Rethinking addiction as a chronic brain disease
nytimes.com
nytimes.com
The growing scientific case for using Ozempic and other GLP-1s to stop addiction -https://news.ycombinator.com/item?id=40357196
https://recursiveadaptation.com/p/the-growing-scientific-cas...
> The consistency that I'm hearing from all across patient groups is gain of control, whereas previously, there was a loss of control… All of a sudden they're able to step back and say, 'oh, well I had this shopping phenomenon that was going on, gambling, addiction, or alcoholism, and all of a sudden, it just stopped,'
- Dr. Gitanjali Srivastava, Vanderbilt Medical Center
What’s interesting is that we’re about to have a large scale natural experiment around addiction and whether it is chronic due to brain chemistry or more willpower as GLP-1 agonist uptake rate skyrockets in the general population (which should result in addiction reduction at scale).
The sci-fi future is what if you could go into a clinic and get your personality tuned up. Yes I'd like to add some humor but not sarcasm to my personality. Give me a bit more motivation, and I'd like to like jazz.
For example, could they significantly change voting preference? Why wouldn't they? Do we not respond to political messages with our "reward centre"? Will we find political charisma more or less entrancing? Will we find calls for vengeance and punishment more or less attractive? Does tinkering with desire and reward dull our emotional response? Will we find compassionate appeals to help less fortunate more or less attractive? Does "enhanced control" manifest as a political preference for rational altruism or as machiavellian selfishness?
It really does highlight how failed the drug war is. The only effective weapon against rampant cartel violence is decriminalization and legalization.
I just watched Sicaro over the weekend, yeah about 4 years late. The thing is a right wing wet dream take on the drug war, and the interesting thing is it's exactly like the vibe that came out of Vietnam war, another failed war.
"The politicians won't let us use unrestrained violence to win". Of course, both the Vietnam were and even more so the drug war are founded on completely illegitimate policy foundations, and only continue because of budgetary territory defense and a lack of desire of unelected officials to maintain power.
It is not selfish to improve yourself and it does not make you sick that somebody else is healthy. You know very well that people who dedicate themselves to being healthy are very eager to help others as well.
It’s like sexual harassment training. Literally no one needs to be “educated” that sexually harassing your coworkers is bad. It’s done to cover the companies ass and for no other reason. The drug companies offered that cover and the rest of the establishment knowingly used it to cover their bad actions. No doctor prescribing hydrocodone thought it was a non-addictive substance.
Perhaps there will be some severe second order long term side effects with GLP-1 drugs. Time will tell, but considering we are nearly 20 years in on these and on 4th and 5th generation therapies I suspect we would have had a small hint of those by now.
I’m extremely cautiously optimistic about these drugs. They seem to be an antidote to the poison that is the modern western lifestyle.
It’s not an ideology of hatred to consider unintended consequences.
This is the plot of like 20% of science fiction, where unintended consequences backfire at a societal level.
That might arise from curiosity, imagination, or concern for the future of our species.
There are studies that show when dopamine receptor activity is inhibited in mice, their motivation for basic survival plummets. They will continue to consume food if it placed in their immediate reach, but they will otherwise put forth only the bare minimum effort to survive.
That is to say, there are very real implications of messing with hormone responses, and it’s definitely not a given that it doesn’t backfire spectacularly down the road.
I also think most people would and should choose the quality of life now, even if that has longer term side effects we don’t know about yet.
It seems as an ideology of hatred to sacrifice the well being and health of real humans to prop up the false belief in something called "society", which has never existed and will never exist.
I have nothing against arguments questioning the side effects of the drugs for the individual, but that's another debate.
Should we also argue against exercise and a healthy diet, since these things also have an impact on people's political views?
https://www.healthline.com/health-news/ozempic-personality-c...?
I deal with my own addictions but I'm not happy about the prospect of trading them for less joy of life in general.
For me Ozempic isn't an option because it's associated with reduced gut motility and I already have serious problems with that.
The article you linked actually gets into that, in a quote from a doctor disputing the validity of the concept of "Ozempic personality".
That said it’s not like there aren’t widely used drugs that mess with reward centers. Stimulants and antidepressants both come to mind.
Drugs affect different people in different ways.
If 20% of ozempic patients have personality changes, that is very significant. Yet you would still have 80% of users going around saying they never had any issues with it and those who are might just be doing it wrong/misunderstanding/confused etc.
anhedonia (noun): an inability to experience pleasure.
