Finding the Brain's Addiction Switch | Steven Laviolette | TEDxWesternU

addiction is an aspect of the human condition that's probably going to affect everyone in this room either directly or indirectly depending on the personal experiences we have in our lives of addiction or the experiences that one of our loved ones has with addiction we can come up with all sorts of different rationalizations to explain why addictive behaviors take place okay so we can think of addiction as a bad habit so something that we've fallen into due to circumstances in our lives beyond our control may be addiction is just a personal choice is addiction may be a moral failing is to do to some sort of intrinsic personality flaw well recently we've been thinking about addiction in terms of it being a disease state now I'm a neuroscientist I've been studying the neurobiology of addiction for almost 20 years now I've come to appreciate the importance of how we conceptualize addiction because it really addresses how we approach the issue of addiction in terms of our research and in terms of how we treat people that are suffering from addiction now the disease model of addiction is probably one that everyone in this room is familiar with it sort of thinks of addiction as being an organic brain state sort of akin to what we think of typical brain disease diseases like Parkinson's or Alzheimer's it's also suggesting that addiction should be thought of as a permanent state of brain pathology the idea that once an addict always an addict sort of encapsulates this idea that addiction might be best represented as a disease state but I'm gonna argue today that this is probably not the best way for us to be approaching addiction or to be thinking about addiction and I'm going to suggest that there's an alternative way to think of addiction more as a disorder of reward and memory pathways in your brain now some of the implications of this model of addiction suggest that addiction is rather a plastic series of brain adaptation it's a dynamic process in the brain rather than a permanent state of brain pathology it's something that we can reverse and finally decide that addiction might be controlled by specific molecular mechanisms in the brain that can actually take you from a healthy non-addicted state to an addicted state okay so the well-known addiction cycle all drugs of abuse begin by producing very strong rewarding effects in my field of a my field of study we look at the rewarding effects and the addictive properties of opiate class drugs so this includes drugs like heroin morphine and more recently prescription narcotics and we've had a tsunami of addictions related to drugs like vicodin percocet oxycodone costing us billions of dollars not to mention the horrendous social cost associated with addiction to these substances now if we take these drugs over an extended period of time what happens is we start developing adaptations in our brain changes in the brain happened in terms of our neural chemistry the molecular substrates controlling these pathways and even structural differences in various brain regions finally we develop psychological and physiological dependence on the drug after a period of exposure to the drug of abuse now this is especially true with opium class drugs we have this very strong physiological dependence syndrome that develops with opiate class drugs now once the drug is taken away from us we almost inevitably are going to go through a period of withdrawal and that's accompanied by these very strong feelings of craving you've got to get this drug back into your system to alleviate those feelings of withdrawal that you're experiencing now finally sort of the fourth part of this chain and we argue is actually extremely important and one that's been under looked for a long time is the importance of memory induced relapse so if I were to inject myself with heroin right now and experience these profound rewarding effects and then I forgot about it in 20 minutes chances are I'm not gonna become addicted what happens when we experience the rewarding effects of a drug of abuse our brain forms associations between those effects of the drug and all of the environmental cues so for example someone that was addicted to heroin and has been clean for 10 even 15 years walking down the street they see some sort of - in their environment that re triggers those addiction memories and they fall right back into relapse so you can see when we look at it in terms of this chain of events to effectively treat addiction we need to break at least one of these links so in a nutshell we can sort of think of addiction as being importantly controlled by reward systems in the brain and memory systems in the brain now in terms of explaining addiction based on many years of animal-based research and clinical research as well there were two sort of general theories of addiction that were sort of popular at the time when I began this sort of research about 15 20 years ago one set of theories were the dopamine reward theories and this was based on the idea that almost every single drug of abuse activates dopamine neurons you get this release of dopamine in the brain so logically we thought that ok drugs would use activate dopamine so that's why I become addicted we activate our dopamine system and that's why we keep taking drugs now on the other side of the spectrum theories sort of focus more on the darker side of the addiction process withdrawal and these sorts of theories suggested that the reason we keep taking drugs of abuse is because we go through the draw and we need to seek out those drugs in our environment to alleviate those unpleasant feelings of withdrawal that we're experiencing so when you think about these theories for a second you sort of realize that there's some obvious problems with both of them in terms of dopamine well as the years went by we realized that dopamine is not as simple as we thought dopamine tomorrow more complicated so for example dopamine is activated even during unpleasant experiences the other problem theory is that it does a good job explaining why we take drugs in the first place but we know that when we continue taking drugs of abuse they're rewarding effects tend to decline over time even the dopamine response can sometimes get lower and lower so how does it account for why we continue taking drugs of abuse for years and years and years now on the other side of the equation withdrawal based theories do a good job of explaining why we fall into a relapse to addiction but they don't do such a good job of explaining why we started taking drugs with use in the first place so an obvious question is is there some sort of link between the brain mechanisms that control these early rewarding effects of drugs and these later effects of withdrawal and I want to present this idea of an addiction switch that can essentially serve as a a mechanism to account for the transition from the healthy non-addictive brain state to the addictive bracelet we know that addiction fundamentally changes the brain I talked about a couple of those changes they have been at the molecular level or chemical level structural level and more importantly looking beyond the brain addiction fundamentally changes the cell it changes your personality changes your cognition it changes your behavior and anyone who has watched a loved one go through the horrible effects of addiction one of the things that stands out in your mind is you remember how much that person's personality and their behavior changes while the while they're under the influence of the drugs of abuse now in terms of opiates one of the most addictive drugs that are potentially available we knew a couple important things about opiates that suggested that there might be some sort of switching mechanism going on between these we knew that in the naive state so before you became addicted to opiates the effects of opiates could be mediated through a dopamine independent pathway so you don't need dopamine to experience the