The Peter Attia Drive - #81 - Debra Kimless, M.D. & Steve Goldner, J.D.: Cannabis – the latest science on CBD & THC

Episode Date: November 25, 2019

In this episode, Dr. Debra Kimless and Steve Goldner share their knowledge on the science, policy, and market evolution of medicinal cannabis. We start with the differences between THC and CBD, how they work in the body, and how they act on the brain. We discuss the many potential benefits of using CBD, THC, hemp in the various forms of administration (smoking, vaping, edibles, oils, etc.) as well as some of the safety issues including the recent uptick in incidents of hospitalization and death linked to vaping. Debra and Steve are both involved with the company, Pure Green—Debra the Chief Medical Officer and Steve the founder and CEO—whose aim is to create the safest, most efficacious form of delivery of cannabis. Their bigger mission is to shift the perception of the cannabis plant, garner acceptance of its medicinal benefits, and ultimately get it descheduled on a federal level so more people can access cannabis for a range of chronic ailments. We discuss: Debra and Steve’s background reason for their interest in medical cannabis [7:00]; The history of medical use of cannabis [11:15]; How THC, CBD, and other cannabinoids work [16:00]; Hemp—What it is, special uses, and the 2018 farm bill [22:45]; The legal status of CBD, Deb and Steve’s clinical trial, and how CBD differs from THC [30:15]; The safety profile of THC [35:00]; Is marijuana as a gateway drug? [45:30]; Smoking vs. vaping vs. edibles—Benefits, risks, and mechanistic differences [53:30]; Can you build up a tolerance to the effects of THC? [1:15:00]; What do people generally want to get from using marijuana? [1:17:15]; Cannabinoid synthetics [1:22:30]; Efficacy of CBD oils as a sleep aid [1:25:00]; Pure Green Cannabis [1:30:30]; Anecdotal evidence and managing the hype surrounding cannabis in medical treatment [1:38:45]; Aspirations for the future of medicinal cannabis, and the legal challenges that await them [1:45:15]; Descheduling cannabis: A human rights issue [2:04:00] and; More. Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/debrakimless-stevegoldner/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Hey everyone, welcome to the Peter Atia Drive. I'm your host, Peter Atia. The drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information

on today's episode and other topics at peteratia-md.com. [♪ OUTRO MUSIC PLAYING [♪ Hey everybody, welcome to this week's episode of The Drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why instead we've chosen to rely entirely on listener support. If you're listening to this, you probably already know, but the two things I care most about, professionally, are how to live longer and how to live better. I have a complete fascination and obsession with this topic.

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and have them pass savings on to you. Again the podcast will remain free to all, but my hope is that many of you will find enough value in one, the podcast itself, and two, the additional content exclusive for members to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce, please consider supporting us directly by signing up from monthly subscription. I guess this week are Dr. Deborah Kimless and Steve Goldner. I'm not going to say much

about them by way of background because I open the interview by asking them to introduce themselves because their backgrounds are so relevant to the discussion we have. I sought out both Deb and Steve because I wanted to have a discussion that would frankly first inform me, but obviously provide the necessary and relevant background information to all of you as listeners on a topic that frankly it confuses me to no end, which is the entire morass of the entire morass of THC, CBD, hemp, cannabis, that whole landscape. And truthfully, I've never fully been able to understand this in part because I think it's just very confusing, in part perhaps because I haven't put enough effort into it. But preparing for this podcast was a great exercise in doing just that.

In this episode, we talk about a lot of things, but we start, frankly, with some of the semantics. What is the difference between THC, CBD, where do these things work? How do they work in the body? What's the difference between what it's doing in the brain and what it's doing elsewhere? And how do molecules work that aren't neat and clean like designer drugs where one molecule hits one receptor, as you'll see cannabis, it works very different from that. We also then get into some of the safety issues. At the time of this recording, which was in late October, 2019, there is obviously an epidemic, at least they perceived epidemic, around the dangers of vaping. We touch on some of the reasons why that may be the case, but really for the past three

years, we have been witnessing both a market evolution, a scientific evolution, and certainly a policy evolution, which may be the most important as it pertains to this subject matter. And again, I think as you'll see in the first few minutes, Deb and Steve are really great people to have this discussion with because collectively between them you have a medical, a pharmacological,

and a regulatory expertise that is brought to bear. Now it's worth pointing out that both Steve and Deborah are involved in a company. Steve is the founder and CEO of Pure Green and Deb is the chief medical officer. And I point that out to say everything must be interpreted with a grain of salt, and obviously Steve and Deb have a commercial interest in this space. Now, I will tell you that after spending two hours with them, or slightly more than two hours during this podcast, also spending another hour with them off-mic, getting into stuff that we

just weren't comfortable talking about on-mic, I come away thinking very highly of them, very highly of their work, and believing that their intentions here go far beyond just the commercial intentions of people involved in this space. This is a confusing topic, and I won't represent that this one podcast is going to answer every possible question you have. The good news is it might not matter if it did, because frankly this is an area that is evolving so much, and I suspect this is a topic that I will need to go back to probably

a year from now. So without further delay, please enjoy my conversation with Steve Goldner and Deborah Kimless. I'm Steve Goldner. Deborah, Steve, thank you so much for making time to come and talk about this stuff today. This is kind of an unusual podcast in that we weren't introduced through anybody.

I sort of organically reached out to you guys on the basis of so much demand and so many questions about this topic, which is something, you know, as I've alluded to, I'm completely ignorant of. So this is a topic I've been really looking forward to learning about because patients ask me about it constantly. I think the implications are only becoming more significant as we watch the evolution of legal environment. So having a physician and a lawyer to talk about this is perfect. Deb, can you give me a bit of background on your interest in this?

You're an anesthesiologist. I know you specialize in pain. Tell me what drew you to this specifically. So what drew me to this is that my mom was dying from a complication from a pharmaceutical drug. And because of that, I started really thinking about what we learned in medical school, how we were trained, and what else could there have been for my mom as an option of than a pharmaceutical. And as she lay dying, my significant other is in Israel, he said, you know, they're studying medical cannabis in Israel.

And unfortunately, my mom didn't have an opportunity to try medical cannabis as a pain reliever because she died. But I spent really since 2013 until now, studying and investigating the veracity of whether or not cannabis truly is a medicinal molecules. Steve, how did you guys meet and how did you get involved in this? Well, I've been involved in pharmaceutical formulations as a scientist for almost 50 years now. As a forensic toxicologist at the New York Medical Examiner, I worked on 18,000 autopsies. So I developed and formulated the liquid drug methodone about 47 years ago because friends of mine were coming back addicted from the Vietnam War. So that worked out pretty well. Developed that formulation. Methodone's done very well of helping people

around the world. And I went on to become FDA attorney working in the pharmaceutical industry, but always working in this arena. I became interested in cannabis as a medicine almost 45 years ago. Friend of mine came back from Vietnam War with PTSD. And he asked me to develop a drug that would help cure him of that. And I noticed that when he smoked marijuana, he felt much better.

When he drank or got pills from the VA, he did not. And so I realized that cannabis could be a medicine, but it just wasn't legal at the time, and I wasn't that right kind of lawyer to get that legalized. Now I have that opportunity to be able to do it. That's what brought me into it. He also, my buddy, who's passed away of Seroce's deliver about seven years ago, made me vow to do this. So developing methadone at the beginning of my career was a first bookend and now developing all these formulations to help people with cannabis is the second bookend on my career. And how did the two of you meet? So I lecture around the country and around the world and I present

studies that I have done on my own. These are case studies. I treat over 400 patients free of charge, a bad business model, but what I've learned from these patients is tremendous using diet changing cannabinoid medicines. And I share them with colleagues so that they too can understand cannabis is medicine. And Steve and I met two years ago in Cologne, Germany, I think it was at IACM where I was presenting a poster and he tracked me down and we had our first conversation there. And together you guys are part of a company. We'll probably hear a little bit about that company today, but the aim of this company I assume is to create sort of what you perceive to be the safest, most efficacious form of delivery of cannabis. Is that a fair assessment? Yes, that's exactly it. I think to understand why you guys do what you do,

we have to understand a whole bunch of things that I don't understand right now. So let's just start with some history. How long has cannabis been consumed by humans to the best of our knowledge? Historically, it's been used as a medicine for over 5,000 years. I mean, this is crazy.

