[Rhonda]: I know you've done a little bit of work on Salvinorin A, and it's not something
I'm so familiar with so much as the kappa-opioid pathway.
A good friend of mine, Sheba Meucci [SP], had told me a little bit about the Salvinorin
A pathway.
He was doing some literature reading on it some years ago for whatever reason, and so
how it came into my awareness.
And he was telling me about how agonism of the kappa-opioid receptor had a feedback loop
effect where it actually caused mu-opioid receptors which bind to beta-endorphins to
become more sensitized to the endorphins.
And so I read up on this, checked the literature and references, and found that indeed the
agonism of it does actually cause mu-opioid receptors to become sensitized to endorphins
and I thought that was very interesting.
Around the same time, I started getting into using the sauna, so heat stress.
And I started to notice...so when I was in graduate school, I was very stressed out,
lots of pressure, failed experiments, and exams.
And so I started using the sauna a lot before I'd go into the lab and I noticed that there
was a very profound effect on my brain because I started to be able to handle stress better.
My anxiety was lower.
I felt good, and these were lasting effects.
I felt good days later.
And so I started reading about what's going on here.
I started reading about heat stress, and I came across the dynorphin pathway which is
an endogenous opioid that we make in our brains, sort of the counter to endorphin because it
sort of makes you feel dysphoric rather than euphoric.
And then I started reading about how dynorphin actually is a part of the...both endorphin
and dynorphin are part of the thermoregulatory pathway.
So dynorphin actually cools the body down.
And when your body heats up, you increase dynorphin to cool it down.
It's sort of a response mechanism.
So when you're sitting in a hot sauna or when you're working out really vigorously and you
feel that sort of uncomfortable heat where you're like, "Oh, I want to stop.
I feel..."
I think that's probably dynorphin.
So dynorphin binds to the kappa-opioid receptor which then sensitizes the mu-opioid receptors.
So now, I was thinking, well, maybe some of these lasting effects from the sauna were
mediated through that.
Of course, that's all anecdotal.
I mean, I know some of the biochemistry is out there, but I don't know if that's necessarily
been shown, but that's how I became really interested in that pathway, my sort of personal
story.
And then I started reading somewhere, someone sent me some article about people that were
addicted to...I think it was opioid, prescription opioid.
They were being treated by giving them the sauna as a detox, "detox," which I don't know
if that's actually legitimate.
But I started thinking about possible, maybe there's some truth to it by resetting the
mu-opioid receptor pathway or something.
So I just thought that was something very interesting that maybe I could send you some
of the studies if you're interested in seeing some of those.
[Roland]: Yeah, yeah.
I'd be interested in that