#344 - Top Chemist Just Discovered How to Hack the Brains Internal DMT Molecule | Chris McCurdy

Watch every episode ad-free & uncensored on Patreon: https://patreon.com/dannyjones Chris McCurdy is a pharmaceutical scientist and pharmacist whose research focuses on the design, synthesis and development of drugs to treat pain and drug abuse. His latest research investigates a naturally occurring molecule that may regulate an enzyme which helps produce the powerful psychedelic compound dimethyltryptamine, or DMT, in the body. SPONSORS https://expressvpn.com/dannyjones - Get up to 4 extra months free. https://www.amentara.com/go/dj - Use code DJ22 for 22% off your first order. https://clean.ver.so/danny - Use code DANNY for 15% off your order. https://whiterabbitenergy.com/?ref=DJP - Use code DJP for 20% off EPISODE LINKS https://pharmacy.ufl.edu/profile/mccurdy-christopherhttps://pubmed.ncbi.nlm.nih.gov/?term=McCurdy+CR&cauthor_id=33213215 FOLLOW DANNY JONES https://www.instagram.com/dannyjoneshttps://twitter.com/jonesdanny OUTLINE 00:00 - The most hallucinogenic plant in existence 09:39 - Natural DMT in our bodies & schizophrenia 19:43 - Finding DMT in spinal fluid 27:06 - Endogenous tripping & transcendental meditation 37:26 - Placebo effect & treating cancer with the brain 47:08 - The flaw in the "healthcare equation" 57:18 - Why coca leaves should be legal 01:13:44 - Only 3 countries where coca leaves are legal 01:17:18 - Kratom's dangerous trajectory 01:29:15 - World's biggest kratom study 01:43:01 - 7 hydroxy products (7-OH) vs. kratom 01:47:12 - The drug with the deadliest withdrawal process 01:59:52 - Why ritalin shouldn't be prescribed to kids 02:07:46 - How Modafinil works 02:14:55 - The kanna plant 02:20:02 - FDA finds how much kratom leads to overdose 02:28:12 - Different strains of kratom leaf Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Danny Jones?

  You can eat well, work out, take supplements, and try to get enough sleep, and you still have no idea whether it's actually changing how your body is aging. But that's what makes True Diagnostics' True Age Test really interesting. True Age uses epigenetics, basically chemical tags on your DNA that change with things like sleep, stress, diet, exercise, and your environment, to estimate how your body is aging. Its methods have been published in peer-reviewed scientific journals and developed with researchers at Harvard, Yale, and Duke. You receive your biological age, how quickly you're aging, and information about how areas like your heart, brain, and liver may be aging, plus recommendations around nutrition, exercise, sleep, supplements, and lifestyle. And it's simple. An at-home finger prick, send the prepaid kit back, and your personalized report arrives online in about three to four weeks.

• 0:45Danny Jones?

  So if you're serious about longevity and curious about how your body is really aging, then this is one of the easiest ways to find out. Right now, go to trudiagnostic.com and use the code DANJONES for 20% off your entire order. That's T-R-U-D-I-A-G-N-O-S-T-I-C.com. Use the code DANJONES and get 20% off.

• 1:07Speaker 01

  Network freedom and flexibility, that's what you want in a healthcare plan. With a Humana Medicare Advantage PPO plan, you can see any doctor in the country who accepts Medicare, including specialists. No referrals, no kidding. Learn more at gethumana.com. See any doctor who accepts Medicare and is willing to bill Humana. Humana PPOs may not be available in all areas. Benefits and costs share may vary. Humana is a Medicare Advantage PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal.

• 1:44Danny Jones?

  I learned about you through Andrew Gallimore, who was on here, and him and New Nautics 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. Before that... Can you give people like a brief history of yourself, your background and your work and your expertise?

• 2:09Speaker 02

  Sure, sure. So, thanks first of all for having me down here and this is, this is pretty cool and it's nice to do this on a local trip too.

• 2:16Danny Jones?

  Yes.

• 2:17Speaker 02

  Cause 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

• 2:59Speaker 02

  and potentially combat diseases that are also coming from nature. So, I believe there's a balance and a yin and a 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, just caffeine from the coffee plant. And interestingly enough, I've ended, you know, more recently studying another plant in the coffee family, Mitragana speciosa, which is the plant that produces kratom. So, we'll talk about, talk about that, I'm sure in more depth, but caffeine, I did a small project in high school, looking at caffeine concentrations in different sodas.

• 3:44Speaker 02

  This was before the FDA required labeling it. And so, we, we found, you know, Mountain Dew was pretty high in caffeine content. There was old Jolt Cola.

• 3:55Danny Jones?

  And sugar.

• 3:56Speaker 02

  Was really high. Oh yeah, they're all loaded.

• 3:57Danny Jones?

  Remember Surge?

• 3:58Speaker 02

  Yes.

• 3:59Danny Jones?

  I think they banned that.

• 4:02Speaker 02

  Yeah, and those are just, um, th- those are good examples of too much sugar and too much caffeine. And that's a formula for, for wildness. Um, and in fact, we were, we were so goody-two-shoe in high school, our Friday nights consisted of a case of Mountain Dew and, um, we would just jam band in the, in the basement. Um, that's what we did. But, uh, moved on from that, went to pharmacy school, um, and then got involved in research when I was in pharmacy school, uh, out of Ohio Northern University, um, graduated, got my pharmacy license, practiced as a retail pharmacist. Um, actually worked originally

• 4:43Speaker 02

  for Publix, uh, pharmacies. Um, so I'm very familiar with how they operate, uh, and really enjoyed those interactions with customers, what we called them back then. Now, um, patients is, is the preferred terminology in, in pharmacy practice. But, um, from there, I went to University of Georgia, did a four-year, um, stint to get a PhD. And I worked with chemicals there that were, um, built to mimic a chemical called lobiline, which came from a plant called Lobella inflata, which was a Native American, um, tobacco plant. So it was, didn't

• 5:25Speaker 02

  have nicotine in it, but it had compounds that we thought interacted with nicotine receptors. Um, and we, we studied that. We did a lot of work, um, never really went anywhere. But then I got an opportunity to do a postdoctoral, kind of like a, a residency for a physician, do a postdoctoral stint at the University of Minnesota for, um, Phil Portegesi, 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, um, chemistry fathers of the opioid, uh, endogenous opioid system in terms of discovering compounds that would block the effects of, uh, opioids. So he defined-

• 6:12Speaker 02

  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 when I arrived there, they had one of the largest repository of natural products samples in the country, didn't have anything studied in the central nervous system. And I thought, man, this is a goldmine to

• 6:55Speaker 02

  walk into. They also have the, well, at the time, the only federally funded marijuana farm. And so we had access. In what year? This was in 2001. Oh, wow. 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

• 7:37Speaker 02

  plant that came into mind was really Salvia divinorum, also called divinor 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 salvinorane. 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

• 8:22Speaker 02

  For opioid receptors has a nitrogen in it. Salvinorone 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 was 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.

• 8:58Speaker 02

  And the kappa opioid receptor is 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 on to the holy grail of very potent painkillers with, you know, 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.

• 9:35Danny Jones?

  Wow, interesting.

• 9:36Speaker 02

  And that's what really fascinated me was people were utilizing salvia divinorum to 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.

• 10:05Danny Jones?

  Really?

• 10:06Speaker 02

  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 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, they these plants are were. Really easy to grow. We got a couple of plants and we propagated them to, you know, a couple hundred easily. But that was a cool project and that project actually led me to Mitragana speciosa because I was invited by the National Institute on Drug Abuse who funded us

• 10:50Speaker 02

  for a grant on salvia divinorum and said, hey,

• 10:54Speaker 02

  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 Mitragana speciosa.

• 11:07Danny Jones?

  I want to get into the, um, that stuff. The kratom stuff, um, but first of all, how did, um, how and why did, did Gallimore and these guys at New Nautics get ahold of you and what were they looking to get you to help them with?

• 11:22Speaker 02

  Yeah. So they were, they were very familiar with my work, um, in, in kratom or kratom. I call it kratom, sort of acquiesced. The American tom is, is really the way it's pronounced in, in Thailand. And interestingly in Thai, I believe it, it translates to home.

• 11:43Danny Jones?

  Oh, interesting.

• 11:43Speaker 02

  Yeah. So it's a, it's interesting. If someone told me that, I'd, I'd have in fact checked that, but, uh, probably should. But yeah, kratom is what we always called it, uh, because we knew it was kratom. Kratom sound like you gotta really emphasize.

• 11:58Danny Jones?

  Yeah. It's a lot of work.

• 11:58Speaker 02

  Yeah. So anyway, kratom took off in the U S, um, and it's become the popular sort of street terminology.

• 12:08Speaker 02

  But, 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, this project? We know about.

• 12:42Speaker 02

  Paper that was published in nineteen seventy seven 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.

• 13:27Speaker 02

  And so what we're searching for is this endogenous inhibitor to see if we can replicate that paper from nineteen seventy seven, first of all, and identify these reported endogenous inhibitors. The importance of that is because they did not characterize them back in nineteen seventy seven. And that paper has just been sitting there untouched, unexplored after that report. And so Andrew was very interested in, hey, can we?

• 13:57Danny Jones?

  Sorry to interrupt. What was the goal of the research that led to that paper in nineteen seventy seven? Like what were they? Who was doing it? And what were they looking for specifically? Do you know?

• 14:05Speaker 02

  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 methyltransferase, 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, and the reason behind wanting to find an inhibitor is there's been an association with an overexpression or overabundance of this enzyme

• 14:45Speaker 02

  in patients that have schizophrenia. And so if you, 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, if we can't utilize the inhibitor peptide itself, then

• 15:26Speaker 02

  my expertise also involves taking peptides, small peptides, and making small molecule memetics of those peptides. So we, we have another project in my lab that really looks at this exact role. And I think that was what made Nudnotics feel really comfortable with what we're doing. We, we understand and respect the natural products world, but we also do a lot of small molecule synthesis based on endogenous peptides and, and the knowledge of those peptides. And so we work on a, a project called Neuropeptide FF, which was thought to be an anti-opioid peptide. So when we secrete endorphins, we also secrete

• 16:07Speaker 02

  this, 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, 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,

• 16:51Speaker 02

  those countermeasure peptides are being released. And when you take away the opioid, it takes a couple of days, forty eight, seventy two hours before that machinery can sort of get re-expressed and turned back on to produce the endorphins. And in the meantime, you you pull away the exogenous opioid, the the tablet that you took or whatnot, and you're flooded with these countermeasures, these these anti-opioid peptides that actually cause you to be in more pain.

• 17:26Speaker 02

  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 they become painful. So example would be if someone pulled a tooth. If if what someone was at the dentist had a tooth extracted, they give you some opioids to go home with and some, you know, 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 run out of the opioid and say,

• 18:08Speaker 02

  you know, 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 the two things would happen.

• 18:53Speaker 02

  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 Right. 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?

• 19:36Speaker 02

  So if we can figure out a way to counteract that with these 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 hyperaldhesia. And all this has been shown to to work in animals, but we've not translated anything towards towards humans yet. But that's a goal. So so that's how new notics, that's a long way around the story, the answer to the question. Yeah. But that's how they got interested. They knew we were passionate about central nervous system. They knew we were passionate about natural products and they knew that we had the knowledge to do this.

• 20:16Danny Jones?

  Going on the internet without Express VPN is like going on a shark dive in a suit made of meat. You're going to get eaten. Using public wifi 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 Express VPN. 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

• 20:58Danny Jones?

