Chris McCurdy, a medicinal chemist from the University of Mississippi, details his discovery of an endogenous inhibitor blocking DMT synthesis, potentially offering schizophrenia treatments while enabling natural "endogenous tripping." He contrasts this with DARPA-funded PTSD research and highlights spermidine's link to six extra years of life. The discussion critically analyzes kratom as a safer opioid alternative compared to alcohol or benzodiazepines, noting its mild withdrawal profile versus the fatal risks of GABA depressants, while warning against heavy metal toxicity in high-dose extracts and advocating for balanced federal funding over current regulatory hurdles. [Automatically generated summary]
Transcriber: CohereLabs/cohere-transcribe-03-2026, WAV2VEC2_ASR_BASE_960H, sat-12l-sm, script v26.04.01, and large-v3-turbo
Time
Text
From Pharmacist to Plant Researcher00:03:39
I learned about you through Andrew Gallimore, who was on here, and he and Newnautics were working together on a project they wanted you to get involved with to figure out this endogenous DMT production stuff.
I want to start by talking about that stuff.
But before that, can you give people a brief history of yourself, your background, and your work and your expertise?
Sure, sure.
So, thanks, first of all, for having me down here.
And this is pretty cool.
And it's nice to do this on a local trip, too.
Yes.
Because I come just from Gainesville, about two and a half hours up the road.
I am at the University of Florida.
I am originally trained as a pharmacist.
And then I went to graduate school to go a little deeper into medicinal chemistry, which is really drug architecture, drug design, and drug development.
And my interest has always been in natural products and pursuing natural products for benefit.
Of humankind.
First and foremost, because nature, I believe, has put plants out there for us, other natural products out there for us on this earth to use to benefit our use, benefit our health, and potentially combat diseases that are also coming from nature.
So I believe there's a balance in the yin and the yang there.
But I've always been interested in more psychoactive plants.
Really, the first one was in high school and it was just caffeine.
Caffeine from the coffee plant.
And interestingly enough, I've ended, you know, more recently studying another plant in the coffee family, Mitrigana speciosa, which is the plant that produces kratom.
So we'll talk about that, I'm sure, in more depth.
But caffeine, I did a small project in high school looking at the caffeine concentrations in different sodas.
This was before the FDA required labeling it.
And so we found.
You know, Mountain Dew was pretty high in caffeine content.
There was an old Jolt Cola.
And sugar was really high.
Oh, yeah, they're all low.
Remember Surge?
Yes.
I think they banned that.
Yeah.
And those are just good examples of too much sugar and too much caffeine.
And that's a formula for wildness.
And in fact, we were so goody two shoe in high school.
Our Friday nights consisted of a case of Mountain Dew and we would just jam band in the basement.
That's what we did.
But moved on from that, went to pharmacy school, and then got involved in research when I was in pharmacy school at Ohio Northern University.
Graduated, got my pharmacy license, practiced as a retail pharmacist.
Actually, worked originally for Publix pharmacies.
So I'm very familiar with how they operate and really enjoyed those interactions with.
Customers, what we called them back then, now patients is the preferred terminology in pharmacy practice.
But from there, I went to the University of Georgia, did a four year stint to get a PhD.
And I worked with chemicals there that were built to mimic a chemical called lobaline, which came from a plant called Lobella inflata, which was a Native American tobacco plant.
The Endogenous Inhibitor Discovery00:10:30
So it didn't have nicotine in it.
But it had compounds that we thought interacted with nicotine receptors.
And we studied that.
We did a lot of work, never really went anywhere.
But then I got an opportunity to do a postdoctoral, kind of like a residency for a physician, do a postdoctoral stint at the University of Minnesota for Phil Portaghese, who is a distinguished professor of medicinal chemistry there.
He was the editor in chief of the journal Medicinal Chemistry, but he's considered to be one of the real chemistry fathers of the opioid, endogenous opioid system, in terms of discovering compounds that would block the effects of opioids.
So.
He defined that there are three opioid receptors before genetically we knew that there was actually three distinct opioid receptors.
He did that through chemistry.
And so, getting training with him, working directly with opioids and opioid chemistry isolated from the poppies, I got more and more interested.
Started my career in 2001 at the University of Mississippi, which is well known for natural products research.
And And when I arrived there, they had one of the largest repositories of natural product samples in the country, didn't have anything studied in the central nervous system.
And I thought, man, this is a gold mine to walk into.
They also have the, well, at the time, the only federally funded marijuana farm.
And so we had access.
This was in 2001.
The marijuana farm actually predates the National Institute on Drug Abuse.
So it was funded.
All the way up until very recently, by the National Institute on Drug Abuse, and served as the only source for studies that could be funded from the government to look at marijuana, the effects of marijuana.
And so there was experience with very controversial plants there.
They weren't shy for me to study what I wanted to study.
And the first plant that came into mind was really Salvia divinorum, also called diviner sage or magic mint.
It's a mint plant.
And it has probably one of the most potent hallucinogenic compounds ever discovered in it called salvinorna.
And nobody knew how this compound interacted in the body.
And then Brian Roth, who's at the University of North Carolina, actually did a full screening panel on it and published this amazing paper showing that it was highly selective for the kappa opioid receptor.
Well, it was a total mind blow because.
Every compound that's ever been described for opioid receptors has a nitrogen in it.
Salvinorin A doesn't have a nitrogen at all in the molecule structure.
And so it broke all the rules of what a structure had to look like or contain to interact with opioid receptors.
And that's really what started us down that pathway how in the heck is this thing interacting with opioid receptors, particularly kappa opioid receptor, which is dysphoric in its function instead of euphoric, like?
The mu opioid receptor.
So, the mu opioid receptor is the target for things like morphine and heroin and fentanyl.
And the kappa opioid receptor is sort of the yin to that yang that caused you to feel miserable.
And in fact, they were developing compounds in pharmaceutical companies that were very selective for kappa opioid receptors way back when.
And animals weren't liking those compounds.
They wouldn't take them, but they gave great pain relief.
And they thought they were onto the holy grail of.
Very potent painkillers with no abuse potential.
And then they started human trials, and all the humans ran for the doors after their first dose because it was so dysphoric.
Oh, wow.
Interesting.
And that's what really fascinated me people were utilizing salvia divinorum to get high and have this sort of hallucinogenic experience, many times described as being a very dark hallucinogenic experience.
And then it became famous because Miley Cyrus actually had a YouTube video where she was smoking salvia divinorum and it sort of blew up in the early 2000s.
Really?
Most people really didn't get.
That much from it.
I mean, it was a fad thing and I think it kind of faded away.
Some people really like it.
Some people still tell me they use it and come across it.
It's very easy to grow.
It's a mint plant.
So if you've ever had mint growing in your garden, it's almost impossible to kill it once it's established because it just keeps coming back.
But yeah, these plants were really easy to grow.
We got a couple plants and we propagated them to a couple hundred easily.
Wow.
But that was a cool project.
And that project actually led me to Mitrigana speciosa because I was invited by the National Institute on Drug Abuse, who funded us for a grant on Salvia divinorum and said, hey, we want you to come and talk on naturally occurring analgesics or painkillers.
Right.
So that led me into researching the literature.
And that's where I came across Mitrigana speciosa.
Okay.
I want to get into that stuff, the Kratom stuff.
But.
First of all, how and why did Gallimore and these guys at New Nautics get a hold of you and what were they looking to get you to help them with?
Yeah, so they were very familiar with my work in Kratom or Kratom.
I call it Kratom.
I sort of acquiesced to that.
The American Kratom is really the way it's pronounced in Thailand.
Right.
And interestingly, in Thai, I believe it translates to home.
Oh, interesting.
Yeah.
So it's interesting.
Someone told me that.
I haven't fact checked that, but probably should.
But yeah, Kratom is what we always called it because we knew it was Kratom, Kratom's son.
Like you got to really emphasize it.
Yeah, it's a lot of work.
Yeah.
So anyway, Kratom took off in the U.S. and it's become the popular sort of street terminology.
But they were very familiar with my work.
I've been to.
Several conferences that were involved with a lot of psychedelics because kratom is a psychoactive plant.
I was getting invited to come speak on this because people just weren't familiar with it.
So they were really excited about the work that we did, the thoroughness, and sort of the rigor that we applied to doing our work.
And then approached me and said, Hey, would you be interested in this project?
We know about a paper that was published in 1977 that indicated.
There's an endogenous inhibitor in mammals.
It was done really in rabbits.
They also confirmed it in humans that there's this peptide in our bodies just floating around that actually can block the synthesis of dimethyltryptamine.
So, endogenous dimethyltryptamine that our body is producing, there's enzymes that have to synthesize that because you start with tryptophan, the amino acid, and then our bodies start to build that into tryptamine.
And then it starts to methylate with these what are called indole and methyltransferase enzymes.
And so what we're searching for is this endogenous inhibitor to see if we can replicate that paper from 1977, first of all, and identify these reported endogenous inhibitors.
The importance of that is because they did not characterize them back in 1977.
And that paper has just been sitting there untouched, unexplored after that report.
And so Andrew was very interested in, hey, can we sorry to interrupt.
What was the goal of the research that led to that paper in 1977?
Like, what were they doing it and what were they looking for specifically?
Do you know?
Yeah, I'm not even familiar with who was doing it, and I should be.
But the work was done really to see if this indole and methotransferase, which produces other things besides DMT as well, but is there an endogenous system that inhibits it?
Because that's what they were looking for.
And that's what they found.
And the reason behind wanting to find an inhibitor is there's been an association with an overexpression or overabundance of this enzyme in patients that have schizophrenia.
And so, if you think about that, an overabundance of the enzyme should produce an overabundance of endogenous DMT.
That DMT will cause hallucinations, whether they're visual, auditory, or just.
Mind, you know, playing tricks on itself, which are a lot of the hallmark features of schizophrenia.
And so the whole point was if we can find this peptide, it will be potentially a new way to treat schizophrenics.
The inhibitor peptide.
The inhibitor peptide.
If we can't utilize the inhibitor peptide itself, then my expertise also involves taking peptides, small peptides, and making small molecule memetics of those.
Peptides.
So, we have another project in my lab that really looks at this exact role.
And I think that was what made neuronatics feel really comfortable with what we're doing.
We understand and respect the natural products world, but we also do a lot of small molecule synthesis based on endogenous peptides and the knowledge of those peptides.
Balancing Opioid Systems Naturally00:04:48
And so, we work on a project called Neuropeptide FF, which was thought to be an anti opioid peptide.
So, when we secrete endorphins, we also secrete this.
Sort of anti opioid peptides to keep our bodies in balance, and we won't become tolerant to our own endogenous opioid system.
We won't become, you know, sort of non responsive when that system is activated.
So, this is how our body sort of keeps the balance.
Well, what happens is if you take a prescription opioid or an illicit opioid, you shut down endogenous production of endorphins.
Because the body says, hey, our system is working.
We don't need to produce more of these peptides.
Interesting.
So it shuts it down.
But because that system's activated, those countermeasure peptides are being released.
And when you take away the opioid, it takes a couple of days 48, 72 hours before that machinery can sort of get re expressed and turned back on to produce the endorphins.
And in the meantime, you pull away the exogenous opioid, the tablet that you took or whatnot, and you're flooded with these countermeasures, these anti opioid peptides that actually cause you to be in more pain.
And so it's a phenomenon called opioid induced hyperalgesia.
Hyperalgesia means you're more sensitive to stimuli that shouldn't be painful, but they become painful.
So, an example would be if someone pulled a tooth.
If someone was at the dentist had a tooth extracted, they give you some opioids to go home with and some anti-inflammatories like ibuprofen or something to knock down the inflammation because the pain is really coming from the inflammation and the irritation that they did to take that tooth out.
Within a few days or a week, that should all be resolved and there shouldn't be any pain left.
But many times people will run out of the opioid and say, oh, I feel it throbbing now and it's really in pain.
And the dentist could look at it and say, well, all the inflammation's gone.
It shouldn't be a problem anymore.
But they're complaining of such severe pain still.
What happens?
They get another prescription for an opioid.
Right.
And it sort of starts down this potential pathway, right, that they could become physically dependent on those opioids.
And so this is a project that we've been working on for a number of years as well, trying to find small molecule blockers of that system that you could essentially give with oxycodone or morphine or whatever.
Opioid agonist at the same time, and that two things would happen.
One is it would slow or block completely the tolerance development, so you could use the same low dose of opioid for a long period of time to get pain relief and not have to develop tolerance, so you wouldn't have to increase the amount that you need to take.
And then, that increasing the amount that you need to take, our bodies develop tolerance to opioid pain.
Killing faster than they develop tolerance to the constipative effects or the respiratory depressive effects of opioids.
And so, as you start to increase the dose to get the pain relief, you start to get closer and closer to more and more increased constipation, right?
And more chances of respiratory depression, right?
So, if we can figure out a way to counteract that with these peptide memetics, give them at the same time, then hopefully you wouldn't develop tolerance.
And then, when you go off of the medication, You would also not develop that opioid induced hyperalgesia.
And all this has been shown to work in animals, but we've not translated anything towards humans yet.
But that's a goal.
So that's how neonatics, that's a long way around the store, the answer to the question.
But that's how they got interested.
They knew we were passionate about the central nervous system, they knew we were passionate about natural products, and they knew that we had the knowledge to do this.
Going on the internet without ExpressVPN is like going on a shark dive in a suit made of meat.
