🐛 Bug Salad 🐞 ‘Matthew’s Morals’ Ep #4 | Official FULL Episode | Nick

🐛 Bug Salad 🐞 ‘Matthew’s Morals’ Ep #4 | Official FULL Episode | Nick


[music playing] Drink, drink up, little angel darling! Come on, man. [music playing] [crashing] Hooray, crash! Matthew! Hey, my lawn children! [screeching] Rest in peace. Yeah, rest in peace… Doosh! Don’t copy him, Winston! Hey, Matthew! You’re being a bad person,
I question your morals! She’s right, Winston,
that kind of behavior– Hey! What are you doing?
You piece of trash! [kicking] [crashing] – Hey, look, free cookies!
– Oh! [eating] [gasping] You know, Matthew,
I’m just gonna come out and say it, you may be the worst person
I’ve ever met. And you’re officially
rubbing off on Winston! No! [hitting] – It’s OK.
– What’s happening to me? You’re a good boy! – He’s copying you, Matthew!
– So what? I’m great. Wrong! Winston’s bad behavior
is all your fault! And if you can’t clean up your act,
then… Then you can’t hang out with him anymore! [gasping] [screaming] We’re doing this ’cause we’re upset! [screaming] Stop that! I’d like to still hang out
with Winston, please? Well, then you need to start learning
acts of kindness right now, Mr. Man! Where am I? Matthew, this is the perfect place
for you to do some nice deeds. I’m gonna be good! [moaning] Oh, great, a weirdo! Er, Matthew,
I think she may just be hungry. Oh, I got this! [screaming] [crunching] I’m good! Er… Er… [groaning] [explosion] Matthew, why d’you do that?
That was bad! I dunno, I’ll try harder! – What I miss?
– Oh! I pushed her, I saw myself do it! Why, Matthew, why? I dunno, I just looked over and– Oh no, I did it again, I did it again! Try again, try again! Rats, rats, rats, rats! [groaning] Matthew, stop! It’s no use, we’re never gonna be able
to hang out again! [crying] Ssh, ssh, ssh, tender child. You are correct. [screaming] Stop that! I gotta try again, I can get this right,
I can get this right! Alright! One more chance! Feed me. [gasping] – Phew!
– Phew! I’m so excited to eat my food. [humming] Huh? Oh no, my body wants to punch him! [screaming} [groaning] I’m ready to eat still. [screaming] I can be good! I can be… Good! [screaming] Mmm. Matthew, you did it! Oh, I did it, I did it,
I’m good, I’m good, I’m good, I’m good! I’m good! Ugh, guess one got loose. Goo– [crashing] [wailing] I’m a good person. [crashing] [moaning] [music playing]

Insect Pest Control : How to Get Rid of Fleas in the Yard Naturally

Insect Pest Control : How to Get Rid of Fleas in the Yard Naturally


I’m Trevor with Monster Pest Control, located
in American Fork, UT, we’re talking about ridding your home of insects, the topic today
is ridding your yard, naturally, from fleas. I’ve got some, what we call diatomaceous earth,
and using diatomaceous earth you can use it on the outside of your home. I’ve got it in
a bulb duster. Basically, when you find an area that’s infested with fleas, you can take
and you can put the dust out on there, out on the different areas. I’ll pour some out
so you can see it. You can take the diatomaceous earth, it is made of like crushed fossils
shells, things like that, so it’s all natural. Basically, pour it around the different areas.
You can put it throughout your whole yard if you want to do so or find those areas that
are most infested, to get rid of the fleas. Also, because it is a natural product, you
can rub it on your animals, dogs, and cats. I recommend, often, to talk to a vet before
you attempt to do something like that and read the label from the diatomaceous earth,
to make sure you do it correctly.