I started Ozempic about 3 months ago, prescribed by a nutrologist, first with the minimal weekly dose of 0.25mg, then 0.5mg, now back to 0.25mg to control my glucose levels (prediabetes). During this period, I lost about 25 lbs, which is fine (but I lose weight easily, just by exercising, so I wouldn't call this phenomenal by itself).
The biggest difference I felt was indeed in gain of control, being more aware of my body and living in the moment. I've been practicing meditation for a long time, and what I can say is that the drug keeps you in a medidative state for longer (most of the week).
The result is that I still like fatty foods and sweets, but I don't crave them. Binge eating has stopped, and all addictive/obsessive behavior, including social network / news sites / porn consumption has stopped.
I am normaly hyperfocused, but my standard m.o. has been peaks of absurdly high performance interspaced with a hiatus of low productivity/creativity. Right now, the the ability to focus on what I want/need to instead of what serendipity brings my way has been awesome.
My perception of some foods is different as well. For instance, as I mentioned, fat still tastes good but doesn't attract me as much any more. Fish otoh tastes much better.
I actually hate eating and routinely have conflicts of "I'm physically hungry but have no appetite". I wonder if Ozempic would make me gain weight.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859965/
[2] https://www.sciencedirect.com/science/article/abs/pii/S01651...
It's not all rainbows, though. One thing I have to do is to set an alarm to drink water (otherwise I'll spend 6, 8 hours without water and have a headache).
Also, I might be the perfect Ozempic patient as I just entered the prediabetes spectrum with 5.7% glycated hemoglobin and have high muscle mass.
Like it or not, you (yes, you) are a slave to your internal chemistry. No amount of willpower or happy thoughts will cause your hormones or neurotransmitter levels into the homeostasis you want. If your chemistry is off, your physical and emotional behavior will be off.
You are a sentient pile of molecular machines ticking along because the chemistry happens to work out. There is nothing special about you, you're exactly like every other plant, animal, and fungus on this planet.
So yes, plenty of mental, behavioral, and physical disorders arise from chemical imbalances. If you take this fact, consider what happens when you indtroduce foreign and extremely powerful chemicals into such a complex organic system.
If you come back with the assertion that addiction is a question of willpower, you didn't understand the assignment.
so it's likely that just "wishing something very deeply" doesn't actually lead to anything, but acting in a way that affects your mental chemistry (be it via creating feedback loops that make your brain crave more of X or simply by taking certain medicine that does it for you) does
welcome to being human :-)
Define, "off". Who gets to decide what's normal?
When I do something bad, then it’s time for “hey, I’m just a pile of chemically influenced meat.”
Now, you could argue “yea, behavior can change neurotransmitters and it is in my framework so what is your point?”
The point is that your framework can easily be take the wrong way to that we are more or less all doomed, us being mechanistically no free will slaves. At least, that’s the vibe that I feel when reading it. I think I am not alone in that.
And while I agree with that, I’d argue that focusing on optimistic interpretations of your framework is much more fruitful. Optimism being characterized as a bias towards positivity while still staying fully grounded in reality.
It has only been recently that I started to do some hardcore meditation (2 hours per day). I kickstarted it by making a deal with a friend: for each hour we miss, we pay 100 euros to each other. So far I haven’t missed anything and am on day 4. I am low-key dreaming of solving meditation motivation and spinning that up into a startup as it has been the biggest problem in my life (one could imagine it being my biggest problem since my username is related to metta meditation).
No guided meditation here.
The necessity for an early morning meditation becomes abundantly clear, as it is much easier to frame that you only have to meditate one hour every if and only if you meditate for one hour immediately after waking.
Feel free to email me if you have more questions.
It’s not that simple – there are feedback effects. There is plenty of evidence that thoughts shape chemistry as well. This is why therapy works, for example.
edit: This is also why you can “hype yourself up” or “talk yourself down”. Those are thoughts/words leading to measurable physical and chemical effects in the body. You really can raise your cortisol just by thinking the right thoughts
Behavioral-only therapies are effective, even if they're not as effective as we'd like. We have the ability to modulate our own chemistry.
A few days ago, this article[0] has been discussed here on hacker news. I shows how the naive theory of chemical imbalances can be harmful for treating Schizophrenia.
> In this vision, mental disorders were best understood as brain dysfunctions that could be traced to abnormal genes. Schizophrenia stemmed from an imbalance of the neurotransmitter dopamine. Depression was a serotonin imbalance. Bipolar disorder was a lithium imbalance. ADHD a deficiency of norepinephrine. These conditions, of course, could be triggered by life events, but they were ultimately biological. It was a reincarnation of the ancient Greek humoral theory, which saw the various forms of madness as imbalances in the four humours: blood, phlegm, yellow bile, black bile.
