We’ll never have a good drug to treat addiction

Chemists, molecular biologists, neurophysiologists, pharmacologists and 30 more types of  -ologists know a Hell of a lot about addicting drugs — where they go in the brain, what they do when they get there, the proteins that bind them, their chemical structure.  On and on and on.  We pretty much know how mind benders do what they do. Yet, in my humble opinion,  we’ll never have a drug we  can give an addict to effectively stop the craving and the addictive behavior when they’re back in their day to day environment.  Here’s why.

These thoughts come to mind after two nights free of needing to take a narcotic (vicoden 2.5 milligrams) to stop coughing or a benzodiazepine (valium 2.5 milligrams) to finally get some sleep, due to the flu — see https://luysii.wordpress.com/2011/03/24/scopolamine-where-is-thy-sting/ for the gory details.

I was grateful for the rest, but loathed the way I felt the following day — totally blah, not caring about anything I usually like (even music). Some people like this sort of detachment.

Historical vignette #1:  1968 – 1970 — as an Army doc stateside with 500,000 men in Vietnam, I was quite worried about an impending heroin epidemic in the USA. Why? According to people I talked to who were over there (NCOs, officers, grunts) about 30% of the troops were taking heroin to get through their one year tour of duty.  Since it was coming from Thailand, right across the border, the heroin was (relatively) uncut and pure.   If heroin was as addicting as claimed, we should have had 150,000 new heroin addicts each year in the US.  Sure, as a neurologist, I was called in for the occasional withdrawal convulsion, but the vast majority just stopped the stuff once no one was shooting at them.  It’s just not that addicting, not that anyone should mess with it.

Historical vignette #2: Nowadays docs seem to be in the hospital all the time (hospitalists, ER docs) or never in the hospital (office practice).  Back in the day it wasn’t like that.  I wouldn’t have liked either — a steady hospital diet is depressing and a steady outpatient diet is boring (to me at least).  So I’d see and diagnose patients with back pain, some of whom needed surgery.  I’d visit them post-op in the hospital the evening of surgery.  Usually, if they were going to do well, they were hurting from the surgery (which was far more invasive then than it is now), but free of the back and leg pain that led them to surgery in the first place.  Since I was teaching neuropharmacology a few days a year to med students, and drugs were as much a problem then as they are now, I was interested to see how what they thought of the narcotics (demerol was big back then) they were getting for post-op pain.   I got two types of response:

#1  — “I hate feeling like this”  “I don’t care about anything”  “I like to be in control but I’m not”   “The pain relief is great, but you can have the rest”

#2 — “I love it !”  “I don’t have a care in the world”  “I’m just floating along watching the world go by”  “The pain relief is great”

Now which do you think is more common?  Remember these were not druggies, just the run of the mill back patients (with a high percentage of working men).

It broke down 95% #1 responses, 5% #2.

The main point is that both #1 and #2 were describing the identical experience as far as I could tell.  So you can know all you want about the G protein coupled receptor for mu opiates, receptor number location etc. etc.  and it won’t explain the difference.  Of course it’s the 5% of #2’s that are going to get in trouble with drugs.  It’s why you never give benzodiazepines to a recovered alcoholic.

Historical vignette #3:  People who abuse drugs often get their brains in trouble.  Enter the neurologist.  Unfortunately some of these people were docs in the community.  One particularly intelligent GP (what family practicioners were called back then) got in trouble with drugs again and again.  He’d been a friend before he became a patient.  One day, when he was relatively intact, I asked him why he did drugs. I knew him pretty and it wasn’t lack of money, lack of family, lack of brains etc. etc.   His response:   “The difference between me and you is that you like reality and I don’t”.  This leads to a realistic possiblity about people who use drugs — maybe they are using them to treat the way they feel without drugs.  This is certainly reasonable for the soldier being shot at in Vietnam.

Over the years there have been lots of studies showing all sorts of brain changes associated with drugs (All we really know is that the changes are associated with drug use.  What we really want to know is whether the changes are due to the drugs).  There is one exception to this — alcohol abuse causes shrinkage of the brain.  How do we know? — because when an alcoholic stops their brain expands.  Here’s a study on 20 cocaine users [ Neuron vol. 60 pp. 174 -188 ’08 ] showing a variety of abnormalities. We may be on the verge of finding out if they come first, or whether they are due to the drugs.   There is currently a study in progress (sorry I can’t find a reference tonight) which will do serial MRIs on 2,000 European adolescents as they mature.  Some of them are (statistically) certain to develop drug problems. We’ll then know if the brain changes preceded or followed the drug use.

So we can tell you all you want to know and more about dopamine release in the nucleus accumbens septi (mostly in rats but some work has been done in man) due to cocaine (acute and chronic), but we can’t tell you why some people like the experience but most don’t.  That is not chemical, not pharmacologic but probably lies in the deep recesses of the soul.  This may explain why the treatment of alcoholism with the highest success rate remains AA.

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