I think the work of Nora Volkow and others with PET imaging of the reward centers really shows a very powerful picture of changes in the brain reward circuits and chemistry as a result of drug use. The work of Mark Schuckitt with young adults and tolerance shows that having the ability to tolerate alcohol influenced the risk of addiction later. The Natural History of Alcoholism-revisited by Vaillant is a landmark 50 year follow up study of the progression to addiction. I hope this helps.

Work of Volkow is great for start. Maybe try the article of Dalley on imaging and obesity/food compulsive user.

For Animals (that could bring some translational research information), publications from Belin, Dalley and Everitt/Robbins teams could provide some good clues.

Maybe take a look at publication investigating link between "personnality" traits and drug abuse disorders.

Those are both good responses but still narrow. You need to begin by examining addiction as a bio-psycho-social phenomenon and not just the individual biological and psychological processes but the social context of use (and also consider the way you conceptualize and addictive drug). If you e-mail me at [email protected] I will shamelessly refer you to my own book : )

Conceptualizing addiction as a form of conditioning has been central to the field's scientific since the 1950's. I can think of nothing more important for understanding the topic. I suggest beginning with O'Brien, C.P. and Gardner, E.L. (2005) Critical assessment of how to study addiction and its treatment: human and non-human animal models. Pharmacol Ther 108, 18-58. Much of the recent research can be seen as an effort to understand the underlying brain mechanisms for the reinforcement process.

Although, interestingly, there is relatively little evidence that treatments that are underpinned by conditioning models are particularly effective (see the cue exposure literature for example) suggesting that whilst conditioning models are of theoretical interest, a broader psycho social model of addiction is required.

There is actually a great deal of evidence for the role of conditioning in the treatment of addiction. Please see my Chapter in Principles of Addiction Medicine(Fourth Edition 2009, Chapter 61 Aversion Therapies. There are multiple studies demonstrating improved outcome with the addition of aversion. Beyond aversion, much of the process of recovery is not simply making a decision to quit but retraining how one reacts to a variety of internal and external stimuli which are associated with increased craving for drug or alcohol use. Much of the brain imaging has been focused on the early acute period of addiction, when the addict is either recently sober or just part of a research program. These studies show high activity in the areas of nucleus accumbens with presentation of drug or using cues but not with neutral cues. The research we would like to see would be to see the results of these studies after a person completes a particular treatment program and look at its prediction of future recovery.

Patrick, would you have a pdf file of your chapter available? If you do, would it be possible for you to send it to me? John

John,

Thank you for your interest. I will have to check with the publisher about sending out the chapter.

I would be interested to read your chapter as well patrick. i have conducted two treatment trials using an exposure based approach and neither demonstrated greater efficacy than standard cbt. I have not come across other RCT's in which exposure based treatment was found to be more efficacious than CBT approaches including more recent RCT's by Kavanagh so i am keen to update my knowledge.

Thanks Patrick. I hope you have a kind publisher! John

Coming back to the question. The answer is complex. Most researchers postulate the leading role of operant conditioning and a secondary (minor) role of classical (R.Griffiths, C.R.Schuster, J.Katz, N.Volkow, N.Mello, J.Koob, W.Bickel). Others think that the role of classical conditioning is much bigger but still addiction cannot be explained without operant conditioning (A.Wikler, E.Gardner, R.Wise, C.O’Brien, R.Foltin, S.Goldberg, K.Silverman, Y.Shaham). A few researchers reject the very existence of operant behavior (A.Norman, V.Tsibulsky) on the ground of internal contradictions of the theory challenged by a number of paradoxes. If you are a psychologist probably you will gravitate toward the first or the second group. If you are a physiologist and/or pharmacologist you would take the last point of view seriously as the most scientific (free of paradoxes). It is difficult to explain drug taking behavior in humans from exclusively classical point of view. But who says that the problem is easy? At least in animals the theory of Pavlovain conditioning explains this behavior nicely.

From a scientific point of view, addiction and physical dependence on a drug are closely inter-related but subtly different things.