You're going to get eaten.
Using public Wi Fi in cafes, hotels, and airports is a feast for the sharks.
And Pierogi from Scammer Payback actually told me the same thing.
Any hacker on the same network can snag your passwords, bank logins, credit card info.
It's not hard.
A smart 12 year old could do it.
Hackers can score thousands of dollars by selling your info on the dark web.
And that's why I use ExpressVPN.
Hunting Peptides in Spinal Fluid00:10:24
It creates a secure, encrypted tunnel between your device and the internet so your data stays private.
It works on everything phones, laptops, tablets, and it's easy to use.
You open the app, hit one button, and boom, you're protected.
It's used by CNET and The Verge.
I use their identity defender plan, which scrubs my info from data brokers, and their VPN keeps me and my family protected.
So secure your online data today at expressvpn.comslash Danny Jones.
That's EXPRESSVPN.com slash Danny Jones for up to four extra months for free.
ExpressVPN.com slash Danny Jones.
It's linked down below.
Now back to the show.
Isn't it, I could be wrong, but isn't it contested that the body makes endogenous DMT and which parts of the body?
Isn't there a lot of speculation, like back and forth?
People haven't really set it in stone.
Yeah.
So I think, First of all, DMT has a very short half life in our bodies.
Right.
And so it's very quickly metabolized and it's hard to capture.
You know, is it there?
You can see evidence of it, but you can see more evidence of things like tryptamine, which is sort of the metabolism byproduct of that, or N-methyltryptamine instead of dimethyltryptamine.
You just have one methyl group there.
Those tend to be present as well, but we know that the one that's most psychoactive is the dimethyltryptamine.
And so.
It's questionable as to how much exists at any one given time in our bodies.
And if it is, I mean, I think it's pretty well proven that the machinery is there to produce it and the levels have been detected.
But again, it's difficult to say, just like any other neurotransmitter, like dopamine, for example, we can't give dopamine as a drug for people to take because it's just, Not well absorbed into our body.
And it also has an incredibly short half life.
So you can't get a lasting effect from it.
Interesting.
And the idea is that the brain and the lungs make DMT specifically?
So the enzymes seem to be present at the highest levels in the lungs.
Now, why is that?
I don't know.
I mean, obviously, you're not going to get psychoactivity in your lungs.
So there may be some other mechanism or role that it's playing.
As I said, this enzyme can methylate other things.
So it can do metabolism of other products that would be similar in structure to something like tryptamine or dopamine or other molecules that we take into our system.
So those enzymes are present mainly in the lung and in the brain.
They're very high concentration in.
Rabbit lungs and that's what we're actually using to try and isolate this.
So it would be a rabbit enzyme, not a human enzyme.
We're looking for the analogous thing in rabbit brains, so it's very highly expressed in rabbit brains, and then we will, if we can confirm all those things, get the enzyme out, get the activity assay set up so we can really start looking for this inhibitor.
Then we can get human cerebral spinal fluid and then start looking to see if the analogous enzyme and inhibitors are present.
in human spinal fluid as well.
Why would you choose spinal fluid?
Well, we can't get human brains.
So we can't sample human brains.
And the literature has reported that the enzyme is present in the spinal fluid.
So we think we should be able to get it from spinal fluid.
And believe it or not, you can purchase pulled human spinal fluid from medical supply companies.
From dead people?
Usually from surgical patients.
And so, what we have the opportunity to do, although we're not, let me be clear, we're not doing this as of right now, but it is a possibility we would have to get all of the ethical approvals accomplished.
Right.
But our anesthesiologists could, when they have someone under anesthesia and if they have to do a spinal tap for whatever purpose, they could be able to access some cerebral spinal fluid for research purposes and give that to us directly.
So, we could study those.
And it would be pretty interesting if that ever turns out to be something that we end up getting to that point in the project where we want to look at what is the human equivalent of this.
This website sells human pooled cerebral spinal fluid for $250.
Yeah.
So, they would have to be like, if a woman's going to do a C section, they're going to be like, we'll do a spinal tap.
Do you mind if we take a couple grams of your spinal fluid?
Yes.
It's pretty much that, right?
And then I assume that you don't need.
Like your body will make more of it.
Yeah.
It's not like, okay.
It's actually, I mean, it's not like blood in terms of you can't really donate cerebral spinal fluid.
Right.
But certainly, you're constantly producing it.
We produce it in our brains.
And then it's something that replenishes itself.
I mean, it's also something that you want to be much more careful about how much you remove versus like something like blood, where we know.
We know what the limits are in both cases where you don't, you're not going to remove a pint of cerebral spinal fluid like you would a pint of blood.
Right, right.
So you could do a test theoretically on schizophrenics.
And if you can figure out how to isolate this inhibitor molecule peptide and give them more of it and see if it alleviates their schizophrenia.
Yeah, that would be the first step, right?
Now, what about if you wanted to get rid of some of this inhibitor in you and you wanted to trip on DMT endogenously without having to digest anything?
You know, that's the other side of the story, right?
And that's the funny thing Terrence McKenna would always say it's illegal, but everyone's holding.
Right, right, right.
Exactly.
And yeah, and his brother, Dennis, is actually the one that pulled the conferences together where I got to meet Egon and the new Nautics team for the first time.
But yeah, the McKennas have quite an incredible legacy.
But yeah, if we can determine how to inhibit this enzyme, Then you can also obviously determine how to potentially accelerate the enzyme, right?
So if there are disease states where people are deficient in this enzyme, maybe we could help those people by making the enzyme more efficient.
If there are opportunities to also work in psychiatry to help modulate mind, You know, areas like so much work going on now with psilocybin, so many other psychoactive substances that are showing benefit in some populations.
And so, if we can get an understanding of how to regulate this enzyme and potentially regulate DMT production endogenously, there's a lot of possibilities there.
I mean, the first and foremost would be can we do something to help schizophrenics because it's a terrible, debilitating disease?
Do we know the.
The biological function of DMT?
Like, what is, why do humans need DMT?
It's a great question.
We don't know that.
We don't know that.
But, you know, there's a lot of things we don't know.
There's a lot of things we don't understand about dream states.
Right.
You know, when you're dreaming, what's happening?
I mean, we understand what the brain is doing in terms of brain waves and these types of things.
But, yeah, there's consciousness there.
There's another scientist, Bruce, and I'm forgetting his last name now, but he presented at the Ethnopharmacological Search for Psychoactive Drugs meeting.
And, In both 2017 and 2023, we had the 50th gathering or the 50 year gathering of this meeting.
That was probably the most important drug conference that no one's ever heard of.
It was sponsored originally by the federal government in 1967, it was the first ethnopharmacological search for psychoactive drugs meeting.
So, this is before the Controlled Substances Act.
But everyone met in San Francisco and discussed that McKenna's were there.
Terrence was really instrumental in organizing that meeting.
Alexander Shulgin, many of the luminaries of that area.
Strassman was probably there.
Yeah.
Timothy Leary.
I mean, all these guys.
And they had this wonderful meeting and a proceedings book was put together.
And so Dennis McKenna decided, in honor of his brother and in honor of that meeting that happened, to reignite it and redo it in the 50th.
Anniversary of it.
So in 2017, in a beautiful countryside home in England, we all gathered there.
And that's when he invited me to come and talk about Kratom because nobody knew about it back in the 60s.
This was a new thing and we're interested in looking into it.
And so Bruce Dahmer?
Yeah, Bruce Dahmer.
That's it.
Bruce is fascinating.
Astrobiologist.
Yeah.
So he talks about endogenous tripping.
Breathing Techniques for Consciousness00:05:09
So, where you can actually get your mind into spaces where you can have just very positive, loving spaces where you can see incredible colors.
You can do all these things that you would do, say, on psilocybin.
Like you can use breathing techniques and stuff.
But without that, yeah, I'm not sure exactly what his techniques are, but he would be a cool person for you to talk to, I'm sure.
He.
You know, he was describing all of this.
And when I came back from the meeting where he presented this, this one was in 2023, I actually had just started practicing transcendental meditation.
And transcendental meditation, for me at least, would do a lot of that, what he described.
So you get your mind into a space where you're focused and you transcend where you are.
So you're conscious, but it's another level of consciousness.
So you're completely still.
You're quiet.
There's no breathing techniques.
There's no techniques with it.
It's a mantra associated, sound associated trance that you put yourself into.
And then I don't know if trance is the right word, but it's just a state of mind that you get into.
And then I've had experiences during meditation and it's only 20 minute meditation twice a day.
But I've had the experiences where I've had these incredible floods of colors and different, just kaleidoscope visions of things.
And I'm not taking anything, no medications or anything.
Do you listen to music?
No, no, you're completely in quiet space.
But Transcendental Meditation, TM, it's TM.org is the main website.
It's Ayurvedic, comes from the Vedas of India.
It's very rooted in this sort of peace, love, relaxation.
It's probably one of the meditative techniques that has the most science behind it as well, in terms of the benefits and outcomes that it has.
They have a whole TM program called Heal the Healers for physicians, nurses, healthcare practitioners.
How often do you do this?
Every day.
And what specific benefits do you get from it?
Just focus, calmness.
A lot of times it's a stress reliever.
So I go to the gym.
Five days a week, sometimes four days a week.
And that's a big stress reliever from a physical standpoint.
But the mental stress relief I really get from the meditation.
So just sitting quietly, first thing when I wake up in the morning, before the dogs get up, before I even have coffee, do that.
And then sometime in the afternoon, many times it's before I leave my office for the day, just shut everything down, sit quietly in my office, meditate for 20 minutes, come out of that.
Come out of that, takes a couple minutes to come out of that state because your body actually gets so relaxed that you could hurt yourself if you try to get up too fast.
Interesting.
But you're totally conscious of what's happening around you.
So, like if I hear, if I'm in my office and someone knocks on the door, I know they knocked on the door.
I can hear other colleagues, actually, your senses become kind of heightened, right?
You start to hear other colleagues faintly in their offices.
Wow.
But you can.
You can choose to focus on those things, or you can just choose to continue to perform the practice of the TM.
And they show with brainwave measurements, they show how it can really put you in this altered state of consciousness naturally.
It's not like I don't ever feel like I've gotten high, or I've never had a bad experience.
Let's just put it that way.
It's always a relaxing sort of, you know, kind of.
Okay, that stress is gone out of my life.
You never saw any interdimensional aliens when you were there?
No, no DMT like experiences.
No people have approached me.
But it's interesting because you kind of mentally think to yourself that you're actually descending below the waves into the calmness of the ocean.
So that all that craziness that's in front of you all day long, you're just taking time to.
To bring it down and let all that stress out.
Tremendous stress reliever.
Amanita Muscaria and Anxiety Relief00:03:03
I mean, I can't believe it.
I used to literally just clinch my jaws and grind my teeth.
All that's been gone since I've been doing this.
How long have you been doing it?
Just about, I started on March 14th.
I remember the day of 2021.
So it was after COVID. coming sort of coming back into reality.
I found a teacher locally in Gainesville and she taught me the technique.
And then we communicate still almost every month just to check in with each other.
We meditate together for 10 minutes and just kind of a bonus meditation in the middle of the day with my teacher.
And that's just really great.
But she makes sure that I'm keeping up and doing things right and still doing the practice correctly because a lot of people start, they learn.
And they quit halfway through learning and they don't get the technique down just right.
And then you can do it wrong and you won't get the benefits from it.
So, but it's very simple.
I mean, it's, I think, one of the hallmarks of what they talk about is how easy it is.
And it truly, truly, truly easy.
One out of eight Americans is currently prescribed to anti anxiety medications.
And that's why the Amanita muscaria mushroom is growing in popularity because of its ability to ease anxiety.
Even better, it's non addictive and it activates the same GABA receptors as benzodiazepines and alcohol, making Amanita a great natural way to help taper dependency.
Stress and anxiety make it easy to slip back into addiction, and that's why thousands are turning to Amanita muscaria from Minnesota Nice.
It's not a magic bullet.
Full recovery still needs community and support.
Its founder, Christian Rasmussen, used Amanita muscaria to overcome his own withdrawal and built Minnesota Nice to make natural healing accessible and affordable.
Their capsules kick in within an hour and last up to six to eight hours.
And the cost is a fraction of pharmaceuticals.
Minnesota Nice isn't hype.
They're building a legit Amanita market in the US, and that's why I'm super proud to have them sponsoring this episode.
Plus, they give back, like donating $12,000 to the Fungi Foundation and leading new research with Brain Mechanics.
Minnesota Nice wants to help you find harmony.
Head on over to mniceethno.comslash DJ and use my code DJ22 for 22% off your first order.
That's MNNICETHNO.
N I C E T H N O dot com slash DJ and use code DJ22.
Yeah, consciousness is such a funny thing how you can tinker with it by doing things like meditation and other stuff like that.
But it's also just so interesting to hear about ways you can tinker with the chemistry of the human body to alter consciousness.
Medical Malpractice and Cancer Risks00:15:20
It's like it's just this mystery that we keep poking at.
We can't seem to solve the riddle.
And not only that, I mean, I always think.
Being in the pharmaceutical world, you know, we always use placebos as controls.
So there's nothing there, but there's a thing called the placebo effect, right?
Yeah.
So people are thinking they're getting the benefit that they're supposed to be getting, even though they're taking nothing.
And so, what is the power of the mind doing in those situations?
Right.
