Rewiring the Brain against Addiction
Scientists are discovering brain chemistry that prevents, and reverses, addiction.
Stopping craving 'upstream.'
What if you could take a drug that would cure addiction?
While some look for answers to addiction in religion, 12-step programs and the power of positive thinking, scientists are pushing forward the frontiers of neurobiology.
Researchers are figuring out how addiction rewires the brain. The goal is to eventually be able to rewire an addicted brain back to the way it was, before the drugs, the cravings, and the self-destruction.
Before we get to the research, some brain science basics to digest:
Humans take addictive drugs for the same reason they take aspirin when they have a headache: they want to feel better. For many, drug use begins as a release, a euphoric detachment from fears, pain, and troubles. But with each use, a wire is threaded in your brain, a wire that connects the drug to the varied list of things that you need and want. With each use the connection grows stronger and the list shrinks until eventually there is one want and one need that is greater than all others: drugs.
Dopamine is a central chemical in addiction that rules the pleasure and motivation system of the brain, making our biological drives, like eating and sex, enjoyable. Practically all addictive drugs increase dopamine and have a "feel-good" aspect to their effects. As a result, the dopamine circuitry that governs motivation and reward is the focal point of most addiction research.
But the dopamine system cannot explain all the features of addiction on its own. So researchers are trying to find out all they can about a brain chemical called orexin.
Blocking addiction upstream
New research published in Neuron by a team at the University of California looked at how orexin triggers the brain circuitry that increases arousal and gets you craving good things like food and water. This circuitry is upstream from the pleasure pay-off of dopamine. It is the craving before the feel-good.
Craving is a big part of addiction, so researchers looked at whether orexin is playing a part in wiring addiction.
The University of California team knew that when you give doses of cocaine to rats over time, the rats respond with higher and higher levels of physical activity. "You give [the drug] over five days and the animals run around more and more," Dr. Stephanie Borgland, the primary author of the research, told The Tyee.
This running around is more than an immediate reaction to the drug. It is an escalating expression of dependency and craving that models features of addiction in humans. In short, it is observable evidence of the addiction circuitry.
Researchers call this process "sensitization" to the drug.
This sensitization circuitry remains in place long after the drugs are no longer in the body -- part of the reason that an addict, even after laying off drugs for a long time, can be hooked again with a single dose.
But this sensitization won't occur if, at the beginning of cocaine use and throughout, the same brain is also dosed with a chemical that blocks the flow of orexin.
Borgland's research team came to this conclusion after giving regular doses of cocaine to two sets of rats. One group also received an orexin blocker, delivered through a tube directly to their brains.
Rats that received the orexin blocker before each cocaine injection did not develop a sensitization to cocaine.
The researchers conclude that blocking the activity of orexin in the brain when cocaine exposure was started prevented cocaine from wiring addictive behaviour into the brains of the rats.
The findings raise some interesting questions that would have to be addressed if therapeutics based on this research were developed for humans.
What if we were able to develop a "blocker" that allowed people to take highly pleasurable drugs like cocaine without becoming addicted?
Would more people use cocaine, which has other bad health effects?
Would an addiction blocker make the prescription of addictive medical narcotics, like codeine and oxycotin, less risky?
How would such a "blocker" change our society's relationship with currently addictive drugs?
Reversing addiction?
The University of California experiment with an orexin blocker points towards a way to prevent the wiring of the brain for addiction. But orexin blockers would not be able to fix rewiring once it occurred; they could help you from getting addicted, but once you were hooked they wouldn't help.
How, then, might addiction get wired out of the brain? That is the question being pursued by a research team out of UBC. And they may be on the verge of an answer.
"[Our research] is aimed at restoring the connections in the brain that may have existed before the exposure to the addictive substances," said Dr. Karen Brebner, neuroscientist and co-author of research recently published in Science.
The UBC research team thought that addiction could get wired in the brain just like a normal memory would be. So they took their knowledge of how memory works in the brain and applied it to the same behavioural test that was used in the orexin study.