rewarding effects of opiates when you're first starting out taking the drugs obviously in the naive state there's an absence of withdrawal mechanisms in the brain there's a very minimal amount of molecular changes that are taking place but then we looked at the effects of opiates in the addicted State and we saw a profound difference so first of all we noticed that the rewarding effects of opiates once you're addicted opiates activate the dopamine system so you need to have a switch to a dopamine system there is very strong feelings of withdrawal and craving there's obviously profound molecular alterations and various brand reward pathways that are very important so the question that was posed when I actually began looking at this question about about 15 years ago back University of Toronto was whether or not we can find this elusive hypothetical switching mechanism in the brain that controls this transition from a non-addictive state to an addicted state so without going through the minutia and the years of research that led to these conclusions what we were able to find was that when we focus on an area of the brain called the ventral tegmental area neuro Anonymous like coming up with these unpronounceable words but we're just going to call it the VTA for the sake of simplicity this is an area in the middle part of your brain sort of the base your brain and it contains the dopamine system and it's very important for drugs of abuse because almost all drugs of abuse produce their effects through the VTA so in a very simplified explanation of this what we found was that gaba-a receptors which is a type of inhibitory receptor located in that area of the brain was actually able to serve as a molecular switching mechanism between a non addicted state and in it an addicted state so normally you can think of the GABA a receptor as controlling the bio electrical properties of a neuron they control whether a neuron is on or off and remarkably what we found was that in the non addicted state the gob a receptor acted normally it produced inhibitory signals to the neuron it shut down neurons but once we looked at an addicted brain the function of GABA a receptor switched to an excitatory State so essentially we're looking at a mechanism that controls reward signaling for a non-addictive grant award pathway versus a system that is switched on in the addicted state and transfers reward signals through an addiction brain reward pathway so that's great we found this hypothetical switching mechanism in the brain but remember that I said that addiction is more than reward we also need to experience memory we're talking about it memory is a very critical component of addiction so for example as I mentioned before we need to form these associate memories in our brain in order to continue that addiction cycle and we next look at an area of the brain called the basal lateral amygdala and then another one of these unpronounceable terms we're just going to call it the VLA now this is an area of the brain located in your temporal lobes and it's extremely important for your ability to form associative memories between the effects of drugs of abuse and their related environmental cues so we looked at this region of the brain called the PLA to see if this might serve as a memory switch between the non addicted state and what we found was that in the non addicted brain the ability to form opiate addiction reward memories depended on a receptor substrate called the d1 and it modulated a downstream molecule we're just gonna call it earth so a non dependent drug naive molecular mechanism in the BL a controlling addiction memories in the naive state we looked at the addicted brain and what we found was that there was a switch between this d1 receptor mechanism to a completely different brain reward mechanism for the formation of addiction memories and now we were dealing with a system that relied on a type of receptor called the d2 receptor and an entirely different molecular downstream signaling pathway both cam kinase 2 so again just like in terms of processing the rewarding effects of drugs of abuse when we look at the difference between the addictive state and a non-addictive state the ability to form drug addiction memories is also under the control of a discrete switching mechanism and the really cool thing about this is that we were able to target those molecules in the amygdala and switch the brain back and forth from an addicted state to a non addicted state so this is really exciting because to suggest that instead of thinking of addiction as this chronic permanent irreversible state we can actually go into these brain areas we can target these molecular pathways and we can actually switch the brain from a non-addictive state to an addicted state and back and forth so this really calls into the question the need for us to do a new paradigm for conceptualizing what's really going on in addiction we know that in the non dependence state we're dealing with an entirely different set of molecular and neuroanatomical mechanisms that control how you perceive the rewarding effects of a drug like heroin for example but once you become addicted to that drug something switches in your brain there's a switch two entirely separate molecular and neuronal systems in the brain that control how you perceive that rewarding effective drugs of abuse so this is really thinking of addiction much more in terms of a plastic dynamic process that allows us to go back and forth between these different states so where do we go from here I think one of the most important questions to ask let's go back to the beginning and address the issue of whether or not the disease model of addiction has really served us well and I'm going to argue that no it hasn't really been an effective model for us in terms of our ability to understand what's going on in the brain and more importantly in terms of developing effective treatments for addiction because remember after many decades and many thousands and thousands of research papers from all sorts of disciplines we have yet to develop a truly effective treatment for dealing with the devastating effects of addiction the problem with the disease model of addiction is twofold the first problem is that it doesn't take into account these dynamic processes that are happening in your brain as you go from a non-addictive state to an addictive state because I said at the outset we think of diseases as these sort of permanent static processes as opposed to these more dynamics switching mechanisms that go on in the brain the second problem is that when we use a disease model of addiction whether we're talking about forming questions for our research or developing more effective cycle therapies for treating addiction we tend to focus more on the effects of addiction we focus on the symptoms of a dish instead of the underlying causes of addiction now having said that I think that there's enough evidence out there it's Jess that a better way of thinking of addictions are that we're dealing with an altered but reversible state of the brain it's controlled by a series of molecular mechanisms that control the switch of a non-addictive state an addicted state and as I said before what's most exciting about this that allows us to go into the brain target these molecular pathways and potentially develop more effective pharmacal therapeutics or more effective psychotherapeutic approaches to dealing with addiction by appreciating some of these dynamic mechanisms so as I said at the outset one of the important things about addiction in terms of understanding how it processes the rewarding effects of drugs of abuse is this idea that we can identify a switch and ultimately turn off the effects of addiction in the brain

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Keywords: TEDxTalks, English, Canada, Health, Behavior, Brain, Choice, Mental health, Morality

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Length: 16min 35sec (995 seconds)

Published: Tue Feb 14 2017