You’ll Never Guess Who Has a Parasite Infection? – Podcast #86

You’ll Never Guess Who Has a Parasite Infection? – Podcast #86


Dr. Justin Marchegiani: Evan Brand, how you
doing this morning? It’s Friday. Evan Brand: It is Friday. Hey, I’m great. We’re in the trenches again on ourselves
today. So this is fun. Dr. Justin Marchegiani: Yeah, today’s gonna
be a different kind of podcast. I think we are pushing the envelope regarding
functional medicine and functional health podcasting, because we’re doing tests on
ourselves. So today we’re gonna be talking about some
stool test that came in for yourself. And we already talked about them earlier this
week and we’re just excited to share them with the general public because we know your
story and my story will be able to help hopefully tens of thousands of potential patients and
people out there. Evan Brand: Absolutely so to give a little
of history here about why we suspected something was going on is when I first moved to Texas. I was about 160 lbs and I quickly after moving
there, I quickly began to lose weight without changing much of the diet. Paleo was pretty much my diet template. I was still exercising but not as much and
I began to slowly lose weight and I bottomed out at like 138 lbs. So we’re talking about 22 lbs lost in about
a year, maybe a year and some change, and when I—I remember the first I came over
to your house, you were like, “Dude, Evan, you got a parasite. That’s not normal like you’re getting
skinny, man. Like your muscle’s disappearing.” And I had just attributed it to adrenal fatigue
because I ran a cortisol rhythm test on myself, too, and showed pretty low cortisol even though
I had good DHEA. And so that kinda made sense but it wouldn’t
explain that significant weight loss. So you even said, you know, over 6 months
ago, “You better run a test for a parasite and see what’s going on.” And so I finally got around to it and turns
out I popped up positive for cryptosporidium and also Giardia which are 2 different parasites
that can be found or that you can get exposure to in different water sources. And so when I was talking to Dr. Kurt yesterday,
he said, “Evan,” he goes, “Did you swim in any sources of water that were a little
bit lower than normal like a drought-stricken place?” And I was like, “Oh my God, Lake Austin,
Lake Travis–” Dr. Justin Marchegiani: Yeah. Evan Brand: Barton Springs. Dr. Justin Marchegiani: Barton Springs. Evan Brand: Krause Springs, like everywhere
I went in Austin on the weekend was some sort of water source that– Dr. Justin Marchegiani: Uh-hmm. Evan Brand: Could have potentially exposed
me to it. And so the light bulb really went off and
I’m glad that we found these things because now we’re gonna get into the treatment stuff. Dr. Justin Marchegiani: Absolutely. And one of the interesting things about this
infection as well—well, first off, I saw pictures of you in the past before I knew
you and you just looked bigger, more—more fuller in your—in your facial structure,
and then when I met you in person a year or two later, I—I asked, I said, “Evan, you
know, have you changed your diet at all recently?” Because I know you’re a big Paleo guy, so
I–imagine you weren’t eating much sugar or carbs back then. You went, “No, I’m just losing weight
and my diet’s pretty much the same.” And we did a diet review and you were like,
exactly what you said, I’m like, “You have infection. There’s no way you’re losing this kind
of weight without some kind of internal malabsorption.” And then we saw your fingernails, too, and
we saw these vertical ridging and we’re like, I’m just, “There’s some kind of
protein or fat malnutrition.” I know you kinda sat on it and then over time
you were telling me some of the—you know, your cold hands, cold feet, you have it, every
now and then you mentioned you’d have some kind of blood sugar or panic attacks explaining
that we were connecting to some adrenal stress, and then we were saying, “Well, how is this
adrenal stress happening because you’re so many good things right? And then we finally got this testing done
and we were able to quantify that this is more than likely the driving factor and anyone
of these infections by themselves is a pretty big deal, whether it’s Giardia or crypto
by themselves. You have them together, so it’s like, you
know, with—with the—all these forces combining it’s really an exponential issue. It’s gonna be far worse than having this
one at a time. Evan Brand: A double whammy. Yeah, and so I had a—a slide here that was
from the Institute of Functional Medicine’s Intestinal Permeability Lecture and it was
saying “a recent study revealed a 23.5% of clinical samples tested positive for at
least one parasite”. So just go ahead and round that up to 25%
of people that were getting tested had at least one parasite, and so we’re talking
1 in 4 basically. For me, it seems to be 1 in 3. And Blastocystis hominis was the number one
at 12.5% and then you have Dientamoeba fragilis– Dr. Justin Marchegiani: Yup. Evan Brand: And they had Entamoeba and then
you had blah, blah, blah, and then Giardia’s at the bottom, 0.7%. So apparently Giardia’s pretty rare to even
show up or to even have. So for me to have that and the crypto, you
and I and Dr. Kurt, too, was also like, “Wow! This is rare to have.” And Kalish same thing, I’ve looked up a
couple of his lectures and he said he had only seen it like once before of having the
double whammy. Dr. Justin Marchegiani: Yeah, and here’s
the real important thing, too, is well, most conventional laboratories especially in a
hospital setting aren’t gonna pick up the infection. Again, I think you said it to me, we did a
401H on you, they—where it came up and I don’t think it came up on every single sample
because there’s 4 or 5 samples on that 401H test by BioHealth. We’ll give them a plug because they’re
a really good lab testing company. How many samples do you—are you aware of
that it came up on? Evan Brand: I’m not aware of the number
but it was, yeah, 5 or 6 samples over a 3-day period. So if we missed it on day 1, which if you’re
doing the conventional stool test—actually, I had a—a female client last week that she
actually had some really weird type of stools and so she ended up going to the hospital
and getting a stool test there. It showed up negative for everything. So I’m waiting on her results for the same
tests that I ran on myself. I’ll be so thrilled if we find something
just to prove that those conventional ones fail once again. Dr. Justin Marchegiani: And I’m finding
even BioHealth, I’m teaming up with some other labs that are doing the PCR/DNA stool
testing because it’s about 2 to 3,000 times more sensitive. Evan Brand: Yeah. Dr. Justin Marchegiani: Now sometimes BioHealth
will pick certain things up that other labs don’t. So I’m gonna be really curious to get your
DNA testing back either from DRG or GI-MAP because I think we’ll find maybe even something
else there as well and here’s the real important take home, is you didn’t have a lot of the
major conventional symptoms for Giardia. So like a lot of the conventional symptoms
for Giardia are gonna be like lots of diarrhea, lots of gas, lots of bloating, right? You didn’t have a lot of those major, major
symptoms. We did see, you know, we did see the malabsorption. I saw that more on the outside, but again
a typical individual won’t make that connection because they’re not looking at your diet
and how good it is. They—they’re not gonna be able to appreciate
a conventional—a conventional physician won’t be able to appreciate a Paleo diet
especially with the massive changes in weight you have. So I was able to notice that but you didn’t
have a lot of those conventional Giardia symptoms and that’s why I just think it’s so important
where if you have any health issues that you can’t quite put your finger on, and you’re
going to a conventional doctor to think that they’re gonna be able to pick this up. A lot of times they’re not because most
people—you didn’t have violent diarrhea. You didn’t have massive abdominal cramping. You didn’t have excessive gas or upset stomach
or massive nausea, right? Evan Brand: No, not really, I mean– Dr. Justin Marchegiani: Not really. Evan Brand: That—that one day of food poisoning
or whatever—whatever that was, we talked about it on a previous episode but that was
the only real episode where I thought, “Wow!” Something was up with my gut and so it’s
crazy. I didn’t wanna read in which I kind of alluded
to already where you could pick this up, but you know, the Mayo Clinic, they write about
how people become infected with Giardia and that’s after swallowing contaminated water
that could—you know, where the Giardia parasite is found in lakes, ponds, rivers, streams,
municipal water supplies, cisterns, swimming pools, water parks, and spas. And so I almost thought about we should title
this episode like the downsides of being primal or something, because I go barefoot a lot
of the time– Dr. Justin Marchegiani: Right. Evan Brand: Which I read that you can get
exposed to somebody’s parasites via soil, and maybe I’m not soaping myself enough,
you know, I will use from Dr. Bronner`s organic soap you know on the important areas. Dr. Justin Marchegiani: Yes. Evan Brand: And maybe—maybe sometimes I
wasn’t cleaning myself enough and I was taking it too far with the whole dirt is good
for you, you know, going barefoot, putting my hands in the dirt, in the mud in the backyard
all the time. I could have picked something up that way,
too. Dr. Justin Marchegiani: Absolutely and the
big issue, too, is with these—with these different infections, they can be spread fecal-oral,
but Giardia and crypto can also be spread via water. So I do a lot of water skiing in Lake Austin
every week so I’m—I’m gonna make sure I’m tested, you know, a couple times a year
because you’re gonna get these infections two kinds of ways. You’re gonna get it, number one, where you’re
chronically stressed whether it’s physical, chemical, emotional stress accumulating and
the chemical could be food allergens, gluten. It could be blood sugar swings, skipping meals,
not eating—not eating nutrient-dense foods. It could be toxicity issues. It could be a whole bunch of things, low stomach
acid and enzymes and then that chronic stressor opens you up so when you get exposed to something,
it’s able to set up shop and create basically a niche in your gut and start to proliferate
more cysts and spores for other offspring. And that’s kinda like one, where you—the
chronically ill person gets exposure. And then there’s people like you that are
just—they’re healthier but they just get exposed to a large bolus of it over a period
of time, maybe just all at once or maybe at multiple times throughout the week like you
mentioned, like your symptoms are perfect, right? It’s a perfect script for it, and then—boom—now
it sets up shop and then you’ve been gone from Austin for over a year and you’re not
quite doing that same type of thing you were in Austin but look, you got two infections
now. So more than likely the water issue was a–a
big driving factor and you know, I’m gonna get myself tested like we talked about again
because I do it yearly with a couple of different tests all at once and we’ll do a podcast
analyzing my test results soon as well. Evan Brand: Yeah, so looking back on what
I think was definitely some of the factors that—that led me to this. I mean, I was still working at the supplement
company, directly for the CEO, super– Dr. Justin Marchegiani: Right. Evan Brand: High position, super high stress
position, and then I was also running my clinic on the side at the time. And this is when you and I were being able
to—we got to hang out locally and I was just seeing clients, you know, outside of
my basically 8 to 5 hours during the workday at the office and then coming home and spending
more hours looking at research, looking at labs, talking with people, that low adrenal
function, I had to burn myself through. I had to burn through stage 1. I probably had high cortisol, gave some leaky
gut condition, maybe made myself more susceptible to all this stuff, made the perform storm
of stressors, and maybe even lack of sleep from the stress that set me up. Now quickly which is kinda crazy actually,
even though I still tested positive for these two parasites, I was still able to put on—I’ve
put on about 6 lbs since I’ve moved back. I’ve got back in the gym, my strength’s
coming back, my injury where I thought I had a hernia has healed. And so it’s amazing to see the progress
that I’ve already made just by reducing the stress and being able to have more social
interaction, being back in a—a place that I call home that makes me feel comfortable. Dr. Justin Marchegiani: Yeah. Evan Brand: So I’m excited to see what happens
once we get these things knocked out, how my progress especially with my strength and
my weight coming back will—will be. Dr. Justin Marchegiani: Absolutely and also
there are over 40 different kinds of Giardia. The main one that we get exposure to as humans
is Giardia lamblia and that’s the—the so-called Beaver Fever that you can get exposed
to in the water. It can also be spread fecal-orally so at some
point, we’ll have to get your wife tested as well and make sure she’s treated because
don’t want—we wanna make sure that vector isn’t being passed back and forth as well. Evan Brand: Yeah, I looked at her fingernails. She’s got some vertical ridges, too. But you and I talked about off air, even if
we were to get a positive results on her with the baby growing in her tummy, we can’t
treat her right now anyway. Dr. Justin Marchegiani: Right. Evan Brand: So we’ll just have to wait until
after the baby’s coming and—and look at it then. Dr. Justin Marchegiani: Absolutely and also
a big vector for Giardia, I’m gonna say it now because it just happened last month
with a patient, is gonna be your pets especially dogs because dogs love to lick and there’s
you know, a big article over at Petsandparasites.org, right? Dog owners and Giardia that’s a big one,
but I had a patient come in and we had diagnosed her with Giardia the month before, the next
month she came in and said, “By the way, my dog was having some issues, we brought
him to the vet, and the vet said he had Giardia.” And she kinda felt bad because she thought
maybe that she gave the dog Giardia and I said, “Other way around, he vectored that
Giardia to you.” So for all these pet owners out there, be
very careful of playing kissy-face with your—with your dogs because you know, they’re licking
something else, if you know what I mean, and they’re going home and licking you and licking
your face or licking your hands. So if they’re licking your face, that’s
a no-no, and if they’re licking your hands, make sure you wash it off because they can
vector these parasites, and I’ve seen many people that have worked with pets and with
dogs and with animals, trainers and veterinarians, and they almost always come back with Giardia
and multiple other infections. Evan Brand: I wouldn’t doubt it if I got
it from our Shih Tzu because if I’m playing with her and she’s slobbering all over the
toy, I may not go and wash my hands right after I play with the toy and then I could
touch my face and maybe even touch my mouth by accident. Dr. Justin Marchegiani: Yes. Evan Brand: So who knows? You know, Lucy, our Shih Tzu, she may have
Giardia as well. Dr. Justin Marchegiani: Yeah, it’s very
possible. I would say one, we could get her tested,
but al lot of times the conventional vet tests don’t work a bit, they aren’t awesome,
but it’s worth a try, or you can just do a human-based test and see what happens on
that. But number two, it may even be worth just
treating your—your dog with the conventional antibiotics for that infection. So for the Giardia, that would be like Flagyl
or metronidazole. Again, I typically don’t recommend the antibiotics
for most people. You can do it. Some people will do it like the Flagyl or
the metronidazole or Alinia or like the—the go-to antibiotics for the infections. I like the herbs better just because of the
fact that the side-effects with the antibiotics can be very, very severe and a lot of times
you get the better exposure with the herbs over a longer period of time. Because with the Giardia and other infections,
the Giardia may be there but there may be a massive imbalance of other bad stuff and
the herbs can kind of help knock that back down without all the side-effects. If someone wants to go the antibiotics route,
then we’ll typically do antibiotics and then follow-up with herbs as well. The only issue with dogs—it just depends. If you can do herbs with your pet, that’s
great. A lot of times it’s difficult to do that
especially every single day. It’s easier just to do it with an antibiotic,
you know knock down the vector and then come in with some good probiotics afterwards. But again herbs for humans are gonna be my
number one—number one go-to with that, and I’ve knocked out hundreds in the past. Evan Brand: Yeah, so let’s talk about the
protocol that we’re gonna start with because antibiotics are the conventional option, the
go-to thing for these types of infection, but you and I talked about it and we’re
like, “Let’s—let’s go herbal route.” So we don’t have to go specifically over
every single ingredient but wormwood and some of these other natural antiparasitic, antimicrobials,
oil of oregano and then a—a few other supplements is gonna be the treatment protocol that I’m
gonna be starting on. Everything’s ordered, I should have everything
to my door in a few days and I’m gonna be started ASAP and then for the timeline– Dr. Justin Marchegiani: I just wanna touch
upon just one thing­– Evan Brand: Yeah. Dr. Justin Marchegiani: Real quick. Evan Brand: Yeah. Dr. Justin Marchegiani: We—we didn’t quite
highlight crypto yet, but crypto is another waterborne parasite but it can also be, you
know, fecal-oral spread meaning some type of fecal material from whether it’s intercourse
or whether it’s from poor preparations or not cleaning hands, that’s another vector
these things can be spread by, but crypto is that other major parasite and again, like
in the mid-90s I think it was Milwaukee, they had a major outbreak in the water supply where
I think 500,000 people were infected with crypto. I think even 4 died. Evan Brand: Yeah. Dr. Justin Marchegiani: So crypto is another
big one. We’ve been giving Giardia a lot of love
here, but crypto is another one that can be basically hide in the crypts. The crypts of Lieberkühn in the intestinal
tract in between the microvilli buried deep out—deep down into the intestinal wall and
that’s another infection that we’re dealing with here, that typically we have to kind
of separate how we treat both of them because Giardia can move and get into the bile ducts
and affect fat digestion and crypto can bury deep into the intestinal tract and in between
those crypts where the microvilli are close by. So different infections, a lot of times will
call for different treatments and both can be spread via water, fecal-oral, and a lot
of the side-effects and symptoms may be the same, and again immuno-compromised people
tend to have that, like a lot of your AIDS patients and such, but you know, you’re
not in that camp, and you may just been stressed and got exposed to it, so it’s not just
the super immuno-compromised that the conventional medicine people say. It could be someone like Evan who—who is
super healthy and productive, and has a lot of energy—a lot of energy, too. Evan Brand: Yeah, it’s amazing how much
I’ve got done. You and I were kinda laughing like how productive
I’ve been despite having these two type of infections simultaneously. So I can’t wait to see what happens as we
kind of work through this protocol which the timeline that you and I have kinda discussed
is about 2 months that we’re hoping we can knock these things out and retest and see
what see what happens and then something on hand that I have for die-off, just some activated
charcoal I ordered some of that just in case, and then I’ll be using a probiotic at night,
too, just to try to help out with inflammation and then obviously I’m gonna stick with
the probiotic, too. Once I’m done through this protocol and
try to just focus a little bit more on gut healing and try to repair any type of damage
that’s been done. Dr. Justin Marchegiani: Exactly. And even with the cryptosporidium it’s known
that cryptosporidium causes zinc issues, zinc malabsorption. Well, let’s think about that, right? If we have low zinc, we need zinc to make
hydrochloric acid. We need zinc to make our—especially testosterone,
our hormones, it’s a really important building block for hormonal health. So if we have that, if we have low stomach
acid now because we have now low zinc, we need zinc for our immune system, right? The zinc fingers are really important epigenetic
factor for our DNA, and then we need stomach acid, we need our sex hormones, so you can
see what happens here when you get an infection, the sequelae of how you tend to get sicker
or symptoms get worse overtime because of malabsorption, lack of ability to break down
food, low nutrients compromised immune system, compromised sex hormones, compromised ability
to make more digestive secretions to break things down, different infections can hide
in the bile ducts like Giardia and then create inability to shoot out bile so now we have
an inability break down fat soluble nutrients, well, there goes vitamin A, D, E, K, all your
EPA, DHA fats, cholesterol, and now we have this kind of bottleneck and then we miss all
of these buildings blocks to make our hormones and be really healthy. Evan Brand: Yeah, and I would like to add
one other thing to it, too. We ran an organics and looked over that, and
we were just talking about that together, too, which showed high arabinose; therefore,
meaning that I have some candida issues going on on top of all of this. So kind of a triple whammy and it’s funny
because I haven’t felt that bad and now thinking back a little bit though when I went,
I guess this was a couple of years ago when I was kind of geeking out on the whole pyroluria
topic. Dr. Justin Marchegiani: Yes. Evan Brand: And I ran the kryptopyrrole test
which showed very, very high issues where I was gonna be lacking in the zinc and the
B6. Dr. Justin Marchegiani: Ah, see! Evan Brand: Yeah, so I’m wondering if it
were—what, you know, chicken or egg here. Was it the kryptopyrrole issue first or was
it the infection that led to the problems with zinc which elevated py—you know, the
pyrroles. Dr. Justin Marchegiani: Right. Evan Brand: I mean, what do you think? That’s—that’s a hard—hard thing to
try to figure out. Dr. Justin Marchegiani: Well, again I’m
partial to these infections causing a whole host of issues. Evan Brand: Yeah. Dr. Justin Marchegiani: And the big thing
I wanna hammer home is you didn’t have a lot of the conventional symptoms so anyone
that’s listening to this and think, “Well, I don’t have the main conventional symptoms. My conventional doctor said it couldn’t
be this.” Think again. Evan is a perfect example right now and Evan
is a super healthy guy and—and look what’s happening here. We saw symptoms in and around different areas
and because of the fact that, I know you mentioned like maybe some—some anxiety at—at times,
it’s very possible because of the protein and stuff. We looked on your organics, we’ll do a separate
podcast on this. We saw some lower neurotransmitters. Evan Brand: Yup. Dr. Justin Marchegiani: I think in—in the
dopamine and catecholamines side of the fence and we need hydrochloric acid and we need
healthy digestion to break down protein to convert those proteins to your brain chemicals. So it’s very possible this was driving some
of the underlying, you know, slight anxiety under the surface as well. Evan Brand: Yeah, and I’ve told you this,
and I’ve told the listeners probably a dozen times, I’m not an anxious person– Dr. Justin Marchegiani: Right. Evan Brand: By nature. And so that was really odd for me to have
some of these feelings of panic and anxiety overwhelming me where I literally had to leave
the movie theater one time. Dr. Justin Marchegiani: Right. Evan Brand: Because I was having a panic episode
and I tell people this all the time, it’s not you necessarily. Like it’s not you as a person, that’s
anxious. It’s your biochemistry. It’s your neurotransmitters. It’s the imbalance. It’s the overgrowth of bad guys in the gut. It’s—these are creating a toxic situation
where it doesn’t matter who you are as a person, you can get overwhelmed and that’s
what happened to me is that, sort of a good guy versus the bad guy, the light versus dark,
the dark started to win on me a little bit so– Dr. Justin Marchegiani: Yeah. Evan Brand: Really looking forward to get
going with this thing and I—I can’t wait to see what you have. I mean, because you’re in—you’re in
the water probably more now than I was, so– Dr. Justin Marchegiani: It’s true. It’s true. Evan Brand: I can’t wait to see what’s
up. Dr. Justin Marchegiani: I know, I’ll be
really curious, you know, healthier IgA, healthier hydrochloric acid can help because it’s
like a disinfectant. You got a dirty table, the hydrochloric acid
and/or IgA can come in there and clean that table off. In my real world analogy, that’s like using
bleach, right? You– Evan Brand: Yeah. Dr. Justin Marchegiani: Pour on the bleach
out or using your—your Seven Generation natural cleaner for all everyone here that’s
more naturally oriented. We’ll use that stuff, get it clean and then—boom—you
got a nice table that you can eat off of, that’s kinda like your intestinal tract
where you have IgA and hydrochloric acid that can basically pinch hit for that bleach in
our real world analogy. Evan Brand: Right. So just to finish off, I’m sure– Dr. Justin Marchegiani: Yeah. Evan Brand: People are curious. A couple other pieces to the puzzle that I’m
still keeping support nutritionally, obviously keeping the diet dialed in, keeping the sleep
dialed in, I—I can’t imagine if someone didn’t have all the things that I have dialed
in. How awful they would feel to have two infections
at the same time? Dr. Justin Marchegiani: Oh, my God. Evan Brand: And so I really think, and you
probably agree that this is the only way that I’ve been able to stay so productive is
having the lifestyle and nutrition and the stress and the adrenals and all that in check,
because otherwise I’d probably be a wreck. I don’t know. I don’t even wanna know really. Dr. Justin Marchegiani: Right, right. Evan Brand: But I’m—I’m doing the fish
oil, you know, I’m doing, you know, high potency. I’m trying to get at least a gram per day
and then also doing some enzymes, doing some HCl, a little bit of oxbow, because thinking
back and I don’t think I mentioned this to you before, when I first tried to start
MCT oil, I was in such severe pain. I was rolling on the floor, you know– Dr. Justin Marchegiani: Wow. Evan Brand: Grabbing my stomach from literally
one teaspoon of MCT, and so this infection is making me—this makes me think that I
was unable to digest fats because my gallbladder was impaired like you were mentioning. So this is—it’s kinda crazy now that I’m
gathering all of these pieces that I didn’t think anything of when they happened in such
isolated fashion. Dr. Justin Marchegiani: Yeah, well, let’s
just—I know you only got a few more minutes left here, Evan. Let’s just go into treatment real quick. I already alluded with the Giardia, the conventional
is gonna be your Flagyl or metronidazole, your typical conventional. Some of the more functional medicine MDs or—or
even people like myself sometimes we’ll use an antibiotics called Alinia, and we’ll
use that as well. But you gotta be careful, there can be a lot
of side-effects and I’ve seen many people already gone through antibiotics and still
have the infection. I’ve seen it dozens and dozens and dozens
of times just this week. So the—the moral of that story is don’t
think because you get the antibiotics that it’s a slam dunk and it’s gone. Just don’t have that assumption and if you
do the antibiotic route, you still wanna follow up with the herbs anyway because there’s
a whole bunch of gastrointestinal imbalance that’s gonna be there and you wanna clean
everything up. Evan Brand: Yeah, so to be clear, we have
both kind of talked about this and we’re not going antibiotic route. Yes, technically, we’re doing some natural
antiparasitic, natural antimicrobials but not the conventional antibiotics, and we’re
gonna be this for about 2 months and then we’re gonna re-test and see what happens
after we use some of these remedies and see what type of results we get and then hopefully
when we re-test we’ll see that it’s gone and we’ve wiped it out successfully and
that’ll be another one for the books. Dr. Justin Marchegiani: Yeah, and we’ll
just kinda list off a couple of things that we’re doing but we’re doing higher dose
oil of oregano, higher dose wormwood, higher dose berberines and black walnut and grapefruit
seed extract. We’re gonna be adding in neem. We’re gonna be adding in bittermelon, barberry,
and other different families of berberines. We may even talk about adding in some silver,
and then there’s a couple of other herbal blends that we’ll do because we have to
open up the crypts so we can get good exposure to these antimicrobials for the cryptosporidium,
so we’re kind of doing two infections at the same time which is harder but I know you’re
healthy enough to handle it but these are a whole bunch of families of herbs we’re
using and you gotta be careful, too, because higher doses of wormwood can be very effective
but they can also raise liver enzymes so we may have to add in binding support and liver
support. So you really wanna make sure you’re working
with someone that has experience. So one, you make sure you get a therapeutic
dose, and two, you have the die-off binder support so if you start having too much of
these biotoxins from these infections accumulation, you could have support there and maybe even
have someone monitor your liver enzymes if needed as well. Evan Brand: Yeah, definitely. So obviously, we’re a little bit biased
here. But without a doubt, for your health and for
your overall wellness, even if you don’t have any symptoms at all which my own symptoms
were really the nails and the cold hands and the cold feet, get tested, you know, reach
out to one of us. Get tested. Run yourself through just for general wellness. You don’t have to be one of those people
that wait—wait until you get sick or wait until you have 30 symptoms and you’re on
5 pharmaceuticals and then you get tested. Take the proactive approach like we’ve done. I could have been just fine. I could have just said, “Well, it’s winter
time. It’s 20 degrees outside, hmm, I have cold
hands and feet. No big deal.” I lost some weight, whatever, it was stress,
and I could have just ignored this stuff. But just trying to be a little bit more proactive
can really save your health and really save you from, I mean, not to bring up the—the
big C word but I mean from cancer and other­– Dr. Justin Marchegiani: Yeah. Evan Brand: Chronic illnesses that could happen. If I were to—what if I were to keep this
infection for 20 or 30 years­? Dr. Justin Marchegiani: Yeah. Evan Brand: And then finally get discovered. I mean, oh, my Lord. Dr. Justin Marchegiani: My God. And the big thing, too, is—oh, I think one
other thing we’ll—we’ll add in. We’ll put links so people if people wanna
get access to some of the stool tests then they can at least click below, but you wanna
make sure you get interpretation either someone like myself or Evan or a good functional medicine
doctor that’s trained in—in what the next steps are because the big thing that you’re
doing here, that we haven’t emphasized you—you mentioned it briefly, is you’re doing all
the diet and lifestyle and adrenal stuff and we’re even getting you on some brain stuff
as well, which is you know gonna help you go through this whole protocol without the
side-effects and keep you functioning at an optimal level so you can help, you know, all
the patients that you’re helping. Evan Brand: Right, and luckily I have a little
bit more of a relaxed lifestyle where I’m at home so if I need to take it easy on myself
and block out some more time then I’ll be able to do that, but the goal is to maintain
productivity and a lot of people they don’t have time to—to be sick and be laid out. So we’re trying to craft this protocol here
to where I’m still being able to be on hustle mode and still work through this thing, so
excited to get going and I’m really happy that we—that we could share this with you
all today. Dr. Justin Marchegiani: I am, too, and this
is such a clinically relevant podcast so please refer to all of your potential, you know,
candidates or friends or family, anyone listening that could resonate with this, please share
it out there because it’s so clinical and I think people that hear it and resonate are
gonna actually be able to take direct action from this podcast and that may help bring
some closure to some of the underlying chronic symptoms that may be there. Evan Brand: Absolutely and just to hit—hit
that drum a little bit harder one more time. This is not a theory podcast where our goal,
which I did this for a hundred episodes successfully. We’ve hit 4 million downloads on iTunes,
etc. you know, what I started with NotJustPaleo podcast was very successful and very enjoyable
but it hit a certain point, and especially, you know, in our careers where we’re realizing,
look we don’t have to have some random new name on the podcast every single week because
what we have going with our clinics and what we’re actually doing in the trenches to
me is becoming more important than having some new voice or new perspective on every
week. So I’m glad that you guys—we’re still
seeing the numbers of the downloads go up significantly when Dr. J and I are doing these
episodes together, so thanks for your support and thanks for really digging deep with us
and not just looking for the next piece of brain candy. We’re actually sharing the things that may
get a little bit repetitive but every single person is different and for this type of scenario,
for me, the practitioner to have a two parasites myself, it’s like wow! This stuff can happen to anyone so– Dr. Justin Marchegiani: Absolutely, and then
Evan, do I have your permission to post up your—your lab work for this test online
so people can actually see that this is the real deal. Evan Brand: Yeah, of course. Dr. Justin Marchegiani: That’s great, and
I know, we’re both running late, we both have patients because we’re in the trenches. We’re doing it. We’re rolling up our sleeves trying to help
people get their health back, so Evan, thanks for this awesome show. Super inspired today with your story and I
know that we’re just gonna help so many more. Evan Brand: Yeah, well, take care. Dr. Justin Marchegiani: Thanks, Evan. You, too. Evan Brand: Bye.

Can I Get A Yeast Infection From A Dirty Toilet?

Can I Get A Yeast Infection From A Dirty Toilet?


Good day, Eric Bakker, naturopath, author
of Candida Crusher with another frequently asked question. This is quite an interesting
question. Can I get a yeast infection from a dirty toilet? Well, I don’t know how to answer that one.
Your toilet would have to be pretty dirty and pretty grubby for you to get a yeast infection.
I personally wouldn’t use toilets that were that unhygienic that I would be concerned.
I would probably choose a better toilet or a cleaner toilet or perhaps use one of those
paper things you can put on the toilet seat before you sit on the toilet. So, it’s not really likely that you’re going
to get a yeast infection from a dirty toilet. I would question why you would need to use
a toilet that dirty for you to be concerned about getting an infection. I don’t think I’d pay too much attention to
this question really. Practice a bit more hygiene and if you do use a dirty toilet,
maybe have a shower when you get home and clean up properly. It is more likely that you’re going to get
a yeast infection from a locker room or gym floor or having a shower in those sorts of
areas where you can pick up a foot fungal infection, but not likely you’re going to
pick up thrush or vaginal or genital yeast infections from a toilet seat. You wouldn’t
want to be sitting on a toilet seat that you had any suspect issues about anyway. I hope that answers your question.

