Key Points

  • The largest review of opioids for acute pain to date, covering 59 systematic reviews and more than 50 conditions, found the drugs provided only small, short-lived relief compared with placebo for most conditions, often lasting just a few hours.
  • For several specific conditions, including kidney stone pain, some limb surgeries, and post-tonsillectomy pain, opioids showed no clear advantage over placebo.
  • Persistent use can develop quickly after a first prescription, sometimes within days. Many people who develop opioid use disorder were first introduced to opioids through a legitimate prescription.
  • Brain imaging shows measurably smaller hippocampal volumes in both hemispheres of people with opioid use disorder, with the largest effect in the posterior right hippocampus, a region tied to detailed contextual memory.
  • People with a severe mental illness such as a psychotic disorder or bipolar disorder face a 16% higher risk of leaving opioid agonist treatment during their first episode of care.
  • The risk of dropping out decreases across successive treatment episodes, pointing to the need to front-load intensive support from the very beginning of care.

Addiction News Weekly Episode 1.7

In This Episode:

Episode Transcript

Welcome to Addiction News Weekly by Rehab.com, where we break down the biggest stories in addiction, recovery, and public health. This week we go deep on opioids from three angles, including what the largest review to date says about how well opioids actually treat short-term pain and how fast dependence can start, what chronic opioid use looks like in the brain, and why staying in treatment is so hard when a serious mental illness is also in the picture, plus what the evidence says helps. Let’s get into it.

Opioids and Short-Term Pain: What the Largest Review Found

We start with a sweeping new look at opioids for short-term pain. Researchers at the University of Sydney led the largest review to date of opioid medications for acute pain, published in the journal Drugs.1,2 They pulled together 59 systematic reviews covering more than 50 acute pain conditions in children and adults.

The researchers looked at how well drugs like codeine, morphine, oxycodone, and tramadol actually work. For most acute pain conditions, lead author Associate Professor Christina Abdel Shaheed reported that opioids gave only small, short-lived relief compared with a placebo, often lasting just a few hours.1 For acute musculoskeletal pain, which opioids are often prescribed for, oral opioids were only slightly better than placebo in the first 6 to 48 hours.

For several conditions, including kidney stone pain, some limb surgeries, and pain after tonsil removal, opioids offered no clear advantage over placebo at all. Alongside that limited benefit sits real risk. The reviewers flagged familiar side effects like nausea and vomiting, and noted that regular use carries the risks of tolerance, dependence, misuse, overdose, and death.

Co-first author Dr. Stephanie Mathieson noted that persistent use can develop quickly after a first prescription, sometimes within days.1 Many of those who develop opioid use disorder are first introduced to opioids through a completely legitimate prescription. However, none of this means avoiding needed pain care. Rather, it means that cravings, rising doses, using opioids deliberately, or withdrawal between doses are all early signs worth raising with a clinician.

What Chronic Opioid Use Does to the Brain

Our second story is about what opioid addiction does to the brain, and it comes with an important nuance. A new study in Drug and Alcohol Dependence compared brain scans from 94 people with opioid use disorder to 40 people without a substance use disorder, and found that the hippocampus, the brain’s hub for memory, was measurably smaller in both hemispheres of those with opioid use disorder.3 The effect was strongest in the back portion of the right hippocampus.

For the clinical read, here is Rehab.com Medical Officer Dr. Sylvie Stacy. This study quantifies something that we encounter in clinical practice all the time. That is that having a severe mental illness like a psychotic disorder or bipolar disorder makes staying in treatment for opioid use disorder significantly more difficult, especially at the very beginning of treatment. The study shows that the risk of dropping out of care during the first treatment episode is 16% higher for these individuals.

This matters because our care systems often treat mental health and substance use as separate issues. In fact, Dr. Stacy recently had a patient with severe bipolar disorder who was trying to stabilize on methadone, but the methadone program did not offer comprehensive mental health management. It only offered treatment for opioid use disorder, along with some care coordination and referrals for other healthcare services. So when this patient had a manic episode, his life became really disorganized. He missed his clinic appointments and ended up dropping out of treatment.

Because he was out of care, he returned to illicit fentanyl use and suffered a severe but nonfatal overdose. Dr. Stacy notes that the risk of dropping out actually diminishes over successive treatment attempts, meaning that the highest intensity support needs to be front-loaded at the start of care. Having mental health treatment in place from the beginning would have not only stabilized this patient’s mental health issues, but helped him stabilize on methadone as well. Moving forward, the field needs to transition away from standard medical protocols that require a level of administrative stability a patient in a psychiatric crisis cannot meet, and toward integrated low-barrier clinics where a patient can receive psychiatric medications and treatment for opioid use disorder in the same visit.

