Is addiction a brain disease?

[Cotcha Yankinov]

1.- Why can't you reverse your point? addiction is a psychosocial disease despite has brain correlates? When I say it is not a brain disease I mean that with the current state of science we don't have enough knkowledge to think addiction in brain terms in a useful way for the people who are suffering. Imagine you are dealing with an addict. Will you talk about orbitofrontal cortex or about families, friends and hope?

Once again I have to reiterate that there is evidence that the OFC dysfunction is causal and not just correlative. Your reference #5 also talks about neuropsychiatric co-morbidity being a large driver of addiction and there is much research showing that such neuropsychiatric conditions are also "brain diseases".

The matter of what I would say to an individual addict, the family, or where I would choose to put funds are three different matters. It makes sense to talk with an addict about the reasons they have to stop using, what they stand to lose if they keep using et cetera.

But if I had the choice between putting 10 billion dollars into funding research into ibogaine derivatives or 10 billion dollars into increasing availability of CBT to addicts/reasoning with them about what they have to lose, I would go with research into ibogaine derivatives. This is partly because of potency differences between the two therapy modalities, but also because many addicts keep on using even though they're aware that they are losing everything (they are simply unable to stop using), and many addicts have already lost everything (Its hard to motivate them to get sober and withstand withdrawals/cravings for their family if they have none).

See here, when you 'destory' me you go to the psychosocial view of addiction, being willing to lose health family and money. Thats the discourse I believe explains better addiction and not the changes in orbitofrontal cortex seen in skewed models of addicted rats.

I think there is some resistance to reduce psychology down to biology here. See your earlier quote regarding love as well.

If we believe that its the biology that produces the psychology, then psychology can be viewed as a more abstracted and intuitive phenomenon rather than something completely separate from the biology, a summary of the biology put into an intuitive framework if you will.

Being willing to lose family/health/finances can be mapped onto biology in specific manners that aren't very intuitive, nor very satisfactory for the average person (increased dendritic arborization is not satisfactory to Joe Average), or it could be mapped onto psychology in a more intuitive manner that is less objective. There are of course benefits to viewing phenomenon in different manners.

Subjectively, we know why addicts should choose family/health/finances over drugs, but subjectively the addicts often have little idea why they keep repeating their behavior. However there are objective/scientific reasons for their behavior that are useful to understand, because they help us develop therapies.

There is much more than just animal research showing that OFC circuitry is involved in the pathology of addiction. If you want more human research, see for example

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767245/
https://www.nature.com/npp/journal/v26/n1/full/1395777a.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462342/

You may dismiss the animal literature as not being relevant to humans but taking into account the full body of empirical evidence and the known function of OFC/prefrontal circuitry in healthy humans and dysfunction of OFC in other disorders (we can go as far back as Phineas Gage), the animal studies are still very useful. Especially for outright determining causality/eliminating confounders.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435881/
https://www.ncbi.nlm.nih.gov/pubmed/15585037 -

"The current literature suggests that in addition to the brain's reward system, two frontal cortical regions (anterior cingulate and orbitofrontal cortices), critical in inhibitory control over reward-related behaviour, are dysfunctional in addicted individuals. These same regions have been implicated in other compulsive conditions characterized by deficits in inhibitory control over maladaptive behaviours, such as obsessive-compulsive disorder.
CONCLUSIONS:

We propose that in chronically addicted individuals, maladaptive behaviours and high relapse rates may be better conceptualized as being 'compulsive' in nature as a result of dysfunction within inhibitory brain circuitry, particularly during symptomatic states. This model may help to explain why some addicts lose control over their drug use, and engage in repetitive self-destructive patterns of drug-seeking and drug-taking that takes place at the expense of other important activities.

This model may also have clinical utility, as it allows for the adoption of treatments effective in other disorders of inhibitory dysregulation."

Your citations refer to studies with rats and monkeys, except the one of Nora Volkow, wich is in PET. Nora recognized in a supplement of an article published in the BJM last year (the second reference I give in the first post) that most of the addicted brains are like the normal brains and despite there are significant differences with healthy controls there are not out of the range of normality. She says this is due to the limited technology we have now, and I believe so.

You'll see I included more human neuroimaging studies above

Volkow has written more recently on the neurobiology of addiction here https://www.ncbi.nlm.nih.gov/pubmed/27475769

I suggest we acknowledge that instruments like PET/fMRI are relatively blunt and low resolution but there are still valid differences in the brains of addicts and healthy controls that seem to be causal of addiction.