Physical dependence occurs when a person takes a psychoactive drug regularly enough and for long enough for their nervous system to begin adapting to its presence. Your nervous system seeks homeostasis. It tries to regulate its internal chemistry to keep things in balance. All psychoactive drugs interfere with this, by mimicking the effect of naturally occurring ("endogenous") neurotransmitters and hormones.

They either directly stimulate the receptors that these endogenous chemicals are meant to engage with, or they elevate the levels of these endogenous chemicals by blocking or reversing the flow of structures called transporter proteins and re-uptake pumps that are meant to clean up excess levels of them.

If you take a drug once you will not become dependent. But your brain is a responsive and adaptive organ. It's job is to modify itself to fit your environment, and to learn from experience. If you take any psychoactive drug regularly, your brain will try to adapt to that as well.

On one level, brain function is a delicate balancing act between thousands of these endogenous chemicals. Your nervous systemn does not know what a drug like (say) methamphetamine is. If you take meth regularly your nervous systemn will interpret this as an excess of, (or dysregulation of), the neurotransmitters that meth releases into your synapses; (dopamine, serotonin, and (nor)adrenaline). It will respond by naturally releasing less of these chemicals ("down-regulation") and by making receptors for these chemicals less responsive ("de-sensitisation").

This is why people develop a tolerance to any psychoactive drug they take regularly. The "flip-side" of tolerance is physical dependence. Once someone's brain is habituated to the drug, they will only feel "normal" when they have a certain amount of it in their systemn. If they abstain, they will experience withdrawal symptoms. This is the basis of drug dependence.

The person’s nervous system will also form associations between places, people, or events that are associated with drug use. If they always use when in certain situations, with certain people, or to deal with certain social situations or stresses, these “cues to relapse” are physically hard-wired into their brain. This is the basis of drug addiction.

Because of neuroplasticity, they will eventually feel "normal" again. "Recovery" from physical dependence is the process of the person's nervous systemn re-adapting to a changed environment, and "un-learning" the changes that were made in response to the drug use. “Recovery” from addiction is the process of unlearning all the knee-jerk, habitual responses to environmental cues that have been associated with taking the drug.

So, there is nothing "unnatural" about addiction. Addiction is a learned behaviour. When you were born, your brain had roughly the same number of neurons it does now. But (assuming you are an adult) your brain has quadrupled in size since you were born. You haven't increased the number of brain cells, you've grown many more connections between them. When you learn anything, new pathways are physically burned in your brain, connecting neurons that were not connected before.

If this is the first time you have encountered this information, then reading this paragraph has subtly changed the structure of your brain, just now.

Using heroin every day changes your brain structure.

But then, so does playing the piano every day, or learning to surf, or type, or play a video game etc, or learning a second language. Other experiences are less benign, but still modify both your brain chemistry and structure- for example acute trauma or being subjected to high levels of chronic stress.

London cab drivers have to learn the whole layout of the cities central business district by heart before they are licensed- it's a grueling testing process that takes most people months or years to complete. When scientists put them in fMRI scanners they can actually see structural differences in the part of the brain that is most involved in spatial navigation and spatial memory (see link below).

A similar study looked at people from religious minorities who are schooled in dogmatically narrow ways of thinking, and who are subjected to social stressors because of their beliefs. In later life the part of their brain that stores memory becomes (on average) smaller, not just shrinking but also growing new connections more slowly than people of the same age who come from less stressed, more open-minded backgrounds. (See link below).

So, to summarise, if you repeat any experience that modifies your brain chemistry regularly enough, then your nervous systemn will change the way it regulates it’s chemistry to adapt, and it will learn to expect the drug when exposed to certain situations, places and people.

Whether you are addicted to heroin, chocolate, gambling, or jogging each day, what has happened is that your nervous system has learned a way to regulate your moods and feelings. This level of your nervous systemn is kind of lazy and only concerned with your immediate circumstances. If you abstain from the conditioned behaviour, it will initially seek the simplest, quickest way to make things go back to what it has learned to see as "normal"- and that's called "relapsing".

If you stop the accustomed activity abruptly you will crave the activity until your nervous system learns a different way of regulating itself. With drugs we call this re-adjustment “withdrawal.”

