Tuesday, May 02, 2006

URB597 - Runners High in a Pill?

I've been tracking recent research regarding anandamide, the chemical now believed to be responsible for the runners high (check here for my original overview, and here and here for updates to that story). Scientists stumbled upon the connection a few years ago while trying to understand how THC (the active ingredient in marijuana) stimulated the body to reduce pain and create a euphoric feeling. Lo and behold, they found a group of neurons called "endocannabinoids" that accounted for the effect, and these neurons were naturally stimulated by things such as endurance running. Since then the "race has been on" to isolate the chemical effect in hopes to create a drug that can tap into the positive effects more efficiently than marijuana.

(A running dream, I think, courtesy of Kidsrunning.com)

It now appears that stimulation of anandamide has been controlled using a chemical called URB597, and has produced improved moods among test patients in early clinical tests. Bottom line - we could have runners high in a pill!

The key to this breakthrough by UC Irvine researchers was using URB597 to increase the production of anandamide by blocking their degradation, resulting in measurable antidepressant effects. Anandamide, like other endocannabinoids, is a very fragile compound, so slowing degradation can have as powerful an effect as producing more. The result? Improved mood with less side effects than similar anti-depressants like THC, and far less wear and tear on your body than a 90-mile per week regiment.

However, it may not be for everybody; a quote from the press release clarifies:
"The results were similar to the effect we might expect from the use of commonly prescribed antidepressants, which are effective on only around 30% of the population," explains Dr. Gobbi. "Our discovery strengthens the case for URB597 as a safer, non-addictive, non-psychotropic alternative to cannabis for the treatment of pain and depression and provides hope for the development of an alternate line of antidepressants, with a wider range of effectiveness."
Eager to try it out? It appears you can buy the chemical directly from Cayman Chemical, or you can wait for Kadmus Pharmaceuticals to finish their human clinical trials. I've already contacted Kadmus to let them know I'm available. ;-)

I get very excited when reading about this research, simply because I have been a much happier person since finding trail running. I've found a spiritual and physical connection with the world that I didn't know existed. There is a lot more to this sensation than the runners high (ie, being outdoors, regular exercise, escape from media, etc.), but it gives me hope that some people might be able to get the same feeling even if their knees can't keep pace.

And how funny is it that it's called URB597 (herb? get it?)? If Stan Jensen hadn't already claimed the domain name, perhaps we could rename it "RUN100". ;-)

Thanks for letting me geek out on you guys a bit.

- SD

PS - In other anandamide research (in case you are doing a paper or something), recent studies by Oliver Ullrich and colleagues shows that the anandamide endocannabinoid protects neurons from inflammation after brain injury by suppressing the production of inflammation-causing nitric oxide, which would otherwise cause brain injury. Although this is unrelated to the neurological effects (ie, runners high), it does point to an additional role of anandamide - that of "gatekeeper" between the brain and the immune system - which could lead to applications to help brain disease like multiple sclerosis.


  1. URB397 might help getting a 'runner's high' without running; but there's more to running(sights, getaway, etc) than just the high..So if you want the whole package, GO RUN! :-)

  2. Cool post. I don't often feel a physical "high" but there's no doubt I'm happier and healthier then I've ever been with my endurance training. And often I will tell my road running buds that I need to "recharge the batteries" by getting out on a trail.

  3. I've read theories that endogenous DMT may play a role in 'runners high.' I wonder if anyone knows for sure. Cacao contains anandamide. A few tablespoons of raw cacao nibs has noticable euphoric effects, but I hear the levels of anandamide are pretty low.

  4. I am a 50 something woman who has always been very physically active but now have nerve issues that keep me from doing the intense work out it takes to get the 'high' I need to keep from being depressed.
    Partook a bit 2 years ago and a part of my brain got unlocked that I hadn't seen in over 20 years. I live where it is illegal and I am a good citizen. So, I am perplexed and do not even know if it is safe to tell my physician about this whole thing. I am one who began getting high on cannabis when i was only 14. I destroyed my brain's natural ability to produce this chemical. so, any help...

  5. endocannabinoids are neurochemicals, not neurons.

  6. Cut and pasted from Reddit -

    Our ED50 for producing stimulus effects in rats and mice WITH co-administration of a low dose of anandamide was about 3 mg/kg. So if you want to try this you're going to need somewhere over 200 mg from cayman chemical and this will run you in the hundreds of dollars... (not to mention it will be a one time thing) I think I'll stick to my bag of herb for now ;)

  7. Also from Reddit -

    To be correct, URB597 is a fatty acid amide hydrolase inhibitor, so it blocks the catabolism of anandamide.

  8. actually, endorphins are most likely responsible for runner's high, not so much anandamide according to a study done at Georgia Tech in 04. Also, a German study has recently shown that there is higher opioid receptor activity after running, which would make sense that there would be a high afterward due to the intoxicating effects of opiates.

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  10. Hi Scott. i just wrote this long comment and it got erased by mistake. ooff [as we say in israel to express something disappointing].

    i was really impressed and enthusiastic about the idea of getting and starting a running regime, hopefully being able to be in a good enough shape to feel the "runners high" you mentioned. i got here after reading a lot about the urb597 and as i hope development of it will be soon as i suffer from a lot of depression problems which many antidepressants didn't resolve.
    so i thought if i could get the energy and the motivation to start running regularly and get in good shape [right now only able to run for a half hour] it might bring something of this positive feelings, at least another factor that could help..

    so i was wondering if you could share with me information of how to be able to sustain such extreme exercise on a regular schedule without tearing your body too much and cause stopping this..
    any info like how to prevent injuries and strains with such long running [of course hoping to get there slowly], i know there could be knee problems and things like that and wondered how do you [or other known information you could link me to] prevent and keep that from happening..

    any info and tips would be greatly appreciated.
    with my most respect to your wonderful blog and sharing this great thing with others, thanks,



    by the way, i hope you get to read comments from way back like this one.


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