No one monitors their brain waves, no one monitors what their neurotransmitters are doing when they're taking the placebo.
Right.
You know, there could be a whole, just personal psychoactive experience.
Happening in there that's making you feel like you've got this benefit.
It's crazy.
And then you have people that are like hypochondriacs that think, like, when they have a headache, they're dying of brain cancer.
I know people like this.
They get a headache and they go to the hospital.
And that can, I imagine, if you are in that state of mind and you're constantly believing something is wrong with you, maybe that could turn into something real or actually manifest into something real.
It's possible.
We always joked in pharmacy school we have to take.
A class called pathophysiology.
So you learn about all the things that go wrong when you have a disease.
And when you're learning about a new disease, it presents all the symptoms of that disease to you.
And so we would all sit there thinking, oh man, I meet a lot of criteria for this disease.
Do I have this disease?
Right.
So it does mess with your head a little bit.
And I don't know.
I mean, there's a lot of people that strongly believe if you believe it, it will happen.
If you believe that you're going to get cancer, you're going to have that manifestation happen.
But then there's the statistics and the odds of how many people are going to develop.
Cancer, anyway.
So it's a hard thing to manage, but I think the mind is just so powerful.
It would be interesting to see a study on this, you know, like people who are newly diagnosed with cancer.
That's like the thing.
It's like, that's a really unethical study to do.
Like to take one group and basically do it the way communicate, like have the doctors and the physicians communicate to the patient in a way that's like, you know, look, you have cancer.
It's not good.
You have X amount of days to live.
And then the other group being like, look, you have cancer, you're going to be totally fine.
Go outside, eat good food, you have a good chance to live, and see what the difference would be.
I would be curious to see what the difference would be.
Because I don't think, you know, if the person believes that they have a high chance of survivability and they're put into an environment that's positive and that's uplifting, and they don't have this self fulfilling prophecy that's hanging over their head like a dark cloud.
I bet you there would be a stark difference in outcomes.
Right.
And there may very well be.
I know, you know, I had a wife that passed away from cancer and she had a surgery where they believed it was going to be 100% curable surgery.
Once they removed the cancer, they thought it was going to be great.
She would be fine.
She would follow with radiation and chemotherapy just to make sure everything was gone.
During the radiation phase of that treatment, she developed another cancer.
And by the time that they got done with the radiation treatment and they figured out she was gaining all this fluid and putting on all this fluid weight, they realized that she had something called malignant ascites, which is actually the body fluid of your body fluid turns into cancer.
So it's liquid cancer.
There's no way to treat it, there's no way to cure it.
So essentially, you know, we went back in for a follow up visit and they said, unfortunately, the fluid we took off of you is.
You know, you're at stage four.
And this was just, this was literally a few months after her initial surgery that removed all the cancer.
All her cancer markers were gone.
And somehow it reverted itself.
And she was positive.
You know, she was being positive that we're on the right path.
But as soon as they told her what that new diagnosis was, she actually passed away within a couple of weeks.
It was awful.
It was just awful to watch and see that.
That's sort of both.
I actually lived that both sides of that story.
And my wife, my current wife now, just we're actually today is a one year anniversary of her biopsy for breast cancer.
And she ended up having breast cancer and had a bilateral mastectomy and a rebuild done.
And it's been, you know, she's quote unquote cured of cancer and didn't have to do chemotherapy or radiation.
Is a real blessing.
But the difficulty from the surgery, the pain, and all the changes of her body, the mental aspects of it, it's just been a hell of a year.
Wow.
I have a friend, one of my best friends from high school, when he was, I think he was probably two or three, he got diagnosed with leukemia and he fought it for like 10 years.
And his dad, And his mom were like, every day they were bringing in all kinds of people to like do magic tricks for him.
He's bringing in like WWE wrestlers in there to like say hi to him, like bringing him everywhere, outside, taking him on rides, getting him out of the hospital every day, playing games with him every day.
And like, not like he had no conception.
He like the way his dad and his mom communicated to him, he had like he had no conception in his mind that cancer was something that was going to kill him.
Like he didn't, and this would last from like three to maybe like 12 or 13, I want to say.
And he was in and out of the hospital the whole time.
And he said, like, during that time, like he knew he was sick, but he never felt like his life was in danger.
And the crazy thing about this is when he finally got cancer free in his life, I want to say it was between 10 and 12 or something like this, 13.
Like, literally a couple weeks later, his dad got diagnosed with that same child leukemia, which is like, according to him, it's this is like so incredibly rare that an adult gets that same child leukemia.
But his dad got it and like died instantly, like right after his son got cleared of it.
Wow.
And he's still in remission after all those years.
That's, yeah, it's an interesting story.
My son, my oldest son, actually has.
Was diagnosed with the old man's leukemia when he was, let's see, he's two years, he's 20 years old.
And he was diagnosed with CML, which is chronic myeloid leukemia, which is usually what happens to 50, 60 year old men, not young, healthy, supposedly healthy adults.
And it presented to him just as sort of allergies and feeling sick.
And we never really thought.
Twice about it.
And my wife is an oncology specialist, oncology nurse, and you just wouldn't really think about it.
But he called and said he couldn't keep food down and he was coughing up blood.
And I said, You need to go see the physician.
And they did blood work on him.
And sure enough, his white blood cell count was incredibly elevated, dangerously elevated.
And they ended up immediately getting him in the emergency room.
And it was lucky for us because we have.
connections in the medical world and in the pharmacy world to research world to find who are the best physicians to take care of this.
And we ended up getting the physician for him that was able to bring a lot of the drugs to market for this disease through clinical trials.
And he wanted to take him on because they don't see young men with this type of cancer.
So he said, this is something I really want to study.
And have him a part of us.
And, you know, it brought up a lot of discussions in our home about healthcare access.
You know, we're fortunate being in the system.
You know how to navigate the system very easily.
Yeah.
And because of the people we know, we were able to get him the best treatment very quickly.
But it also created a long discussion for us about healthcare access.
And the average person doesn't know how to navigate this system and certainly doesn't know how to do it.
I think it's like it's created to be confusing.
Yeah.
And there's this guy, this former UFC fighter, Ben Askrin, who just got an infection.
And it somehow got into his lungs, and he had to have a double lung transplant.
Wow.
And his insurance denied it, like straight up just denied his coverage.
And he had to get, he did like a GoFundMe.
And Jake Paul, I think, actually raised a bunch of money because he did like a boxing match with Jake Paul a couple of years ago.
And Jake Paul, like, I think he donated like $500,000 to fund this.
Wow.
But like, what a crazy world we live in when we have, we have like the worst insurance.
Like the worst insurance, whatever, in the world.
Like our insurance and our healthcare and all this stuff is like so backwards.
It's crazy.
It's so difficult too because it's literally a triangle.
It's like you have quality of healthcare, you have access to healthcare, and then you have payment for healthcare.
And we always hear politicians say, oh, yeah, we're going to improve access, we're going to improve quality, and we're going to reduce costs.
That doesn't work in the equation.
So, if you reduce one thing, you reduce the quality, you reduce the access, because the only way to reduce costs is to unfortunately reduce access or reduce quality.
So, it's a very difficult place to be.
And I think that the reason that we haven't had a very successful healthcare overall plan or discussion as a nation is because of that factor.
Everybody makes the promise and runs on the promise of, you know, we're going to do these things.
But when it comes down to reality, you just, you just can't do it in healthcare economics.
One of the most absurd things that I learned about a couple of years ago was that if you go to the doctor and you tell them you don't have health insurance, they literally will cut your price down by like 40% or something crazy.
Like just because you have insurance, they automatically inflate the price.
And they, I think it's legal.
It's part of the law now.
If you tell them you don't have insurance and you're self out, you're paying out of pocket or whatever, the price drops like huge.
It's amazing that the insurance companies have driven the cost of healthcare as much as they have.
And essentially, providers will bill to see how much the insurance company will pay.
And then the insurance company comes back and says, We're going to pay this much.
But that's higher than, like you said, what they would normally charge anyway.
So it's kind of a mess.
And we still end up.
Pushing all the fingers to point at the pharmaceutical companies for the cost of drugs.
And no one ever talks about the insurance being out of whack and being really what's causing a lot of this healthcare cost to just skyrocket.
Right, right, totally.
Yeah, and then to the cancer thing too, it is crazy that after all of the decades that we've been researching cancer treatments and all this stuff, we haven't found anything better than radiating people.
No.
You know, it seems like such a primitive form of treatment for something that we've been studying and spending so much, dumping so much money into for so many years.
Yeah.
I mean, we've had, there are some really good success stories, but you're right.
Overall, most people that end up with some sort of form of cancer end up with a radiation and a chemotherapy plan to follow through with it.
Very few times is it just a surgery that can take care of the situation.
And a lot of people dismiss that surgery as, oh, you're cured of cancer.
It's all good.
But that surgery could be disforming, it could be something that now creates pain for the rest of your life.
So there are other problems.
Yeah.
Yeah, and surgeries, I think it was like the second leading cause of death in America was like mistakes in surgery or like medical malpractice and like people getting infected in hospitals and.
Yes.
Mistakes, medical mistakes in hospitals.
As they say, hospitals are no place to get well.
Right.
And the mantra of pharmacists is drugs are to sell, not to take.
So, you know, there's a lot of side effects with medications, and unfortunately, people end up treating.
Some of the side effects with more medications.
And so you end up in this sort of catch 22 space.
And I've also, what is this, Steve?
Medical malpractice deaths are a significant cause of death, but there's no single leading cause of malpractice deaths.
Widely cited 2016 John Hopkins study found that medical malpractice errors are the third leading cause of death in the U.S.
Okay.
So in 2016, it was the third with an estimated quarter million deaths annually.
God.
Holy crap.
That's a lot, man.
That's a lot.
True.
So it's scary.
It is scary.
It's scary to think about that.
And it's scary to think about how opioid overdose has come close to that number as well.
You know, the preventable causes of death, I think, you know, all preventable causes of death are unfortunately the leading causes of death, right?
Yeah.
Slowing Aging with Spermidine00:02:19
Another thing I've always been fascinated by is like this.
Idea of gain of function research when it comes to medications and drugs, similar to like what Brian Roth is doing with his in North Carolina with that grant.
I think he got a grant from DARPA to take the psychedelic trip out of psychedelic drugs to treat things like PTSD for soldiers and stuff like that.
Which is, I mean, I've talked to many people about this on here and I'm like, and I've always wondered how you would get the benefits of psychedelic drugs without the psychedelic trip.
It seems like that is like the Most important aspect of the drug.
Aging isn't just about getting wrinkles or feeling tired all the time.
Inside your body, there are 12 hallmarks for aging that determine how well and how fast you age.
When these systems start to fail, it's not just about how you look or feel.
It's the same biological breakdown that leads to Alzheimer's, cancer, heart disease, immune failure, and loss of mobility.
Your energy drops, inflammation becomes constant, and your cells lose their ability to repair themselves.
The damage builds silently for years until it shows up as disease.
Scientists have discovered a compound.
That helps slow all 12 hallmarks of aging.
It's called spermidine, a molecule your body makes naturally, but produces a lot less as you get older.
You can find traces in soybeans, mushrooms, and aged cheese, but not enough to make a difference.
Most spermidine supplements come from wheat germ extracts that vary in potency and don't provide enough of the active molecule to be effective.
And that is why I take Clean Being by Verso.
It uses a pure, third party test of spermidine paired with ingredients that calm inflammation and protect your cells, targeting multiple causes of aging.
In a long term human study, people who consumed the most spermidine lived almost six years longer than those who consumed the least and had lower rates of heart disease and early death.
And after taking clean being for some time, I've noticed it helps me fall asleep faster.
I wake up way less groggy in a far better mood.
My hair's growing better.
I don't get sick as often.
And believe it or not, it's actually improved my vision.
You can't stop aging yet, but you can slow it down.
Head on over to ver.so and use the coupon code DANI at checkout to save.
15% on your order or go to ver.so slash Danny.
Altitude Sickness and Coca Leaves00:02:54
It's linked down below.
Now back to the show.
And so I think, you know, we have to learn that, right?
Yeah.
You have to learn if that's really the case or not.
Certainly, you know, some would argue it's going to be a lot safer if you're not going to have a trip, right?
Because you could have a good trip or you could have a really, really bad trip.
And, you know, taking that variable out of the equation, if you can still get a benefit.
Yeah.
It would be pretty big.
Yeah, but it's like safety, like physical safety is obviously important.
But I mean, even if you have a bad trip, you're not in physical danger.
And oftentimes the bad trips are the most beneficial ones psychologically.
That's what people say too.
So, you know, it'll all bear out over time.
It's just this weird stigma too that's involved with these types of drugs and how, you know, politicians and media.
Pundits try to like label them as evil, dangerous, going to kill people.
But, like, you know, parents are evil.
You know, parents that smoke weed or get high around their kids are, you know, irresponsible and doing harm to their kids.
And, like, the problem is these people that project this narrative to the public for the most part have never experienced any of these drugs before.
And I think there's a, I think there's a, one of, Joe Rogan's bits in one of his comedy specials, where he's actually talking about that.
He's like, Is it?
He's like, They say it's dangerous that I smoke weed when I'm around my kids.
And he's like, You know what happens when I get high and I'm around my kids?
They maybe get a few extra hugs and I worry about objects more.
Yeah.
Yeah.
It's really interesting.
You know, I mean, I think there's a lot of things that get completely twisted and taken out of context.