I recommend reading the whole thing but I really liked this part of linking it to the Greek humoral theory.
In the end of the day, there isn't any scientific evidence that it is "just chemical imbalances". The reality is more complex. Medication has its place and it absolutely can help but it just one tool to help patients.
There is a good reason the brain disease narrative is so tempting: It avoids having to look at environmental factors. It avoids having to talk about how society is driving people mad. It is easier to say someone's brain is broken than having to talk about societal issues. It also leaves patients powerless, giving them the idea that their brain is just "broken" and they can't do anything about it instead of giving them the tools to create a better life for themselves and others.
In the end of the day we are all a parts of interdependent systems that form society. Mental health issues are more often than not societal issues more than individual issues.
[0] https://aeon.co/essays/how-the-psychiatric-narrative-hinders...
- Mickey Mouse
And yes, notwithstanding that there are cases where people are, owing to genetics, more susceptible to x/y/z, or where interventions can be insufficient. But that's the first line of defense, and should be.
There's a lot of anecdotes surrounding this but a popular one is rate of morphine abuse during and after the Vietnam war. The rates plummeted.
A really good book on the topic of addiction is the Biology of Desire by Marc Lewis.
I would also caution against any conflation of environmental and behavioral intervention as "willpower". These are not the same things (you didn't say they are, but you didn't give any credence to intervention). Willpower may be highly overrated, but ultimately, you can't "force" someone to rehabilitate in any way shape or form. They have to want to, they have to make the choice, and commit. As for therapy/rehab, some of these have been thoroughly studied. Interventions help (and therapy such as CBT or 3rd-wave CBT), considerably.
https://en.wikipedia.org/wiki/Naltrexone
The Sinclair Method uses naltrexone to help people get their alcohol use under control:
Naltrexone is at the heart of the Sinclair Method (TSM)
for Alcoholism. When you take Naltrexone prior to
drinking, it blocks endorphins, the naturally occurring
opiates in the brain, from being released when alcohol
is consumed.
When the endorphins are blocked, there is no “buzz” or
rewarding experience, and the alcohol doesn’t make you
feel the pleasure that drives you to drink excessively.
Over time, your brain learns not to associate alcohol
with pleasure, resulting in reduced cravings and
improved control over alcohol use. Naltrexone must be
taken at least one hour before your first drink.
Your brain has to learn how to be "buzzed", thus the experience is a function of your very complicated physiology and neurochemistry.
If you are susceptible and drink often enough, your brain will begin to associate drinking and its effects with certain activities. The addiction arises when your brain tells you it's a good idea, and you comply.
I tell younger people this, but when you're an alcoholic, you don't realize it until you're not addicted to alcohol. I went through this when I was maybe 20, and when I quit, I was often surprised when and where I suddenly felt the urge to look for a drink. After, I saw it all around me in others. As soon as a remotely stressful situation, and they began pouring themselves drinks, often maintaining a certain level until their day ended. Most of them never got drunk, and many could drink several drinks before they reached a point where they "felt" it.
It doesn't have to be overtly pleasurable to be felt. Sometimes, it's merely the removal of difficult feelings that drives someone.
Emotional and physical stress increases the brain's use of glucose.
Alcohol has 7 calories per gram. I think the main use of alcohol in the brain is as acetate (vinegar) - that is, Ethanol is transformed by the liver into acetate, which is one of the brain's alternative fuel sources.
For people with broken metabolisms, ethanol also provides calories to allow their brain to function.
Increased brain uptake and oxidation of acetate in heavy drinkers - https://www.jci.org/articles/view/65153
The goal is to deassociate alcohol with pleasure. One way to do this is to abstain for a long period of time so that the association gradually weakens, but 1) this requires constant willpower and 2) takes a long time for the association to decay.
If you instead take a pill that blocks the pleasure from alcohol consumption, you can undo the association very quickly and with basically 0 willpower (it’s not like your brain currently has an association between taking the pill and experiencing pain).
I have no experience with alcohol dependence, but this is a great confirmation of the reinforcement patterns of the brain.
We have been here before with the first wonder drug "Prozac" back in the late 80's. A cure all for everything.
yet there was no research to support those chemical imbalance claims.
I worked as a methadone dispenser for 15 years and this is not my experience of addiction.