If we had more studies on the so-called "microstructural" differences then we wouldn't need to be discussing gross metabolism/volume differences or differences in e.g. receptor expression, but our in-vivo imaging technology/body of research is progressing rapidly and we'll also have more and more post-mortem analyses as time goes on. That is to say that neuroscience is still in its infancy and shouldn't be expected to have all the answers/evidence yet, therefore any absence of evidence is not evidence of absence.

https://www.ncbi.nlm.nih.gov/pubmed/28485734
https://www.ncbi.nlm.nih.gov/pubmed/28367515 - "Our findings indicate similar white-matter microstructural alterations across addictions that cannot be attributed solely to exposure to drugs or alcohol and thus may be a vulnerability mechanism for addictive disorders"

I'd also want to add that the main risk factor for having problems with drugs is poor education, low income, and not being white (I could not give evidence of the last one). Of course the way your brain is wired matters, some of that you are born with and some of that is built on education and family. Anyway, I'd not want to offend white well-educated people who have problems with drugs, there is a lot of other factors, but when we refer to a crisis and massive problems I think the main maintaining causes are poverty, poor education and lack of attractive alternatives to drug use.

I just want to reiterate that societal and environmental causes of a disease don't make that disease any less of a brain disease. As an example, it could be that poor education/chronic stress results in hypofunction of the OFC circuitry, and partly hence the increased risk of addiction with poverty - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330514/

"The Long-Term Impact of Early Life Poverty on Orbitofrontal Cortex Volume in Adulthood: Results from a Prospective Study Over 25 Years"

We can talk about the etiology of addiction too, but this thread was not about the etiology but rather whether the state of addiction itself is a brain disease. Preventing people from becoming addicts by increasing upward social mobility et cetera is a fabulous idea but that doesn't do too much for the millions and millions of people around the globe who are already addicted, who, I hate to say, are part of the problem in terms of giving children crappy childhoods and increasing their kids likelihood of becoming an addict.

So you can look at it this way - many people who become addicts have addicts for parents. This could be partly due to the various neurobiological adverse effects of having an addict for a parent. That means that correcting the parent's active addiction with biological therapies is one avenue to reduce the risk of the child becoming an addict in the future. So treating people who are actively addicted with a biological therapy can help reduce the creation of future addicts.

To say nothing of the fact that correcting our society's fundamental flaws is a... rather large undertaking. Whereas a fairly successful anti-addiction drug could be right around the corner for all we know. I'm speaking in particular of ibogaine derivatives and drugs that have similar mechanisms of action.

 

[5HT2c]

Sorry I don't know... which gene is it?

 

[Cotcha Yankinov]

I wouldn't necessarily say that there is any one gene for neuropsychiatric conditions - most tend to be "polygenic" meaning that many genes can contribute to increased risk. Individual genes may have a relatively small effect, though environment X gene interactions may prove more potent.

@5-HT2C - just FYI I made another post on the previous page, just in case you didn't see it

 

[5HT2c]

I've seen it, but need time for that man, will take long to chew!

PS: Cakeinup: With all genes combined the predictive strength is still lower than asking if your parents had issues with addiction.

 

[juansalar]