  Info from data brokers and their VPN keeps me and my family protected. So, secure your online data today at expressvpn.com/dannyjones. That's E X P R E S S V P N dot com slash Danny Jones for up to four extra months for free. Expressvpn.com/dannyjones. 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 spec, like back and forth? People haven't really set, it's not set in stone?

• 21:36Speaker 02

  Yeah, so I think, first of all, DMT has a very short half-life in our bodies.

• 21:42Danny Jones?

  Right.

• 21:42Speaker 02

  And so, it's very quickly metabolized and it's hard to capture. You know, is it, 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.

• 22:04Speaker 02

  Those tend to be present as well, but we know that the one that's most psychoactive is the dimethyltryptamine. And so, it's, 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, it's difficult to say. Just like any other neurotransmitter, like dopamine, for example. You can't, we can't give dopamine as a drug for people to take because it, it's just not well absorbed into our body.

• 22:47Speaker 02

  And it also has an incredibly short half-life, so you can't get a lasting effect from it.

• 22:55Danny Jones?

  Interesting. And the idea is that the brain and the lungs make DMT specifically?

• 23:02Speaker 02

  So the the enzymes seem to be present at the highest levels in the lungs. Now, what, 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 that it's playing. Or, 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 other molecules that we take into our system. So those enzymes are present mainly in the lung and in the brain.

• 23:46Speaker 02

  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. Then we're looking for the analogous thing in rabbit brains. So that's very highly expressed in rabbit brains.

• 24:05Speaker 02

  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.

• 24:29Danny Jones?

  Why would you choose spinal fluid?

• 24:31Speaker 02

  That's the, well, we can't get human brains. So we can't sample human brains. And the the the literature has reported that the enzyme is present in the spinal fluid. So 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.

• 24:56Danny Jones?

  From dead people?

• 24:57Speaker 02

  Um, usually from surgical patients. And so what, 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.

• 25:13Danny Jones?

  Right.

• 25:14Speaker 02

  But our anesthesiologists could, um, when, 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. Um, so we could study those, uh, and it would be pretty interesting if, if that ever turns out to be, you know, something that we, we end up getting to that point in the project where we want to look at what is the human equivalent of this.

• 25:47Danny Jones?

  This website sells human, uh, pooled cerebral spinal fluid for 250 bucks.

• 25:52Speaker 02

  Yeah.

• 25:53Danny Jones?

  So they would have to be like, if a woman's going to give, do a C-section, they're gonna be like, we'll do a spinal tap. Uh, do you mind if we take a couple of grams of your spinal fluid?

• 26:00Speaker 02

  Yes. It's, it's pretty much that, right?

• 26:03Danny Jones?

  And then I assume that you don't need, like, your body will make more of it.

• 26:07Speaker 02

  It's just, it's, it's actually, I mean, it's not, it's not like blood in terms of you, you can't really donate cerebral spinal fluid. But, but certainly, um, you, you're constantly producing it. We produce it in our brains. Um, and then it's, it's, it's something that replenishes itself. I mean, you, it's also something that you want to be much more careful about how much you remove versus, um, like something like blood where we, you know, we know, we know what the limits are in both cases where, where you don't, you're, you're not going to remove a pint of cerebral spinal fluid like you would a pint of blood.

• 26:46Danny Jones?

  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.

• 26:58Speaker 02

  Yeah, that would, that would be the first step, right?

• 27:01Danny Jones?

  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 ingest anything?

• 27:09Speaker 02

  You know, that's the other side of the story, right?

• 27:11Danny Jones?

  And that's the funny thing Terrence McKenna would always say is like, it's illegal, but everyone's holding.

• 27:16Speaker 02

  Right, right, right. Exactly. And, um, yeah, and his brother Dennis is actually the one that pulled the conferences together where I got to meet uh, Egon and the new Nautics team for the first time. But, um, yeah, the, the McKennys have quite, quite an incredible legacy. But yeah, if, if we can determine how to inhibit this enzyme, um, then you can also obviously determine how to potentially accelerate the enzyme, right? So if, if people, um, if there are disease states where people are deficient in this enzyme, um, maybe we could help those people by making the enzyme more efficient.

• 27:59Speaker 02

  Um, if there are, um, opportunities to also work in, in psychiatry to help modulate mind, um, you know, areas like so much work going on now with psilocybin, so many other psychoactive substances.

• 28:19Danny Jones?

  Yeah.

• 28:19Speaker 02

  Um, 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, um, there's, there's a lot of possibilities there. I mean, the, the first and foremost would be can we do something to help schizophrenics? Because it's a terrible debilitating disease.

• 28:43Danny Jones?

  Do we know the, the, um, the biological function of DMT? Like what is, why do humans need DMT?

• 28:53Speaker 02

  It's a great question.

• 28:54Danny Jones?

  We don't know that.

• 28:55Speaker 02

  We don't know that. But you know, there's, there's a lot of things we don't know. There's a lot of things we don't understand about dream states.

• 29:02Danny Jones?

  Right.

• 29:02Speaker 02

  You know, when you're dreaming, what's, what's happening? I mean, we understand what the brain is doing in terms of brainwaves and these types of things, but

• 29:11Speaker 02

  yeah, there's, there's, there's consciousness there. Um, there's, there's a, another scientist, um, Bruce and, and I'm I'm forgetting his last name now, but he presented at the Ethno- Ethno pharmacological search for psychoactive drugs meeting, um, in, in both, uh, 2017 and 2023, we had the, the 50th gathering or the 50 year gathering of this meeting. That was the, probably the most important, um, drug conference that no one's ever heard of. It was sponsored originally by the federal government in 1967 was the first

• 29:51Speaker 02

  Ethno pharmacological search for psychoactive drugs meeting. So this is before, 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, um, many of the luminaries of, of that area.

• 30:11Danny Jones?

  Straspin was probably there.

• 30:12Speaker 02

  Yeah. Uh, Timothy Leary, I mean, all these guys. And, um, they had this wonderful meeting and a proceedings book was put together. Uh, and so Dennis McKenna decided in honor of his brother and in honor of that meeting that happened to reignite it and, and redo it in the 50th anniversary of it. So in 2017 in a beautiful countryside home in England, we, 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 sixties. Um, this was a new thing and, and we're interested in, uh, looking into it. And so

• 30:55Danny Jones?

  Bruce Dahmer?

• 30:56Speaker 02

  Yeah, Bruce Dahmer. That's, that's it. Bruce, um, Bruce is fascinating.

• 31:01Danny Jones?

  Astrobiologist.

• 31:03Speaker 02

  Yeah. He, so he, he can, he talks about endogenous tripping.

• 31:08Speaker 02

  So where you can actually get your mind into spaces where you can, 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.

• 31:29Danny Jones?

  Like you can use like breathing techniques and stuff.

• 31:31Speaker 02

  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.

• 31:39Speaker 02

  He, you know, he was describing all of this. And when I, when I came back from the meeting where he presented this, this one was in twenty twenty-three, I was actually had just started practicing transcendental meditation. And transcendental meditation, for me at least, would would do a lot of that, what he described. So you get your mind into a space where you're focused and and you transcend where you are. So you're conscious, but it's a, it's another level of consciousness. So you're, you're completely still, you're, you're quiet. There's no breathing techniques, there's no techniques with it.

• 32:24Speaker 02

  It's a, 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 twenty-minute meditation twice a day. But I've had the experiences where I've had these incredible floods of colors and, and different just kaleidoscope visions of of things. And I'm not taking anything, no, no medications or anything, but.

• 32:59Danny Jones?

  Do you listen to music?

• 33:00Speaker 02

  No, no, you're completely in quiet space. But Transcendental Meditation TM, it's TM.org is the main website. It's Aravedic, comes from the Vedas of India. It's very rooted in, you know, this, 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 for, called Heal the Healers for physicians, nurses, healthcare practitioners.

• 33:42Danny Jones?

  How often do you do this?

• 33:43Speaker 02

  Every day.

• 33:44Danny Jones?

  Every day?

• 33:44Speaker 02

  Every day.

• 33:45Danny Jones?

  And what, what specific benefits do you get from it?

• 33:48Speaker 02

  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, 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, it takes a couple of minutes to come out of that state

• 34:33Speaker 02

  because your body actually gets so relaxed that you, you, you, you could hurt yourself if you try to get up too fast.

• 34:41Danny Jones?

  Interesting.

• 34:42Speaker 02

  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 sentence, senses become kind of heightened, right? You start to hear other colleagues faintly in their offices. But you can, you can, you can choose to focus on those things or you can just choose to, to continue to. To perform the, the practice of the TM and they, they show with brainwave measurements, they show how it can really

• 35:24Speaker 02

  put you in this altered state of consciousness naturally. It's not like, I, I don't ever feel like I've gotten high or, 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, is, is gone out of my body.

• 35:43Danny Jones?

  Never saw any interdimensional aliens when doing this?

• 35:45Speaker 02

  No, no, no DMT like experiences. No, no people have approached me, but I, you know, it's, it's interesting because you kind of, you kind of mentally think to yourself that you're, you're, you're actually descending below the waves into the calmness of, of the ocean. So that, that all that craziness that's in front of you all day long, you're just taking time to, to bring it down and, and let all that stress out. Tremendous stress reliever. I, I, I mean, I can't believe it. I used to, literally used to just clinch my jaws and grind my teeth. All that's, all that's been gone since I've been doing this, but.

• 36:28Danny Jones?

  How long have you been doing it?

• 36:31Speaker 02

  Just about.

• 36:34Speaker 02

  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, 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 this is this is really great. But she makes sure that I'm keeping up and, and you know, doing things right and still doing the practice correctly because a lot of people start,

• 37:19Speaker 02

  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, one of the hallmarks of what they talk about is how easy it is. And it truly, it's truly, truly easy.

• 37:42Danny Jones?

  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,

• 38:26Danny Jones?

  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 M N Nice Ethno dot com slash DJ and use my code DJ22 for 22% off your first order. That's M N N I C E 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, by doing things like meditation and,

• 39:12Danny Jones?

  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. It's like, um, it's just this mystery that we keep poking at. We can't seem to solve the riddle.

• 39:28Speaker 02

  And not only that, I mean, I always think being in 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?

• 39:39Danny Jones?

  Yeah.

• 39:40Speaker 02

  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?

• 39:49Danny Jones?

  Right.

• 39:50Speaker 02

  No one, no one monitors the brainwaves. No one monitors what their neurotransmitters are doing when they're taking the placebo.

• 39:57Danny Jones?

  Right.

• 39:58Speaker 02

  You know, there could be a whole, a whole just personal psychoactive experience happening in there. That's, that's making you feel like you've gotten this benefit.

• 40:07Danny Jones?

  And then you have people that are like hypochondriacs that think like when they have like a headache, they're dying of brain cancer. I know people like this and they just, they, they get a headache and they go to the hospital. And that can, I imagine if, 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 like manifest as something real.

• 40:29Speaker 02

  It's, it's possible. We, 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, 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,

• 40:51Danny Jones?

  Right.

• 40:52Speaker 02

  for this disease. Do I have this disease, right? So it is, 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, if you believe it, it will happen. If you, if you believe that you're going to get cancer, you're gonna 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.

• 41:22Danny Jones?

  It would be interesting to see a study on this, you know, like people like who are newly diagnosed with cancer. That's like the fact of the thing. It's like, that's a really unethical study to do, like to take, to take one group and basically do it the way communicate, like have the, 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 like what the difference, I would be curious to see what the difference would be.

• 42:05Danny Jones?

  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.

• 42:27Speaker 02

  Right. And there may very well be. I know.