"We found that blocking one type of rewiring in normal memory formation also plays a role in the formation of rewiring in drug addiction," said Dr. Tak Pan Wong, co-author and researcher at UBC's Brain Research Centre.
The UBC team noted that one way memories come into being is when neurons change their firing to a slow and steady pulse to alter circuitry in the brain. The UBC team made a very, very small protein fragment that prevents the change in rate of firing and thus blocks the formation of a circuit that could form a memory. The researchers tried their memory-blocking protein on mice that had been getting injections of amphetamine.
The UBC team believes it worked as they had hoped. The mice "looked like animals that were receiving the drug for the first time," said Dr. Brebner.
The protein made mice that were like addicts behave like mice that never had amphetamine before. When the signalling that was responsible for reinforcing the addictive behaviour was shut down, the addictive "memory" was erased. Which means that the protein that the UBC team made could potentially reset the wiring in the brain that is responsible for the cravings that remain long after the drugs are gone.
Decades away?
Medications based on blocking orexin might be available to people within a few years since drugs working on the pathway are already being tested in humans with sleeping disorders.
However, addiction reversal therapies based on the UBC research are going to be a much longer wait. Researchers don't expect to see human applications for at least 15 to 20 years.
Resetting the addicted brain to a non-addicted state could help a lot of people get off destructive drugs and stay clean.
Currently there is very little that medicine can offer addicts, other than dulling the chemical rush or treating the symptoms of withdrawal. Just ask Mike. No medical treatments helped him kick drugs. Now middle aged, Mike has been clean for seven years. His struggle with addiction started in his teens with cocaine and then moved to heroin once he came to Vancouver.
Withdrawal was hell. "It's like your worst flu times 50," said Mike. He didn't sleep for a month. He lay in his bunk at the recovery house and watched a traffic light change colour while his bones ached and his body cried out for heroin.
Mike has heard about medications that block cravings before, but he is not optimistic.
"I think that if you don't get it right in your heart and realize that you need to make a change...then you will never, ever get well," said Mike. "What works is getting honest and actually looking at the problem and realizing and shedding any reservations you might have."
Jeffrey Helm, a former neuroscientist, is writing about science issues for The Tyee this summer. ![[Tyee]](http://thetyee.cachefly.net/ui/img/ico_fishie.png){kind=small}
- Shadow Workers of the World, Revolt!
- 'The Kids Are All Right'
- 'Leave Your Shoes On'
- Economist Calls Gateway Pipeline an Inflationary 'Threat'
- Glaciers, BC Hydro's Melting 'Batteries'
- Too Much Energy Used to Mine, Move Bitumen Says BC Firm
- Frankie Rose Makes Life Tougher for Journalists
- Could SOPA Pervade Canadian Copyright Law?
- Would You Buy a Used Car from These Libs?
- Who Pays Huge Power Bills for Clark's Gas Plants?
- Shadow Workers of the World, Revolt!
- Eleven Oily Questions for Every MP
- Economist Calls Gateway Pipeline an Inflationary 'Threat'
- Is Canada Ignoring Signs of a Coming Economic Collapse?
- Bill Rees' Last Lecture
- How First Nations Are Gearing Up for Legal Battle Against Gateway
- Too Much Energy Used to Mine, Move Bitumen Says BC Firm
- Bruce Carson Scandal Greased by Harper's Oil Sands Agenda
- Harper in China
- Overhaul BC's Private College Regulator: Critics
- How First Nations Are Gearing Up for Legal Battle Against Gateway
- Shadow Workers of the World, Revolt!
- Make It the Canadian Webcasting Corporation
- Harper in China
- With Trade Deal, Will Canada Give EU 'Right to Profit' on Water?
- Foreign Trade Zones Eyed for Vancouver, Prince Rupert, Prince George
- Skating into 2012, More Resolutions
- Glaciers, BC Hydro's Melting 'Batteries'
- 'Leave Your Shoes On'
- Who Pays Huge Power Bills for Clark's Gas Plants?
