At least 80% of opioid overdoses aren't fatal, but how do they affect
the brain?

Date:
August 30, 2021
Source:
West Virginia University
Summary:
Scientists still know little about how opioid overdoses affect
the brain and cognition. Researchers found that, while evidence
exists to support a link between overdose, cognitive impairment
and brain abnormalities, more research is needed in this area.



FULL STORY ==========================================================================
An opioid overdose isn't a death sentence. In fact, estimates indicate
that in the United States, only 4% to 18% of opioid overdoses that are
treated in a hospital or pre-hospital setting -- such as an ambulance
or someone's home - - actually kill the patient. But there's a lot that scientists still don't know about what nonfatal overdoses do to the brain.


==========================================================================
To better understand the topic, Erin Winstanley and James Mahoney -
- researchers with the West Virginia University School of Medicine
and Rockefeller Neuroscience Institute -- reviewed 79 studies of
neurocognitive impairments and brain abnormalities associated with
nonfatal opioid overdoses in humans. The studies all had limitations,
a sign that more precise research is needed in this area. Yet despite
the studies' shortcomings, their findings still suggested that brain abnormalities and cognitive impairments are linked to overdose.

"I think there's probably a host of morbidities associated with
experiencing a nonfatal opioid-related overdose that's largely neglected
in the published literature and -- to a certain extent -- from a public
health standpoint," said Winstanley, an associate professor in the
Department of Behavioral Medicine and Psychiatry and the Department of Neuroscience. "We should first focus on saving lives. That's definitely
the appropriate step. But we probably should start paying attention to
some of these other issues, too. Given the proportion of people who have experienced a nonfatal overdose, the number of deaths is just the tip
of the iceberg." Their findings appear in Drug and Alcohol Dependence.

Winstanley, Mahoney and their colleagues -- Felipe Castillo and Sandra
Comer of Columbia University -- performed a systematic review of journal articles published between 1973 and 2020.

Overall, the studies lacked the level of detail and consistency that
would have made many direct comparisons and inferences possible.



==========================================================================
For instance, fewer than half of the studies reported toxicology
results confirming an opioid overdose. Only 27.8% reported results of neuropsychological testing, and only 64.6% reported magnetic resonance
imaging -- or MRI -- results of the brain.

The team discovered that all of the studies were at risk of one
form of bias or another. Some studies, for example, failed to measure participants' intellectual functioning, consider whether they had received prompt overdose treatment or reported whether they were using anything
besides opioids.

"Independent of overdose, addiction research is complicated in general
because of all these numerous confounding variables," said Mahoney,
an associate professor and clinical neuropsychologist in the WVU
Department of Behavioral Medicine and Psychiatry and the Department of Neuroscience. "There are often medical and psychiatric comorbidities
and several other factors that may be impacting the cognition of these individuals. On top of that, co-occurring substance use in addition
to opioids is more the norm than the exception." The overdose itself complicates matters further. How long was the individual's brain
deprived of oxygen? Did they receive adequate treatment in time? How
long post-overdose was neuroimaging or cognitive testing done? All of
these variables -- and many others -- can influence a study's results.

"Also, there are so many different measurements that are used to test
cognitive functioning, making it even more difficult to compare findings
across the literature," Mahoney said.



========================================================================== Despite these inconsistencies, the studies provided evidence that an
opioid overdose has the potential to change how someone's brain appears
or behaves. In turn, those changes could influence someone's attention
span, memory, executive function or other higher-order thinking skills.

"This news is quite positive in the sense that if we can start to
do early identification and screening for neurocognitive deficits --
whether they're associated with overdose or not -- we might actually
have the right kind of rehabilitation therapy for them, including some promising new treatments for cognitive deficits," Winstanley said.

That's important because neurocognitive deficits make poor treatment
outcomes more likely for people who want to stop using opioids or other substances.

"If we are able to target those at a higher risk of cognitive impairment -
- perhaps those who have had five or six overdoses -- and individualize
their treatment plans to address those deficits as early in the treatment process as possible, we may be able to improve their outcomes, given
what is known about cognition and treatment dropout," Mahoney said.

To gain more insight into those deficits and how they can be addressed, Winstanley, Mahoney and their colleagues at WVU and Columbia University
have begun a new project. They're comparing the cognition of two groups
of people with opioid use disorder: those with a past history of overdose
and those without any overdose history.

The researchers have had all participants complete the same comprehensive battery of neurocognitive tests. As they gather and analyze the data,
the researchers will take into account characteristics such as the participants' age, education level and intellectual functioning; how
long they have been using substances; and which substances they have used.

In addition, the team has used functional MRI to form images of some
of the participants' brains to provide insight into how the brain is
actually working as they completed working-memory tasks.

"While the neurocognitive testing lets us know how these individuals
are actually performing on various thinking tasks, the fMRI data will
also give us a sense neuroanatomically of how the brain is functioning,
how the various brain networks are engaged and how different areas of
the brain are interacting with one another," Mahoney said. "We will
have the opportunity to gain better insight into what factors other than
their opioid use and overdose -- such as the co-occurring use of other substances -- may be impacting these brain networks." Insights into
how opioid use, overdose and other variables affect the brain could
lead to novel neuromodulation treatments, including ones that Mahoney
is now exploring.

Neuromodulation involves altering the activity of specific brain areas
and networks through the application of electrical pulses, a magnetic
field, of other forms of stimulation.

In 2019, Mahoney was part of a team of scientists from RNI
and WVU Medicine that launched the world's first Food and Drug Administration-approved clinical trial of deep brain stimulation to
treat opioid use disorder.

He's also investigating the use of transcranial magnetic stimulation
-- another form of neuromodulation -- to fight addiction, as well as low-intensity focused ultrasound, which has been studied for several
disorders but is in the infancy of exploration as a potential treatment
for substance use disorder.

"By helping to rewire those areas of the brain that are involved
in craving and cognition, such as disinhibition, decision making,
attention and higher-order executive functions, we can hopefully
improve cognitive functioning, which would subsequently improve
treatment outcomes," he said. "It's unrealistic to think that
neuromodulation will simply 'fix' addiction, but when used in
combination with the standard of care -- comprehensive behavioral
treatment with medication for opioid use disorder -- we will hopefully
be able to provide another strategy to help people achieve abstinence." ========================================================================== Story Source: Materials provided by West_Virginia_University. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Erin L. Winstanley, James J. Mahoney, Felipe Castillo, Sandra
D. Comer.

Neurocognitive impairments and brain abnormalities resulting from
opioid- related overdoses: A systematic review. Drug and Alcohol
Dependence, 2021; 226: 108838 DOI: 10.1016/j.drugalcdep.2021.108838 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210830123238.htm

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