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New Study Identifies Brain Mechanism Involved in Impulse Disorders

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Pinnacle Team
2 years ago
Pinnacle Icon
Pinnacle Team •
2 years ago

Over the past three years, the COVID-19 pandemic dominated virtually all national public health news in the U.S. For good reason: to date, over a million people in the U.S. have died from COVID-19, and every death is a tragedy. However, another public health crisis has also claimed the lives of over a million people in the U.S.: the drug overdose and opioid epidemic, which now involves stimulants like cocaine, amphetamine, and methamphetamine. Granted, those million deaths happened over the past 24 years, as opposed to the past three years, but our point is this: the overdose epidemic did not disappear during COVID.

Instead, it got worse.

For the latest information on the crisis – and to learn about the overdose increases related to COVID-19 – please read the following articles on the blog section of our website:

Data-Driven Approach to the Opioid Crisis in Hamilton County, Ohio

Opioid Crisis Report: Need for Fentanyl Detox Increases

Substance Abuse and Addiction: The Opioid Crisis in New Jersey

One thing that’s made a significant difference in our work to mitigate the harm caused by the opioid epidemic is the increased use of medications for opioid use disorder (MOUD) in federally approved medication-assisted treatment programs (MAT) for people with opioid use disorder (OUD). The facts are simple: MAT works. People with OUD who participate in MAT programs have lower relapse rates, increased time-in-treatment, improved psychosocial functioning, and reduced overall mortality, compared to people with OUD who don’t participate in MAT programs.

That’s why MAT for OUD is considered the gold standard approach: it improves outcomes across the board for people with OUD.

That’s also why researchers are involved in a continuous effort to find medications that work for other substance use disorders (SUDs). A medication called Antabuse helps people with alcohol use disorder (AUD), but there are no other known medications that work as well as the established MOUDs for opioid use disorder – but research published in July 2022 contains findings that may change that.

Medication-Assisted Treatment for Stimulants?

In a new study on cocaine seeking behavior in the rodent model, researchers have identified areas and mechanisms in the brain related to impulse control, which also have a significant impact on cocaine-seeking and voluntary cocaine use.

This is an important development, because the contours of the overdose epidemic in the U.S. have changed over the past three years. Whereas the first three phases of the overdose crisis were driven by opioid use, heroin use, and the appearance of fentanyl in various illicit drugs around 2016, the new phase – the fourth phase which we’re in now – is characterized by polysubstance use and an increase in the use and misuse of stimulants like cocaine and psychostimulants like methamphetamine.

Before we talk about the study, we’ll offer the latest data on cocaine use and methamphetamine use in the U.S.

We’ll start with cocaine use.

Here are most recent facts and figures, as published in the 2021 National Survey on Drug Use and Health (2021 NSDUH)

Cocaine Use in the Past Year Among People 12+ in 2021

  • Overall: 1.7%
    • 4.8 million people
  • Young adults 18 to 25: 3.5 percent
    • 1.2 million people
  • Adults 26+: 1.6%
    • 3.6 million people
  • Adolescents 12 to 17: 0.2%
      • 40,000 people

Those statistics are easy to read and understand: millions of people in the U.S. used cocaine in 2021. Now we’ll look at the number of people in the U.S. who meet the clinical criteria for cocaine use disorder, a.k.a. cocaine addiction.

Cocaine Use Disorder in the Past Year Among People 12+ in 2021

  • Overall: 0.5%
    • 1.4 million people
  • Adolescents 12 to 17: 0.1%
    • 7,000 people
  • Young adults 18 to 25: 0.8%
    • 252,000 people
  • Adults 26+: 0.5%
    • 1.1 million people

Those statistics are also easy to read and understand: close to three million people in the U.S. reported cocaine addiction in 2021: that’s more than most of us realize.

Next, we’ll look at the latest data on methamphetamine use in the U.S.

Methamphetamine Use in the Past Year Among People 12+ in 2021

  • Overall: 0.9%
    • 2.5 million people
  • Adolescents 12 to 17: 0.1%
    • 37,000 people
  • Young adults 18 to 25: 0.5%
    • 66,000 people
  • Adults 26 1.1%
    • 2.3 million people

Again, those facts are straightforward. Although methamphetamine is less familiar to most people than cocaine, the numbers show that like cocaine, millions of people in the U.S. used methamphetamine in 2021.

Now we’ll look at the number of people in the U.S. who meet the clinical criteria for methamphetamine use disorder, a.k.a. methamphetamine addiction.

Methamphetamine Use Disorder in the Past Year Among People 12+ in 2021

  • Overall: 0.6%
    • 1.6 million people
  • Adolescents 12 to 17: 0.1%*
    • 20,000 people
  • Young adults 18 to 25: 0.3%
    • 111,000 people
  • Adults 26+: 0.7%
    • 1.5 million people

*This percentage is rounded up from 0.06%*

Like these other data sets, this one is also straightforward. Methamphetamine may be less well known than cocaine, but these numbers tell us that, like cocaine addiction, around three million people in the U.S. reported methamphetamine addiction in 2021. And like cocaine, that number is far larger than most people realize.