18
Login or register to post comments
Truman Green
5 years ago
Comments on "Rewiring the Brain against Addiction"
I was very happy to read that memory-blocking drugs won't be coming on to the market for 15-20 years because, not only do scientists have only a fuzzy notion of the memory firing apparatus in the brain, (if any, notwithstanding the suggestion that they do) but because, at least in this article there is no indication that such memory blockage would be specific only to addictive substances. In other words, this kind of research, notwithstanding the pleasurable brain responses of grant recipients, seems a bit too much like the current deep brain stimulation techniques, frontal lobe dissection and electro-convulsive therapy, now mediated by tranquilzers to diminish the disturbing spectre of flailing patients.
I would strongly encourage these researchers to pay close attention to the requirement that such memory blockers be opiate specific and will not merely exacerbate the problem of losing one's keys.
Rats are an excellent surrogate for much biological research, (unfortunately) but addictive behaviour in humans is a tad more complicated, and involves suchs things as the culture of addiction, reaction to traumatic stress, learning disabilities, familial abuse, and mental illness.
In fact, I actually think that the problem of memory specificity will eventually cause the abandonment of such research.
Hopefully, in our ten to fifteen year window (before memory depressors come on stream) our society will learn to deal more effectively with drug addiction, with methods commensurate to what it really is: a social and medical problem--instead of trying to invent more chemicals to deal with chemical abuse.
jeffrey helm
5 years ago
I agree Mr. Green that fooling around with memory would be...problematic.
but memory in the case of this research is referring to a mode of imprinting the wiring for addiction into the brain, and the mechanism for it that is talked about in the article is very specific type of imprinting in addiction. I should have maybe elaborated more on that point in the article...
oh...but editors don't like it when i "elaborate" *sigh*
of course the scientists will be looking to see what else is affected, but so far they haven't found anything else that gets gummed up.
remember this is all ongoing stuff...
the exciting thing is that this research is hitting on wiring and mechanisms in the brain that are specific to and potentially underlie all types of addiction, not just opiates or stimulants.
this research IS dealing with addiction as more of a medical problem because it is focusing on underlying physiology in the brain that causes addiction, not just managing symptoms...
which to me seems like a better path to follow then just substituting an addictive drug with another drug like it that's just less addictive...
gkam
5 years ago
At least ten years ago, I read of an addict from New York, who, unable to kick his heroin habit, moved to Africa, where drugs were cheap and family stigma absent. After taking a native hallucinogen, Ibogaine, he realized he was cured of his addictions.
Researching it locally, he found it also worked on gambling and alcohol addictions, which implied an addiction center in the brain. At the time, cocaine was still a big deal, but I would read of NO government entities who would study this drug.
Since, I have seen occasional references to it, but nothing big.
Is it related to the orexin blocker in the article? I don't know, but it seems that we have been ignoring this potential cure for one of mankind's demons, for one reason or another.
jeffrey helm
5 years ago
well i took a quick look around and Ibogaine isn't being ignored, there is quite a bit of current research on it...and it doesn't look like it's related to orexin.
hmm...
i'll look into it, there might be a story there.
thanks for the tip gkam.
Truman Green
5 years ago
Excellent gkam, and I think you'll find that the difficulty of getting patents on naturally-occurring substances (unlike the engineered peptides that prevent cocaine-behaviour sensitivity in rats) and the fact that ibogaine is only to be used on ONE occasion has much to do with the fact that it is not being actively pursued by pharmaceutical companies.
The big money is in treatment medications which must be used many times and have high-end dosage costs.
Remember, the Pharmacorps are only interested in public health in so far as it rewards them and their shareholders.
Go here for a revealing look at ibogaine, which is derived from an African plant:
http://www.ibogaine.co.uk/ibogaine6.htm
gkam
5 years ago
To jeffery helm,
Good idea. If there is the potential I think is there, it could genuinely transform society.