It's new for us now, but it's not a new medication. In Asia, the king vented himself a pharmacist and he was treating people for all sorts of disorders from gout to absent memory. Believe it or not, even though people are like, dude, where's my car? Here he was helping people with memory loss with it. The ancient Greeks used it topically on their horses, which is why I do know that the acid forms of the cannabis medicine actually work

because they love their war horses. They applied the cannabis leaves to the horses' bodies to reduce the swelling inflammation and infection after a war or a battle. Historically, when did it fall out of favor back in favor? It's said, I mean, for most people, when they think about marijuana, they think of the 60s and 70s as this era in which the public got to know it and it became demonized. When was it actually scheduled Steve?

I think that was the beginning of around 1930 or so. That is, there were a number of individuals who thought that this was just a completely inappropriate drug to be allowed out, a recreational drug. And there was a lot of movement towards controlling people's appetites in many ways, including drinking alcohol that have floated in and out through America and across the world.

So it began then with an idea of prohibition. And it was really given a much more emphatic push under the Nixon administration for it's often said for their own political purposes of being able to disenfranchise people who would utilize marijuana, young people or people of color. And that became essentially the war on drugs policy that was promulgated

through the United Nations and around the world because the United States often was the funder of those activities. That's continued for quite some time, but is now, as everyone knows, dramatically, dramatically changing. Now, unlike this sort of psychedelics, which were actually scheduled only about 50 years ago, you're saying marijuana was scheduled in the 30s. I mean, that's it before the FDA. Well, FDA has been around for at least that long, and the originally scheduling of this was under DEA as a narcotic drug, and therefore it would not be allowed and DEA really had much more

of a law enforcement orientation while FDA does have a staff of essentially policemen working with them. They're not organized in that manner. So they're much more organized towards what is a medicine, what's a food and how to be able to keep our American health policies the best possible for people. You talked a moment ago Deb about topically applying this. How did people do that?

Was that an oil? And what was it? I mean, not that you were there at the time, and we could go back and figure that out, but to the best of our understanding, what is it that was being applied to, for example, a horse, or how was it being used medicinaly 5,000 years ago? It varied depending upon the indication and what they wanted to do, but the horse example was they were actually applying leaves to these horses, the actual, you know, families or regular leaves. There are small amounts of trichomes on those

leaves with cannabinoids in them. So of course it would work. It was really interesting. In India, they would mix it with heat and milk and make something called BANG, the H&J, and they would drink it as an anesthetic for people. So it really did vary. It was very interesting that people applied these things in different ways.

So today when people think about marijuana, the thing they probably have in the back of their mind is more related to the properties of THC, is that correct? Yeah, I think that most people, when they think of cannabis, think about it as THC intoxication and smoking. So let's talk a little bit about that. So you've used the funny reference of dude, whereas my car, so Jeff Spakoli, falling out of the van, big plume of smoke coming out after him.

He is taking a leaf, he is smoking that leaf. More, I mean, he's with broken pieces of it rolled up into a joint and being smoked. Right, so cannabis as a plan is very interesting, right? So when it grows in nature, it grows as a flower. The leaf does have some cannabinoids in it or some of those medicines in it, but really the most bang-fear buck it comes from the flower, where that's what it is. So, Spakoli was probably buying off the street and maybe he's getting some leaf, but he's hoping for some flour because that's where the majority of the medicine is. And you know, drawing it out and rolling it up and then combusting it.

The interesting thing is you can eat the cannabis plant all day long. You may get a belly ache from all the fiber, but you won't get that intoxicating feeling because its chemical constituents are not in a way that can get you intoxicated. I see. Okay. So let's talk about how that intoxication works. What is THC stand for? Tetrahydra canabino.

And what does it do in the brain? So our brains have these sort of docking stations called receptors, and chemicals act on different docking stations or receptors in order to affect a change. So THC works on these docking stations in our brain and our peripheral nervous system known as CB1 receptor, cannabinoid1 receptor, wasn't very interesting name for it, but that's what they call it. And there are also cannabinoid2 receptors or CB2 receptors were found peripherally predominantly on immune cells but also on other tissue as well and in other organs. And so THC has this really unique ability to activate or sit on these CB1 and CB2 receptors. And did you say both CB1 and 2 are peripheral?

They can be CB2 predominantly is peripheral. CB1 is predominantly in the brain and then other nerves, so the peripheral nervous system. And what is the next chain of events? So once THC binds to these receptors, what happens inside the cells? Oh gosh. So depending upon where and those receptors are located, we'll determine what happens. So for example, if it's in the hippocampus, it may stimulate areas in that area that will help you extinguish memory. So for people with PTSD who cannot stop thinking about certain things, that area of the brain extinguishes memory and helps somebody with PTSD maybe to get some sleep.

How do you think it acts with respect to pain? It's a multimodal different way of doing it. So centrally, it does interfere with parryctal-aquaductal gray areas. These are areas of the brain that conduct pain signaling, where a brain actually understands this., also works perfectly on immune cells to decrease inflammation and reduce cytokine expression. So it works in a whole host of different ways. We're used to thinking in medicine, actually, as an alipaf of a single molecule, single target.

But what you really learn is that that's a great way of understanding how a drug could work, but that's not how it works in a biologic system known as a person or an animal. And so contrasting this with what you talked about with respect to your mom's care, for example, she was probably being prescribed opiates I'm assuming. So my mom actually died from fracturing to death from a pharmaceutical known as a bisfosophony from Phosamax. The weird thing about my mom is that she was one of the 20 to 30 percent of people who when they took opiates had an enhanced response to pain, not a decreased response to pain. So basically she was, you know, using, see a

benefit in non-steroidal to try to reduce her pain, which when she spontaneously blew out her pelvis, you know, didn't really help that much. So we were just hoping that since medical cannabis works in different methods for pain relief, it could have been an option for her. We're gonna cure it or but could have helped her. Now one of the other effects of inhaling marijuana for many people seems to be an increase in appetite. Do we have a sense of why that's the case? And I remember certainly in medical school that was even something that we talked about a lot, was patients that had wasting syndromes either with cancer or AIDS.

This would be a great way to help them eat. Exactly. So there are areas of the brain that control appetite and nausea and vomiting as well in the area in the medulla. And those areas is replete with CB1 receptors. So when those areas are stimulated, your appetite is stimulated and you actually have a desire to eat, which your right is life saving for somebody who has wasting syndrome or who has chemotherapy induced nausea and vomiting. There's this other thing that now people talk about a lot called CBD. I probably hadn't even heard of this until maybe four or five years ago.

I mean, Steve, how long has CBD been understood as a distinct part of this equation? So, this is a truly revolutionary, new molecule to come out into the public consciousness so quickly. It's always been in the plant and available to use, but it's because people were so entranced with the idea of let's get stoned or then let's do some science on this stoning aspect of THC, that that drew most of the attention. It's just really in the last two or three years that CBD, because of its non-Holucinogenic effects, has become interesting to people because it appears to have, it does have so many medicinal applications, and at the same time same time doesn't get a person stone.

How is that possible? What is it doing chemically to create that distinction? So different than THC, CBD does not sit directly on CB1 receptors or CB2 receptors, but works either indirectly activating the endocannabinoid system, or it works on completely different receptors. And so together it has a synergistic effect with THC, or all the other molecules that live in the cannabis plant, or by itself, is pretty effective as a medicine. Now in nature, do they come lockstep one in one for every molecule of THC is one CBD coming with it, or how does that work?

So in nature, it doesn't exist at all, right? It isn't until you apply time and temperature and get rid of that acid form, that carboxyl group on either THC or CBD or any of the other cannabinoids. So that's kind of interesting, it was a baseline anyway. But CBD, there are cultivars or plant strains as known in the street can grow in higher concentrations in certain

cultivars. It can occur as a one to one, one molecule to one molecule. It depends upon the strain that you're growing. The legal definition of hemp is something that's hiring CBDA and less than 0.3% THC. I'm glad you brought that up. Tell us a little bit more about the difference between hemp and cannabis, specifically, and again, using the CBD THC delineation. So the legal definition is for hemp cultivar is to have less than 0.3% by weight of THC or THCA, actually, compared to the rest of the biomass or the rest of the molecules in the plant. Technically, that would make anything hemp that doesn't have THC in it, right? Exactly. So people use cannabis plants and just

crossbreed so that THC is less than 0.3% so that they can grow it. But, you know, the term of industrial hemp back in the day when our constitution was written and sales were, you know, being made out of hemp, it's a totally different plant as it is today, just because of crossbreeding and farming the way we're doing it. Steve, the farm bill brought this to the forefront recently. Tell us about the farm bill and why that's relevant. I want to come back to this, but just while we're on the topic of hemp, it's important. I think for people who understand this distinction. The Congress decided, pushed forward by several legislators who had large numbers of farmers,

that this would be a really good cash crop for them. When you think of it, these products are selling for thousands of dollars a pound compared to 50 cents or a dollar a pound for lettuce or tomatoes. So if you're a farmer, you'd much rather grow something that you can get thousands of dollars for. The idea was put forward that this should be something that's allowed now. We can see across America that people really are interested

in it, that medicine can be developed from it. So it was with this idea that a number of legislators, particularly Senator McConnell, had a number of farmers in his jurisdiction wanted to be able to help them in their businesses and in their personal lives to be able to develop this. Otherwise, these products are imported from overseas, and we'd like the American population to be able to have a good, well-regulated source of product here. I think that was the entire idea behind it was that we would bring the U.S. Department

of Agriculture, as well as other scientific bodies like FDA, to be able to begin to study these products and help the growers. All of the growers that have worked on cannabis hemp products have had to do this for generations without having someone like the USDA around to tell them what pesticides were appropriate to use, how to grow it, how to have good growing conditions for it. So this has really helped, I think, to be able to advance it. Was the Farm Bill basically just an economic package that made it more attractive, or was there some legalization that was previously not there?

