Vivek Kumar is conducting an investigation into the genetic basis of addiction. PHOTO BY JACQUELINE WEAVER

Treating drug addiction as a disease

BAR HARBOR — Jackson Lab scientist Elissa Chesler spends her days hunting through mountains of data in search of connections between genes and behavior, specifically addictive behavior.

A colleague, Vivek Kumar, is conducting his own investigation into the genetic basis of addiction.

Both have long seen evidence of what policy makers from the White House to the State House have only recently embraced — that drug addiction, whether to alcohol or opiates — is a disease.

Chesler and Kumar compare alcoholism and addiction to opiates such as heroin to diabetes and hypertension.

The diseases, they say, all have a genetic, neurobiological and environmental component.

“There is a biology here,” said Chesler, whose specialty is bioinformatics and computational biology. “People are suffering and need help.”

Jackson Lab scientist Elissa Chesler  at work. PHOTO BY JACQUELINE WEAVER
Jackson Lab scientist Elissa Chesler at work.

Kumar said the genetic contribution to alcoholism and opiate addiction ranges from 20 percent to 80 percent, depending on the individual’s genetic makeup and the drug taken.

These numbers are comparable to the genetic contributions to diabetes and hypertension, he said.

The detective work to identify what genes are involved is more than a lifetime’s undertaking.

The brain is home to billions of neurons that make trillions of tiny connections.

Drugs affect the delicate circuitries in the brain that control thoughts, actions and emotions — in other words, the areas that make a human human.

Both Chesler and Kumar say it is difficult for those who are not addicted to imagine the dramatic neurobiological event users experience in their initial exposure to drugs.

For someone taking heroin, the drug effectively lights a neuronal bonfire along the way to the brain’s reward center, which releases a flood of dopamine, they said.

Alcohol and opiates travel the same pathways that make eating, sleeping and having sex pleasurable — all designed for survival of the species.

But unlike those “normal” drives, the drugs “hijack” the system, taking it over to an extent the researchers have not seen duplicated with any other substance.

And the hijacking occurs in several areas of the brain, among them the pre-frontal cortex, which is critical to executive functions such as planning and action.

The researchers say susceptible individuals experience a euphoria that then induces them to recreate the experience over and over, a phenomenon Chesler has observed when mice quickly learn to activate a lever that releases a mood-altering drug.

“We never look in a cage and say: ‘You’re a bad mouse.’ Why don’t we allow that of people?” Chesler said.

In late 2013, Kumar reported in the prestigious journal Science that mice carrying a mutation in a gene known as Cyfip2 have abnormal neuronal structure in a key part of the brain known for its role in behaviors, among them addiction.

These neurons, he found, have fewer dendritic spines — hair like projections that are important sites of neurochemical signaling.

“A single nucleotide change causes a large behavioral difference,” he said.

Another area that interests Kumar is determining the genes and pathways that regulate proper functioning of the mesolimbic reward pathway.

This neural circuit plays a crucial role in impulse control and motivation and can quickly be captivated by certain drugs.

The goal is to identify components that can be targeted for treatment.

“If we can find the genes, then we can point to the therapeutics,” Chesler said. “For me, the knowledge itself is incredibly powerful in helping people understand themselves.”

She said punitive policies “have had a dramatic effect on a population with so much economic potential, so much human potential. That affects me the most. There is something very tragic about it.”

Kumar said relapse is expected with hypertension and diabetes, but no physician would entertain withholding medication that might help right the ship.

In the case of a heroin addict, the medication might be Suboxone, methadone or their derivatives.

What Chesler envisions is information that can be used to teach young people what it means to be addicted along with the knowledge to recognize early on when addiction is setting in.

“Does anyone really want to be the mouse in the box who can’t stop pressing the lever?” Chesler said.

She believes it is this same lack of knowledge that has guided much of the public policy regarding alcoholism and drug addiction.

“Most college students drink. Most stop when college is over,” Chesler said. “It’s hard for those people who drink alcohol and then can stop to see it as a disease.”

Chesler said the fact that drugs affect the brain does not mean that change is impossible.

“You can change a brain by talking to a person,” she said. “And you can affect behavior with pharmacology.”

Punishment, she said, might be a wake-up call, but it is unlikely to address many aspects of the situation.

Chesler said the addictive process also is a road map to drug overdoses.

When a person takes heroin in a familiar environment, each step of the process — tying the arm, seeing the needle — raises the heart rate.

The rush of heroin then depresses the heart rate.

However, if an addicted individual uses in an unfamiliar environment, his or her respiratory rate is not likely to increase as much, therefore when it is depressed by the drug it can stop the heart.

“It’s based on the opponent process theory,” she said. “A lot of overdosing is when someone takes drugs in an unusual environment.”

Another aspect some people might not understand, Kumar said, are the permanent changes drugs such as heroin can make to the brain — the suppression or total loss of neurons.

Adolescents with developing brains are particularly susceptible to permanent neuronal damage from drug use, he said.

“Our brains rapidly change until we are in our 20s, and much of the critical neurodevelopment that controls our behavior and emotions occur after birth,” Kumar said in an editorial on this aspect of the drug problem.

Between the ages of 10 to 19, regions of the brain that control emotion, cognition, decision making and impulse control are maturing, he said.

“Adolescents who flood their brains with chemicals do lasting damage at a very critical age of neurodevelopment,” Kumar said.

Maine averaged more than five drug deaths per week in 2015. “That is five families every week losing a loved one,” said Attorney General Janet Mills. Most of the 272 people who died from drug overdoses took heroin, heroin laced with fentanyl or prescription opiates. The number represents a 31 percent increase over the prior year. Ellsworth Police report four drug overdose deaths so far in 2016, two occurring the weekend of April 30-May 1. There was one overdose death in Bar Harbor the same weekend, and several more are suspected.
Jacqueline Weaver

Jacqueline Weaver

Reporter at The Ellsworth American
Jacqueline's beat covers the eastern Hancock County towns of Lamoine through Gouldsboro as well as Steuben in Washington County. She was a reporter for the New York Times, United Press International and Reuters before moving to Maine. She also publicized medical research at Yale School of Medicine and scientific findings at Yale University for nine years.[email protected]
Jacqueline Weaver

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