Hello
An interesting question with a rich and lengthy history... it is entwined with moral and subjective issues and is an example of 'nature vs nurture' or 'biology vs environment'.
I have a strong professional as well as a personal interest in the implications of answers to this question.
Needless to say, this is a very complex issue: counterintuitively the issue becomes more ambiguous and the answer less certain and authoritative the more you drill down into the detail and examine individual circumstances.
...I won't attempt to tackle the complexities or provide an answer that is definitive in any way. Clinical research and vast quantities of empirical data show an undeniable relationship between addiction and biological changes in the central nervous system and hormone levels, specifically endorphins and opiate receptors. Most western nations classify addiction as a 'chronic relapsing disease'. The nature and exact definition of 'disease' is the subject of debate however,.. does addiction constitute an unavoidable physical (viral / bacterial / genetic) affliction? And as a biological disease, should treatment consist of exclusively medical interventions?
My own opinion is that although addiction undeniably has genetic and biological factors and origins, personal choice and other social/environmental factors play a significant part in the incidence, progression and severity of the condition. And whilst it's completely wrong to argue addiction is rooted in some sort of moral failure and poor personal decisions, personal development, counselling and beneficial environments are all instrumental in treating addiction.
If we define 'addiction' as a disease it is helpful and illuminating to compare it with some Long Term Conditions such as Type 1 diabetes.
Whilst it's undeniable that Type 1 Diabetes is a genetic disorder caused by physical factors, it is also significantly influenced by environmental factors and the severity of symptoms is greatly dependent on individual choice and freedom to live a healthy life.
Given the right environmental factors, personal, familial and social conditions, Type 1 diabetes can 'sometimes' be controlled and curtailed from birth to the extent that the adverse impact on health and wellbeing is minimal. Conversely, with adverse environmental factors and personal choices harmful to health, the condition can be extremely debilitating.
I think the situation is similar with addiction: despite possessing the genetic predisposition to addiction, healthy / risk adverse personal decision-making and a positive environment may be sufficient to contain the adverse implications of an addictive brain disease.
Often though, particularly combined with depression and oppressive environmental factors, the freedom to make positive healthy choices is diminished.
Addiction is a brain disease but one powerfully affected by the environment. The opposite is also true. Recent scientific research has demonstrated the significance of biological factors on social and psychological conditions: for example depression has been shown to sometimes be caused by a virus or an inflammatory response to infection.
The distinction between biological and environmental causes is becoming blurred and changing the definition of 'disease' to an extent that it's starting to become unhelpful to establish an artificial boundary between the two factors.

 

[Cotcha Yankinov]

With all genes combined the predictive strength is still lower than asking if your parents had issues with addiction.

I'll chime in that this is a moot point in terms of addiction being a brain disease because the same can be said of schizophrenia (family history is a very powerful predictor for schizophrenia as well).

In fact, heritability of a disease could be considered to some extent a genetic (biological) predisposition to a disease, although there are certainly other reasons aside from genetics as to why diseases can run in families (although this can be controlled for with careful studies in twins/adopted kids)

I'll reiterate again that I think this discussion is getting lost in etiology - whether addiction is caused by a crappy society or crappy genetics has no say on whether or not the addicted brain is diseased. The environment is also known to be able to play a large role in the risk of developing schizophrenia.

If we want to take this discussion towards the genetic risk factors for addiction we can certainly go down that route, because to me that implies a biological component to the behavior. There is a plethora of evidence that genetic risk factors can predispose people to addiction, but I'm sure there is still much work to do (genetic research is only in its infancy). I'm not saying that is by any means the whole picture, but it can certainly play a significant role.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506170/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879628/
https://www.ncbi.nlm.nih.gov/pubmed/18494843/
https://www.ncbi.nlm.nih.gov/pubmed/17622222/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147879/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442454/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603686/

 

[Jabberwocky]

I think the real question is, what do we mean when we say disease.

Is it a disease like syphilis or HIV? No. Is it a disease like mental illness? Yes (I'd actually argue, as a kind of developmental/learning disorder, it is a form of mental illness itself). I definitely see "addiction" (what a horribly dated concept) as more akin to the disease of poverty than something like a communicable disease.

Two books worth reading: Chasing the Scream (lots of great footnotes on this topic) and Creating the American Junkie: Addiction Research in the Classic Era of Narcotic Control. Also worth reading this paper on the subject of some of the issues that plague this debate (granted it's a tad highfalutin): http://www.ijdp.org/article/S0955-3959(13)00010-8/fulltext

The seemingly never ending debate between folks more interested in a biological and cognitive approach versus a more sociological and learning based approach is so frustrating to me, because at their essence I don't see them as mutually exclusive frameworks. Rather, they tend to inform one another, painting a much more accurate picture together than in isolation.

I have yet to find a framework exploring "addiction" that is more valuable than a learning based approach (learning is also effected by biological conditions, genetics, etc, but it certainly isn't limited on a fundamental level by them either). But identifying a drug as the program as opposed to how we deal with a drug on a social level is far easier for folks getting their funding by a government deeply invested in prohibition and the war on drugs.

One truly cannot get at this debate without exploring the politics of why so much of the research is focused on the cognitive side of the debate in the US (well, internationally too).

 

[Zilpe]

It depends on what you classify as a brain disease. All mental illness is a brain disease. But what exactly constitutes a behavioural disorder and what falls in the normal spectrum of behaviour? Well ultimately it's an arbitrary distinction that is made. The mental illness/health dichotomy is quite reductionist. When is someone a sociopath and when are they just an asshole? When are they attention seeking and when are they narcissistic? It just comes down to a line that somebody draws.

