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Problem Drinkers, Endorphins, Naltrexone and Testosterone - Part 1
[Part 2 never got written...]

Alexander DeLuca, M.D.; Originally posted 2001-06-16; Last minor editing and formatting: 2006-03-08
See also:
Naltrexone and Alcoholism Treatment - SAMHSA Treatment Improvement Protocol (TIP) # 28 - O'Malley, 1998
Disulfiram collection  ;  Acamprosate collection  ;  Naltrexone collection
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I have been asked to explain naltrexone's effect on endorphin levels, and Suze, having seen my (truly awful) drawings about how naltrexone might help normalize brain anatomy and chemistry that has been distorted by alcohol and drug use has encouraged me to expound on this issue.

<sigh> It's easier to explain with pictures, but first I thought, "why re-invent the wheel" and I surfed over to
[the "" website that used to be affiliated with the Univ. of Penn and is now, 2006,  apparently, defunct, but what was 'the all naltrexone, all the time internet site'] where, I thought, surely there would be deep and learned explanation would be there for the taking. But, what I found at recovery2000 is typical of a lot of 'explanations for patients' you get on such websites. It's not that it's badly written or inaccurate, it just seems, ahhh, lightweight and fluffy to me. You be the judge: Here is an example of from Recovery2000's FAQ # 2: "Why does naltrexone help for alcoholism?"

"While the precise mechanism of action for naltrexone's effect is unknown, reports from successfully treated patients suggest three kinds of effects. First, naltrexone can reduce craving, which is the urge or desire to drink. Second, naltrexone helps patients remain abstinent. Third, naltrexone can interfere with the tendency to want to drink more if a recovering patient slips and has a drink."

To me, this doesn't really explain anything; it doesn't tell you how naltrexone might be helping, just that it seems to help.

So, let me try to explain what we think is going on with opiate receptors and endorphins in the reward pathways of the brain (limbic system) and what this has to do with craving.

One of my very favorite papers is by Gianoulakis and her team in Quebec, Canada. From the abstract of her paper entitled "Implication of the endogenous opioid system in excessive ethanol consumption" published in the journal Alcohol in 1996:

"In human studies, plasma levels of subjects genetically at high risk for excessive alcohol consumption showed lower basal activity of beta-endorphin, and more pronounced release of beta-endorphin in response to ethanol."

What this means is that people predisposed to problem drinking have:

1) lower levels of beta-endorphin (a rewarding neurotransmitter chemical that feels good) to begin with, and,

2) when you give such folk alcohol, they respond with an more pronounced outpouring of endorphin compared to people not predisposed to problem drinking.

Such an endorphin surge in response to a drink of alcohol is a powerfully rewarding neural event. Your brain is telling you: "What you just did (ingest alcohol) was GOOD; do it again! NOW!"

Note here that Gianoulakis found that "normals" had naturally higher endorphin levels, and that "normals" did not respond to alcohol with the endorphic spike she noted in excessive drinkers. This might correlate to the "social drinkers" experience of being able to have one or two drinks without feeling any particular urge to have another (and another).

If this were in fact the case, then one effect of naltrexone would be to block the (abnormal) enhanced endorphic response to alcohol thereby aborting the "That was GOOD, do it again, NOW!" limbic command that problem drinkers seem to experience.

OK, with me so far? Good. Back to the Gianoulakis abstract:

"... An important factor in the development of excessive ethanol consumption is the increase in opioidergic activity shortly after individuals begin drinking ethanol. Increased opioidergic activity could mediate the rewarding effects of ethanol, reinforce the act of drinking, and increase ethanol consumption. Human and animal studies, in which the administration of the opioid antagonists naloxone and naltrexone decreased ethanol consumption both by
ethanol-preferring animals and by recovering alcoholics, support this hypothesis."

What she is saying is that when you produce this endorphic surge in humans and animals ("increased opioidergic activity" means the same thing as "endorphic surge") by giving them alcohol, you can also decrease their alcohol consumption by using opiate-blocking medications like naltrexone! Pretty exciting, huh? (At least it is to neurophiz nerds like me.)

OK, so this might explain part of the puzzle, the 'why problem drinkers, having had one or two drinks, find it very difficult to stop drinking,' and why naltrexone, which would block "increased opioidergic activity" might help us 'endorphically-challenged' (as Suze refers to us) types find it easier to control our alcohol intake.

But wait! There's more! In Part 2 we'll think about why some people have lower endorphic tone that others and what all this has to do with testosterone anyway.

[END: Problem drinkers, endorphins, naltrexone, and testosterone - Part 1]


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Alexander DeLuca, M.D.

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Originally posted: 2001-06-16

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