• 42:31Speaker 02

  You know, I had a wife that passed away from cancer and she had a surgery where they, they believed it was going to be a hundred percent 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,

• 42:55Speaker 02

  she developed another cancer. And, 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, 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 flu we took off of you is, you know, you're at stage four. Um, and this was just, this was

• 43:37Speaker 02

  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, she actually passed away within a couple of weeks. It was, it was, it was awful. It was just awful to watch and see that, that sort of both, I actually lived that both sides of that story and my wife, my current wife now just, we're, we're actually, today is a one year anniversary of her biopsy for breast cancer.

• 44:19Speaker 02

  And she ended up, she ended up having breast cancer and had a bilateral mastectomy and a rebuild done. And, and it's been, you know, she's, she's quote unquote cured of cancer and didn't have to do chemotherapy or radiation is a real blessing, but the, the difficulty from the surgery, the pain and all the, the changes of her body, the mental aspects of it.

• 44:47Danny Jones?

  Yeah.

• 44:48Speaker 02

  It's just been, it's been a hell of a year.

• 44:50Danny Jones?

  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, and his dad and his mom were like, every day they were bringing in all kinds of people to like do magic tricks form. 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,

• 45:36Danny Jones?

  He had no conception in his mind that cancer was something that was gonna kill him. Like he didn't, and this would last from like three to maybe like 12 or 13, I wanna say. And he was in and out of the hospital the whole time and um, he said like during that time, like he knew he was sick. And um, but he never like felt like his life was in danger. And um, the crazy thing about this is when he finally got the cancer free in his life. I wanna say it was between 10 and 12 or something like this, 13. Like literally a couple of weeks later, his dad got diagnosed with that same child, child leukemia.

• 46:21Danny Jones?

  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. And he's still, he's still in remission after all those years.

• 46:37Speaker 02

  That's, I, yeah, it's a, it's an interesting story. My, my son, my oldest son actually has um, was diagnosed with an old man's leukemia. Um, when he was, uh, let's see, he's two years, he's 20, 20 years old.

• 46:57Speaker 02

  And he was diagnosed with CML, which is chronic myeloid leukemia, which is usually what happens to 50, 60 year old men, not, not, not young, young, healthy, supposedly healthy adults and, and it presented to him just as um, sort of allergies and, and feeling sick. And we never really thought twice about it. And my wife is a, is a oncology specialist, oncology nurse and we, we, you just wouldn't really think about it, but um, 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, and sure enough, his, his white blood cell count was incredibly elevated, dangerously elevated.

• 47:42Speaker 02

  And they ended up immediately getting him in emergency. Room and and it was lucky for us because we have the 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, we ended up getting the physician for him that that was able to bring a lot of the drugs to market for this disease through clinical trials and and he wanted to take him on because they don't see young, young men with this type of cancer. So he said, this is something I really want to study and and have him a part of us. And, you know, it brought up

• 48:23Speaker 02

  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 and because of, 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, you know, the the average person doesn't know how to navigate the system and certainly doesn't know what to do.

• 48:56Danny Jones?

  It's like it's created to be confusing. Yeah. You know, there's this guy, this former UFC fighter, Ben Askren, who just got a, he got an infection and it somehow got into his lungs and he had to have a double lung transplant 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. But like, what a crazy world we live in. When we have, we have like the the worst insurance.

• 49:39Danny Jones?

  Uh, like the worst insurance, whatever in the, in the world, like our insurance and our healthcare and all this stuff is like so backwards. It's crazy.

• 49:49Speaker 02

  It's so difficult too, because it's, it's, it's literally a triangle. It's like you have, 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, 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, it's a very difficult place to be. And I think that the reason that we haven't

• 50:29Speaker 02

  had a very successful healthcare overall plan or, or discussion as a nation is because of that factor. Everybody makes the promise and runs on a promise of, you know, we're going to do these things, but when it comes down to reality, um, you, you just, you just can't do it in healthcare economics.

• 50:49Danny Jones?

  One of the most absurd things that I, 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 the, 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.

• 51:15Speaker 02

  It's amazing, um, that the insurance companies have driven the costs of healthcare as much as they have. Um, and, 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.

• 51:38Danny Jones?

  Yeah.

• 51:39Speaker 02

  Anyway, so it's kind of a, it's kind of a, a mess and we still end up pushing all the fingers, uh, to point at the pharmaceutical companies for the cost of drugs. Um, and, and no one ever talks about the insurance.

• 51:57Danny Jones?

  Right.

• 51:58Speaker 02

  Being out of whack and being really what's causing, uh, a lot of this healthcare costs to just skyrocket.

• 52:05Danny Jones?

  Right, right. Totally. Yeah. And then to the cancer thing, too. It is crazy that, you know, 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.

• 52:19Speaker 02

  Yeah.

• 52:20Danny Jones?

  You know, it seems like it seems like such a primitive form of of treatment for something that we've been studying and spending so much dumping so much money into for so many years.

• 52:28Speaker 02

  Yeah. I mean, we've had there. There are some really good success stories, but you're right. Overall, you know, most people that end up with some sort of form of cancer end up with a radiation and a chemotherapy plan to to follow through with it. Very few times is it just a surgery that can can take care of the situation. And and a lot of people dismiss that surgery as, oh, your cure of cancer is all good, but that surgery could be disforming. It could be, you know, something that now creates pain for the rest of your life. So there's there's other other problems.

• 53:04Danny Jones?

  Yeah. Yeah. And surgeries, I think it was, 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

• 53:18Speaker 02

  Yes.

• 53:18Danny Jones?

  mistakes, medical mistakes in hospitals.

• 53:21Speaker 02

  As they say, hospitals are no place to get well. And and and the mantra of pharmacists, drugs are to sell, not to take. So, you know, there's, 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.

• 53:47Danny Jones?

  And I've also, what is this, Steve? Medical malpractice deaths are significant cause of death, but there's no single leading cause of malpractice deaths. Wiley cited 2016 John Hopkins study found that medical malpractice errors are the third leading cause of death in the US. Okay. So in 2016, it was the third with an estimated quarter million deaths annually. God.

• 54:08Danny Jones?

  That's a lot, man.

• 54:10Speaker 02

  That's a lot.

• 54:12Speaker 02

  So it's.

• 54:15Danny Jones?

  That's scary.

• 54:16Speaker 02

  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.

• 54:31Speaker 02

  You know, all preventable causes of death are the, unfortunately, the leading causes of death.

• 54:38Danny Jones?

  Yeah.

• 54:41Danny Jones?

  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.

• 55:05Danny Jones?

  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 drip. 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.

• 55:47Danny Jones?

  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 tested 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.

• 56:33Danny Jones?

  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 is 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 dot S O and use the coupon code Danny at checkout to save 15% on your order. Or go to ver dot S O slash Danny. It's linked down below. Now back to the show.

• 57:03Speaker 02

  And so I think, um, you know, well, we have to learn that, right? You have to learn if that's really, if that's really the case or not. Certainly, um, you know, some, 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.

• 57:24Danny Jones?

  Right.

• 57:26Speaker 02

  You know, taking that variable out of the equation, if you can still get a benefit.

• 57:30Danny Jones?

  Yeah.

• 57:32Speaker 02

  Would be pretty big.

• 57:33Danny Jones?

  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.

• 57:46Speaker 02

  That's, that's what people say too. So, you know, it'll, it'll all bear out over time.

• 57:52Danny Jones?

  It's just this weird stigma too, that's involved with these types of drugs and how, um, 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, that smoke weed or get high around their kids are, are, you know.

• 58:15Danny Jones?

  Are irresponsible and doing harm to their kids and like the problem is these people that that project this narrative to the public for the most part have never experienced any of these drugs before.

• 58:27Speaker 02

  Right.

• 58:28Danny Jones?

  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.

• 58:50Speaker 02

  Yeah, there's, it's, it's really interesting, you know? I mean, I, I think there's a lot of things that get completely twisted and, and taken out of context. The perfect one for me right now, um, and work that we're, we're hoping to start soon. We're just waiting for our shipment to arrive of, 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, you know, couple hundred to possibly a few more hundred

• 59:32Speaker 02

  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.

• 59:43Danny Jones?

  Right. It's supposed to be helpful for that, right?

• 59:45Speaker 02

  It's good for altitude sickness. It's also good for stamina, energy. Um, you know, we, we basically hiked this mountain for three and a half hours. No, not one time did I get hungry, not one time did I get exhausted, winded. Uh, and I'm not a, a mountain hiker at all anyway. So, uh, it was just a cool, cool experience and, and experiencing coca leaf firsthand. Um, I didn't feel anything psychoactively. Yeah, my, my mouth got a little bit numb. Like kind of when you go to the dentist and you feel that, um, you get Novocain or whatever they give you for. Or anesthetic, local anesthetic and you, you know, you'll drool out of your mouth for a while

• 1:00:29Speaker 02

  or you might bite yourself.

• 1:00:31Danny Jones?

  Yeah.

• 1:00:32Speaker 02

  It's nowhere near that intense.

• 1:00:33Danny Jones?

  Interesting.

• 1:00:35Speaker 02

  But that that's the same type of feeling. It's almost like when you're finally coming off and you, you, you feel it.

• 1:00:41Danny Jones?

  Yeah.

• 1:00:41Speaker 02

  But, but you, you can still chew and drink and do all the things that you would do.

• 1:00:47Danny Jones?

  So what, what is it comparable to in your opinion? Is there anything that you could compare it to?

• 1:00:54Speaker 02

  So, I mean, energy wise, I would, I would definitely say something like a good, strong cup of coffee or, or energy beverage, highly caffeinated beverage. But there's no caffeine in it, of course, but the stimulant, the stimulant effect is definitely there. But there's absolutely no, there's no psychoactivity. So what, what happened? This is why I'm saying this is really interesting to me because 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.

• 1:01:37Danny Jones?

  What year was cocaine first created? Wasn't it like before World War One?

• 1:01:41Speaker 02

  Yeah, it was in the 1800s.

• 1:01:42Danny Jones?

  1800s, yeah.

• 1:01:43Speaker 02

  In the mid 1800s, I believe. And maybe we can, Steve can fact check.

• 1:01:47Danny Jones?

  Steve will find it for us.

• 1:01:49Speaker 02

  But morphine was 1802. And I think cocaine was 1820s. Let's see if my trivia is, 1859.

• 1:01:58Danny Jones?

  1859 by the German alchemist. Albert Neiman.

• 1:02:03Speaker 02

  Albert Neiman. So these guys were both pharmacists. He was a pharmacist and then Frederick Sir Turner 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 a, a 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 just wild, crazy where, where things went. The thing is, is that people started using these things and stopped using

• 1:02:46Speaker 02

  the other things that they were having problems with because these were much better, right? So

• 1:02:51Danny Jones?

  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.

• 1:03:02Speaker 02

  Oh, yeah.

• 1:03:03Danny Jones?

  From like thousands of years ago, and he found cocaine.

• 1:03:06Speaker 02

  Yeah.

• 1:03:07Danny Jones?

  Have you heard of this?

• 1:03:08Speaker 02

  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

• 1:03:21Speaker 02

  ethnobotanist 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

• 1:03:35Speaker 02

  tombs in the Andi Mountains, right? People were buried, people were buried with coca leaf. Either in their mouths. Or in their body, like they would have them in bags with them. 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 the climate is similar, they could grow the plants and and, you know, not exactly the same species.

• 1:04:17Speaker 02

  But 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

• 1:04:30Speaker 02

  other psychoactive substances and mushrooms. Different types of things that that have also been been shown.

• 1:04:43Danny Jones?

  What does he say, Steve?