Shiki: Epidemic – Episode 3 (An Abridged Series) | BYTE

Shiki: Epidemic – Episode 3 (An Abridged Series) | BYTE


TOSHIO: Seishin. Thanks for coming over, my man. I got some big news to share. SEISHIN: Well, it’s always nice to talk to you, Toshio, When you’re not in one of your moods. So, what’s the occasion? TOSHIO: I finally figured out what’s been causing all these recent deaths. SEISHIN: What? SEISHIN: What? Really? TOSHIO: And no, Before you say it, It’s not AIDS. SEISHIN: This is great, Toshio. Since you know what disease has been rampaging through the village, you- TOSHIO: It’s vampires. SEISHIN: Toshio, SEISHIN: Toshio, how much sleep have you had recently? TOSHIO: What does that have to do with anything? SEISHIN: I know this is hilarious coming from a religious monk, But have you thought of a more scientific explanation? TOSHIO: No, it’s vampires, alright. And I know just how to prove it. RITSUKO: Thank you for agreeing to stay overnight at the clinic. SETSUKO: No problem, missy. But are you sure someone with my condition is safe here? RITSUKO: I assure you, ma’am, You’re perfectly safe with us. [AKIRA humming] KAORI: Akira, KAORI: Akira, we’re going up to Megumi’s grave. You shouldn’t be so happy. AKIRA: I can’t help it, Sis. I can finally prove what’s causing all these deaths. KAORI: AIDS? AKIRA: No, Sis. AKIRA: No, Sis. Vampires. You know how people started dying after the Kanemasa people showed up. Well, I decided to scope out their castle last week. And imagine my surprise when I saw one of our dead neighbors entering the place in the middle of the night sporting red eyes and fangs. They thought they were so clever, But they didn’t count on Akira Tanaka to be on the case! [AKIRA laughs] KAORI: You think this is funny? AKIRA: N-no. AKIRA: N-no. I didn’t mean it like- KAORI: AIDS is not a joke. People are dying. And you’re just trying to make light of the situation with- Oh. And he’s here AKIRA: Hey, Natsuno. How are you doing, buddy? NATSUNO: Here. AKIRA: Neat. NATSUNO: Let’s move out. AKIRA: Oh! Yeah, Sis. I didn’t tell you how we met. Yesterday, I planned on assaulting Kanemasa KAORI: I thought, “What’s dead was dead.” AKIRA: to take out those nasty vampires, when suddenly, NATSUNO: I’m just making sure it stays that way. AKIRA: Natsuno showed up. At first, I thought I was- AKIRA: Oh! And we’re here. NATSUNO: Okay. You remember the plan? AKIRA: Yeah! If anyone asks, we’re- volunteers from the church. NATSUNO: That’s right. Now, let’s get started. [Alarm bells ringing] KAORI: Guys?! KAORI: Guys?! Are we about to dig up Megumi’s grave?! AKIRA: Yeah. AKIRA: Yeah. I thought it was obvious. KAORI: Am I the only one who sees about messed up this is?! NATSUNO: No one’s keeping you here. KAORI: You know what? You’re right. I’m going home! [KAORI stomps away] AKIRA: Kaori, come back! Natsuno didn’t mean it like that! [Root snaps] [KAORI screams] [KAORI gasps] KAORI: What’s this doing out here? AKIRA: What? KAORI: This was KAORI: This was the good luck charm I got Mr. Muroi to bury with Megumi. KAORI: H-how did it get out of the grave? NATSUNO: Only one way to find out. AKIRA: Alright! AKIRA: Alright! It’s time to bust this case wide open! [KAORI whimpering] TOSHIO: Well, well, well. Look who’s decided to show up. Mr. “I-don’t-believe-in-vampires.” SEISHIN: I’m just making sure you don’t hurt anyone. TOSHIO: You know, for a man who believes someone sat under a tree for 7 years, You have surprisingly little- SETSUKO: I’m here. [Door opens] SETSUKO: I’m here, child! SEISHIN: What in the world? [Window rattling] TOSHIO: Seishin, TOSHIO: Seishin, there’s something at the window. SETSUKO: It’s ripe for the picking! Let my sustenance nourish you! My expiration dawns soon! Consume my essence! [SETSUKO screaming] NAO: Oh… Hi guys. You wouldn’t mind opening that window- TOSHIO: Get the fuck out of my clinic! This is not a feeding ground! [NAO hisses] TOSHIO: Alright, Seishin! How do you explain that?! SEISHIN: Okay… SEISHIN: Okay…There’s a logical explanation for this. TOSHIO: That was a dead woman, TOSHIO: That was a dead woman, with red eyes and fangs, Floating out the 2nd-story window! Fucking vampires! [Someone walking] NATSUNO: Alright. NATSUNO: Alright. Moment of truth. AKIRA: It’s empty! Ha! Ha! It has to be vampires! AIDS can’t make bodies disappear, right? NATSUNO: No, AIDS can’t make bodies disappear. AKIRA: O-of course. AKIRA: O-of course. Everybody knows that. I was just asking for my sister. She’s a bit slow. NATSUNO: Wait… NATSUNO: Wait…Where’s your sister? [KAORI muffled screaming] AKIRA: Kaori! [KAORI muffled whimpering] ???: Girl, I worked all last night. I need something to eat. KAORI: (thinking) Protect me, good luck charm! ???: Ah! KAORI: Hey, it worked. AKIRA: Sis, are you okay? KAORI: Natsuno, I’m so sorry that I was mean to you. I thought you were a bad person after what you said at Megumi’s funeral. But when you risked your life to save mine before that guy- NATSUNO: It’s fine. I was in the wrong. AKIRA: Seriously, Natsuno. Thank you for saving my sister. Pretty sure you killed that guy, though. NATSUNO: He was already dead. AKIRA: That was badass. NATSUNO: No, I mean literally. Have a feel. AKIRA: Holy shit! AKIRA: Holy shit! It’s ice cold. KAORI: Does that mean… AKIRA: Fucking vampires. NATSUNO: Anyone got a stake on them? KAORI: You mean you don’t? AKIRA: Well, what are we going to do with the body? KAORI: Are you sure that’s deep enough to hold him? NATSUNO: I don’t care. KYOKO: Come on. You gotta eat something. [TOSHIO sleep mumbling] KYOKO: Wow. KYOKO: Wow. No snarky comment. This must be serious. I’m almost worried about him. My God, it’s so boring out here. There’s got to be something fun to do. Hmm? Why hello tall, pale, and handsome. AKIRA: Hey, Natsuno! So, what are we going to do about the vampire? KAORI: Wait… KAORI: Wait… The grave. AKIRA: What?! AKIRA: What?! How?! NATSUNO: Looks like our vampire friend was busy last night. [NATSUNO sighs] NATSUNO: I should have dug a deeper hole. Hello, everybody. Robert Wiggins of BYTE here. Thank you all for watching. And I’d like to thank all the fantastic voice actors and actresses who appeared in this video. Also, if you want to subscribe, Make sure you also subscribe to “BYT Info” because Article 13 is here and my body isn’t ready. That’s all for now. And as always, ???: God damn kids. All I wanted was a snack, And they smack me in the head with a shovel. No respect, no respect for their elders, I say.

How to Avoid UTIs and Yeast Infections at Burning Man

How to Avoid UTIs and Yeast Infections at Burning Man


It’s 143 days til the Man burns and today we’re talking about vaginas again! Everyone knows about playa foot, if you don’t I’ll do a video on it just for you. But, what a lot of people don’t know about is playa vagina or you know UTIs and yeast infections, because they happen a lot at Burning Man. It’s something to do with the alkaline in the playa dust it messes with the delicate ecosystem between our legs. It happens… So, pre burning man if you can get your hands on like cranberry pills and probiotics especially the ones designed for ladies and lady health, then you know, that’s just going to help your body kind of build up some protection against it, hopefully! It doesn’t work for everyone. Some people are still going to end up getting hit by it, but you know anything you can do right? Like I always say I’m not a scientist or a doctor, like I don’t know if that stuff works but the people at the health shop seem to think it works so why not? Even if you take all of the pills, you follow all of the advice anyone gives, you drink cranberry juice like it was the only liquid on planet earth, some of you are still going to get hit by something. The best thing you can do is go to the doctor before hand, explain the situation, you know tell them, it is known…this happens a lot, and hopefully they’re going to prescribe you something just in case it happens to you, and you know, while you’re there ask them for some tips you know, is there anything you would suggest I do to try and prevent it from happening, because you know prevention is the best thing ever. For yeast infections there are quite a lot of over-the-counter solutions, so pick one of those up as well, just have it in your medical kit just in case. While you’re there you’ll want to keep things nice and clean and fresh, I mean you can be the cleanest person in the world and still getting hit by something like this, it’s not like…it’s not like if you get it you’re dirty and disgusting or something you know, it happens to many many people. But I suggest bringing extra knickers with you especially you know like cotton breathable ones, because think about it, like playa dust is going to get on your clothes it’s going to get on your knickers and it’s like alkaline, it’s just going to be rubbing against your vag all day, like it’s asking for trouble. Lots of people like to bring double the amount they think they need and change them twice a day. Obviously every time you change them make sure you have a good clean down there as well otherwise it kind of defeats the point a bit. Aside from anything else, changing your knickers are brushing your teeth, it makes you feel amazing when you’re at Burning Man, you feel like a princess out there, fresh knickers, fresh teeth hmm! Obviously you want to store all these somewhere where they’re not going to be getting covered in playa dust because otherwise that would kind of defeat the point. So, you know, a big ziplock bag or something is perfect, keep that in your tent or you know, somewhere it’s protected as much as you can from the dust, if it’s possible to protect anything from dust at Burning Man. Even though baby wipes are like the number one choice for keeping things clean down there and I mean we use them on babies butts so they’ve got to be good for ours right? Getting some ph balanced feminine wipes can be good as well because the pH balance is kind of the problem, it’s the alkaline in the dust and you want things to be pH balanced down there. If you’re planning on going nude while you’re at Burning Man you want to bring a towel or something that you can sit on, I mean, it’s considered etiquette anyway to do that, you know, don’t go rubbing your butt over other people’s stuff, but it’s also going to mean you know if you decide to sit on the floor you’re not going to be sitting directly on playa dust. Peeing is very important as well, you know, pee when you need to go don’t…don’t hold it for hours and hours just because it’s super inconvenient you know, and if you have any sexual contact with someone then pee afterwards as well because that’s a really known cause of UTI. So I know it’s not very romantic, it kills the mood to be like “I’m just going to go pee so I won’t get a UTI” but seriously, be unromantic, do it look out for number one! So I know I already mentioned cotton panties, but I know that some of you out there are like “I’m not wearing granny knickers to Burning Man! I’m going to be wearing this sexy g-string i just bought with the tassels and the beads and stuff” that’s great, you know go for it, but be aware that those things are a bit more irritating to vaginas, and maybe bring along some cotton panties as well just to be on the safe side because you probably don’t want to be stuck in an uncomfortable g-string the whole time you’re at Burning Man. It’s also a great kind of nap time option, you know, if you just want to have a sleep then you can put on your cotton grannies and have a sleep where everything can breathe, or you know if you’re comfortable with it if you have a tent or something that you’re sleeping in go bare butt naked and really let everything breathe down there. So that is it guys you know, sometimes bad things happen to good people and one of those good people might be you so be prepared for the worst! I hope this is helpful, if you have any questions or comments or tips or anything like that let me know in the comments section, and if you’re at Burning Man this year feel free to come and say hi to me if you spot me roaming around. Bye!

Termite Protection | Stroud Homes

Termite Protection | Stroud Homes


Hi, Bryan here from Stroud Homes Brisbane
South. I want to talk to you today about termite
protection. No matter where you build your new home in
Australia, you need a reputable termite protection system. Look, over the past 20 years or so, Stroud
Homes have tried many different systems that are on the market, but for the last 9 years,
we have used exclusively, Termiglass. What we like about the Termiglass system,
it’s natural. So, there’s no chemicals, there’s no poisons,
there’s no toxins. It’s made entirely from crushed glass, very
simple. The termites can’t eat, lift, or burrow through
the perimeter protection. There’s no maintenance, there’s no topping
up. I love that part of it. Once the product is in, it’s in. Within the plumbing pipe, you can probably
see a few of them behind me here, a normal standard system would just have the plumbing
pipe coming up out of the slab. Over time you will have movement, even a very
small bit of movement will allow space for a termite to get through. So, Termiglass use a product called Frisbee
collars, now that sounds nice and fancy, it’s essentially a collar that actually wraps and
seals that pipe, making sure that when there is movement, there is no chance for the termite
to get in. Look, it’s Australian standards approved. That’s extremely important. And it comes with a lifetime warranty direct
from the manufacturer. All they ask is that you do a once-a-year
check, and you honestly should be doing that anyway. Look, best of all, we haven’t had a single
termite infraction since the manufacturer’s product has been used in our homes. Look, I hope this has been of some help. Thanks for your time.

Square dancing helps teens deal with a  suicide epidemic in their community | Twilight Dancers

Square dancing helps teens deal with a suicide epidemic in their community | Twilight Dancers


(lively fiddle music) – I’ve played the River
Red Jig so many times, since I’ve learned it, I’ve witnessed so
many great jiggers, and that’s my preference, just to play the River
Red and see others jig to my music. – I always get a
really good feedback on what I do on behalf
of my performances. They just say “Oh it’s
just jigging Des.” (laughs) No, it’s not just jigging, it’s actually something
I grew up doing, something I love to do. (kids mumbling) (Cherish giggling) – Cherish come here,
you have to come and comb your hair too. – CrossLake Competition
is happening right now, square dancing is on Saturday. Sometimes we win, and
sometimes we don’t, but it’s all about having fun. – [Abel] Cherish and
Demi you should start going to the school! – [Girl] Did Demi already leave? – [Abel] Yep, she’s outside. – [Girl] Okay. – They’re having a floor
hockey tournament outside, or something. (upbeat fiddle music) – [Desmond] I was
dancing since I was like 5 years old man (laughs), since I was a little boy. I remember my first time, I
was in my mom’s living room, and everyone was dancing,
everyone was dancing, and one of my brothers,
he’s like “Des. and that’s when I
was like, “Why, what “are you gonna do to me, man?” He’s like, And so I tried it, it didn’t
work out well. (laughs) It was funny, and
kind of embarrassing. This is what my brother
always used to say to me, “Just because you don’t
know how to dance now “Doesn’t mean that you’ll
never know to dance “in the future.” – [Woman] Okay Aleisha
and Anisha, ready? How! Yeah, you and Demi,
you and Chloe, how! (kids giggling) – I love teaching square
dancing, honestly. Not only for future generations, but to help them, it helps, even when
you’re going through a lot in life. Not only I’m teaching
them, but I’m also teaching myself. Not just to become
a better dancer, but to also to become
a better person. – Stage is right there! – Square dancing is fun, sometimes we get our
dances from YouTube, and then we bring a little
bit of our moves in there. – I basically use
square dancing for fun, to have fun, and I can
forget about stuff. – I like learning new
steps and all that, I really like the double step, it’s the certain step
everyone knows and does. If you know how to
do the double step you can do any type of
step in square dancing, jigging, and whatever. – One time, just one time. (yelling dancing directions) Okay, one, two, three, go. – [Cherish] When
the music starts you have to tell your
team “One, two, three”, and then you start
dancing all together. To know when you’re
going to make a move, you have to say “how”. How! (laughs) (lively fiddle music) – My thoughts on how
our land was colonized, and the residential came to be, the residential school,
it’s very sad because there was so much
hidden abuse behind it, and to take away the
important identity of who we were as a people in the beginning before
this ever happened. The new generation
that we’re having, we’re having a mixture of tunes, and we’re seeing a lot
of step dancing now, into the square dancing. – Square dancing
I think was always part of the culture growing up. Old times, eh, both my
grandpas played fiddle, and they held dances
in a local hall here. They would square dance there, and have a little competition. – [Woman] How! – I think square dancing
came from white people, (laughs) I don’t know. – The colonizers did
bring us square dancing in terms of teams
and what not, eh, but there was, of course,
the First Nations People incorporated some other
moves into the dance, eh? The colonizers, they
just used their feet, not so much the body, eh? Then First Nations
incorporated their dancing into the whole body, right? That’s the influence
the First Nations had on square dancing. – I know other people
that square dance but, sometimes they don’t want to, some kids like to judge, and act how they dance. Bullying, it happens
a lot, and suicides. (slow sad music) – Everybody out there,
doesn’t matter if it’s child, going on to elder,
everybody’s in pain. “Why would they do such a thing, to take their own life?” Some people don’t even
know how to express themselves no more because, there’s barely people
out there listening. – Some people commit suicide
because they get bullied. People like to bring down
each other on social media. They like to judge,
and then tease, and everything else. – Growing up in
my community here, bullying has always
become, main thing, either you’re a part of it, or you’re the one doing it, or you’re the one
getting bullied. I’ve been a part of both sides, but I’ve learned as I grew
up not to be like that, because I was losing friends, and I was only picking sides, and I knew that was
wrong, and right away I switched up my mind,
and bullying hurts. – I kind of do like living here, and I kind of don’t. Sometimes I don’t like
staying here because of the bullying. – I don’t like
bullying just because, I lost a good friend of
mine to it, to suicide. It was really hard. (melancholic music) – I haven’t danced
last festival, and I didn’t dance
in Indian Days, due to the suicide epidemic, and what was going
on, I couldn’t do it. The most tragic thing
that happened to me in my life is losing a brother. It was very devastating. I grew up in a violent place. Couldn’t focus on school
due to getting bullied, because of the color I wear. We kind of joined that violence, but that’s the past,
a past that I probably never want to go back to, never. (upbeat jig music) (tap shoes clinking) (energetic fiddle music) – When I play I always
recognize my community. They’ve been a
big support of me, from when I first started. This is me, and if
you can accept that, I promise you,
hate me or love me, that I’m gonna be the
best person as I could be, and showing my
respect for my people, and other people of
my Native culture. Pimicikamak Cree all over. – [Kelson Voiceover] It’s
kind of different how people dance, eh? How
they make their moves. – [Keshton Voiceover]
It’s probably coming from your spirit inside, that is letting you free
of what you’re doing, it’s going with the
music, the rhythm. – [Demi Voiceover] Before I
go on stage I’ll be nervous, you know when you
get butterflies, but then you know
it’s gonna be good when you get butterflies. – [Kassidy Voiceover] Five
seconds, and the music starts, and you know when to dance,
so you just start dancing. – [Cherish Voiceover] Kind of
nervous when you get on stage, cause everybody’s
looking at you. “Okay, do I remember
the dance?”, and stuff like that. – People are dreaming
of what cars, or a nice house, or
something, you know? My dream was to dance
with my brother, to light up that stage. (shoes tapping rhythymically) (lively jig music) (audience cheers) (audience cheers) – [Host] Way to go
there, Twilight Dancers! – I’ve seen who’s shoe
that broke, I’ve seen it, But tell her, that didn’t
stop her from you guys getting the crowd
going, you guys did! – [Woman] Everyone check
their shoe right now! – That’s how you dance! (cheers) Make the crowd go wild! (lively fiddle music) – The last fewest words
my brother told me, those words that got me
going everyday in life, throughout those years. (speaks in foreign language) Which means “Never give up.” And so I took it. – [Host] Twilight Dancers. – [Host] Desmond Colombe. (melancholy music) – I do believe that there
does come a time where us youths think about our lives, and what we wanna do, and it’s then on our choice to follow those dreams and
the right steps to take. We have the opportunity,
we just have to make them happen,
and when we do get them, make sure you don’t hold back, cause you might regret it
for the rest of your life. (melancholy music) – Everybody in this
community, as we speak, is a survivor. They survived through that 2016. And through the roughest,
the roughest year, toughest. We’re hurt, we’re
damaged, we’re broken, but we’re still standing strong. That’s the important thing
about this community, no matter what happens, to each and everyone
of us out here, all I know, that every
individual in this community, is one tough warrior. (rapid jig music) (crowd cheering) (upbeat jig music)

