Exercise and Endogenous Morphine Release

[needshelpnow]

Just curious as to if anyone has a speculation of how much endogenous morphine/opiates can be released during physical exercise?

I personally doubt this could ever even be measured, but I once read in a forum/article that one person compared 1 hour of strenuous weight lifting to a release of 50MG of endogenous morphine...

Figured it would be an interesting topic for discussion, no reason to flame me as I know it's a pretty crazy question and probably immeasurable, but perhaps one of you crazy scientists may shed some light on the situation?

 

[Hammilton]

Endogenous morphine is absolutely miniscule, it's never even been proven to exist in living humans, just in carefully constructed in vitro settings.

The opiopeptides are far more important AFAICT.

 

[negrogesic]

I think he means endogenous endorphins or more specifically "endomorphins".

And lifting weights is certainly not equal to 50mg of morphine. Perhaps 1-2mg at most; the effect is not that strong. Plus, exercise also modulates neurotransmitters...

Running or cycling (endurance cardio) releases more endorphins than weight-lifting...

 

[permastoned]

Interesting little fact, exercisers have been shown to have a higher opioid tolerance as a group, on account of their constantly higher levels of endogenous opioid peptide release than the slacky fatties. A higher dose of opioid was required in order to elicit the same physiological response as the control group.

What I found ironic about this is that it shows that the whole idea of exercising in order to release endorphins is moot, unless you are someone who generally does no exercise, and spontaneously jog a lap of an oval.

Why? Because once you get a tolerance and your receptors down-regulate, the activation by the endorphins is compensated for, and the resulting symptoms (euphoria, pain relief, anxiolysis) are no longer experienced by the individual, as the activation of the opioid system returns to the basal level. Yes, homeostasis is an utter bitch ladies and gentlemen. Amusingly, the only purpose the opioid system then serves in regards to exercise is to provide a disincentive to stop exercising, as doing so initiates a mild opioid withdrawal (I have experienced this myself upon sudden cessation of years of intense physical exercise).

In injury the opioid system acts as your most loyal friend, soothing you and bringing you psychological relief. In exercise it acts as your mother, urging you to continue your regime lest there be negative consequences, such as a smack on the bottom.

Musings on homeostasis are the reasons that I am finding myself less and less inclined to believe that a pharmaceutical can truly cause happiness/cure depression. This is because the brain makes the individual feel how it wants to make the individual feel, by altering the setpoint of the dopamine and opioid receptor levels. Psychotherapy or soul searching/meditation/training/habituation may be the only way to affect these setpoints, unless the mechanism for the determination of their levels is discovered, in which case we may be able to invent drugs that hijack this mechanism. These drugs could truly cause wonders in my opinion.

 

[leungkachong]

I don't have time to find particular references right now... but the idea that endorphins as meaningful in the cognitive effects of exercise is not supported very well. The increase in beta-endorphin (and other endogenous opioids) is just as, if not less impressive than the increase in 5-HIAA/5-HT, anandamide, DA, and adrenaline. Not only this, but naloxone/naltrexone do NOT block the cognitive effects of exercise. This suggests that endorphins play little (if any) role in the desired effects.

Wives tales don't make a good basis for speculation.

 

[seep]

I don't have time to find particular references right now... but the idea that endorphins as meaningful in the cognitive effects of exercise is not supported very well. The increase in beta-endorphin (and other endogenous opioids) is just as, if not less impressive than the increase in 5-HIAA/5-HT, anandamide, DA, and adrenaline. Not only this, but naloxone/naltrexone do NOT block the cognitive effects of exercise. This suggests that endorphins play little (if any) role in the desired effects.

Wives tales don't make a good basis for speculation.

It's hardly a wives' tale.

To say their role is overrated is one thing, but to say they play no role is just wrong. "The cognitive effects of exercise" are not a monolithic block of subjective feeling-states and thought-process characteristics. And cognition itself is not the central component of exercise. Nociception and dyspnea are far more obtrusive to an athlete than attitude (which may be little more than an epiphenomenon). I can psyche myself as much as humanly possible, but I'm still going to get toasted in a long-distance run if my breath control and pain supression capabilities are not sharp--and for those two processes, you can't discount the role of b-endorphin/enkephalin/endogenous opiopeptides or whatever you want to call the little guys.

And to answer OP's question: they measure serum endorphin levels all the time by chopping mice's heads off and quantifying markers. Or (in one study) they simply stuck syringes into people running marathons around Tokyo (Japanese nurses are nimble).