• 1:04:46Speaker 02

  Uh, Hennet Tau was, was the mummy that they found cocaine in.

• 1:04:51Danny Jones?

  A priestess from ancient Egypt and other remains, the toxicologist and her team. They found this, they found the coke though, they found uh, traces of cocaine, nicotine, hashish in the mummy's hair, bone and soft tissue. Whoa.

• 1:05:07Speaker 02

  Yeah, so it's, it, it's, it's pretty well known that substances were being used. There was another talk at this meeting. Where many of the stories um, in, in the Old Testament of the Bible, which is the foundation for, you know, our three main global religions, Christianity, Judaism and Muslim, um, the Quran. So many of the stories that are in there um, are thought to be explained by hallucinogenic substances.

• 1:05:40Danny Jones?

  Yeah, there's lots of theories, yeah.

• 1:05:42Speaker 02

  And so it was interesting discussions in the meeting and talking about this, but uh, there have always been a lot of speculation, but really no hard evidence um, 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 uh, when they were either mummified or just buried and entombed with many, many um, different trinkets or, or pouches or whatnot that were filled with um, psychoactive substances.

• 1:06:15Danny Jones?

  Yeah. Yeah, there, there is so many theories uh, when it comes to uh, like psychedelics being the foundation of religion and stuff like that. But there is um, I mean, there's tons of eviden- like, have you ever heard of Galen? Marcus Aurelius's physician, he has, he's written uh, more than 10% of all of the.

• 1:06:39Danny Jones?

  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 like all of the prescriptions and medications, cocktails that he was putting together and testing on people. And giving to Marcus Aurelius, including like opium. And he was creating these these venomous cocktails with with vipers. Like he would use like 11 different North African viper venoms and viper flesh.

• 1:07:23Danny Jones?

  Combined with opium into this cocktail called a theriak 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's was the most common way of assassinating somebody. Was like getting them with like scorpion poison or snake venom or something like that. So he was every day drinking this theriak concoction to keep his immune system robust against the stuff. It's just fascinating to learn about. You know, ancient medicine being used in Jesus times.

• 1:07:53Speaker 02

  Yeah, I mean, it's it's interesting today because. You know, 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 know, you you hear about peanut allergies. Sometimes when you're on a flight, severe nut allergies, don't use any any nuts. That was never an issue up until they came out with this wacky study

• 1:08:36Speaker 02

  that told parents not to give peanuts. And then the American Academy of Pediatrics or somebody sort of validated that as a 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

• 1:08:55Danny Jones?

  Really?

• 1:08:56Speaker 02

  I got that out of the new FDA Commissioner Marty Makary's book, most recent book, which is is really highly recommended reading, but one of the chapters in there is this whole peanut allergy.

• 1:09:09Danny Jones?

  What's this guy's name?

• 1:09:10Speaker 02

  Marty Makary.

• 1:09:12Danny Jones?

  Marty McCurdy?

• 1:09:13Speaker 02

  Marty Makary.

• 1:09:14Danny Jones?

  Makary.

• 1:09:15Speaker 02

  M A K A R Y. He's the current FDA Commissioner.

• 1:09:19Danny Jones?

  Oh, okay.

• 1:09:20Speaker 02

  Yeah.

• 1:09:21Danny Jones?

  Interesting.

• 1:09:22Speaker 02

  So it's really good stuff.

• 1:09:24Danny Jones?

  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?

• 1:09:34Speaker 02

  I mean, these kids are, these kids are so unexposed to the peanuts that if they get exposed even to it in the air, they can have anaphylactic reactions. So it's, it really is about having kids being exposed to peanut butter, peanut, you know, containing foods.

• 1:09:54Danny Jones?

  Early in their life.

• 1:09:55Speaker 02

  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.

• 1:10:06Danny Jones?

  Right.

• 1:10:07Speaker 02

  I mean, I love my peanuts.

• 1:10:10Danny Jones?

  Yeah.

• 1:10:10Speaker 02

  Have a hard time giving them up. So I'm glad I wasn't born during that time when, when all the peanut allergies started.

• 1:10:18Danny Jones?

  Yeah. No, what my, my kids, elementary school, wouldn't let them have peanut butter jelly sandwiches. They had to do like sunflower butter or some, some goofy stuff.

• 1:10:26Speaker 02

  Yeah, they've changed cashew butter.

• 1:10:28Danny Jones?

  Yeah, so crazy.

• 1:10:28Speaker 02

  Whatever, whatever it is.

• 1:10:30Danny Jones?

  Yeah.

• 1:10:30Speaker 02

  Almond butter.

• 1:10:31Danny Jones?

  Yeah.

• 1:10:32Speaker 02

  Many different things.

• 1:10:33Danny Jones?

  Maybe they can come up with peanut vaccines and they can sell those, make some money.

• 1:10:38Speaker 02

  Would be good. Yeah, it was this, this prevalence really.

• 1:10:42Danny Jones?

  What is this? Peanut allergies were not always so common. The prevalence in American children more than tripled between 97 and 2008. Oh, my God.

• 1:10:52Speaker 02

  Yeah. So it's, it's a, it's a sad thing. I mean, the peanut allergy rates across the globe are almost unheard of because you just don't, you don't hear people talking about it in, in other countries outside of the United States.

• 1:11:09Danny Jones?

  Yeah. So going back to coca.

• 1:11:12Speaker 02

  Yeah.

• 1:11:13Danny Jones?

  Coca seems like it could be similar to nicotine or caffeine, maybe some in that group. So why is it illegal in the US? Is it specifically because it's connection to cocaine?

• 1:11:25Speaker 02

  So interestingly, yes. First, the answer is the connection to cocaine. But more interestingly, actually, the US has it in a restricted category of Schedule II of the Controlled Substances Act, which means it's it's legal to use that has a medical benefit.

• 1:11:45Danny Jones?

  Oh, really?

• 1:11:45Speaker 02

  Although.

• 1:11:45Danny Jones?

  Like cocaine, like for?

• 1:11:47Speaker 02

  Well, because cocaine is still extracted from the plant itself. And so if you make the plant Schedule One, then you can't actually use it to get to the pharmaceutical grade cocaine.

• 1:11:59Danny Jones?

  Because they use it for like eye surgeries and things like that.

• 1:12:02Speaker 02

  Surgery, yeah. And in fact, all the coca leaf that that has been imported into the United States for the last, I don't know, hundred 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 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,

• 1:12:44Speaker 02

  but obviously no cocaine in those formulas. And Coke 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.

• 1:13:04Danny Jones?

  This stuff sucks.

• 1:13:05Speaker 02

  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, the remaining extract goes to Coca-Cola as part of the formula. So.

• 1:13:34Danny Jones?

  So they're the only ones who are allowed to have.

• 1:13:36Speaker 02

  Right now, they, they seem to have a monopoly on it. So we're finally getting to the point where,

• 1:13:44Speaker 02

  you know, I, 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 a air carrier that will bring it into the United States.

• 1:14:11Danny Jones?

  An air carrier?

• 1:14:12Speaker 02

  Yeah, like FedEx or DHL.

• 1:14:15Danny Jones?

  So you have to go contact one of them or, and get them to?

• 1:14:18Speaker 02

  So they're, they're, they're, they're not interested in carrying controlled substance in large quantities. We'll get it worked out at some point, but it's.

• 1:14:29Danny Jones?

  I got a guy.

• 1:14:30Speaker 02

  Been a problem. Yeah.

• 1:14:31Danny Jones?

  I got a guy for you.

• 1:14:32Speaker 02

  I could potentially go down there myself and do it with, cause I have the import permit, but.

• 1:14:37Danny Jones?

  We got Roger Reeves. We got, I don't know if you remember Roger Reeves. We got this guy who was a, he was a pilot for the cartel back in the eighties 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, he was smuggling like millions of dollars of pot and cocaine every single day between Mexico and the US. 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.

• 1:15:06Speaker 02

  I have to find that.

• 1:15:07Danny Jones?

  It's with. American made. American made, Tom Cruise, yeah.

• 1:15:09Speaker 02

  American made. Oh, Tom Cruise. One of his lesser.

• 1:15:13Danny Jones?

  I'll get you his number.

• 1:15:15Speaker 02

  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 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 part part and part the major producer of the illicit supply of cocaine.

• 1:15:57Speaker 02

  But there are registered and and growing areas of getting conversations with a faculty member of the University of the Andes. And it's really fascinating. They're doing metabolomic studies and 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.

• 1:16:26Speaker 02

  But it they they actually want to start doing it like the wine industry does, you know, terroir makes a big difference on the flavor profile of of the grape that's produced in the wine industry. And so they're saying, they're making this argument in the coca industry.

• 1:16:44Speaker 02

  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 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. So I immediately ordered coca leaf tea, had my coca leaf tea. So I was definitely testing positive for cocaine at that point.

• 1:17:16Speaker 02

  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. Um, around this planet, researchers, tribal, um, you know, leaders in South America and have a, a week-long discussion around everything. Um, 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.

• 1:17:59Speaker 02

  It may still be restricted, but they might pull it completely out. There's no indications that coca leaf can be, um, habit-forming or addictive. But obviously, if you pull the cocaine out, you know, it's a much, much bigger danger, um, by itself.

• 1:18:18Danny Jones?

  Which is not an easy task. I mean, you have to have like, you have to use gasoline or diesel fuel.

• 1:18:25Speaker 02

  That's the way they do, the cartels do it, right?

• 1:18:27Danny Jones?

  Yeah. Oh, there's a, there's like a nicer, easier way to do it.

• 1:18:29Speaker 02

  Yeah, there's a more elegant way to do it. Like the companies in the United States that are refining it for the pharmaceutical industry. It's completely different grade of things that are done.

• 1:18:41Danny Jones?

  So this is something that somebody could do in their basement if they wanted to?

• 1:18:44Speaker 02

  Um, if they wanted to, it would be a lot of work to get enough cocaine to actually work with.

• 1:18:52Danny Jones?

  Right.

• 1:18:52Speaker 02

  Uh, and, and have something happen, but that's been the fear. 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. Uh, it's, it's not that simple.

• 1:19:09Speaker 02

  That's, that's been a big analogy for us right recently. Because, uh, I, I, I just have this feeling that, uh, Kratom is headed, or Kratom is headed in that, in that direction. So the, the leaf is what first showed benefit, you know, for centuries in Southeast Asia. The, the leaf has been used by laborers to in- increase. Increase their endurance, increase their energy, elevate their moods, working out in that hot sun environment.

• 1:19:43Speaker 02

  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 increased the amount of kratom or kratom kratom that they take and they wouldn't have as bad a withdrawals. That's where we got interested in this in the first place was with the opioid crisis ongoing. Could we, like I said before, could we find a solution from, from nature? I mean, opioids came from nature. There should be something out there in nature to counteract or counterbalance that existence.

• 1:20:16Danny Jones?

  Yeah.

• 1:20:17Speaker 02

  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.

• 1:20:47Speaker 02

  So they, they have nothing to do with the natural product anymore, but they were inspired by, you know, the learnings of that. So it's, it's really a cool basis and we wanted to learn that with kratom leaf. So we, we started studying kratom leaf and then as things have evolved,

• 1:21:06Danny Jones?

  When did this start? What year?

• 1:21:07Speaker 02

  So I started this in about 2004, 2005. So we've been going 20 years on this.

• 1:21:16Danny Jones?

  That's wild. I only heard about it a year and a half ago.

• 1:21:19Speaker 02

  Well, it's really become popular in the last few years, particularly after COVID. The first popularity really with in the United States was in 2016, the DEA announced an intention to place kratom, metroganin and seven hydroxy metroganin into schedule one of the Controlled Substances Act. And that's what.

