A Combo of Existing Drugs Could Treat Cocaine Addiction

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Two drugs currently used to treat heroin and prescription painkiller addiction may work together to fight cocaine as well — without causing dependence themselves, according to a new study in rats.

A clinical trial in humans is currently enrolling patients, and if future research is successful, the new drug combination — buprenorphine plus naltrexone — could be the first medication developed for the treatment of cocaine addiction. The drug would likely work for methamphetamine and other stimulant addictions, too.

The new research originated with Dr. Nora Volkow, director of the National Institute on Drug Abuse, who asked George Koob of the Scripps Institute in California to lead the study. “I had been intrigued by the clinical trials showing that when you use buprenorphine, use of cocaine goes down significantly,” says Volkow, referring to previous studies of people with heroin addiction who reduced their use of cocaine while being treated with buprenorphine.

But buprenorphine (Suboxone, Subutex) is an opioid, which means that it can cause physical dependence and has the potential for misuse. So, for people who use cocaine but aren’t already addicted to heroin or a similar drug, buprenorphine could make their problem worse. The last thing addiction treatment providers want to do is add a new class of drug to a client’s repertoire.

That complication precluded the possibility of testing buprenorphine on its own in cocaine addicts. It was scientifically plausible, however, to think that using it in combination with another medication that blocks some of its opioid effects could prevent this problem. As it turns out, naltrexone (reVia, Vivitrol) fits the bill.

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Buprenorphine itself is a marvel of multiplicity. At low doses, it acts like an opioid, cutting physical and emotional pain and reducing anxiety by activating a class of opioid receptors, known as mu receptors. At high doses, it has the opposite effect: preventing opioid-like action and inducing withdrawal symptoms rather than relief. That’s what makes it an especially safe drug for maintenance of people with opioid addictions. But buprenorphine has another action as well: it blocks the kappa opioid receptor, a target that has long intrigued pharmacologists because it seems to be one of the “brakes” on the pleasure-producing dopamine system.

When people repeatedly take drugs — particularly stimulants like cocaine and methamphetamine — the brain releases excessive amounts of dopamine. This triggers a feedback loop: it overactivates kappa opioid receptors, which in turn shuts dopamine down. Now “it’s payback time,” says Koob, because your brain’s pleasure pathways conform to an austerity plan, getting increasingly stingy with the joy juice.

The distress and dysphoria associated with rising kappa activation seem to be what drives addicts to seek more drugs, in a vain attempt to feel better. Ultimately, however, that makes matters worse as the feedback dials the pleasure volume down even further. “I call it pharmacological Calvinism,” Koob says, noting that while the human brain is wired to enjoy everyday pleasures, frequent drug use triggers the stress system, which prevents the party from lasting forever.

“The reward system’s sensitivity decreases profoundly and that leads the addicted person to feel very little pleasure from almost any reward, including the drug itself,” Volkow says.

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So, how do you allow buprenorphine’s positive effects on kappa receptors while blocking its effect on the mu receptors associated with addiction? Add naltrexone, which blocks only mu. To test whether this drug combo could actually reduce the distress associated with cocaine addiction without leading to opioid dependence, researchers studied the cocktail in rats.

The animals were studied in two conditions: one comparable to casual cocaine users, the other similar to cocaine addicts. The casual users were the “short access” rats: they were given access to cocaine for only one hour a day. Like many weekend-only human users, these rats “really don’t develop any signs of dependence,” says Koob, noting that he’s had animals in this condition for more than a year without seeing compulsive behavior.

Rodents given access to cocaine for six hours a day, however, have a different story, especially if they are offered few alternative activities. These rats will compulsively seek cocaine and put in more and more work to get it, if you make the drug more difficult to obtain.

The scientists figured that if kappa activation is indeed causing the pain and distress of addiction by turning down the dopamine system, treating addicted rats with buprenorphine and naltrexone should reduce their cocaine use, since their compulsion is caused by the feedback loop. In rats that aren’t compulsive, however, blocking kappa activation shouldn’t matter because they haven’t experienced the extreme dopamine elevations that would have caused the feedback loop to kick in.

And indeed, that is what the study showed, at least for treatment combinations that included the lowest dose of naltrexone. While higher doses of naltrexone prevented buprenorphine from reducing cocaine use, at the lowest dose, the drug combo was able to cut drug use in compulsive rats, but not the others.

Most importantly, this dose was still adequate to prevent significant withdrawal symptoms from occurring when the buprenorphine was stopped.  That suggests that it hit the sweet spot and allowed buprenorphine to reduce dysphoria and cravings without triggering a high or dependence.

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“When I heard the results, I was very pleased,” says Volkow of the study, which was published this week in Science Translational Medicine. The initial clinical trial in humans is being conducted in people who use both cocaine and opioids, but if the combination works for them without producing withdrawal, future trials may include people with cocaine addiction alone. Since methamphetamine and cocaine act similarly in the brain, Volkow thinks the treatment could work for meth users as well.

And because buprenorphine and naltrexone are already approved for medical use, if clinical trials pan out, the treatment could potentially be used immediately to help the 1 million Americans who struggle with cocaine addiction and the several hundred thousand who have other stimulant addictions.