The Farm Bill really provided legal cover for farmers to be able to grow the hemp, and then to be able for processors, then to be able to process it into oil and be able to turn it on into other products. So it started out as something to just aid farmers, but now it is moving through the economic distribution chain and that's why we can see it now in nearly every drug store or big box store as finished goods on the shelf. What are some of the products that come from the hemp plant? There are vape cartridges certainly, although they're not at the moment, not all that perhaps professionally done,

except by those who are licensed to be able to do it. There's a very large gray or black market in it, but there are lotions, creams, ointments. You can find CBD products in ice cream and tea. Soon it'll be in coffee and nearly every other consumer product that's available. Is the idea that there are certain hemp products that do not contain CBD and certain hemp products that do? Or is the implication that all hemp products are containing CBD? So I think what you're asking is about the industrial uses of hemp beyond the cannabinoid.

And so you can put that flower into seed and make hemp seeds from it, which has a wonderful profile of omega-3 to omega-6, probably better than anything, and a wonderful source of protein as well. The fiber that it comes from, hemp fire, has a tensile strength of steel or greater than steel. Where you see plastic goods, you can actually substitute for hemp. It's just really expensive machinery for now,

and it just displaces the petroleum and plastic, or what is it displacing? Yes, it displaces the petroleum and plastic. So you can make a credit card out of hemp fiber. You can make hemp crepe. So instead of concrete, you can actually use it, make it to make it concrete.

You can, there are BMWs right now that are using parts of their door panels and dashboards using hemp. You can make cloth, you can make clothing, you can make sellers sales. Do you have a sense of, you take all of the biomass that's being produced in the United States from a hemp crop today, how much of it is being used for all of these industrial uses and how much is being used just for CBD. I assume the latter is a tiny fraction of it. Oh, no, I think CBD is a lion's share of it because that's where the money is. Right now,

you know, the decoertication machine, the machine that is required to break down this stock, which is incredibly fibrous and tough, is very expensive right now. But I think that there's such a huge interest, at least in the United States, everywhere, but especially in the United States, for CBD as a potential medicine or tonic, that's where the money is. So it's a lot easier to extract and make derivative products than it is to create a lot of these other iterations

that I just described as an industrial use. But let me just interject that some of these other uses are just remarkable and have been around for a long time. Henry Ford personally was very proud of having developed a hemp mobile, and he actually built a car that ran and its fuel was fueled by hemp oil. So the entire car in the 1930s could have been put out on the road and they had to shelve that project because suddenly hemp was illegal because it came from the marijuana marijuana sought marijuana plants. When did CBD become federally legal? I assume it is federally legal today

or is it still state regulated? Well, it certainly is state regulated and each state has its own regulations. The federal regulation of it is continuing to unfold. The farm bill has legalized hemp itself. It has not directly said that CBD is okay to put into products. Rather, there's been an intense push on the Food and Drug Administration whose responsibility it is to regulate those kind of consumer products that they should move expeditiously and actually Deb testified before FDA about five months or so

ago on the safety and effectiveness of CBD to help them in their data gathering. So when you spoke to the FDA, Deb, what were the main points you tried to get across? The main points that we discussed was about a clinical trial that we ran using a water soluble iteration of CBD for mild to moderate pain in a 16 patient cohort and the results of it. And I wanted to share that with safety, efficacy,

and our results. Let's talk a little bit about that. So you said 16 patients that had mild to moderate pain, meaning what was the etiology of their pain? So it was multifactorial. I didn't just stratify to one condition because I just wanted to see. It was a proof of concept trial. And I actually didn't think it was gonna work. Steve was kind enough to let me formulate an ultra low dose, five milligrams of CBD with some curated terpenes in a water soluble tablet.

I gave it to 16 patients who had mild to moderate pain for which they were treating their pain with an over-the-counter medication. And we ran this trial for two weeks, and we had statistically significant decrease in pain across all 16 patients. How do you control for the placebo effect there? Was there a control in that study? There was nine. Again, it was a proof of concept study to see if this ultra low dose of CBD would even work and it did.

There's no control for placebo, for really for anything. I mean, I know lots of patients, I'm sure you do as well, that seem to really respond to a whole host of medicines, whether it comes from a double blind randomized trial or not. How does CBD in your mind differ from THC? We know obviously how it does from an intoxication standpoint. How do you think it differs in the remainder of the profile? It works in a different mechanisms of action.

You know, so for example, CBD doesn't sit on a CB1 receptor. But what it does is it interacts with the breakdown products of our naturally occurring endocannabinoids, which does sit on a CB1 receptor. So by enhancing that, that's one pain relieving mechanism of action. You know, it interfered and interacts with dopamine, neuropinephyron, epinephrine type receptors, and enhances those chemicals as well. So it works in a multimodal way, just like all of our other medications. I'm trying to, in my mind, wrap this idea around a Venn diagram of THC and CBD, where

does this make sense, where you have certain things that they both do, and then things that are unique to each of them? Does that make sense to think of it that way? It does and it doesn't. So I understand as Nalipath physician that that's how we like to look at things. That's a very reductionist view of it. And I think it's, this is really a botanical medicine. We really have a lot of different constituents within it.

There's over a hundred different cannabinoids, over 80 plus terpenes, flavonoids, and probably constituents who are not smart enough yet to even have figured out. One of the terpenes do. Terpenes occur in nature, in all kinds of plants and foods that are giving the taste and the scent to all kinds of things. And they're anti-inflammatory. They're actually secondary metabolites, like the cannabinoids as well. And it's used for the plant, not for our benefit, but for its benefit as a natural pesticide,

a antioxidant. And it works that way in our bodies as well. I want to come back to sort of the THC side of the equation. Let's start talking about some of the health risks and or benefits. And let's start with the risks. What do you think are the most important risks to understand from THC use? So I think everybody is different. We're all on end of one.

And we all respond differently to the same type of thing. So if I give one person an aspirin, their headache may go away. Somebody else may die of, you know, an allergic reaction to it. In some people who are very sensitive to THC, they may not just feel intoxicated, but they may feel so much anxiety and panic that they are incredibly uncomfortable. And some is dose-dependent, but some experience that even with a small amount. Some people experience a feeling of well-being with a little bit of THC. Some people have a rapid heartbeat and their blood pressure shoots up and have an uncomfortable experience. How much of that do we think is setting dependent?

So if you took the same person administered the exact same dose by the same route, but under different settings, either the actual physical setting they're in or the emotional state they're in, how much can that impact the response? I think anytime you're dealing with something that plays around with neurochemistry, set and setting is always a huge important thing. You know, same thing with alcohol. I think there's one part of this is while we're talking about the safety or potential adverse events from this that we should also address.

