There is something of an addiction theme out in the blogosphere today. Mark Sisson is talking kicking the junkfood habit, and Dr. BG is talking politics and CRACK. I thought I would throw in a little neuromapping of pleasure and pain, as hey, apparently folks like a bit of neuroanatomy (who'd a thunk?) with their grain-free Evolutionary Psychiatry. Also, there's a new medicine for weight loss that will likely approved by the FDA, called "Contrave," and how it works has everything to do with subverting and modulating pleasure. So let's dive in.
My source for today's post is mostly the clever Dr. John J. Medina, who writes a "Molecules of the Mind" column for Psychiatric Times. Finally, someone with a geekier column than "Evolutionary Psychiatry."
Pleasure in the brain is primarily mediated through the neurotransmitter dopamine. Neurons in the ventral tegmental area (the starting post for those dopamine tracts I talked about a few days ago) respond to sex, drugs, rock n' roll, food, and communicate with some other neurons in the nucleus accumbens, and a third neural network in the amygdala and the ventromedial prefrontal cortex. These are all segments of the "medial dopamine tracts" I reviewed at some length a few days ago. It may be of interest that those of you who derive pleasure from other people's pain (schadenfreude) experience your mischievous pleasure here as well.
Pain is experienced in the aptly named "cortical pain network," which are regions of the brain a little separated from the pleasure centers. The different areas of the pain network collect sensory pain (such as a splinter in one's finger) and emotional pain. Typically, experiments used to isolate pain circuitry in the brain involve "aversive stimuli" such as electric shock.
So it turns out that social pleasure and pain have hijacked these evolutionary circuits of pleasure and pain, so that if you score a date with that hot chick and share a high five with your frat brothers, or you get arrested for that meth lab you are running in the basement of the chemistry building at school, you will experience the pleasure and pain in the same areas of the brain that you experience sex and electric shock. It hurts to be human, sometimes. If you feel that you are fairly treated and are feeling cooperative, your pleasure centers are stimulated. If you grieve the loss of a loved one, your cortical pain network lights up.
And what about opiates or wheat exorphins or binge eating? Turns out those activities stimulate the dopamine reward centers of the nucleus accumbens. That new weight loss drug is a combination of two older drugs, naltrexone and buproprion (wellbutrin). Naltrexone is a straight-up opiate blocker. It is FDA-approved to reduce cravings for alcohol, but to be honest I use it more often for people trying to kick an oxycodone or heroin habit. You have to be off opiates for a couple weeks or risk an exceedingly uncomfortable precipitated withdrawal, and once you are on naltrexone, your opiate tolerance will drop like a rock, so if you go back to using like you used to, you could easily overdose. But naltrexone isn't a controlled substance, and if you take your medicine as prescribed and try to use opiate drugs on top of it, those drugs won't work. There's nothing like a pharmacologic lock on the opiate system to help out an opiate addict. Naltrexone has been studied in binge eating and in gambling, and for some people, it seems to help. I've used it on a couple of occasions for sleep eating with extreme carb (grain) cravings with some success, also in patients with celiac who can't seem to kick the wheat habit. Naltrexone use requires monitoring of the liver, and typical side effects include upset stomach. But both of those are less noxious than a heroin habit in my opinion, but every case is different and risks and benefits must be discussed for each situation.
Buproprion (wellbutrin), the other drug in Contrave, was discussed in Antidepressants and Weight Gain or Loss. It helps keep the dopamine systems humming along without interruption, so you don't necessarily need that lift from vegetable oil laden fast food french fries. Wellbutrin can cause seizures, irritability, insomnia, and anxiety, so not a bucket of laughs by any means, but all things considered has some of the fewest side effects of any antidepressant.
I'm not clear that any insurance company in Massachusetts will pay for a combination of two medicines you can likely prescribe cheaply separately for less cost. And I hope that my readers understand that I think a paleolithic (or, if you are a conservative sort, Mediterranean) style diet (Dr. Parker reminds me that I mean carbohydrate-restricted versions of these for most people trying to lose fat) should be attempted along with proper exercise before we hand out pills to lose weight. In the studies, Contrave resulted in 5% weight loss. So that's good for improvement of some health conditions, such as diabetes or hypertension, but it won't make you the star of a hydroxycut commercial by any means.
Addiction is tough. Those who suffer need all the help they can get. Sometimes that means the judicious use of pharmacology. Most of us can get by with a bit of knowledge and (if we're lucky) some self-restraint.
"It may be of interest that those of you who derive pleasure from other people's pain (schadenfreude) experience your mischievous pleasure here as well."ReplyDelete
Name names! Go on - I dare ya!