The perfect one for me right now.
And work that we're hoping to start soon.
We're just waiting for our shipment to arrive of coca leaf from Peru.
But coca leaf is something that I got the experience to try earlier this year in Peru.
I went from Gainesville, Florida, a couple hundred to possibly a few more hundred feet above sea level, to up in the Andes Mountains, where we were 9,000 feet above sea level.
And I hiked a mountain.
I mean, Chewing coca leaf.
Right.
And it's supposed to be helpful for that, right?
It's good for altitude sickness.
It's also good for stamina, energy.
You know, we basically hiked this mountain for three and a half hours.
Ancient Ethnopharmacology History00:07:45
No, not one time did I get hungry.
Not one time did I get exhausted, winded.
And I'm not a mountain hiker at all, anyway.
So it was just a cool, cool experience.
And experiencing coca leaf firsthand, I didn't feel anything.
Psychoactively.
Yeah, my mouth got a little bit numb.
Like, kind of when you go to the dentist and you feel that you get Novocaine or whatever they give you for anesthetic, local anesthetic, and you'll drool out of your mouth for a while or you might bite yourself.
Yeah.
It's nowhere near that intense.
Interesting.
But that's the same type of feeling.
It's almost like when you're finally coming off and you feel it.
Yeah.
But you can still chew and.
Drink and do all the things that you would do.
So, what is it comparable to, in your opinion?
Is there anything that you could compare it to?
So, I mean, energy wise, I would definitely say something like a good, strong cup of coffee or energy beverage, highly caffeinated beverage.
But there's no caffeine in it, of course.
But the stimulant effect is definitely there.
But there's absolutely no.
Um, there's no psychoactivity, so what happened?
This is why I'm saying this is really interesting to me because um, cocaine was the second alkaloid ever discovered, so ever isolated.
Morphine was the first, cocaine was the second.
We know the history of both of those substances.
When did cocaine first created?
Wasn't it like before World War I?
Yeah, it was in the 1800s, 1800s, yeah, in the mid 1800s, I believe.
And maybe we can, Steve, yeah, we'll find it for us.
But um, morphine was 1802.
And I think cocaine was in the 1820s.
Let's see if my trivia is.
Oh, 1859.
1859, by the German alchemist Albert Nieman.
Albert Nieman.
So these guys were both pharmacists.
He was a pharmacist, and then Frederick Serturner was the one that isolated and purified morphine for the first time.
Both Germans, both pharmacists.
And when cocaine was realized, originally cocaine was thought to be.
Good treatment for other addictions.
And so, yeah, heroin was originally marketed as treatments for addictions as well.
And some of these things, it's wild, crazy where things went.
The thing is, is that people started using these things and stopped using the other things that they were having problems with because these were much better, right?
So, that reminds me, I don't mean to interrupt, but there's this guy that we actually have coming in here soon from Germany who.
Took samples from Egyptian mummies.
Oh, yeah.
From like thousands of years ago, and he found cocaine.
Yeah.
Have you heard of this?
Yeah.
Yeah.
So we know, and in fact, in the meeting that I was describing to you, this ethnopharmacological search for psychoactive drugs, there's a lot of ethnobotanists, archaeologists that were in that meeting and talking about many things, some of which were really fascinating to me because they found in Egyptian tombs, they found in Um, tombs in the Andean mountains, right?
People were buried with uh coca leaf either in their mouths or in their body, like they would have them in bags with them.
Um, and so coca leaf has been revered, and it's interesting if you look at the history, we always think it's a South American thing, but coca leaf actually spread across parts of Europe.
And into northern Africa.
So the climate is similar.
They could grow the plants.
And, you know, not exactly the same species, but a very cool story that was unfolding there where they found these.
Not only have they found cocaine in a lot of these, but they found other psychoactive substances and mushrooms, different types of things that have also been shown.
What does he say, Steve?
Henet Tau was the mummy that they found cocaine in.
A priestess from ancient Egypt and other remains, the toxicologist and her team, they found this.
They found the coke, though.
They found traces of cocaine, nicotine, hashish in the mummy's hair, bone, and soft tissue.
Whoa.
Yeah, so it's pretty well known that substances were being used.
There was another talk at this meeting where.
Many of the stories in the Old Testament of the Bible, which is the foundation for our three main global religions Christianity, Judaism, and Muslim, the Koran.
So many of the stories that are in there are thought to be explained by hallucinogenic substances.
Yeah, there's lots of theories.
Yeah.
And so it was interesting discussions in the meeting and talking about this, but there had always been a lot of speculation, but really no.
Hard evidence until the last few decades when they've been able to actually get into some of these tombs and find substances that were buried with people when they were either mummified or just buried and entombed with many, many different trinkets or pouches or whatnot that were filled with psychoactive substances.
Yeah.
Yeah.
There is so many theories when it comes to like psychedelics being the foundation of religion and stuff like that.
But there is.
I mean, there's tons of evidence.
Like, have you ever heard of Galen, Marcus Aurelius' physician?
He has, he's written more than 10% of all of the ancient texts that we have from antiquity in Greek.
And there's tons of books written about him.
There's tons of PhD dissertations written about him because he was just a prolific philosophical mind who also happened to be like, The surgeon general of the Roman Empire.
And he wrote extensively about all of the prescriptions and medications, cocktails that he was putting together and testing on people and giving to Marcus Aurelius, including opium.
And he was creating these venomous cocktails with vipers.
He would use 11 different North African viper venoms and viper flesh combined with opium into this cocktail called a theriac that he was giving to Marcus Aurelius because Marcus Aurelius was paranoid.
That he was going to get assassinated by somebody with poison.
That's how they traditionally, that was the most common way of assassinating somebody, was like getting them with like scorpion poison or snake venom or something like that.
Peanut Allergies and Cocaine Links00:03:29
So he was every day drinking this theriac concoction to keep his immune system robust against the stuff.
It's just fascinating to learn about ancient medicine being used in Jesus' times.
Yeah.
I mean, it's interesting today because the United States is really the only country in the world that has peanut allergies.
And that's because we stopped exposing people to peanuts, infants to peanuts, because of a report that was really not scientifically sound.
But it created a paranoia amongst a lot of parents that stopped giving peanuts to kids.
And here we are today.
You hear about peanut allergies sometimes when you're on a flight, severe nut allergies, don't use any nuts.
That was never an issue up until.
They came out with this wacky study that told parents not to give peanuts.
And then the American Academy of Pediatrics or somebody sort of validated that as an issue.
And then it propagated into what it is today.
And really, we're the only country in the world that has this.
And I got that out of the new FDA commissioner, Marty McCarry's book, most recent book, which is really highly recommended.
Reading, um, but one of the chapters in there is this whole peanut allergy.
What's this guy's name?
Marty McCarty.
Marty McCarty, Marty McCarty, McCarty, M A K A R Y. He's the current FDA commissioner.
Oh, okay, yeah, interesting.
So it's really good stuff.
Um, yeah, it's like, why don't we is there a way to address that now?
Like, what, like now that we have this epidemic of peanut allergies in kids, like, how do you is there a way to reverse that or address that problem?
I mean, these kids are.
So unexposed to the peanuts that if they get exposed even to it in the air, they're going to have anaphylactic reactions.
So it's, it really is about having kids being exposed to peanut butter, peanut, you know, containing foods early in their life.
And yeah, it can be, it can be problematic if they get too much of them early in their life.
But it sets them up to be okay later in life.
Right.
So I mean, I love my peanuts.
Yeah.
Yeah.
Have a hard time getting it done.
So I'm glad I wasn't boring during that time when all the peanut jelly started coming.
No, what my kids' elementary school wouldn't let them have peanut butter jelly sandwiches.
They had to do like sunflower butter or some goofy stuff.
Yeah.
They've changed cashew butter.
Yeah.
So crazy.
Whatever it is.
Yeah.
Almond butter.
Yeah.
Many different things.
Maybe they can come up with peanut vaccines and they could sell those, make some money.
It would be good.
Um, Yeah, it was this prevalence really.
What is this?
Peanut allergies were not always so common.
The prevalence in American children more than tripled between 1997 and 2008.
Yeah.
Oh, my God.
Yeah.
So it's a sad thing.
I mean, the peanut allergy rates across the globe are almost unheard of because you just don't hear people talking about it in other countries outside of the United States.
Yeah.
Kratom Industry Monopolies00:14:01
So going back to coca.
Yeah.
Coca seems like it could be similar to nicotine or caffeine, maybe, in that group.
So, why is it illegal in the U.S.?
Is it specifically because of its connection to cocaine?
So, interestingly, yes.
First, the answer is the connection to cocaine.
But more interestingly, actually, the U.S. has it in a restricted category of Schedule II of the Controlled Substances Act, which means it's legal to use, it has a medical benefit.
Oh, really?
Although, like cocaine, like for.
Well, because cocaine is still extracted from the plant itself.
Right.
And so, if you make the plant schedule one, then you can't actually use it to get to the pharmaceutical grade cocaine.
Because they use it for like eye surgery and nose surgery.
Yeah.
And in fact, all the coca leaf that has been imported into the United States for the last, I don't know, 100 some years has all been done by the Coca Cola company.
And Coca Cola had their original formula, had coca leaf and it had the cola nut.
So you had a Coca Cola name.
And eventually, They made the formula where they took the cocaine and the alkaloids related to cocaine out of the coca leaf extract.
But Coca Cola and Coke Zero are the two formulas that still contain coca leaf extract, but obviously no cocaine in those formulas.
And Coca Cola tried to remove that and distance themselves completely in the 1980s from the coca leaf trade.
But when they did that and they came out with new, Coke, there was a huge backlash of people saying this is terrible.
This stuff sucks.
So they were forced to go back to putting the extract in.
And so they import coca leaf into a company in New Jersey called the Stepan Company.
And that company is a company that then processes the coca leaf, separates out the alkaloids, purifies them, sends them to a company that purifies them for the pharmaceutical industry and the forensics industries.
And then the remaining extract.
Goes to Coca Cola as part of the formula.
So they're the only ones who are allowed to have this formula.
Right now, they seem to have a monopoly on it.
So we're finally getting to the point where, you know, it took me two years to get approval and connections and everything to get Coca Leaf onto my DEA license so that I could do research with it.
So, but we finally crossed all the bureaucratic hurdles.
The last hurdle, believe it or not, it's approved by the federal government in the US that I get it.
It's approved by the government in Peru that they.
Provide it to me.
The last hurdle is an air carrier that will bring it into the United States.
An air carrier?
Yeah, like FedEx or DHS.
So you have to go contact one of them and get them to.
So they're not interested in carrying a controlled substance in large quantities.
We'll get it worked out at some point, but it's been a problem.
I got a guy for you.
I could potentially go down there myself and do it because I have the import permit.
We got Roger Reeves.
We got, I don't know if you remember Roger Reeves.
We got this guy who was a pilot for the cartel back in the 80s or whatever.
And he worked, he hired this guy named Barry Seal during, I haven't heard of Barry Seal during Iran Contra.
Anyways, he was smuggling like millions of dollars of pot and cocaine every single day between Mexico and the U.S.
Oh, I don't know.
He's still got planes.
They made a movie about him.
I'll hit him up.
Yeah, they did.
It's called American something.
American something.
I'll have to find it.
It's with American Made.
American Made with Tom Cruise.
American Made.
Oh.
Tom Cruise, one of his lesser names.
I'll get you his number.
Yeah.
Yeah.
So we can work that out.
But, uh, but yeah, it's been, um, it's been a process to get it.
Now, I, I mentioned the United States actually has one of the least stringent categories globally.
The World Health Organization has banned coca leaf.
So it can't be used anywhere in the world.
It's completely illegal anywhere in the world, except for the countries in South America where it's used in the indigenous population.
So it, It's allowed to exist in Peru, Bolivia, and Colombia.
Of course, Colombia is also in part the major producer of the illicit supply of cocaine.
But there are registered and growing areas.
Getting conversations with a faculty member of the University of the Andes, and it's really fascinating.
They're doing metabolomic studies and studies on the plant where people are growing it in different regions of Colombia and they're talking about it having different flavor profiles.
Even though genetically the plants are exactly the same.
But they actually want to start doing it like the wine industry does.
You know, Tawa makes a big difference on the flavor profile of the grape that's produced in the wine industry.
And so they're saying, they're making this argument in the coca industry that, you know, if they could get legal trade across the globe, then there'll be all these different flavors and types of coca leaf that could come out.
So when I got off the plane in Lima, Peru, First thing that I hit was a kiosk full of coca leaf tea bags and coca leaf powders.
I went to the coffee bar there and you can get coca leaf tea.
Oh, wow.
So I immediately ordered a coca leaf tea, had my coca leaf tea.
So I was definitely testing positive for cocaine at that point.
But I went to this Coca Summit down there in Peru.
And the whole idea of the Coca Summit was to bring together many of the thought leaders around this plant, researchers, tribal.
You know, leaders in South America and have a week long discussion around everything and how could we best position ourselves for what's coming this year.
And that what is coming this year is the World Health Organization sitting down to reconsider the scheduling of coca leaf.
So there's a possibility that the World Health Organization will decide to remove coca leaf globally from this most restricted level.
It may still be restricted.
But they might pull it completely out.
There's no indications that coca leaf can be habit forming or addictive.
But obviously, if you pull the cocaine out, you know, it's a much, much bigger danger by itself.