 

[kidamnesiac]

Interesting little fact, exercisers have been shown to have a higher opioid tolerance as a group, on account of their constantly higher levels of endogenous opioid peptide release than the slacky fatties.

Tell me about it

 

[shibireru]

... unless the mechanism for the determination of their levels is discovered, in which case we may be able to invent drugs that hijack this mechanism. These drugs could truly cause wonders in my opinion.

If I'm not mistaken - and I very well may be - the mechanisms by which receptors lose their sensitivity to ligands are quite well characterized. I shouldn't think that - and again I certainly may be mistaken - it would be all that difficult to find substances that would inhibit or reverse the effects of those molecules within neurons that are responsible for this phenomenon (i.e. Beta-arrestin, phosphate groups attached by protein kinase A to serine/threonine residues, and others that I've forgotten).

The problem of course is targeting the right cells because you certainly wouldn't want to inhibit these mechanisms in all cell types in the body, I needn't tell you. That would be disastrous and almost certainly lethal. So, the question as I see it is how does one specifically target mu-opioid receptor-laden and certain dopamine-receptor laden neurons?

This will probably come off as science-fiction-y / pseudoscientific / naive / fantastical or whatever, but I wonder if a viral vector couldn't be altered to inject its payload through mu-opioid receptors. This RNA payload would do two things: 1) Contain the genetic information necessary for replication, naturally, and 2) Encode enzymes that would prevent desensitization of receptors somehow.

I realize that I'm making this sound like some facile endeavour when in reality it's probably exceptionally difficult, if not impossible. And there are certainly more efficient and lest arduous ways of going about this goal (like DAMGO and phosphodiesterase 4 inhibitors and so forth).

This is something I've been interested in for a very long time since opioids are some of the very few substances that actually alleviate depression for me.

 

[newbie22]

I don't have time to find particular references right now... but the idea that endorphins as meaningful in the cognitive effects of exercise is not supported very well. The increase in beta-endorphin (and other endogenous opioids) is just as, if not less impressive than the increase in 5-HIAA/5-HT, anandamide, DA, and adrenaline. Not only this, but naloxone/naltrexone do NOT block the cognitive effects of exercise. This suggests that endorphins play little (if any) role in the desired effects.

Wives tales don't make a good basis for speculation.

As an opiate user myself I can tell you it's no wives tales. When I exercise in the morning before taking a hit of H I use less than I normally do because I already feel great from working out. I think running produces a better high (the runner's high) than weight lifting and I can guarantee you all the runners who talk about runner's high aren't just lying....there's no reason too. And you can't say "it's nothing like opiates" because I have done lots of opiates. Sure it may not be as strong, but if you run long and hard enough it can really make you feel great afterwards. Not to mention your muscles and body are in pain when you run "all out" so your endorphin system kicks in to help you recover...

 

[seep]

if you run long and hard enough it can really make you feel great afterwards. Not to mention your muscles and body are in pain when you run "all out" so your endorphin system kicks in to help you recover...

Just a tangential question that's not altogether advanced: Does anyone live at high altitudes and run up mountains or steep hills? Before I got a cigarrette habit I ran for more than a decade, and in the Adirondacks, after nearly killing myself for 2 kilometers up a steep path I'd take a gradual 8K downhill route home. After the uphill gallup I'd be panting like a great fucking dane and when I'd get home and shower, the subsequent 4-5 hour feeling of somatic--uh--beatitude, is the closest thing to IV heroin I've felt: better I think than 160 mg oxycodone po. The combination of thinner air and extreme demand for oxygen was the key maybe: it doesn't happen on flat roads at sea level. So then yeah, if anyone runs long distances up mountains and has felt the subsequent heroin-like dolce far niente, just nod or something: I wanna know if it's worth my while to to try to reproduce the conditions and test the notion (it's kind of hard to do when the steepest thing around me is a landfill).

 

[Rectify]

There is endogenous endorphin release from exercise, but not endogenous morphine release.

 

[leungkachong]

As an ex-opioid users (as both a pain patient, and a recreational user) and ex-international competitor in two sports, I am not disputing the surface similarities between the two sensation and cognitive effects. What I am questioning is why the evidence doesn't support it... most specifically the naloxone/naltrexone experiments. Both of you who responded to me used anecdotal, personal experiences as your 'proof' I'm incorrect. Can you explain why antagonists would not block the benefits, if they are due to endogenous ligands at opioid receptors? My personal expectation is that activity in Periaqueductal grey, spinothalamic tract (maybe?), and VTA/N.Acc. account for the sensation's similarity to opioid agonism (same regions, but not via opioid agonists).

