Proglumide

Every chronic pain patient and opiate addict looks forward to the day someone finds the Holy Grail for opiates:  an agent that blocks or reduces tolerance and that eliminates withdrawal.  The two phenomena are linked and so the same agent may help with both problems,  or perhaps instead there will be a better understanding of the myriad interactions involved in opiate tolerance and not a single cure, but rather a number of medications beside the current, insufficient gold standard, clonidine.  A few weeks ago I decided to do some reading on opiate tolerance to see what we have learned lately,  and I started out with Google, searching the phrase “opiate dependence mechanism of tolerance”.  To my surprise, the first ‘hit’ was a NIDA monograph— try it for yourself, and see– then click on the link and scroll to the article in the contents a couple up from the bottom– see anyone there that you know?  That was the first research that I ever did, back in the mid-1980’s with nicotine.  You will see, though, the other articles about opiates;  that is what it was all about even back then, and we assumed that if we figured out tolerance to one drug we would understand tolerance to all drugs.  We now know that things are much more complicated.
The people at NIDA are going to wonder why one of their old monographs got 1000 hits tonight!
As I moved to more recent sources  I found that opiate tolerance is clearly much more complicated than we had hoped years ago.  A few years ago we almost got a drug called ‘morphidex’ that seemed to reduce tolerance in animals, but it didn’t work in humans–  for a minute or two it looked as if simply blocking the NMDA receptor with dextromethorphan would result in  significant tolerance reduction.   The fact that it doesn’t work has not stopped a number of compounding pharmacies from making and selling the combination at a tidy profit!  In reality there are probably multiple mechanisms for tolerance, perhaps different types of tolerance for different types of analgesia.  For example the tolerance that takes away oxycodone analgesia from shingles pain may be different than the tolerance that takes away oxycodone analgesa from broken bone pain.  Multiple transmitters and receptors and subtypes of receptors are involved– so much for brushing up quickly over the weekend.
I am generally skeptical of things– pretty much everything, to be honest.  I’m skeptical about cures for withdrawal because I have seen many of them come and go.  I’m skeptical of cures for baldness because I’ve seen many come and go!  I’m skeptical about global climate change because I remember worrying about the shortened growing seasons written about in the New York Times and Time Magazine in the 1970’s on account of ‘global cooling’.  I still have a clipping that describes the ‘growing concern among scientists that has reached a consensus’ that the earth was already being affected in the form of reduced crop production that surely was only a prelude to global famine…  the Time magazine article even mentioned some of the things that might be needed to ‘save’ the planet, including covering the polar ice caps with soot to absorb more of the sun’s heat! Yep– THAT was a good idea!  Here is a good prediction:  in a couple more years the movies about impending disaster will become cult classics.  Just as we now read the book ‘1984’ and think ‘that was silly’, we will watch movies predicting rises in sea level as we sit in chairs that were SUPPOSED to be under water years earlier.  Did I digress?
Back to opioids, with apologies to those of you who are convinced this is that beginning of the end of the planet.  But first, in case you are interested about my own beliefs, I once read a fabulous book called ‘the Song of the Dodo:  Island biogeography in an age of extinction.  What a fabulous book– it explains how things got to where they are today, and helps understand where things are going tomorrow– with occasional stories about the great explorers from hundreds of years ago, about what it was like for a white man to travel to South America to collect birds…  I can’t do it justice.  But after reading it you will understand very clearly that the Earth is fine.
Yes, we will go through a tough spell where the entire planet wildlife collection will consist of humans, squirrels, rats, grackles, bacteria, and a few plants…  but after humans die off, all of the forces that lead to speciation are still in place, and all of the diversity will return– bet on it!  So while we humans are clearly f#%@#ed, the planet will be fine.  The things that lead to extinction would surprise you until you read the book, then you will see how they are completely inevitable– and completely irrelevant.  This from a person who was a total ‘greenie’ in my younger days!   Read the book– you will stop worrying so much.


Where the heck was I?  I got this message the other day about the medication ‘Afloxan’ and the chemical ‘proglumide’.  Actually, the message is a good fit with the other topics in the book, now that I think about it!  Here is the message:
I’m writing to get your opinion about an anti-inflammatory drug called ‘proglumide’.  This drug was used primarily for GI issues but has the unique characteristics of reducing opiate tolerance.  It works as a cholecystokinin antagonist, the wikipedia link is here.  I’d like to let you know, that whatever the opinion is out there about this drug, I can say that it really works.  I had to take a trip to canada for work, and while I was there I did a ‘cycle’ of Afloxan, which is not proglumide, but metabolizes into proglumide.  I thought this would be better than nothing and in going to canada, I took with me exactly 21 pills of afloxan, 12 10mg hydrocodone, 3 20mg oxycodone, and some number of kratom ‘pills’ i had made for myself (junkies can be real creative when they want to avoid dopesickness).