A Question About Endorphines

[Carl Fredrik Ahl]

Hi,

I have a question about opioids. When you are running for a long period of time the body produces endorphines. Here is a quote from a webiste (https://guenergy.com/blogs/nutrition-lab/runner-s-high-is-it-really-all-endorphins: "Scientists found that running for prolonged periods increased levels of β-endorphins in the body’s circulation. This increase was correlated with increased reports of positive mood changes. The correlation led researchers to conclude that β-endorphins produce the runner’s high." The website says that beta-endorphines is increased in the body. This webiste (https://www.ncbi.nlm.nih.gov/pubmed/8780) says that beta-endorphines are 18-33 more potent than morphine. That would mean that it is also much more potent than heroin? Could that really be right? You couldn't get more high on running than if you took heroin, right? So what do they mean when they say that beta-endophines can be 18-33 times more potent than morphine?

Edited April 1, 2020 by Carl Fredrik Ahl

[Strange]

6 minutes ago, Carl Fredrik Ahl said:

So what do they mean when they say that beta-endophines can be 18-33 times more potent than morphine?

What is says. That the effect of a given quantity of beta-endorphin is 18-33 times greater than the same molar quantity of morphine. Based on the results of a number of (rather unpleasant sounding) tests on mice.

9 minutes ago, Carl Fredrik Ahl said:

You couldn't get more high on running than if you took heroin, right?

How much beta-endorphin is created by running?

How much do heroin users take?

To what extent do tests of physical reactions in mice correspond to "getting high" in humans?

[BabcockHall]

It might take me or someone else some time to find it, but I seem to recall reading somewhere that the connection between runner's high and endorphins has never been established.

[Dagl1]

1 hour ago, BabcockHall said:

It might take me or someone else some time to find it, but I seem to recall reading somewhere that the connection between runner's high and endorphins has never been established.

really quick search found this article: https://www.sciencealert.com/the-reason-you-get-a-runner-s-high-from-a-long-run-isn-t-what-you-think 
But it claims that the reason why runner's high could not be due to endorphins is because they can't pass the blood brain barrier. They then link a study that shows that there are mechanisms by which endorphins are cleaved and can then be transported into the brain (I don't know if they are active or not). But many endorphins are already produced inside the brain (although I am not sure if they are released into the blood (which then means they still have to go through the BBB to reach other brain tissues) or if they are released into the ventricles)...

From the study they quote: https://www.pnas.org/content/112/42/13105.full

Although running mice that received vehicle (P < 0.001) or naloxone (P = 0.004) exhibited increased latencies to react to the hot plate compared with nonrunning controls, AM6545 (P = 0.79), AM251 (1 mg/kgBW, P = 0.47; 3 mg/kgBW, P = 0.91), and AM630 (P = 0.52) inhibited the effect of running on thermal pain sensitivity. Thus, analgesia seems to be also mediated by peripheral CB1 and CB2 receptors.
*AM6545 is a periphery-specific CB1 antagonist. 

So the reasoning in the sciencealert article is a bit meh (I think, but could definitely have overlooked something), but it does seem that there is evidence (based on this one study, didn't check anything else) that runners high (in mice) is mediated by peripheral endocannabinoid release. function (release can be somewhere else)

Did not really read well enough, only pain is changed by peripheral endocannabionoid function. Anxiety-reduction is forebrain-related: 

These acute effects of running, together with a feeling of euphoria, were earlier termed a runner’s high in humans. In a series of experiments, we were able to show that the reduction in anxiety-like behavior after acute long-distance running depends on CB1 receptors on forebrain GABAergic neurons. Pain reduction, in contrast, depends on peripheral CB1 and CB2 receptors. Our data demonstrate that an intact eCB system is crucial for a runner’s high in mice.

Edited April 1, 2020 by Dagl1
Edited last sentence and added a part