BUG BOUNTY METHODOLOGY TIPS TO ALWAYS TEST FOR! with Jason Haddix

BUG BOUNTY METHODOLOGY TIPS TO ALWAYS TEST FOR! with Jason Haddix


…Wow here we go..
alright so. people have been asking me a lot about stök how do you do your recon?
and the thing is that I don’t really do any recon. But when it comes down to
discussing what you do when you first approach a new target.
there’s different kinds of ideas of what you should do so.. i just decided to ask Jason Haddix about it..
So Jason when when you approach a new target what are the
things that are crucial… that a new bounty hunter doesn’t miss?
yeah I think a lot of the new bounty hunters will look at a target like something you have
to login to they’ll just start poking around if the external stuff like
external search forms and parameters on the outside and not really dive into
learning the application like actually using it like a user would if you think
of it like an iceberg and all you’re seeing is the tip when you start but you
need to get way down to the bottom of that iceberg where all the the sensitive
functionality probably is.
-oh yeah absolutely I get it so instead of just
poking around on the outside..
Access Privileges comes in play. Me
personally, what I do is that I you spin up burp and then i spend an hour
or two just walking through the website and trying different kind of things
logging out, logging into another user doing it again, and then eventually I’m
replaying these sessions to see if I’m able to do something as an unprivileged
user and then eventually as an admin – That’s exactly what I do in fact there’s
there’s some burp plug-ins for that kind of stuff but but I just keep everything
marked by hand honestly you sort like a spreadsheet or something and I say X
user can do x and y user can do Y and let’s see if they can do stuff to each
other and that’s the beginning of like my access control testing part which is
like the second tip I usually give people access control bugs and IDOR’s
are really important to to look for in bounty programs because there’s no like
library that fixes those types of bugs if you think of injection bugs a
patch couldn’t fix could fix an injection bug you know applying a
third-party library can fix cross-site scripting bugs but it’s really hard to
fix access control bugs And they are all logical right? yeah all logical – Cool.
Alright so next one.
yeah so when you’re on the site you’re gonna want to see how the site references you as a
user right it’s not it’s not always the cookies that register what you’re
doing or what you’re allowed to do on the site sometimes you know there’s a
unique identifier passed either in the URL or in some parameters someone
identifies you and that’s the first place I look for IDOR’s and stuff
like that but shortly after that its File uploads.
have found a majority of bugs this year on functionality for file uploads so when you log into the
application there’s always like a profile page on
enterprise application stuff or your image when I’m looking at a site I want
to find all the file uploads and identify them right there’s our RCE’s
where you piggyback command injection like image tragic and embedding
JavaScript inside of files you know there’s XML entity injection if if the
file format is based on XML like Word docs and stuff like that so file uploads
have just like a crazy amount of attack surface based on them and so I look at em. And its so challenging for people just to make sure that they sanitize it
all right and this is all that is also where some of the really golden goose
bugs appears it’s a great area to put a lot of research in I spend shit loads of
time you’re designing PDFs payloads inside them manually and I
learned how to write PDFs by hand now it’s a lot of waste of time but then
again my payloads are mmmm´ they are mint.
– yeah and then you
have next time right like once you put the investment in to make the template
for one of those uploads like you have it for next time – in fact mario from
cure 53 they have a repository that you can start with it’s got a on Cure 53s
github there’s a project where they have a whole bunch of file formats that have
XSS attacks in them and you can move off there and start modifying creating your
own directory for file formats and bugs associated to them.
XXEzzzz..
yeah and the other tip there is a lot of days you’re not gonna get the direct feedback
from those types of bugs where the the application view actually shows you
that you have a bug, alot of them are blind nowadays right and what I do is I use
named in certain ways and use unique DNS
lookups for them and have this excel sheet where I overtime just log traffic
to my DNS server so I receive something hits and I know I remember that one
that’s like a month ago since I put that one in and then they you spun
it up again and this shit fucking happens..
Awesome.. alright so third place
where to look now? – what I’m doing is I’m looking at all the parameters and all of
the endpoints that took data so those are called dynamic parameters right and
I’m looking at with what kind of data they took was it a string was it a you
know was an alpha numeric was it just numerals and then eventually the places
that actually take paths and URLs and parse them parameters I’m gonna look at
those very very strictly for bugs like SSRF, local file includes, path
traversal, remote file includes any place that parses a path or a page
or references another place I’m gonna pay special attention to.
– if you are totally new at this, where would you recommend people to start.
um so a lot of times when you get into an application you know there’s an integration section
if it’s an enterprise application they’re trying to hook up other services
to their own site like a lot of fortune 100 companies use API is to pull in all
kinds of stuff. aaah. so its cross-platform
right so in that section of the app first to see if there’s any integrations
that they want to hook up via either web hook those are likely vulnerable, those
integration places are likely vulnerable to SSRF’s I see them a lot of times.
– And those are primarily not always automatable right, so it takes you a
little bit tweaking? it takes me alot of tweaking to find them. And if anyone
tells you SSRF’s are easy they are lying right, unless youre or generic SSRF payload really work out
of the box right it’s either the padding has to be changed like you gotta do
double or triple like you know forward or back slashes you got to reference
your domain like an octal its like all this crazy stuff right so
like I have to play around with them alot very rewarding, but when they pop it’s like I… get goosebumps just thinking about it they are so amazing the the feeling you
have where you can see that it hits your collaborator or hits your DNS server you
know like oh yeah yeah yeah I’ve got something. FOUR: a lot of people focus on
RCE and bugs that I actually think that private data, leaking private
data can be just as damaging in fact most of my authentication bypass type
bugs or logic type bugs or whatever you want to call them so content discovery
is king in this world right basically looking to our hidden paths that are not
linked anywhere on the web site administration panels you know log pages
-Are we talking brute forcing here?
-yeah we’re talking about brute forceing. here yeah so I mean I use a list that I’ve published pretty exclusively to do my my brute
forcing and my content discovery – The Jason Haddix ALL.TXT?
I wonder if its that one? ;)))
– I use that in my content discovery, its a huge list. by finding stuff off that list.
so directory brute forcing is something you wanna you want to do.
– And also if you new try to save all the endpoints that you stumble upon to your list curate your
word list is key Jason crate has created one of the best
lists out there but you have to redefine it because that way you will bring
a unique perspective to each and every engagement you enter.
Yeah and there’s there’s some people out there doing cool research right like the asset note guys
naffy and shubs and michael over there they released the common speak
dictionary which is pretty cool the but as you go you know add add your own
stuff there add your own paths and links when a new open-source project comes out
parse all the paths and add them to your content discovery right eventually
someone’s gonna make a mistake with access control.
Final and last tip. (FIVE)
If you’re on an app that is a messaging platform right the security of
the messages themselves the text of the message is just as important to them as
leaking you know piece of credit card information or getting an RCE
right so like what other than technical vulnerabilities do
care about and that gives me more like space to work in the application if I’m
not just looking for tech bugs absolutely and I totally agree I’ve
found something really really really nice high paying bugs, non-technical stuff
that we just “lying” around there but it didn’t execute until you did certain
kind of step.. fun times okay so thank you very much Jason hopefully this
would be a couple of tips for anyone that’s hungry to get started and starting to
look for ways about testing and bug bounties.. Have a good one and I’ll see
you around buddy