Imagine not putting a million people in US prisons at about $30,000/year apiece. Think of not pounding billions down the DEA rathole. Think of saving lives, of eliminating a huge income for Bad Guys - it all sounds pretty attractive to me.
The reality will certainly fall short of my dreams, but there must surely be something there that we can build on.
Please keep us informed.
RickW
5 years ago
Absolutely amazing how we can marginalize what amounts to an epidemic. And by marginalizing, we can now look for a "cure". Why are we not questioning why milions upon millions of people feel the need to "feel good". Or more accurately, to feel less stressed:
http://en.wikipedia.org/wiki/Recreation
Instead, we maintain (if not increase) the stress levels, and seek to "balance" the inevitable deleterious effects chemically. That is certainly no "solution"....it is only another stopgap, and the stress that is driving "recreational drug use" will find another means of releasing itself.
Bobb999
5 years ago
Yes, it would be great if people could access a therapy that would de-addict the brain and without painful withdrawal, and that people could choose to use, rather than be compelled to by craving and withdrawal symptoms.
My (likely faulty) understanding of part of opiate addiction and withdrawal is that the addict's body stops producing endorphins (the body's natural opioids) once the addict is habituated to consuming opiate drugs. I understand that excruciating withdrawal symptoms stem from an absence of opioids in the blood, not remedied until the body begins to make sufficient (normal) amounts of its own endorphins again. As this process takes a few weeks, the addict suffers for that period. This
is the explanation I had read and believed to this point.
If brain wiring is the key,does this mean endorphins do not also figure into addiction, craving and withdrawal at all?
Josephine
5 years ago
Thank you, author and all who have contributed to this blog.
What a constructive and enlightening discussion.
gkam
5 years ago
Bobb999,
Your note makes sense, but I'm not sure any more that that's how it works. In 1968, I quit an addictive drug cold-turkey. At first, I was okay, but later, went through agonies of hell with muscle cramps, vomiting, chills, sweats, and all the things we used to see in the old movies. That agony's real stuff, and it took me down for 3-4 days. What was it? Nicotine.
Nicotine doesn't work on opiate receptors, to my (meager) knowledge, but the effects were the same.
Later, when I read about Ibogaine, then read of the research into addiction centers in the brain (a thought foreign to me), it started making sense. Finding out that ibogaine also worked with other addictions,(such as gambling), was surprising and welcome. I hope it works out.
Fred Mallach
5 years ago
It was stated in the recent report by the Health Officers' Council of BC (Fall 2005) that one of the reasons that individuals use a substance was because it makes them feel good.
It also reported that the two most widely used substances in Canada, alcohol and tobacco, were responsible for the most deaths from substance use.
Illegal substances, whether they are cocaine, heroin, crystal meth, or marijuana accounted for a negligible number of deaths.
As a society we need to realize that substance use is a part of society and has been since the dawn of civilization. By accepting this fact we can de-stigmatize the use of substances and treat the misuse of substances as a medical condition.
We already accept that there are individuals that cannot use alcohol safely and we try and help them. We have to get to the point were we treat all addictions the same way.
However, for many people, the use of cannabis is a daily occurrence, much like a glass of wine or beer after work, and they do not consider it an addiction. Since marijuana is far less harmful than tobacco or alcohol I wonder how long it will take before it is legalized.
jeffrey helm
5 years ago
hola Bobb999,
you're absolutely right on the opiate withdrawal, that's part of how it works...
and of course endorphins and withdrawal figure into it addiction...
the research in the article outlines just two out of many, perhaps even hundreds of circuits that contribute to wiring addiction into the brain...
there is wiring for craving, building connections and "memory", balancing endorphins against opiates, withdrawal, associating places and drug paraphernalia with getting high...
there’s wiring for all of it, and all of it's a factor.
neuroscience, indeed biology, is based on the idea that there is "wiring" for everything.
mind and body are one entity and not divisible.
