Illustration of human head with brain and pills.
RESEARCH FEATURE

NIH HEAL Initiative: Science taking on pain, opioid misuse—and poor sleep 


The story of the U.S. opioid crisis is often told through numbers. And for many that makes sense, because the numbers are staggering: More than two million Americans suffer from opioid use disorder (OUD), a serious, but treatable chronic illness that claims the lives of more than 130 people every day. Many with OUD carry another burden, however: they are among the more than 50 million adults affected by chronic, often debilitating pain, and their addiction, often the fallout of their quest for relief.

Opioids accounted for nearly 68 percent of the more than 70,000 deaths from U.S. drug overdoses in 2017. And those deaths are no longer confined mainly to white communities. While the epidemic still kills more white Americans, the number of deaths is increasing faster among African Americans and Latinos, according to a report by the National Centers for Disease Control and Prevention.

Sex differences also exist. Men use non-medical opioids at twice the rate of women. They also die at higher rates from prescription overdoses; despite the fact that women are more likely to be prescribed opioids.  

Opioid use disorder is caused by prolonged use of prescribed or illicit opioids such as heroin and fentanyl, a synthetic drug that dealers find much easier to produce. The number of overdose deaths involving fentanyl shot up from 1,663 in 2011 to 18,335 in 2016.

Faced with this public health crisis, the NIH last April launched the NIH HEAL (Helping to End Addiction Long-termSM) Initiative, a comprehensive program to speed the discovery of scientific solutions that stem the epidemic of opioid addiction and help people manage chronic pain in more effective ways. This includes efforts to develop new, non-addictive medications and medical technologies that reduce the need for opioids. 

How NHLBI is playing a part 

Logo of HEAL initiative. Reads: NIH - Helping to End Addiction Long-term
The NIH launched the HEAL (Helping to End Addiction Long-term SM) Initiative to address the opioid epidemic in the United States.

The NIH HEAL InitiativeSM aligns with NHLBI’s vision to support research on pain and opioid use disorders, and those support efforts already have begun. For example, NHLBI is partly funding the Prevention of Opioid Use in Kids Consortium (PRO-Kids,) which is seeking to understand pain mechanisms in sickle cell disease so that more targeted medications can be developed. 

Various other conditions being studied under NHLBI’s large portfolio have direct connections to opioid misuse, as well. For instance, research has found that illegal opioids may exacerbate asthma. More recent studies have shown that opioid dependent patients have asthma at more than twice the rate—17.2 percent—than the national average of 8.3 percent.

Now, as part of the HEAL Initiative, NHLBI’ National Center on Sleep Disorders Research (NCSDR) has begun looking at the connection between sleep and opioid use and misuse. In collaboration with the National Institute on Drug Abuse, the institute is funding projects to better understand the role sleep and circadian rhythms play in opioid use disorder.

Aaron D. Laposky, Ph.D., Program Director, Sleep and Neurobiology with the NCSDR said there is a lot to uncover, and in this interview, he helped explain the timely research opportunities to link sleep and opioid use disorder and why it matters.

Why focus on opioid use and sleep?

“Sleep deficiency, such as insufficient sleep duration, irregular sleep schedules, and poor sleep quality are prevalent co-morbidities in individuals with opioid use disorder,” Laposky said. “We need to determine if sleep deficiency contributes to the overuse of opioids, to addiction and to how individuals respond to medication treatments to overcome addiction.” That way, he added, new therapeutic targets for the prevention and treatment of opioid addiction can be identified and investigated.

Illustration of how opiates bind to opiate receptors.
Opiates binding to opiate receptors in the nucleus accumbens: increased dopamine release.

Are people who misuse opioids more susceptible to sleep disorders? Conversely, are people with sleep disorders more prone to opioid misuse?

The relationship between sleep and opioid use disorder is likely a two-way street, Laposky said. People with opioid use disorder often complain of sleep disturbance and insomnia, particularly during withdrawal and periods of abstinence following medication treatment, he said.

“While opioid exposure disrupts sleep, disturbance to sleep may trigger opioid overuse and dependence. New research supported by the HEAL Initiative will pinpoint how opioid use alters the regulation of sleep and how sleep deficiency may affect the propensity to misuse and become addicted to opioids,” Laposky said.    

Are racial and ethnic minorities particularly affected by opioid related sleep disorders?

American Indian/Alaska Natives and whites have higher rates of non-medical opioid use and overdose deaths, compared to African Americans and Latinos. These disparities make it difficult to fight the national epidemic.

“Studies suggest that sleep deficiency and untreated sleep disorders may be more common among minorities and women,” Laposky said. “However, the direct contribution of racial and ethnic differences in sleep to opioid overuse, addiction and medication treatment outcomes are not yet well understood and require further study.”

Are there common pathways or biological mechanisms that could provide answers about this relationship?

Sleep deprivation, irregular sleep schedules, and poor quality sleep weaken the network of circadian gene regulation in brain cells and affect how well the brain can adapt to stress. Impaired emotional regulation, increased risk-taking behavior, and greater sensitivity to pain increase susceptibility to substance use, Laposky said.

He explained the need to identify the mechanisms that directly connect sleep to the biological causes of opioid use disorder. Once that is done, he said, “we can explore these mechanisms as potential therapeutic targets in the prevention and treatment of opioid addiction.” 

Research has already started to make important connections, Laposky noted. Studies have demonstrated that sleep deprivation alters regions of the brain involved in reward (pleasure-seeking) mechanisms. There are indications that behavioral and molecular mechanisms that trigger opioid use disorders may be directly influenced by the circadian clock. Lastly, opioid withdrawal and sleep are regulated by some of the same brain regions and neurochemical systems.   

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