2018 Demystifying Medicine: The opioid epidemic: how, where, and what can be done?

2018 Demystifying Medicine: The opioid epidemic: how, where, and what can be done?


>>WE ALWAYS COMMENT ON THE BROOKLYN BRIDGE FOR TWO REASONS. ONE, MY GRANDFATHER TOOK THE PICTURE AND IT’S A WONDERFUL LOGO FOR WHAT THIS COURSE IS ABOUT. LINKING UP THE ADVANCES IN ENGINEERING AND BIOLOGICAL SCIENCES AND MEDICINE, ON THE OTHER HAND AND WE’RE LIKE THE FELL FELLOS FELLOWS ON THE CATWALK. THE ABSENCE OF THIS KIND OF A BRIDGE, I THINK, CONSTITUTES ONE OF THE BIG PROBLEMS WE HAVE IN MEDICINE, SCIENCE AND WE DON’T ALWAYS SPEAK A LANGUAGE ANYONE CAN UNDERSTAND OR WE CAN UNDERSTAND WITHIN DIFFERENCES. THERE’S THERE’S AN ADDITIONAL ASPECT. IT’S NOT ONLY A MATTER OF RESEARCH AND SCIENCE BUT MEDICINE AND PATIENTS.>>THERE’S A POWERFUL INFLUENCE OF SOCIETY AND POLITICS AND OF PLANNING AHEAD RATHER THAN BEING REACTIVE. IT’S CALLED AN EPIDEMIC BECAUSE MANY PEOPLE ARE INVOLVED BUT AN EPIDEMIC TO WHICH WE REACT TO AN OCCURRENCE BUT WE DON’T SEEM TO BE GOOD IN THE ANTICIPATING EPIDEMIC OF THIS TYPE AND ESTABLISHING OTHER POLICIES THAT PREVENT IT FROM OCCURRING IN THE FIRST PLACE. MANY PEOPLE HAVE ASKED WHAT IS INE — AN OPIOID. IT’S A CLASS OF DRUGS THAT INCLUDE MANY COMPONENTS. THERE ARE ILLEGAL DRUGS LIKE HEROIN AND SYNTHETIC DRUGS LIKE FENTANYL AND LEGAL PAIN RECEIVERS SUCH AS OXYCODONE AND HYPERCODONE AND MORPHINE OR ANY OTHERS. IS IT’S A CLASS OF DRUGS. AND THERE’S MANY CALLED CHINA LIGHT AND TNT AND THIS IS FENTANYL. I THINK IT’S THE MOST EFFECTIVE PAIN RELIEF MEDICATION THAT’S EVER BEEN CREATED. IT WAS SYNTHESIZED BY A CHEMIST WHO FORMED A PHARMACEUTICAL AND IT WAS GIVEN INITIALLY FOR ATHES THESIA AND APPROVED BY THE FDA. IT’S INTERESTING TO READ SOME OF THAT BECAUSE THERE’S STATEMENTS THAT INDICATE IT SHOULD NOT BE VERY ADDICTIVE AND IT APPEARED IN DIFFERENT FORMS AS IN PATCHES FOR RELIEF. IT TURNED OUT TO BE ONE OF THE MOST ADDICTIVE SUBSTANCES KNOWN. NOW MOST COMES FROM THE UNITED STATES BUT FROM CHINA SMUGGLED IN FROM MEXICO AND CANADA AND IT’S OFTEN MIXED WITH OTHER DRUGS FOR ADDED EFFECTS. AND THE PROPERTIES ARE SUBSTANTIAL. SO FENTANYL AND THE OTHER DRUGS ARE PART OF THIS EPIDEMIC WHICH HAS SHOWN TO HAVE ENORMOUS LETHALITY AND FINALLY HAS AWAKENED THE ALMOSTS OF THE BRIDGE, I ALLUDED TO, TO SOLVE SOME OF THE BIG QUESTIONS. HOW DIT START, WITH WHAT DOES IT CONSISTENT OF AND THE UNDERLYING SCIENCE AND CAN IT BE CONTROLLED AND WHAT CAN WE DO ABOUT IT. WE’RE EXTREMELY FORTUNATE TO HAVE TWO LEADERS IN THE GLOBAL DISCUSSION OUR SPEAKERS TODAY. THE FIRST SPEAKER — WHO, I REMEMBER AS IF IT WAS YESTERDAY, IN MAY, 2003 BECAME THE DIRECTOR OF THE NATIONAL INSTITUTE OF DRUG ABUSE. THAT INSTITUTE SUPPORTS MOST OF THE WORLD’S RESEARCH ON ABUSE AND PREVENTION. SHE IS BEST KNOWN FOR HER IMPORTANT ROLE IN ESTABLISHING THE DRUG INSTITUTIABUSE ABUSE
INSTITUTE. SHE LOOKED AT THE EFFECTS OF DRUGS USED FOR ABUSE AND SIMILAR WORK IN THE NEUROBIOLOGY OF OBESITY. SHE GRADUATED FROM THE MEDICAL UNIVERSITY OF MEXICO AND WAS TRAINED IN PSYCHIATRY AND TRAINED IN UNIVERSITY AND SPENT MOST OF HER PROVINCIAL CAREER IN THE BROOK HAVEN NATIONAL LABORATORY IN NEW YORK WHERE HER MAJOR RESEARCH WAS DONE. AND CHAIRMAN OF THE MEDICAL DEPARTMENT AND A PROFESSOR IN PSYCHIATRY AND AT NYU AND A PROFESSOR AT THE MEDICAL SCHOOL IN STONY BROOK AND HAS RECEIVED AWARDS OF ALL DIFFERENT KINDS. SHE WAS ELECTED TO THE MEMBERSHIP IN THE INSTITUTE OF MEDICINE. HAS BEEN HONORED IN OTHER PLISES — PLACES AROUND THE WORLD. IT’S NOT VERY OFTEN I’VE HAD THE OCCASION TO INTRODUCE SOMEBODY WHO IS ONE OF THE TOP 100 PEOPLE TO SHAPE THE WORLD. ONE OF 20 PEOPLE TO WATCH THE MOST POWERFUL WOMEN IN 2017 AND AWARDS AND SURE IS KNOWN TO ALL OF YOU. SHE WILL SPEAK FIRST. OUR SECOND SPEAKER IS THE DIRECTOR OF NINDS, THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE. HE CAME TO NINDS AS A DEPUTY DIRECTOR IN 2007 AND BEFORE THAT WAS PROFESSOR OF NEUROLOGY AT HARVARD, VICE CHAIR OF NEUROLOGY AT THE MASSACHUSETTS GENERAL HOSPITAL. HE GRADUATE THE PERFECT THE — FROM THE UNIVERSITY OF CHICAGO MEDICAL SCHOOL AND TRAINED IN NEUROLOGY AND HIS RESEARCH HAS BEEN IN BASIC NEUROBIOLOGY AND CLINICAL TRIALS. HE HAS BEEN VERY ACTIVE IN ADDRESSING THE ISSUES INVOLVED IN THE SUBJECT WE’RE HERE ABOUT TODAY THE OPIOID CRISIS.>>IT’S A PLEASURE TO SPEAK WITH YOU ALL TODAY AND MY COLLEAGUE AND IT’S INTERESTING YOU HAVE A BRIDGE AND THAT CAN LEAD TO PLACES WE WOULDN’T GO BEFORE AND EXPAND OUR HORIZONS BUT THERE’S pBRIDGES BUT PAIN WAS THE BRIDGE TO THE OPIOID CRISIS WE’RE AT. I WANT TO USE THAT ANALOGY BECAUSE IT IS VERY DIFFERENT FROM ANYTHING ELSE WE’VE SEEN IN THE ADDICTION WORLD. WE HAVE CREATE THE WORST EPIDEMIC EVER AND THE CREATION STEPS FROM THE HEALTH CARE SYSTEM. AND IT’S COME FROM THE NEED OF PATIENTS SUFFERING FROM PAIN TO GET RELIEF FROM THEIR AILMENTS AND THE OTHER COMPONENT IS THE OPIOIDS ARE FANTASTIC DRUGS FOR TREATING ACUTE SEVERE PAIN AND THERE’S NOT MANY OTHERS OUT THERE. THESE TWO COMPONENT THE ACCESS TO MEDICATION THAT’S EFFECTIVE FOR PAIN IS ULTIMATELY WHAT LED THE HEALTH CARE SYSTEM TO BE OV OVER RELIANT AND CONTRIBUTE TO THE ADDICTION AND ABUSE. BUT IT’S BECOME MORE COMPLEX THAN THAT. I WANT TO START BY — I DON’T GET MANY OPPORTUNITIES SO I’LL TAKE THIS OPPORTUNITY TO HIGHLIGHT THE WORK IN TERMS OF THE ADDITION IS A DISEASE OF THE BRAIN. IT’S POSSIBLE AND I HAVE FOUR HERE AND IT’S A PLEASURE TO COME HERE. SO WHAT IS IT WE KNOW AND WHERE WE ARE? THIS ILLUSTRATES IT. YOU CAN SEE THE NUMBER OF FATALITIES PER HUNDRED THOUSAND INDIVIDUALS IN THE UNITED STATES. YOU HAVE THE HIGHEST MORTALITY RATES IN RED. IN 1999 THERE WERE TWO EPICENTERS ONE NEW MEXICO AND THE OTHER IN THE APPALACHIAN REGION. ADVANCE IT 17 YEARS AND YOU CAN SEE CREEPING THROUGHOUT THE UNITED STATES THE AREA THAT STILL HOLDS THE HIGHEST NUMBER OF FATALITIES IS THE APPALACHIANS AND NOW IT’S VIRGINIA AND KENTUCKY, OHIO, TENNESSEE AND NEW MEXICO AND YOU SEE THE NORTHERN EASTERN PART OF THE UNITED STATES AND FLORIDA. IT’S ENTERING INTO ALASKA AND SOME AREAS ARE MORE AFFECTED THAN OTHERS. THE GEOGRAPHIC DISTRIBUTION REFLECTS THE EPIDEMIC AND ITS ORIGINS. THEORIGINS RELATE, OF COURSE, TO OPIOIDS OPPOSED TO OTHER DRUGS LIKE AMPHETAMINE AND COCAINE AND THERE’S DRUGS THAT DESERVE THEIR RESPECTS THIS ACTIVATE THE RECEPTORS AWARDS THE REWARD PART OF THE BRAIN. AND THEY ARE LOCATED IN THE NETWORK RESPONSIBLE FOR PROCESSING AND PERCEIVING PAIN AND THAT INCLUDES CORTICAL AREAS THAT LOOKS AT THE PAIN AND IT ALLOWS FOR FILTERING OF PAIN AND THERE’S ANOTHER REGION DOWN THERE THAT IS NOT MARKED WHICH IS THE AMYGDALA RESPONSIBLE FOR EMOTIONS AND GIVES THE EMOTIONAL COMPONENT OF PAIN. AND THE OPIOIDS PLAY MULTIPLE ROLES. VERY IMPORTANT IN REGULATING PAIN AND PLEASURABLE RESPONSES. THOSE ARE FUNDAMENTALLY THE WAY THE BRAIN IS WIRED TO MOTE VIT OUR — POET — MOTIVATE SOMEONE. WHEN A MOTHER HOLDS AN INFANT IT’S REWARD BAG BECAUSE OF THE SYSTEM AND WHAT’S REMARKABLE IS WHEN SOMEONE IS IN A LOT OF PAIN AND THEY’LL BE EXPOSED TO A PAINFUL PROCEDURE TO TOUCH THEM AND IT’S THINGS WE DON’T NECESSARILY THINK BUT IS IMPORTANT. IT’S A SYSTEM THE OPIOIDS THAT REGULATE THESE IMPORTANT PROCESSES THAT RELATES TO ATTACHMENT THAT RELATES TO REWARD AND THINGS LIKE FOOD THAT ALLOWS US TO BE MOTIVATE AND CAN ALSO LEAD US TO ADDICTION. LIKE OPIOIDS, ALL THE OTHER DRUGS ARE ACTIVATING THE AREA AND BY DOING THAT, THEY RELEASE DO DOPAMINE LEAD TO OTHER SYSTEMS IN THE BRAIN THAT THEN MAKES YOU VULNERABLE TO IMPULSIVE AND COMPULSIVE BEHAVIORS. SOME ARE RELATE TO A COMMON EFFECT OF THE DRUG AND WE AND OTHERS HAVE SHOWN THE REPEATED STRAEGS OF ADMINISTRATION OF THE DRUGS ADMINISTRATION RELEASES THE RECEPTORS IN THE HUMAN BRAIN. SO DOPAMINE WHICH IS A NEUROTRANSMITTER WHICH IS INVOLVED WITH REWARD AND TAKE THE INFORMATION FROM RECEIVES SIGNALLED THROUGH THE ENDOGENOUS C CANALS AND TRANSLATES IT INTO A SIGNAL AND IT’S AT THE ESSENCE OF MOTIVATION AND THE DOPAMINE RECEPTOR SYSTEM ENABLES US TO REGULATE THE ACTIONS AND IT’S ONE OF THE MAIN SIGNALLING MECHANISMS RELATED TO THE RECEPTOR SYSTEM. WHETHER IT’S PAIN OR DOPAMINE OR HEROIN, YOU’RE INTERFERING WITH SELF-REGULATION AND CONTROL AND THIS IS COMMON IN ADDICTION. WE KNOW THE DRUGS WHICH CAN BE VERY HIGHLY EFFECTIVE AND HAVE THE EFFECT OF PRODUCING ADDICTION. WHAT WAS THE PROBLEM? WE HAVE HAD A PROBLEM OF HEROIN AND IT’S BEEN VERY LOW PREVALENCE AND HEROIN HAS TESTED FOR 20 YEARS UNTIL THE EPIDEMIC AND ONE WOULD SAY 300,000, 400,000 INDIVIDUALS. IT WAS STABLE. AND IT WAS THE PRESCRIPTION OF OPIOIDS THAT STARTED TO UNBALANCE THAT AND LOOK AT HOW RAPIDLY PRESCRIPTIONS WENT. I’M IDENTIFYING TWO CLASSES. THE ONES MOST FREQUENTLY PRESCRIBED, OXYCODONE AND YOU CAN SEE AS OF 2011 THERE WERE 219 MILLION PRESCRIPTIONS IN THAT YEAR PRESCRIBED IN THE UNITED STATES WHICH BASICALLY IMPLIED MOST MALES WOULD BE ABLE TO SUPPLY THEMSELVES FOR A MONTH AND CLEARLY WE’RE NOT AT THAT NEED AND THEY WERE NOT UTILIZED BUT IT LED TO A MARKET AND PEOPLE START TO SEEK THESE AS THE FAVORED DRUG OF ABUSE. AND THEY BELIEVED BECAUSE THEY WERE MEDICATION THEY WERE SAFER AND THAT’S WHERE EVERYTHING COLLAPSE. AND WE NOW RECOGNIZE THE PRESCRIPTIONS ISSUED IN THE UNITED STATES HAS TRIGGERED THE CRISIS. THERE’S BEEN AN AGGRESSIVE CAMPAIGN TO MINIMIZE THE PRESCRIPTIONS GIVEN TO PATIENTS AND WE HAVE STARTED TO SEE A DECREASE IN THE EQUIVALENCE PROVIDED TO PATIENTS. WE’RE GOING IN THE RIGHT DIRECTION. WE STILL HAVE A MASSIVE OVER PRESCRIPTION PROBLEM IN OUR COUNTRY. I THINK IT DESERVES EMPHASIS. THE FACT WE’RE OVER PRESCRIBING OPIOIDS DOES NOT MEAN WE’RE IMPROVING THE PATIENTS WITH SEVERE CHRONIC PAIN. THERE’S NO ASSOCIATION WITH IT OR DO WE KNOW THERE’S BENEFITS IN GENERAL TO OVER PRESCRIBING. WE KNOW FROM CLINICAL EVIDENCE, SOME PATIENTS FOR WHICH NOTHING ELSE WORKS WITH CHRONIC PAIN. YOU MAY JUSTIFY THE USE OF AN OPIOID MEDICATION BUT IT’S VERY RESTRICTIVE CIRCUMSTANCES THAT THESE MEDICATIONS SHOULD BE GIVEN FOR EVERY DAY MANAGEMENT OF CHRONIC PAIN. I WANT TO EMPHASIZE, IT DOESN’T MEAN THEY DON’T HAVE A VALUE. SEVERE CHRONIC PAIN THAT IS NOT PROPERLY TREATED HAS A VERY NEGATIVE OUTCOME AND HIGH RATES OF SUICIDE. WHAT HAS BEEN VERY FRUSTRATING AS WE’RE WATCHING THE OPIOID EPIDEMIC CLIMBING AND CLAIM MORE PEOPLE WHO ARE DYING IS DESPITE THE FACT WE’VE BEEN ABLE TO DECREASE THE NUMBER FOR OPIOIDS, WE HAVE NOT BEEN ABLE TO BRING DOWN THE NUMBER OF FATALITIES FROM OPIOID. THE OFFICIAL OF FATALITIES HAVE BEEN INCREASED AT THE RATE OF A 22% TO 25% INCREASE PER YEAR. IF YOU LOOK AT WHAT’S GOING ON, YOU HAVE AN UNDERSTANDING OF WHY THAT’S HAPPENING. LOOK AT THE PRESCRIPTION IN THE GREENISH LINE AND IT’S STILL GOING UP. SOME PEOPLE SAY IT’S STABILIZING AND SOME OF THE STATES LIKE CALIFORNIA OR ACTUALLY EVEN IN MASSACHUSETTS, THEY’RE SEEING A DECLINE IN OVERDOSES FOR PRESCRIPTION OPIOIDS. BUT HEROIN HAS STARTED TO INCREASE STARTING IN THE EARLY 2000s. VERY HIGH PURITY AND AS RESULT OF PEOPLE BECOMING ADDICTED AND THE ACCESSIBILITY AND THE LOWER COST OF THE DRUG THEY SHIFT FROM USING PRESCRIPTION OPIOIDS TO HEROIN AND IT’S INCREASING THE OVERDOSE OF FATALITIES AND THEN TO MAKE THINGS WORSE, THE BLOCK LINE IS RECENTLY PERHAPS, 2014, MAYBE 2015 WE’VE SEEN AN INCREASE IN THE NUMBER OF FACE — FATALITIES ASSOCIATED WITH PHEN NA — FENTANYL IT’S 50 TIMES MORE POTENT THAN HEROIN AND WHAT THE POTENCY MEANS IS YOU NEED A SMALL DOSE IN ORDER TO PRODUCE THE SAME EFFECT. WHICH MEANS IF YOU’RE A DRUG DEALER IT’S EASIER TO BRING OVER THE BORDER BECAUSE YOU CAN CARRY IT IN YOUR POCKET IN A LITTLE VIAL THAT CAN DISTRIBUTE OVER THOUSANDS OF DOSES AND WITH SYNTHETIC CHEMISTRY BECOMING MORE ADVANCED WE HAVE NEW DRUGS WITH GREATER POTENCY AND ONE MAIN ENTRANCE OF THEM IS THROUGH THE MAIL. MOST IS COMING FROM MANUFACTURERS IN CHINA. SOME IS STARTING TO COME DIRECTLY FROM CHINA OR INDIRECTLY TO MEXICO AND IT’S THE BLACK LINE RESPONSIBLE FOR THE MORE THAN DOUBLING OF THE EPIDEMIC IN THE YEAR. MASSACHUSETTS HAS SEEN A REDUCTION IN PRESCRIPTIONS BUT HAVE SEEN 80% OF THE BEDS FROM OVERDOSES IN MASSACHUSETTS ARE ATTRIBUTED TO FENTANYL AND THEY TRANSFERRING FROM PRESCRIPTION OPIOIDS TO HEROIN TO FENTANYL. AND WHAT OUR PREVENTION EFFORTS HAVE TO TARGET BOTH OF THESE STREET DRUGS. WE CANNOT ABANDON THE PRESCRIPTION OPIOID BUT WE NEED TO FOCUS ALSO ON THE ADDITIONAL STRATEGIES. THIS IS THE TRIANGLE WE NOW EMBRACE AT THE NIH AND BOTH WALTER AND I HAVE BEEN WORKING TO COME UP WITH SOLUTIONS FOR THE CRISIS. I’D LIKE TO PUT AT THE TIP OF OUR STRATEGY, PAIN MANAGEMENT. IF WE DON’T ADDRESS THE NEED TO ADDRESS PAIN THERE WILL ALWAYS BE A BLACK MARKET FOR DRUGS SINCE THEY CAN BE LIFE SAVING BUT WE NEED TO ADDRESS THE STRATEGIES IN ORDER TO PREVENT AND TREAT PEOPLE THAT BECOME ADDICTED AS WELL AS PREVENT AND TREAT THE OVERDOSES BECAUSE THAT IS THE MAIN DRIVER OF THE FATALITIES. AND WE’LL DISCUSS THE ISSUE OF PAIN AND WHAT OUR STRATEGY AS A WHOLE IS TO COME UP WITH ALTERNATIVE TREATMENTS THAT ARE SAFER AND AS EFFECTIVE AS OPIOID MEDICATIONS AND HOPEFULLY MORE EFFECTIVE FOR MANAGEMENT OF CHRONIC PAIN BECAUSE WITH OPIOIDS WE BECOME RAPIDLY TOLERANT WHICH IS A