Researchers map clinical neuroimaging markers for opioid withdrawal.


Within a few months after drug withdrawal, patients in recovery from dependence on prescription pain medications may show signs that the body’s natural reward systems are normalizing. The study from researchers at Penn State University provides evidence of physiological re-regulation of disrupted brain and hormonal responses to pleasurable stimuli, both drug, and nondrug-related.  The opensource study is published in the Journal of Addiction Medicine.

The pilot study included two groups of seven patients in residential treatment for dependence on opioid pain medications. One group had recently gone through medically assisted opioid withdrawal, within the past one to two weeks. The other group was in extended care, and had been drug-free for two to three months. A group of normal controls were studied for comparison.

The researchers performed several tests to assess changes in the brain reward system during early recovery. After drug withdrawal, many people with opioid dependence have persistent changes in the reward and memory circuits, they may experience heightened rewards or pleasure in response to drugs and related stimuli, but greatly reduced responses to naturally pleasurable stimuli (such as good food, or friendship).

This is thought to occur because opiates are potent stimulators of the brain’s reward system; over time, the brain adapts to the high level of stimulation provided by opiates, and naturally rewarding stimuli can’t measure up. Such dysregulation of the natural reward system may contribute to the high risk of relapse during recovery.

In all tests the patient’s prefrontal cortex was monitored with functional near-infrared spectroscopy to image activity in the brain’s reward circuit. The test results showed several significant differences in the reward system between groups. A test of startle reflexes showed that patients with recent drug withdrawal had reduced pleasure responses to natural reward stimuli, for example, pictures of appetizing foods or people having fun.

In brain activity studies, patients with recent drug withdrawal showed heightened responses to drug-related cues, such as pictures of pills. In the extended-care patients, these increased responses to drug cues, in a region of the brain called the prefrontal cortex, involved in attention and self-control, were significantly reduced.

Patients who had recently withdrawn from opiates also had high levels of the stress hormone cortisol (adrenaline). In the patients who had been drug-free for a few months, cortisol levels were somewhat reduced, although not quite as low as in healthy controls. The recently withdrawn group also had pronounced sleep disturbances, while sleep in the extended care group was similar to controls.

All of these changes, brain and hormonal responses to drug cues and natural rewards, as well as sleep disturbances, were correlated with abstinence time. The more days since the patient used drugs, the lower the abnormal responses.

The study supports past research showing dysregulation of the reward system during early recovery from opioid dependence. It also provides evidence that these responses may become re-regulated during several weeks in residential treatment, a period of clinically documented abstinence from opioids.

The team state that this study is a potentially important step forward in addiction medicine research.  It shows that if the patient remains in treatment and off drugs for several months, the body’s natural reward systems may have the capacity to return toward normal, making it easier for them to remain drug-free outside the treatment setting.  With further study, tests of the natural reward system might provide useful, objective markers of recovery, clinical tests that help to evaluate how the patient’s recovery is proceeding.

Such tests might help in managing the difficult problem of prescription opioid dependence, an ongoing epidemic associated with a high risk of relapse after drug withdrawal. The researchers are conducting a follow-up study to determine whether measures of the brain’s reward system, sleep and the stress response system indicate the capacity for re-regulation and the patient’s risk of relapse during recovery.

Source:   Wolters Kluwer Health

A)  Functional near-infrared spectroscopy region of interest; right dorsolateral prefrontal cortex (DLPFC).  Colored areas represent optodes differentiating the recent withdrawal from the extended care groups.   B)  Functional near-infrared spectroscopy region of interest; right dorsolateral prefrontal cortex (DLPFC).  Red area represent optodes differentiating the recent withdrawal from the extended care and healthy control groups.  Possible Evidence for Re-regulation of HPA Axis and Brain Reward Systems Over Time in Treatment in Prescription Opioid-Dependent Patients.  Bunce et al 2014.

A) Functional near-infrared spectroscopy region of interest; right dorsolateral prefrontal cortex (DLPFC). Colored areas represent optodes differentiating the recent withdrawal from the extended care groups. B) Functional near-infrared spectroscopy region of interest; right dorsolateral prefrontal cortex (DLPFC). Red area represent optodes differentiating the recent withdrawal from the extended care and healthy control groups. Possible Evidence for Re-regulation of HPA Axis and Brain Reward Systems Over Time in Treatment in Prescription Opioid-Dependent Patients. Bunce et al 2014.

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