Staying in Treatment When Mental Illness Is Also Present

Our third story is about one of the hardest parts of recovery: staying in treatment. A study published in Drug and Alcohol Dependence followed 14,763 people in New South Wales, Australia, who started opioid agonist treatment for the first time, tracking them from 2006 to 2017 by linking their treatment, hospital, mental health, and mortality records.4 About 13.5% had a severe mental illness, meaning a psychotic or bipolar disorder.

Here is Dr. Stacy again on what they found and why it matters. The data from this study really helps visualize what patients mean when they talk about brain fog or feeling like their memory is failing them. The structural changes the paper describes are not uniform throughout the brain. The volume loss is heavily localized in the posterior region of the hippocampus, and that back part of the hippocampus is responsible for retrieval of very fine details and contextual memory. When that brain tissue is compromised, patients struggle with cognitive tasks that require recall.

In Dr. Stacy’s practice, some patients’ family members, or other clinicians involved in their care, have suspected relapse based on the memory symptoms they were observing. But those patients were not relapsing. The memory difficulties were most likely a structural deficit in the brain’s memory retrieval system. The data also shows that patients on methadone had the smallest hippocampal volumes compared with both controls and those on buprenorphine.

We cannot assume that methadone causes this damage. It is far more likely that patients on methadone represent a group with greater cumulative opioid exposure, higher baseline addiction severity, and more frequent past episodes of hypoxia. Memory issues are separate from a person’s commitment to recovery. They are not a character flaw, and they are not something that can easily be changed. They are another complication of addiction and another area where clinicians can provide support as people move through recovery.

Conclusion

Put these stories together, and the picture of the opioid problem becomes clearer. These medicines often help with short-term pain less than people assume, and dependence can start faster than expected. Chronic addiction leaves a real mark on the brain, and staying in treatment is genuinely hard, especially early and especially alongside a serious mental illness. But there is hope. Targeted treatment is what interrupts exposure, protects the brain, and sharply lowers the risk of death for everyone, including people managing a mental illness at the same time.

If you or a loved one is looking for treatment, Rehab.com lists thousands of verified centers across the country. Free, confidential support is available anytime through the SAMHSA National Helpline at 1-800-662-4357. If you are in crisis, you can call or text 988 at any time.

Those are the top stories in the news. For more, visit Rehab.com. We will be back next week. I am Kay, and thank you for listening.

You Might Also Like

  1. Opioid Addiction and Treatment Options — Comprehensive guide to opioid and opiate substances, mechanisms of addiction, and pathways to treatment
  2. Dual Diagnosis: Understanding Drug Addiction and Mental Health — Explains co-occurring disorders and the importance of integrated treatment for mental health and substance use
  3. Methadone Medication-Assisted Treatment for Opioid Addiction — How methadone works as a long-acting opioid agonist, clinic structure, and what to expect
  4. Opioid Withdrawal: Symptoms and Timeline — Guides readers through the withdrawal process, medications like buprenorphine and methadone, and benefits of professional detox

Sources in This Episode

  1. Mathieson S, Zadro JR, Narayan SW, et al. Efficacy and harms of opioid analgesics for acute pain: overview of systematic reviews and meta-analyses. Drugs. 2026;86(4):533. doi:10.1007/s40265-026-02284-3. https://link.springer.com/article/10.1007/s40265-026-02284-3 Accessed July 14, 2026.
  2. University of Sydney. Researchers warn: opioids aren’t effective for many acute pain conditions. Published February 26, 2026. https://www.sydney.edu.au/news-opinion/news/2026/02/26/researchers-warn-opioids-arent-effective-for-many-acute-pain-conditions.html Accessed July 14, 2026.
  3. Gisev N, Santo T Jr, Lappin J, et al. The impact of severe mental illness on treatment retention and all-cause mortality of people in opioid agonist treatment: a retrospective cohort study. Drug Alcohol Depend. 2025; in press. Available via UNSW National Drug and Alcohol Research Centre: https://www.unsw.edu.au/research/ndarc/ndarc-projects/opioid-agonist-treatment-and-safety-oats-studies
Dr. Sylvie Stacy
By Dr. Sylvie Stacy
Published on July 14, 2026
Sylvie Stacy, MD, MPH, Medical Officer at Rehab.com, is a board-certified addiction medicine specialist with over a decade of experience treating individuals with addictions in diverse clinical settings including residential treatment programs, detox centers, outpatient clinics, and correctional facilities.