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.