In my experience, this has the lowest toxicity potential of any pharmaceutical nearly of almost any product I've ever seen. That is in the course of history, we really do not have any deaths or truly serious events that are attributed to THC or CBD at all. It is so less toxic than what are common over the counter drugs, aspirin, Tylenol, etc. And certainly far and away compared to alcohol, which is truly toxic. What is the reported LD50 of THC? So there really isn't and you cannot explain to people what LD50 is. Okay, so LD50 is the lethal dose that it takes in order to kill off 50% of a population

usually in mice or rats with THC and CBD and all of these cannabinoids. It has never been possible to dose them with enough to be able to do it, so that there is just a simple cut-off generally that it's something more than 5 grams per kilogram. So that's a tremendous, absolutely tremendous amount of cannabis to be able to take on. In the 70s, an attorney for the DEA actually was writing in support of descheduling cannabis said that the lethal dose 50 would take a 75 kilogram man to smoke 1500 pounds of cannabis flour in 15 minutes in order to die and he wouldn't die from

a cardiovascular effect from cannabis. It would be from probably carbon monoxide poisoning. Did Willie Nelson try this? I think so. Okay, but he wasn't able to do it. He's still alive, right? He's still alive, yeah. So it's interesting what Steve was saying is that the receptors, those docking stations,

there are no CB1 receptors or very few in the cardiac respiratory centers of our brain, different than the opioid receptors, the mu receptors, where you overdose because that docking station gets activated by heroin or percassette or oxycontin and you slow down your respirations and you stop breathing and your heart slows down and your heart stops beating and you die. That doesn't happen with cannabinoids because those receptors don't exist in those areas of the brain where that would happen. And so literally to this day, you can over consume cannabis and you may feel like you want

to die with this incredible anxiety or psychotic event, but you're not going to. So it's sort of like LSD in that sense where it really doesn't have a known upper limit of toxicity from a pure cardio respiratory standpoint. By comparison, Steve, you worked in the medical examiner's office for so many years. What's the LD50 of ethanol?

And that's a great question, and I can't remember the answer right off hand. However, I do remember that the level at which people are intoxicated by this, and generally we all know to be one or two shots of alcohol or wine or beer, and that it very quickly becomes a disorienting drug with just a second one. Particularly the problem is that people don't think they're disoriented by it and that they are actually under control. It's a very different situation with cannabis, usually as people take on these substances within their body, they actually know

that they're stoned and have a sense of it and are able to be able to rectify their own behavior. Usually it's called just sit on the couch and watch TV or something like that. Yeah, there's another point here I think on the toxicity that probably is worth mentioning and you could probably speak to this with more accuracy, but it's sort of how I explain toxicity to people. It's not just what the LD50 is, it's how far the LD50 is from the use dose. Consider a Cedamentifin. You'll very easily go and take 1,000 milligrams of acetamentifin.

I don't know what the LD50 is. It's probably between 10 and 20 grams. That's not that far away. That you could be that you could only miss the dose by 10X and kill someone is amazing. I'll tell you a ridiculous story. This is, I don't know why I'm getting it, but it's just an illustrious point. I remember in residency once during our internship, a guy accidentally wrote a prescription for one gram of Adivan instead of one milligram of Adivan. So he wrote for a thousand times more of the dose, which is a clerical error that came from his just being careless.

Unfortunately, the nurse working that day was very new and she took the order as one gram of Adivan. And to make matters worse, the pharmacist on call that day was also new and realized in the PIXAS system. There's only, we only have 20 milligrams here, so that's, you know, 21,000 of what you've ordered. I'll send it up right now and go and get the remaining 980 milligrams. That patient was actually administered 20 milligrams of adivant and of course had a respiratory arrest. That's toxicity. That's a lawsuit.

That's a therapeutic index. And so they say for over the counter drugs, it's like one to 20 you take two aspirin and your headache goes away 40 and you're going to be in the hospital for something like, you know, valium or or adivan, it's usually a one to 10. Yeah, but look at alcohol. That's my really am a point I wanted to make. Look at the therapeutic syndix of alcohol. Three drinks shouldn't kill anybody. 30 would kill anybody. Right, exactly. And they say that for the therapeutic index for cannabis. So 1 to 20 is over the counter, 1 to 10 is like out of

an or value. It's 1 to 20,000 to 1 to 40,000 is the therapeutic index. So the greater that second number, the bigger the safety profile. You know, we call it a therapeutic window. I call that a therapeutic garage door. Right. There are certain drugs that are simply just narrow therapeutic index drugs and need to be very very cautiously prescribed. I should point out for anyone who's listening that there really isn't a therapeutic reason to dose alcohol

as far as I know unless you're rubbing it on an insect bite or something like that. Alcohol is not really recommended for curing any particular disease. I wanna just kinda go back to something that I forgot to ask you earlier because I got distracted in my thinking about the next thing I was interested in.

Why do you think during the prohibition era, alcohol was brought back into favor and marijuana was not? because I think it would be very difficult to make the case that alcohol is less toxic than many things. I mean, alcohol is about as toxic as it comes, and yet it is completely accepted societally. Why do you think it was, I mean, this is again, just speculating on my sense of it was it's the sociology at the time. We live in very difficult times and certainly they were very difficult at those times. And it seemed that people really need to have a release from the tensions of the day,

from the tensions of the day, the idea of creating the prohibition of alcohol was pretty quickly recognized as not successful. That is, it simply drove it underground, people continued to them by bit. And what happened was there was no control, there was no tax stamps, there was no health inspections that went along with it, and the people who

were utilizing it were demonized even more than they were before. So it was sort of a contra indication for the society, although it certainly came out of people in their heart thinking they could make their fellow man better by not having them be allowed to drink. Then cannabis was not brought back. I think at the time it was societally, it was a bridge too far for people to be able to reach. And it was apparently not a plant or an intoxicant that was used by, frankly, the people who were in control of writing the rules and the laws, but the legislators felt pretty comfortable drinking and they didn't think they knew anyone who smoked marijuana.

Well, a lot of people talk about the idea that marijuana is a gateway drug. What is the state of the evidence of that argument? In other words, what are the pros and cons of that state of the evidence of that argument? In other words, what are the pros and cons of that argument to the best of our understanding? So, it's an interesting question. I always say that cannabis is a gateway more towards health than to other drugs, and in fact, Nida, the National Institute of Drug Abuse on their website has agreed with that statement, and no longer considers cannabis as a gateway drug. But I think what people are looking at or concerned about is young people participating

in the intoxicating effects of cannabis or alcohol or high fat and sugar foods, just like anything else can be leading to other addictive behaviors. But there really isn't anything that proves that cannabis is a gateway drug. We sort of have natural experiments that have gone on with the legalization in the states that were at the forefront of this. Are there data that we could take from, I guess, Colorado would be first Washington state would be second? Are there data we can take from, I guess Colorado would be first, Washington state would be second. Are there data we can take from those states that could point to either a rise or fall in the utilization of drugs beyond marijuana that have either gone up or down since the legalization?

It depends on how you're spitting this question. If you're saying to this question that as a gateway drug Colorado has shown proof positive that there is not an enhanced utilization at least of cannabis from the black market in Young people who shouldn't be taking it unless it was for Medicinal purposes only if you're referring to the opioid epidemic, for sure, you know, BakuBur has looked at states with medical legal programs with patients that have access to dispensaries. There has been a statistically significant reduction in opioid prescriptions in patients for those for people have access. Do you think there's an association?

I mean, again, I don't know this literature. So I'm not asking a loaded question. I'm, but I sort of know these arguments, right? Which is nobody takes heroin without first taking marijuana is the argument. Therefore, heroin, the precursor to utilization of that is taking marijuana. Which of course is a silly argument, even if it were true.

I don't know that that's entirely true, but it's a silly argument because you don't know what the denominator is on the other side of that equation. How many people would take marijuana and not go on to use cocaine or opiates or other things like that? So, A is correlated with B, does not mean A causes B, and A proceeds B, does not mean A causes B either. Is there any argument though that one would make from a cautionary perspective about certain individuals who are predisposed to addiction, who, if in the presence of marijuana, are more likely to take on harmful addictions?

I'm not sure that either Deborah or that will qualified in figuring out who could potentially have addictive behavior, nor have I really seen any studies that are able to talk to this. My sense of it, though, is having grown up here in America for quite some time with children myself and even growing up here in lovely New York City, is that as people move through their teenage years, they experiment with lots and lots of things, lots of behaviors that are important, interesting and sometimes risky behaviors. interesting and sometimes risky behaviors. Marijuana is generally more available than any of these other perhaps hardcore drugs, so it may appear that people are starting with marijuana, but frankly you can get cigarettes on every street corner, so therefore I think we should blame cigarettes more for beginning this inappropriate behavior that is sometimes addictive.

I don't think that marijuana itself cannabis in any way causes or leads people on into, let's call it more hardcore drug addiction, and I just have not seen data to be able to prove it or disprove it one way or the other way. How addictive is THC? Like using formal definitions of rats pressing levers and things like that. Compared to things where the addictive potential seems to be very high.

Cocaine, opiates seem to have a very high addictive. Potential LSD seems to be the exact opposite, right? They'll never push that lever again. Where does THC fit on that spectrum? On the low end of the spectrum. For sure. Below alcohol, I believe. It's below alcohol.

