New breakthrough helps drug addicts forget they were addicted

Scientists have found a new chemical that could help drug addicts forget they were ever addicted

In the cult-classic “Eternal Sunshine of the Spotless Mind,” Jim Carrey’s character tries to overcome a painful breakup by erasing his memory and eleven years after the science fiction flick debuted, science may be finally catching up.

Researchers in Florida have discovered a method of wiping away memories, using a specific chemical instead of the fearsome machine featured in the film and unlike Carrey’s character, real patients are unlikely to have second thoughts about the procedure.

That’s because the new procedure only suppresses memories associated with drug use.

Normally, the idea of losing our memories would seem scary. Amnesia is a terrifying and still baffling affliction. Alzheimer’s is, in many ways, the scourge of our modern age and one that all too many people are afflicted and affected by but the scientists behind this new procedure believe their work has the potential to revolutionise drug addiction treatment – possibly enabling millions of drug addicts around the world to literally forget the triggers that can otherwise lead to a life of painful relapses and, in some cases, fatal overdoses.

The big caveat, among others, is that it has not been tested on humans, which means it may or may not ever reach the market. They are currently applying for federal grants and hope to start human trials by 2020.

“The idea is that someone would go into a rehab program with the typical abstinence therapies and while they are in the treatment program they would receive this medication one time and it should remove all of the associations with the drug,” said Courtney Miller, Associate Professor in the Department of Neuroscience at The Scripps Research Institute.

“It’s exciting,” she said.

 

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Difficult to treat

To understand the significance of Miller’s work, it helps to know a bit about drug addiction and the current ways people try to fight their cravings.

“Immediately following withdrawal, most substance users enter a ‘honeymoon’ phase where they report feeling physically and emotionally well, with few cravings,” according to Miller’s study, written with seven other Scripps scientists and published in this month’s Molecular Psychiatry.

“However, approximately 1 to 3 months into recovery, many abstinent individuals report hitting a ‘wall’. This phase of recovery is marked by anhedonia and strong cravings that often result in relapse.”

Drug rehab centers teach patients to abstain from touching the stuff again and many programs also use counselling to treat psychological problems underlying addiction but pharmacological assistance for recovering drug addicts is “extremely limited,” according to Miller’s study.

“A few, moderately effective replacement therapies exist for opiate, nicotine and alcohol dependence. However, no such options exist for psychostimulant – Meth, Cocaine and MDMA – dependence, and further, there are no pharmacotherapies for the prevention of relapse associated with any drug of abuse.”

The biggest problem is the thousands of potential triggers that can send recovering addicts back into a downward spiral. They can range from something obvious, like the sight or smell of a drug, to something seemingly unrelated.

“People can go through rehab and go about their daily lives but these memories, these triggers can last for their entire lives,” said Miller, “they can be clean but then stumble across something that is a trigger for them, reminding them of wanting to use a drug, and then that can induce craving and relapse. These memories are one of the major risk factors.”

Some recovery programs practice “exposure therapy” to re-route or pave over the neural pathways created by drug abuse. But the original trigger remains, buried like a ticking time bomb.

Miller has spent the past 15 years studying how memories and addiction overlap.

“Memory has always fascinated me,” she said. “We are a collection of our memories. That’s what makes things like Alzheimer’s so awful is that you lose that thread of who you are. So I’ve taken my interest in memory and applied it to different ways that we can help people: addiction, PTSD and Alzheimer’s.”

 

 

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Addiction Pathways

Over the past two years Miller and her colleagues have made a series of remarkable discoveries regarding memory and addiction.

In 2013, during experiments in which they plied lab mice with methamphetamine, they discovered that normal memories and “meth memories” are physically different.

“Memories that are storing associations with drugs like methamphetamine seem to be using different mechanisms in the brain than other, more mundane memories,” she said. “When the Meth memory is sort of sitting there in the brain it’s behaving differently than other memories.”

But let’s get technical for a moment.

That memory you have of your aunt Lucy is, on a cellular level, nothing more than a web of connections between neurons in your brain. These connections are called dendritic spines and they are supported by actin, a protein that acts like scaffolding.

“When we learn new things, the actin changes and that allows us to enlarge our dendritic spines and store memories,” Miller said.

In the case of your memory of aunt Lucy, the actin stabilises within minutes.

But in the case of a meth memory – your first hit, for example – the actin never stabilises. And that instability leaves the memory vulnerable.

Last year, Miller and her colleagues discovered a way to exploit that vulnerability.

“We’ve found a way to go in and disrupt that process,” she said. By applying a drug called Latrunculin A, they were able to attack the unstable actin and erase those drug-related memories.

At the time, many addiction experts hailed the 2014 study as a breakthrough.

“The findings here are real game changers,” said Gary S. Lynch, professor of psychiatry and human behaviour at University of California School of Medicine.

“What this points to is a completely new strategy for treatment of addiction. For the past 10 years there have been many challenges to the notion that memories are cemented in. But this study shows that memory really is still a dynamic, malleable business and that there can be another way of dealing with dependency.”

But Lynch’s praise also pointed to a big problem.

“Actin is the most prevalent protein in the body,” Lynch said, “now to find that it is so critical to dependency is breathtaking in its implications.”

Because actin is so prevalent in the human body, however, interfering with the protein would be poisonous.

“That’s how muscles contract, the heart works, cells divide,” Miller said, “so if we inhibited actin it would probably kill a person.”

 

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Developing a treatment

Instead, in their latest study, Miller and her colleagues found another molecule called non-muscle myosin IIB (or myosin) “upstream” of actin that they could inhibit without causing widespread damage.

“That means we can actually work on a drug that people can take,” she said.

The scientists gave meth-addled mice a drug called Blebbistatin that inhibits myosin. Just one dose of Blebb produced a long-lasting disruption of context-induced drug seeking  for at least 30 days – translation: “Meth-associated memory loss.”

Just as important, the mice did not lose any other memories.

“What is particularly exciting is that myosin only has to be inhibited once,” Miller said, “the effect lasted as long as we tested the animals. I hesitate to use the word ‘erased,’ but the memory seems to be gone.”

Theoretically, drug addicts could wipe out their triggers with a single dose but several hurdles remain.

First, Miller and her colleagues have to do more tests to see if Blebb has the same effect for other drugs.

“We honestly don’t know,” she said, “we can’t really predict at this point so we’re going to have to work our way through them.”

Miller said she and her colleagues also have to make Blebb safe for humans.

Lastly, there is the hurdle of convincing people to erase — or at least suppress — parts of their memories. In “Eternal Sunshine of the Spotless Mind,” Carrey’s lovelorn character comes to regret his decision, desperately trying to save his memories from mechanical annihilation but with Blebb, the only memories that are at risk are ones associated with drugs — exactly the ones recovery addicts are desperate to delete.

The idea might be scary, Miller admitted, “but what it really looks like is that Blebb kind of goes in with a scalpel and takes out the memories that are associated with methamphetamine and methamphetamine alone.”

A spotless mind, in other words, and a chance for an addict to start over again.

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