Fine print: I suspect this is the reason I spent so many years hurting people as a PT and now like to see people suffer en masses teaching spin classes.
I heartily agree with a serious trial diet therapy before weight-loss pills. At some point you have to stop the drugs, and then what happens? You guessed it.ReplyDelete
I'm increasingly impressed with serious carbohydrate restriction as a weigh-loss method for many people. I'm talking about 20-40 grams of carb daily rather than the typical American diet of 250-300 grams.
Many true paleo diets derive 40-45% of total energy from carbohydrates. For a 2000 calorie diet, that's about 210 grams. [I'm not talking about the "modern" paleo diets like Sissons and Rob Wolf's - I don't know about theirs.]
Exercise seems to be much more important for prevention of weight regain than for actual weight loss.
Hi Steve - Jamie actually just sent me an updated Konner and Eaton paper from Dec 2010 (their position is very similar to Cordain), and there is still an abject fear of fat in there - lots of time spent on dietary cholesterol and how that isn't such a bad thing, but still perhaps an unwarranted phobia of fat in general that is strong enough to possibly color their results. My dietary approach is based less, actually, on straight up paleo (as the bones and other anthropologic data can only show us so much) and more on healthy traditional foods, reports of more recent neolithic hunter gatherers, and common sense - PaNu -like but I personally don't restrict "safe starches", but if I were trying to lose weight, I would. It's interesting that Konner and Eaton suggest that serum cholesterol levels in modern hunter gatherers average 135, which would suggest a low fat, low sugar diet. Also a little below the plateau range of optimal health in the U shaoed curve I've observed in several studies. So very interesting! I think the other problem is that modern hunter gatherers will obviously live in extreme fringe environments and perhaps subsist on hardscrabble, lean animals and insects that our ancestors would have considered too unfriendly a living situation and would have moved on to more bountiful areas. My husband was reading an account of the French and Indian War and how the soldiers described rowing a boat on Lake Champlain and their boat being lifted out of the water by the large schools of fish. Agree about the exercise - except I find (again and again) that the last 10 pounds comes off much more readily if Im dedicated to exercise.ReplyDelete
Jamie - it's nicer when sociopathic tendencies can be directed in positive ways ;)ReplyDelete
I'm just a dilettante who loves to wonder through your blog and many that you mention or where I notice you make comments. I'm not strict paleo, as I eat quite a bit of dairy, though I'm grain free and certainly vegetable oil free.
You said, "And what about opiates or wheat exorphins or binge eating? Turns out those activities stimulate the dopamine reward centers of the nucleus accumbens." Art Ayers and Dr Davis make this comment also, though I not sure I've ever seen references. Is it fairly well accepted, or a controversial opinion? Later in your post you mention 'vegetable oil laden fast food fries". Are you referring to binge eating vs. the properties of the oils and starch, or are you implying that they may have the same opiate properties as wheat?
I'm curious if you might expand on this comment a bit more, and why you think this has happened:
So it turns out that social pleasure and pain have hijacked these evolutionary circuits of pleasure and pain, so that if you score a date with that hot chick and share a high five with your frat brothers, or you get arrested for that meth lab you are running in the basement of the chemistry building at school, you will experience the pleasure and pain in the same areas of the brain that you experience sex and electric shock.
Love your style and sense of humor.
Hi Nick - opiates and binge eating are definitively known to stimulate the dopamine networks in humans. There are some decent (creepy) papers in mice elucidating all the pieces of wheat becoming opiate-agonist exorphins - take wheat slurry, break it down with stomach enzymes then intestinal enzymes and inject the fragments into mouse brains, for example, and some other evidence that ingested exorphins do enter the brain. As I said, I've had a very few cases where other methods and investigations (counseling, sleep studies, more typical medicine regimens such as topamax) have failed, and I've been able to use naltrexone to decrease cravings, night eating, and binge eating behavior in the specific cases of bread/wheat/cereal craving. Whether this is because naltrexone decreases the activation of the dopamine reward centers overall, or specifically blocks the action of wheat exorphins, I have no idea. The usage of naltrexone for this purpose is not standard and in each case we had a frank discussion about the speculative nature of the treatment. When treating cravings the usual duration of medication is 6 months, so we are not talking forever.ReplyDelete
As to our social pleasures and pain hijacking the older physical pleasure and pain circuits, I think the most likely explanation is that social connection led to improved survival and helped the cohesion of fairly large groups, and positives and negatives of social life played out on the networks already available in the brain.