• 1:21:46Speaker 02

  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

• 1:22:27Speaker 02

  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.

• 1:22:49Danny Jones?

  Right.

• 1:22:50Speaker 02

  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 wean 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

• 1:23:30Speaker 02

  started to appear and as we came out of COVID, those same addiction physicians said, hey, you know, I've got people coming in now that want to get off of these shots and they're not

• 1:23:41Danny Jones?

  Kratom?

• 1:23:42Speaker 02

  Kratom shots and they're not able to get off of these without really help, right?

• 1:23:49Danny Jones?

  Yeah.

• 1:23:50Speaker 02

  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, um, instead of addiction, uh, they're just using it inappropriately, too much of it. It could be dangerous use, um, for, for that person, but they have severe, um, consequences when they stop using it. And that generally is withdrawal. Um, and that withdrawal can be anything from just anxiousness, irritability, or even, um, restless leg syndromes, um, pain, jitters, uh, all these types of things. And so

• 1:24:31Speaker 02

  if they take kratom again, then they, that, 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, uh, interactions. And so serotonin is our, you know, mood, uh, sort of enhancing all the, um, SSRIs like Prozac and, uh, these drugs, uh, inhibit the reuptake of serotonin. So they increase the amount of serotonin

• 1:25:13Speaker 02

  in the brain, which gives us that satiety, that sort of feeling of, of pleasure. Um, yeah, it's really mood enhancement for, and, you know, depression treatment. Um, then we have the adrenergic system, which is our fight or flight system. That's what gives us that stimulant like effect. Um, 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. Right? So we're ignoring the serotonin, we're ignoring the adrenergic piece. And is

• 1:25:55Speaker 02

  that important? Uh, we don't know. Um, but, but I don't know that we're doing the best job in treating that. But as, 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 seven hydroxymetragonin, which is the compound. This is the stuff they just banned? This is banned. Seven OH? Yeah. In the state of Florida, it was emergently banned last week. Yes, and in the federal.

• 1:26:26Danny Jones?

  Does it still have that in there?

• 1:26:27Speaker 02

  Yeah, but a very little, very little amount. I think less than point oh two percent is what it said.

• 1:26:34Danny Jones?

  Less than point oh two. So would this be illegal to sell now?

• 1:26:36Speaker 02

  No.

• 1:26:37Danny Jones?

  No, okay.

• 1:26:38Speaker 02

  It's not illegal.

• 1:26:39Danny Jones?

  White Rabbit, our sponsor. It's brought to you by White Rabbit Cratom.

• 1:26:43Speaker 02

  Yeah.

• 1:26:44Danny Jones?

  My favorite energy drink.

• 1:26:45Speaker 02

  Yeah, it's it's interesting. These, this is, this is typically what we see of leaf material products. Or even many extracts. There's very low level of sevahydroxy, if any detectable sevahydroxy in those products. Sevahydroxy is created in our bodies by metabolism. So the main alkaloid, metrogynin or metragenin is oxidized in our liver and in our intestine to sevahydroxy, uh, metrogynin. 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

• 1:27:30Speaker 02

  the metroganose species or kratom plant, right? So you're getting, uh, I call it a pharmacological shotgun. It's, it's really tons, tons of different systems in our body are getting, um, turned on, turned up. Uh, I think big mixing board is like kind of all kinds of things being adjusted.

• 1:27:50Danny Jones?

  Right.

• 1:27:50Speaker 02

  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 sevahydroxy present in, in the leaf or in many of these products, that it's not economically feasible to extract that and, and try to produce products that are sevahydroxy products. So what they've figured out is that if you take the very concentrated extracts that are mostly seventy-five percent, maybe metrogynin.

• 1:28:22Speaker 02

  You can treat that with chemicals and synthetically produce seven 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, there's two factors of safety here. That's one of them.

• 1:29:02Speaker 02

  The second factor is the seven 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 would find at a pharmacy. You know, you can go to a pharmacy and get a prescription for Oxycontin or morphine sulfate or whatever it is. That's being prescribed to you by a physician. They're, you know, 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.

• 1:29:46Speaker 02

  And, and you know, when you have access to something that powerful, it becomes a public health crisis in the, in the waiting. Because what, what you could eventually have is just a whole new wave of addiction of, of problems where people are succumbing to this seven hydroxy. We don't think, though we don't have definitive answers for a lot of questions around kratom itself, but we really don't think the amount of seven hydroxy that's produced by metabolism in our bodies, when you take the whole kratom product is problematic.

• 1:30:29Danny Jones?

  Right.

• 1:30:30Speaker 02

  If you're using it responsibly. It's kind of like anything, right? Alcohol used responsibly.

• 1:30:34Danny Jones?

  Everything.

• 1:30:35Speaker 02

  Everything's okay.

• 1:30:36Danny Jones?

  I could go to the store across the street right now and buy enough alcohol to kill myself in an hour.

• 1:30:41Speaker 02

  Right.

• 1:30:42Danny Jones?

  Like, yeah, you gotta, everything has to be within moderation. But like, when it comes to drinks like this, for example, this White Rabbit.

• 1:30:51Danny Jones?

  First of all, when you did, you did a study, right, on a, on a wide or a large majority of, of individuals that signed up for the study?

• 1:31:00Speaker 02

  Yep.

• 1:31:01Danny Jones?

  And what were the parameters of the study? And how many people were involved?

• 1:31:06Speaker 02

  So I don't remember exactly how many people were involved in total, but we, we documented

• 1:31:16Speaker 02

  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 ecological momentary assessment. So there'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

• 1:31:57Speaker 02

  were taking their kratom product, they would log in, say how much they were using, say how they were feeling, saying what, 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, we had some small percentages of people that were using it purely to try and get

• 1:32:39Speaker 02

  euphoric highs. But the majority of people that were using kratom were really trying to do it for the benefit, the, you know, perceived benefit that it was giving them energy.

• 1:32:51Danny Jones?

  Oh, really? The stimulant effect.

• 1:32:53Speaker 02

  The stimulant effect, elevating their mood and treating their pain. I mean, those are really the top motivators for why people use this. And and seem to use it responsibly and 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, we know that tolerance in humans seems to develop. So in other words, over time, you need more to get the same effect.

• 1:33:29Danny Jones?

  Right.

• 1:33:30Speaker 02

  I mean, I've talked to most people that generally use two to five grams of powdered material, two to three times a day.

• 1:33:41Speaker 02

  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 to be able to get the benefits. And those people.

• 1:33:58Danny Jones?

  This is how much again?

• 1:34:00Speaker 02

  I think it said 45.

• 1:34:02Danny Jones?

  Forty five milligrams.

• 1:34:04Speaker 02

  Of leaf material in that, so or extract material in that. So it's hard to say.

• 1:34:10Danny Jones?

  Moderate amount.

• 1:34:11Speaker 02

  It would be very moderate. This would be more similar to that range of that two to five gram.

• 1:34:18Danny Jones?

  Yeah.

• 1:34:18Speaker 02

  Level according to their metroganin content, it has 30 milligrams of metroganin. We see about 20, 20 milligrams in a gram of a leaf. So this isn't even really two, two, three grams of leaf material.

• 1:34:36Danny Jones?

  I know one of the biggest problems with it is that it's highly addictive.

• 1:34:42Danny Jones?

  Just like caffeine can be highly addictive. I know nicotine is really, really addictive.

• 1:34:46Speaker 02

  Right.

• 1:34:47Danny Jones?

  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?

• 1:35:04Danny Jones?

  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?

• 1:35:12Speaker 02

  Yeah, so the, we don't know anything clinically about long-term effects and that, 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, 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?

• 1:35:42Danny Jones?

  Right.

• 1:35:43Speaker 02

  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's 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

• 1:36:26Speaker 02

  marker for what, what we could predict will happen in humans, right? And it gives us a good basis of where to start. So that's kind of, you know, what we, 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, 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, you know, anything like I was taking a drug, but I got this benefit

• 1:37:09Speaker 02

  of focus, energy.

• 1:37:12Danny Jones?

  Yeah.

• 1:37:13Speaker 02

  This other benefit of, hey, you know what? My, my knee that's always bothered me doesn't seem to bother me as bad as it used to.

• 1:37:21Danny Jones?

  Right.

• 1:37:21Speaker 02

  Right. And problem is when people start to use these products with, 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 seem, tend to work for quite some time and then.

• 1:37:53Speaker 01

  At Humana, our Medicare Advantage plans are easy to understand and easy on your wallet, like offering more benefits than you'd get from original Medicare alone, and including dental, vision and hearing coverage in every plan. And the best part is every plan has a $0 or low monthly plan premium, which makes it easier to save too. So this Medicare planning season, plan well with Humana. Learn more at gethumana.com. Humana is a Medicare Advantage HMO and PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal. Network freedom and flexibility. That's what you want in a healthcare plan. With a Humana Medicare Advantage PPO plan, you can see any doctor in the country who accepts Medicare,

• 1:38:33Speaker 01

  including specialists. No referrals, no kidding. Learn more at gethumana.com. See any doctor who accepts Medicare and is willing to bill Humana. Humana PPOs may not be available in all areas. Benefits and costs share may vary. Humana is a Medicare Advantage PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal.

• 1:38:53Speaker 02

  That tolerance starts to kick in. And when that tolerance kicks in, we don't know. It could differ for everybody as well. 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, with all types of drugs. And so people that are slow to metabolize drugs generally don't need as much dose.

• 1:39:24Speaker 02

  Because they can use a lower amount, it stays in their system longer. They are slow to get rid of it. They're slow to metabolize it.

• 1:39:30Danny Jones?

  We call that a lightweight.

• 1:39:31Speaker 02

  Yeah.

• 1:39:34Speaker 02

  And then you have your, your ultra metabolizers that, you know, they, they, 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, out of your system faster? You need to take more in order to get back up to those levels.

• 1:40:16Speaker 02

  And, and just like with opioids, I think, and other drugs that create a tolerance situation. You know, you, 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.

• 1:40:54Danny Jones?

  And one of the things about the kratom is it doesn't have the respiratory. This is what Hamilton Morse told me. He said that they, the kratom does not have the respiratory effects that opioids do.

• 1:41:04Speaker 02

  Yeah, it's, it seems to be less respiratory depression. I wouldn't say that it doesn't have it at all.

• 1:41:11Danny Jones?

  Okay.

• 1:41:11Speaker 02

  I think it depends again on the dose, right? It depends on how much someone's taking. And if they're over indulging, it could be the case. But interestingly enough, most of the poison control center data and emergency department data that's been generated or, or collected indicates that overexposure to.

• 1:41:33Speaker 02

  Kratom is actually more similar to a stimulant overdose where people get agitated. They have cardiovascular events. Really? 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. 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 that could be contributing to that. We also know that all three of those pathways are involved in pain control.

• 1:42:17Speaker 02

  I mean, we always think of opioids as being the the primary, you know, 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 to be involved in in pain signaling pathways in our in our brain, in our brain stem, sorry, spinal cord and and how the the signals are communicated.

• 1:42:58Speaker 02

  And so there's this, 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.

• 1:43:23Speaker 02

  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 opioid receptors and they don't, they don't recruit a certain protein called beta-ahroston that is associated.

• 1:43:43Speaker 02

  With some of the side effects like respiratory depression and constipation. That that theory, that sort of bias signaling theory has not really panned out to be solid definition. There's still a camp that believe 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 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 HT 1A receptor, very different from the 5 HT 2 receptors where the psychedelics act.