With some drugs (like caffeine) this withdrawal process is relative quick and easy.

With some (like heroin or morphine) the withdrawals are horrible but unlikely to seriously harm a relatively healthy person.

With some drugs abrupt withdrawal is actually physically dangerous (especially withdrawal from high doses of alcohol or benzodiazepines, which can kill people).

With most drugs a gentle and gradual reduction of dose and frequency of use allows this re-adjustment to take place gradually and relatively easily.

Learning to depend on drugs will change the way your nervous systemn regulates its internal chemistry, and if you stop abruptly you will experience withdrawal until your brain adapts to the fact you are not engaging in regular use anymore.

Learning to depend on drugs will also change aspects of your brain structure. Your nervous systemn will learn to associate certain images, places, people or social situations or stresses with the drug, and will try to prompt the conditioned response- hence "cues to relapse".

There is no magic cure for addiction. If someone has spent years conditioning themselves to dependent use of a drug, and to relying on it to deal with stress or to enjoy themselves, we should expect it might take weeks or months to "unlearn" that behaviour.

Here's some links to relevant research;

.

London Cab Drivers vs Bus Drivers Brains;

http://www.ncbi.nlm.nih.gov/pubmed/17024677

.

Religious affiliation and hippocampal atrophy in later life;

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017006

.

Robinson & Berridge 1993: The neural basis of drug craving: an incentive-sensitization theory of addiction;

http://66.199.228.237/boundary/SA/craving.pdf

.

Robinson & Berridge 2000 The psychology and neurobiology of addiction:

an incentive–sensitization view;

http://dionysus.psych.wisc.edu/lit/articles/RobinsonT2000a.pdf

.

Koob & Le Moal 2001 Drug addiction, dysregulation of reward, and allostasis; http://dionysus.psych.wisc.edu/coursewebsites/PSY411/Articles/KoobG2001a.pdf

.

Koob et al., 1998 Neuroscience of addiction. Review;

http://66.199.228.237/boundary/addiction/neuroscience_of_addiction.pdf

.

Koob 2008 Neurocircuitry of addiction;

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805560/

.

Everitt & Robbins 2005 Neural systems of reinforcement for drug

addiction: from actions to habits to compulsion;

http://66.199.228.237/boundary/addiction/conditionedresponse.pdf

.

Hope my discussion, and these links, are interesting and maybe useful for you all.

Paul.

John and Sharon,

I will need an e-mail to send the chapter to you.

I am enjoying the above discussion. We agree that recovery from addiction requires retraining and a recognition that once the brain has so adapted, it can be retriggered and hence addiction must be treated like a chronic illness, wherein one continues to prevent recurrence. This is by preventing re-intake of the substance but also preventing reactivation of the rewarding memory to the point that pursuit of the drug is inevitable or a level of distress is experienced for which the addict feels that only the drug will be able to provide the required relief.

Hi Patrick,

I'd love to see a copy of that chapter as well.

Regards,

Paul.

Hi Patrick,

Thanks very much.

I will send you my e-mail address via RG messaging.

Best wishes for 2014.

Regards,

John

Hi Paul,

Thanks for the info and the links to the papers.

Best wishes for 2014.

Regards,

John

Wow thank you so much guys,

I have really enjoyed reading everyone's contributions to my question! I have been away from the computer for a while so it was a big surprise to see so much of a response.

Paul those references were spot on thank you for those, they really helped me to develop my essay further. Unfortunately I couldn't write about everything said on here as there was a darn word limit!! otherwise I could have wrote for hours :)

I look forward to creating more discussions like these,

Kind Regards and Happy New Year.

