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Opioids vs Endorphins

tricomb

tricomb

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Jan 21, 2012
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I don't post much in ADD but I like to lurk, so if this isn't ADD material feel free to perform moderator actions.

So your body's natural opioids are endorphins, as everyone always says.

I have a few questions:

* Do endorphins bind to opioid receptors?
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If so,

* Do opioids have a higher binding affinity than endorphins? In other words, when you take opioids does it "block" endorphins, or have negative effects on your body's reward system and the production of endorphins?
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I'm a chronic pain patient and likely will be on opioids for life, and have been on them for years already, although not in very high doses as of late, so:

*Does my taking opioids block my ability to get a "runners high" after performing extensive cardio exercise?
 
Yes endorphins bind to many of the same opioid receptors. There are several classes of endogenous opioidergic peptides, some of which are selective for the mu, delta, kappa etc. (enkaphalins = delta, endorphins = MuOR, dynorphins = kappa)

I am pretty sure that most endogenous opioid peptides have higher binding affinity (but likely less intrinsic activity...maybe not though) than the majority of traditional exogenous opiates, perhaps with the exception of super high-affinity bentley compounds (dihydroetorphine, etorphine and buprenorphine) and open-chain fentanyl analogues (carfentinil).

I'll check some papers/databases for affinities when I get done with work...running a couple rxns right now.

And yes chronic opioid use is going to impact the ability to feel "natural" opioidergic-mediated reward b/c of receptor desensitization/downregulation and whole host of other regulatory phenomena that come with tolerance.
 
There are actually quite a few opioidergic peptides in the human body, as alkap555 touched on. beta-endorphin is surely the most "famous", but dynorphins, enkephalins et cetera also share opioidergic action. No one peptide is totally "selective" over one receptor type, though.

The value I have heard quoted is beta-endorphin has something like 80x the binding affinity of morphine. I think most of the opioid peptides are fairly strong agonists as measured by in vitro tests - this means a little less when they are bulky peptide compounds that don't make it very far from their "release point" before being eaten alive by peptidases, though, so they have never panned out as systemic opioid agonists like the alkaloids have.

Your body does step down production of opioid peptides after continued full agonist opioid therapy, this is part of what causes withdrawal.

Regarding the runner's high, I have read many studies that suggest that feeling good from running is more mediated from a cannabinoidergic standpoint than any opioids - naloxone doesn't block the pleasurable feeling from running.
 
Thank you both for your contributions, I look forward to reading any literature you guys feel is relevant.

@sekio, yeah I've heard about that regarding the cannabinoid action. I'm a regular user of high potency cannabis extracts, does this effect my runners high?
 
Endorphins also seem to lead to extremely rapid receptor internalization vs common opioids, but interestingly enough leads to less degradation of the receptors.
 
How can I increase enkaphalins, dynorphins, and endorphins?

I currently diet and exercise and take supplements. Are there any modifications I could make to my diet, exercise, or supplements?
 
Other than that I really do not think there is surefire way to increase endogenous opioidergic transmission. I wouldn't really worry about it too much.

I know there are a few enkephalinase/endorphinase etc inhibitors mainly used in research. They would in theory act similar to MAOI or AChE-inhibitors, increasing synpatic concentrations of enkephalins/endorphins (as well as other substrates). Still years away from market, if they ever get that far.
 
"Increasing endorphins" is kind of like "increasing dopamine" -

There's no "one way" to do it. Moreover there are no "easy" ways to do so.
It's not going to produce the "expected results" for very long. (euphoria)
Your body has multiple mechanisms regulating the levels of neurotransmitters anyway.
Exogenous endorphin is rapidly broken down by peptidases.

If you have a good intake of protiens and the necesary dietary cofactors you shouldn't have to worry about endorphin levels. Otherwise you need compounds that essentially throw a wrench into your body's protien breakdown circuitry, which could in theory lead to your own endorphins causing your breathing to stop in the worst case.

I'm a regular user of high potency cannabis extracts, does this effect my runners high?
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I don't know - you tell me. What I have heard is that the runner's high is similar to any other enjoyment you derive from mental or physical activity and is not mediated by any one neurotransmitter. Effects "seem" to be blocked by cannabinoid antagonists. That's all I can really tell you. As far as I know, Michael Phelps (or anyone else who is active and a cannabis smoker) can still derive enjoyment from activity just like any of us.
 
Do you actually get a "runner's high" in the sense that you feel inebriated? All I've ever gotten from running (~5 miles) is maybe a slight elevation in mood. Only once did I truly feel stoned, but that was after a half-marathon (wouldn't do that again even if the "high" felt like heroin lol).
 
The runners high is not very significant but it's definitely noticeable. It's highly variable though, I've gotten incredible effects from running 1 mile and was disappointed after running 5. I've noticed it is much more pronounced after hardcore swimming vs running, because IIRC, swimming is more of a workout. Swimming is a much easier option for me as a chronic pain patient, the weightlessness feels great sometimes.

And I probably can't give an objective response Sekio, as usually after exercise I consume cannabinoids.
 
The runners high is not very significant but it's definitely noticeable.
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I think you have your answer there. In any case, imbibing cannabinoids won't do you much harm if it's after excercise :p
 
hah, your location is hilarious.

Well it would appear as another case of "if it looks too good to be true, it is", I can't change my diet, supplements, or exercise to get better effects.

Ten Four.
 
Very cool paper.

Just a bit of anecdotal stuff: I have a friend from college who runs at least 5+ miles per day. But if she for some reason does not run, she exhibits the classical symptoms of THC "withdrawal"--irritability, lack of appetite etc. Normally she is a quite and high-strung person, but after her runs she is talkative, relaxed and social, and eats like a fat kid post-blunt. I've always thought that in some people the reward associated with exercise can be quite addicting. I sure wish I was addicted to running.

Another recent paper on CB1 KO mice and decreased voluntary running (but otherwise normal locomotor behavior):

We wish to add that such a hypothesis, which is supported by a vast array of experimental data gathered in different animal species, may possibly extend to one particular form of motor behavior that was not addressed in the aforementioned review: namely voluntary running. Thus we have recently shown that male mice lacking CB1 receptors display decreased voluntary running when housed with a running wheel for several weeks compared with their wild-type littermates
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Free: http://physiologyonline.physiology.org/content/26/2/76.long
Pmed: http://www.ncbi.nlm.nih.gov/pubmed/21487025
 
Eating cheese high in casomorphine (like Brie, though that's not endogenous), masturbating, taking hot showers, and having sex are all ways to increase endorphins. That's why they usually feel good when you do those activities.
 
MMPA said:
Eating cheese high in casomorphine (like Brie, though that's not endogenous), masturbating, taking hot showers, and having sex are all ways to increase endorphins. That's why they usually feel good when you do those activities.
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I thought that was dopamine at work?
 
dopamine is responsible for the "rush" and the desire/anticipation of the coming effects. those effects are most likely caused by serotonin release. serotonin and dopamine have a kind of inhibitory effect on each other
 
MMPA said:
Eating cheese high in casomorphine (like Brie, though that's not endogenous), masturbating, taking hot showers, and having sex are all ways to increase endorphins. That's why they usually feel good when you do those activities.
Click to expand...

I love Brie
 
A runner's high is a composite effect of several euphoriant neurochemicals whose biosynthesis is (for some, greatly) increased during exercise. Beta-endorphin, anandamide, and phenethylamine are ones that have been identified in medical literature.
 
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