We can ultimately trace addiction to the brain because we can trace all behaviour to the brain. And it certainly seems to be the case that some individuals are wired a certain way that leaves them extra vulnerable to addictive behaviour. Whether or not you call this a disease I think is a less profound question than some would have you think.

 

[5HT2c]

Hi to all and especially to Cotcha, that was waiting for my response to his previous post. Let me apologize for disappearing for almost a month. Personal stuff going on.


I totally agree with toothpastedog and also with Cotcha when he acknowledges that we are lost in ethimology or semantics. Also, ‘I'll chime in that this is a moot point in terms of addiction being a brain disease because the same can be said of schizophrenia (family history is a very powerful predictor for schizophrenia as well)’
Good point, you’ve got me


Just to refresh my point: I believe everything happens in the brain. I believe that in the future psychiatry and neurology will merge. I can tell however, that to the date, there is not enough evidence to support addiction as a brain disease like for example the case of parkinson’s disease.


Now answering Cotcha’s previous point:
‘Once again I have to reiterate that there is evidence that the OFC dysfunction is causal and not just correlative’ I’m not aware of any evidence of that, at least in humans. Please give me the references so we can discuss it.


I’d also invest in ibogaine trials. I think it is a good idea. But take into account that most people struggling with drugs do not have vocabulary or access to very simple concepts like ‘trigger’, ‘behavioral craving’ or ‘alternative reinforcement’ among others. Giving these simple tools to the most part of addicts that lack them is a priority in my opinion. Then there are cases when CBT has nothing to do, of course. Even that I would insist that giving a job to the ones who lack them is still something that has a high benefit for a low cost in the most severe cases (just because the same case is more severe if there is socio-economoblems).


About my resistance to reduce psychology to biology you have rised a good point. At the end, as almost anyone in science I am a materialist monist. This means I believe there is only one stuff (call it energy-mass) and this stuff is what our body and brain are made of. I do not believe in the existence of another dimension full of souls or minds. I have faith that someday biology will be able to explain addiction as well as psychology and social science. But I have to acknowledge that is faith, faith in the development of science. In the current state of evidence, we do not have enough data to support that the differences seen in humans of addicted subjects compared to non-addicted ones are related to a disease.


From the articles you cite, just to share my critical view of them:


The first one (Bolla et al 2003) finds differences in orbitofrontal cortex between cocaine-addicted participants and healthy controls. However they over-reach in the conclusions about the meaning. As this is not a longitudinal study and we can’t know what was in their brains before they started using cocaine, you can’t say that these differences are due to their cocaine use. Even you cannot call them changes or abnormalities. To be able to show changes you shoud have recruited these participants before they started using and follow them. Obviously, due to ethical reasons this is not possible to do. You cannot either say abnormalities because there is no standardized dada of what is the normal range of activation of orbitofrontal cortex when performing these tasks. In summary, you could say that addicted participants are shorter than healthy controls but you cannot say that cocaine is what made them shorter. Additionally you cannot say that they are too short without comparing with the population normal range. Maybe being shorter is better, you don’t know!


The study of Paulus 2002 has the same general problems as the study of bolla.


The study of Goldstein 2011 is a review where the authors create a narrative from data of previous publications. Different narratives or models can be created from the same data. But just to give an example to you of how much they over-reach in the conclusions they state:
“Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.”
Talking about free will in a paper like that is just scientific misconduct. Free will is a philosophical term and it is not measured either defined in the paper. In this case how you dare to conclude that the free will is eroded if this has nothing to do with your data?!?




Lubman et al. (2004) review previous literature and propose a model. However this is 13 years ago and despite they statement that their model can have clinical utility in 2017 I haven’t seen this clinical utility. Also, in science models are not incompatible, so their model could be right and interesting (especially when we have better ways to study the brain) but is still a model that tries to explain the same that has been explained in much simpler psychosocial models.


I cannot make a critical commentary of the Fanous (2012) because of my limited knowledge in animal experiments. In any case, as we all agree addiction (and love, learning and everything) has a brain correlate. That has been never questioned. What I understand from the studies is that the authors study the brain correlates in rats of their induced model of addiction. I’d finally said that probably these kind of studies are invalidated by the work of Alexander Bruce and the rat park, but I can’t tell.