Riane

3rd year undergraduate student at The University of Salford

Psychology & Criminology Honours Degree

Recently studies of the neurobiology of drug addiction point to Pavlovian sign-tracking as a major contributor to the transition from voluntary drug use into poorly controlled drug abuse. Sign-tracking is the Pavlovian conditioning of directed motor action that arises from pairings of an object that signals a reward. Subjects become so object-centric that they lose many of the available rewards, indicating a disconnect between action and intention. When the drug is located inside the object, sign-tracking of the object will encourage involuntary and reflexive drug-taking. Subjects prone to sign-track are highly vulnerable to drug addiction. I have published several reviews of the behavioral literature, and Terry Robinson and his associates have reviewed the neuroscience literature,

The Tail of the Raccoon: Secrets of Addiction

The dangers of experimenting with drug use are the topic of a scientific short story about sign-tracking and the disconnect between action and intention, that transitions drug use into drug abuse. The educational website, www.tailoftheraccoon.com, provides more information about the stories of The Sign Tracker Trilogy and the intriguing scientific research upon which they are based.

Thanks for this Arthur.

Hi Arthur,

Thanks for that link.

Paul.

It is very clear that Clonninger type 2 alcoholics have a gene or genes such that the first taste (taste not the first drunk) of alcohol lights up their limbic system. There are very important gene-environment-drug interactions that drive addictions. At AA meetings, which are heavily type 2s, you will hear again and again that with the first drink, be it at age 8 or age 25, they knew that is what they wanted to do. They also have low biological markers for 5HT activity--low 5HT and 5HIAA n the CSF, low fHIAA in the urine (90% from the gut), low SERT and MAO-B activity in the platelets (same proteins as in the 5HT nerve endings). A body wide deficiency that will always be there. For others, the addiction becomes a learned pattern--my grandfather would say, "You're not a man unless quit smoking at least once a week." I was at a day-long workshop and during a break talked with a counselor who himself had been in recovery for 15 years, but was in a near panic attack because during the presentation by a narc, baggies of confiscated crack and heroin off the street had been passed around. 30 min later his hands were still shaking. That is a very powerful grip.

There are clearly genetic predispositions that confer vulnerability to alcoholism. The G variant of the Aii8 polymorphism is a single nucleotide polymorphism that alters the structure of the opiate mu receptor, making it more receptive of beta-endorphin, which is released by alcohol. Carriers of the G variant find alcohol more stimulating, pleasurable, and rewarding. They are far more prone to alcoholism than the A variant carriers, who are less likely to respond so positively to alcohol. It makes sense that the more rewarding the drug, the more likely the drug will be abused. What transcribes reward into loss of control is the next question. Sign-tracking is a hot candidate on the neuroscience scene.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755398/

Operant learning and classical conditioning are part of the addictive process. That's why we teach patients to avoid high risk situations, identify triggers and cues, especially in early recovery since these triggers and cues prompt cravings which may lead to relapse. Dr. Ben Kelch

Some good points on here, but too many generalizations. For instance, there is no solid evidence of a disease called addiction which 'makes' people take drugs. All that conditioning theory stuff works well with rats (and maybe students), but grown-up humans are far more complicated (they have cognitive processes, for one). Regular drug use is a decision people make every day, like watching TV (an example most of us can relate to). Regular drug use (I can't use that stupid word 'addiction') is often just down to choice and social context. For instance, I had a methamphetamine habit when I was younger. After a couple of years, I was inevitably in a poor state of health, and one day I thought 'sod this' and I stopped. I was pretty exhausted and messed up for a few weeks, but there was no craving - on the contrary, the thought of the buzzy white powder now made me nauseous. Fifteen years later (last year), I visited a friend, and they were shooting up methamphetamine. I was curious, but had no desire at all to repeat the experience. I picked up the powder and looked at it, and like Gandalf handling the One Ring, I thought 'what a powerful buzz this drug causes. I used to like that, but I don't any more'. My hands didn't get sweaty at the perception of this 'cue'. Maybe its individual differences, but I prefer to think addiction is a myth. You pays your money, and you takes your choice.