There is no chemical or hormonal imbalance when you become addicted to drugs that relieve you from the psychotic hallucinations you experience daily or the young woman who did not know her boyfriend was a heroin addict and started chasing the dragon with him or even the young stressed out mother who's husband has abandined her who has been told by endless TV advertising that a glass of red wine a day is good for you or the young man who has sufferred sexual and psychological abuse as a child who drinks to forget.
Wegovy a cure for everything from the flu to cancer.
When my mom got diagnosed with pancreatic stage 4 cancer and I couldn't cope with it and I was already in a drug explorer mindset at the time and I started taking her opioids and I became quite addicted (no she wasn't deprived of any of her medications she was fine). This whole process absolutely was chemical imbalance. Years before in high school I stopped taking all of my ADHD medication and then started spiraling out of control dabbling in all sorts of disassociative and psychedelic drugs. If I didn't stop taking my Adderall in high school I wouldn't have gone down any of that path.
You could think that maybe willpower/mental energy is a resource you have to consume to suppress natural instincts like overeating or consuming a drug that triggers pleasure in order to achieve some long term goal. But then you find that some people routinely engage in behaviors that contradict basic natural instincts, and in fact find it very hard to stop doing those behaviors (e.g. cutting or other self-harm behaviors, suicidal tendencies). Are they just a font of mental energy?
Name it what you like, but your theory does have to account for people's lived experience. Why does studying make you tired? Actively using certain parts of your brain is a limited resource in some respect no matter how you swing it. The rules are super weird so maybe energy is a bad name but it's the best we have right now.
But there is no obvious relationship between this and the concept of "expending mental energy" on combating your cravings. It's not at all clear that there is any measurable "effort" involved in not doing something like eating a sweet. Chess masters consume more calories during a tournament. People who avoid eating cake at a birthday party don't.
And yes, I have of course experienced the difficulty with not giving in to a craving. But I'm not at all convinced that it is the same thing as the difficulty of taking a math exam. If anything, my experience is that it's easier to control my cravings after accomplishing a difficult mental task then it is if I've just idly been watching TV all day.
Yet, if you actually believe in biological determinism, there is no way you could have taken anything but that path.
If it's all about the dosage, then we need to focus on a different narrative. Besides, I'm sure a lot of very sane, and very performant people, met lots of these, actually enjoy the regular micro-dosing of alcohol or tobacco...
Besides you can be absolutely sure there is very clean stuff out there on the streets.
All I’m saying is that bros are effectively micro-dosing to cater to condition and there are lots of people taking this in very regular manner.
It's not hypocritical. You seem to have a line of thought you couldn't escape from when writing these replies where the bad guy in this scenario is microdosing and tech Bros.
It's like saying a software bug is an electromagnetic imbalance in the hard drive. Well, technically yes, but there's also more to it than that.
On the one hand, it can help people understand that a condition is real and not imagined, especially other than the sufferer. "Look at this brain scan, it looks different from a healthy person's" is quite tangible and convincing.
On the other hand, it can lead to a sense of helplessness, and notions that because there's a physical element to the mental illness, it's a permanent disability, or to be exclusively treated with pills and injections. That just doesn't follow. Sometimes it's true, but in many cases, lifestyle interventions can help, talk therapy can help.
And not every neurological disorder is fixable. And the question of whether this is "sometimes" or "in many cases" is still in the air, unless you can provide solid citations proving otherwise. So there is no need for this kind of judgement.
For example, in the case of ADHD, it s clear that patients have a reduced dopamine receptor count. It's not just a chemical imbalance, it's structural. Medication is the only effective solution for severe cases, and the result is night and day. Knowing this helps me make better decisions around my diagnosis, and also alleviates the great shame and anxiety that come hand in hand with ADHD.
I don't wish to devolve into an argument and I apologize if my initial comment was too aggressive.
My 2 cents, from someone with a [strong] non-addictive trait but having witnessed people with various addictions, including gambling.
You can’t boil everything down the chemicals.
Life boils down to choices. Some are easier and some are harder, but as soon as you take away the fact that it’s all a choice, you find yourself in a very dark place where you’re always a victim of your circumstances.
At the end of the day though, whether you believe me or not, your reality will reflect your beliefs. If you believe you can’t, you won’t. If you believe you can, you will.
It’s an unpopular and rather inconvenient truth that we have choice, but accepting that leads to a far better life than believing everything is just chemicals.
Categorizing disease as having a set of characteristics in the body doesn't make it solely rooted within those characteristics.
