Endogenous Opioid Supply May Predict Medication Overuse

Endogenous Opioid Supply May Predict Medication Overuse
Environmental, genetic and lifestyle factors are at play in projecting which patients will be at risk of misusing pain medication.

People living with chronic stress are more likely to develop opioid use disorder, a connection that Vanderbilt University Medical Center researcher and clinical psychologist Stephen Bruehl, Ph.D., says is likely tied to low endogenous opioid and endocannabinoid reserves in the brain.

Bruehl’s work is part of a NIH-backed project to determine the impact of stress on patients prescribed pain medication and whether the condition puts them at higher risk for opioid dependence.

Stress can be anything from minor tribulations of daily life to societal pressures such as poverty and crime, Bruehl said.

Natural Responses

The body’s natural response to stress is regulated by the release of endogenous opioids, natural chemicals such as enkephalins and endorphins that act in the same manner as drugs such as morphine.

Activity in the endocannabinoid system, with its lipid-signaling molecules that mimic the activity of THC, the key active ingredient in marijuana, also helps regulate the stress response.

When supplies of endogenous opioids and endocannabinoids become depleted, which may happen in cases of prolonged stress or chronic pain, the effects of pain medication like morphine and hydrocodone become more pronounced. The result is both greater analgesia and intensification of appealing side effects such as euphoria.

Patients Who Benefit Most

Through his research, Bruehl is testing whether reductions in endogenous opioids and endocannabinoids caused by stress are contributing factors in opioid dependence.

In earlier research, Bruehl looked at endogenous opioid and endocannabinoid activity as they relate to morphine responsiveness, finding that “analgesic medications like morphine may work best in individuals having low natural pain inhibitory capacity, both opioid and non-opioid (i.e., endocannabinoid).”

The goal of both lines of research is to personalize the practice of treating pain by determining how to identify patients who can benefit most from certain pain medications without creating a high risk of misuse, he said.

The roles of anxiety, depression, and heightened pain sensitivity are among factors being examined in relation to the depletion of endogenous opioids. Stressful childhoods, chronic stress, sedentary lifestyle and chronic pain may also affect these systems, Bruehl said.

Non-opioid Options

Understanding more about biological mechanisms that influence risk for opioid dependence could give patients opportunity to mitigate their own situation, Bruehl said.

“We have found in our prior studies that people with chronic pain who do aerobic exercise find their pain decreases, and this is linked to elevated endogenous opioids that produce the feeling called a runner’s high,” he said.

Other practices such as relaxation training and meditation also have been known to stimulate a natural anti-pain and anti-stress response that may involve endogenous opioids. Interventions such as these that increase our body’s natural ability to inhibit pain potentially could also reduce risk for opioid dependence.

A closer look at the mechanisms of pain and opioid medication risks will begin in spring 2022, as the team begins a five-year study to examine individual differences in opioid responses in 120 people with chronic low back pain.