Tobacco is probably one of the higher percentages than heroin. Believe it or not below tobacco. And I think they say the studies are 9%. You know, remember, these are recreational markets or using animals that high doses leave repressing. So it doesn't really reflect real world behaviors. To take that a little bit further,

there are medical centers right now that are running clinical trials, utilizing a CBD and sometimes CBD with THC as dosage forms to move people off of other addicted substances. So that's to move people off of methadone, to move people off of heroin. So it may very well be that THC and CBD are truly an exit drug, not an entry drug. We know about the effect of THC on a developing brain versus a more developed brain. So the three of us sitting here presumably have done most of our brain development, but the 15-year-old is still probably in the throes of developing.

What do we know about differences under those circumstances? So what I say to patients and other physicians is that I don't think we're advocating using any kind of chemical substance on a developing brain unless they need it. But do we have actual data? Because the I know that I did try to look into this about a year ago, maybe two years ago, at the request of a patient. And what I found difficult at the time, and I'm hoping maybe you have better data, is that we just didn't have great studies, because everything was confounded by recreational use without control. So even though at first principles, it seems illogical that a 15-year-old is going to benefit from using marijuana, It wasn't really clear

from the data what the case was. So two years later, with legalization in some states or decriminalization, can we say any more than that? Not really. Unfortunately, there haven't been the robust double-blind randomized trials in people. But when you talk about the 15 year old and should cannabis be used, again, people think of cannabis as inhalation. So let's, you know, take that off the table for a second. Let's think about it as a medicine. So if this 15 year old has a seizure disorder, and there are constituents in this in this plant that can help with that. That makes sense to use. If this 15-year-old has attention deficit or anxiety or depression and other medicines are not working or maybe the risks of those other medicines are a lot greater. I think these are our reasonable tools and our

medical toolbox that can be used. I mean people think about just THC is a very high, you know, intoxicating chemical. It doesn't have to be. You have to have the receptor. You have to have the drug that sits on that receptor. And you have to have enough of that drug to sit on those receptors to get that intoxicating effect. So let's go back to something we talked about a little while ago, which is the different modes or routes of administration. So we talked about the Spakoli route. And I guess the advantage of that route is it's relatively quickly. The active ingredients become engaged with the receptors, both peripherally and within

the CNS in a very short period of time. I'm guessing one of the drawbacks of that route of administration is dose-to-dose consistency, and presumably you're inhaling other things that might not be too good for your lungs. Is there data on that? So you're correct. So your bioavailability in an inhalational method is fast and furious. You miss the whole GI tract, which is great. So if you're somebody with MS and has muscle spasms that's acute, inhalation method could be a godsend for them for sure. You're right that the length or duration of action is a lot shorter than other methods of administration. So if you're somebody with a chronic pain issue, that's probably not your method of administration

that you want to employ. Yes, you get products of combustion. So if you're smoking plant material, you have a whole bunch of other things No differently than tobacco that can cause some issues. There have been no studies. In fact, Dr. Tashkin has shown that there has not been an association between lung cancer and smoking cannabis flowers. Yeah, why do you think that is by the way? I'm sort of surprised, but I think it's a dose effect or or maybe it's the anti-inflammatory effects of the cannabinoids themselves that sort of are kind of pre-treating it. I don't know. I'm not smart enough to know that.

That was one study. Maybe we need to look at other studies. I can't answer that. What I can say, though, is we do know that heat does cause cellular change. So for that reason, I'm always concerned about it. And for my, you know, patients that I treat, I don't recommend an inhalation method at all. Any inhalation method? I don't. Only because I don't understand how to help them titrate because inhalation is different. A small inhalation gives you one dose.

A deeper inhalation gives you a different dose. Your inhalation is different. A small inhalation gives you one dose. A deeper inhalation gives you a different dose. Your inhalation is different than somebody else's. So thinking about this as an anesthesiologist from a clinical perspective outside of anesthesia where we're totally controlled, we don't like to give drugs or we don't know the dose. I think patients who are really sick want their hands held in a way that they can wrap their head around it as much as I can. So if I say use X, Y, and Z and they come back to me and say it works, then we understand what they should take. If I say take X, Y, and Z, and maybe it doesn't work or it only does partway, then we have an understanding as to how to go, how to pivot from that point. Inhalation doesn't allow or it only does partway. Then we have an understanding as to how to go, how to pivot from that point.

Inhalation doesn't allow me to do that. Is there anything else, Steve, from a chemical perspective? So when I think of inhalation, I guess I think of two vehicles. I think of the sort of Bong joint method where the temperature is like literally from the flame burning the material,

combusting it, that then gets inhaled. And then you think of sort of the vaping method where... Well, tell us how vaping works actually. Vaping works at a lower temperature than the pyrolysis that goes on when you use a bong and some people even take it a little bit further and heat up a substance using a settling torch on a nail and then inhaling it. That's really hot. The vaping goes on at a much lower temperature and there are other dosage forms that are going to come out soon that are simply inhalers, like bronco inhalers, where they won't be any temperature gradient at all, and the product will be brought into the

lungs through an inert carrier gas. So that will allow a much more controlled dose. Those just aren't really on the market very effectively yet. There's been a lot of talk about vaping lately, and this is both from the lens of the use of THC and nicotine itself, totally separately. What do you guys know about this as it pertains to safety? Let's start with that. That's an interesting question.

I don't think anyone really can put a finger on a specific reason for this problem that these v-parchers are causing. Tell people what the problems are that we're seeing. So it looks like an acute respiratory distress syndrome. So it almost looks like a chemical burn to a lung where people have a respiratory failure that requires a huge amount of support in the intensive care unit, including intubation and ventilation and other support measures.

So it's pretty severe and pretty significant. When you extract cannabis, it comes out as a thick, goopy oil and you need to refine that oil in order to put it into cartridges and those methods of getting the right viscosity for that oil to be put in that cartridge is done in a whole host of different ways.

And I don't think it was done intentionally to hurt people. I think people thought, oh, let's thin this oil out using PG or P.E.G. because it's a grass ingredient generally guarded is safe, but it's generally regarded as safe if you eat it. And no one really understood what happens when you combust it. For those two things, I think it's formaldehyde gets created when you combust or heat up PG or PEJ. Other people are using, we're using vitamin E acetate. Again, generally guarded is safe. If you ingest it, not if you heat it up to a vapor or steam.

Does the FDA not require a reanalysis? If the FDA says substance A has a grass designation, and substance A has historically been consumed at room temperature and subject to a first pacific in the liver, can anybody come along and say, I'm going to burn said substance and it still maintains its grass designation? How does the FDA think about that? The FDA allows something to be grass generally recognized as safe for particularly uses either

as direct food ingredients, indirect food ingredients, part of packaging. But once the product is out there in the marketplace and available to use, it's America. People will do whatever they wish with it. And that brings us to part of the issue here is that this is, while this is a regulated environment within the states, there are many actors, many producers who are not yet regulated. It's kind of like alcohol was legalized, and then there were still bathtub gin being

made for many, many years. There were hundreds, thousands of deaths from it on this vaping issue. In particular, I had some experiences at the New York Medical Examiner's some years ago on a syndrome that came to be called SIDs, sudden infant death syndrome, where we had to look at the lungs of a number of infants that had died in this way. And so something similar is happening here. We're in the midst of a quiet, slow-moving epidemic, where there are now thousands of people in hospital. I think we have over 34 deaths directly attributed to it, and week by week the toll continues

to mount. It's just not been brought out all that widely. It does look like these are chemical burns within the lungs, but then the lungs seem to be not regenerating themselves, but the wounds are getting worse. So does it behave like ARDS? That's what it sounds like. It's a lot of cellular recruitment and then oxygenation, you know, doesn't occur, but they're not 100% sure. Are they getting edema as well? There's so far been a good deal of a lid kept on a lot of the discussion as both CDC as well as other health organizations are trying to find epidemiologic locuses where events have occurred.