I think there will always be a desire to solve disease with a single pharmaceutical, as that would be an incredible thing. However the existence of drugs that do not work for everyone doesn't necessitate that the signals for characterizing disease are off or that a pharmaceutical isn't useful to some people.
Organisms are incredibly complex, even those composed of relatively few cells. Thinking there is always some magic bullet to address a biological or emergent phenomenon is probably not the answer, but neither is being dismissive of treatments that don't meet that criteria.
This is also a lazy argument that tends to get a strong response without being meaningful. It's basically equivalent to saying "it's convenient for big speaker that all music requires sound". Chemicals are the regulation system in most living things. They are necessary and that can't be ignored. Some can be artificially manipulated to get desirable responses, hence "chemical imbalance".
I'm also not sure how your examples are relevant to your argument. #1 is a pretty exceptional case, but hard to take as a representative argument. The rest are all secondary effects from human interaction, drugs are incidental to the outcome you describe.
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Ultimately, humans respond to positive and negative reinforcements. This is a pretty primal level thing and can be seen in nearly every other living thing. Do X, receive Y, reinforcement. Living things need these positive reinforcement cycles to thrive. For the most case, these are "mundane" things like talking with other humans, eating normal meals, drinking water, etc, etc. They guide people to keep doing things that make them feel good, even if those things are overall harmful.
GLP-1 drugs are rather exceptional as they seem to temper people's responses to certain reinforcement. Particularly, addictive or addictive-like reinforcements, like overeating. Whether this is the result of a "chemical imbalance" is pretty much just semantics. It's not really meaningful.
They also have some strong, powerful secondary effects, but really only by happen-stance. Patients who eat less, are less likely to develop diabetes. Patients who have less desire to drink alcohol are less likely to develop cancer. Patients who have less desire to do drugs are less likely to become addicts, etc, etc, etc.
Thinking of all psychological issues as if they're some innate property of the person and not something that's a consequence of _their environment_ is going to lead to bad results. People see that drug addicts are unhappy and think the drug addiction is causing the unhappiness, but that might be reversing cause and effect. Happy people with satisfying lives don't generally develop debilitating drug addictions, and I think that just making people satisfied with living in a bad environment is a bad solution. It's bad for them as an individual and bad for society. Sometimes the solution for depression and other stuff is to just get your shit together and take control of your life -- and drugs can have a role in getting you off your ass and doing something, but I worry about just pushing them as a long term permanent solution.
At some point during addiction your body depends on these substances to operate and stopping becomes much more difficult. Alcoholics need to taper or take benzodiazepines to quit otherwise they may seize or die when going through withdrawals.
I would say anyone who begins drinking to numb the feeling of withdrawals (morning or middle of the night) is beginning the journey of serious alcoholism. That’s not really a craving it’s more of a need at that point.
I'm not saying alcoholism isn't a thing, but the way some people discuss alcohol seems like they're blaming the symptoms rather than the root cause. Low impulse control, not seeking novelty enough, and otherwise living a messy life is the actual problem.
Of course this depends on the addiction. With some hard drugs or coffee the physical dependency is the bigger factor
Good luck with that.
If our schools were better, and more honest, we would explain the biology of addiction well enough that no one who understood the lessen would become addicted.
The lesson is simply this: Any pleasurable experience results in a normal and natural down-regulation by the body of the receptors that are responsible for that experience.
It is impossible to repeat the same dose (whether drug, food, roulette wheel, or skydiving) and have an equally intense experience until enough time has elapsed that the receptors have been up-regulated back to their original levels.
The hallmark of addiction, "chasing the dragon", is therefore pointless and quickly becomez harmful.
The other important lesson, of course, is that quality control is essential. Variations in the drug (concentration, impurities, improperly attached bungee cords) are solely responsible for the non-dragon-related dangers.
However, since you seem to like logic, let us take it to the extreme - Can you do anything you like? Because, the thing you like will become your dragon.. (This is your second point)
Drug impact variations can also happen because of the state of your body. Hence nothing can be done and should be done (Third point).
Now I am wondering if I am responding to a robot :(
Are you asserting that no nurses, doctors, or social workers are affected by addiction? All would have learned its mechanisms during their professional education.
This lesson is reductive and dangerous. It ignores that some responses are stronger than other responses and that some of those strong responses are stronger than conscience willpower.
This is such a misunderstanding of how humans work. Knowing that something will hurt you has never, in the whole history of humanity, stopped some people from trying that thing. And many of the people who do things that they know will hurt them are the exact ones who pushed further than others.