At the end I believe we both agree. As you acknowledge “That is to say that neuroscience is still in its infancy and shouldn't be expected to have all the answers/evidence yet, therefore any absence of evidence is not evidence of absence.”


What I just say is that but with other wording. Neuroscience is in its infancy and there is not enough evidence to support the brain model of addiction. We both have faith that we will gather that information soon for the benefit of everyone. But it is very important to acknowledge where are we now and don’t let our faith in progress over-interpret our data.


“We can talk about the etiology of addiction too, but this thread was not about the etiology but rather whether the state of addiction itself is a brain disease. Preventing people from becoming addicts by increasing upward social mobility et cetera is a fabulous idea but that doesn't do too much for the millions and millions of people around the globe who are already addicted, who, I hate to say, are part of the problem in terms of giving children crappy childhoods and increasing their kids likelihood of becoming an addict.”


Here I strongly disagree. There is very strong evidence that giving conditioned jobs to addicted and unemployed people has a tremendous effect in recovery. Also there is crushing evidence of the efficacy of cognitive behavioral therapy and motivational interviewing. Also, we know that the strict methadone programs (including more interactions with professionals and not simply administering the medication) double the efficacy of the loose ones.


I agree that an effective biologic therapy for addiction would be a great advancement and would help millions of people and potentially their offspring. Sadly all this money we spend in the kind of studies you cite it’s not invested in testing empirically the efficacy of ibogaine, psylocibin, MDMA-assisted psychotherapy and many other interesting biological therapies. I believe this is unfair for the people who would benefit from that research, as no one benefits from knowing that methamphetamine users have something different than healthy controls in the orbitofrontal cortex.

 

[Seppi]

Here I strongly disagree. There is very strong evidence that giving conditioned jobs to addicted and unemployed people has a tremendous effect in recovery. Also there is crushing evidence of the efficacy of cognitive behavioral therapy and motivational interviewing. Also, we know that the strict methadone programs (including more interactions with professionals and not simply administering the medication) double the efficacy of the loose ones.


I agree that an effective biologic therapy for addiction would be a great advancement and would help millions of people and potentially their offspring. Sadly all this money we spend in the kind of studies you cite it’s not invested in testing empirically the efficacy of ibogaine, psylocibin, MDMA-assisted psychotherapy and many other interesting biological therapies. I believe this is unfair for the people who would benefit from that research, as no one benefits from knowing that methamphetamine users have something different than healthy controls in the orbitofrontal cortex.

The efficacy of motivational interviewing and CBT is limited for the treatment of severe addictions and for addictions which have no approved pharmacological treatment, like methamphetamine which has a very high relapse rate. I really doubt there is any small molecule-based drug therapy that would effectively treat all addictions either.

Also, no one in this thread seems to have acknowledged the abundance of research into the transcriptional and epigenetic changes in neurons that have been found to mediate the development of addictions. If one assumes that addiction does not arise from persistently dysfunctional neural processes that give rise to cognition (NB: a brain disease), then it logically follows from that assumption that all of the money that has been spent on studying the mechanisms that underlie these changes has been completely wasted.

 

[5HT2c]

I overstepped in that point. CBT, MI and CM (contingency management e.g. giving jobs to unemployed) have strong evidence but limited efficacy. Their efficacy, however, is the same or higher than any available pharmacotherapy.

I agree also that it's unlikely that one drug will be able to treat all addictions.

Finally, I disagree with your last point. As I have said before it is undeniable that addiction correlates with specific neural processes. Studying this neural processes is important to understand addiction and develop new therapies. What I question is the causality, when you say "arise" is where I would say "correlate" because there is no evidence of causality, as most of the studies done in humans are cross-sectional and don't consider temporality prospectively.

 

[Seppi]

I overstepped in that point. CBT, MI and CM (contingency management e.g. giving jobs to unemployed) have strong evidence but limited efficacy. Their efficacy, however, is the same or higher than any available pharmacotherapy.

I agree also that it's unlikely that one drug will be able to treat all addictions.

Finally, I disagree with your last point. As I have said before it is undeniable that addiction correlates with specific neural processes. Studying this neural processes is important to understand addiction and develop new therapies. What I question is the causality, when you say "arise" is where I would say "correlate" because there is no evidence of causality, as most of the studies done in humans are cross-sectional and don't consider temporality prospectively.