In a couple of cases, they've been able to identify that there were individuals who made some vape cartridges where there is a higher proportion of people who have been hurt from other vape cartridges, but there is just no clear-cut etiology so far. So, if I'm understanding you correctly, we have no idea if the uptick in these acute toxicities is potentially manufacturing-related,

low-ci-related, diffuse, we don't know any of those things yet. That's exactly correct. From having worked in this industry for a long time, I'm very familiar with every time a new product, even if it's something as innocuous as a lipstick. It's changed. There is a slight uptick in adverse events, even from just changing a coloration in a lipstick

or an eyeshadow, because there are millions of uses of it. You're able to see what happens in products like that that are where people are using them external to their body is it's a slight irritation. The person simply decides, I won't use that eyeshadow anymore or that lipstick anymore and they self-select out of the population. Here this is a sudden onset of a serious nature but even with all of these numbers of well terrible amount more than 30 deaths and hundreds thousands in hospital. This is against millions and millions of uses, and that just doesn't seem to be a clear

cause that we're able to find so far. You said something a moment ago, and I want to make sure I understand it because it seems staggering to me. The FDA, if you go down to the grocery store, the corner store, and you buy a bag at, I don't know, jelly beans, and they come in a plastic container. Does the FDA have oversight into the plastic that holds the jelly beans? Yes, they do. And the FDA says this plastic is grass.

Yes, that the individual chemicals that went into making that, they don't look at the overall plastic bag, but rather the individual polymers or monomers or the colorants have all gone through extensive testing. Now, let's say I'm an idiot and I decide to create a new product, which is I'm going to take the plastic, I'm going to take those concisitive elements in that plastic bag that holds the jelly beans and I'm going to combust those constituent of elements in that plastic bag that holds the jelly beans, and I'm going to combust it for inhalational use. So new use of previously agreed upon grass constituents. Does the FDA say, Peter, you can't do that?

Or does the FDA say, well, gee, whiz, each of those things were safe to be touching jelly beans, therefore you can be learning them. FDA actually would be very annoyed at you. What's the legal recourse? Oh, the legal recourse was if you had turned that into a business, is they would come and shut you down. Okay. So the FDA still has their pants on and they would still be looking out to protect

people from me doing that. Yes. Absolutely. But not in the cannabis world. Why? Because it's federally illegal and the FDA is not a participant. So you're saying that the fact that cannabis is still illegal federally means this entire discussion is moot and it would be at the state's discretion to police this type of use switching. Exactly. That's exactly correct. And that is part of the difficulty right now is that state agencies are not used to having the scientific horsepower or the manpower or woman power is much better to be able to figure out what of these

ingredients can or cannot be added to it. And on top of that, the producers of the products are not required to test them for safety or efficacy before they start shipping the products, or safety or efficacy before they start shipping the products, which is very different than products sold under FDA ospices, where you have to demonstrate at least safety for foods, products, and for drugs, you also have to prove efficacy before you can make it and ship it. Prior to the explosion of these acute events of toxicity, I was much more personally curious about chronic toxicity. Let's take tobacco as an example. Very few people have acute toxicity to tobacco use,

but by the middle of the 1960s, it was abundantly clear what the chronic toxicity was from tobacco use. Alcohol is an interesting one. Alcohol has lots of acute toxicity. You could kill yourself in a moment with alcohol. That's a very easy thing to do. But I don't know if your friend who died of cirrhosis had complications of alcohol use or whether it was hepatitis, but certainly the chronic toxicity of alcohol in this country

is the longest, fattest, widest tale we see, along with tobacco perhaps, maybe fatter actually. What do we think is the chronic toxicity, or do we believe that there's any evidence of or against chronic toxicity from vaping? Things that we just haven't, it hasn't been around long enough,

and we don't know, but you're sort of playing with fire, that logic. I mean, that's a feeling feeling because it really hasn't been available as widespread as it is now. Remember, 2014, 2013, was when really other states started really coming on board. I mean, California was the first in 2009. There was nobody vaping then. People were, you know, using cannabis as a flower to smoke. People were using it in foodstuffs to eat.

But nobody was using this vaping thing. I don't think it was until the popularity of vaping through the e-cigarette market when the cannabis market turned and went, this is an interesting business, an interesting mode of administration, no products of combustion. So people will feel a lot better about it. And I think people honestly and truly thought it was a better maushtrap. Do you know what the people who favor that approach will argue in their defense? So there's a couple of arguments.

One is it's better than smoking and getting products of combustion. Two, it's helping me get off nicotine. So I'm vaping instead. So that's better. And three, people who have an acute pain issue or muscle spasm feel like the instantaneous nature of the effects of this is what they require. I think that manufacturers of cannabinoid medicine

are looking to do things with the cannabinoids. I know we are and I don't want to push for a product, but we are looking at changing the sciability from a fat-ciable to the water-ciable method of administration makes the bioavailability a heck of a lot faster, just not available across the country because we have a state license in Michigan and we can't sell it across state lines. Yeah, I want to come back to talk a lot about your product because when you said that a moment ago, Deb, I couldn't understand how you were talking about water solubility of

this. So let's between the three of us remember to park that and come back to that because I could use the chemistry lesson. Going back to the toxicity point, we talked briefly about edibles earlier, or we didn't, we sort of indirectly did. You said that if specoli ate that flower, he might have got a belly upset, but he wouldn't have got high. Why is it that when people consume edibles, they get high?

Because it's a different constituent. They're not using the raw plant. They're heating those chemicals. So when people are making brownies, yes, the batter's yummy, but they generally bake it at a certain temperature for a certain amount of time. And there are actual curves that show when THC in its acid form, in its raw form, gets converted to, or some people call it activated form, into THC. So it takes time and it takes temperature before you make that conversion. And at that point, when you eat it, that's when you can, those chemicals can sit on the receptors that make you feel

higher and toxicated. So it's again, it's very unlikely you'll make two batches of brownies identically because time, the area under the curve is almost always going to be different. So everybody gets a different brownie. Now, when you get the candies or things like that, is it the extraction of the THC required heating to get the active ingredient into these commercial edible products? So it depends on what you're making. I mean, there are medicinal chocolates,

the candies and stuff. But there are medicinal properties in the raw form, as well as the heated form. So if you're making it for the direct purpose of intoxication, you're going to heat it, starting material first, you know, the active ingredient first, the THC, and then you're going to put it into your chocolate. So this might be a bad analogy, but you know how any time you make coffee, you're basically running hot water across a bean, but if you're a real coffee snob, you'll do a cold brew

so that you can extract the flavor without the temperature and you avoid the bitterness. It seems to me that whether you're talking about smoking a joint, lighting a bong, vaping or eating a candy or chocolate or a brownie, heat always seems to be required if you're going to get this active ingredient out. Is that the case? If you're trying to get the... It's for intoxication, yes. For intoxication.

So the answer is yes. You have to apply time and temperature in order to make THC and then you put that THC as your starter ingredient into whatever it is. And the variables for the edibles is not just the preparation of the food, but that our digestive process varies, our to our person to person, as well as our body mass and how we feel about things and what the time of day is and the circadian rhythm. So it's almost impossible to expect out of eating any food that contains THC or CBD to expect that you will get a reliable, repeatable dosage experience from that.

Even if the label is completely correct and completely accurate. And that's a big if. It's huge. Yes, it is. The legitimate laboratories in cannabis have gotten better and better and better all the time. But still, when you make a batch of a thousand brownies and you just sample one or two of them, there's an awfully good chance that the batter may not have been mixed appropriately.

Pharmaceuticals sort of solve that because of the consistency by which we make things in a pharmaceutical way, but foods are not quite that precise. And you know, you can buy a brownie at a store one day and then buy a homemade brownie the next day and it can taste very different. How many strains are there of cannabis that are commonly used? From what I've heard, there's over 800, but people are crossing and back crossing all the time. But back to the edible thing that I think is even more important is that when you eat something and it goes through your stomach and it goes to the liver and gets cleared,

it gets chemically converted. And so therefore, you're really not even ingesting THC anymore. You're ingesting its metabolite, and that metabolite is even more intoxicating than THC itself. So there are people who are experienced in inolational methods of THC,

they do it all the time, they say they can't even eat a THC brownie or a gummy bear or drinking a soda with it in because it's far more intoxicating. Do you think there are any, a period might be the wrong word, but just call it, what are the best use cases for edibles? I think the best case use edibles are for somebody with a chronic pain. So let's take example, somebody with a chronic pain

that can't sleep at night. Let's take an extreme case. Somebody with cancer that's spread to their bones. Right. And they literally can't sleep. So what I would do with a patient is I would trial them on a certain edible or something that I believe is consistent. It wouldn't be held within a food stuff. It would most likely be in a capsule or a tablet because it makes sense. Again, remember we talked about wanting to understand the dose and wanting to understand what it is. We would dose it in a way that would be the same time every night for this patient.

And we would see how they would sleep. The bioavailability takes about 60 to 90 minutes in the best case scenario. You only get about 8% of whatever it is that you're taking, but it can last up to 8 to 10 hours. We haven't talked about tachyflaxis or tolerance. How does the body respond to repeated administration of THC?