CHALLENGE BECAUSE YOU NEED HIGHER AND HIGHER DOSES. THE HIGHER DOSE YOU NEED THE GREATER THE RISK OF ADDICTION AND OVERDOSE. THIS IS WHERE THE BEAUTY OF SCIENCE IT. IT SHOWS WE CAN NOW UNDERSTAND HOW IT INTERACTS WITH THE RECEPTOR. IN THE PAST WE ASSUMED THE PATH WAYS AND IN FACT ONE OF OUR GRANTEES IS COMING UP WITH REMARKABLE DATA SHOWING AND PERHAPS ADDRESSING THE QUESTION AND SAYING WE KNOW THE ENDOGENOUS RECEPTOR IS FOR PAIN BUT WHY HAVE WE BECOME TOLERANT SO A NEW PAPER SHOWS THE ENDOGENOUS PEPTIDES BINDING TO THE RECEPTOR ARE SIGNALLING WHEN THEY GET INTERNALIZED INSIDE THE CELL AND THE SIGNALLING PROCESS IS DIFFERENT FROM THAT OF THE CURRENT DRUGS. AGAIN, I’M PROVIDING BY THIS KNOWLEDGE ONE CAN LOOK AT THE MECHANISMS OF TOLERANCE. AND THIS IS A DIFFERENT CONCEPT WHICH IS NOW BEING FOLLOWED UP BY THE PHARMACEUTICAL INDUSTRIES AND THAT WOULD BE DEVOID OF THE EFFECTS OF MOST OPIOID DRUGS THAT TAKES ADVANTAGE INTO ENGAGING THE SYSTEM BUT NOT THE INTRACELLULAR RESTING ONE. WHETHER IT’S SUCCESSFUL OR NOT WE’LL FIND OUT SOON BECAUSE THE COMPOUND IS A CLINICAL TRIAL AND EVALUATED. AND I WANT TO LOOK TO THE TREATMENTS. THERE’S THREE CLASSES. THREE MEDICATIONS. MORE THAN FOR BASICALLY ALL THE OTHER DRUGS OF ABUSE OTHER THAN ALCOHOL AND TICK — NICOTINE AND ONE HAS FULL EFFECTS THEN WE HAVE A PROTAGONIST AND YOU HAVE TO AND YOU HAVE TO [AUDIO DIFFICULTIES]>>AND THEY’VE BEEN SHOWN TO DECREASE OPIOID USE AND DECREASE CRIMINAL ACTIVITY AND TRANSMISSION SUCH AS HIV, HEPATITIS C AND RETAINING TREATMENT AND THEY’RE NOT BEING USED AND IF YOU GO INTO BASICALLY OBSERVE THROUGHOUT THE UNITED STATES, TREATMENT PROGRAMS THAT ARE FOR OPIOID USE DISORDERS LESS THAN ONE-THIRD OFFER ACCESS TO MEDICATION AND IT’S THE STIGMA. THE STIGMA BRAIN. AND IT REACTS TO THE EFFECTS. THE FASTER THE EFFECTS THE MORE THE REWARD AND WHEN YOU INJECT THE DRUG IT’S MORE ADDICTIVE BECAUSE THE SLOWER ROUTE SLOWS THE PHARMACOGENETICS AND IT’S THE CRAVING THAT EMERGES IN THE OPIOID SIGNALLING SYSTEM THAT HAPPENS WHEN THE MORPHINE DISASSOCIATES. SO THERE’S LOTS OF MISUNDERSTANDING OF HOW THE MEDICATION WORKS THAT HAS LED TO PEOPLE NOT UTILIZE IT TO THE EXTENT AND THEY’RE EFFECTIVE AND ONE OF THE BIG STRATEGIES IS HOW DO WE IMPROVE ACCESS TO THE MEDICATIONS. THERE’S ANOTHER CAVEAT WE HAVE TO RECOGNIZE. AS EFFECTIVE AS THEY ARE, THEY STILL HAVE A RATE OF PEOPLE ON TREATMENT. 50% WERE RELAPSING IN SIX MONTHS. YOU THINK THAT’S A BIG RELAPSE RATE BUT IF YOU DON’T TREAT THEM 95% WILL RELAPSE IN ONE WEEK, IF NOT THREE DAYS. THE DIFFERENCES ARE VERY LARGE. AT THE SAME TIME, THAT IS CONSTRAINED. 50% RELAPSE IN SIX MONTHS IS NOT ACCEPTABLE BECAUSE PATIENTS HAVE A HIGH RISK OF OVERDOSE WHEN THEY RELAPSE. HOW DO WE IMPROVE THE NUMBERS TO DECREASE THE RELAPSE RATES? LET’S START WITH THE CAS INDICATED — CASCADE OF OPIOID USE DISORDER AND THERE’S PRESCRIPTION OPIOIDS AND FENTAN FENTANYL. WE HAVE DIAGNOSED TWO OF THIS — TWO-THIRDS AND OF EVERY STEP OF THE WAY YOU SEE THE ENORMOUS AMOUNT OF GAP, THE HUGE GAP THAT EXISTS BETWEEN WHERE WE SHOULD BE AND WHERE WE ARE AND IF WE NEED TO SOLVE THE CRISIS WE HAVE TO REDUCE THAT GAP DRAMATICALLY AND THE OTHER IS YES, WE WANT TO HAVE TREATMENT TO MAKE IT EASIER FOR INDIVIDUALS TO BE COMPLIANT WITH THEIR MEDICATION AND WE’RE FAVORING EXTENDED-RELEASE FORMULATIONS BECAUSE THEY’RE LOW-HANGING GROUP. IF YOU DON’T HAVE TO THINK OF GOING TO A METHADONE CLINIC ON A DAILY BASIS, IF YOU’RE TRYING TO RECOVER AND START WORK, THIS IS EXTREMELY DIFFICULT TO DO. HOW CAN WE MAKE IT AN EASY FORMULATION. THERE ARE OTHER STRATEGIES FROM DRUG COMBINATIONS TO NEW TARGETS TO VACCINES TO OTHER TREATMENTS. AND THERE’S AN EXAMPLE OF HOW SUCCESSFUL IT CAN BE IS THE FORMULATION FOR THE DRUG AND IT GOES BY THE TERM OF VIVITROL AS A TREATMENT FOR THE DISORDER. AND YOU HAVE OPIOIDS IN PLACEBO AND IN VIVITROL THERE WERE CLOSE TO 90% WHO WERE ABLE TO BE COMPLETELY ABSTINENT DURING THE PERIOD OF THE TRIAL CLOSE TO SIX MONTHS. RECENTLY, WE’VE PARTNERED WITH RAYBURN TO DEVELOP A SIX-MONTH IMPLANT TO MAKE IT EASIER FOR THEM TO BE COMPLAINT WITH THE MEDICATION AND THIS WAS APPROVED IN MAY 26, 2016. IT CAN ONLY DELIVER EIGHT MILLIGRAMS AND MOST PATIENTS REQUIRE 16 AND 20 MILLIGRAMS SO IT CAN ONLY BE USED IN WHAT IS ESTIMATED TO BE 20% TO 30% OF PATIENTS THAT CAN TOLERATE SUCH A LOW DOSE. AND THIS IS DATA FOR VIVITROL TO COMPARE TREATMENT VERSUS THE ROW LAPSED TREATMENT AND YOU CAN SEE THE DIFFERENCES IN THE MEDICATION AND YOU LOOK AT HOW EFFECTIVE THEY WERE. AND THIS IS SOME OF OUR BEST MEDICAL CENTERS IN THE UNITED STATES LINKED TO THE CRIMINAL JUSTICE SYSTEM AND THIS IS NOT BASED ON HIGH RATE OF MORTALITY. THERE WERE NONE TREATED WITH VIVITROL. HIGHLIGHTING THE IMPORTANCE OF EXPANDING ACCESS TO THESE MEDICATIONS AS A WAY TO PREVENT FATALITIES. IN THE MEANTIME, WE ARE ALSO AWARE AS A RESULT OF RESEARCH WE HAVE COME TO UNDERSTAND THE CHANGES IN THE BRAIN THAT OCCUR WITH ADDITION AND HAVE BEEN ABLE HOW THEY RELATE TO THE CONTROL D AND WHETHER IT’S ALCOHOLISM AND WE NOW LOOK AT IT AS HTARGETING AS MOLECULAR TARGETS OR STIMULATION TECHNOLOGIES SUCH AS MAGNETIC STIMULATION AS A MEAN TO MODULATE THE SEQUENCE. THAT’S RESEARCH THAT IS ONGOING. AND AN AREA WE’VE DONE RESEARCH AS IT RELATES TO LOOK AT VACCINES OR PASSIVE IMMUNIZATION AGAINST DRUGS. THE IDEA IS LIKE WITH ANY OTHER DRUG. YOU VACCINE AGAINST HEROIN OR FENTANYL AND YOUR BODY PRODUCES ANTIBODIES THAT ARE CIRCULATING IF THE DRUG SO WHEN YOU TAKE THE DRUG AND IT’S IN YOUR BLOOD, THE ANTIBODIES BIND TO THE DRUG AND THIS INTERFERES WITH THE PASSAGE TO THE BLOOD BRAIN BARRIER AND THE DRUG IS SEQUESTERED AND CANNOT LEAVE THE BLOOD. IT WORKS WELL. WE CAN PREVENT THEM FROM TAKING DRUGS AND FROM DYING FROM FENTANYL OVERDOSES IN MICE. THE BIG CHALLENGE IS TO TRANSLATE THIS TO HUMANS WHICH WERE LOOKING AT THE VACCINES WHICH HAVE NOT BEEN STRONG ENOUGH TO PREVENT THE DRUG FROM ENTERING THE BRAIN IN SUFFICIENTLY HIGH QUANTS. AND NOW THE PASSIVE IMMUNIZATION CAN GENERATE HIGHER ANTIBODIES IS ANOTHER STRATEGY THAT IS LIKELY TO BE EASIER TO APPLY. RESEARCHERS ARE WORKING AT IT AND ANTIBODIES HAVE BEEN FORMED TO TACKLE HEROIN AND FENTANYL ANIMALS.VENTS FATALITIES IN – THAT IS FROM THE MEDICATION DEVELOPMENT. FROM THE PERSPECTIVE IN THE NEEDS OF PATIENTS TO GIVE THEM ACCESS TO MEDICATION. IF YOU LOOK AT THE NUMBER OF SPECIALIZED TREATMENT CENTERS IN OUR COUNTRY YOU’LL FIND OUT THEY’RE NOT SUFFICIENT TO TAKE CARE OF PATIENTS AND THOSE IN THE HEALTH CARE SYSTEM RECOGNIZE THAT BECAUSE PATIENTS ARE COMING TO THE HOSPITAL AND THERE’S NOT SUFFICIENT TREATMENT PROGRAMS. THE HEALTH CARE SYSTEM AND THE HEALTH CARE SYSTEM ITSELF HAS START TO COME UP TO ADDRESS THE NEED OF PATIENTS SUFFERING FROM AN OPIOID USE DISORDER AND WE HAVE DEVELOPED NEW MODELS OF CARE THAT TAKE ADVANTAGE OF SYSTEMS WHERE PATIENTS CAN BE TREATED. WE FOCUS SPECIFICALLY IN TWO SYSTEMS THAT INCREASE ALL OVER THE UNITED STATES. THE HEALTH CARE SYSTEM AND THE CRIMINAL JUSTICE SYSTEM AS ONE THAT WE CAN ENROLL IN TO GETTING ACTIVE IN THE SCREENING OF INDIVIDUALS WITH OPIOID USE DISORDER. THIS IS AN ILLUSTRATION OF TWO APPROACHES THAT ARE BEING DONE. AGAIN, THE IMPLEMENTATION STRATEGIES FOR DELIVERING IN THIS CASE, DIFFERENT DRUGS AND YOU CAN SEE EMERGENCY ROOM ADMISSIONS AS A FUNCTION OF THE ENROLLMENT FROM PHYSICIANS WORKING IN CLOSE COLLABORATION WITH NURSES. THIS IS IMPORTANT BECAUSE IT’S A MODEL THAT SUS STAINS US. AS WE RECOGNIZE HOW MANY PEOPLE REQUIRE TREATMENT WE HAVE TO LOOK AT BROAD ACCESS TO PATIENTS SUSTAINS THE ABILITY. AND YOU CAN SEE IN SIX MONTHS IN PURPLE AND AT 12 MONTHS AND 12 MONTHS VERSUS THE EMERGENCY ROOM ADMISSIONS BEFORE THE OPE NEF RIN — THE DRUG HAS BEEN IMPLEMENTED IN THE STATES OF MASSACHUSETTS WHICH HAS BEEN ONE OF THE MOST ACTIVE IN ENROLLING THE AGENCY IF THE TREATMENT OF OPIOID USE DISORDER. ON THE RIGHT IS ANOTHER STRATEGY FOR THE SYSTEM. THEY DID A PILOT STUDY TO INVOLVING THE PHYSICIANS ON PRESCRIBING IT WHEN THE PATIENTS ENDED UP IN THE EMERGENCY DEPARTMENT. WHAT THEY SHOW IS WHEN THEY DID THAT, THAT SIMPLE INTERVENTION OF INITIATING THE DRUG IN THE EMERGENCY DEPARTMENT OPPOSED TO A BRIEF INTERVENTION THEY DECREASED THE USE AND INCREASED THE TREATMENT AND PATIENT FACILITIES. NOW WE’RE DOING A MULTIPLE CLINICAL TRIAL INVOLVING SITES IN THE UNITED STATES TO IMPLEMENT THE ADMINISTRATION TO PATIENTS WHERE IT’S A UNIQUE OPPORTUNITY TO BE ABLE TO ENGAGE THEM TO TREATMENT. WE’RE SEEING MORE AND MORE PEOPLE BEING REVERTED FROM AN OVERDOSE IN RESPONSE TO NALOXONE AND REPEATED OVERDOSES, IN MANY INSTANCES, 10, 20, 30 IN A YEAR AND WHEN A PATIENT OVERDOSES THE LIKELIHOOD OF A REOCCURRENCE IS HIGH. IF YOU END UP IN AN EMERGENCY ROOM WITH AN OVERDOSE OF OPIOID WHAT IS THE LIKELIHOOD OF SOMEONE DYING AND 10% OF PATIENTS WILL BE DEAD WITHIN A YEAR. THESE ARE PATIENTS THAT ARE NOT PROTECTED FROM DYING AND THEY ARE CREATING MODES OF CARE WHETHER YOU CREATE THE BREACH THAT WILL BRING THEM INTO THE TREATMENT. IT SEEMS TO BE SOMETHING THAT COULD DECREASE THE HIGH MORTALITY ASSOCIATED WITH THE EPISODES. SOME INDIVIDUALS ARE AT HIGHER RISK OF THE DRUG. AND WHETHER ONE STARTS WITH THE CRIMINALIZATION OF DRUG ADDICTION WHICH WE DON’T SUPPORT. IF YOU’RE GOING TO PUT THEM IN JAIL, WHAT IS CLEAR IS YOU SHOULD TREAT THEM. OU IMPACTFUL THAT IS, THIS IS A STORY FROM ENGLAND IN WHICH THEY AGGRESSIVELY INITIATED TREATMENT SYSTEM AND WHEN THEY DO THAT, – THEY’LL BE TREATED WITH THE REDUCTION IN MORTALITY IN THE FIRST YEAR WHERE THEY DID SOMETHING SIMILAR THEY INITIATED THE TREATMENT THROUGHOUT THE PRISON SYSTEM IN RHODE ISLAND AND WHAT THEY SHOWED WAS THAT IMPLEMENTATION PRODUCED A SIGNIFICANT RELEASE DECREASING TE NUMBER OF OVERDOSE DEATHS. AT THE POPULATION LEVEL, 12.5% DECREASED AND THE REST OF THE COUNTRY IS INCREASING AND IF YOU LOOK AT THE INCREASE IN MORTALITY OF THOSE WHO LEFT THE PRISON SYSTEM, THEY DECREASED IT BY 50% COMPARED TO 2016. HIGHLIGHTS THE UNIQUE OPPORTUNITY WE HAVE TO ENSURE THERE IS TREATMENT IN THOSE WHO HAVE AN OPIOID USE DISORDER IN JAIL AND CREATE A PROGRAM SO WHEN THEY LEAVE THEY’RE LINKED WITH A HEALTH CARE SYSTEM AND WE’RE PROMOTING RESEARCH. THE LAST SERIES OF SLIDES COME FROM ANOTHER ASPECT WE DON’T DWELL MUCH ON. HAVE YOU DATA FROM 2016 FOR DRUG POISONING DEATHS. IT ILLUSTRATES THIS IS INCREASED IN POPULATIONS OF POVERTY AND IT’S DECREASED IN A LIFE TIME EXPECTANCY OF AMERICANS LIVING NOW OPPOSED TO OTHER AREAS OF THE WORLD WHERE BASICALLY LIFE EXPECTANCY AND THOSE WHO HAVE SIMILAR OR LOWER ECONOMIC BACKGROUNDS IS INCREASING AND THERE’S SIGNIFICANT DECREASES IN SUICIDE AND TREATMENT. THESE ARE DISEASES OF DESPAIR. IT’S IMPORTANT TO THINK ABOUT. AS WE DISCUSSED IN HOW WE PREVENT OVERDOSES, WE HAVE TO KEEP OUR EYES ON THE INDIVIDUALS THAT ARE BORN OUT OF CONDITIONS WHERE HOPELESSNESS AND VULNERABLELESS MAKE THEM MORE PRONE TO TAKING DRUGS AND I CANNOT THINK OF ANY OTHER IMAGE THAT CAN PORTRAY THE SENSE OF DISTRESS AND DESPAIR THIS HAS GENERATED IN THE COUNTRY. THANK YOU VERY MUCH.>>THANK YOU. THAT WAS GREAT. YOU SHOWED A CORRELATION BETWEEN THE OVERDOSE ASSOCIATED DEATHS AND THE INCOME OF THE PEOPLE AND HOW IT WORK WITH THE INCOME OF THE AREA. IS IT PEOPLE ARE DYING BECAUSE THEY’RE NOT RECEIVING PROPERTY TREATMENT?>>THIS IS AN EPIDEMIC. WE’RE GETTING PEOPLE THAT ARE BECOMING ADDICTED AND DYING AND THEY’RE GETTING MEDICATIONS AND THEN THEY OVERDOSE. WE’RE SEEING MORE WHITE WOMEN DYING BECAUSE THEY HAVE MORE ACCESS TO TREATMENT AND THEY HAVE ACCESS TO OPIOIDS. WE’RE SEEING IN AREAS LIKE APPALACHIA THERE’S NOT MANY ALTERNATIVES. PEOPLE DON’T HAVE A GOOD EDUCATION. AND GIVE THEM OPPORTUNITIES TO LOOK FORWARD. IF YOU DON’T HAVE ANY THE LIKELIHOOD YOU WOULDN’T ENGAGE ON THIS TYPE IS HIGHER. THE GREATER STRESSORS YOU HAVE IN YOUR LIFE THE LESS YOU HAVE THE OPPORTUNITIES FOR DEVELOPING YOURSELF. THEN THERE’S AN OPPORTUNITY FOR EXPLORATION WHERE A YOUNG PERSON AND YOU SEE THE ABILITY OF MALES ENGAGING IN RISKY BEHAVIOR IN CERTAIN STAGES OF THEIR LIFE AND THERE’S RANDOMNESS AND FRIENDS SAY YOU HAVE TO TRY THIS DRUG AND THEY TRANSITION. WHAT I JUST WANTED TO SHOW IS WE TEND TO FORGET THAT COMPONENT OR THE SOCIAL ASPECT OF ADDICTION. AND HOW IMPORTANT IT IS FOR US TO PREVENT PEOPLE FROM BECOMING ADDICTED. WE ALSO HAVE TO RECOGNIZE WE HAVE TO DO PREVENTION FROM PEOPLE EXPERIMENTING FROM DRUGS AND STARTING TO GET INVOLVED WITH DRUGS SUCH AS FENTANYL. IT’S BOTH SIDES. THIS IS THE ONE THAT’S FORGOTTEN. [INDISCERNIBLE]>>IN OPIOID WITHDRAWING WE UNDERSTAND THE INTRACELLULAR MECHANISMS ARE COMPLETELY DISRUPTED. THAT’S ONE OF THE MECHANISMS ASSOCIATED WITH THE WITHDRAWAL AT THE CELLULAR LEVEL. WE ALSO — THERE IS ALSO ADAPTATION AT THE NEUROCIRCUITRY LEVEL THAT CREATE A STRESS RESPONSE WITH THE HYPOTHALAMUS AND AMYGDALA AND THE OTHER ENDOGENOUS SYSTEM INVOLVED IN THE NEGATIVE ASPECTS IS THE RECEPTORS. I SPOKE ABOUT THE RECEPTOR AND THAT IS IS AN AVERSE SIGNALLING COMPONENT. WHERE THE OPIOID SYSTEM IS REWARDING. THE SYSTEM IS RESERVIVE. IT CAN CREATE A DYSPHORIA WHEN SOMEONE IS IN WITHDRAWAL.>>WHY [QUESTION INAUDIBLE]>>WE HOPE TO UNDERSTAND THE MEC NICHES THAT LEAD TO THIS AND ALLOW US TO ACCELERATE THE MEDICATIONS FOR PAIN AND OPIOID USE DISORDER. THAT’S OUTSIDE OF OUR CONTROL RIGHT NOW. THIS HAS BECOME ONE OF THE PIRATES OF THE NIH AND BRING TOGETHER THE DIFFERENT AGENCIES BECAUSE IT WON’T BE SOLVED BY ONE AGENCY.>>YOU MENTION THE LAP RATE IS HIGH. DO WE UNDERSTAND WHAT WE KNOW ABOUT THE DRUG RESISTANCE IN A WAY ON THIS SITUATION. YOU HAVE SOMEONE ON ANTIDEPRESSANT AND DOING WELL AND THEN RELAPSE. THE RELAPSE RATE CAN BE CLEARLY ASSOCIATED WITH ANOTHER STRESSOR. A LOVED PERSON DIES AND THE STRESSOR CAN LEAD YOU TO RELAPSE. AND I THINK IT DOES MAKE SENSE THERE MAY BE A TOLERANCE MECHANISM. THERE’S NOWHERE TO ANSWER THAT QUESTION.>>IS THERE A LINK BETWEEN THE LEGALIZATION AND MARIJUANA AND THE OVER OUTILIZE UTILIZATION OF
