Pleasure, Pain, Wheat, and Psychopharm

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.