Thursday, June 23, 2011

Drug Cessation and Weight Gain

Commenter "mem", who has been practicing healthcare for 30+ years, made an interesting remark that I think is relevant to this discussion:
Recovering substance dependent people often put on lots of weight and it is not uncommon for them to become obese or morbidly obese.
This relates to the question that commenter "Gunther Gatherer" and I have been pondering in the comments: can stimulating reward pathways through non-food stimuli influence body fatness?  

It's clear that smoking cigarettes, taking cocaine and certain other pleasure drugs suppress appetite and can prevent weight gain.  These drugs all activate dopamine-dependent reward centers, which is why they're addictive.  Cocaine in particular directly inhibits dopamine clearance from the synapse (neuron-neuron junction), increasing its availability for signaling.

A number of studies have shown that people who quit smoking gain a substantial amount of weight*.  Perhaps the most interesting study showed that one year after quitting smoking, volunteers had gained 18 pounds (8.2 kg), and 69 percent of the weight gain could be attributed to an increase in food intake (1).  They had no change in resting metabolic rate.  That's not consistent with the idea that changes in fat burning were the primary driver of fat gain, but it may be consistent with the reward hypothesis of body fat regulation. 

So what causes the increased food intake following smoking cessation?  A paper by Dr. Leonard Epstein's group offers some insight (2).  They used a combination of genetic screening and drug intervention in smokers, and came to the following conclusion:
These results provide new evidence that the increase in body weight that occurs following smoking cessation is related to increases in food reward, and that food reward is partly determined by genetic factors.
I haven't been able to find much information on what happens to weight when people stop taking other drugs, but one study did report an 18.2 pound (8.3 kg) weight gain in just a couple of months after quitting cocaine (3).  Other investigators have reported weight gains during treatment for unspecified drug addictions (4).  If anyone has other references or anecdotes to add, please put them in the comments.

A Clarification on Obesity and Addiction

I want to clarify my position on the relationship between addiction and obesity.  I don't necessarily think all or even most obese people are "addicted to food", although many people in general have poor control over their consumption of highly rewarding food.  I know this from firsthand experience**.  It remains to be seen whether obese people are addicted to food, and there is still a lot of controversy about it in the psychology literature.  Personally, I'm not sure the average obese person can be called addicted, using the definition applied to drugs.  Yet, obese people do show some brain activity patterns that resemble those of addiction, and that tells us something useful: it reinforces the link between reward systems and body fat regulation. That's the main reason I wrote about it in the last post. 

A Cautionary Note about Dopamine Signaling and Neuroscience in General

The reward system, including dopamine signaling, is complex and will not always conform to armchair speculations on how it should behave.  Saying "this and that increases or decreases dopamine" doesn't mean a whole lot in terms of real life outcomes, unless you know where dopamine is being increased, by how much and for how long.  How are downstream cells reacting to it?  What receptors do they express and how are those coupled to downstream signals?  Do downstream cells decrease dopamine receptor expression after prolonged exposure?  The point is that speculation is generally futile, except as a thought exercise.  Empirical evidence is what you need if you want to predict outcomes.  If the brain were so easy to predict, I'd be out of business. 

* Some have attributed this to the fact that smoking increases lipolysis, or fat release from fat cells.  But if you think about that a little bit, you realize that lipolysis is irrelevant unless the fat is getting burned after its release from fat cells.  Otherwise it just gets re-incorporated into fat tissue after hanging around in the blood for a while.  Increased lipolysis due to smoking increases free fatty acid levels in the blood, which is probably why smokers tend to be more insulin resistant (yet leaner, imagine that??).

** For most of my life, I've been unable to sit at a table with donuts without stuffing my face.  At this point, I have virtually zero desire for donuts and I can sit in front of them all day without being tempted, even if I'm bored out of my mind.  I do think food reward pathways can eventually be "reset" to a healthier level, but it takes a prolonged period of avoiding junk food and consuming real food.  Conditioned responses such as the irresistible drive to scarf donuts eventually fade if you don't reinforce them by eating donuts.  This is called "extinction" in the psych literature.


Beth@WeightMaven said...

I think you're right that the "average" obese person has poor control over highly rewarding food, but that this doesn't necessarily equate to addiction. But I thought Yale's Neural Correlates of Food Addiction was compelling: "Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence: elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake."

BTW, did you see this on smoking and weight gain (also from Yale)? "Nicotine activates a small set of neurons in a section of the hypothalamus that signals the body has had enough to eat ... Nicotine accomplishes this trick by activating a different set of receptors on the surface of neurons than those that trigger a craving for tobacco."

David Pier said...
This comment has been removed by the author.
John said...


I've had the same experience as you with junk food. People always comment about how I'm so disciplined, but I always respond that it takes no willpower (anymore) because there is literally zero consideration. Everyone wants the "secret," but it was simply a slow gradual process: first, any "cheat" food was acceptable; next, vegetable oils were completely removed; next, HFCS; etc.

Squatchy said...

What do you think about serotonin and it's links with appetite? What about weight gain associated with taking antidepressants and especially mood stabilizers and antipsychotics?

mem said...

Just to be clear: I am a Registered Nurse. I do practice healthcare and practice in healthcare, of course. I wanted to make this clear, as people might otherwise make incorrct assumptions.

More to say on this latest blog entry's a exciting series!

bentleyj74 said...

In reference to your donut anecdote I wonder if there may be more to it than simple extinction.

themondays said...

When my brother quit smoking after many years, I clearly remember him commenting that he couldn't believe how flavorful everything suddenly tasted. Don't know if the smoking dulled his sense of taste alone or his sense of smell as well, but once he quit he marveled at his improved sense of taste.

Michel Blomgren said...

Hi! Great post!

I have another angle on this whole issue. I'm definitely not saying you're wrong about food reward, I believe it's absolutely true, but from my own experience and experience with others (that are crazy enough to take my advice) I have come to a theory that involves the following:

Stress hormones (possibly "overusage" of these), desensitization of adrenergic & glucocorticoid receptors (due to overusage), recovery (resensitization of receptors due to underusage), and "rebound" effect of levels of stress hormones after using the hormones (primarily down, but could also be up).

I have a wide range of studies as support for this theory, but leave them out of this comment unless someone wants them.

Any stress hormone induced activity (physical activity, especially high intensity, caffeine, nicotine, amphetamine, very low calorie diet, low carb diet, etc) would *contribute* to a blunted appetite since they all elevate stress hormones. Low carbers usually cite some studies where they injected the "master recovery hormone" insulin which would immediately lead to feeding. Of course, insulin is never on it's own when you're eating carbs, but that's another issue. Ketogenic diets are known to elevate stress hormones (cortisol and epinephrine). Since insulin sensitivity is not such a good thing when not eating any carbs, glucose is spared so that muscles are "forced" to use fatty acids (and ketones) instead - which leads to low insulin levels. The combination low insulin, high stress hormones blunts appetite. The same thing is seen in very low calorie diet experiments. Nicotine, caffeine, amphetamine, high intensity exercise (especially high intensity for an hour, time trial style) all elevate cortisol - which would seem to work the same way as low carb and VLCD - appetite is blunted during and after long low/medium intensity exercise and shorter high intensity exercise (until you recover).

So, my theory is based on that feeding/overeating is due to "stuff" that leads to either low stress hormones or the inability of the body to react to them (desensitization = overusage).

Physical activity is of course not similar to "substance abuse", but the stress hormone thing is similar. Several studies have confirmed that exercise (especially endurance exercise) elevate stress hormones during activity and lower them substantially during rest/sleep. In one study they were puzzled that the endurance athletes had worse (compensated) lipolysis than sedentary during rest (but of course the reverse during exercise), and I believe this is due to lower stress hormones when you're not "on" the "CNS stimulating substance" - compensation. Same thing can be seen with coffee withdrawl, blood pressure goes down and also cortisol levels. People feel sluggish, tired and have a lower heart rate. Athletes (like my self) have a ridiculously low resting heart rate and usually low systolic blood pressure, and (at least in my case) it's not all due to a huge stroke volume - when I rest for several days my resting heart rate and systolic BP goes up, something I share with many other endurance athletes. Of course, overtraining and overabusing of stimuli substances means that early morning resting heart rate and blood pressure is elevated. In studies on overtraining cortisol and epinephrine is higher and testosterone is lower (also seen during chronic stress of various types, like sleep deprivation).

To be continued...

Michel Blomgren said...

Continued from last comment...

My simplified picture is:

Substance or exercise = elevated stress hormones while "on" the stimuli = lower stress hormones while "off" the stimuli = worse satiety, possibly due to the body wanting to recover.

Overuse or overexercise = chronically elevated stress hormones = unexplained weight loss, no appetite, elevated resting heart rate, elevated blood pressure. You have to exercise at low/medium intensity for many hours a day to achieve this.

Stopping overuse or overexercise = crash, possibly due to desensitization of adrenaline/cortisol receptors. Of course, this could happen if you exercise 8 hours a day and then noticing (after a week or so) that you can not get out of bed one morning (possibly due to the body unable to regulate blood pressure since the body has decided not to react anymore).

