Protein Regulator Shows Promise Against Addiction

US News & World Report

Little things can make a big difference in the brain. Case in point: A tiny snippet of RNA may help guard cocaine-using rats against addiction to the drug, a new study shows.

The minuscule molecular guard is a hairpin-shaped piece of RNA known as a microRNA. Raising levels of a microRNA called miR-212 in the brains of cocaine-using rats led the animals to take less of the drug than rats with normal microRNA levels, researchers report in the July 8 Nature. Similarly, blocking the microRNA’s action increased the rats’ cocaine use.

If the results hold true in people, researchers may be able to develop new therapies for treating addiction to cocaine and other drugs of abuse. “Once you get out of whack, this is something that might help bring you back,” says Yale neuroscientist Marina Picciotto, who was not involved in the study.

It’s unlikely that the research will lead to gene therapy to raise levels of microRNAs in people’s brains. But small-molecule drugs that mimic the microRNA’s action might be helpful.

Just 21 to 23 RNA units long, microRNAs are major regulatory molecules that govern part of the process by which instructions contained in DNA are transformed into proteins. The molecules generally block protein production. So it was a surprise to find levels of a protein called CREB increase with rising levels of miR-212, says Paul Kenny, a neuroscientist at the Scripps Research Institute in Jupiter, Fla.

CREB has been found to help fight addiction by decreasing the rewarding experience of taking cocaine, sometimes to the point that rats actually develop an aversion to the drug. It took Kenny and his colleagues years to work out exactly how cocaine use boosts miR-212 production and how the microRNA, in turn, increases production of CREB protein. The process involves several steps and intermediate proteins, including a protein called Raf1 that had never before been shown to be involved in the response to drugs.

The miR-212 microRNA blocks an inhibitor of Raf1 in the striatum, a part of the brain involved in learning habits like driving a car and learning to avoid making the same mistake twice. With its inhibitor in check, Raf1 is free to stimulate CREB production, Kenny and his colleagues show in the new study.

Protecting against cocaine addiction may be a side benefit of mir-212’s normal job of regulating CREB production and other biochemical processes in the brain, Kenny says. The microRNA helps set the correct level of CREB production to keep it from getting too low, which leads to addiction and anxiety, or too high, which leads to depression.

Any therapy targeting CREB would have to strike this delicate balance as well, he says. “Obviously there could be some very profound side effects,” Kenny says.

The researchers are investigating how mir-212 is regulated and whether it is protective against other drugs, such as nicotine and alcohol addiction.

Once a Homeless Drug Addict, Man now Helps Others

Milwaukee Journal

For too many years, Daviene Smittie was lost in a haze of drugs, crime and homelessness.

"The drugs," he knows now that his mind is clear, "were doing me. I allowed drugs to take over my life."

Not anymore. The man with the last name that doubles perfectly as a nickname is now working as a substance abuse counselor himself. He has a home and a college degree and a valid driver's license. He has a wife.

At age 49, Smittie has his dignity back.

How did he do it? He points to several factors.

First of all, he was lucky to come from a functional family. Growing up in Pine Bluff, Ark., he was the youngest of eight children born to loving parents who took him to church and stressed the value of education and hard work. He finished high school and two years of college.

Second was a stinging statement spoken to him by a fellow inmate during one of the many times he went to jail, mostly for misdemeanor stuff such as drug paraphernalia, disorderly conduct and battery.

"This young man, I helped him with his case a lot. He said to me, 'Mr. Smittie, it seems like every time I hear you talk, you talk about drugs.' Right then and there, I didn't want drugs to be part of my life anymore."

That resolve was interrupted by a few more stumbles on the way. But then the third fortuitous thing happened. About six years ago, a raggedy and unshaven Smittie was walking down an east side street in Milwaukee when he met Jim Salinsky, who was working in his front yard.

"I said, 'Hey, what are you doing?' He said, 'I'm doing a flower bed.' I said, 'I need to make a few bucks. Would you mind a hand?' I really don't know what was in him to say, 'OK, c'mon,' " Smittie said.

Salinsky, 47, a global Webmaster at GE Healthcare, said Smittie told him he was homeless and needed money to rent a room.

"As I ran out of projects for him, I got to know him as a gentle and intelligent man. I learned about his drug abuse background and many run-ins with the law," he said.

Salinsky helped him get a job as a custodian at his synagogue, Congregation Sinai. But Smittie had one more setback in him. He was arrested for selling crack cocaine to an undercover police officer on the city's north side. Back to jail he went for six months.

He got out in 2006 and headed back to see Salinsky, who recalls, "Soon after he was released, we were sitting at my kitchen table, and he told me that he wanted to help others in his situation as an alcohol and drug abuse counselor. We researched what training he would need, what the different levels of certification were, etc."

During one of Smittie's own trips through drug rehab in Wisconsin, a counselor told him he needed to be in a job where he could help people. He learned about addiction the hard way, starting out drinking and smoking pot in his teens and moving on to crack cocaine.

He moved to Milwaukee in the early 1990s, and brought his bad habits with him.

"It cost me a lot. It cost me some good relationships. It cost me some jobs. It cost me some friction in the family," including a sister who lived in Milwaukee and sometimes had to use tough love and turn Smittie away from her home. He would stay at a homeless shelter or live on the street.