The drug combination might also be useful in chronic pain, depression, obsessive-compulsive disorder and schizophrenia — all disorders in which kappa receptors may be involved in tuning pleasure levels down too low and distorting motivation. Although researchers are seeking kappa-blocking drugs that aren’t also opioids, as buprenorphine is, so far none of the compounds has proved both safe and effective.

“I think this is an understudied area, but a rich target,” says Koob.

Maia Szalavitz is a health writer at TIME.com. Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland’s Facebook page and on Twitter at @TIMEHealthland.

9 comments
O.o
O.o

Just to let ALL of you know - this entire article is literally FULL of incorrect information and myths about the bup. + naloxone combo (AKA Suboxone) BTW nalTREXONE is the brand name for nalaxone/narcan and suboxone is correctly listed on the packaging as "Buprenorphine / Naloxone"...Anyway -- *Please take it from someone like myself who has been on this 'combo' for years now and has had an experienced past riddled with very, (i stress very) heavy opiate & cocaine addictions.....SO. This 'blurb' in particular drives me banana sandwiches: 

""At low doses, it acts like an opioid, cutting physical and emotional pain and reducing anxiety by activating a class of opioid receptors, known as mu receptors. At high doses, it has the opposite effect: preventing opioid-like action and inducing withdrawal symptoms rather than relief. That’s what makes it an especially safe drug for maintenance of people with opioid addictions""

Buprenorphine does NOT induce w/d symptoms in anyone unless they are opioid dependent AND have a FULL agonist Opiate/oid in their system already (in particular their receptors in their brains)....stupid stupid people is my opinion. Oh and one of the biggest myths surrounding this drug combo is that the naloxone will block opiate receptors because it is an antagonist to them, therefore the patient cannot get high on opiates. Also, that if a patient attempts to shoot (I.V) the medication that it will send them into Precipitated W/D. Both of these things I can ASSURE you from Personal experience are complete and utter BULLsOhNiEtY. 

My advice to ANYone thinking about getting on this medicine is this: Do your OWN extensive research where you can compare what the Pharmaceutical companies (because we all know they wouldnt lie to us right?!? Pffft >.<) are telling you, to what the people/addicts/pain management ppl/w/e you want to call them who actually know from extended personal experience are telling you and make your own educated decision before jumping into this option seeking a panacea.....Truthfully i could've done more research myself years ago when choosing this option (not that i regret it b/c without this option I literally would've been 6ft. under probably 6 yrs. ago) but there wasn't as much info as there is now on the net. So use it. Just my 2 cents on this all.....

Glob bless you all

deuces  

-O.o-

tlittelton
tlittelton

There is a basic reason that a person has decided to take drugs. If you do not address the root cause and only use another type of drug or drug cocktail; you are only going to make matters worse; at best, they will now be addicted to more than one drug. Why give a human something to ingest that we have no idea what the effects will be? Who then is the real lab rat.

violaball0
violaball0

While we don't know the impact after combining Buprenorphine and naltrexone will have on a person, I do think this is a good start for treating cocaine addiction. For people who have no idea what Buprenorphine and Naltrexone are, Buprenorphine is a semi-synthetic and it is used to treat opiate addiction and also used to control chronic pain. Naltrexone is an opioid receptor antagonist used primarily to manage alcohol dependence and opioid addiction.

Dr. Viola Ball

 help for drug addiction

Addictional Mytha
Addictional Mytha

Studies of addiction in rats are not applicable to humans.  This was demonstrated in the "Rat Park" experiments of the 1970's which showed that rat addicts were quickly cured when put in natural environments, even when heroin was freely available.  They showed little interest.

Same for people.  They take drugs because either they want to, or they are forced to.  But never because they are 'addicted'.  Any attempt to cure drug addiction through drugs is doomed to failure because it fails to appreciate that drug use is a choice, and the user will simply switch to another drug to maintain the 'addict' lifestyle.

http://AddictionMyth.com

KaleoK
KaleoK

Why is it that print and other media always include images of drugs and/or drug use in reports? Do you not realize that it encourages use? Or that these images and video trigger cravings in recovering and current addicts?

O.o
O.o

@tlitteltonYou should really educate yourself on this topic/issue of addiction. And In particular, opioid addiction (which although legitimate & more effectively, regulated use has helped make great strides in medicine, has been plaguing man since as far back as the Sumerians!) Before posting such ignorant things :/ I know you're entitled to your opinion, but educated opinions are best....Heres a lil history on the plant ALL of these drugs come from one way or another, naturally occ. or synthetically. ((note its even from our own DEA  http://www.deamuseum.org/ccp/opium/history.html )) 

In short - we aren't the 'lab rats' in this case really, because we know what the predominant and re-occurring effects of these drugs are and due to such strict fda/dea GL's/Regs we pretty much have to let the rats suffer -.-


-O.o-

HensterGroenewald
HensterGroenewald

@Addictional Mytha 

So very true. I'm an addict. I'm an honest addict. Fact. We can blame the world, but in the end of the day it stays our choice. 

HensterGroenewald
HensterGroenewald

@KaleoK 

Interristing topic. Come to think of it, no one ever taught me how to shoot up. All i did was watch The Self Help To Heroin Addiction - Trainspotting.