (≥12 weeks): opioids were no more effective than the comparison, and the results actually leaned slightly in favour of non-opioid treatment.
What the pain scores showed
When the researchers looked at reported pain scores, they saw a similar pattern – a trend towards opioids helping less as time went on. However, this particular trend was not statistically significant, partly because the differences in pain between the groups were small at every time point.
What does this mean for people living with chronic pain?
Taken together, the trials suggest that opioids are most likely to provide meaningful relief in the short term — within about four weeks. Beyond 12 weeks, the added benefit over placebo or opioid-sparing care appears to fade, and may even tip the other way.
Osteoarthritis and chronic low back pain are, by their nature, long-term conditions that need ongoing management. This review is a reminder that the balance of benefits and risks can shift over time. It supports checking regularly whether an opioid is still helping, and weighing that against the risk of side effects such as dependence. As always, these are decisions to make with a doctor, not alone.
The researchers noted some limitations. The included trials varied widely in design, and there were signs of publication bias. For example, smaller studies with less favourable results appeared to be missing. Interestingly, that bias would tend to make opioids look better, not worse, which strengthens the review’s main message rather than undermining it.
Speak to a specialist today
Long-term pain can be difficult to manage, and no single treatment suits everyone. If your current pain relief is not working well, it is worth discussing your options with your GP or a qualified specialist, who can review your history and tailor a plan to you.
In the UK, unlicensed cannabis-based medicinal products may be considered by a specialist for certain long-term pain conditions when licensed treatments have not helped or are unsuitable. The evidence for these products is still developing, and they are not a first-line treatment. If you would like to understand more about how they are assessed and prescribed, you can complete our free online eligibility check to find out whether a consultation with one of our specialists could be a suitable next step.
