Eternal sunshine on a spotless mind?

Hannah -   Next, we meet up with a scientist to find out about a new treatment for addiction and posttraumatic stress disorder.  

Barry -   I'm Barry Everitt.  I'm a Professor of Behavioural Neuroscience in the Department of Experimental Psychology at the University of Cambridge. 

Hannah -   Hello, Barry.  So, we've just been talking to somebody who experienced quite severe addiction for a number of years and he spoke about overcoming his addiction and rewriting the script as it were, so removing associations that he had whether it be particular environment, particular social situations, with his addiction to alcohol.  I wondered if you could tell us a little bit about the research that's going on in this area of rewriting the script in your brain.  

Barry -   Yes and that's an interesting thing that this person has done.  So, when people begin taking drugs and then make a transition to becoming addicted to them, what happens is, generally, they take their drugs in a very ritualistic way in a very restricted range of environment, and in the presence of rather few specific stimuli that are related to their drug taking, obviously, for drinking alcohol is often in bars and with certain people, and it's true for people taking cocaine as well.  They have certain kinds of equipment that they use in certain places, sometimes with certain people.

And quite naturally, those stimuli become associated with the effects of taking the drug or drinking alcohol through a learning process that we've known about for well over a hundred years called Pavlovian conditioning and everybody remembers about Pavlov's dogs and bells, and salivation.  So, a restricted range of otherwise innocuous stimuli in the environment become alcohol cues or cocaine cues, or heroine cues. 

Now, it turns out what we've come to understand from our work and others in a clinical situation is those stimuli become very, very significant in the course of addiction because they can evoke craving.  

Hannah -   So, if somebody may have gotten over the physiological addiction to the particular drug and then after that, there's a second wave where they have to get over this association with the habit?  

Barry -   Yes.  In fact, you don't ever really unlearn those associations except recent research has suggested that it might be possible to unlearn or eradicate their meaning. 

Now, this has been known for many years in some treatment centres for addiction where clinicians have used something called cue exposure therapy.  So here, what happens is that people seeking to become abstinent - for example, to stop drinking - go in to the clinic through questioning and discussion, their particular cues are identified, and those are presented repeatedly, but without alcohol and this is what the person you were describing earlier has been doing by visiting places where he used to drink, but hasn't drunk.  And so, you keep repeating over and over again, presentation of these cues and it turns out that they elicit less and less, and less craving whether you measure that in terms of how people feel or you measure some objective - physiological measure like their heart rate or their skin conduction, a measure of some sweating on the palms. 

And this process in psychology is called extinction.  Now, that's all well and good, but it turns out that extinction is very context or situation dependent. 

So, if you bring somebody to the clinic, extinguish those cues so they're not responding to them.  When they go back out into the real world and encounter those same cues, but in the context in which their normally present, you find they haven't been extinguished at all.  So, it's not a very successful treatment.  

Hannah -   So, it's a bit like taking someone into the clinic and presenting them maybe with some beer bottles or particular advertising associated with alcohol which is a very different situation to meeting up with your friends on a Friday night in a restaurant where there's wine or there's beer available?

Barry -   Exactly so.  So, how do you get over that?  A couple of things have happened recently which have suggested that the memories elicited by drug-associated stimuli, drug use, can indeed be erased, and this was a big surprise when it was appreciated in about 2000. 

When you retrieve a memory in the point where the memory is active again, and in the case of drugs, when the cue has elicited your memories of drinking and cause you to crave, that memory becomes labile in a new active and transient state in the brain neurochemically.  It has to be re-stabilised in the brain. 

It turns out through another round of protein synthesis in cells in the brain, and that's kind of, but not exactly the same as, the process that would've occurred when those memories are being formed in the first place.  So, we talk about consolidating new learning to form memories and this process where the memory becomes plastic and must be re-stabilised to gain a retrieval, it's called reconsolidation.  

Hannah -   And so, that reconsolidation of the memory that point when the memory is quite labile and quite plastic may be a point where therapeutically, you could intervene and start some kind of treatment to dissociate that habit, that association with the drug?

Barry -   Exactly, right.  Now, it turns out that a very common drug used to treat hypertension, propranolol which is a beta receptor blocker can block that reconsolidation, that re-stabilisation process. 

So, if you retrieve a memory in the presence of a beta receptor blocker and then come back and look a day or a weak or a month later, you find that memory has been erased. 

Now, that's being translated to a clinical setting in the case of posttraumatic stress disorder, people who are greatly affected by horrific and intrusive memories of terrible events like war or accidents, or rape, and it turns out if you retrieve the memory under beta receptor blockade, not just once but two or three times, there's an enormous reduction in the intrusiveness of the memory and people are much less bothered by it. 

Now, that particular approach to treatment hasn't yet been applied to drug addiction, but it's something we are planning to do here in our alcohol study.  

Hannah -   And how do you make sure that you're not going to be erasing any other memories at the same time whilst administering this beta blocker because that must be a bit of a concern that you would erase a person's memory?  

Barry -   Like the eternal sunshine of the spotless mind, that's one of those fears that people always bring up, but actually, the conditions under which you can make the memory labile and can influence it are incredibly precisely defined.  So, you would only ever be able to modulate a memory by focusing on the conditions specific to that memory and reactivating it.  

Hannah -   And which areas of the brain are these memories, these associations, being affected by the beta blocker?  

Barry -   The amygdala which is well-known to be associated with emotional learning and memory.  It is certainly the case for drug cue and fear cue memories, but also the hippocampus which is much more to do with spaces and places, and contextual memories. 

So, that's a treatment that's based on something that is now called reconsolidation blockade, but it's also the case that in the last couple of years, it's become clear that you can take the first process that I spoke about which is extinction and the second process I spoke about which is reconsolidation and put them together because they interact in a very interesting and unexpected way. 

Now, what's recently being investigated in the very exciting way is that if you briefly retrieve a memory and then wait a little while, 10 minutes or an hour, and then do extinction, that combination of brief retrieval delay extinction training, actually results in the true erasure of the memory, particularly if it's done perhaps on a couple of three times, and the memory never spontaneously recovers.  You can never cue it back into existence again. 

Now, that combination of treatments has been done experimentally in a drug setting, in a lab in China, and this was published in Science.  And there, they've taken heroin addicts and brought them into a treatment centre, briefly exposed them to heroin cues to retrieve the memory, they've waited a little while and then taken them through extinction training room.  They've done that two or three times and discovered that subsequently, those cues have lost their ability to elicit craving and they've lost their ability to activate the physiological measures of the impact of those cues in terms of reduced heart rates and reduced sweating skin conductance.  

Hannah -   And do you think that holds promising in terms of translating into the real world situation where you have more of these social cue?  

Barry -   The evidence is, that reconsolidation blockade and this extinction following brief memory retrieval which some people call super extinction is not constrained by context.  So, you can do it in one place and it transfers to other places.  So, that's really quite an exciting development because it suggests you could take advantage of what already goes on. 

For example, in the treatment of PTSD or phobias you would conduct a normal cognitive behavioural therapy session where you'd bring someone in and actually go through an extinction process, but you do it under these conditions of brief memory retrieval followed by extinction.  In a consultation, there's already going on, just a subtle change in the way you conduct it and it might have a profound impact on the success of the extinction training.

Hannah -   That was Professor Barry Everitt from Cambridge University.