I'm not referring to neural correlates here since I'm not talking about cognitive processes being mapped to neural activity as is normally done in clinical studies. I am stating outright that biological processes (neural activity) are necessary and responsible for cognition. My last statement is supported by the fact that acute brain injury in humans has a marked impact on certain forms of cognition, as measured by neuropsychological function and performance tests. Moreover, cutting out parts of the brain that are not necessary for life in lab animals can have a significant effect on their behavior (e.g., cutting out the nucleus accumbens causes rats to starve to death even when food is in front of them). Cutting out every part of the brain that is not required for survival (i.e., not the brainstem and a few other regions) will cause an animal to enter a persistent and irreversible vegetative state.

So, in a nutshell, what I'm saying is this: cognition doesn't arise from a vacuum; you think with your brain, not with your foot, another part of the body, or via a magical pink bunny in the sky that's moving you like a marionett doll.

 

[5HT2c]

And the opposed way? Is not cognition necessary and responsible for some brain changes?

http://www.sciencedirect.com/science/article/pii/S0925492710002234

Beutel, M. E., Stark, R., Pan, H., Silbersweig, D., & Dietrich, S. (2010). Changes of brain activation pre- post short-term psychodynamic inpatient psychotherapy: An fMRI study of panic disorder patients. Psychiatry Research: Neuroimaging, 184, 96–104. https://doi.org/10.1016/j.pscychresns.2010.06.005

 

[elvis_wears_nikes]

Again it comes down to the age old argument of nature versus nurture but addiction as a disease most probably transcends both. On a biological level (regardless of substance or behaviour) there is definitely a genetic element involved that creates a predisposition to addictive behaviour as well as addiction itself involving circuitry related to brain reward, motivation and memory.

There are also obvious environmental factors involved such as exposure to trauma or abuse, substance use in the family or among peers as well as exposure to popular culture references encouraging drug use (to name a few) that can also contribute to an increase probability of addictive behaviour. Psychological factors may involve both biology and environment and may include personality traits like impulsivity and sensation seeking as well as many other mental health conditions such as depression, anxiety and personality disorders.

“Brain disease” - perhaps. I do believe that addiction is definitely a mental health disorder that manifests in biological, psychological, social as well as spiritual dysfunction which should point towards the need of more of a holistic and inclusive approach to addiction treatment and management.

 

[5HT2c]

I agree with your view elvis, I would add then that since the brain disease model became predominant, research funds have been unfairly distributed among the biolgical, psychological, social and spiritual levels of understanding

 

[Cotcha Yankinov]

As this is not a longitudinal study and we can’t know what was in their brains before they started using cocaine, you can’t say that these differences are due to their cocaine use.

I'm glad you've raised points about causality and the need for longitudinal studies - I couldn't agree more. We do have some data at this point, but not nearly as much as I'd like. See the following for example -

https://www.ncbi.nlm.nih.gov/pubmed/28387975
https://www.ncbi.nlm.nih.gov/pubmed/28338724
https://www.ncbi.nlm.nih.gov/pubmed/28547854

 

[5HT2c]

Hitting hard with those papers. I have to admit I am not as up to date as you are. Hope to read them soon!

 

[Seppi]

And the opposed way? Is not cognition necessary and responsible for some brain changes?

http://www.sciencedirect.com/science/article/pii/S0925492710002234

Beutel, M. E., Stark, R., Pan, H., Silbersweig, D., & Dietrich, S. (2010). Changes of brain activation pre- post short-term psychodynamic inpatient psychotherapy: An fMRI study of panic disorder patients. Psychiatry Research: Neuroimaging, 184, 96–104. https://doi.org/10.1016/j.pscychresns.2010.06.005

Activity-dependent neuroplasticity is a well-established phenomenon, but that's tangential to the real issue here. Drug-induced neuroplasticity is the core driver of an addiction,^[1] because that form of neuroplasticity is precisely what modifies the brain and consequently cognition in a chronic (addictive) drug user as they develop an addiction.^[1][2][3] The drug itself is what makes a person an addict (via its long-term effects on gene and protein expression),^[1][2][3] not the individual's initial motivation for drug use, like the pleasurable effects of a drug;^{[see diagram]} this assertion is evidenced by the fact that individuals who initially took an addictive drug for pleasure/euphoria will continue taking the drug even when it no longer provides any pleasure.