• 1:44:27Danny Jones?

  Psychedelic, yeah.

• 1:44:28Speaker 02

  So 5 HT 1A 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.

• 1:45:03Danny Jones?

  Right. Wow. I gotta take a leak real quick. We'll be right back.

• 1:45:09Speaker 02

  It's funny, I just did an emergency department at North Florida Hospital in Gainesville. I talked to their emergency department this morning about kratom and all the products.

• 1:45:20Danny Jones?

  Oh, really?

• 1:45:21Speaker 02

  Yeah. Give the did it in service for them.

• 1:45:24Danny Jones?

  What were they asking specifically? Like, what do they want to know?

• 1:45:28Speaker 02

  They, 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?

• 1:45:37Danny Jones?

  Yeah.

• 1:45:39Speaker 02

  And many people are talking about seven hydroxy products as if they are kratom. And I think that's been the biggest thing with kratom is it's, one of the commentaries we've published recently is that not all kratom is equal. And

• 1:45:54Danny Jones?

  It's like calling it, it's like alcohol, right? There are types of alcohol.

• 1:45:57Speaker 02

  Yeah, it's, it's, you definitely have um the, the, that whole spectrum there uh where you have I always sort of talk about like even the seltzer um alcohol seltzers like White Claw or like beer is, is more, more closer related to something like the leaf that is got, got the alcohol in it, but not a lot, right? And the leaf has the alkaloids in it, but not a lot.

• 1:46:23Danny Jones?

  Right.

• 1:46:24Speaker 02

  Um, but as we move into concentrated extracts and then heavy concentrates, you move into things like

• 1:46:32Danny Jones?

  Tequila.

• 1:46:32Speaker 02

  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 ninety five percent alcohol. Um, and we know there's

• 1:46:54Danny Jones?

  And that's gonna bypass the stimulant effect, right?

• 1:46:56Speaker 02

  Oh, yeah.

• 1:46:56Danny Jones?

  And go straight to the uh

• 1:46:58Speaker 02

  That seven hydroxy is just pure opioid effect. And so that's what, what, what people are getting is that sort of equivalent. Um, I, I had a woman email me uh after another podcast I did, and she said, you've left out an entire population of users that you didn't report on. And, 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, or moved away. And so they've resorted to

• 1:47:36Speaker 02

  removing them from uh 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 this, these um enhanced extract products or uh seven O H products were perfect because now they can have it shipped right to their front door um and get the benefit of Those same drugs without having to worry about doctor shopping or going out and getting Right. You know, stealing essentially from their, from their neighbors and friends. And so

• 1:48:21Speaker 02

  that, that's what really tipped me off into realizing that the 7OH products are, are really not something that should be out in Gas stations. Gas stations. They, they, they may have a legitimate place in medicine and I want to be clear on that. Right. Because if they do As does morphine. Yeah, yeah, yeah. I mean, but if seven hydroxy has less respiratory depression than morphine. Might be, yeah. It might be a more beneficial painkiller. Hmm. Because it could be 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, and what their abuse liability is, how addictive they are.

• 1:49:07Speaker 02

  When you talk about kratom addiction, just to the leaf material.

• 1:49:15Speaker 02

  You know, most people have reported and even the scientific studies that have been done with humans show that has a very low withdrawal rating. What, what they would call mild, which is where coffee is as well. Full spectrum leaf. Full, full spectrum leaf. And again, it's a caveat that these are being in low doses and short amount 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 that, what they call the subjective opioid withdrawal scale or SAWS.

• 1:49:58Speaker 02

  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.

• 1:50:26Danny Jones?

  Which one, where's alcohol land?

• 1:50:28Speaker 02

  That's an interesting question. I don't know because it's

• 1:50:30Danny Jones?

  I heard alcohol is like the, it's the one of the one things when you're withdrawn from it, you can actually die.

• 1:50:35Speaker 02

  It's, it's bad. Um, and, and

• 1:50:38Danny Jones?

  Type in alcohol withdrawal, Steve.

• 1:50:40Speaker 02

  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. Um, you know, medically, they're

• 1:51:04Danny Jones?

  You'll always survive that.

• 1:51:06Speaker 02

  Pretty much.

• 1:51:07Danny Jones?

  Wow.

• 1:51:07Speaker 02

  Pretty much. Um, you know, I've heard stories where the, they basically put you into the withdrawal state. And you could be in a padded room or some other things and have

• 1:51:19Danny Jones?

  Give me some stats.

• 1:51:21Speaker 02

  Things there, but yeah, alcohol withdrawal takes days.

• 1:51:24Danny Jones?

  Yeah.

• 1:51:24Speaker 02

  And there's no way to immediately withdraw somebody from it. And so you go through, um, all kinds of different symptoms over those, those several days. And it's interesting. I, I told you, my wife is a nurse. And so when they get addicts that end up in their, in their units, they say the, the more honest you are with us about your drug use, the less withdrawal you're going to go through.

• 1:51:49Danny Jones?

  Right.

• 1:51:50Speaker 02

  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, is that they start going into horrible, horrible withdrawals in the hospital.

• 1:52:05Danny Jones?

  If they are addicted to something like heroin or cocaine or something, you can like titrate them down.

• 1:52:10Speaker 02

  Right.

• 1:52:11Danny Jones?

  Naturally.

• 1:52:12Speaker 02

  Or there's ways to at least monitor and be more cautious and use other substances to, to make that up. But generally these people tend to turn into some of the meanest individuals, um, that, that now the nursing staff has to deal with, uh, on a regular basis as they're withdrawing. They can be physically, uh, you know, harmful, depending on the size of the individual.

• 1:52:38Speaker 02

  It could be a dangerous situation. And so the, the more honest they are, the better treatment they're going to receive, but Um, most people don't want to admit that they're using four or five different substances and they go into these withdrawals. And so, um, but yeah, you, you do have, uh, the, the alcohol withdrawal. I think the, the stats are, he's found some stats, but

• 1:53:04Danny Jones?

  This is, 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, other drugs. Yeah.

• 1:53:17Speaker 02

  Yeah. But it is pretty fascinating because it, like I said, it takes days to withdraw from alcohol.

• 1:53:22Danny Jones?

  It's just interesting how like some of the drugs that are ubiquitous in Western society that, that are, you can buy anywhere, like alcohol are like so dangerous if, if used the wrong way and can kill so many people. And it's, it's always just, you know, fascinated me, the drugs that are illegal that seem to be far less dangerous.

• 1:53:44Speaker 02

  Right, right.

• 1:53:45Danny Jones?

  You know?

• 1:53:46Speaker 02

  Right.

• 1:53:47Danny Jones?

  And like, like, like, how, and how many, going back to coca, like, how many drugs are, are literally banned worldwide by the CDC like that, like coca leaf?

• 1:53:56Speaker 02

  Uh, by the WHO, there's, there's

• 1:53:58Danny Jones?

  The WHO, yeah.

• 1:53:59Speaker 02

  There's many, many drugs that are banned globally.

• 1:54:02Danny Jones?

  What about cot? Have you heard, you know about cot?

• 1:54:05Speaker 02

  Yeah, from Africa, for sure. Uh, 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, chewing cot.

• 1:54:16Danny Jones?

  Is that illegal here?

• 1:54:17Speaker 02

  Uh, yeah. It's illegal here as well, but, um, but certainly, you know, it was something that they had used culturally. I, I think I read some crazy stat that, um, in, in some of those countries in Africa around Somalia, Ethiopia, like 90 some percent of the population uses cot. So it, it's just a cultural thing that's done, just like probably 90% of our population uses coffee and tea or caffeinated beverages to, to say whatever. Um, so, you know, it, it's a cultural norm. It's, are they all dependent on it? Probably. Is most

• 1:54:56Speaker 02

  of America dependent on coffee? Yes. So, so, you know, the severity of this, this really depends, right?

• 1:55:05Danny Jones?

  So there's two drugs that the withdrawal can actually kill you. Number one is alcohol and number two is benzodiazepines.

• 1:55:12Speaker 02

  Right.

• 1:55:13Danny Jones?

  Opioids rarely kill people. Stimulants don't kill people. Cannabis doesn't and neither does nicotine. Seizure risk for alcohol is high, five to 15 percent. Seizure risk for benzos is also high. But opioids, stimulants, cannabis and nicotine have low or no seizure risk.

• 1:55:31Speaker 02

  Yeah. And so I think what's interesting here and, and something that a lot of people may or may not know, I don't, I don't know. I know this because of a pharmacy, but benzodiazepines, alcohol interacts with the benzodiazepine receptor. So its main, its main target in our brains is the GABA receptor, which is where benzodiazepines act. And so.

• 1:55:52Danny Jones?

  And for people who don't know, what is a benzodiazepine? How do you classify that?

• 1:55:55Speaker 02

  Benzodiazepine is actually the, the chemical structure. So benzo stands for benzene that's in it. Diazide is actually two nitrogens and the peen 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 Ativan, it's Xanax, it's Valium.

• 1:56:21Danny Jones?

  And how is that different from stuff like, um, um,

• 1:56:27Danny Jones?

  like, uh, traditional opiates, like, um,

• 1:56:31Danny Jones?

  why am I blanking on all these names? Like, not like morphine or, um,

• 1:56:35Speaker 02

  Heroin or oxycodone.

• 1:56:36Danny Jones?

  Oxycodone, right.

• 1:56:38Speaker 02

  So they, they interact with two completely different systems in our body.

• 1:56:42Danny Jones?

  Okay.

• 1:56:42Speaker 02

  So GABA is the primary gamma amino buteric acid, GABA, G A B A, is the major neurotransmitter in our brain, period. Um, is also the, the main depressant neurotransmitter in our brain. So it slows things down. It, it's the, our sort of brake, if you will, in our minds.

• 1:57:06Speaker 02

  And so a lot of people use alcohol because alcohol interacts with that same receptor that GABA interacts with. And, 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.

• 1:57:39Danny Jones?

  Okay.

• 1:57:40Speaker 02

  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.

• 1:57:52Danny Jones?

  Xanax is the same class.

• 1:57:53Speaker 02

  Xanax, 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 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.

• 1:58:19Danny Jones?

  Okay.

• 1:58:20Speaker 02

  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.

• 1:59:05Speaker 02

  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, um, you know, originally isolated out of the poppy.

• 1:59:33Danny Jones?

  It's just fascinating how withdrawal from benzos can kill you, but opioids can't.

• 1:59:38Speaker 02

  Yeah, so let's talk about what is withdrawal. Withdrawal is the absolute opposite effect that you get from the substance.

• 1:59:48Speaker 02

  So think about, think about what we just talked about with benzodiazepines and alcohol, right? They're depressing everything.

• 1:59:54Danny Jones?

  Mm hmm.

• 1:59:55Speaker 02

  They're slowing everything down. So if we take that brake off and we just let the gas pedal go, the brain's going to be over excited and can run into seizure activity.

• 2:00:08Danny Jones?

  Ah, and a seizure, the cause of death?

• 2:00:11Speaker 02

  Many times.

• 2:00:13Danny Jones?

  Oh, okay.

• 2:00:14Speaker 02

  seizure or, 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.

• 2:00:38Danny Jones?

  Right.

• 2:00:39Speaker 02

  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, you know, some other effect from that brain dysregulation.

• 2:00:58Danny Jones?

  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.

• 2:01:10Speaker 02

  Yeah. And I think you have to realize that the stimulant includes caffeine, right? So caffeine, caffeine in high amounts, caffeine will actually cause you to be very anxious and paranoid.

• 2:01:25Danny Jones?

  Mm hmm.