THE STREET DRUGS IN COMBINATION WITH FENTANYL. THE INTERACTION WE LIKE TO SAY THERE ARE TWO PAPERS THAT LOOK AT THE DATA ON MEDICAID AND MEDICARE IN WHICH THEY SHOW INDIVIDUALS THAT CAME FROM STATES WHERE THEY HAD LEGALIZED MEDICAL MARIJUANA REDUCED THE NUMBER OF OPIOID PRESCRIPTIONS AND THE THOUGHT WAS YOU SHOULD MAKE MARIJUANA MEDICALLY LEGAL. I DO NOT NEGATE THAT IN SOME PATIENTS THIS MAY BE THE CASE. I THINK IT NEEDS TO BE TESTED AND THERE’S DATA THAT SHOWS THOSE INDIVIDUALS THAT WERE SMOKING MARIJUANA THEY WERE MORE LIKELY ONE OR TWO YEARS LATER TO BE ADDICTED TO OPIOIDS. IT WAS A PRIMING EFFECT TO MAKE YOU MORE VULNERABLE TO THE ADDICTIVENESS. YOU CAN HAVE A POPULATION THAT IS BASICALLY EXPERIMENTING ON USING IT RECREATIONALLY INCREASING THE LIKELIHOOD OF ADDICTION AND INCREASES THE LIKELIHOOD OF AN OPIATE. WE NEED TO DO BETTER RESEARCH TO UNDERSTAND HOW THE CHANGES IN POLICIES ARE EFFECTING PATIENTS ON ADDICTION AND AT THIS TIME, A LOT OF THE INFORMATION IS ANECDOTAL OR LOOKING AT DATABASES SPEAKING AT THE MULTIPLE LEVELS.>>YOU SHOWED THE EXPRESSION PATTERNS IN HEALTHY INDIVIDUALS EARLY ON IN THE DOPAMINE RECEPTORS. DID THESE EXPRESSION PATTERNS EVER RETURN TO NORMAL AFTER THE PEOPLE PRESUMABLY MAKE A RECOVERY.>>WE SEE SOME PATIENTS RECOVER AND IN ANIMAL EXPERIMENTS THEY’VE SEEN THE RELATION OF THE DOPAMINE RECEPTORS ARE STILL PRESENT. IN RODENTS THERE’S A VIABILITY. WE KNOW IN A STRESSFUL ENVIRONMENT IT CAN IMPACT THE RECEPTORS. IT’S NOT JUST THE ONE TO ONE EFFECT. I’M GIVING THE MICROPHONE TO WALTER. pI’M SORRY.STIONS. THE DOCTOR WILL BE HERE AT THE END OF THE SECOND TALK. PLEASE SAVE SOME QUESTION.>>FORTUNATELY, I’LL HAVE TO BE QUICK. I HAVE TO GO TO THE AIRPORT. I JUST WANT TO SAY THE PROBLEM WE’RE IN NOW HAS BEEN REPEATED SINCE 3400 B.C. OPIUM WAS CULTIVATE AND HIPPOCRATES WROTE ABOUT IT AND WAS A PROBLEM ESPECIALLY FOR WOMEN, WHICH WE’LL TALK ABOUT AND IT SPREAD IN THE WORLD AND IN PERIODS OF EUROPE IT DISAPPEARED AND CONSIDERED TO BE AN EVIL TYPE OF AGENT. THEN IN THE 1500s THE DUTCH WERE ABLE TO GET THE CHINESE HOOKED ON SMOKING OPIUM. THEY BROUGHT OPIUM INTO CHINA AND ADDICT THE COUNTRY. THE CHINESE COUNTRY TRIED TO STOP THIS AND THE BRITISH DEFEAT THE CHINESE WHO WERE TRYING TO PREVENT THEM FROM SELLING OPIUM. THE BUSINESS OF CREATING ADDICTED POPULATIONS AND PEOPLE MAKING MONEY HAS BEEN IN HISTORY. IN THE U.S., OPIUM HAS BEEN THROUGHOUT OUR HISTORY. IT WAS USED FOR PAIN AND IN REVOLUTION WARTIME THERE WAS A BIG PROBLEM AFTER THE CIVIL WAR. IT WAS ESTIMATED 10 MILLION OPIUM PILLS WERE HANDED OUT TO THE WAR SOLDIERS. THE INTRAVENOUS SYRINGE WAS INTRODUCED AND START THE INTRAVENOUS INTRODUCTION OF MORPHINE AND CHEMISTS WERE ABLE TO PURIFY HEROIN AND IT WAS USED TO GET PEOPLE OFF MORPHINE. IT DIDN’T WORK SO WELL. IT LED TO A PROBLEM IN THE U.S. THE MORPHINE ADDICTION IN THE 1890s SUPPOSEDEDLY EFFECTED ONE
OF TWO AMERICANS SO WE’RE NOT AS ABOUT AS 1890. BUT THE USE OF INJECTABLE DRUGS IS MORE OF A PROBLEM NOW. WHEN I TRAINED HEROIN ADDICTION WAS COMMON IN THE AREA WHERE I WORKED. THE COMPLICATIONS OF HEROIN ADDICTION AND OVERDOSE DEATH WAS NOT THE BIGGEST PROBLEM IN THAT TIME FRAME. IT WAS INFECTIONS AND PEOPLE WOULD HAVE FOUR HEART VALVE SURGERIES AND THE VALVES GOT EFFECTIVE. THEY PUT A NEW VALVE IN AND THAT WOULD GET INFECTED. AND THEY TRAINED THE CARDIAC SURGEON OF CHICAGO. SO THIS HAS BEEN A HORRIBLE PROBLEM. HOW WE GET HERE IN THIS INSTANCE IS BECAUSE OF THIS COMMON CONDITION WHICH IS PAIN. IN THE U.S., 40 MILLION HAVE SEVERE PAIN AND 8 MILLION REPORT PAIN INTERFERES WITH LIFESTYLE AND THAT WAS A MOMENT TO TREAT PAIN AS THE FIFTH VITAL SIGN. WHEN YOU GO TO THE DOCTOR THEY ASK YOU HOW MUCH PAIN HAVE YOU ON THE SCALE OF 1-10. I NEVER HAVE NO PAIN. THEY SAID SHOULD WE TREAT? NO, OKAY. I’M FINE. IT LED TO MORE TREATMENT OF PAIN AND THIS WAS ALSO THE THOUGHT WAS IT WAS SO SLOWLY ACTING WAS IT GET PEOPLE HIGH OR ADDICTIVE. PHYSICIANS WERE STARTING TO GET PEOPLE ADDICT AND WHEN WE STARTED OUT 75% TO 80% OF PEOPLE GOING TO HEROIN WERE COMING OFF PRESCRIPTION OPIOIDS. NOW IT’S LESS THAN 50%. WE HAVE OTHER BAD ACTORS BRINGING IN FENTANYL TO MAKE MONEY OFF PRESCRIPTION MEDS AND NOW THEY’RE GOING STRAIGHT TO YOUNGER FOLKS GETTING STRAIGHT ONTO HEROIN AND FENTANYL. ONCE YOU TAKE THE DRUGS, YOUR BRAIN IS REWIRED AND IT’S A CHRONIC DISEASE AFTER THAT. THERE’S PAIN AND PLEASURE AS SOVEREIGN MASTERS. THEY’RE THE MOST PRIMITIVE FACTS THAT DRIVE BEHAVIOR. THAT’S WHY WE STAY AWAY FROM INJURY WHEN WE CAN. THE OPIOID SYSTEM IS INVOLVED IN PLEASURE AND PAIN. AND THEY USE SIMILAR PATH WAYS. FOR US TO TAKE ADVANTAGE OF SCIENCE TO BEAT WHAT HAPPENS IN 3400 B.C. WITH THE DISCOVERY OF OPIUM WE HAVE TO DISEN TANGLE THE TWO PROPHECIES. YOU CAN SEVERE PAIN. I DON’T KNOW IF PEOPLE WATCHED THE BOSTON MARATHON YESTERDAY BUT THERE’S A LOT OF PAIN IN THOSE PEOPLE BEFORE THE CROSS THE LINE. IT DOESN’T STOP THEM BECAUSE THE REWARD AND THE CHEMISTRY IN THERE ALL THE ENDORPHINS ARE DRIVING THE SYSTEM SO YOU CAN DECREASE WHAT YOU PERCEIVE IS THE PAIN. THE NERVE IMPULSE IN YOUR KNEES AREN’T AFFECTED THAT MUCH BUT HOW YOU DEAL WITH THE PAIN IS REDUCED BY THE REWARD SYSTEM YOU HAVE. WHEN YOU ADD IN THE OPIOID RECEPTOR THE ANTAGONIST DOESN’T WORK ANY MORE AND IT CAN DRIVE THE ANIMAL TO GET THE PLEASURABLE STIMULUS AND THAT IS BY ADDING IN THE OPIOID RECEPTOR. THE PAIN AND PLEASURE SYSTEM DRIVE BEHAVIOR AND THE OPIOID SYSTEM IS INVOLVED IN BOTH OF THESE. AND THE OPIOID SYSTEM IS NOT JUST USED FOR PAIN AND PLEASURE, BUT UNFORTUNATELY, IT’S ALSO USED IN OTHER NERVE SYSTEMS PARTICULARLY THE RESPIRATORY SYSTEM. THERE’S A PROBLEM WITH THE OPIOIDS IS THEY STRESS RESPIRATION AND YOU NEED LOW BLOOD PLEASURE AND THE DRUGS ON THE STREET THEY’RE CUTTING HEROIN WITH, PEOPLE STOP BREATHING BEFORE THEY FINISH THE INJECT. WE HAVE TO PIECE APART THE DIFFERENT PATH WAYS. AT NIH IN TERMS OF DEALING WITH THE PAIN, THERE’S A LOT OF INSTITUTES WHO WORK ON PAIN ACROSS NIH AND THERE’S A CONSORTIUM THAT EXIST AND WE HAVE AN INTERAGENCY PAIN COORDINATING COMMITTEE WHICH IS AGENCIES AND ADVOCATES AND PEOPLE FROM DIFFERENT COMMUNITIES OUTSIDE THE GOVERNMENT AND THEY WORK TO TRY TO GET BETTER PAIN CONTROL, LESS ADDICTION THROUGHOUT THE COUNTRY AND PUT OUT WHAT’S CALLED THE NATIONAL PAIN STRATEGY THAT IS A POPULATION MESSAGE AND LOOKING AT MANAGING PAIN BY DECREASING THE CHANCE OF ADDICTION. THERE ARE THINGS WE CAN DO TO TURN THE TIDE BACK TO LOOK AT THE INFORMATION THAT’S AVAILABLE NOW. THERE’S A GROUP THAT’S GOT THE FEDERAL RESEARCH STRATEGY WHICH GUIDES NIH AND THE RESEARCH THEY THINK IS IMPORTANT. SO A LOT OF IT IS PREVENTION. THE IDEA THAT THERE’S ACUTE PAIN. WE ALL FEEL ACUTE PAIN AND IN SOME PEOPLE IT GOES ON TO CHRONIC PAIN. SOME OF THOSE PEOPLE IT’S DISABLING. SO THEY NEED SOME TYPE OF TREATMENT TO BE ABLE TO FUNCTION BECAUSE OF THEIR CHRONIC PAIN. AND WHAT WE DON’T UNDERSTAND IS WHY SOME PEOPLE GO INTO SURGERY AND IT HURTS, NO QUESTION IT HURTS, A COUPLE WEEKS LATER, SOME ARE DOING BETTER, THREE MONTHS LATER YOU’RE BACK IN THE GYM AND OTHER PEOPLE HAVE CHRONIC PAIN THAT NEVER GOES AWAY AND REQUIRE QUOTE, UNQUOTE, OPIOIDS. THOUGH THE EVIDENCE IN OPE WROTES HELPS THE CHRONIC PAIN SITUATION WHICH SLIM OR NON EXISTENT. IT CAN HELP INTERMITTENTLY BUT MAY ALSO AGGRAVATE CHRONIC PAIN BECAUSE IF YOU’RE ON OPIOIDS AND TRY TO COME OFF THEM IT THE INDUCE THE CHRONIC PAIN. CONGRESS SAYS MY MOTHER WENT TO THE HOSPITAL AND THEY GAVE HER 180 VICODIN PILLS AND WHY’D THEY DO THAT? THEY WOKE ME MOTHER UP IN THE MIDDLE OF THE NIGHT AND ASKED IF SHE HAD PAIN AND INJECTED HER WITH PAIN MEDICINE. TRYING TO UNDERSTAND HOW WE CAN BEST MANAGE ACUTE PAIN IS IMPORTANT. A AND THE TRANSITION IS IF YOU KNOW WHAT HAPPENS GOING FROM ACUTE TO CHRONIC PAIN YOU CAN PREVENT IT. AT NIH THERE’S WORK ON THE PROGRAM TO TEACH PHYSICIANS ON THE BEST MANAGEMENT TEAM AND LOWERING THE ADDICTION POTENTIAL. AND YOU THINK ABOUT PAIN THERE’S LOTS OF DIFFERENT NODES IN THE SYSTEM. SO IF YOU THINK WAY OUT IN THE PERIPHERY YOU CAN HAVE PAIN AND THE RECEPTORS IN THE SKIN AND APPLYING A LIDOCAINE IS IMPORTANT IN BLOCKING OUT THE PAIN STIMULUS AND HAVE YOU THE NEXT NODE IN THE DORSAL
GANANGLION CELLS HAVE OTHER RECEPTORS. TURNS OUT THEY HAVE RECEPTORS FOR A GROWTH FACTOR WHICH WAS IDENTIFIED AND IT CAUSES FEWERO FEWERONS — NEURONS WERE TARGET AND THERE ARE RECEPTORS ON THE DORSAL ROOT GANGLION AND THEY ELEVATE YOUR PAIN RECEPTION. SO NOW THERE ARE COMPANIES WITH ANTIBODIES WHICH ARE QUITE POTENT AT PREVENTING PAIN AND THAT’S GETTING AWAY FROM THE ADDICTION SYSTEM AND IT GOES TO THE SPINAL SYSTEM AND THERE WITH KNOW AS AN ANIMAL DEVELOPS CHRONIC PAIN SYSTEM THERE’S A PLASTICITY OCCURRING AND THAT IS THE AVENUE WHERE WE THINK WE CAN UNDERSTAND THE BLOCK AND WE MAY BE ABLE TO PREVENT THE TRANSITION IN ACUTE TO CHRONIC PAIN. THEN IT GOES INTO THE BRAVE — — BRAIN AND GETS MESSY. THE THALAMUS IS WHERE THE SENSORY SYMPTOMS CONVERGE AND THE THALAMUS HAS LONG-TERM PAIN THAT CAN OCCUR IN CERTAIN INSTANCES. ONE THING SO KNOW IS THERE IS THIS IDEA, WITH CHRONIC PAIN THE PAIN GETS MORE CENTRAL. AND SOME GET SUICIDE TYPE PAIN IT’S SO HORRIBLE AND YOU CUT THE NERVE AND IT GOES AWAY AND THEN IT GOES AWAY AND GOES TO A GANGLION AND THEN YOU ARE IN PAIN AND IT COMES BACK AND YOU CUT THAT AND THEN IT WINDS UP COMING BACK. THE PAIN SYSTEM CHANGES WITH CHRONIC PAIN. THERE’S LOTS OF POTENTIAL TO THE SCIENCE AND NOW LOTS OF PAIN RECEPTORS WE NOW KNOW ABOUT. WE HAVE EXAMPLES OF PEOPLE BORN WITHOUT A PARTICULAR AREA THAT RECEIVES PAIN AND SOME DON’T RECEIVE ANN — ANY PAIN. YOU WANT TO BUILD A DRUG TO BLOCK THOSE RECEPTOR TO NOT FEEL PAIN, BUT SOMETIMES THOSE WHO DON’T FEEL PAIN ARE IN TROUBLE BECAUSE THEN THEY GET BURNED, THEY HAVE TERRIBLE INJURIES TO THEIR JOINTS AND IT’S NOT AS SIMPLE AS IT OFTEN TIME SEEMS WHEN YOU FIRST GET INTO THIS. IT DOES MEAN THAT THERE ARE WAYS OF MANIPULATING THE SYSTEM AND YOU HAVE TO GET IN THE SWEET SPOT. AND IT WAS FOUND THAT A NEUROTRANSMITTER WAS FOUND DURING THE ACT OF A MIGRAINE. IF YOU GIVE CRG TO PEOPLE YOU CREATE PAIN AND NOW THERE ARE DRUGS THAT ARE AT THE FDA ABOUT TO BE APPROVED AND CAN BLOCK THE HEADACHE IN THIS GROUP OF PATIENTS. SO ANOTHER EXAMPLE OF MOVING OUT OF THE OPIOID SYSTEM TO THE PAIN SYSTEM. SPINAL CORD STIMULATERS AND THE TRANSMISSION OF SIGNALS UP TO THE SPINAL CORD USED FOR A LONG TIME. THIS SHOWS PEOPLE WITH CHRONIC PAIN YOU CAN IMPROVE THEIR CLINICAL OUTCOME. THIS IS SOMETHING A LOT OF PEOPLE DON’T DO BECAUSE IT’S INVASIVE. YOU HAVE TO PUT IT OVER THE SPINAL CORD ITSELF BUT IN A CRISIS WHERE PEOPLE ARE DYING OF OVERDOSE IT’S SOMETHING TO THINK ABOUT WITH CHRONIC LOW BACK PAIN. ANOTHER EXAMPLE OF STIMULATING THE NERVE ITSELF IS JUST APPROVED THE VAGUS NERVE STIMULATOR FOR MIGRAINE. IT’S EFFECTIVE IN CLUSTER AND SOME PEOPLE WITH HEADACHE AND DOES EXTREMELY WELL. THIS STIMULATES THE VAGUS NERVE AND BACK TO THE BRAIN STEM AND SOMEHOW INTERFERES WITH THE PAIN SYSTEM THAT CREATES THE HEADACHES. WE DON’T UNDERSTAND HOW. IN THE BRAIN INITIATIVE WHICH NIH HAS BEEN AN AMAZING PROJECT TO DEVELOP TOOLS TO SEE CIRCUIT ACTIVITY IN ACTION. THIS IS A TRANSGENIC MECHANISM AND YOU CAN SEE THE CELLS LIGHT UP. NOW WE HAVE THE ABILITY TO SEE ACTIVITY IN THE PAIN CIRCUITS IN REAL TIME GIVING US HOPEFULLY NEW TOOLS TO INTERFERE IN THE PAIN SYSTEM FOR HEALTH BENEFITS. IN THE CURRENT ATMOSPHERE WE NEED PATIENTS TO GET THE KIND OF SPECIAL CARE YOU WOULD GET IF YOU HAD A HEART ATTACK OR A SEVERE LEUKEMIA. YOU WOULD GO TO AN ONCOLOGIST OR LEUKEMIA SPECIALIST OR TO A CARDIOLOGIST FOR HEART TROUBLE. PAIN, THERE’S LITTLE ABILITY TO GET TREATED BY EXPERTS. MAINLY BECAUSE IT’S AN A HEARD AREA. — IT’S A HARD AREA AND TO TAKE CARE OF PEOPLE WITH CHRONIC PAIN IS MISERABLE. I USED TO RUN THE CLINICAL SERVICE AT MASS GENERAL AND THE HEADACHE DOCTOR LOST $100,000 A YEAR BECAUSE THE PATIENTS TAKE SO MUCH TIME AND YOU GET BUILD FOR SEEING PATIENTS EVERY 15 MINUTES AND IT’S JUST NOT POSSIBLE. WE NEED TO CHANGE THE SYSTEM SO PEOPLE GET THE PAIN CARE THEY NEED WHICH NOT SOMEBODY WHO IS JUST GOING TO WRITE A PRESCRIPTION WHICH IS HOW WE GOT IN THE TROUBLE IN THE FIRST PLACE. WE NEED PEOPLE TO BE COUNSELLED ON PAIN MANAGEMENT. YOU CAN LISTEN TO SOOTHING MUSIC AND TURN THE PLEASURE BAROMETER UP OR EXERCISE SO YOU’RE NOT STIFF ALL THE TIME FOR BACK PAIN. THERE ARE WAYS TO MANAGE THIS WITHOUT DRUGS AND IF YOU’RE GOING TO GIVE DRUGS, YOU BETTER