Which is not an easy task.
I mean, you have to have like, you have to use gasoline or diesel fuel and stuff like that.
This is the way they do it, the cartels do it, right?
Yeah.
Oh, there's like a nicer, easier way to do it?
Yeah.
There's a more elegant way to do it.
Oh, okay.
Like the companies.
In the United States, that are refining it for the pharmaceutical industry, it's a completely different grade of things that are so.
This is something that somebody could do in their basement if they wanted to.
Um, if they wanted to, it would be a lot of work to get enough cocaine to actually work with, right?
Uh, and have something happen.
But that's been the fear that if you make the leaf widely available to people, they're gonna abuse it and turn it into cocaine.
It's not that simple.
That's been a big analogy for us right recently because I just have this feeling that Kratom is headed in that direction.
So the leaf is what first showed benefit for centuries in Southeast Asia.
The leaf has been used by laborers to increase their endurance, increase their energy.
Elevate their moods from working out in that hot sun environment.
And then they also realized that they could lessen the withdrawal they had if they didn't have their opium or their heroin.
They just increase the amount of kratom or kratom that they take, and they wouldn't have as bad of withdrawals.
That's where we got interested in this in the first place with the opioid crisis ongoing, could we, like I said before, could we find a solution from nature?
I mean, opioids came from nature.
There should be something out there in nature to.
Counteract or counterbalance that existence.
Always been a philosophy of mine since I was a teenager, actually, and really why I wanted to go into pharmacy.
Most of our drugs that are prescription drugs are either direct natural products or influenced from natural products.
So that about 25% are derived from natural products directly, and about 75% were inspired by natural products in one way or another.
So, they have nothing to do with the natural product anymore, but they were inspired by the learnings of that.
So, it's really a cool basis.
And we wanted to learn that with Crotom Leaf.
So, we started studying Crotom Leaf.
And then, as things have evolved, when did this start?
What year?
So, I started this in about 2004, 2005.
So, we've been going 20 years on this.
That's wild.
I only heard about it a year and a half ago.
Yeah.
Well, it's really become popular in the last few years, particularly after COVID.
The first popularity, really, with it in the United States was in 2016, the DEA announced an intention to place kratom mitragynin and 7-hydroxymitragynin into Schedule I of the Controlled Substances Act.
And that's what, when people had never heard of it before, suddenly they heard of it and, whoa, the DEA is interested in this and they want to.
Put it into the most restrictive category where all the really hardcore drugs of abuse are.
So let's go try this stuff out, right?
A lot of people tried out at that point in time, it was really only leaf products.
That point in time, most people realized that it wasn't that interesting from the standpoint of you're not going to get high from it.
It's just this leaf material, it's energizing, it does things for you, but it wasn't that great.
And so a lot of the interest fell off at that point.
But then some of the manufacturers started taking the leaf material and extracting it and making extracts and concentrates.
And so making it more and more potent, more and more powerful, so that you ended up with now something that could deliver you a bit of a punch, if you will.
Right.
And then that was what happened really during COVID.
And we saw use start to really increase during COVID.
You know, pre COVID, I have lunch with addiction physicians, and they're like, Hey, some of our folks are self treating themselves with kratom, and it seems to be helping them with their opioid use, limiting their opioid use.
It immediately brings to thought of what we just talked about earlier, right?
Is this just a substitute for their opioid use?
Is it a substitute, or is it really helping win them off?
And that's been a lot of the science we've been trying to study and figure out.
But certainly, as these extracts started to appear, and as we came out of COVID, those same addiction physicians said, Hey, you know, I got people coming in now that want to get off of these shots and not Kratom shots, and they're not able to get off of these without really help, right?
And we don't understand what's the right treatment for it, even.
So, most physicians, if they see someone with a What we call um, kratom use disorder instead of addiction, they're just using it inappropriately, too much of it.
It could be dangerous use for that person, but they have severe consequences when they stop using it, and that generally is withdrawal.
And that withdrawal can be anything from just anxiousness, irritability, or even um, restless leg syndromes, pain, jitters, all these types of things, and so that if they Take kratom again, then they all that goes away, and so they're sort of now stuck physically dependent on this stuff.
So, how do we get them off?
Most physicians are using buprenorphine or Suboxone, like the opioid treatments, but the pharmacology is so much more complex than just opioid.
These have very strong serotonin and very strong adrenergic interactions, and so serotonin is our you know mood, sort of enhancing all the.
SSRIs like Prozac and these drugs inhibit the reuptake of serotonin.
Stimulant Overdose Risks Explained00:15:48
So they increase the amount of serotonin in the brain, which gives us that satiety, that sort of feeling of pleasure.
It's really mood enhancement for depression treatment.
Then we have the adrenergic system, which is our fight or flight system.
That's what gives us that stimulant like effect.
And so you're getting all of these activities, including the opioid activity with that.
But What we're looking at in treating people that are having this use disorder or overuse is only hitting the opioid component of that with something like buprenorphine or Suboxone.
Right.
So we're ignoring the serotonin, we're ignoring the adrenergic piece.
And is that important?
We don't know.
But I don't know that we're doing the best job in treating that.
But as those extracts have gotten stronger and stronger and stronger, they've realized that they can convert.
These very concentrated extracts into a compound called 7-hydroxymitriganin, which is the compound.
Is this the stuff they just banned?
This is banned.
7-OH?
Yeah.
In the state of Florida, it was emerging.
Just last week.
Banned last week.
Yes.
And then the federal.
Does this stuff have that in there?
Yeah, but a very little, very little amount.
I think less than 0.02% is what it said on the website.
Less than 0.02%.
So would this be illegal to sell now in Florida?
No.
Okay.
It's not illegal.
White Rabbit.
Our sponsor.
It's brought to you by White Rabbit Kratom.
Yeah.
My favorite energy drink.
Yeah, it's interesting.
This is typically what we see of leaf material products or even many extracts.
There's a very low level of 7-hydroxy, if any detectable 7-hydroxy in those products.
7-hydroxy is created in our bodies by metabolism.
So the main alkaloid, mitragynin or mitragynine, is oxidized in our liver and in our intestine to 7-hydroxy mitragynin.
And so it's a small percentage of the total amount that's converted.
So it's not like you're taking it pure and it's also being taken in context with all the other alkaloids and all the other metabolites that are coming with the Mitrigana speciosa or Kratom plant, right?
So you're getting, I call it a pharmacological shotgun.
It's really tons of different systems in our body are getting turned on, turned up.
I think big mixing board is like kind of all kinds of things being adjusted.
I've always referred to it as a complex symphony orchestra.
But what was realized is, and as we said, there's such small amount of 7-hydroxy present in the leaf or in many of these products that it's not economically feasible to extract that and try to produce products that are 7-hydroxy products.
So what they've figured out is that if you take the very concentrated extracts that are mostly 75% maybe mitragynin, you can treat that with chemicals and synthetically produce 7-hydroxy.
And so, a lot of this work is obviously not being done in FDA approved laboratories that are clean and safe.
And then there's a whole slew of byproducts that are also within that mixture that are being put into these products.
Many of those byproducts, we don't know what they are, if they're dangerous, if they're more addictive, less addictive, whatnot.
And so, there's two factors of safety here.
That's one of them.
The second factor is the 7-hydroxy compound is very purely opioid in its activity.
So it only really interacts with opioid receptors, just like prescription opioids.
And so that's what you will find at a pharmacy.
You can go to the pharmacy and get a prescription for Oxycontin or morphine, sulfate, or whatever it is.
That's being prescribed to you by a physician.
Hopefully, things are being monitored and regulated, and you know.
How that person's using that prescription product.
This is essentially a prescription product that's available at smoke shops without a prescription.
Without a prescription.
And, you know, when you have access to something that powerful, it becomes a public health crisis in the waiting.
Because what you could eventually have is just a whole new wave of addiction, of problems where people are succumbing to this 7-hydroxy.
We don't think, although we don't have definitive answers for a lot of questions around kratom itself, but we really don't think the amount of 7-hydroxy that's produced by metabolism in our bodies when you take the whole kratom product is problematic.
Right.
If you're using it responsibly, it's kind of like anything, right?
Alcohol used responsibly.
Everything.
Everything's okay.
I can go to the store across the street right now and buy enough alcohol to kill myself in an hour.
Right.
Like, yeah, you gotta, everything has to be within moderation.
But, like, when it comes to drinks like this, for example, this white rabbit, first of all, when you did a study, right, on a wide or a large majority of individuals that signed up for the study.
And what were the parameters of the study and how many people were involved?
So, I don't remember exactly how many people were involved in total, but we documented.
Tens of thousands of use events.
So, this was conducted by a colleague of mine, Dr. Kirsten Smith at Johns Hopkins University.
She is, her PhD is in more or less the social work, social sciences aspect of interacting with humans and understanding how they use substances and why they use substances, right?
And so, she designed what's called an EMA study or an.
Ecological momentary assessment.
So that's a lot of words.
EMA is much easier to say.
But what she was able to do was develop an app where people could, every time they were taking their Kratom product, they would log in, say how much they were using, say how they were feeling, saying what time of day it was.
So we were able to get thousands, tens of thousands of user events across a period of time.
To see how that worked.
And, you know, these people volunteered for the study.
So these were people that really wanted to contribute knowledge and also probably want to help keep this product available in the marketplace.
We didn't have people that were, I shouldn't say we didn't have, we had some small percentages of people that were using it purely to try and get euphoric highs.
But the majority of people that were using Kratom were really trying to do it for the benefit.
You know, perceived benefit that it was giving them energy.
Oh, really?
The stimulant effect?
The stimulant effect, elevating their mood and treating their pain.
I mean, those are really the top motivators for why people use this and seem to use it responsibly.
It seems to be beneficial to them.
What we don't understand is where the benefit starts to cross over into a harm and how much time that takes, how often someone uses it.
We know that tolerance.
And humans seem to develop.
So, in other words, over time, you need more to get the same effect.
Right.
I mean, I've talked to most people that generally use two to five grams of powdered material two to three times a day.
And I've gotten emails from people that are consuming, so, two to five grams a day, three times a day is maximum 15 grams a day.
I've gotten emails from people that are consuming 90 to 120 grams a day.
Um, to be able to get the benefits, and those people, this is how much again?
I think it said 45 milligrams of leaf material in that, so or extract material in that.
So, very it's hard to say, moderate amount, it would be a very moderate amount.
This would be more similar to that range of that two to five gram, yeah, uh, level according to their mitragynin content.
It has 30 milligrams of mitragynin.
We see about um.
20 milligrams in a gram of leaf.
So, this isn't even really two, three grams of leaf material.
And I know one of the biggest problems with it is that it's highly addictive.
Just like caffeine can be highly addictive.
I know nicotine is really, really addictive.
Right.
And everybody's different with how much they can handle with addictive substances.
But me, subjectively, like that's, I'm no more addicted to that than I am coffee every day.
And Like, are there any studies or do we know what do we know about like long term effects of this of people using it responsibly and not abusing it?
Yeah.
So, we don't know anything clinically about long term effects.
And that's a big limitation with all of this work.
We don't even know anything in animals on long term effects.
It's difficult and expensive to do long term studies in animals.
And then at the end of the day, how translatable is that study that you just spent months of your life doing in an animal like a rat?
How similar is that really to the human experience and what happens in humans?
We know that our bodies.
Our human bodies metabolize kratom differently than do dogs, monkeys, mice, and rats.
So, we already know that there are differences.
Humans get a different exposure to the alkaloids when we give a tea product, say, to a rat versus a human in a clinical setting.
We can measure their blood and we can see that the ratios of the alkaloids actually are different.
In those different species.
And so it's not a directly translatable thing, but the animal studies still give us the best marker for what we could predict will happen in humans, right?
And gives us a good basis of where to start.
So that's kind of what we know right now.
And then, as I said, chronic use, the only thing we have to go by are what people self report to us.
And so if someone says, hey, I've been using, Two grams every day, uh, twice a day or three times a day for the last 10 years, and I've been very strict about limiting how much I use.
I've never felt anything psychoactive, I've never felt, um, you know, anything like I was taking a drug, but I got this benefit of focus, energy, yeah, and I got this other benefit of hey, you know what, my knee that's always bothered me doesn't seem to bother me as bad as it used to, right?
Problem is when people start to use these products with the intent of getting high or the intent of replacing their opioid that they were taking before to get that pain relief.
And it works a while.
It works for a while.
What we understand, again, nothing in the clinics, nothing controlled trials, but they tend to work for quite some time.
And then, That tolerance starts to kick in, and when that tolerance kicks in, we don't know it could differ for everybody as well.
Um, people can metabolize these things differently.
We know that there's what we call slow metabolizers, normal quote unquote metabolizers, and then rapid metabolizers.
And so, and we know that with all types of drugs.
Um, and so people that are slow to metabolize drugs generally don't need as much dose because they can use a lower amount, it stays in their system longer.
Are slow to get rid of it.
They're slow to metabolize it.
We call that a lightweight.
Yeah.
And then you have your ultra metabolizers that, you know, they start to eliminate things much faster.
They need more of it more often to get that benefit.
Then drugs themselves can actually induce that activity.
So they can induce our metabolism to speed up.
So these are many things we still don't know about kratom.
In long term use, does it actually increase the liver's efficiency and metabolism so that you're depleting the alkaloids out of your system faster?
You need to take more in order to get back up to those levels.