• 2:01:25Speaker 02

  And so, you know, you hear about people getting jitters from caffeine. That's usually when you're, when you're getting too much. So you, if you, if you've ever experienced where you've drank too much coffee throughout the day, where you can start getting really sort of jumpy and anxious, it actually causes anxiety to happen.

• 2:01:48Danny Jones?

  So would meth and cocaine be considered stimulants in this?

• 2:01:51Speaker 02

  Yes.

• 2:01:52Danny Jones?

  Okay.

• 2:01:52Speaker 02

  Yeah.

• 2:01:54Danny Jones?

  And very low fatality rate for those two as well.

• 2:01:56Speaker 02

  Yeah.

• 2:01:58Speaker 02

  Methamphetamine a little different because it can actually cause your brain, your body temperature to be super elevated and you can die from from meth overdose.

• 2:02:09Danny Jones?

  Right.

• 2:02:09Speaker 02

  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.

• 2:02:20Danny Jones?

  Yeah.

• 2:02:20Speaker 02

  And they fried an egg. That's kind of what is, is the analogy for what methamphetamine can do to your, to your brain.

• 2:02:30Danny Jones?

  Yeah, it always, uh, concerns me because I know so many people who have been prescribed things like, um, Ritalin or Adderall since they've been little kids, like in, in middle school.

• 2:02:42Speaker 02

  Yeah.

• 2:02:42Danny Jones?

  Essentially.

• 2:02:43Speaker 02

  Yeah.

• 2:02:43Danny Jones?

  And, um, you know, I know people who have been taking that stuff since grade school and now are like fully formed adults in their thirties, late forties, or thirty, like early forties, late thirties. That are like, some of them are like having children and they're saying, okay, you gotta stop your Adderall prescription now that you're pregnant. And, uh, you know, bring this baby to term and then you can start your prescription again. And they're like

• 2:03:09Danny Jones?

  losing their minds because they've been on this stuff since they were, you know, in their teens. And now is the first time in their life, they have to go cold turkey for nine months. And it's just crazy to win to, to, to see that.

• 2:03:20Speaker 02

  Yeah, 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, they're fine.

• 2:03:37Danny Jones?

  Yeah.

• 2:03:37Speaker 02

  Big deal. There's no addiction issue or problems or withdrawal. I don't know. I mean, I don't know. It's, it's a controversial thing to me. So Ritalin.

• 2:03:50Danny Jones?

  It's crazy just how ubiquitous it is.

• 2:03:52Speaker 02

  Ritalin is very fascinating because Ritalin binds.

• 2:03:56Speaker 02

  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

• 2:04:40Speaker 02

  effect and makes you more alert and focused.

• 2:04:43Danny Jones?

  Yeah.

• 2:04:45Speaker 02

  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.

• 2:04:58Danny Jones?

  As Ritalin?

• 2:04:59Speaker 02

  As Ritalin.

• 2:04:59Danny Jones?

  And our Adderall and these other drugs like Vivance and Metformin, these are all the same thing?

• 2:05:06Speaker 02

  Well, Metformin is a diabetes drug.

• 2:05:08Danny Jones?

  I mean, not Metformin.

• 2:05:09Speaker 02

  Methamphetamine.

• 2:05:10Danny Jones?

  I'm thinking of something different.

• 2:05:11Speaker 02

  Methamphetamine.

• 2:05:12Danny Jones?

  Modafinil is what I'm thinking of.

• 2:05:13Speaker 02

  Modafinil is a different beast, too.

• 2:05:15Danny Jones?

  Okay.

• 2:05:16Speaker 02

  But Adderall, basically amphetamines, methamphetamine, they interact with another transporter called the V-mat 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.

• 2:05:55Danny Jones?

  Wow.

• 2:05:56Speaker 02

  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.

• 2:06:06Speaker 02

  A brain imager and they looked at the 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 population going forward, right? And and that causes 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.

• 2:06:42Danny Jones?

  Really?

• 2:06:43Speaker 02

  Yeah. So people that end up getting hooked to some of these other substances is because it's elevating that 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

• 2:07:05Danny Jones?

  What about crack?

• 2:07:06Speaker 02

  Crack is in the same ballpark as cocaine. Now, the the reason that Ritalin and cocaine are very different, you don't, 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 a 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 opioid receptor in the same

• 2:07:43Speaker 02

  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, this is a hallmark of a sub 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

• 2:08:21Speaker 02

  it goes out extremely fast. So it hits really hard, gives you this boom explosion of of, you know, 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.

• 2:08:52Danny Jones?

  Right.

• 2:08:53Speaker 02

  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, of the drug itself.

• 2:09:08Danny Jones?

  So it helps your body maintain more of a balance internally, like a more of an endogenous balance compared to the drugs in your body versus cocaine. It's like in, out, and it kind of like leaves you.

• 2:09:18Speaker 02

  Yeah, our, our bodies want to get rid of anything foreign that gets into them.

• 2:09:22Danny Jones?

  Right.

• 2:09:22Speaker 02

  Right. And so that we do that as, 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, 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 gotta have more. Methylphenamine is different because the highs from methylphenamine can last for 24 hours

• 2:10:06Speaker 02

  or more from a single dose. So it gets into the brain fast as well, but as I mentioned, it, it dumps out dopamine and then it blocks and leaves it there. It just has a more devastating effect overall on our, on, on our brain chemistry.

• 2:10:23Danny Jones?

  And what is the difference with this modafinil stuff? I've heard a lot, I've heard a lot about it. I know that fighter pilots take it.

• 2:10:31Speaker 02

  Modafinil, actually, the very first case report that we ever published with kratom was someone that was taking modafinil and had a seizure.

• 2:10:42Speaker 02

  So they, they weren't prescribed modafinil, their, their spouse was. Modafinil is used as a treatment for sleep disorders, is used for narcoleptics. So it gives you the 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, that actually,

• 2:11:10Speaker 02

  a lot of the kamikaze pilots in Japan took this stuff to be able to fly all night and, and have the bravery and courage or craziness to use their planes and themselves as, as weapons.

• 2:11:22Danny Jones?

  The Russians are taking it right now in the Russia, Ukraine war.

• 2:11:25Speaker 02

  I wouldn't, I wouldn't doubt it for a second. So this is something that is a well-known fact.

• 2:11:33Danny Jones?

  Captagon, I think is what they're calling it.

• 2:11:35Speaker 02

  Wow. But yeah, so modafinil, interesting molecule. The trade name, the brand name when it came out is called Pro Vigil.

• 2:11:42Danny Jones?

  Yes.

• 2:11:43Speaker 02

  Stands for pro vigilance, right? Makes you more vigilant, increases your vigilance. It interacts with different systems in our body. One of those systems is called orexin system or also 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're, they have far less of these orexin type activities in their brain. So if you give them something like Pro Vigil or modafinil,

• 2:12:26Speaker 02

  you can actually restore some of that and then.

• 2:12:31Speaker 02

  Cause that balance to to be there. So they're not just falling asleep at the table, literally as we're sitting here talking.

• 2:12:39Danny Jones?

  So it's a completely different chemical makeup than stuff like Adderall or Ritalin.

• 2:12:45Speaker 02

  Correct. And again, targeting a totally different system than any of the things that we've been talking about.

• 2:12:51Danny Jones?

  Would it be safer than those other other ones?

• 2:12:54Speaker 02

  It's, well, I mean, we have an approved drug on the market, so it's a couple of approved drugs on the market. So it seems to be safe in those populations that need to be using it.

• 2:13:05Speaker 02

  If they, um, you know, I don't, I don't know. There's been a lot of investigations looking at modophenyl for treatment of, um, 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 is something that looked really interesting and promising in animals and didn't really pan out in humans. So.

• 2:13:33Danny Jones?

  Right, right.

• 2:13:36Danny Jones?

  So what do you have on the horizon as far as like studies that you're planning on working other than the DMT one? Which is going to be interesting to see.

• 2:13:43Speaker 02

  The DMT one is underway. Um, we're, we're pretty excited. We, we've been working on isolating and purifying the enzyme right now. Um, and that's, that's going pretty well.

• 2:13:56Speaker 02

  We're, obviously we're still working on kratom. That's going to be a lifelong project. We're, we're trying to figure out, um, next directions that, uh, some of the more nefarious players out there are going to go once certain things get banned, uh, like seven hydroxy, what's going to come in to fill that void? What may be the next, uh, product? In other words, um, we've been working on a lot of that. Uh, as I said, we've got coca leaf and the horizon really literally on the horizon that we're, we're just waiting for the shipment to come, uh, 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.

• 2:14:40Danny Jones?

  For Ritalin?

• 2:14:41Speaker 02

  For Ritalin.

• 2:14:41Danny Jones?

  Oh, interesting.

• 2:14:42Speaker 02

  ADHD, really increasing focus, increasing, you know, your mental acuity awareness. And so that's something we're really interested in looking at there.

• 2:14:57Danny Jones?

  Now, 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?

• 2:15:08Speaker 02

  Oh, it would always be an alternative, right?

• 2:15:10Danny Jones?

  Right.

• 2:15:10Speaker 02

  It would have to, and it's going to be a really difficult thing to do.

• 2:15:13Danny Jones?

  Yeah. How do you, how do you get a pharmaceutical company to patent?

• 2:15:17Speaker 02

  Yeah. They're not, they're not, right? So you have to come up with some sort of unique formulation like Coca-Cola did.

• 2:15:23Danny Jones?

  Right.

• 2:15:23Speaker 02

  Uh, or some.

• 2:15:24Danny Jones?

  I would imagine they would lobby against it.

• 2:15:26Speaker 02

  Yeah, I'm, I'm, I'm not surprised by anything anymore. But I, 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?

• 2:16:08Speaker 02

  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 I, my, 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, and safe for people as a whole plant, because I, I.

• 2:16:51Speaker 02

  I think Jack Henningfield, one of our colleagues that 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. And here's this plant, right?

• 2:17:08Danny Jones?

  Yeah.

• 2:17:08Speaker 02

  That seems to be okay. Coca leaf's a great example. Doesn't doesn't have addiction properties with the coca leaf itself, but sure enough, you pull out cocaine, you've got it.

• 2:17:17Danny Jones?

  Right.

• 2:17:18Speaker 02

  Kratom, 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.

• 2:17:33Speaker 02

  Those are some of the things. And then the the most recent thing that we've embarked on is actually looking at Kana. And I'm not, 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.

• 2:18:08Danny Jones?

  Oh, wow.

• 2:18:09Speaker 02

  And it's 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. And so I have a student working on that project. Now we've got some of the plant extracts in in the lab and we're we're we're sort of very early in the development of that project. We're we're just isolating some of the alkaloids from it, characterizing those alkaloids. A lot of that work's already been done by others, but we are.

• 2:18:46Danny Jones?

  Is this stuff legal in the US?

• 2:18:47Speaker 02

  Putting, yes.

• 2:18:48Danny Jones?

  Oh, it is?

• 2:18:49Speaker 02

  You can buy this on Amazon, actually.

• 2:18:51Danny Jones?

  Kana?

• 2:18:51Speaker 02

  Yeah, yeah.

• 2:18:52Danny Jones?

  And it's a very similar effect to coca leaf and kratom.

• 2:18:55Speaker 02

  And kratom, in terms of focus and energy, right? So.

• 2:18:59Danny Jones?

  Okay, add this to my grocery list.

• 2:19:01Speaker 02

  So it's Galedium tortosum is the actual plant's name.

• 2:19:09Danny Jones?

  Are there any products that, do they make any like special like drinks or anything?