In 2006, Smittie met a woman, Sandy, through church. Both had just lost a sibling to illness. They were drawn together. They married in 2007, and they now live in West Allis.

Sandy Smittie doesn't drink and says she never tried street drugs. She's assistant manager of Chuck E. Cheese in West Allis, and she hopes to open her own bakery someday. She has watched her husband blossom, especially in his profession.

"He's very passionate about it, passionate with a capital P," she said. And if anything at work frustrates him, it's that he can't fix everybody right away.

In the early days of their relationship, he would want to drive through the old neighborhoods to remind himself how far he had come. But that urge passed. He's dedicated to his recovery. "He's clean for a day, that's his mantra," Sandy said.

Smittie has worked and trained at a variety of agencies. These days he does counseling and assessment at M&S Clinical Services, ironically one of the places he came to for help for his own crack addiction treatment. Now, he has an office there. He's careful about mentioning his past to clients; sometimes it raises his street cred, but it also can cut into the respect he gets.

After three years of weekend classes, he just earned a bachelor's degree from Springfield College School of Human Services, which has a campus in downtown Milwaukee.

Smittie is licensed by the state as a Wisconsin substance abuse treatment counselor in training, and he's studying for the next level of certification. He's thinking about shooting for a master's degree.

Salinsky, or Dr. J as Smittie calls him, is proud of what his friend has accomplished.

"The easiest thing in the world," Salinsky said, "is to write a check and imagine that you're making a difference in someone's life. The more challenging thing is to get involved, get informed and learn what might motivate that person to help himself."

For too long, Smittie had nothing to show for his life, he said. But he's modest about his success.

"People do this every day, man. I'm not doing anything spectacular. I'm just doing what I need to move on with my life."

Opinion: Deal with Addiction

Tallahassee.com

Florida needs leaders who will address the growing public health crisis that is substance abuse. To date in Florida, both alcohol and drug abuse are treated largely as a criminal justice issue, but that is an unsustainable, unaffordable and fundamentally unhelpful approach that does almost nothing to change behaviors so costly to society.

"We need to get rid of the stigma," said Mark Fontaine of the Florida Alcohol and Drug Abuse Association. "Substance abuse needs to be front and center as a health care issue."

Mr. Fontaine, along with Ellen Piekalkiewicz of the Florida Substance Abuse and Mental Health Corp. and Leon County Commissioner Bryan Desloge, met with the Tallahassee Democrat Editorial Board this week to advocate for a multipronged, community-based approach for addressing substance abuse in our state.

Resetting current policy to address this public health issue, which severely affects our criminal justice system including county jails, will take the dedication of statesmen willing to reframe the arguments and address the ramifications caused by substance abuse and its serious economic costs.

In local communities, public health groups must come together to develop models that support community-based care at every step, from prevention and early intervention through ongoing recovery. Individually, addressing substance-abuse issues will take candor in admitting that every person knows someone (or knows someone who knows someone) who has battled with a drug and or alcohol addiction.

Bottom line, bottom dollar

Although drug abuse and alcohol rehab and abuse made a $43 billion annual impact in Florida by robbing the state's economy of viable workers and production and adding to health care, law-enforcement and other costs, there are few resource exclusively committed to addressing the issue.

An excise tax on alcohol, stagnant since 1999, has been swept into the state's general revenue fund instead of being used (like money from the state's tobacco settlement) to address alcohol-abuse related issues.

Most city and county budgets, including ours in the capital city, lack provisions to specifically address drug abuse, and end up paying the price in wholesale incarceration and some temporary treatment of individuals who grapple with addiction. As Mr. Desloge said Tuesday, Leon County spends $30 million to run the jail and $30 million for the sheriff's office, and the city spends about $40 million for the police department — but how much less the figures might be if well more than half of jail inmates weren't housed for addiction-related violations. They belong in treatment programs such as alcoholics anonymous.

Continuing to operate at such high costs without isolating and addressing the root causes cannot continue. Yet diversionary and treatment programs aren't politically popular in our lock-'em-up state, and candidates or sitting lawmakers likely wouldn't see a return on their investment during their short terms in office.

With redirected funds, Leon County could better address local need — as with a recent addiction treatment program at Bond Community Health Center and Apalachee Center. Our law-enforcement officers do benefit from training to recognize substance-abuse issues when they apprehend a subject — another step wise application of our resources.

It starts with you

But legislation, spending reform and the promotion of centers equipped to deal with the needs of the addict are only parts of the solution. To truly advance viable alternatives, individuals must come forward and acknowledge their support for such changes.

Ms. Piekalkiewicz reminds us that substance abuse "is on every street, it's in every community," yet at every turn, this public health pandemic is treated with silence, shame and anonymity.

As Mr. Fontaine pointed out, with substance abuse, there is no "Walk for Recovery," no well-orchestrated campaign to battle it.

The first step to encouraging our lawmakers to revisit current policies is to express community support for such a change. It can begin with the simple admission that we know someone who struggles, and we are committed — with our votes, our time and our dollars — to changing the final impact on our communities and our economy by speaking up.