USE EVERYTHING ELSE THAT’S NOT DRUGS AS YOU DO THAT. WE DON’T HAVE A GOOD SYSTEM STIMULATE U.S. AS A MATTER OF FACT, MUCH OF WHAT HAPPENED IN RURAL AMERICA IS PEOPLE CAME IN AND THEY JUST STARTED PRESCRIPTIONS FOR PAIN MEDS AND THEY WERE BASICALLY CROOKS AND ONE DOCTOR IN VIRGINIA WAS WRITING 1,000 PRESCRIPTIONS A DAY AND HE WAS JUST GETTING PAID FOR WRITING PRESCRIPTIONS. SO THERE’S THE HEAL INITIATIVE HELPING TO END ADDICTION AND LONG-TERM INITIATIVE AND IT’S GOT TWO AREAS. ONE IS TO PREVENT ADDICTION TO ENHANCE PAIN MANAGEMENT AND THE OTHER IS TO IMPROVE DISORDER AND ADDICTION. WE’RE HOPING TO ROLL THESE THINGS OUT. THERE’S A WHOLE OF ACTIVITIES AND EXTRA MURAL PLANS AS WELL. ONE OF THE BIG AREAS WE NEED TO MAKE PROGRESS ON IS TO GET AWAY FROM A SUBJECTIVE PAIN SCALE AND GET TO SOMETHING MORE BIOLOGICALLY RELATED TO THE PAIN. IF WE’RE GOING INTERACT WE NEED READ OUTS AND WE DON’T HAVE THOSE NOW. FOR PEOPLE WHO TAKE CARE OF PATIENTS WITH PAIN IT’S HARD TO UNDERSTAND WHEN THEY’RE COMING TO YOU WITH PAIN VERSUS DRUG SEEKING. SOME DRUG SEEK BECAUSE THEY DON’T FEEL GOOD WITHOUT THE DRUGS. THAT’S HARD TO DISASSOCIATE THAT FROM PAIN. THERE ARE A COUPLE AREAS IN THE FUNCTIONAL MLIs SPACE AND THERE’S NOW A CONSORTIUM AROUND THE WORLD TRYING TO GET PAIN SIGNALS FROM FUNCTIONAL MR. THEY STIMULATE AND ARE GETTING SIGNALS IN THE BRIN OF THE AREAS THAT GET ACTIVATED THAT CORRELATE WITH THE INTENSITY OF THE STIMULUS WHICH IS GREAT. IN ADDITION THEY’RE SEEING AREA ACTIVATED NOT JUST BY THE INTENSITY BUT THE PAIN. THINK OF IT AS TWO ASPECTS. ONE IS STIMULUS COMING IN AND THE OTHER IS HOW DO YOU PERCEIVE IT. THE MARATHON RUNNER THEY DON’T PERCEIVE IT AS BAD UNTIL THE RACE IS OVER. THOSE TWO THINGS ARE IN LOTS OF AREAS TO THINK ABOUT WITH THE GANGLION AND THE SPINAL CORD AND THE DIRECTOR’S FUND IS GOING TO LAUNCH A PROJECT TRYING TO UNDERSTAND THE PREDICTIVE MARKERS FOR THE TRANSITION FROM ACUTE TO CHRONIC PAIN WITH THE HOPE WE CAN INTERVENE AND PREVENT SPINAL PAIN. YOU CAN SEE WE’RE ATTACKING THE OPIOID EPIDEMIC AND SOME SHORT TERM AND SOME LONG TERM ON THE PAIN SIDE AND ALSO ON THE VICTIMS SIDE. WITH THAT, I WANT TO THANK EVERYBODY FOR THEIR ATTENTION. I CAN TAKE ONE QUESTION AND IN THE GOT TO RUN.>>ARE YOU LOOKING AT GENDING DIFFERENCES IN PAIN TREATMENT AND THE BIOLOGICAL DIFFERENCES?>>CHRONIC PAIN IS MORE PROMINENT IN WOMEN. IN THE 1890s THE ADDICTION WAS PRIMARILY IN WOMEN. HEADACHE WAS MORE COMMON IN WOMEN AND OPIOID, HEROIN USE, WHEN I WAS TRAINING WAS ALMOST ENTIRELY MEN AND WITH THE PRESCRIPTION OPIOIDS, UNFORTUNATELY, THE WOMEN AND MEN WERE EQUAL. THE GENDER ISSUES ARE CRITICAL HERE.>>REGARDING THE PAIN SIGNATURE AND THE BIOLOGICAL MARKER, SO THE GOAL IS TO TRY TO DEFINE SOMETHING UNIQUE TO PAIN AND THEN FROM NORAH’S TALK WE KNOW THERE’S OVERLAP BETWEEN THE A ED BRAIN AND CHRONIC PAIN BRAIN. THAT WORK IS GREAT BUT IT’S ONLY FOCUSSING ON THE PAIN BRAIN. WHAT IS THE THINKING ON THAT FROM YOUR PERSPECTIVE?>>WE BELIEVE WE NEED A MARKER TO TEST FOR THE EFFICACY OF A NEW THERAPY. CAN WE GET SOMETHING THAT IS MORE PREDICTIVE OF WHETHER A TREATMENT IS WORKING AGAINST PAIN THEN SIMPLY ASKING SOMEBODY. WE’RE AT THE VERY PRIMITIVE LEVEL. NOT AT THE LEVEL OF TRYING TO DISTINGUISH PAIN, PLEASURE IN AN OPIOID ADDICTED PERSON. THAT WOULD BE REALLY COMPLICATED. [QUESTION INAUDIBLE]>>THAT’S A GOOD POINT FOR PEOPLE WITH CHRONIC PAIN.>>WHILE OBJECTIVELY MEASURING THE PAIN, DO YOU THINK WE pPROBABLY NEED TO GO ALL THE WAY IT THE BRAIN OR MAYBE YOU WOULD PREPARE ALL SIGNALS LIKE PHYSIOLOGY.>>THERE COULD BE DIFFERENT THINGS TO MEASURE AND THE AUTONOMIC ACUTE PAIN SHOULD BE EASIER TO GET TO THAN THIS. WITH PEOPLE IN BACK PAIN INSTEAD OF ASKING EVERY THREE MONTHS YOU CAN BASICALLY MONITOR HOW THEY WALK OVER MONTHS AND ALSO KNOW IF THEY’RE PLAYING GOLF WITHOUT TELLING YOU.>>I WAS WONDERING, IN THE OPIOID OVERDOSE IF IT OVERLAPS WITH THE MAP OF PAIN WHICH IS WELL KNOWN IN A PHYSICIAN’S RECORD. IF THE MAP OF PAIN OVERLAPS WITH THE MAP OF OPIOID OVERDOSE? THE UNITED STATES MAP.>>IT DID UP TO FOUR YEARS AGO AND NOW IT’S CHANGING BECAUSE PEOPLE ARE GOING STRAIGHT TO HEROIN AND BYPASSING PRESCRIPTION OPIOIDS. NOW IT’S DIFFERENT. NOW IT’S MOVING INTO CITIES MORE AND THE RURAL AREAS. THESE PEOPLE WHO ARE DEALERS ARE REALLY BAD ACTOR. THEY’LL GO ANYWHERE TO MAKE MONEY AND THEY GET PEOPLE HOOKED. THEY’LL MAKE MONEY.>>WHEN A PATIENT GOES TO THE PAIN DOCTOR AND THEY ASK HIM HOW MUCH PAIN DO YOU HAVE AND IN ORDER TO GET THE MEDICATION THEY SAY THE PAIN’S 10. BUT IF THEY GO TO THE DOCTOR TO GET RID OF THEIR ADDICTION AND ASK HOW MUCH PAIN DO YOU FOR A PROGRAM, IT’S TWO. IS THERE ANY WAY WE CAN USE A MEASUREMENT TO PINPOINT AND HELP THE DOCTOR TO KNOW HOW MUCH PAIN THE PERSON’S IN?>>THAT’S THE PROBLEM. WE DON’T HAVE THE ABILITY. THAT’S THE HOPE BEHIND THE WAIVER STUFF. THERE’S NO REASON WHY WE CAN’T LOOK AT THOSE WHEN WE HAVE BETTER TOOLS.>>THE MAIN KILLER IS FENTANYL. IT’S BELIEVED THE FENTANYL IS COMING FROM CHINA. [APPLAUSE]>>ARE THERE OTHER QUESTIONS?>>I’M AN INVESTIGATOR AND HAVE BEEN TALKING ABOUT DOING A RETREAT AT THE INTERSECTION OF PAIN AND ADDICTION AND WE USE MODELS OF REWARD. MY FINAL QUESTION WOULD BE WHERE DO YOU THINK WE SHOULD WORK AT THE INTERSECTION TO GET PAIN AND ADDICTION COMMUNITIES TALKING TO EACH OTHER. DO YOU THINK TESTING PAIN IN INDIVIDUALS WITH SUBSTANCE USE DISORDERS WOULD HELP US MOVE FORWARD. WHERE DO YOU SEE THE BEST PLACE FOR GROWTH WHERE WE CAN WORK WITH EACH OTHER IN THE UNIQUE SETTING IN THE INTERMURAL PROGRAM?>>I VIEW IT FROM IN TERMS OF THE BASIC UNDERSTANDING OF THE CONNECTIONS BETWEEN THE PLEASURE OF PAIN CENTERS. TO THE DOPAMINE CELLS ARE ACTIVATED BY PAINFUL STIMULI. UNDERSTANDING THE DIFFERENCE CELLS AND THE PROJECTIONS AND THE BASIC ASPECT OF RESEARCH AND ANOTHER IMPORTANT ASPECT OF RESEARCH THAT WHEN WE DO ADMINISTRATION OF A DRUG AND THE CHAN CHANGES HAVE BEEN LOOKED AT IN THE AMYGDALA AND IT TRIGGERS CHANGES IN THE EXPRESSION OF THE RECEPTORS SIGNALLING. THAT SAME PROCESS IS THE SAME ONE THAT IS IN MEMORY AND SYNAPTIC EFFECTS AND WE CAN PREDICT THE SAME MOLECULAR TARGETS WILL BE THERE AND BASED ON THE RESEARCH AND THE EXPERTISE IT WOULD BE A FASCINATING AREA OF RESEARCH. TO WHAT EXTENTS THE CHANGES ARE ENGAGED FOR ADDICTION AND PAIN. FROM THE PERSPECTIVE OF CLINICAL RESEARCH TO THE QUESTIONS OF FOR EXAMPLE, WHAT IS ULTIMATELY THE NEUROCIRCUITRY ASSOCIATED WITH PLEASURE, WE DO A LOT OF RESEARCH IN ADDITION TO CUES. I’M TRYING TO MAP OUT THE DIFFERENCES. THERE ARE SO MANY QUESTIONS THAT THE ANSWER WILL COME FROM PUTTING PEOPLE TOGETHER AND SEEING GREATER OPPORTUNITY ON ADVANCING THE FIELD FORWARD. AND AGAIN IT’S THE ISSUE OF BRINGING PEOPLE TOGETHER AND HE CAME AND SPOKE TO OUR GROUP AND HE WAS PRESENTING DATA AND HE WAS SHOWING THAT THE RECEPTORS PREVENTS TOLERANCE TO OPIOIDS OR ENHANCES THE ANALGESIC EFFECTS. IT BLEW MY MIND. THEY WERE DOING RESEARCH RELEVANT TO THE OPIOID CRISIS AND TO START WITH TO CONNECT THE POINTS YOU HAVE TO BRING PEOPLE TOGETHER AND I THINK THERE’S MANY OPPORTUNITIES.>>TO WHAT EXTENT IS THIS A GLOBAL PROBLEM? >>WE’RE NOW SEEING A MASSIVE PROBLEM IN VANCOUVER. THEY’RE AFFECTING CANADA. I DON’T THINK AT THE SAME EXTENT AS US AND THE UNITED KINGDOM IS REPORTING INCREASES IN OVERDOSES. NORTHERN PARTS OF EUROPE. NOW WITH THE WEB AND THE WAY THE SYNTHETIC OPIOIDS ARE COMING, ONE MAIN SOURCE IS THROUGH THE MAIL. YOU CAN THINK ABOUT THE POTENTIAL OF DISSEMINATION OF GLOBALIZATION. THEY’RE EASY TO SYNTHESIZE AND EASY TO SNEAK IN AND HIGHLY ADDICTIVE AND ENORMOUS PROFIT. IT FORCES PEOPLE TO DO REALLY MEAN THINGS AND BAD THINGS. I BELIEVE IT’S INCREDIBLY IMPORTANT THE OTHER COUNTRIES LEARN FROM THE UNITED STATES TO PREVENT THIS EPIDEMIC FROM DISSEMINATING. OTHERWISE IT’S LIKE AN INFECTION HOUSE DISEASE. IT WILL GROW BEYOND THE UNITED STATES AND CANADA.>>HOW DO YOU THINK OTHER COUNTRIES SHOULD GO ABOUT DOING THAT AND WHAT MEASURES SHOULD CERTAIN COUNTRIES TAKE TO LEARN FROM THE U.S. AND CAN YOU TALK A LITTLE BIT ABOUT THE UNIQUE METABOLISM OF OPIOIDS AND HOW THEY STAY IN THE SYSTEM THAN TYPICAL DRUGS AND DOES IT MAKE IT DIFFICULT TO TREAT ADDICTION AND TRY TO KICK PEOPLE OFF ADDICTIVE BEHAVIORS.>>IN THE UNITED STATES WITH CANADA HAVE HIGH RATES OF PRESCRIPTION PRACTICES FOR OPIOIDS. IN MEXICO WHERE A LOT OF THE HEROIN IS PRODUCED HAS A LOWER, MINIMAL OPIOID PROBLEM IN THE BORDER STATES. THEY HAVE NOT BEEN EXPOSED AND IT WAS A GOOD BREACH TO ENTERING AND GETTING THE COUNTRY READY FOR EXPANDING OPIOID MEDICATIONS. HEROIN WAS PREVALENT IN THE MARKET AND BEING ABLE TO MINIMIZE THE AVAILABILITY AND ACCESS TO THE DRUG DETERMINES HOW LIKELY PEOPLE ARE TO GET EXPOSED. IN TERMS OF PREVENTION, ONE OF THE LESSONS WE WANT TO LEARN FROM WHAT HAPPENED TO US IS YOU HAVE TO BE CAREFUL IN HOW YOU PRESCRIBE OPIOID MEDICATIONS IF YOU HAVE ACUTE OR CHRONIC PAIN, IT HAS TO BE UNDER LIMITED DOSE DURATION AND EXPOSURE AND CLOSE OVERSIGHT AND WE BECAME CMPLACENT. AND COUNTRIES HAVE BEEN FIGHTING LIKE WALTER MENTIONED ABOUT THE PROBLEM OF OPIOIDS IN CHINA. THERE’S NOT ZWLUFT ONE CAMPAIGN. NOT WHAT IS DEALING WITH OPIOIDS BEING MORE ADDICTIVE OR DANGEROUS THAN SOMETHING ELSE. THE DRUGS THAT ARE SHORT LASTING. FENTANYL HAS A SHORTER SHELF LIFE THAN OTHER DRUGS. IT’S NOT THE DURATION OF THE DRUG IN YOUR BODIES. THE SPEED AT WHICH IT INTERACTS WITH THE RECEPTOR AND THE POTENCY DETERMINES ITS EFFECTIVENESS. MARIJUANA HAS A SLOW RELEASE.>>DO YOU THINK THE FDA COULD HAVE BEEN MORE PROACTIVE IN REGULATING OPIOID USE?>>I THINK WE COULD HAVE BEEN MORE PROACTIVE. I THINK THE WAY I VIEW IT IS WHERE WERE THE HOLES THAT ALLOWED THIS TO HAPPEN AND LOOKING AT IT WOULD SAY YOU NEED TO HAVE BEEN MUCH MORE OBSERVANT OF FOLLOW-UP OF THE PATIENTS NOW THE FDA IS DEMANDING. IF YOU HAVE AN EXTENDED RELEASE FORMULATION YOU HAVE TO FOLLOW INDIVIDUALS TO SEE IF [INDISCERNIBLE] THE COMPOUND AND ONE OF THE OPIOID MEDICATIONS WAS DISAPPROVED BY THE FDA. YES, IF WE HAVE KNOWN, WE SHOULD HAVE BEEN MORE OBSERVANT AND SHOULD HAVE LOOKED AT REGULATION IN ADVERTISEMENTS FROM THE PHARMACEUTICAL INDUSTRY AND WHEN I WAS A STUDENT THE BIG MEETINGS WERE TO SUPPORT THE PHARMACEUTICAL INDUSTRY AND THEY WOULD COME TO THE HOSPITAL TO ADVERTISE ABOUT THE MEDICATIONS AND GIVE US SAMPLES TO THE PATIENTS. AND SOME PRACTICES THAT SHOULD HAVE NEVER HAVE BEEN ALLOWED TO HAPPEN, HAPPEN. NOW WE NEED TO LEARN AND STOP IT. SAME THING PHYSICIANS. THEY SHOULD HAVE NOT BEEN ACTUALLY SO COMPLACENT. YOU’RE NOT GOING TO ADDRESS THE NEEDS OF A PATIENT AND YOU GIVE THEM A PRESCRIPTION AND NURSES DON’T GET TRAINING ON ADDICTION AND PHARMACISTS, DENTISTS. MULTIPLE HOLES AT MULTIPLE LEVELS THAT ALLOWED THE CRISIS TO HAPPEN.>>WHAT ABOUT THE AVAILABILITY OF NALOXONE ACROSS THE BOARD? IF A PATIENT IS OUT OF THE STREET AND SOMEBODY’S DYING, HOW DO YOU — >>THE BEAUTY OF A PRESCRIPTION YOU DON’T NEED A WHOLE PRESCRIPTION BUT I’M A STRONG PROPONENT OF GIVING NALOXONE OVER THE COUNTER AND MY SPSHTH PERSPECTIVE PERSPECTIVE IS WE THESE TO SAVE AS MANY LIVES AS POSSIBLE. IF YOU HAVE IT OVER THE COUNTER AND ARE NO LONGER BEING REIMBURSED, WILL THAT LIMIT THE NUMBER OF PEOPLE WHO CAN GET AS ACCESS. FOR SOMEONE PAYING $150 IT MAY LIMIT THEIR WILLINGNESS TO GET IT. WE’LL FIND OUT.>>YOU MENTIONED NEW THINGS WE HAVE LEARN FROM THE OPIOID ISSU ISSUES WE ARE INCORPORATING MOVING THIS FORWARD TO PREVENT THIS FROM HAPPENING. FROM THE PAIN SIDE OF VIEW, ARE THEY ALSO INCORPORATING THE NEW MEASUREMENTS WITH THE DEVELOPMENT OF NEW TARGETS FOR PAIN BECAUSE THE OVERLAP IS CONCERNING TO ME. THE TREATMENT THE ANTAGONIST, WOULD IT BE PROBLEMATIC IN THE FUTURE. WHATEVER IT IS WE FIND THAT MIGHT BE A MAGIC BULLET FOR PAIN, HOW DO WE PREVENT IT FROM BECOMING ALSO LOOKING AT THE NEXT EPIDEMIC.>>NO, THERE’S BEEN AN ENORMOUS AMOUNT OF ADVANCES THAT ALLOW YOU TO PREDICT WHEN A DRUG WILL HAVE THE LIKELIHOOD OF ADIRECTIVE POTENTIAL. AND SOME ARE UNLIKELY TO HAVE AN EFFECT. THE AMYGDALA IS MORE LINKED WITH EMOTIONAL. SOMETIMES WE FIND THAT DRUGSZ DRUGS DRUGS WEREN’T ACTIVATING WERE HIGHLIGHTING WHY EVERY SINGLE DRUG THAT IS GOING TO HAVE A CENTRAL EFFECT REQUIRES THE FDA TO DOCUMENT IT’S NOT REGARDING THIS ZONE TO DETERMINE IF WHAT’S ITS SCHEDULE IS AND WHAT PRECAUTIONS YOU SHOULD TAKE. I WONDER IF YOU CAN TALK ABOUT MENTAL PAIN, MENTAL DISORDERS AND SUFFERING AND HOW PEOPLE ARE USING THIS TO SELF-MEDICATE AND THERE’S A DEEPER ISSUE AND WE HAVEN’T BEEN EDUCATING PEOPLE ON THE ACCESS.>>IT’S A GOOD QUESTION. AND RESEARCHERS HAVE ALREADY COMMENTED ON THE OVERLAP WITH PSYCHOLOGICAL AND PHYSICAL PAIN. THERE’S A LOT OF OVERLAP. THAT COULD EXPLAIN WHY, FOR EXAMPLE, 50% OF THE OPIATE PRESCRIPTIONS ARE PRESCRIBED TO PEOPLE WITH A MENTAL ILLNESS, MOST WITH A MOOD DISORDER. TO ME IT’S TELLING YOU SOMETHING FUNDAMENTAL. THOSE WITH A MOOD DISORDER ARE A HIGHER RATE OF SUFFERING FROM CHRONIC PAIN CONDITIONS. WOMEN ARE MORE SENSITIVE AND THAT IS RELEVANT BECAUSE IF WE WANT TO UNDERSTAND AND PREVENT PAIN WE NEED TO HAVE A COMPREHENSIVE UNDERSTANDING IN WHAT MAKES YOU VULNERABLE AND ONE IS BEING A FEMALE AND CATATHOPHIZING MAKING YOU MORE LIKELY FOR ADDICTION.>>THANK YOU VERY MUCH.