Beyond Omics: Integrating Subjective Responses in Opioid Use Risk Prediction

Megan Rolfzen, MD

The opioid epidemic continues to evolve. The “third wave” is an era marked by illicit fentanyl, which claims 220 lives per day in the United States. On Friday, May 1, at the 2026 Annual Meeting, presented by IARS and SOCCA, the “Opioid Misuse Risk Stratification: Role for Assessment of Subjective Responses to Opioids” session brought together three engaging speakers who challenged the status quo of risk stratification. They argued that the future of preventing opioid misuse, opioid use disorder, and new persistent opioid use, may lie not just in a patient’s history, but their unique subjective response to the drugs themselves.

Chad Brummett, MD, a professor of Anesthesiology, senior associate chair for Research, and co-director of the Overdose Prevention Engagement Network (OPEN) at the University of Michigan, opened the session by highlighting the sobering reality that prescription opioids around the time of surgery are the starting point for new persistent use. Data show that new persistent opioid use, defined as use longer than would be expected for normal surgical recovery, occurs in 6-19% of patients, depending on surgery subtype. However, this phenomenon is not universal. Research by Ladha et al. in JAMA Network Open shows there is large variability in the use of opioids in different countries, with higher rates in the United States and Canada, and lower rates in Sweden. Traditionally, clinicians identify high-risk patients using variables like community deprivation, male sex, and histories of psychiatric illness. Recent studies have demonstrated a correlation between the number of opioids consumed in the first 30 days after surgery and the probability of persistent use. Despite policy shifts to smaller initial prescriptions and lower refill rates, a uniquely vulnerable subset of patients continues to slip through the cracks.

The challenge is to identify that vulnerability before it’s too late. Daniel Larach, MD, MS, MA, an associate professor of Anesthesiology at Vanderbilt University Medical Center, is focusing efforts on the “preaddiction” stage: a critical, but understudied window before opioid use disorder is diagnosed. Referencing the three-stage model of addiction, proposed by George Koob, PhD, National Institute on Alcohol Abuse and Alcoholism director, and Nora Volkow, National Institute on Drug Abuse director, he explained the neurobiological underpinnings for the transition from initial opioid use to dependence. However, there is a notable gap in longitudinal human data. Dr. Larach argues that if the initial rewarding response (“the high”) and subsequent negative affect (“the crash”) can be confirmed as reliable predictors of opioid use disorder, the field can move toward precision opioid prescribing. Essentially, a patient’s subjective experience can dictate their management plan.

Closing the session, Marie Eikemo, PhD, senior researcher and principal investigator with joint appointments at the University of Oslo and Oslo University Hospital in Norway, discussed how a person’s affective state during opioid administration or use can affect the subjective response. Dr. Eikemo introduced the ongoing Norway Operations and Opioids (NorOp), a prospective trial of surgical patients in Norway examining how a patient’s emotional state at the time of exposure influences their risk. Her preliminary results suggest that emotional context is key: stress increases self-administration of oxycodone, particularly in men. Furthermore, the evidence suggests an exposure paradox: the odds of improved well-being ratings after opioid consumption are higher in patients with previous opioid exposure. Intriguingly, opioid-induced improvement in subjective well-being is relatively less frequent in opioid naïve individuals. Given the variation in opioid prescribing practices in Scandinavian countries, these findings offer food for thought in countries where opioid prescription and use are more common.

The combined work presented in this session reminds clinicians that monitoring for the “euphoria factor” may be just as important as monitoring for the “analgesic factor.” The evolution of the opioid crisis offers a parallel to the evolution of risk prediction and stratification. By moving beyond broad population metrics and animal models towards a personalized safety model, anesthesiologists can be at the forefront of identifying vulnerable individuals during a standardized “stress” event in the hospital. By confronting the issue before inception, perioperative providers might be able to effect change before a transition from perioperative opioid use to persistent use or a disorder occurs.