Underexercising or underusing your stress hormones = the "unexplained" weight gain experienced by (mostly amateur, noncompetitative) cardiovascular exercisers. Low- to medium intensity exercise for just 1-2 hours a day, or high-intensity exercise for just 30 minutes a day = really low stress hormones at night = burning less calories at rest (also spontaneously moving less) = bad stress/insulin "ratio" which probably explains the ravanging hyper-caloric hunger seen in some people after this type of under-exercise routine. Could be aggrevated by people wanting to be more "healthy" by cutting out coffee at the same time (even less cortisol).

One would think that a low carb diet would help here - keeping stress hormones up and insulin low, but it was not true in my case and not in a whole lot of other people I've come across. What I do today is something completely different, but not something for this comment. I think I've come to "master" the catabolic side of things (using stress hormones the right way, either with exercise or - believe it or not - coffee, although in moderation) and mastering the recovery side of things (which is to lower stress hormones as low as possibly and elevating insulin, preferably as fast as possible = rapid recovery = resensitization of adrenergic receptors = hightend sensitivty to both exercise (i.e going faster, harder, stronger, etc) and coffee which would all equal to feeling more alive).

Using your stress hormones a lot = burning more calories (more alert, more active, sleeping/resting less)

Overrecovering/underexercising or recovering from substance abuse = burning less calories, having lower stress hormones and thus being hungrier = eating more.

Of course I don't mean that it's this simple, I've completely left out dopamine for example (but it's there in the theory also, it's all connected), but I believe it *contributes* to the whole picture.

Underpressure said...

I met an old neighbor last week, I didn´t see him for about 18 years. He was heavy on amfetamin, and what is needed for getting out of a heavy period of abusing.

He had lost some teeth and put on at least 10 kg, maybe even 15 kg, but he was really thinn before.

Sunna said...

There is a difference between drug use and addiction. The DSM IV criteria for addiction are pretty clear and some patterns of eating such as binge eating do fit those criteria very well. If I restate the question of whether obesity is caused by food addiction and instead ask whether obesity is caused by using food as a drug, I see an undeniable connection. Apart from the victims of rare metabolic disorders nobody becomes obese by eating purely to satisfy hunger. There is always an element of using food as means of experiencing pleasure. What makes it contentious to propose that it’s the use of food as a drug that leads to obesity, is that everyone indulges in the practice to some extent. Using food as a source of pleasure or as self medication is considered to be completely normal and socially unacceptable. I see many parallels between the way we use alcohol in western society and the way we eat for pleasure. Most people can drink alcohol without becoming addicted but we know that alcohol has addictive properties and that for some people drinking it can lead to addiction that matches the DSM IV criteria. The factors that make people vulnerable to alcoholism are the same factors that make people vulnerable to 'food addiction', in particular a genetic predisposition and stress. In western culture the consumption of alcohol has a much longer history than the consumption of sugar. We have many socially enforced rules pertaining to alcohol that help prevent a decline from alcohol use to abuse to addiction. When alcohol was introduced to cultures that had no experience with it, particularly where that coincided with stress, alcoholism often became rampant. We have removed or relaxed many social norms that limited our use of food as pleasure. While we recognize the dangers of alcohol and nicotine and regulate their availability and regulate their promotion we do not recognize the dangers of highly rewarding foods. It’s no great insight that weight gain is linked to indulgence. The huge insight is that failure to moderate eating is not a failure in the prefrontal cortex but a failure in the nucleus accumbens. We don’t expect heroin addicts to be able to make rational decisions about anything in their life but we expect everyone, even children, to be able to make rational decisions about eating.

I have been reading your blog for almost 2 years now, Stephan. When you introduced the concept of food reward I could see where you were heading and I desperately wanted you to be wrong. I came across your blog when I became interested in the Paleolithic diet. I was hoping that I would find a way to become slim naturally and without having to forsake the pleasure of food. The change to a Paleolithic diet made me healthier and happier but it did not make me lose weight. It was perhaps a very necessary transition phase for me to give up some pleasures (sugar and pasta in particular) while reintroducing others (fat in all its glorious forms). The low carb diet is my methadone. It has taken me weeks of reading up on dopamine and the mechanisms of addiction and weeks of constant thought experiments where I tried to recast my own experiences with weight gain (and loss) in this new context. I am now grudgingly coming to the conclusion that you really are on to something here.

CAH said...

First comment, long time reader.

Interesting entry. I've worked in mental health and addictions treatment for the last decade and have personal experience in recovery as well. I have seen this "post-recovery" weight gain too many times to count. However, many of us need to gain weight (chronic stimulant, heroin, or alcohol users). And many lose weight once in recovery (particularly the "bloated" alcoholics and those with co-occuring drug dependence and bulimia).

I think it's obvious with stimulant users that they will lose weight when using and gain weight once they stop. However I have met plenty of obese meth addicts before. Seems puzzling upon first glance, but who knows. Some people--particularly those with certain chronic mental illness--react conversely to stimulants and opiates, even down to their food consumption and weight maintenance. Methamphetamine will put them to sleep and heroin will have them doing push-ups and drinking protein shakes.

I agree with an above comment about using the word "addiction" carefully when it comes to food. A true "food addiction" is far more rare than our rates of obesity might suggest.

Many substance abusers/addicts find that they unwittingly replace their drug of choice with food when forced to be abstinent for periods of time--this is obviously different than being addicted to the food itself. I think a good example of this is smokers who snack incessantly when in a non-smoking environment like an airplane, movie theater, or at work.

Another strange one I've noticed over the years--opiate addicts often find sucking/chewing on candy constantly throughout the day helps immensely with cravings. I've also seen this with eating disorder patients. It could have something to do with an oral fixation (with bulimics or compulsive overeaters) or need to keep the senses occupied, or it could just be the sugar stimulating the brain. But it is always sweets for the opiate addicts. When I was still active in my addiction, I went through several packs of hard or chewy candy every day. I hazily attributed it to the candy making me feel "happy" despite my addiction constantly chipping away at my dopamine supply.

As for quitting smoking--I don't doubt that there are chemically-based explanations for why we tend to eat more when we quit. However, I would bet that most smokers would tell you it's simply the oral fixation. Many friends of mine have quit and maintained their weight by chewing on mint- or herb-flavored toothpicks between meals. This satisfies the oral craving without unnecessary food consumption.

Smoking definitely inhibits taste and smell and I've heard people say they eat LESS when they quit because everything tastes so strong suddenly that it's nauseating. I've experienced this too.

And the other obvious reason would be that cigarettes are stimulants--they consistently inhibit appetite yet increase gastric motility and transit time. Many a wonderful meal have been ruined by my pre-meal smoke!

I'll shut up now--thanks for the article. This is a very interesting series on food-reward.

gunther gatherer said...

Hi Stephan. Can you give a brief summary of the kind of meditation you do, or at least somewhere interested folks can look to "rewire" their reward centers? Like you, I haven't been tempted by donuts in years, but I tend to overeat cheese, steak, cream and other low-carb foods, which does cause weight gain (imagine that!).

Also, are you saying that being lean or fat is only about caloric intake, and not at all about resting energy expenditure? Because studies seem to show that REE goes up significantly the better your D2 receptors work (I'm think of Bromocriptine and other drugs that do this). That and the fact that all of us have anecdotal evidence of someone we know who can eat all the crapinabag want and stay skinny...

Beth@WeightMaven said...

gunther, I know you asked Stephan, but may I recommend checking into HeartMath? I think of it as facilitated meditation. I've got both their portable unit and the Mac desktop and have used them twice daily since the beginning of the year. This has been a huge help for me in terms of dealing with cravings and triggers (and I have no financial interest in the company).

Sunna, you write "I was hoping that I would find a way to become slim naturally and without having to forsake the pleasure of food." I suspect it's unlikely anyone would need to forsake the pleasure of food. For one, I think that getting off the hyperpalatable foods makes regular whole foods more pleasurable.

Secondly, I liked what Harry Mavros said on my blog: the trick is to learn "intelligent control of a very specific sub-set of foods; i.e. hyper-palatable foods."

For me, that means that, assuming other factors are controlled, eating whatever you want on special occasions (holidays, weddings) shouldn't be a problem. I think the trick is to avoid stringing multiple meals together that might trigger reward problems (e.g., the cruise ship phenomenon).

Sharky said...

I just listened to an interview with neurophysiologist David Linden on NPR's Fresh
Air show. His new book, The Compass of Pleasure, is all about the pleasure circuits of the brain, including a discussion of food reward, overeating, and obesity. Check out

John said...


What does it matter whether it "forgets" or is "enlightened"? Doing so with kale or potatoes or meat is an unnecessary restriction; doing so with donuts is beneficial.


What studies show elevated cortisol and [nor]epinephrine in long term keto dieters? I've seen unchanged cortisol--epinephrine increase only in one rat study. Peter once showed ODers cortisol levels as normal too. I don't think insulin and "stress" hormones have a simple inverse proportional relationship.

Chris said...

Maybe your time would be profitably spent trying to find/talk with others in addiction research or obesity research who may be familiar with this line of thinking. As you mentioned, the dopamine connection has been floated before, which suggests to me that it has also been considered and/or dismissed before.