Control of behavior is not a black and white phenomenon. There are differences in how drugs/etoh affect people's brains and at different points in their life. PET scans show clearly differences in the reactions of brain reward centers in patients with hx of heavy drug use with response to drug cues. Cognitive control of behavior is partly learned and partly a process of development. Conditioned responses are clearly learned automatic responses. Training is a real phenomenon. All of these things lead to brain changes. At the core of addiction is the loss of control of the behavior. Some people do stop their alcohol and drug use after getting a period of sickness or an accident and that is enough to alter the valence of the drug and alcohol memory. However, some people have a much harder time stopping the alcohol and drug use. Vaillant in his landmark book,, The Natural History of Alcoholism which followed a sample of inner city youth and college graduates for over 30 years provides a great deal of information. On page 197 he clearly shows that there is a relationship between the number a problems the person had related to his drinking using Vaillant's Problem Drinking Scale(which listed problems in different areas of the person's life related to alcohol) and the amount of treatment and 12 step intervention needed to develop a sustained sobriety. This indicates that the reward memory of the addiction or the level of dependence or whatever other construct one has for addiction, is so strong that the person is willing to undergo all these problems to still experience the drug effect and the number and amount of interventions needed to break that hold will be greater. For people who stopped with few problems Willpower clearly got the most credit, but for those whose addiction had lead them to greater problems, more outside intervention and retraining was needed.

Problem Drinking Scale:

Employer complains Single hospital,clinic or AA Visit

multiple job losses 3+ visits to clinics

Family /friends complain 2+ blakcouts

Marital problems Going on Wagon

Medical problem Morning tremulousness/drinking

Multiple medical problems Tardiness or sick leave

Diagnosis by clinician Admits problem with control

Alcohol related arrest 3+ Alcohol related arrests

(one point for each item)

Percentage of men with different PDS scores citing selected factors in abstinence.

Problem Drinking Scores

4-7 8-11 12-16

n=15 n=22 n=12

Willpower 73% 45% 25%

Substitute Dependency 53% 45% 62%

New Love Relationship 20% 18% 42%

Clinic Treatment 0 23% 83%

Alcoholics Anonymous 13% 41% 92%

The problem drinking scale and the table in my previous response was distorted when I submitted it.

Here is another way of presenting it:

Problems Drinking Scale (PDS) one point for each item

Employer complains

multiple job losses

Single hospital,clinic or AA Visit

3+ visits to clinics

2+ blakcouts

Family /friends complain

Marital problems

Going on Wagon

Medical problem

Multiple medical problems

Morning tremulousness/drinking

Tardiness or sick leave

Diagnosis by clinician

Admits problem with control

Alcohol related arrest

3+ Alcohol related arrests

Percentage of men with different PDS scores citing selected factors in abstinence.

Problem Drinking Scores_________4-7_____8-11_____12-16

____________________________n=15____n=22_____n=12

Willpower_____________________73%_____45%_____25%

Substitute Dependency__________53%_____45%_____62%

New Love Relationship__________20%_____18%_____42%

Clinic Treatment________________0_______23%_____83%

Alcoholics Anonymous__________13%_____41%_____92%

I suggest you look up open-access articles and especially reviews by Kent Berridge of barry Everitt to cover this question, e.g. http://www.ncbi.nlm.nih.gov/pubmed/18640920 or http://www.ncbi.nlm.nih.gov/pubmed/22285426

Be sure not to miss a classic explanation about learning theory and addiction:

Wikler, A. (1973). Dynamics of drug dependence: Implications of a conditioning theory for research and treatment Archives of General Psychiatry (Vol. 28, pp. 611-616).

A few points:  quitting is easy, it's the not starting that is hard.  Or as my grandfather put it to me, "Your not a man unless you quit smoking at least once a week."  In that vein, I did the typical middle school thing of stealing a pack of my mother's cigarettes and went with two friends to the back of the park and we lit up.  Cough, hack...I said that this was really stupid.  Never smoked tobacco again.  Three years later by two friends were 16-year old "pack-a-day men."  Why did they get hooked and I didn't?  