And just like with opioids, I think, and other drugs that create a tolerance situation, you build a tolerance to one effect that you're trying to seek while you don't build tolerance to other effects.
Like with opioids, you see tolerance to the pain control much faster than you see to the constipative or respiratory depressive effects.
And as you have to increase the amount of opioid to Still take care of the pain you're experiencing, you're getting closer and closer to having more constipation and closer to respiratory depressive effects.
And one of the things about the kratom is it doesn't have the respiratory effects.
This is what Hamilton Morris told me.
He said that the kratom does not have the respiratory effects that opioids do.
Yeah, it seems to be less respiratory depression.
I wouldn't say that it doesn't have it at all.
Okay.
I think it depends again on the dose, right?
It depends on how much someone's taking and if they're.
Overindulging, it could be the case.
But interestingly enough, most of the poison control center data and emergency department data that's been generated or collected indicates that overexposure to kratom is actually more similar to a stimulant overdose where people get agitated, they have cardiovascular events, and they can have seizures.
And so these are all more associated with stimulant.
Type overdose like cocaine overdose.
It also could be causing a phenomenon called serotonin syndrome, where you get too much serotonin in your body.
That gives you the same type of effect.
Managing Complex Withdrawal Symptoms00:12:53
And we know that these kratom alkaloids interact with, as I said before, opioids, serotonin, and adrenergic receptors.
Interesting.
You have all this stuff sort of going on at once that could be contributing to that.
We also know that all three of those pathways are involved in pain control.
I mean, we always think of opioids as being the The primary gold standard for treating severe pain.
But we do use serotonin compounds that can modulate serotonin levels for chronic pain.
So we use some tricyclic antidepressants like amitriptyline, has been used to treat neuropathic pains.
And then the adrenergic system has also been known to be involved in pain signaling pathways in our brain and our.
Brain stem, sorry, spinal cord, and how the signals are communicated.
And so there's this sort of triple whammy effect going on in terms of pain relief that it's really fascinated and opened up new doors because we've never pharmaceutically thought to treat someone's pain through all three mechanisms at once.
And kratom seems to potentially be doing that.
Coming back to the respiratory depression is really a fascinating story because there's one camp that says this is due to how the molecules are interacting with the opioid receptors and they don't recruit a certain protein called beta arrestin that is associated with some of the side effects like respiratory depression and constipation.
That theory, that sort of bias signaling theory, has not really panned out to be.
Solid definition.
There's still a camp that believes in that, and there's a camp of researchers that don't really believe in that.
I tend to think that what's happening with kratom and the way that it is having less respiratory depression is because it has all of this pharmacological activity in it.
And we know that one of the serotonin receptors, called the 5 HT1A receptor, is very different from the 5 HT2 receptors where the psychedelics act.
It's a psychedelic, right?
Yeah.
So 5 HT1A actually activation of that receptor is known to decrease opioid induced respiratory depression.
And so I personally think.
It's probably this soup of pharmacology, this pharmacological shotgun that's activating many different systems in our brain that's affecting the respiratory depression aspects of this.
So you're not getting as much respiratory depression because you're activating other systems that are keeping that respiration center healthy and going.
Right.
Wow.
I got to take a leak real quick.
We'll be right back.
It's funny.
I just did an emergency department.
At North Florida Hospital in Gainesville.
I talked to the emergency department this morning about kratom and all the products.
Oh, really?
Yeah.
Did an in service for them.
What were they asking specifically?
Like, what do they want to know?
I mean, most physicians just don't know anything about it.
So they want to know more about it.
They wanted to know, you know, what is this thing that got banned last week?
Yeah.
And many people are talking about seven hydroxy products as if they are kratom.
And I think that's been the.
The biggest thing with kratom is it's one of the commentaries we've published recently is that not all kratom is equal.
It's like calling it, it's like alcohol, right?
Different types of alcohol.
Yeah.
You definitely have that whole spectrum there where you have, I always sort of talk about like even the seltzer, alcohol seltzers like white claw or white beer is more closer related to something like the leaf that has got the alcohol in it, but.
Not a lot, right?
The leaf has the alkaloids in it, but not a lot, right?
Um, but as we move into concentrated extracts and then heavy concentrates, you move into things like tequila, tequila, um, you know, vodka, um, and then I like to say we move into the barrel strength, uh, spirits, the barrel strength whiskeys, and things like that.
And then with the seven hydroxy product, it's almost like Everclear, where you're drinking 95 alcohol, um.
And we know there's that's going to bypass the stimulant effect, right?
Oh, yeah.
And go straight to the.
That 7-hydroxy is just pure opioid effect.
And so that's what people are getting is that sort of equivalent.
I had a woman email me after another podcast I did, and she said, You've left out an entire population of users that you didn't report on.
And I honestly didn't know it existed.
But people that have become addicted to.
Uh, prescription medications, but are no longer able to get prescription medications because their doctors have cut them off or moved away, and so they've resorted to removing them from their neighbors' houses when they go there, go to the bathroom, they go through their closets and steal the medications from them.
Um, and then they, you know, they obviously know that they have problems, but they can't get access to the prescription medications anymore.
And they said these enhanced extract products or 70H products were perfect because now they could have it shipped right to their front door and get the benefit of those same drugs without having to worry about doctor shopping or going out and getting, you know, stealing essentially from their neighbors and friends.
And so that's what really tipped me off into realizing that the 70H products are.
Really, not something that should be out in gas stations.
They may have a legitimate place in medicine.
And I want to be clear on that.
Right.
Because if they do have.
As does morphine.
Yeah.
I mean, but if 7-hydroxy has less respiratory depression than morphine, it might be a more beneficial painkiller because it could be a safer painkiller.
But it has to be taken through the right steps with the FDA.
It has to have medical supervision.
It has to be really.
Done the right way because we know the dangers of these types of medication and what their abuse liability is, how addictive they are.
When you talk about kratom addiction, just to the leaf material, you know, most people have reported, and even the scientific studies that have been done with humans show that it has a very low withdrawal rating, what they would call mild, which is where coffee is as well.
A full spectrum leaf.
And again, it's a caveat that these are being in low doses and short amounts of time with people, right?
Where they stop using it, they get a little irritated, they might get a headache.
Yeah.
Sounds very much like coffee withdrawal, right?
It's what we call mild withdrawal on what they call the subjective opioid withdrawal scale or SALs.
It's a scale that goes from zero to 30.
Zero obviously would be no signs of any kind of addiction or dependency.
So, zero to 10 is what we call mild.
11 to 20 is moderate.
21 to 30 is severe.
Oh, wow.
So, 21 to 30 is where people that are on prescription opioids, if they go into withdrawal, they're in that high category.
Which one, where's alcohol land?
That's an interesting question.
I don't know because it's.
I heard alcohol is like the one of the one things when you're withdrawn from it, you can actually die.
It's bad.
And it takes an alcohol withdrawal, Steve.
Yeah, it takes a while to withdraw from alcohol.
It's not something that happens quickly.
So you can be medically withdrawn from opioids.
They do precipitated withdrawal with naloxone or Narcan.
They'll inject it into you.
You go through withdrawal within hours.
People say it might be the worst feeling they've ever had, but they survive and they're fine medically.
They're fine.
You'll always survive.
That pretty much wow, pretty much.
Um, you know, I've heard stories where that they basically put you into the withdrawal state, um, and you could be in a padded room or some other things and have give me some stats things there, but yeah, alcohol withdrawal takes days, yeah, and there's no way to immediately withdraw somebody from it, and so you go through all kinds of different symptoms over those several days.
And it's interesting, I told you, my wife is a nurse, and so when they get addicts that end up In their units, they say that the more honest you are with us about your drug use, the less withdrawal you're going to go through.
Right.
Because we can supplement certain things for you so you don't go into withdrawal, you know, medically supervised, of course, and whatnot.
But a lot of these people are so afraid to admit what their drug use is that they start going into horrible, horrible withdrawals in the hospital.
Well, if they are addicted to something like heroin or cocaine or something, you can like titrate them down naturally.
Or there's ways to at least monitor and be more cautious and use other substances to make that up.
But, Generally, these people tend to turn into some of the meanest individuals that now the nursing staff has to deal with on a regular basis as they're withdrawing.
They can be physically harmful depending on the size of the individual.
It could be a dangerous situation.
And so the more honest they are, the better treatment they're going to receive.
But most people don't want to admit that they're using four or five different substances and they go into these withdrawals.
Um, but yeah, you do have uh the alcohol withdrawal.
I think the stats are he's found some stats, but this is yeah, yeah.
I was looking for like one of those AI that shows you overviews that shows you like stats on the country, like how many people like how dangerous it is compared to other withdrawals, drug withdrawals from other drugs.
Yeah, yeah, but it's pretty fascinating because it, like I said, it takes days to withdraw from alcohol.
It's just interesting how like some of the drugs that are ubiquitous in Western society that are.
You can buy anywhere, like alcohol, are like so dangerous if used the wrong way and can kill so many people.
And it's always just fascinated me the drugs that are illegal that seem to be far less dangerous.
Right, right.
You know?
Right.
And how many, going back to coca, how many drugs are literally banned worldwide by the CDC, like that, like coca leaf?
By the WHO.
There's many, many drugs that are banned.
Really globally.
What about cot?
Have you heard?
You know about cot?
Yeah, from Africa.
Yeah, for sure.
When I lived in Minnesota, when I live in Minneapolis, there's a huge Somali population, and a lot of the taxi drivers were chewing cot.
Is that illegal here?
Yeah, it's illegal here as well.
But certainly, you know, it was something that they had used culturally.
I think I read some crazy stat that in some of those countries, In Africa, around Somalia, Ethiopia, like 90 some percent of the population uses cotton.
So it's just a cultural thing that's done, just like probably 90% of our population uses coffee and tea or caffeinated beverages to say whatever.
So, you know, it's a cultural norm.
Dopamine Transporter Interactions00:15:29
Are they all dependent on it?
Probably.
Is most of America dependent on coffee?
Yes.
So, you know, the severity of this really depends, right?
So, there's two drugs that the withdrawal can actually kill you.
Number one is alcohol, and number two is benzodiazepines.
Right.
Opioids rarely kill people.
Stimulants don't kill people.
Cannabis doesn't, and neither does nicotine.
Seizure risk for alcohol is high 5 to 15%.
Seizure risk for benzos is also high.
But opioid stimulants, cannabis, and nicotine have low or no seizure risk.
Yeah.
And so, I think what's interesting here, and something that a lot of people may or may not know, I don't know.
I know this because of a pharmacy, but.
Benzodiazepines, alcohol interacts with the benzodiazepine receptors.
So, its main target in our brains is the GABA receptor, which is where benzodiazepines act.
And so.
And for people who don't know, what is a benzodiazepine?
How do you classify that?
Benzodiazepine is actually the chemical structure.
So, benzo stands for benzene that's in it.
Diaza is actually two nitrogens.
And the pene indicates a seven membered ring with at least one double bond in it.
So, to get technical, that's what benzodiazepine actually means.
What is a benzodiazepine?
It's Adivan, it's Xanax, it's Valium.
And how is that different from stuff like traditional opiates?
Like, why am I blanking on all these things?
Morphine.
Not like morphine or.
Heroin or oxycodone.
Oxycodone, right.
So they interact with two completely different systems in our body.
Okay.
So GABA is the primary gamma immunobutyric acid, GABA.
GABA is the major neurotransmitter in our brain, period.
It is also the main depressant neurotransmitter in our brain.
So it slows things down.
It's our sort of break, if you will, in our minds.
And so a lot of people use alcohol because alcohol interacts with that same receptor that GABA interacts with and actually helps slow things down.
It's a CNS depressant.
Uh, central nervous system depressant alcohol, right?
So, it's alcohol is naturally putting on the brakes, it lowers your inhibitions, right?
It allows you to be more socially lubricated and get out and do things until you hit the point where you pass out and it has done the full CNS depressant thing, okay?
Which is what benzodiazepines are also designed to do.
Benzodiazepines like Valium treat anxiety, they help lower that.
That anxious feeling they make you more comfortable in certain situations.
A lot of San X is the same class, yeah.
A lot of people have to use those to fly, uh, you know, get on an airplane.
A lot of people just go to the bar before they go on the airplane.
It's basically a similar, um, pharmacologically similar mechanism because benzodiazepines bind directly to that GABA receptor as well.
The GABA receptor is a completely different neurotransmitter system than the opioid system, okay.
And so, opioid receptors are.
A whole different thing.
They only accept our endogenous opioid peptides like endorphins, but they also were defined by molecules like morphine.
Morphine was named after Morpheus, the god of dreams, and the mu receptor where morphine acts was named the mu receptor because they just took the Greek letter M to represent that Morpheus, god of dreams.
Target in the body, right?
So this is these are different stimulants interact with different receptors as well.
Cannabis interacts with cannabinoid receptors.
So totally different system again.
And then nicotine interacts with nicotinic receptors.
Interestingly enough, you can tell that these receptor systems were actually defined by many of the natural products, right?
So nicotine receptors were defined by nicotine.
Cannabinoid receptors were defined by cannabinoids.
Opioid receptors were defined by The opioids that were originally isolated out of the poppy.
It's just fascinating how withdrawal from benzos can kill you, but opioids can't.
Yeah.
So let's talk about what is withdrawal.
Withdrawal is the absolute opposite effect that you get from the substance.
So think about what we just talked about with benzodiazepines and alcohol, right?