So I'm not discounting opioid-like activity... I'm discounting the unsupported etiology of endorphins and enkephalins as the cause (with experimental data via concammint administration of antagonists)? Any evidence which can explain this away? Otherwise the PAG/VTA/ST tract explanation explains your assertion while not contradicting data.

 

[PsychedelicPeptide]

This will probably come off as science-fiction-y / pseudoscientific / naive / fantastical or whatever, but I wonder if a viral vector couldn't be altered to inject its payload through mu-opioid receptors. This RNA payload would do two things: 1) Contain the genetic information necessary for replication, naturally, and 2) Encode enzymes that would prevent desensitization of receptors somehow.

Yes you should really read up on the biochemistry behind these systems. Its not that there is anything wrong with sputtering out mumbo-jumbo, but you should recognize that your interest in this sort of subject and most importantly free will to openly entertain your mind with thoughts on ways to create novel biological entities that fulfill certain ideals you wish to see come to fruition would be much better off if you were prepared to make such thoughts with adequate knowledge of the subject beforehand so that you might actually come up with something realistic and useful. ;-P

 

[Hammilton]

^ It mostly comes off as ill informed.

 

[Tsukasa]

it's definately not equivalent to 50mg's... It's more like 10mg's if you run a 6 mile marathon. 50mg's can kill even a tolerant person. It hasn't been proven yet that morphine is endogenous, but it's possible. Strenuous excercise actually releases other b-endorphin and other endorphins and neurotransmitters, which has been proven in a recent 2008 study.

 

[seep]

As an ex-opioid users (as both a pain patient, and a recreational user) and ex-international competitor in two sports, I am not disputing the surface similarities between the two sensation and cognitive effects. What I am questioning is why the evidence doesn't support it... most specifically the naloxone/naltrexone experiments. Both of you who responded to me used anecdotal, personal experiences as your 'proof' I'm incorrect. Can you explain why antagonists would not block the benefits, if they are due to endogenous ligands at opioid receptors?

You're right, but the burden of proof is on you. Naloxone has often been shown to interfere with the homeostasis that accompanies strenuous activity. And since serum endorphin levels do rise during and after exercise, it needs to be demonstrated that they are not the crucial psychoactive agents felt during the refractory stage.

 

[Hammilton]

It is? You must suck at logic. How is he supposed to prove a negative? How is anyone?

Naloxone has no effect the subjective effects associated with the runners high. How much more proof can you get? You can't get much better than that.

We accept that if an analgesic isn't blocked by naloxone it isn't an opioid, so asking for more here is more than a little illogical.

 

[Recept]

From what I understand, it is widely believed that release of endorphins is only one of the factors in runner's high. Endocannabinoids (anandamide) might also contribute to the phenomenon, as well as several monoamine neurotransmitters.

 

[Hammilton]

Based on what the naloxone trial finds, they have no impact on the runner's high.

Endocannabinoids + monoamines seem more likely.

 

[seep]

It is? You must suck at logic. How is he supposed to prove a negative? How is anyone?

Naloxone has no effect the subjective effects associated with the runners high. How much more proof can you get? You can't get much better than that.

We accept that if an analgesic isn't blocked by naloxone it isn't an opioid, so asking for more here is more than a little illogical.

Proof by contradiction is proving a negative. It's my current fucking nightmare as I'm working on something called the Riemann zeta function (the thing that put John Nash in touch with martians). Here, though, it's much simpler. Let's call what we're talking about the "runner's high." It's a suite of emotions and sensations that feel as if they were produced by opioids. Are endorphins released during strenuous activity? Yes. This leads to the hypothesis that the runner's high is mediated by centrally-active endorphin. So then we're countering that naloxone has been administered and the runner's high has nevertheless been felt. That very-reasonably suggests the endorphin hypothesis was wrong.

But where is the write-up of the study that suggested this? And the subsequent reproduction of the results? I may not be looking deeply enough into the past. In the meantime, last year's German study that supports the 1st hypothesis is pretty sophisticated:

http://cercor.oxfordjournals.org/cgi/content/abstract/18/11/2523

"voxelwise"!