That's really interesting. THC sits on these docking stations and those receptors, and there are chances of overconsuming THC and down rate regulating these receptors that actually can be reset very quickly by just stopping for a couple of days. But there's an interesting study out of the Netherlands since they've had a medical program for a very long time, I think since 2012 or something or 10,

where they looked at patients, the average patient only takes 750 milligrams of cannabis a day, and you would imagine if there was so much tacky flaxis, you would have seen an increase for a rise in that, and you didn't seem like they stabilized it, 750 milligrams, and that was it, which is contrary to what I just said. So explain the opposite. Talk about opiates. You've obviously, as an anesthesiologist, had lots of experience with them.

What typically happens to a patient who has prescribed opiates for pain? That's the problem with opiates. Opiates sit on their own docking station and they do down-regulate very quickly, which means that you require more and more for the same effect, and then it does something really strange. It flips. And after a certain amount of opiates, your pain gets enhanced, not decreased. And it's called hyperalgesia. It's a strange phenomenon.

And you said 20 to 30% of people experience that? No, actually, 20, 30% of people experience that from the beginning, where they experience an opposite reaction to pain relief. but I'm saying people who traditionally get pain relief, who require more and more and more for the same amount of pain relief, suddenly they are experiencing a hyperalgesia, an increase in pain, whereas before a month ago, you know, two months ago, they were actually getting pain relief. Nobody talks about that. So we don't think that this is necessarily happening

with THC and the CB1 or CB2 receptor. No, we're not saying that yet as of now. Let's talk a little bit about how THC mixes with other drugs. What happens when THC is combined with alcohol, for example? Alcohol is a known depressant of the central nervous system. I still don't really understand what THC is doing in the CNS. I'm still confused by the intoxicating versus non-intoxicating effects. I know that I can tell what you're thinking, which is Peter, that's the point. It's a plant, it's complex, it's doing many things, but... It's multimodal, actually.

So a little bit of THC won't cause any intoxication. You need the receptor, you need the drug drug and you need enough drug sitting on all those receptors in order to express those things. And I joke with Steve and say I like to be called the queen basically, but the queen of microdose, which means I like to use very small amounts of cannabinoids to activate things on a cellular level so you actually don't feel the intoxicating effects because most patients don't want to be sidelined by their pain and they don't want to be sidelined by their pain medicine.

So that's kind of off topic. Is that the majority of your personal focus? I mean, I want to come back to obviously what your company pure does. That makes sense there. But what about people who actually want some of the intoxicating effects? Because, well, let me unpack that a little bit more. I was about to say because of things like anxiety or stress. But you could make the argument that if one has their anxiety and stress reduced

without intoxication, that might be just as beneficial. Have you thought much about the particular demand, the consumer demand? What is it that people actually want from THC? My sense of it is that they would actually like relief. That is over and over again, I did an extensive survey of in Michigan, we have over 400,000 people with medical marijuana cards.

And if people who were going into cannabis dispensaries, two thirds of them were really there for medical reasons, not to get stone. They had learned over the course of their lives that they could reduce their pain, often chronic pain from very serious accidents or operations, they could reduce their anxiety, and they had learned that they could find strains of marijuana, and they were using them and

smoking them, because it was all that they had available to them. So these are people, generally, who were just looking to live happy normal lives, like all the rest of us, and that they have found that this is a relatively inexpensive and pretty harmless way to manage what are otherwise very, very severe symptoms, so that if going back to your question about utilizing alcohol at the same time. There are some people who utilize alcohol regularly in order to frankly numb the pain. Even without listening to any Frank Sinatra songs about the heartache and why we're all still in a bar at three o'clock in the morning, it's for pain relief, for it's psychological and sometimes straightforward

physical pain relief. Once people discover that they can achieve that by using a small, relatively easy titration form. People who utilize cannabis smoking or vaping are readily able to titrate themselves, which is just remarkable to be able to do that. Certainly, I did when I was smoking cigarettes, I could learn how to accelerate my heart rate or relax by just puffing in a different way. I gave up that addiction myself. Interesting. I don't think I appreciated that you could have that distinction from I get presumably

from the nicotine depending on the state. Yes, but by the speed at which you take on that nicotine, I could either excite myself to be able to get up for something or you could use it to calm down and relax by just simply dosing in a different manner. Do you think there are certain medical conditions that are contraindicated from the use of THC? For example, I'm making this up, I have no idea. Someone with schizophrenia or someone with severe psychiatric illness

can it be exacerbated by THC? The short answer is yes, but that doesn't mean that they should not be avail to cannabinoids, because again they should not be a veil to cannabinoids, because again, there's over a hundred different cannabinoids specific to the cannabis plant that could be and has shown to be incredibly useful. So yes, high dose THC alone could stimulate somebody who has schizophrenia to have an exacerbation of those things, but CBD and maybe even a low level of THC along with it could actually be hugely beneficial. Back to your question about THC and other

drugs, THC plus opiates has shown that a reduction in opiates with a greater pain relieving efficacy without that tacky phylaxis or tolerance that we know to be true for opioid use. How much time do you still spend in a hospital setting or an inpatient setting? Do you have any, you spend any time there? Zero, any more. Do you have any sense of how long it will be before THC and or CBD make their way

into the, for example, post-op surgical patient world. Journavinal, which is a synthetic THC, has been on the market since the 1980s and we as doctors are allowed to write prescriptions for it across the country and patients can travel with it. That's available now, and it's being used for chemotherapy-induced nausea and vomiting in some settings, not very well because straight up THC is really uncomfortable. Does increase your heart rate, does make your mouth dry, does make you feel agitated and uncomfortable.

I mean, the rest of the constituents within the plant sort of modulate all of that. I'm glad you brought this up because I was going to ask you about the synthetics. The synthetics have a pretty bad rap. There's sort of the teleologic argument of, you know, nature always packs the right amount of this antidote versus that antidote. I mean, what is your take on synthetics through that lens in particular? That's a complicated answer. I mean, I think what I'm really wanting to talk focus more about is a single molecule,

as opposed to looking at many of the molecules within the cannabis plant and try to find utilization. So a single molecule like CBD from Epidylex from GWFORMA came from a plant, but it is isolated and purified to 99.99% and it required a tremendous amount to get the effect that GWF1 wanted to get on to types of seizures. We formulate using isolated cannabinoids, but we join them together along with other constituents so that we use less and we capitalize on the synergistic effects of a lot of the molecules. No differently than what we do in medicine

as an anesthesiologist, we just don't push one medication. We push a lot of different medications to lower the bad effects of one particular medicine and capitalize on the good effects of all of them. Same more about the GW CBD for epilepsy. What is the purity of it? You said it's 99. It's pretty high. It's greater than 90 percent.

Tell me about the success and utilization of that. So it's plant-arrived, but it's isolated, so it's purified. And they have it for two particular types of seizures, those kids with these rare seizure forms that are refractory to multiple other traditional pharmaceuticals. I think they have like a 30% reduction in their seizures, but there's side effects. I mean, there's GI effects, there's liver issues. I mean, there's side effects in high, high doses of epidile X. What do you think is the potential for CBD and sleep?

Something that gets talked about a lot. What does your take on the efficacy of CBD oils? Let's start with the oils oils which are very commercially abundant. Well, let me first mention my bias. I took it this morning at 1 o'clock in the morning because as usual, I'm up for an hour trying to do something and it's a little noisy in this city and I need you to go back to sleep. So it is in our hands and in our experience, it works.

It simply works. That is, people are able to take CBD. We think that taking it as an oil is less effective than taking it in a water-soluble form. But it is certainly effective. We have pharmacovigilance data on several hundred thousand people. The demonstrates that they generally go to sleep pretty quickly, have a great night's sleep, and wake up refreshed with no feeling of what other sleep aids give, of groggyness, or anything like that.

Most people think it is just fabulous. Do you have any insight into what the mechanism of action is? So, remember, multimodal mechanisms of action. So, anti-inflammatory, it also activates the GABA receptor, decreases anxiety, and a lot of people have that three-year-old running around in their head at night and prevents them from going to sleep. So we think it is central activation of GABA that is would be one of the more potent mediated. There's a molecule out there called fenabute, which is an oral form of GABA that crosses the blood brain barrier. Now the FDA has not designated it grass, so therefore it's no longer available

easily. But for something that was for so long over the counter, it was kind of a remarkable sleep aid. So one shouldn't underestimate the potency of CNS GABA activation. Is there any sort of polysom data that talks about staging of sleep with CBD. In other words, it's one thing to say, great, a person can sleep for this many hours uninterrupted. But do we have any sense of the impact of CBD on sleep architecture? I haven't seen any data like that and your questions are remarkably and remarkably perceptive.