My good friend the late Bob Myers (RD Myers if you want to do a lit search) got started on alcoholism research after he had gone to a faculty mixer at Colgate College.  He and another young new assistant professor met and had two drinks each.  Bob showed up to teach class the next day, his new friend disappeared for two weeks.  Turned out he was "on the wagon" and the two drinks threw him off--one drink was too many and 1,000 were not enough.  Bob reasoned that they were the same age, sex, race, education, and they had taken the same dose of drug.  Therefore, the chemistry in his new friend's brain had to be different.  If you go to AA meetings, you will hear over and over again, "The first time I had a drink, I knew that is what I wanted to do."  Not a drunk, a drink--age 8, 14, 25 whenever that first drink comes.  These are Type 2 alcoholics (Cloninger categories, 1987) or Cluster 2 alcoholics (Moss 2007).  Likewise, at NA meetings if the conversation dies down, ask them about "the Void."  

You will not be able to understand the theories on learning and brain chemistry unless you actually go to AA and NA meetings, let them know why you are there, and LISTEN to their stories.

Drugs that are addictive have two major functions. They stimulate the reward system and they suppress your own ability to stimulate your reward system through your natural chemistry. Genetics plays a big role in this. Drugs teach with a classic carrot and stick process. If the drug is not rewarding and only makes you cough, vomit, it will be hard to get addicted to it. The status of the brain's reward chemistry also plays a role, if the reward system is chemically out of balance, drugs provide relief. Hence, nature plays a big role, but so can nurture.   The ability of a person to meet his or her needs and tolerate feelings also plays a role in drug/alcohol dependence. If you are very cold, a hot shower feels very good. If you are very hot, a cool pool feels very good. If you don't know how to meet your needs then, drugs provide an artificial reward and a way to disconnect from the distress of caring. Hence the earlier a person begins to drink or use, the more vulnerable they are to addiction because they are not developing their skills to meet their needs, set boundaries,  process complex feelings, etc. the more the drug shuts down your own reward system, the more you lose confidence in your self and learn: "Drug works, I don't". Learning how to tolerate caring about something that you have no control over is part of managing one's feelings and is one of the cores of spirituality. Drugs disconnect you from caring, for a while. The drugs also reward you for being with people who support your habit and avoiding/rejecting people who interfere with it. Hence, both nature and nurture play roles.

Recovery, is a process of re-righting the biochemical ship (both detoxification and where appropriate mood stabilization) and retraining how to manage feelings and get non-addictive rewards.It is developing a structure that supports recovery of a chronic illness. It is also confronting the shame of not being in control and respecting yourself as an addict which the 12 steps address head on.

• There seems actually to be no proof that sign-tracking is a direct motor (Tomie) reflex - it might be better conceived e.g. as the perception of cues signaling the reciprocal of discount in own maximal expandable effort as this is an essential information at early stages of appropriation cycles (Treviranus) - which is the evolutionarily group-advantageous expression at the curious or sanguine extreme which in humans we call uncertainty-orientation - and at the other choleric end: certainty-orientation (Richard M. Sorrentino, The uncertain mind).
• whereas the above input as "value" is 1-dimensional ((%) and manageable by only 4-D symbolic frontal cognition (Graeme Halford, Brisbane), operant Konorskian conditioning requires parietal high-dimensional movement related cognition (Rizzolatti) and complex considerations of worth and appropriation leading to intentional actions. Thus was understood by Karl Marx, but can't be grasped by current positivistic "neuro-economists" -financed e.g. by UBS with 100mio CHF.
• Thus "value" engulfes "worth" and habits astonishingly become a kind of cue to the obvious detriment of research...
• Addiction maybe install itself when UOs or COs  after defeats switch from goal attainment to minimization of further losses mode (depression) whereby their uncertainty-style switches to the opposite pole whereafter they don't know how to handle their unfamiliar weighting of the sequence along the appropriation cycle anymore, since their impulsive preference to just do it or else to think about the less effortful model beforehand has switched to the opposite. www.biposuisse.ch

Drugs of abuse are all reinforcing and follow the law of operant and respondent conditioning. That was established beyond a doubt 50 years ago, and all major liability testing, diagnosis and most treatments follow those principles.

BTW:  The Schick-Shadle Clinic, Seattle, WA still uses classical Pavlovian aversion training as a mainstay of treatment.  Load up with Antabuse, put them in a bar and let them have their favorite drink and then hand them the vomit bucket.