Heroin Addiction Linked to Long-Term Brain Changes

According to the United Nations Office on Drugs and Crime, nearly half a million Americans are addicted to heroin, a habit-forming narcotic drug derived from the poppy plant. Many heroin addicts will attempt to kick the habit, but they run a high risk of relapse for the rest of their lives, particularly in response to stress or life challenges. Now, researchers at Beijing Institute of Basic Medical Science have reported that persistent changes to the brain associated with heroin addiction may underlie that heightened risk—and offer new suggestions for how to stage successful treatment.

Disorder vs. disease

It remains an ongoing debate in the medical community:  Is addiction a disorder or a disease? The Diagnostic and Statistical Manual of Mental Disorders (DSM-V) categorizes substance abuse as a disorder. That is, a cluster of symptoms with no implication of source, as opposed to a disease where the underlying cause is known. But, time and time again, neuroscientific investigations suggest that addiction causes distinct changes to the brain, with observed dysfunction in specific neural pathways involved in appetitive behavior, risk, and reward processing. It is time to accept that addiction is a disease, plain and simple, says Mary Jeanne Kreek at Rockefeller University, who has been studying addiction for decades.

“We’ve known for some time that addiction has a partly genetic basis. Multiple variants of multiple genes contribute 60% or more of the relative risk in development an addiction,” she says. “But we also see that addiction is linked to physiologic changes in the human brain—at the cellular level and in terms of connectivity. Taken together, these findings given even more sustenance to the fact that addiction is a brain disease, not a disorder.”

Work in Kreek’s lab, among others, has shown that recovered heroin addicts show an abnormal stress response, and that response remains altered for some time. Other studies have shown changes to the resting state activity of the mesocortical limbic circuit, a brain pathway dedicated to appetitive behavior and reward processing, in addicts who have been clean for a short period of time. But would those resting state changes persist over extended periods of time—and perhaps explain why recovered addicts, even after years of abstinence, can still have such strident cravings for the drug?

Long-term changes

To see whether abnormal brain connectivity patterns would remain long after an addict had his or her last hit, Lubin Wang and colleagues at the Beijing Institute of Basic Medical Science used functional magnetic resonance imaging (fMRI) to scan the brains of 30 abstinent addicts from the Sanshui Drug Detoxification and Rehabilitation Center in Guangdong, China, and 30 non-addicts.

“Previous longitudinal follow-up studies reported high relapse rates, 70-90%, among heroin and other drug addicts, including those who cease usage. Even in a 33-year follow-up study, it was found that, even among heroin users abstinent for as long as 15 years, a quarter eventually relapsed,” says Lubin Wang. “So we suspected there may be some latent neural vulnerabilities that led to this.”

When Wang and colleagues compared resting state activity in the nucleus accumbens (NAc), part of the mesocortical limbic circuit, between the former addicts and healthy controls, they found significant dysfunctional activity. Compared with healthy controls, the former addicts showed greater functional connectivity between the NAc and prefrontal cortex and reduced connectivity between the NAc and other key brain areas involved with reward processing.

“The most surprising result of this study is that abnormal functional organization in heroin addicts persists even after years of abstinence,” says Wang. “Understanding the patterns of nucleus accumbens activity with other brain regions may contribute to a better understanding of the neural mechanisms underlying drug dependence.”

Marcus Raichle, a neurologist at the Washington University at St. Louis School of Medicine, who pioneered research efforts into resting state activity, calls this finding compelling. “It speaks to the fact that you have to appreciate that addicts, even those who cease using, have changes to the basic organization of the brain,” he says. “And it probably explains a good bit about why people relapse, even if they’ve gone through various programs or attempts to quit, because the brain has changed, and it isn’t about to go flipping back on a moment’s notice.”

Raichle, also a member of the Dana Alliance for Brain Initiatives, has long argued that the brain is in the “prediction business.” Its resting state helps provide it with the proper information to make those important predictions. “This is why healthy intrinsic activity is so important. If those connections aren’t well-organized, it could explain all kinds of problems ranging from differences in personalities, to differences in behavior, to whether we’ll become or stay addicted to a drug.”

Moving forward

Wang says these findings may act as a biomarker of persistent drug addiction—which may, in the future, help clinicians evaluate the effect of treatments for individuals. They may also predict who is most at risk for relapse and explain why everyday life stressors can be such triggers in abstinent addicts. But what these results can’t tell us is whether such perturbations to the resting state of the brain, particularly in this key region, were present before addiction took root. Still, Kreek says it provides additional evidence that addiction should be defined as a disease—and doctors need to take note of these long-term changes when considering treatment.

“People who meet the criteria for an opiate addiction need to get into effective treatment programs. That means methadone maintenance or buprenorphine maintenance, coupled with counseling and behavioral therapy,” she says. “And yes, addicts are going to be in treatment for a long time. We don’t know how long, exactly. Many may be in treatment for the rest of their lives, much as someone with a chronic condition like diabetes, hypertension, or a thyroid disorder will be in treatment for the rest of their lives. This is a disease. We see that the brain has clearly changed and we need to offer treatments that acknowledge that it has.”