As I pointed out, while dopamine may play some role in explaining reward from food, biochemical reward (which is not inherently pathological) is not an explanation of behavior patterns. And as food, unlike cocaine, is unavoidable, it isn't in itself an actionable theory, either. It also tells us nothing about the relative health value of various foods.

Anna said...

Drug treatment anecdotal:

My husband worked several years in a religiously-based residential drug & alcohol treatment program (1 year in duration) located in the south-central part of the U.S.

The men (it was adult men only) entered the program already medically detoxed (from prison or rehab unit). They were more thin than the average population, some even underweight. The food served was SAD, but did include grassfed meat a fair ratio of the time.

Within that year, most would either acheive a normal BMI or were slightly overweight from outward appearance. Keep in mind, as part of the program, they did quite a bit of outdoor labor, sometimes 8-10 hours in peak season. They had three meals a day, 5-6 days a week, and had special meals on Sunday or other holidays. In their spare time, they could engage in a few sports or weight lift.

The meals were generally NOT all-you-could-eat, usually portioned out and seconds only allowed if everyone had eaten the first round. Pantry was locked between meals.

The men often commented on how they had never eaten so well in their lives.

trix said...

My sister and her husband teach Vipassana Meditation courses in Northern California. I seem to recall that this may be the method that Stephan practices...(Dr. Kurt Harris too.)


bentleyj74 said...

Dopamine signaling is as natural as breathing and may very well be affected by what and how we eat.

I consider that completely relevant perhaps even revelatory and wait for new installments impatiently.

I want to see how this all fits together. Maybe some of the problem is that prior research into this was primarily focussed on trying to get people to be able to consume super stimulants without being super stimulated.

Helen said...

Stephan & John -

I've had the same experience with junk food and sweets. Don't eat it, don't want it. Occasionally, I'll have a small slice of gluten-free cake I've made for a family birthday, but the hit is so small it doesn't make me spiral into habitual consumption. A little orthorexia slso helps here. My aversion to foods I've decided are harmful overrides any desire I might have for them.

Some people even comment that I'm "depriving" myself. I really don't feel that way, since I just don't want the donut, king-sized Snickers, or whatever. Some things like ice cream still look kind of good to me - but most "treats" look, and taste, just like what they are - junk.

For some reason, the sweet junk food causes me more aversion than the savory. But I still don't have much trouble forgoing chips, commercial onion dip, and the like.

That said, my appetite and weight both increased considerably on the dairy-fat-rich WAPF diet, even though I was eating no sugar and almost no fruit. Goodbye to all that, Sally Fallon. And I'm eating fruit again.

j said...

been following VLC for about 3-4 years and my cravings for sweets has not diminished at all.

it amazes me to the point of disbelief when people say they dont have cravings for sweets either in general or after following low carb.

im just that addicted to it that i cant empathize with a person who is not craving sweet/junky food at all hours.

even as i type this im trying to hold back running to the food court to buy a donought!!

i literally have to exert constant force not to gorge on these foods all day everyday and it doesnt seem to get better. the amount of effort it takes is herculean and i grow concerned at my ability to keep it up as i grow older.

there must be some better way to combat it. ive tried total avoidance for long streches...nothing, then tried weekly treats...nothing, then occassional semi-sweet treats like dark chocolate or coffee to combat cravings, and it did nothing.

gawd i need a piece of cake right now!!!! ha!!!

i dont buy into the idea that a few months of sugar avoidance has any material impact on people unless they werent as addicted to surgar as they believe.

for the hardcore sweets addict, whats a boy to do?

bentleyj74 said...

@ Helen

I tend to agree and would even expand by saying that the more fruit is included in my diet the less other sweets appeal to me.

A milky way bar has no pull if I have just eaten peaches to satisfaction/satiation.

This is partly why I'm inclined to think that there is a relationship between both the dopamine signaling of super stimulant foods AND the dopamine signaling of say...hunter gatherer tribes surrounded by abundant fruit/tubers with no cultural admonishment to limit them.

I somewhat doubt that it'd be common practice to overhear kitavans saying to one another "gee, I really still want more of this pineapple but I better not"

Perhaps this contributes to the speed and intensity with which they become not just obese but VERY obese when removed from that environment and apply that approach to eating industrial foods.

Perhaps it also contributes to what seems counter intuitive to me...trying to find ways to CURB rather than satisfy the appetite.

"Eating/drinking X helps me not feel hungry"

That brings metabolic issues into the question and that may be justified for some...anecdotally though I have seen a lot of fat white people go native in PNG and come out super lean.

bentleyj74 said...


I craved sweets intensely on low carb. So much so that for the first time in my life I considered the possibility of food addiction.

Beth@WeightMaven said...

Here's another read from Dr. Robert Pretlow, a pediatrician who specializes in treating overweight children & teens: Addiction to Highly Pleasurable Food as a Cause of the Childhood Obesity Epidemic: A Qualitative Internet Study (PDF)

Whether or not you buy the food & addiction concept, it seems to me that kids are having a much harder time of it. Perhaps that's because they are growing up on what Stephan calls "professionally designed industrial foods" easily available to fit into today's stress-filled lives. Or perhaps it's due to pre- and post-natal differences for this generation. Or both.

I'm not a low-carber (had a cup and a half of rice with last night's dinner -- thanks Perfect Health Diet ;). But I've found my cravings have really diminished by avoiding industrial food. But the neurofeedback/meditation is what's helped with the triggers.

Michel Blomgren said...


I simplified matters a lot around low-carb and from the simple picture cortisol is not elevated either short-term or long-term. It depends on what you do on your low-carb diet (and what you compare it to)...

The low-CHO diet was associated with a larger rise in plasma cortisol during exercise

The case of low carb is a lot more complex than the other stimuli, things happen to the metabolism of cortisol rather than the *resting* cortisol levels themselves during low carb...

A low-carbohydrate diet alters cortisol metabolism independently of weight loss. In obese men, this enhances cortisol regeneration by 11beta-HSD1 and reduces cortisol inactivation by A-ring reductases in liver without affecting sc adipose 11beta-HSD1.

Cortisol was not elevated throughout the day in these subjects, but the rate of appearance of cortisol was elevated...

Once again, baseline is not elevated (I would even dare to bet it's lower during long-term low-carb, which is also part of my hypothesis). When you get moving it's a whole different matter.

The same thing can be said by habitual coffee consumption, cortisol is really not that much higher when you're used to coffee. Habitual coffee consumers also don't experience the same "rush" as first-timers. Same can be said by nicotine of course.

Taking away coffee for a long-term coffee consumer means crashing. Switching from one year on a ketogenic diet straight to high-carb also means crashing. The reasons are also a lot more complex for diet than for substance use/abuse.

With lowcarb compared to highcarb there are other stuff to consider. Free testosterone to cortisol is often used as a measure of overtraining in athletes...
fTC ratio decreased significantly from pre-study resting measurement (Pre 1) to the final post-study resting measurement (Rest) in the low-CHO group (-43%), but no change occurred in the control-CHO group (-3%). Findings suggest if the fTC ratio is utilized as a marker of training stress or imbalance it is necessary for a moderately high diet of CHO to be consumed to maintain validity of any observed changes in the ratio value.

It has however been concluded that the amount of protein in the diet affects cortisol...

cortisol concentrations were consistently lower during the high carbohydrate diet than during the high protein diet

ACTH was significantly increased following the 1200 hr and 1600 hr meals with the high protein diet. We conclude that dietary protein plays an important role in meal stimulated cortisol release.

increase in cortisol depended on the proportion of protein in the meal, increasing after the high-protein but not the low-protein meal. The extent of this increase in cortisol correlated significantly with poor psychological well-being in women.

Another one

Anna said...

Should add to my Drug Addiction Anecdote:

Many of the residents at the treatment center mentioned above drank copious amounts of "cowboy coffee", i.e., stuff so strong it could float a horseshoe. And the ubiquitous soda and energy drinks - though less so. I asked my husband about the caffeine and he shrugged his shoulders. "At least its legal and if the coffee runs out, they have to deal with the headache."

Laura said...

I am finding this series very interesting. Much of the conversation is over my head, but I'll add my anecdote. I was relatively thin as a child; started smoking at about age 18 and quit at about age 40. No weight gain after quitting for 5 years; then about 20 lbs.

About 3 months ago I went to avoiding industrial foods (although there weren't really a lot of them in the diet before) - also am watching salt intake. With virtually no effort and no hunger, I have lost 7 lbs. Hoping this continues...

I sympathize with the sugar craver, but I have never particularly craved sweet foods, even as an infant. I always wanted salt, but may have changed that particular craving. Foods taste different.

allison said...

Hormones also influence weight gain. Any woman who has ever taken birth control pills knows this well. Pregancy also causes weight gain due to the influence of hormonal changes. And I suspect any male athlete who has ever used an anabolic steroid will tell you they lost fat.

And any middle age person knows too well how easy it is to gain weight when age related hormone changes take place.

I'm wonder how the lipoprotein lipase and the hormone dependent lipases come into play with food reward theory? Insulin obviously plays an important role.

Dr Bob said...

The Pain Management literature contains several studies that describe weight gain and increased consumption of sugar when opiate medications are started to treat chronic pain. This is just the opposite of what one would expect assuming the reward theory of over-eating.I will find the references when I get home.