• 2:19:14Speaker 02

  Um, I'm not aware of specific drink products. There's a lot of capsule products available. Leaf products, um, what are shown there, they're a little bit harder to find.

• 2:19:29Speaker 02

  Even though it says you can buy them, usually when you go there, they're out of stock or they don't have it. Um, but there's a, there's a compound, there's a, um, a product called Zembrin. Z E M B R I N, I think, which is actually a standardized extract of this plant that is, uh, sold. And that is another guy, uh, Nigel Gurkey, who was at the ESPD meeting and spoke on this plant there. And at the time I was so deep wasted into, uh, kratom that we didn't have time to even think or look at anything else.

• 2:20:09Speaker 02

  And now, um, with, with having enough research funding and enough, um, 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, with some of that. And so to give students that are pursuing a PhD or, 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.

• 2:20:47Danny Jones?

  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, um, a illicit substance? Or what, what do you think, based on your research and other research is going to happen?

• 2:21:01Speaker 02

  Yeah, I, I think the research is going to determine the outcomes. Um, I mean, it's not up to us to, 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 this. Seven hydroxy compounds is because that definitely shows a 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.

• 2:21:43Speaker 02

  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 seven hydroxy metrogan in in schedule one said this is not about the leaf kratom, we're not interested in going after that, we'll leave that alone. It seems to be fine. The federal government has put a lot of money, over a hundred million dollars into studying kratom now. Wow. Yeah, and we've been, we've been lucky to benefit from that. We've had about twenty million dollars into our lab.

• 2:22:29Speaker 02

  Alone plus a fifty million dollar collaboration with the National Institutes of Health with their internal programs.

• 2:22:37Speaker 02

  To really study it and then the FDA, the FDA has put money into looking at clinical evaluation of 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, 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.

• 2:23:22Speaker 02

  And after three grams, there was no

• 2:23:26Speaker 02

  effects still. People said that we don't feel like we're taking anything. That 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.

• 2:23:48Speaker 02

  But they did not have any adverse event or what they considered a a significant adverse event that they had to stop dosing. So we went from the eight gram dose to the 10 gram dose to 12 gram dose, which is the end of the study. And again, I said, the typical normal quote unquote dose or serving size is 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

• 2:24:32Speaker 02

  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 that was one of the things we noted.

• 2:24:53Danny Jones?

  Interesting. And don't stimulants make people's pupils dilate?

• 2:24:56Speaker 02

  Right, correct. So so you get this opposite effects with those. So what what that did, the FDA actually ended up 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, no, no clinically significant event happened. So that would include death, of course.

• 2:25:26Danny Jones?

  Yeah.

• 2:25:27Speaker 02

  But I think it surprised the FDA as well.

• 2:25:30Danny Jones?

  Nobody's ever died from kratom?

• 2:25:32Speaker 02

  That's, that's a very hard question to answer.

• 2:25:35Danny Jones?

  Right, because I'm sure if there, somebody could die and have kratom in their system and also have a slew of other things.

• 2:25:41Speaker 02

  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 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, this is problematic. But to, to come out and generally state that no one could die just from kratom,

• 2:26:26Speaker 02

  I think is factually not, not right either. Because you can die from anything. If you consume enough of something, it, it can kill you. Sure. And yeah, water's, water's a great example. I mean, people die from water intoxication. It's not drowning. It's actually you drank too much water and your system basically explodes internally.

• 2:26:52Speaker 02

  That's not really what happens. But, but I, you know, it can be fatal. And 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, the, the poison is in the dose. So, you know, many- Paracelsus? Yeah. So many, many poisons, as we talked about earlier with Marcus Aurelius writing 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.

• 2:27:35Speaker 02

  So it's, I think, very similar for all substances. It just depends on, 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,

• 2:28:08Speaker 02

  that, that could potentially be, you know, getting them closer to, to a bad situation. There's, 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, most of the responsible companies will actually measure the heavy metals and make sure that, you know, 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

• 2:28:52Speaker 02

  on the package. You're not going to exceed lead levels. We've, 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

• 2:29:35Speaker 02

  a day, if they're taking five grams of leaf, you're, you're, you're butting up against the edge of, of lead limits in a day, according to the FDA. So, so people that are taking greater than 20 grams a day are at risk of, of lead issues. And, you know, certainly someone who's taking 90 grams or 100 grams of kratom a day is also getting

• 2:30:03Danny Jones?

  And this would be, this is not with the extracts, right? This is only with the leaf?

• 2:30:08Speaker 02

  Correct, only with the leaf.

• 2:30:09Danny Jones?

  Only with the leaf.

• 2:30:10Speaker 02

  Only with the leaf. The extracts will have the metals, the metals will come out in the process because of the extract process.

• 2:30:16Danny Jones?

  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 washed it down with

• 2:30:34Speaker 02

  Toss and wash.

• 2:30:34Danny Jones?

  He literally, he washed down the kratom powder with his kratom energy drink. I was like, whoa, bro. That's a lot.

• 2:30:43Speaker 02

  That's intense.

• 2:30:44Danny Jones?

  Yeah. So the powder is the leaf, right?

• 2:30:47Speaker 02

  Right.

• 2:30:47Danny Jones?

  Okay, gotcha.

• 2:30:48Speaker 02

  Right.

• 2:30:48Danny Jones?

  And he called it white vein.

• 2:30:50Speaker 02

  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.

• 2:31:06Speaker 02

  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 and 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.

• 2:31:42Speaker 02

  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, what's happening with, 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

• 2:32:12Danny Jones?

  Okay.

• 2:32:12Speaker 02

  what, 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, you know, white vein sometimes, all the way up to a reddish colored powder that often gets marketed as red vein.

• 2:32:35Danny Jones?

  Got it.

• 2:32:36Speaker 02

  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. Salvinorane, we talked about before, is a neocladine-diterpene. It does not have any nitrogen in it either. Alkaloids by definition contain nitrogen. So, we know that there's other classes of chemicals within kratom. And we know that that drying process, those color changes

• 2:33:14Speaker 02

  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. 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. It allows you for more SKUs of your product. It also allows you to have a more consistent product base, where you know you're going to get

• 2:33:59Speaker 02

  these five different colors.

• 2:34:01Danny Jones?

  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?

• 2:34:16Speaker 02

  So cannabinoids have way, way exceeded that.

• 2:34:20Danny Jones?

  Oh, really?

• 2:34:21Speaker 02

  Yeah, yeah, for sure. Because you got to look at the time, too, that's been put into it.

• 2:34:28Danny Jones?

  Right, that's true.

• 2:34:29Speaker 02

  So if we, 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.

• 2:34:43Speaker 02

  Um, underneath that grant, we awarded faculty members small grants that were NIH money um, to study plants that they were interested in. I was one of the recipients of one of those small projects. It was a hundred and fifty thousand dollars a year and I had it for almost ten years to look at that. So there's one and a half million dollars there, right? And that's before, that was, that started in around two thousand and seven or two thousand and eight when we started getting that money.

• 2:35:13Danny Jones?

  Wow.

• 2:35:14Speaker 02

  So you, you have to go all the way back to then to see when it was started. I mentioned cannabis work has been done, um, actually predates the National Institute on Drug Abuse, the federal funding for cannabis research. And so the National Institute on Drug Abuse was, was founded after the Controlled Substance Act went into place. Um, and that's what's been going on. So here you go.

• 2:35:41Danny Jones?

  One point five billion in cannabis research between two thousand and two thousand and eighteen.

• 2:35:44Speaker 02

  Yeah. So, so way more money.

• 2:35:47Danny Jones?

  Wow.

• 2:35:47Speaker 02

  On cannabis than, than kratom.

• 2:35:50Danny Jones?

  Crazy.

• 2:35:52Speaker 02

  Yeah. And, and you know, there's, there's all kinds of grants that are being, um, put out to, to really look at medical potential for many of these plants. Now cannabis research is, is a, a garbage can definition, right?

• 2:36:11Danny Jones?

  Yeah.

• 2:36:11Speaker 02

  So it's all the CBD work.

• 2:36:13Danny Jones?

  Right.

• 2:36:13Speaker 02

  That's been done. All the hemp work that's been done. You know, all the really high-end THC, uh, containing cannabis work that's been done. So there's a lot there. Not only has a, 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.

• 2:36:36Danny Jones?

  Mm-hmm.

• 2:36:37Speaker 02

  Because, um, as a federally funded university, like the University of Florida or any state university, um, cannabis is still Schedule One at the federal level. So we risk losing

• 2:36:52Speaker 02

  Using federal funding if we bring cannabis from a dispensary onto campus to study or do research with, we can't do it.

• 2:37:00Danny Jones?

  Wow.

• 2:37:01Speaker 02

  So, um, all of the material that comes, plant material that's been used in studies is what have been grown at the University of Mississippi. That's the only federal supply for researchers.

• 2:37:15Speaker 02

  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, 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.

• 2:37:44Danny Jones?

  Well, Chris, this has been fascinating. I learned a ton. Um, thank you for doing this, first of all.

• 2:37:50Speaker 02

  Yeah, absolutely. Thank you for inviting me.

• 2:37:51Danny Jones?

  Yeah, of course. And then talking about where can people, uh, find more of your research that you've done or get in contact with you or anything like that?

• 2:37:57Speaker 02

  So I'm, I'm, uh, always, uh, available by email.

• 2:38:03Speaker 02

  Email is, is, um, c [email protected]. That's my Florida, University of Florida. Email and, um, that's really how you can reach out. I get lots of emails from, uh, users, um, you know, people that are willing to volunteer for trials. We don't do any human research in my lab. My lab is, is totally plant-based, uh, chemistry-based, pharmacology-based. Uh, I do all my collaborative work with some amazing individuals, um, that, that work with the animals. Uh, we supply them with all the drugs. We're the drug dealer. Uh, and, um, you know, our papers are, are readily available. Many of them are free to download.

• 2:38:49Speaker 02

  On the government, um, the Library of Congress, uh, PubMed website, um, PubMed.com, I think it is. And, uh, you search, search McCurdy CR. And kratom and you'll see that there's eighty some papers. If you search kratom, you'll see there's just shy of a thousand. I think there's nine hundred and eighty or so papers total published on kratom.

• 2:39:16Danny Jones?

  And you've done eighty of them?

• 2:39:17Speaker 02

  Yeah, we've, we've, 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, and then the federal funding really helped catalyze and boost the amount of work we were able to do and publish and share. The whole goal is to share and educate the public and, and get that information out 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 either keep something available for, for

• 2:39:58Speaker 02

  public consumption or restricted. And so, again, we don't make that decision, but we, we have an obligation with our funding and our work to, to produce the science.

• 2:40:10Danny Jones?

  Well, and then also, we, 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.

• 2:40:19Speaker 02

  Absolutely. And I'm, you know, hey, there, 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 Koka. Hopefully we'll be knee deep in Koka leaf, literally pretty soon.

• 2:40:35Danny Jones?

  Yes. Sign, where do, let me know where to sign up for that trial.

• 2:40:40Danny Jones?

  All right, man. Thanks again for your time. I really appreciate it. All right. Good night, everybody.

• 2:40:43Speaker 01

  Network freedom and flexibility. That's what you want in a healthcare plan. With a Humana Medicare Advantage PPO plan, you can see any doctor in the country who accepts Medicare, including specialists. No referrals, no kidding. Learn more at gethumana.com. See any doctor who accepts Medicare and is willing to bill Humana. Humana PPOs may not be available in all areas. Benefits and costs share may vary. Humana is a Medicare Advantage PPO organization with a Medicare contract. Enrollment in any Humana plan depends on contract renewal.