Also, genetics only influences how likely an individual is to use individual addictive drugs and the rate at which they develop an addiction to individual drugs, not whether or not they develop an addiction from the use of addictive drugs. Genetics and environmental factors are risk factors for drug use (NB: NOT mechanisms that mediate the development of addiction; they only determine one's vulnerability to developing an addiction, not whether or not one actually develops an addiction).^[1] Genetic risk factors and environmental risk factors each account for about 50% of the variability in addiction vulnerability across individuals.^[1]

Developing an addiction from the use of addictive drugs is mediated by the epigenetic and transcriptional changes in the brain that are wrought by chronic drug use.^[1][2][3] Moreover, literally anyone can become an addict,^[1] provided that they're chronically exposed to an addictive drug at concentrations which are sufficiently high to induce transcriptional and epigenetic modifications in neurons in the brain.^[1][2][3]



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References:


^[1] Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues Clin. Neurosci. 15 ( 4 ): 431–443. PMC 3898681. PMID 24459410.

DESPITE THE IMPORTANCE OF NUMEROUS PSYCHOSOCIAL FACTORS, AT ITS CORE, DRUG ADDICTION INVOLVES A BIOLOGICAL PROCESS: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ...

Drug addiction, which can be defined as the compulsive seeking and taking of drugs despite horrendous consequences or loss of control over drug use, is caused by long-lasting drug-induced changes that occur in certain brain regions.1 Only some individuals, however, succumb to addiction in the face of repeated drug exposure, while others are capable of using a drug casually and escaping an addiction syndrome. Genetic factors account for roughly 50% of this individual variability in addiction vulnerability, and this degree of heritability holds true for all major classes of addictive drugs, including stimulants, opiates, alcohol, nicotine, and cannabinoids.2 It has not yet been possible to identify most of the genes that comprise this genetic risk, likely due to the involvement of perhaps hundreds of genetic variations summating in a single individual to confer addiction vulnerability (or, in other individuals, resistance).

The other 50% of the risk for addiction is due to a host of environmental factors, occurring throughout a lifetime, that interact with an individual's genetic composition to render him or her vulnerable to addiction to a greater or lesser extent. Several types of environmental factors have been implicated in addiction, including psychosocial stresses, but by far the most powerful factor is exposure to a drug of abuse itself. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict. ...

A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.

[Emphasis added as bold and underline; the all caps text is from the abstract]

^[2] Koob GF, Volkow ND (August 2016). "Neurobiology of addiction: a neurocircuitry analysis". Lancet Psychiatry. 3 ( 8 ): 760–773. PMID 27475769. doi:10.1016/S2215-0366(16)00104-8.

Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala. The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex and insula, including glutamate, to the basal ganglia and extended amygdala. Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction. ...

Substance-induced changes in transcription factors can also produce competing effects on reward function.141 For example, repeated substance use activates accumulating levels of ΔFosB, and animals with elevated ΔFosB exhibit exaggerated sensitivity to the rewarding effects of drugs of abuse, leading to the hypothesis that ΔFosB might be a sustained molecular trigger or switch that helps initiate and maintain a state of addiction.141,142

[Emphasis added as bold]

^[3] Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". Am. J. Drug Alcohol Abuse. 40 ( 6 ): 428–437. PMID 25083822. doi:10.3109/00952990.2014.933840.

Conclusions

ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88 ), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a ‘‘molecular switch’’ (34).

As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.

[Emphasis added as bold and underline]

 

[Seppi]

I also want to follow up on what I wrote earlier and say this: the whole point of studying the molecular neurobiology of addiction is to identify the molecular mechanisms that mediate addiction and develop highly targeted biologically-based treatments to reverse them. As I said before, I doubt that there exists any small molecule-based drug therapy that can effectively treat all addictions; however, I think it is likely that some form of gene therapy using viral transduction (i.e., viral vector-mediated gene transfer) could actually be used to treat any addiction in the future.

 

[5HT2c]

In any case… what are the results of all the neurobiological research until now? I mean real stuff that is helping people now. We all know the promises and potential benefits.

Main biological therapies for addiction as far as I know: Methadone, disulfiram, naltrexone, nicotine. The first two I think they are from the sixties and the others from the late 80 or early 90. Since then tons of money spent and… what?

If neuroscience of addiction were a company it would have gone to bankruptcy fifteen years ago…