Dr. Bob

John said...


The problem is that all of the exercise studies use "low carb" for a matter of days, and many times they're too high in protein. Also, I have seen a few where high carb diets were "better" for recovery, but this was without controlling for calorie intake (ie, the high carb groups ate much more).

There's an extended ketogenic trial (forget the author) where athletic performance didn't change after 6 weeks, except for a slight decrease in sprint [cycling] performance, which was only high intensity, not max. I'd guess that low carb only hinders performance in people who do low rest circuit training, 200-800m runs, etc. Low-moderate intensity and max intensity performance shouldn't get worse.


I have no idea why you crave things, but I ate tons of sugar throughout my childhood (I did at least eat nutritious foods too). I probably went through a box of cereal and half-gallon of whole milk every other day in addition to lots of candy and ice cream. When I started reading about nutrition in college, I was still eating lots of crap, especially ice cream. One problem for me was that I've always been lean/muscular, so I never saw/felt any damage from it.

I still know that it tastes good, but I simply don't give consideration to actually eating it--and there's no willpower or stress involved.

Dr Bob said...

The Pain Management literature includes several studies that report weight gain and increased consumption of sugar after starting opiate medication to treat chronic pain. This runs contradictory to the reward theory as the opiates are rewarding but their use increases weight and sugar consumption. I will post references after I get home tonight.

Stargazey said...

Antispirit said, To be fair, I stopped wanting kale, seaweed and potatoes when I went zero carb. After a few months, I didn't even view it as food.

I had the same experience after I had done low-carb for a year or so. I would have dreams about cake or other forbidden treats, but as long as I stayed away from them in real life, the cravings gradually lessened. It also helped when I realized that I had put cake, donuts, bread and other carbs into the "not food" part of my brain. Just like I can look at a bag of dog food and not crave it because it is "not food" in my universe, I can look at pie, ice cream, chips and cookies and not crave them because they are "not food" as far as I'm concerned.

denny said...

Hi, I’m Heidi, not Denny. I’m using my husband’s account as I didn’t feel like creating a whole new account just to post a comment or two.

Excellent series on food reward Stephan, and very stimulating comments from everyone else.

I have done some pretty extreme (and successful) diet experimentation dealing with food reward. Like Stephan I use to be unable to sit at a table with donuts without stuffing my face. I extinguished my cravings for donuts using a much more drastic measure. Avoiding them (and other addictive foods) for long periods of time did not work for me. My personal explorations have also led me to the conclusion that food reward is a dominant factor in weight gain and obesity. However, I think that which foods are too rewarding or addictive may vary according to the individual.

I first explored food reward theories via Seth Roberts. Starting in the late fall of 2007, I began nose clipping a large percentage of my food, thus making my diet quite bland. I had great success on this diet for a number of years. (I easily lost 20 pounds that I’d never been able to lose, and was the thinnest that I’d ever been in my adult life.) However, I was disappointed that nose clipping did not address my underlying food craving issues. I really wanted to unravel my lifetime of food reward programming.

I devised a method to do this by creating a non-addictive diet. I determined which foods were healthy and non-addictive for me. Non-addictive foods taste good when you are hungry. They don’t taste so good when you are full. It’s impossible to overeat them. Examples of non-addictive food for me would be salad (without dressing), vegetables (without butter), meat or fish (simply prepared without sauces), legumes, eggs, low fat yogurt, most seeds. Almost all other food for me was either subtly or blatantly addictive. I would still crave and eat those foods even if I was full. Those foods would keep me locked into cycles of overeating and cravings.

I decided to no longer consume addictive foods, but instead would taste them and spit them out. I know that it sounds crazy and is disgusting, but I really wanted my body to unlearn the flavor and reward associations with those foods. If one tastes and spits out food over a period of time the flavor of the food will gradually change. It is pretty amazing when a delicious tasting junk food starts to taste disgusting. It takes a lot of work and perseverance, but one can recondition oneself to no longer like highly rewarding foods.

denny said...

Heidi finishing my comment:

I began this diet a year ago. I am still doing it. After being on this diet for a short time, I discovered that I had a huge parasite problem (which is probably the driving force behind my food addiction). My deconditioning process is probably exceptionally slow due to the huge numbers of ascaris roundworms that I pass on a daily basis. However, I also discovered that each food and combination of food needs to be individually deconditioned. Some foods decondition rapidly, but other foods take a much longer time. Also, I am trying to get to the point where I dislike pastry and junk food. This takes longer as well. The diet has been incredibly successful for me so far, which is why I continue to stick with it. In a visceral experiential way I have come to deeply understand food reward.

I’ve also noticed that there is a lot of confusion as to what kinds of food stimulate food reward conditioning. One can enjoy certain foods and not stimulate reward conditioning. For example, I still received tremendous pleasure from eating when I nose-clipped most of my food. The food pleasure was there but muted enough that it didn’t over-stimulate me. Also food does not have to be bland. For me, salt, spices, and herbs do not trigger food reward stimulation. For example, I can season vegetables as much as I want and not overeat them. However, if I douse them with butter or other flavorful fats, their food reward level escalates. Conversely, plain heavy cream is quite bland but is an extremely rewarding food for me. So is coconut milk. Also, food reward is a gradual spectrum. Adding butter, sauces, and dressings gradually ramps up the ante.

I discovered that my diet is extremely controversial to most people. I rarely tell anyone about it for that reason. I hesitated to post about it here. I have never had anorexia, bulimia, or any kind of eating disorder. However, I was not able to give up carbs until I came up with this diet. Those who want to read about my diet in more detail can do so at and,24.0.html

Michel Blomgren said...


First, I don't consider 62-64% of vo2max as high intensity (as in Phinney's study), it's somewhere around 75-78% of maximum heart rate - that's medium (or medium+) intensity or "fast distance" intensity, but not time trial intensity or "race conditions". High intensity for me, and any other competitative athlete is at or slightly below lactic threshold where the best performance measure of endurance is how many watts you can maintain for one hour (FTP) per kg of body weight.

Of course, I have no idea how well trained these people were, but most well-trained people can sustain 75-80% of vo2max for 2 hours (so 64% is not high enough in other words). Even if I'm not an elite, my LT is around 80% of vo2max given enough time to warm up.

Second, you're commeting a study on medium intensity exercise compared to what endurance sports are all about - you would never be in a race at that low intensity (or you'll loose, especially in short intense races). That is basically for fast distance training, not racing. If you want to do an endurance performance measure you do a time trial at FTP (functional threshold power).

The cyclists performance was indeed decreased, he (Phinney) just didn't bother to measure it although he noticed it while they were training. A cyclist who can not follow an attack (or make an attack and keep it) will loose, cycling is all about attacking either from the pack, at the end or in the hills/mountains (i.e some type of sprint capacity).

Anyway, I wasn't talking about physical performance anyhow - it's got nothing to do with elevated cortisol while exercising. In all sport studies on low- vs high carb RPE is elevated when you take away the carbs (i.e it's harder at the same intensity compared to controls). Phinney noticed the same thing given that the intensity was where it should have been.

I'd definitely be interested in seeing a study on long-term low carb and cortisol levels at exercise (at the *correct* intensity of course).

Might-o'chondri-AL said...
This comment has been removed by the author.
Me said...

I recently discovered that if I use urine test strips for ketones (such as KetoStix) and test clearly in at least the "moderate range" I have zero cravings. I actually don't feel like eating anything! The opposite is also true. When I suddenly experience cravings the test strips show little or no ketones.

I used to think I was eating VLC (even though I still had cravings) and the strips just didn't work but recent experience has shown that to be wrong in my case.

James Kimbell said...

I can corroborate the vegetarian side of antispirit's comment. It didn't take long without meat for me to forget that it was food. "Forget" is the right word, too, because when I saw other people eating meat it felt (ridiculously, I know) surprising.

And I definitely think that this was more a case of thoughts conforming to actions than it was of me deciding to think that way.

mem said...

This is quite the collection of webcasts with great bearing on the discussion @ hand. I am just starting in on them and believe some here might be very interested too...It includes quite a number of folks who like Stephan, are devoting their professional lives to the issue...Should add to more lively discussion!

I was also remembering last night a old adage in alcohol recovery circles: "Nobody ever got pulled over for bein' fat!"

Sara said...

A big part of losing weight, and keeping it off, for me has involved reconnecting with things that are fun and satisfying (rewarding). When I had a boring job and was stressed with no time to read, play or exercise then food became something that assumed a role of easy pleasure when everything else was boring, stressful or hard work.

I think this is a big part of 'food addiction'. Most people live lives that offer few other means to the 'reward system'. Food is legal and easy - you don't have to work for it like you do with exercise endorphins and you don't have to organize yourself, as is required if you want to curl up with a great book.

I also think that people are increasingly addicted from an easy age to easy reward - bigger TV's, games that reward you with success every 10 seconds, sports with a 'no losers' policy (*rolls eyes*).

ItsTheWooo said...

You seem to be stuck on this "pleasure" link. "Pleasure" is not the reason people eat more when they have deficient D2 receptor signaling.