We’re almost ready to share the data from the study. First, though, we’ll offer general information about cocaine and methamphetamine we think everyone should know.

Additional Facts: Cocaine and Methamphetamine

To ensure we’re all on the same page, we’ll take a moment to offer the basic facts about cocaine and methamphetamine.

Cocaine Basics:

  • Powerful stimulant for the nervous system
  • Illegal
  • Highly addictive
  • Can be inhaled through the nose, smoked, or injected
  • Cocaine was involved in an estimated 12,300 overdose deaths in 2019

Methamphetamine Basics:

  • Central nervous system psychostimulant
  • Highly addictive
  • Illegal (but can be prescribed in some cases)
  • Laboratory-made
  • Can be inhaled through the nose, smoked, or injected
  • Methamphetamine and other psychostimulants were involved in an estimated 16,00 overdose deaths in 2019

That’s all: we want everyone to know that these two drugs are very powerful and very addictive. In addition, both cocaine use and methamphetamine use are associated with risk of fatal overdose.

Now that we know why this research is important – all the facts above make the case – let’s take a look at that study.

Reduced Inhibition Means Increased Drug Use

Previous research in neuroscience demonstrates that a specific brain area – the lateral habenula (LHb) – plays a critical role in regulating impulse control in the human brain. To test whether blocking the action of that brain area might have an effect on drug seeking behavior, scientists designed an experiment in the rodent model.

Here’s how they did it.

With a standard behavioral protocol called a Go/NoGo model, researchers trained rodents to self-administer cocaine. They trained the rodents to understand that when they pressed a specific lever, they’d receive cocaine. They then trained the rodents to recognize that when the light in the test chamber was on, they’d receive cocaine (go), but when it was off (nogo), they would not. All rodents quickly adapted, and learned not to press the lever when the light was off.

Then researchers gave the rodents – all trained in cocaine self-administration – an experimental medication that blocked the action of the lateral habenula (LBh).

Here’s what they found:

  • In rodents with the LHb receptors blocked, cocaine seeking increased
  • Rodents sought cocaine even with go light turned off
  • Therefore, the researcher concluded, the LHb acts as an impulse regulator for drug seeking behavior

The first two points are important, and that last point is critical. We now know about a specific brain area directly involved in stimulant-seeking behavior. Further, we now know that when we block the action of that brain area, stimulant seeking increases.

The next step?

Let’s see what the experts say.

Why This Research Matters

First, we’ll define the role of the LHb in more detail.

In an article in the online science magazine Science Daily, Dr. Carl Lupica, head of the Electrophysiology Research Section of the Computational and Systems Neuroscience at NIDA, describes the role of the LHb this way:

“The LHb acts like an interface between rational thought in the forebrain and the modulation of neurotransmitters like dopamine and serotonin that originate in the midbrain, which are important in regulating decision processes and emotions.”

That helps us understand why blocking the action of the LHb results in increased drug seeking behavior. Without the modulating effect of the LHb, drug seeking increases. The absence of a check on the action of the midbrain – an area involved in emotion, reward, and pleasure – means the impulse to seek drugs goes unimpeded.

That has clear implications for drug use, but Dr. Lupica thinks the value of the research goes beyond drug addiction. He continues:

“While the immediate results of this study are related to cocaine seeking, there are also greater implications for impulsivity as it relates to other drugs as well as to psychiatric conditions like obsessive-compulsive disorder (OCD).”

That’s something we didn’t think of. We did not consider the relationship between impulse control and mental health disorders like OCD. We’ll leave that last comment from Dr. Lupica right there. Since our primary role is treating people with substance use disorder (SUD) as opposed to mental health disorders, another result of this research has our attention.

We’ll discuss that now.

Potential MAT for Stimulant Use Disorders

In the same article, Dr. Nora Volkow, Director of the National Institute on Drug Abuse (NIDA), shares her take on the importance of this research:

“This discovery gives researchers a new, specific target toward solving a problem that has long been elusive – developing treatments for cocaine addiction. As we have seen with medications to treat opioid use disorder, adding this tool to clinical care could save lives from overdose and drastically improve health and quality of life.”

We know that for people with opioid use disorder (OUD), medication-assisted treatment (MAT) with medications for opioid use disorder (MOUD) improves outcomes in almost all areas. Most importantly, it reduces the likelihood of premature mortality caused by opioid use. If research shows that we have a viable, effective medication for stimulant use disorders, then we may see similarly improved outcomes for people with cocaine use disorder and methamphetamine use disorder.

When we consider this potential alongside what we know about the fourth phase of the overdose crisis – namely, the increase in stimulant-related overdose deaths – this research may be a significant step forward in addiction treatment, at exactly the time we need it most.

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