So if we take that break off and we just let the gas pedal go, the brain's going to be overexcited and can run into seizure activity.
And is seizure the cause of death?
Many times.
Oh, man.
Seizure or just a seizure is unregulated brain activity.
And what can happen is our brain and our brain stem are really controlling all the other mechanisms in our body, right?
They're making sure our heart is beating.
They're making sure we blink our eyes.
They're making sure we do all those things we never have to think about doing.
Our body's doing it for us.
Right.
When you hijack the brain, you interfere with all of those systems.
And so, this is what can sometimes kill you.
It's a high risk of seizure, but it's maybe not the seizure that kills you.
It could be some other effect from that brain dysregulation.
So, the things on here that are the most common are the most deadly.
Well, I don't know if benzos are more common than nicotine or cannabis.
I think cannabis and nicotine are probably the most, are probably far more common than the others.
Yeah.
And I think you have to realize that the stimulant includes caffeine, right?
So, caffeine in high amounts, caffeine will actually cause you to be very anxious and paranoid.
And so, you know, you hear about people getting jitters from caffeine.
That's usually when you're getting too much.
So, if you've ever experienced where you've drank too much coffee throughout the day, or you can start getting really sort of jumpy and anxious.
It actually causes anxiety to happen.
So, would meth and cocaine be considered stimulants in this?
Yes.
Okay.
Yeah.
And very low fatality rate for those two as well.
Yeah.
Methamphetamine, a little different because it can actually cause your brain, your body temperature to be super elevated and you can die from meth overdose because of that.
You could come out and be fine as well, but that could really, when they had those old commercials, this is your brain on drugs.
And they fried an egg.
That's kind of what is the analogy for what methamphetamine can do to your brain.
Yeah, it always concerns me because I know so many people who have been prescribed things like Ritalin or Adderall since they've been little kids, like in middle school, essentially.
And I know people who have been taking that stuff since grade school and now are like fully formed adults in their 30s, late 40s, or 30s, like.
Early 40s, late 30s, that are like some of them are like having children and they're saying, Okay, you got to stop your Adderall prescription now that you're pregnant and, you know, bring this baby to term and then you can start your prescription again.
And they're like losing their minds because they've been on this stuff since they were, you know, in their teens.
And now it's the first time in their life they have to go cold turkey for nine months.
And it's just crazy to see that.
I was always concerned about the, you know, pediatric patients taking.
Things like Ritalin.
You know, I talked to physicians about it, and they're like, look, we take the kids to camp for a week.
We make them stop for the whole week.
They're fine.
No big deal.
There's no addiction issue or problems or withdrawal.
I don't know.
I mean, I don't know.
It's a controversial thing to me.
So, Ritalin.
It's crazy just how ubiquitous it is.
Ritalin is very fascinating because Ritalin binds and has its action at what's called the dopamine transporter.
The dopamine transporter is what regulates the amount of dopamine, free dopamine is out and available in our bodies to interact with dopamine receptors.
So, dopamine transporter is like a vacuum cleaner.
It sucks it back up into the neuron to store it for later.
Of course, dopamine can be metabolized too.
That's another issue.
But what happens is Ritalin blocks the dopamine transporter from being able to reuptake dopamine into the neuron.
So, it leaves a higher level of dopamine available to interact with dopamine receptors, which then gives that sort of stimulant effect.
And makes you more alert and focused.
Yeah.
What's really fascinating about it is that Ritalin interacts with the exact same amino acid residues on the dopamine transporter that cocaine does.
So cocaine has exactly the same effect.
As Ritalin?
As Ritalin.
And our Adderall and these other drugs like Vivance and Metformin, these are all the same thing.
Well, Metformin is a diabetes drug.
I mean, not Metformin.
Methamphetamine.
I'm thinking of something different.
Medafinel is what they call it.
Medafinel is a different beast, too.
Oh, okay.
But Adderall, basically amphetamines, methamphetamine, they interact with another transporter called the VMAT or these different monoamine transporters.
They're interesting molecules.
Methamphetamine, particularly interesting because it actually causes not only does it block reuptake, but it causes stored dopamine to be released.
So, it forces dopamine out and it blocks it from coming up.
So, methamphetamine is much more addictive, causes much more free dopamine to be available in the brain than does cocaine, even.
Wow.
So, they've measured studies that this was work done by the National Institute on Drug Abuse, actually, the current director, I believe, Nora Volkow.
She's an imager, a brain imager.
And they looked at the most pleasurable experience that you can have as a human is an orgasm.
That's the most rewarding experience.
It's built that way so that we ensure we have a population going forward.
Right.
And that causes a 200% relative release of dopamine.
So it doubles your dopamine levels that you normally have.
Right.
So interestingly enough, cocaine, opioids do the same thing, but about that 200% level.
Really?
Yeah.
So people that.
End up getting hooked to some of these other substances is because it's elevating that dopamine, that pleasure molecule in your brain.
And that's why you get that euphoria.
That's why you get that feeling.
Methamphetamine does it to a level of 600 times, 600%.
So, what about crack?
Crack is in the same ballpark as cocaine.
Now, the reason that Ritalin and cocaine are very different, you do hear about Ritalin abuse, right?
You do hear about people.
Using it the wrong way, not so much to get high, but people use it off label for party drugs and other things, not to get the euphoric effect they would get with cocaine.
So, I always explain this, and I use the same analogy for something like buprenorphine, which we use for opioid use disorder treatment versus heroin.
They both interact with the opioid receptor in the same location in the body.
But one is a Ferrari, and one is a beat up old Volkswagen Beetle from the 70s that can still get you from A to B, right?
But it's not going to be as sexy and as quick.
Something like heroin.
Or cocaine, they are constructed to get into the brain so fast.
And this is a hallmark of an abuse substance, a really highly abused substance, is that it's taken, it's absorbed quickly into the body, it gets into the brain extremely fast, and it goes out extremely fast.
So it hits really hard, gives you this boom explosion of a rocket ship or a firework, and it's over quick.
Whereas something like methylphenidate, Ritalin, or buprenorphine is that old car that's just barely getting there.
It gets there, it gets there, it gets into the brain, it stays in there for a while, a while, a while.
It doesn't pack a punch and then it comes out.
Right.
So it's what we call pharmacokinetics.
It's what our body actually does to these substances, how our body actually manages these substances.
And it's totally dependent on the chemical structure and features of the drug itself.
So, it helps your body maintain more of a balance internally, like a more endogenous balance compared to the drug that's in your body versus cocaine.
It's like in out and it kind of like leaves you.
Yeah, our bodies want to get rid of anything foreign that gets into them.
Right.
Right.
And so, we do that as quickly as we can through drug metabolism.
Our bodies, our livers chew up everything and spit it out, but a lot of your organs can metabolize.
And so, drugs that get into the brain really fast also get into the liver really fast.
And so they can be chewed up and eliminated really quickly as well.
But they've done their sort of damage, right?
They get in the brain so fast that they hit it so hard and then they're gone.
And then that's the other aspect of this is like, oh, I got to have more methamphetamine is different because the highs for methamphetamine can last for 24 hours or more from a single dose.
So it gets into the brain fast as well.
But as I mentioned, it dumps out dopamine and then it blocks and leaves it there.
It just has a more devastating effect overall on our brain chemistry.
Modafinil vs Kratom Abuse Potential00:15:12
And what is the difference with this modafinil stuff?
I've heard a lot about it.
I know that fighter pilots take it.
Modafinil, actually, the very first case report that we ever published with Kratom was someone that was taking modafinil and had a seizure.
Oh, wow.
So they weren't prescribed modafinil, their spouse was.
Modafinil is used as.
A treatment for sleep disorders.
It's used for narcoleptics.
So it gives you that alertness, that awakeness, hence why fighter pilots could use it.
You know, methamphetamine was a spoil of World War II.
It was a German chemist concoction that actually a lot of the kamikaze pilots in Japan took this stuff to be able to fly all night and have the bravery and courage or craziness to use their planes and themselves as.
As weapons, right?
The Russians are taking it right now in the Russia Ukraine war.
I wouldn't doubt it for a second.
So, this is something that is a well known.
Captagon, I think is what they're calling it.
Yeah, wow.
But yeah, so, Medafinil, interesting molecule.
The trade name, the brand name when it came out is called Provigil.
Yes.
Stands for Provigilance, right?
Makes you more vigilant, increases your vigilance.
It interacts with different systems in our body.
One of those systems is called a Rexin system, or also Provigil.
Called hypocretin system.
And there's a lot of knowledge that we don't have about that system and how it really works and what's going on.
But we do know that in patients that have narcolepsy, they have far less of these arexin type activities in their brain.
So if you give them something like provigil or modafinil, you can actually restore some of that and then.
Cause that balance to be there so they're not just falling asleep at the table, literally as we're sitting here talking.
So it's a completely different chemical makeup than stuff like Adderall or Ridlin.
Correct.
And again, targeting a totally different system than any of the things that we've been talking about.
Would it be safer than those other ones?
Well, I mean, we have an approved drug on the market.
So it's a couple approved drugs on the market.
So it seems to be safe in those populations that need to be using it.
Um, if they, um, you know, I don't know.
There's been a lot of investigations looking at modafinil for treatment of just kind of drugs of abuse as well.
There's been a lot of failed studies, they thought it might be really beneficial for methamphetamine or cocaine treatment.
Didn't seem to pan out.
Um, again, and that's something that looked really interesting and promising in animals and didn't really pan out in humans, so right, right.
So, what do you have on the horizon as far as like studies that you're planning on working on other than the DMT one, which is going to be interesting to see?
So, the DMT one is underway.
We're pretty excited.
We've been working on isolating and purifying the enzyme right now, and that's going pretty well.
Obviously, we're still working on kratom.
That's going to be a lifelong project where we're trying to figure out next directions that some of the more nefarious.
Players out there are going to go once certain things get banned, like 7-hydroxy.
What's going to come in to fill that void?
What may be the next product, in other words?
We've been working on a lot of that.
As I said, we've got Coca-Leaf in the horizon, really literally on the horizon, that we're just waiting for the shipment to come and really start investigating a lot of things with that.
But one of the main areas that we're interested in with Coca-Leaf is a replacement for Ritalin.
For Ritalin.
For Ritalin.
Oh, interesting.
ADHD, really increasing focus, increasing your mental acuity, awareness.
And so that's something we're really interested in looking at there.
And then.
Now, what would be.
What sort of hurdles would you guys have to leap to get this to replace Ritalin?
Would it be an alternative to it?
It would always be an alternative, right?
Right.
It would have to.
And it's going to be a really difficult thing to do.
Yeah, how do you get a pharmaceutical company to patent Coca-Cola?
They're not, right?
So you have to come up with some sort of unique formulation like Coca-Cola did.
Right.
Or some I would imagine they would lobby against it.
Yeah, I'm not surprised by anything anymore.
But I think what some of the ideas, just like what we've done with kratom, is once we've isolated the alkaloids and we understand the pharmacology of that alkaloid, you can't patent that alkaloid, it belongs to nature.
But we can use that alkaloid to really inspire us to create something synthetically that might mimic its effects, right?
So, what have we learned from this plant?
What has it taught us?
How can we use those teachings?
To help us make something better safer, hopefully more effective as well, for human use, that could be patented, that could be of interest to pharmaceutical companies.
That's kind of what we do as medicinal chemists that's, we take that inspiration from nature, but in my mind, we have to understand everything that nature is trying to teach us.
What is this plant telling us?
What is it, what is it gifting to us, and what do we need to receive from that, and how do we need to then Process it and make it into something different?
So, my intention has never been to get rid of plants or replace the plants altogether, but to figure out how to use the plants in the best way that can be most effective and safe for people as a whole plant.
Because I think Jack Henningfield, one of our colleagues that was at Johns Hopkins at the National Institute on Drug Abuse for many years, he said, Nature oftentimes gets it right.
Nature's worked on the chemistry and everything for all these years.
Here's this plant, right?
Yeah, that seems to be okay.
Coca leaf's a great example.
Doesn't have addiction properties with the coca leaf itself, but sure enough, you pull out cocaine, you've got it.
Cortom, maybe a little bit closer to having more addictive properties than something like coca leaf, but very mild as long as it's used in moderation.
Those are some of the things.
And then the most recent thing that we've embarked on is actually looking at kana.
I don't know if you're familiar with Kana.
It's from South Africa, K A N N A.
It's another plant that's used traditionally by bushmen and hunters.
They would ingest this to get more energy, to also increase stamina, decrease thirst and hunger, to be able to go out and hunt in South Africa on long hunting excursions.
Oh, wow.
And it's really got a fascinating history around it.
It sounds almost like a mixture of coca leaf and kratom, and that's kind of where we got interested in this sort of intersection of many shared benefits.
Um, and so I have a student uh working on that project now.
We've got um some of the plant extracts in the lab, and we're we're sort of very early in the development of that project.
We're just isolating some of the alkaloids from it, characterizing those alkaloids.
A lot of that work's already been done by others.
Um, but we are is this stuff legal in the US?
Yes, oh, it is.
You can buy this on Amazon actually, Kana, yeah, yeah, and it's a very similar effect to coca leaf and kratom and kratom in terms of focus and energy, right?
So, okay, add this to my grocery list.
So, uh, it's galetium tortosium is the actual um plant's name.
Are there any products that uh do they make any like special like um drinks or anything?