The reason such people eat more is because dopamine is a major metabolic controller which has influence on cell level energy using processes, and thus appetite. While I was in the actively growing obese state, I would often eat food and feel nothing. I enjoyed food and craved it, but I never truly got pleasure from it. I was driven to eat out of hunger and an inability to feel satisfaction or nausea.

I enjoy food much more now that I am thin. While in the thin state, if I attempt to over eat I first become full, then become nauseated.
Food loses all pleasure at that point, and it usually occurs at a calorie intake that would represent just an average day of eating while I was morbidly obese.

While morbidly obese, due to deficient neurotransmitter signaling, I never felt full, was incapable of nausea, there was no ability what so ever to stop eating, and I always wanted to eat. 2 hrs after eating I wanted more.

It's not about pleasure and reward, it's about dopamine altering cell level energy using processes, preventing normal satiety and nausea upon eating, causing glucose intolerance, lowering FFAs. This then leading to fat gain and increased eating (BTW these are independent functions of dopamine deficiency, although the former serves to augment the latter).

People who have been on addictive drugs (alcohol, meth, heroin, nicotine) are in a state of dopamine receptor deficiency, and opiate receptor deficiency in some cases as well. As a result of this, they are in a temporary state of obesity from a nervous system standpoint. Their brain looks and works just like an obese person, a person with the disease of obesity, and their body is subsequently driven to fatten. THe difference is that this is temporary in the drug addict and after extended abstinence their deficient dopamine receptors will recover and they will lose weight.

In the person with the disease of obesity, down regulated dopamine receptors in response to high glucose diet is an evolutionarily conserved stable functional trait - it will never go away, it can only be controlled by a diet which lowers blood glucose (either calorie restricted and/or carb restricted).

John said...


You said, "I'd definitely be interested in seeing a study on long-term low carb and cortisol levels at exercise (at the *correct* intensity of course)."

I'm curious as to why that matters to you [assuming fasting cortisol is normal] and how/why one would want to adjust diet based on it [if it's high/low].

I personally exercise almost exclusively at near-max intensity (weightlifting, short sprints). I do play tennis and basketball sometimes though too.

Might-o'chondri-AL said...
This comment has been removed by the author.
Michel Blomgren said...

it's all in my first comment.

Speaking of physical performance it means one could go faster/harder without (as much) desensitization of muscle cells. It's the standard recovery stuff from sports science and not really a subject which sticks to the matter in this post even if it's the same thing - recovery means to upregulate sensitivity.

The body would do this without diet, it doesn't matter, exercise will still alter cortisol levels. Not overtraining (regardless of intensity) = lower cortisol at rest. Overtraining = higher cortisol at rest (regardless of diet).

Tim said...


Unrelated question which I would really appreciate you answering:

I was doing some research into the role that gelatin plays in our health.

I understand that Vitamin C is primarily required for collagen synthesis.

More specifically, for the hydroxylation of proline and lysine.

One molecule of ascorbic acid is destroyed for each hydroxylated amino acid.

Gelatin supplies pre-built hydroxylated proline and lysine.

It has been noted by Linus Pauling that heart disease is a collagen disorder.

Heart disease has become much more common since people stopped consuming genuine stocks.

My question is can we use these hydroxylated amino acids directly and thereby reduce our Vitamin C requirements?


Melanie Williams said...

This is off on a tangent, but Heidi's comment about intestinal parasites raises this question. Could many of these cravings for industrial high-reward foods be our parasites and/or bad gut bacteria talking? Perhaps the "extinction" phenomenon occurs when we've starved our bad gut bacteria of the foods they crave, leading them (the bad bacteria) to actual extinction within us.

Might-o'chondri-AL said...
This comment has been removed by the author.
mem said...

First, MitochondriAL, thanks so much for your posts. When you get deep, deep in, sometimes I get lost, but even still, gain alot from them. How I wish you had a blog!

Here's a smattering of all kinds of info worth a look:

Judy Hollis, therapist is well known in recovery circles. She wrote the book : When AA's Go to OA" in 1986.Prior to the late 90's it would have been very hard to find recovery programs that dually diagnosed alcoholics in treatment. The mantra and working rule of thumb was an addict needed to be clean and sober for a minimum of 6 months prior to serious consideration of comorbidity and treatment. This all changed radically in the late 90's in *most* treatment environments.

The point here is that the need for OA for many AA's during 75-at least 95, would not have been related to antipsychotic, neuroleptic or mood stabilizing meds, which are now common in a percentage of the recovering population. I have had lots of exposure, both professionally and personally (family tree with lots of ETOHers, thus I introduced myself to Alanon and CODA in 75) and progressive,large weight gain through years of recovery, in an appreciable number was prominent, not just acute weight gain in the immediate post treatment period.

As stated, currently the waters are muddied by the fact that medications taken by some in recovery have weight gain, for many, as a common side effect. Interestingly, meds like Prozac and Paxil (and other SSRIs) will often lead to an initial weight LOSS, but within a number of months, the tables are turned and the weight begins to pile on. Some here may remember in the early 90's when Prozac was actually being touted as a possible "diet pill" due to that intial, short term weight loss effect. Also interestingly, I have known Docs who got around this effect by progressively pushing up the Prozac dose when the wieght gained started with the effect of stopping the weight gain and often actually returning to the weight loss effect. So, there would be multiple bumps in Prozac from 20-40-60-80mg/d in an attempt to beat back this effect. And it worked,as long as the client could tolerate the increased dose otherwise. But not forever...eventually "habituation" to the 80mg dose occurred too.

Here's a link to Hollis' book which now appears to be out of print or hard to find -

mem said...

Correction to my just previous post: I wrote: "antipsychotic, neuroleptic or mood stabilizing meds." I meant to write: neuroleptic, mood stabilizing or ANTIDEPRESSANT meds."

Beth@WeightMaven said...

Thanks mem for the link to the obesity summit. Looking at the first speaker's bio, I came across an interesting rat study: Transition from Moderate to Excessive Drug Intake: Change in Hedonic Set Point (PDF). Basically, whether or not drug use escalated to addiction was dependent on length of access (which reminded me of a similar point Gladwell made in The Tipping Point re cigarettes and teen smoking). Interesting ... perhaps this applies to industrial food as well? Might explain part of the differences between individuals.

Beth@WeightMaven said...

Oh, and here's another one! Stress, Eating and the Reward System (PDF). Money quote:

"Changes in neuroendocrine balance (high cortisol and insulin) from eating when under stress might further sensitize the reward center of the brain, leading to a positive feedback loop drive to maintain opioid stimulation from palatable food. ... Thus, stress eating is a feed forward process. In the end, it is unclear whether continued stress is even necessary to maintain the drive for palatable food, since hedonic withdrawal may be enough to sustain continued drive without stress."

There's no doubt that our environment today is generally stressful, but I wonder if researchers are considering the extent to which excess weight may be like carrying around a perpetual stress factory. Feel bad about yourself, eat to feel better, gain weight, and repeat. Talk about a feedback loop!

mem said...

Thanks, Beth. I will check these out. Be sure to watch Eric Stice's presentation. I have to do it in PDF as the sound stoped early on in his webcast only. But, I still watched the slide presentation.

His conclusion (without hearing the sound..) is that BOTH under-reward and over-reward theories may be right. And that sort of makes intuitive sense to me...

And I much agree re: effects of carrying around alot of extra fat, especially if it is chronic. We know we suffer endocrine derangement... and I am betting that yeah, just like repeated hits of cocaine or meth or other substances lead to neuro function changes (we will let MitochondriAL/Stephan elaborate specifically on these! ;) then I have a sneaking suspicion that indeed, neuro changes also come about with industrial food chronic mega-hits to the brain too.

I am also very much on board with Dr. Emily Deans' "unified theory of inflammation" and if inflammation is the Grandaddy/Momma of disease/disorder....

So it begins to look like a complex interaction of inborn/genetic stuff, combined with not even just easy access, but virtual BOMBARDMENT of hyperstimulating/industrialized food-stuffs...and we are off and running to bigtime neuro changes and receptor changes as studied in addictions + the whole inflammatory hotbed with all the n-6 heavyload and other fakey food chemicals...

Also, when the inflammation really takes over in the brain (as in,induces depression and or anxiety) then we have a human whose ability to choose well/differently, and often energy and focus to choose, with good guidance/care, is not infrequently profoundly impaired...

Yes, rather primitive explanation...but, we have lots of scientists here to repack it into science-ese...;) (And peck it apart as well, lol!)

Alan said...

>>To be fair, I stopped wanting kale, seaweed and potatoes when I went zero carb. After a few months, I didn't even view it as food.

Irrelevant. What would be relevant to this discussion is, if you stopped wanting (say for example) butter.

Unknown said...

Mitochondrial Al is hinted without saying precisely what I have been saying on my blog. It is the Hypocretin/orexin neurons that dictate the energy balance of the system. There is no set point; Humans have 50K total HC neurons. They get knocked out by obesity long term via multiple mechanism (celiac and Molecular Mimicry being most common) and as they go we basically get fatter because we cant respond to leptin. The side effect is our sleep gets worse as well. The model for this mechanism is narcolepsy. Lusi de Lecea at Stanford has worked it all out. This series was a great read but its all just the Outflow tracts that have little to do with CNS control. Dr Bob has already alluded to a problem with the theory with opiates. If you look at the HC neuron biology you will begin to see the hypothalamus is where this control resides. All the outflow tracts respond to the inputs of the HC neurons in mammals.

mem said...