BobbyPeru
5 years ago
This reminds me of the movie "A Clockwork Orange" where they try to rewire and reprogramme Malcom McDowell's criminal mind. After successfully weaning this criminal off lust and violent tendencies they return him to society. But, he is only a shell of what he used to be as a person. Devoid of unique thoughts he becomes a dull, politically correct drone. And that cuts to the movie's theme- that the ability to choose between good and evil, right and wrong is what makes humans unique. And once you take that away you extinguish the other great things humans are capable of accomplishing.
It's so nice to think that we can push those evil pharma companies to develop some easy drug that specifically eradicates addiction to drugs that make us feel high. It's nice to think that individual free choice is an enzyme or simple factor that can be readily controlled with medication.
Ultimately, you make the choice if you want any drug to play a role in your life.
jeffrey helm
5 years ago
thanks to everybody for reading, getting engaged in the piece, and commenting.
and big thanks to D. Beers for all his patience and help in getting the article ship-shape.
and of course thanks go to all the other darlings at the Tyee as well.
hopefully this is the first of many pieces that I will be writing for this publication.
ciao
RickW
5 years ago
Thomas Hobbes, in Leviathan:
Is this what we are trying to prevent with our copious use of drugs, or is this what we will become because of it?
Bobb999
5 years ago
Thanks Jeffery for the clarification about endorphins and brain wiring, and that they interrelate.
I've heard of Ibogaine being used to treat addictions. The infamous pot prince Marc Emery (before he was bankrupted by DEA & Friends)was involved in treating heroin addicts with Ibogaine. Is Ibogaine considered a psychedelic? Some psychedelics have apparently been used successfully in treating addictions. Ayahuasca is commonly used in various South American countries as a therapeutic
drug, to treat addictions and psychological and emotional problems. The Brazilian gov't initially looked into the drug with a view to possibly banning a psychedelic which was growing in popularity. But what they discovered was the drug had apparently overwhelmingly positive results for those using it, with few negative effects. So it remains legal.
The Native American Church legally uses peyote (even in the drug warring USA)in its therapeutic rituals.It's a church made up of a number of first nations, some in Canada, including some Lakota in Alberta,I believe.Many alcoholics and drug addicts who joined credit the church and its sacrament peyote for healing them, and freeing them of their addictions.
Diogenes
5 years ago
Please start here
http://www.cognitiveliberty.org/mission.html
http://www.cognitiveliberty.org/index.html
http://www.cognitiveliberty.org/issues/pharmacotherapy.html
Re: Ibogane
I first recall reading about Ibogane about 30 or more years ago
It seem there is strong resistance to natural substances
Mark Emery has been reported to paid for Ibogane treant for some of Vancouver’s heroin addicts
Mt question is
“what is the holdup?â€
Diogenes
5 years ago
oops
shoulda!
sorry
http://www.ibogainetreatment.com/
It is exrememly difficult know in advance, which kind of experience a specific individuum can expect during an ibogaine-session. Personal background, opinions, one's preparation,the quantity of ibogaine ingested, the environment during the session, the drug of choice, one's potential for change, all will influence the session.
But after more than 400 treatments we dare to make the following general statements about the effects of ibogaine:
90% of the patients will experience visions for a time-period of one hour to four hours.
In almost 100% the withdrawal signs and symptoms will be eliminated 80% to 100%.
Most of the visions are not easily understood, many are elating, some of them are intense, some might be negative, but Ibogaine always prooved to be a benign drug. It can almost be compared to a good teacher, which at times stresses the student, but will never overburden him or her.
About one third of the patients experience some nausea and vomiting. However due to the short duration of these bouts they are well tolerated.
Even if one treatment should not be conclusive to stop the abuse of drugs, ibogaine nonetheless will trigger a maturation process that more often than not will eventually lead to a way out of dependancy. Thus the patient might find the strength to follow thru with another form of therapy like a comunity or a substitutional therapy.