Um, I'm not aware of specific.
Drink products.
There's a lot of capsule products available.
Leaf products, what are shown there, they're a little bit harder to find.
Even though it says you can buy them, usually when you go there, they're out of stock or they don't have it.
But there's a compound, there's a product called Zembrin, Z E M B R I N, I think, which is actually a standardized extract of this plant that is sold.
And that is.
Another guy, Nigel Gerke, who was at the ESPD meeting and spoke on this plant there.
And at the time, I was so deep wasted into Kratom that we didn't have time to even think or look at anything else.
And now, with having enough research funding and enough things that we know what we need to do with Kratom from a chemistry perspective to provide to our Collaborators that are doing the pharmacology that are doing some of the other things with it, we've got it worked out to really a cookbook methodology.
So, I have undergraduate students really helping in the lab with some of that.
And so, to give students that are pursuing a PhD or post PhD work something new and novel to work on, that's why we've branched out into some of these new plants and looking at them.
What do you think is going to be like the future of kratom?
Do you think there's any chance that it gets classified as an illicit substance, or what do you think?
Based on your research and other research, is going to happen.
Yeah, I think the research is going to determine the outcomes.
I mean, it's not up to us to schedule things or recommend things as scientists.
It's just to produce the data that supports those regulators making a decision, right?
And so, what we've seen up to this point in time, and the reason that they've decided to take action on the seven hydroxy compounds is because that definitely shows.
High abuse potential by all the methodology that FDA wants to have used to show abuse potential, it checks every box, and so that's why it's being considered.
Um, kratom leaf material itself does not check all the boxes, and so it's could be potentially habit forming, of course, but it's not as high abuse potential as there.
And so, the FDA clearly, when they announced the intention to put 7 hydroxymitrogen in Schedule 1 said this is not about the leaf kratom.
We're not interested in going after that.
We will leave that alone.
It seems to be fine.
The federal government has put a lot of money, over $100 million, into studying kratom now.
Wow.
Yeah.
And we've been lucky to benefit from that.
We've had about $20 million into our lab alone, plus a $50 million collaboration with the National Institutes of Health with their internal programs.
To really study it.
And then the FDA, the FDA has put money into looking at clinical evaluation of kratom leaf.
And so we finished one clinical trial with the FDA already that was what they call a dose range finding study or a single ascending dose study, where they start with a very low dose.
So we started with one gram of leaf material administered to healthy volunteers.
And then you look at all the safety data after that.
Single dose was done.
You look at what their blood chemistries were before, after.
You look at what their subjective effect feeling was.
So we did one gram, we did two grams, we did three grams.
And after three grams, there was no effects still.
People said, We don't feel like we're taking anything.
We don't feel like it's a drug.
We don't feel anything.
And so the FDA said, Let's skip the next couple doses and just jump up to eight grams of leaf material.
And when we did that, then a couple of people said, Yeah, I'm feeling something now.
But they did not have any adverse event or what they considered a significant adverse event that they had to stop dosing.
So we went from the 8 gram dose to the 10 gram dose to the 12 gram dose, which is the end of the study.
And again, I said the typical normal quote unquote dose or serving side is two to five grams of kratom leaf powder.
So we went all the way up to 12 grams.
And what we saw in that cohort was some nausea and vomiting.
And we saw a small amount of pupil shrinkage.
So, this is a typical hallmark opioid sign.
When someone's taking an opioid, their pupils will actually shrink or contract.
And so, it was mild.
It wasn't like someone was taking morphine or oxycodone to where they get very small pupils, but the pupil diameter changed.
And that was one of the things we noted.
Interesting.
And don't stimulants make people's pupils dilate?
Right, correct.
So you get this opposite effect with those.
So, what that did, the FDA actually ended up showing that kratom leaf, all the way up to 12 grams in a single consumption, was generally well tolerated, right?
Which I think surprised no clinically significant event happened.
That's wild.
So, that would include death, of course.
Yeah.
But I think it surprised the FDA as well.
Nobody's ever died from kratom?
That's a very hard question to answer.
Heavy Metals in Vein Extracts00:07:56
Right, because I'm sure somebody could die and have kratom in their system and also have a slew of other things.
Well, yeah, many of the deaths that have been attributed to kratom have also contained multiple substances.
I mean, we live in a society where people are generally not, if they're trying to get high or they're abusing substances, they're not using one thing, they're using many things.
Right.
And they're using many things to counteract the effects of one or the other so that they can get high and then come down faster, whatever, right?
And so we don't know how all those things play with each other as it is, let alone in the presence of something as complex as kratom that has 40 different compounds in it as well, right?
So this is problematic.
But to come out and generally state that no one could die just from kratom, I think is factually not right either.
Um, because you can die from anything.
If you consume enough of something, it can kill you, sure?
Um, and yeah, water's a.
Water's a great example.
I mean, people die from water intoxication.
Um, it's not drowning, it's actually you drank too much water and your system basically explodes internally.
Um, that's not really what happens, but but I you know it can be fatal.
Um it any any, any substance can be there.
And this is, I always go back to quoting Paracelsus, one of the famous ancient Greek physicians that made famous the poison is in the dose.
So, you know, many.
Paracelsus?
Yeah.
So, many, many poisons, as we talked about earlier with Marcus Aurelius, right?
And Galen, you can give poisons in low amounts that won't kill you.
Right.
But once you hit that amount that will kill you, there's no coming back.
Right.
So, it's, I think.
Very similar for all substances and just depends on exposure.
And this is another reason why chronic studies with kratom are needed so much because we don't understand what's happening when tolerance develops, when harm starts to creep in.
You know, if people are taking two to five grams two to three times a day, it doesn't seem to be problematic.
But I've got, like I told you, people that are telling me 90 grams, 120 grams a day.
That could potentially be getting them closer to a bad situation.
There's another thing that never gets talked about.
Although the FDA had reported this in the past, they had seized a lot of kratom because of heavy metal contaminants.
Most of the responsible companies will actually measure the heavy metals and make sure that you're getting a loud amount.
Of the substance.
But that's for that, again, two to five gram dose, what serving size they recommend on the package.
You're not going to exceed lead levels.
We've been working with Baylor University and FDA on the now human abuse potential of kratom leaf.
And we're starting at eight grams, 12 grams, which was the ending dose of the previous study.
And then we're going to 16 grams.
Of material for the highest dose in that study.
And we haven't been able to qualify a batch of leaf material that can be safely dosed at 16 grams because of heavy metals.
So if you think about that, and we've talked about people that have been taking 15 grams a day, if they're taking five grams of leaf, you're butting up against the edge of lead limits in a day.
According to the FDA.
So, people that are taking greater than 20 grams a day are at risk of lead issues.
And certainly, someone who's taking 90 grams or 100 grams of kratom a day is also getting lead toxicity.
And this is not with the extracts, right?
This is only with the lead.
Correct.
Only with the lead.
The extracts will have the metals.
The metals will come out in the process because of the extract process.
We had this guy in here one day who, before we started the podcast, he took.
A handful of kratom capsules.
He was drinking a kratom tall energy drink, like twice the size of mine.
And right before we started recording, he took a giant scoop of powder and just downed it in his mouth, like and washed it down with a toss and washed it.
He literally washed down the kratom powder with his kratom energy drink.
I was like, whoa, bro.
That's a lot.
That's intense.
Yeah.
So the powder is the leaf, right?
Right.
Okay.
Gotcha.
And he called it white vein.
White vein.
Yeah.
So there's interesting stories with the veins.
And in the very early days, there was this whole big deal made about the different strains of kratom that are available.
There's white vein, red vein, green vein.
And in reality, if you're able to ever see a tree growing, you'll see that these leaves are all on the same tree.
It's a matter of, in a function of the age of the leaf, where it is in exposure to light, various things.
But it's still been used as a marketing tool because there were.
There were reports back from Thailand and Malaysia that white vein had different effects than red vein.
And red vein, white vein and green vein are essentially the same.
But red vein had different effects.
And one of the studies said red vein was more potent.
And the other study said white vein was more potent.
And so no one really knows what's happening with these things.
What we do know is there are five colors of powder that come in.
That are imported.
And the powder, the leaf powder color is dependent on how the drying process took place and what was done.
So you have green leaf that comes in that they often market as green vein.
Then you have sort of yellow or light brown that they'll market as white vein sometimes, all the way up to a reddish colored powder that often gets marketed as red vein.
Got it.
Now, this is another interesting piece.
And alkaloids are not the only class of chemicals that are present in the kratom leaf.
There's other classes of chemicals, just like cannabinoids are not alkaloids.
Cannabinoids don't have nitrogens in them.
Salvinorin A, we talked about before, is a neoclaridine diterpene that does not have any nitrogen in it either.
Alkaloids, by definition, contain nitrogen.
So we know that there are other classes of chemicals within kratom.
And we know that the drying process, those color changes are chemical changes.
They're chemistry driven color changes, right?
And so it could be that there is some truth to the differences because we haven't studied anything outside of the alkaloids.
Federal Funding for Cannabis Research00:06:47
So there could be differences that people are actually really noticing.
Nobody's really studied it or looked at it yet.
But more or less, we feel like it's.
More or less a marketing issue allows you for more skews of your product.
It also allows you to have a more consistent product base where you know you're going to get these five different colors.
What out of all, I think you said that there's $100 million being a federal money that's being pumped into Kratom Research.
What other types of drugs get that kind of money?
So cannabinoids have way, way exceeded that.
Oh, really?
Yeah, yeah, for sure.
Because you got to look at the time, too, that's been put into it.
Right, that's true.
So if we go back to some of the first federal funding that even the National Institutes of Health didn't know was going to fund projects on Kratom.
So we had a grant at the University of Mississippi called Natural Products for Neuroscience.
Underneath that grant, we awarded faculty members small grants that were NIH money.
to study plants that they were interested in.
I was one of the recipients of one of those small projects.
It was $150,000 a year, and I had it for almost 10 years to look at that.
So there's $1.5 million there, right?
And that's before that started in around 2007 or 2008 when we started getting that money.
Wow.
So you have to go all the way back to then to see when it was started.
I mentioned cannabis work has been done.
Actually, it predates the National Institute on Drug Abuse, the federal funding for cannabis research.
And so the National Institute on Drug Abuse was founded after the Controlled Substance Act went into place.
And that's what's been going on.
So $2.5 billion in cannabis research between 2000 and 2018.
Yeah.
So way more money on cannabis than Kratom.
Crazy.
Yeah.
And, you know, there are all kinds of grants that are being.
Put out to really look at medical potential for many of these plants.
Now, cannabis research is a garbage can definition, right?
So it's all the CBD work that's been done, all the hemp work that's been done, all the really high end THC containing cannabis work that's been done.
So there's a lot there.
Not only has A good bit of that work focused on the plant itself, but many of the studies that have been funded from the government are really looking at outcomes because, as a federally funded university like the University of Florida or any state university, cannabis is still schedule one at the federal level.
So we risk losing federal funding if we bring cannabis from a dispensary onto campus to study or do research with.
We can't do it.
Wow.
So all of the material that comes, plant material that's been used in studies is what had been grown at the University of Mississippi.
That's the only federal supply for researchers.
And so there's a huge disconnect because the stuff that was grown in Mississippi was much lower THC concentration than what's out in dispensaries, right?
So we can't even do those studies.
But what we can do is we can talk to people that are getting their materials from dispensaries.
What are you getting it for?
What percentage are you getting?
What is your outcome?
What is your benefit that you're perceiving?
So, a lot of money goes into that type of research as well.
Well, Chris, this has been fascinating.
I learned a ton.
Thank you for doing this, first of all.
Yeah, absolutely.
Thank you for inviting me.
Yeah, of course.
And then, second of all, where can people find more of your research that you've done or get in contact with you or anything like that?
Yeah, so I'm always available by email.
Email is cmcurdie at ufl.edu.
That's my Florida, University of Florida email.
And that's really how you can reach out.
I get lots of emails from users, people that are willing to volunteer for trials.
We don't do any human research in my lab.
My lab is totally plant based, chemistry based, pharmacology based.
I do all my collaborative work with.
Some amazing individuals that work with the animals.
We supply them with all the drugs.
We're the drug dealer.
And, you know, our papers are readily available.
Many of them are free to download on the government, the Library of Congress PubMed website, pubmed.com, I think it is.
And you search McCurdy, CR, and Craddam, and you'll see that there are 80 some papers.
If you search Craddam, you'll see there's just shy of 1,000.
I think there are 980 or so papers total published on Craddam.
And you've done 80 of them?
Yeah.
We've done.
A large percentage of of the work and and again, it's because it spans back to, you know, many years before people were interested in it and uh, and then the federal funding really helped catalyze and boost the amount of work we were able to do and publish and share uh.
The whole goal is to share and educate the public and and get that information out uh to to not only public benefit and science benefit but, you know, to be available to the regulators so that they can make those decisions that uh Either keep something available for public consumption or restrict it.
And so, again, we don't make that decision, but we have an obligation with our funding and our work to produce the science.
Well, and then also, I think we should do a follow up down the road once you guys are able to get some research on this DMT stuff.
I'm definitely interested to hear how this pans out.
Educating Regulators on Plant Science00:00:23
Absolutely.
And I'm, you know, there could be the DMT story, and then we could continue on to what we've learned about Kana and where hopefully we'll be with Coca.
Hopefully, we'll be knee deep in coca leaf, literally, pretty solid soil.