The is the URL or name of your blog?

Megan said...

Over the last couple of years I have lost over 50lb on a low-carb diet, but had another 20lb or so to lose.

Five months ago I was put on Ramipril by my GP because of high blood pressure.

I have now put a horrendous 24lb of my lost weight back on, which is extremely depressing.

I *know* I am eating more because I feel so hungry all the time, but I put that down to the cold spring and summer here in the UK.

When I read this blog I Googled Ramipril +dopamine and loads of references came up!

So now I know what's causing the hunger, but what to do about it??

ItsTheWooo said...


That information on PTEN is extremely interesting, thank you. I strongly relate to that description of personality. I don't know anything about this either way, it's just interesting to me as I have always wondered how my personality is even possible. My mind is so frigging INTENSE , in everything I do, and the results of that speak for themselves - my artwork, my lengthy and copious writings which mostly reflect my thoughts, anywhere I go I leave a slime like trail of ridiculous mental intensity. LOL. But, in every single other dimension, I look like someone with no dopamine sensitivity. I hate people, I hate novelty, I fatten easily unless I do a low carb diet. I mean um wut.

Incidentally I independently came up with a hypothesis that in my particular brain serotonin was especially dopamine suppressive.

I assumed this may be the case as I have noticed that if I take serotonergic substances (e.g. carbs, for example, or 5-htp) I get symptoms like dopamine deficiency (low motivation and fatigue and even paradoxical depression and difficulty moving and glucose problems).
However, if I do not eat food and even starve, I feel high as a kite. I am at my peak if I have been subjected to stress, while not eating, while taking caffeine. HIGH as hell. I do not eat at work. I do not eat if I have to learn. I only eat if I am going to be not performing at all.

I also attributed this tendency to people who are predisposed to eating disorders like anorexia nervosa, I assumed they suffered similar problems (of serotonin suppressing dopamine too much) and starving was how they coped.

Regarding dopamine regulating exhilaration/craving/drive vs pleasure yes I agree... trust me I know it. I've been "high" due to my mood issues and while high you are pressured as hell to do many things, but satisfaction is infuriatingly impossible. When I am high like this, I will start doing one thing, only for my mind to immediately think of something else. I will run back and forth cleaning and organizing and feeling torn in a million directions. Lots of motivation, drive. I literally feel torn and pulled all over the place by the various impulses and plans I make.
Serotonin and opiates especially regulate pleasure and satisfaction. Serotonin is more like "peaceful contentment" whereas opiates are more like, actual pleasure itself. Dopamine is just drive and pressure and exhilaration.
When I take mild opiates I feel excitement and pleasure in everything, without that uncomfortable edgy irritation and frustration associated with say, hypomanic symptoms.

I think another major mood / psychological symptom associated with dopamine is feelings of power. At 25 I had a period of my life where I frequently had manic symptoms and I often felt an intense sense of power. After observing and reading I've decided most manic symptoms are related to dopamine and norepinephrine, I tend to believe dopamine is responsible for feelings of power. Feeling "powerful" is hard to describe. It's just this internal sense that you ARE powerful and can do anything.

Cluster of symptoms: everything feels exiciting, you feel pressured, you have a lot of ideas, everything you think is exciting, everything you do feels amazing, and you have this chronic sense of "power" . You also have feelings as if you are flying, or as if you can reach through the sky.
I associate this cluster of symptoms with high dopamine, and thus in my case, hypomania. It happens during predictable "manic" triggers such as increased bright light or decreased sleep.
But that power is very distinct, and one time I wrote a long piece regarding the subtleties between being high vs being happy, and I decided POWER Is the difference. When high you do not feel happy, you feel elated and POWERFUL. When you are happy, you feel content. Being high (in a psychostimulant/manic sense) is in fact the opposite of being happy as contentment is impossible, it's all exhilaration and pressure.

ItsTheWooo said...

Re: serotonin and nausea...
Yes serotonin plays a role in nausea too, as does dopamine. I was speaking of a type of nausea one might experience after eating, after food was digested. Not a "nervous stomach" but rather more of a "fat is being burned so much because of high dopamine, any attempt to eat more will result in nausea, as excessive fatty acids tend to do". When dopamine is low, fat in blood decreases glucose tolerance also drops, and so one finds themselves in a state where they can eat and eat and eat and never experience fullness or nausea.
Again, I am fairly sure it is dopamine specifically - if I take 5-htp which presumably raises serotonin (but lowers dopamine), I feel hungry and tired , I NEVER feel more stimulated and my appetite never decreases. I relate this not so much due to higher serotonin, but because high serotonin and high melatonin from 5-htp will then suppress dopamine. 5-htp makes me feel the way carbohydrate diets do. Tired and hungrier. It pushes me that direction. but on the other hand, it often calms me down if I am over stimulate and hyper.
ON the other hand stimulants do the opposite.

The serotonin effect of drugs like tramadol is independent of its opiate effects. Opiates do not affect serotonin; tramadol merely happens to affect serotonin, norepi, as well as opiate receptor.

Michel Blomgren said...

Ramipril seem to increase the exrection of dopamine. Catecholamines (e.g dopamine and adrenaline) and cortisol are all "vasopressors" (cortisol enhances the effect of noradrenaline, but the others do it directly) - they elevate blood pressure so if you pee them out it would probably mean less of the stuff (which would be bad for hunger since having them high means no interest in food, well, short-term anyway).

But, according to this one it didn't lower cortisol, but did however lower T4 (thyroxine) which *could* mean a slow metabolism (burning less calories)...

But, ramipril does alter cortisol metabolism...

For sure, it screws with several hormones.

However, if you calorie restrict you will lower your blood pressure, remove your medication (speak to your doc first!), and loose weight. Low carb only works health-wise if you don't overeat and all major effects in the beginning is due to spontaneous calorie restriction (but that's true with any diet). Yeah, I know, easier said than done. All the vasopressors (dopamine, adrenaline, etc) go down during calorie restriction.

Calorie restriction could however mean that you elevate blood pressure above baseline (above where you started, i.e higher BP than when you started low carb)...

High blood pressure is usually really easy to treat (and I have coached a few people with great success), but that's another story.

Anonymous said...


every single word in your last comment i relate to 100%. EVERYTHING you said.... i felt like i could have written that myself.

wow.... so what to do?

Michel Blomgren said...

Actually carbs lower all catecholamines and cortisol. Serotonin is of course increased, but for another reason. Lowering the catecholamines could mean serious hunger if not "in balance".

Here in Sweden we even have a word for the "coma" after (particularly fat) carb meals. It's a sweet sensation but would only occur if one is in need of rest. Same thing really with the "rebound" effect of exercise leading to low heart rate and lower blood pressure during rest (and tiredness of course).

Coffee and other stimulants take away this effect. Keeping them high means burning more calories, but eventually the body wants to rest which means crashing if it's pushed too far (or binge-eating after weight loss, particularly fast and many pounds).

Megan said...

@ Michel

Thans for making some sense of the Ramipril/dopamine research - it's interesting - but confusing!

Megan said...

After reading Michel's comments I wondered if increasing dopamine levels would help subdue hunger?

I understand that increasing dietary protein helps to increase dopamine - am I correct?

Michel Blomgren said...


The only thing I know is that more dietary protein means more dopamine excretion through urine (which would mean more dopamine).

I guess this approach would only be of value if it's signalling in the brain (D1, D2, etc, receptors) and even then one is dependent on the density of these receptors (which can vary depending on type of diet) in various parts of the brain - truly complex stuff.

Protein also increases cortisol a lot and different amino acids seem to be responsible for this (but if dietary muscle protein is increased, these amino acids are of course also increased).

Several researchers stand by the theory that protein is the most satiating macronutrient. I would agree of course, but I would also agree that speed (methamphetamine) is even more impressive for weight loss - doesn't make it the best thing for health though IMHO.

And yes, amphetamine also leads to more dopamine, indirectly...

Another issue with cortisol...

These data show that HPA axis reactivity to pharmacological stimulation predicts subsequent food intake and suggest that cortisol itself may directly stimulate food consumption in humans. Understanding the physiological mechanisms that underlie stress-related eating may prove useful in efforts to attack the public health crises created by obesity.

I leave it to others to interpret that one, I'm probably a bit biased on this issue ;-)

Megan said...

Is this study on high dietary fat and dopamine also relevant? Combined with the high-protein studies Michel posted would this explain why people feel better, and more able to stick to their WOE on a low-carb diet?

Michel Blomgren said...

Could be, there are other studies though, but the effect is similar. This one didn't seem to be isocaloric, i.e did the high-fat mice eat more calories than the other group? The abstract suggests that.

In my logic it would mean trouble when stopping either the diet or (as it seems) overeating. I.e the "reward" was upregulated and "balanced" at a higher level and the other diet the mice ate was simply not as "rewarding" as it was initially. The abstract doesn't go that far though.

The high-fat diet induced increase of D2 receptor and decrease of DAT binding may have occurred due to defensive control over dopaminergic activity in response to a positive energy balance.

Once again I'm always back to my favourite drug, turns out amphetamine has *similar* effects ;-)

Michel Blomgren said...

Forgot the other favourite drug which has the same effect...

Michel Blomgren said...

So, what would a "mirror" diet to low-carb high-protein do? And what would caffeine (or other drug) withdrawl do?

The opposite of course...

Withdrawn from high caffeine consumtion is - IMHO - the same thing as withdrawing from a high-protein or low-carb diet, i.e crashing (tiredness, sleeping, "insulincoma", etc).

But, there are benefits. The sensitivty is upregulated so when you drink just a small amount of coffee again your body reacts as if you had 10 cups while (ab)using the drug. I believe this is also the reason why low-carb diets are really good to lose weight short-term, but stalls after a few months to 1 or 2 years (desensitization).

In sport science the period of "resensitization" is called "recovery" (i.e chemical recovery, not structurual). The chemical recovery means, among other things, that muscle cells become more sensitive to stress hormones (adrenaline), adrenergic receptors are down-regulated by high-stress exercise and upregulated when recovered. Overtraining doesn't upregulate this system and performance is worse or any exercise that used to enhance performance now simply maintains it. A few smart people invented the concept of "supercompensation" or "periodization" (overtraining for a short period of time followed by over-recovery). I believe that similar principals can be applied to losing weight, feeling great and even be healthy (or enhance health).

Anna said...

Wooo2 -

What you describe with dopamine deficiency sounds much like the COMT Gene variation Val-158Met:

And, interestingly, is often tied to executive function disorders, including autism:

Which may explain your "manic" episodes, inability to focus, organize, etc. I suggest this from my personal experience, having sought out professional diagnosis for Asperger's Syndrome as an adult.

I am also thinking through dietary shifts which may help the dopamine degradation - one of which may be lower methionine, if I understand the process correctly.

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Megan said...

@ Michel.

If I've read your last post correctly you're suggesting that eating carbs for a while after low-carbing for some years, then re-starting the low-carb diet, *should* render it effective again?

I can't say that's been my experience in the past - usually it just takes longer to start losing anything, but given that I *have* been eating more carbs in the last five months, and I *have* just returned to a low-carb, higher-fat, higher-protein diet, I *should* lose weight again?

We shall see - but I suspect that food isn't quite the same as exercise.

Michel Blomgren said...

@ Megan,

Sort of, yes, but nothing is that easy. For me personally it took 3 months of constant weight gain and unstoppable appetite (post low-carb) until the body had enough followed by 6 months of slow (but smart) weight loss doing the opposite thing. Unfurtunatly it's been the case with many other ex-lowcarbers I've come in contact with through my blog. I guess Matt Stone has the "english equivalent" although different than my ideas in many ways.

So, I have no idea if long-term low-carb can be tackled by carbing up short-term. I have not chosen that path myself, so I wouldn't know what to think. I do know however that a low-carb "guru" over here recommends carbing up when weight loss stalls, which is pretty cool since most low-carbers here are really strict. "Carbing up" to what extent I don't know.

In fitness/bodybuilding the concept of over-recovery while "cutting" is called a "refeed" where a low-calorie diet is broken (maybe once or twice a week) with a feast of high calorie high carb food (the leptin theory - carbs, i.e insulin raise leptin). Scott Abel's method is one example. The same thing applies to intermittent fasting, but instead of a low calorie diet it's a no-calorie diet broken by a feast (like Martin Berkhan or Brad Pilon).

But, in the end it's all calories in, calories out. Whatever diet you can eat to satiety that leads to spontaneous long-term calorie restriction would work (if it's not too low in calories that is).

Of course, it's the same thing with long-term energy expenditure. If you feel like being hyper-active every day it will burn a lot of calories and vice versa.

The problem with modern life is that we are "under-trained" (i.e physically inactive despite perhaps a daily exercise routine) yet use our stress hormones too much (psychological stress doesn't burn near as many calories as physical stress, but it uses the same system and requires the same recovery). Figuring out how to tackle that is - IMHO - the key (or at least one of them) to weight loss.

Exercise would be great, but then there's the problem that exercise lowers stress hormones during rest, which means while one is sitting by the office desk all day typing one may not burn that many fat calories (fat burning is lower during rest in exercised people than untrained people, probably thanks to lower cortisol). Also, the low cortisol levels at work may lead to keys stucking in your forehead when you fall asleep over the keyboard. Of course, coffee may help, keeps cortisol high and turns on the exercised persons fat burning during rest. It's not over-training that leads to tiredness in most cases, but under-training since all exercise that is not overtraining leads to low cortisol and catecholamine levels at rest (overtraining keeps them high all the time leading to loss of appetite and weight loss even if one tries to eat a lot). Of course, too much stress would backfire as would too much rest - with similar result in both cases. One person burns out and the other person becomes incapacitated by "insulin coma" and too low stress hormones. A balance - leaning slightly towards the catabolic side - would mean steady long-term weight loss with enough recovery to never reach the "burned out" state. Sounds easy, but is really hard in practice.

Megan said...

Thanks Michel - I've tried to leave a comment on your blog but it won't let me for some reason.

Kris said...

Regarding your point about the cocaine addicts gaining weight after quitting.

As a former drug addict I can tell you that most people using these types of drugs are already way underweight.

I would think that the weight gain they experience after quitting is the result of reverting back to their normal weight, instead of overeating so as to exceed their bodyfat setpoint.

And I can also say, having many years of experience of fighting addiction, that junk food cravings have the EXACT same effects.

They're not nearly as strong as nicotine or amphetamine addiction, but they still feel exactly the same.

4.5 years after quitting drugs, drinking, smoking and all that stuff I still struggle with junk food and have not been able to successfully quit eating it except for a few days at a time.

In my opinion, junk food addiction is a fact even though it may not strictly meet some specific "guidelines" for defining addiction.

Michel Blomgren said...

Kris makes a great point. All of these drugs (including caffeine) has the same effect as junk food, at least if we believe the studies on mice and rats. One of those studies on mice cited above showed a similar effect on dopamine and its receptors with a combo of sugar+fat as drugs. Of course, nothing like illicit drugs, but still pointing in that direction.

By quitting the illicit stuff one also becomes more sensitive (after withdrawal) which would mean that legal drugs like coffee would start to be rewarding (until that option is exhausted), and - of course - also junk food due to its high calorie fat+sugar combo.

Stephan Guyenet said...

Hi Everyone,

Nice discussion. I've been following the comments but I won't be able to respond to them individually this time. I particularly appreciate the firsthand accounts that several people offered about how they reacted to drug cessation.

A few people made the comment that some of the post-cessation weight gain could simply reflect returning to a normal weight, which is a good point. Still, I think the evidence from drug use fits the hypothesis that reward (including non-food reward) can influence body fatness. I find it interesting that people seem to seek alternative forms of reward after drug cessation, implying that we really do seek a certain amount of reward out of each day.

Beth@WeightMaven said...

Stephan, not sure if you've come across this in your travels, but it's a paper relevant to this thread (also from the collection mem pointed to): Weight gain after adolescent drug addiction treatment and supervised abstinence. FYI!

Might-o'chondri-AL said...
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Anonymous said...

mitochondrialal... after reading your last comment, i got a weird thought but wouldnt what you said also make someting like homosexuality a brain disorder?

Yves said...

Some of my own n=1 experiments to throw a monkey wrench. I found when I was on dopamine agonists, they not only increased appetite (they're suppose to, if anything, decrease appetite), but made me gravitate towards sweets.

Also, lately I've been eating ice cream liberally but rounding it out with a nutritious diet. No weight gain or increased caloric intake despite 20-30% calories coming from ice cream. I think the danger of the junk foods isn't so much the palability, but that the easily and quickly absorbed calories may be metabolically stimulating in the short run (as the body responds to a surge in calories) but runs up a "nutrient debt" that triggers the body to eat again. It's probably this phenomonom that blows the feedback mechanism that would put a check on appetite. If you could make a meal of potatoes, liver, and spinach taste, smell, look, and feel like eating dorritos, cake, or whatever, I would be willing to bet people would simply not develop the pathology people are talking about.

All the examples of drugs and junk food do exactly that, the send a signal that the body is "fed" without actually feeding the body. The body responds my desensitizing itself to the stimulate and you get a vicious cycle. I think, and my own short term observations confer, you can eat a lot of 'addictive' foods if you fill the gaps with super nutrient-dense foods like liver, greens, etc. and exercise.

Joshua said...

hello, thanks for the important information.. it is really a point of concern.. thank you..


Beth@WeightMaven said...

mem, I found via a comment he wrote on the previous post that "John" is actually Dr. Jack Kruse, who is blogging here:

Gian said...

Nice article
really I like it :)

Primal Toad said...

I, like you, have virtually no sugar cravings these days. I can sit in front of a dozen donuts and be bored out of my mind and not eat them either. They just simply do not interest me. Not even for a split second.

If it was berries then that would be different. Sure, its sugar, but its also nutrition.

A rewarding food for me is 70-99% dark chocolate. But, I can only handle a block or 2 at a time due to the high phytic acid content.

Might-o'chondri-AL said...
This comment has been removed by the author.
ItsTheWooo said...

Malpaz - regarding how you relate to my description of what I go through and my perception perhaps serotonin may be too dopamine suppressive in my brain...

Well the way I deal with it is I eat a low carbohydrate diet, which I find allows me to eat calories without feeling tired and dim and depressed the way I do on starch and sugar. If I eat a high fat diet, I feel similar to how I do when I don't eat... energetic and alert.

I can't at all relate to "normal" people when they say low carb diets make them depressed. I can't realte to "normal" people who eat food for comfort, people who feel good after eating brownies and ice cream. NEVER experience that.

I only feel "happy and good' when I drink coffee, avoid starch/sugar, eat moderately of a low carb high fat diet. Coffee makes me feel like food restriction. Low carb moderate energy diets do as well.
High carb and high calorie makes me feel polar opposite - depressed, tired, dim, dead.

My advice to you would be to avoid carbs like the plague; you can retain some of the cognative/emotional benefits of starving without requiring malnourishment.

ItsTheWooo said...

Homosexuality is not a brain disorder, typically it is the result of endocrine abnormalities pre and early post natal.

Females with adrenal disorders which result in higher than normal levels of androgens before birth are more frequently lesbian or masculine behaving exhibiting lower levels of stereotypically feminine behaviors. CAH is a genetic disease where the enzyme to synthesize cortisol frm its precursor is partially or totally nonfunctional. The precursor increases, which the body shunts into testosterone synthesis. Females with this genetic disorder can develop sexually ambiguous genitalia, and about 50% develop into lesbian or bisexual adults.

Males who are exposed to very high levels of testosterone may experience paradoxical feminizing of the brain. This is the "younger brother effect" - males with a lot of older brothers are more frequently homosexual, because each brother exposed to higher and higher levels of testosterone during development.
It is believed that the maternal immune system reacts to the testosterone after each male birth; it may be that this immune reactivity is increasing testosterone in the body but preventing it from affecting the fetal brain the way it sh9ould.

Anyway, homosexuality and gender identity atypicalities are not "brain disorders", but they are the symptomatic result of having been exposed to abnormal hormone levels or abnormal hormone binding before birth or shortly after birth as this is when gender and sexual orientation are programmed.

I disagree strongly with mitochondrial's view that oxytocin and being "super friendly/super bonding" will cause homosexuality. This is extremely unlikely; most likely there is hard-wired area(s) of the brain responsible for sexual interest and sexual response and sexual behavior, which is sexually dimorphic between males and females. Being exposed to high testosterone vs high estrogen determines how these areas develop, and thus, whether you are attracted to masculine people or feminine people, whether you want to have a lot of sex with many partners or a little with few partners, whether you initiate sex or are feminine/passive, etc.

Just like we are born with mental "hardware" that can instantly recognize a human face - and remember it - we are also born with mental "Hardware" that can detect signs of femininity or masculinity and respond with sexual arousal and interest.

whether or not one develops "masculine" sexual mental hardware or "feminine" sexual mental hardware depends on the hormone situation in their brain before /shortly after birth... the same structures differentiate into either male or female ones, just as our gonads differentiate into either ovaries or testicles, or a clitoris vs penis, etc.

ItsTheWooo said...

I should also clarify that it is possible for the external body to appear sex congruent (normal male or female anatomy) but the brain may be feminized or masculinized in an opposite direction of the genitals.

Depending on the timing of the hormone fluctuations, a child may have normal male (or female) anatomy, but the brain structure is sexually ambiguous and highly feminine (or masculine). The child will grow up a boy but feel like a girl and have a sexual response/interest to males. These are transsexual/gendered people.

There is a psychological component to sexual and gender behavior, but the research is pretty clear that male and female brains are anatomically different and transsexuals/homosexuals show ambiguity in their brain structures.

It is no different than an intersex condition (hormone abnormalities resulting in the primary sex characteristics being "in between" not fully male or fully female)... the only difference is that the brain is MUCH more sensitive than the external body, and it is relatively easy to induce some type of gender or sexuality incongruency with relatively mild low level hormone fluctuations. It is much more rare to be intersex because that requires a very severe hormone disorder prenatally.

ItsTheWooo said...

Heterosexual / sexually typical male animals with amygdala problems are not homosexual - their inability to mate with females is not because of a lack of sexual interest (and an interest in males) , its because of a fear/freeze/depressive response suppressing sexual behavior.

This would be like a heterosexual person who is traumatized refusing to have sex (e.g. sexual abuse victim). This is NOT homosexuality.

Homosexuality features normal sexual motivation/interest, however the sexual interest is incongruent with primary sex characteristics.
Scientists can and have created same-sex preferring animals by manipulating prenatal sex steroids hormones at certain periods of development prenatally.

ItsTheWooo said...

Yves - I am curious what dopamine agonists you have taken that increased appetite.

Multiple factors can operate at once; just because dopamine agonists are promoting weight stability does not necessarily mean any drug that raises dopamine should reduce weight. If the drug is antihistamine, or if it raises serotonin more than it does dopamine, or if it is a dopamine agonist-antagonist, weight gain may occur.

For example, if someone is on seroquel (very fattening serotonin dopamine antagonist + antihistamine) but adds in wellbutrin (dopamine/norepinephrine boosting) they may gain weight... but it's not because of the wellbutrin its the seroquel.

Lark said...

I wonder how the cycle of hormones over the course of a day might play into this? In general I find food to be far less "rewarding" (tempting) in the AM, which makes intermittent fasting easy for me. I can comfortably go til 1 or 2 pm without consuming anything but a cup of coffee black or with cream. At lunch time I want a good dose of protein and fat. But come evening, the carb and alcohol cravings sometimes hit hard. Carbs and alcohol seem to be somewhat interchangeable to me. Last night I had a plate of nachos and a glass of wine... if not for the nachos I might have needed 2-3 glasses to be satisfied.

karl said...

If it were so simple -

Please realize that we have the following:


L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine.

But Phenylalanine and Tyrosine are not addictive foods...

Yves said...

ItsTheWooo2 - It was Bromocriptine (Parlodel). Increased my appetite and gained a few pounds, but calorie partitioning was favorable. It's been shown in studies to increase insulin sensitivity and was re-branded a a T2 diabetes drug in recent years.

AlexandraMMR said...

How about sibutramine and the drugs that contain it? i know that sportsmen use it but it is illegal so, what if you want to buy it and use it would it do something bad to you? i mean it says you should exercise a lot but what if you dont? also what do you think about those drugs and pills that you take as meal replacements? i saw some on but i'm not sure if they will help me lose weight fast...did any of you use something similar?

Steph R said...

On your point about “ I don't necessarily think all or even most obese people are "addicted to food",” I was wondering what you made of the research from the Griesel’s regarding heavily processed foods being addictive because the added chemicals trigger the same kinds of brain activity seen in substance dependence?
Thank you @Beth for all the great follow up reads!

Catt said...

I chain smoked for 7 years, quitting at age 22. When a smoker, I had over the years gradually slimmed slightly from my pre-smoking 15-year-old, despite eating fast food through my teens. In college, I would have coffee and cigarettes for breakfast, go to school, smoking all the way, and then finally eat when I got to work at 3PM, sometimes not till the evening. Not eating was a matter of time and not really caring about food. But once I ate, I was starving and it was something huge, but that was all I'd have until the next day. It was like a fiend's Warrior Diet.

Anyway, when I quit, I remember how shocked I was that _within the month_ I couldn't zip up my pants. I also noticed how food was now crossing my mind -- I would crave it -- and I could order a sandwich, a side salad, and a platter of that pre-made sushi all for lunch. I started getting muffins on campus during the day; and stopping off to order out Chinese food to eat before work. Granted I wasn't "fat", but I wasn't the slim little thing I was used to being. I definitely was needing a better fitting wardrobe. What I brought away from all this was that cigarettes are a potent appetite suppressant. Food went from a back-burner issue to something I always wanted.

(I'm not starving hungry anymore, years later, but I've only attained that skinnier figure that I had before--albeit with better muscular development--by eating primal.)

Unknown said...

Excellent post,thanks for sharing this.If you are suffering from binge eating disorder, please have the guts to accept and confess to your family members that you are facing problems.

Unknown said...

Ive been clean from methamphetamine for 6 months. My longest clean time was 5 years and got a degree in fitness technology. Ive been addicted to the drug. For 14 years. The drug kept me effortlessly thin throughout most of my use but the last 5 years it was not as affective. I have found very little information on why. What I did find was that my metabolism must have gotten so badly tapped out and familiar with the drug that it just didnt have the same effect. I'm extremely obsessed with body image. Gaining even more weight now that I'm clean again has put me in constant depression. What I have learned is the my metabolism was in starvation mode and was losing muscle mass. Muscle burns fat. With less muscle the body is going to need to take in even less calories and exercise even more. trying to count calories and exercise the way in normal person wouldn't want to lose weight would be ridiculous. Instead I need to be patient and eat nutritious healthy meals focusing on my proteins and building muscle mass by exercise.

Unknown said...

Great Post, I love to read articles that are informative and actually have good content. Thank you for sharing your experiences and I look forward to reading more.