You have to realize that at this current time because of the still illegality of THC and the confused legality about all of the others that pretty much every university, especially medical universities, do not allow research to be done on the facility unless someone has a DEA license, and even then getting the DEA license is a long drawn out process, so that very little work is able to be done, and there are thousands of medical researchers who would love to work on these problems, but they can't, just like they haven't been able to for 50 years. But is CBD not permitted for research if the THC level is low enough?

That's only come about in the last few months. So it certainly takes a lot longer for research protocols to be developed, to move through NIH, to move through whatever funding opportunity there is. And I expect that in the next year or two or three that there'll be much more research done on that, it's still a highly restricted, highly restrained, and frankly, the university administration in almost all of these schools and universities are very, very worried about jeopardizing their federal funding for billions of dollars of other projects.

In other words, it's not that there's a dearth of funding. If a philanthropist came along and said to somebody at the University of Michigan and Ann Arbor, hey, here's $5 million. I want you to study the effect of CBD on sleep duration and architecture. The university would say, well, thank you for that, but I don't want to jeopardize the billion dollars of NIH funding I have. Is that, am I understanding you correctly?

Yeah, well, I wouldn't pick on you of them because my wife works in pathology there. So, but it's a great school, terrific school, footballs coming back folks, that any university in these stages will move much more carefully to consider what the research is and who is the researcher simply because of 50, 60 years of illegality. It's just so surprising to see how far behind THC and CBD are when you have a beautiful road map from organizations that have been funding so much psychedelic research.

I mean, when you look at maps, the multidisciplinary association for psychedelic studies started by Rick Doblin. I mean, started this organization in 1986. 33 years later, they are now in phase three studies using MDMA, which is, as you know, obviously, schedule one. I'm kind of amazed. Is there not a comparable group that is advocating for the judicious study of THC and CBD? We are.

We run clinical trials. Regularly, Dr. Kimless here is running clinical trials right now. And there are others, but they're from, let's call it private sources. So is that the business model of your company is that you have a product that you sell and the proceeds of that help fund the research? Yeah, that's pretty much it. We came up with formulations that we felt would work, and then we ran pilot clinical trials

to see how they would do in a small patient population. And once we saw that that was getting a very good response among people, then we were able to distribute the products within the state because we were state licensed to be able to do that. And now we are taking the funds from essentially from that cash flow and scaling up to be able to do studies under FDA office ospices, which are frankly much more expensive to do because of all the controls that go along with it. Talk to me now about this idea that we alluded to twice already, which is the water solubilization of something

that I didn't assume could be water solubilized. We have a number of patents on it, and a number of them are moving through, so you'll have to forgive me for speaking generically about that. We have one issued patent out of the seven that we've filed for, and that was to figure out, we figured out how to freeze dry cannabis.

And that's an industrial process, and it helps. So that's an awarded patent, and anyone can look that one up. THC and CBD, and all of the molecules that are in cannabis that appear to be useful and viable are oil soluble. They are not, they are not water soluble. So if you put them in a glass of water and start, you'll have little oil globules on it. So we figured out how to be able to convert that instantly into a water soluble molecule so that when a person puts a drop of this or a powder of this on their tongue, it doesn't taste oily, it doesn't feel oily, and it doesn't act like an oil. And as everyone knows, yeah, you can have some oil and vinegar

maybe on your salad, but the body doesn't really like to have a lot of oil in it on a regular basis, whereas everybody can drink pints and pints of water, gallons of water, perhaps a day. So these molecules are rendered to be water soluble, and because they're put into very, very fast rapid dissolving tablets that disintegrate in about 15 seconds or so. Do they disintegrate under the tongue, and therefore escape the first pass effect of the liver?

That's exactly right. Under the tongue, on top of the tongue, mushed around the tongue. But they're not to be swallowed. They're not to be swallowed. They're not to be swallowed. They're called sublingual because it's under the tongue, but what happens is, as the tablet disintegrates, literally in the mouth, the molecules move towards the tissues of the mouth, the tongue, or throughout the oral cavity. What we see is in about a minute the molecules have moved into the bloodstream and for those who are sensitive enough they can actually feel their toes tingle in two minutes

which teaches us that we have full systemic absorption, frankly the molecules of reach persons tolls. And then we find following that that people are able to experience whatever effect medical effect that we are looking for in about eight to 10 minutes. So that's the onset of sleep for sleep formulations, the onset of pain relief for pain relief, for anxiety. So that has the advantage it avoids first-pass metabolism. It gets much more of the active drug into the bloodstream and to be distributed throughout the body.

So in theory, you could actually lower the levels of drug that are necessary to do, which how potent is this? Is this a millimolar or micromolar drug? I would say that this is closer to micromolar, that is someone who's, we found very effectively that sleep works in someone who takes 10 milligrams of CBD and one milligram of THC, and that's spread across a body that's maybe 70 kilograms, 80 kilograms of weight. This is really interesting to me, is that the optimal cocktail for sleep may actually have some THC in it,, opposed to just pure CBD. It's our experience over and over again that this concept that's called the entourage

effect when it's applied to cannabis, but yet this is used throughout medicine. As Deb mentioned, as an anesthesiologist, she used a cocktail of medicine, certainly in oncology. It's very, very common to prescribe multiple drugs at the same time, or in oncology, it's very, very common to prescribe multiple drugs at the same time or in some sequence. We've found exactly the same effect and did it by clinical trials of seeing how it would be with patients getting feedback from them,

revising the formulations, redosing them and seeing how those effects changed. Does your company have a 501c3 attached to it that allows people to fund research in the way that maps works? No, it doesn't. So far, it's me. I drained my retirement account in order to do this. As you said, though, as you move towards the more and more rigorous FDA studies, it's something you should consider. I mean, I think the public support for this type of research is strong. I think the public's appetite for this is strong.

You know, if you think about it, you have a harder problem, in my opinion, to solve than the psychedelic community does, because at least there, there's no ambiguity about the molecule. We know what psilocybin is. We know what LSD is, we know what MDMA is, there is no purity concern. I mean, there is if you go to a club or a party or something like that, but from the standpoint of doing clinical research, we know exactly what we're talking about. Whereas you're dealing with in many ways a more complicated set of molecules. So you have two issues, right, which is not just the straightforward, safety, efficacy,

effectiveness, chain of phase one, phase two, phase three. You have a problem that lies beneath the surface of that, which is route of administration, cocktail, chemical composition, all of these other things. I mean, I generally try not to give unsolicited advice, but my view is, I don't know that you want to go alone at this problem because I think the work you're doing is very important. You know, I was at a dinner the other day and you know, somebody at the dinner table was talking about, you know, telling a story and you hear these stories all the time, right? So I think the person is totally well-intentioned, but and I just sort of sat there silently because I didn't really feel like debating it. But the claim was a friend of my

friend's father was in hospice with stage 4 pancreatic cancer, had weeks to live, and they put them, you know, the family snuck in CBD oil for him, and two weeks later he was home and cured. And, you know, the problem with those types of stories is not only that they're almost assuredly incorrect, it's that they sort of damage the credibility of a body of research because you start to have absurd claims that are thrown in with sort of legitimate claims. How do you think about the sort of stigmatization of this and trying to manage the hype and the potential? That's a really awfully good question. So I should point out while there's only two of us here in the room, this is a research team with a great deal of depth and breath. That is everyone I've worked with in pharmaceuticals for the last 40 years. I've said, oh my goodness, please let me work with you on this.

And so we have that as well as a number of people who are fairly well to do, who are looking at this as a business opportunity and an investment, which I really appreciate and my wife is especially appreciative of. So I can stop draining our own retirement account. Many of these anecdotal experiences are true.

I wouldn't have believed it myself, honestly, except for the fact that we have now sold six 700,000 tablets to tens of thousands of patients repetitively in Michigan. And I watched, it sounds funny to say, the week in the lane get up out of their wheelchair and move and say, I don't know how to tell you this, but what the heck is in your tablet? I just say, well, it's THC or it's CBD in a particular ratio with these terpenes. And families would say, thank God, my husband is living, my mother is living, my child's anxiety is greatly reduced. And I know to classically train scientists and physicians that in this society at this time, that seems damaging or inappropriate. But in other societies, it is not that way.

This is a sociologic event that is just beginning to spread. And I know among many of my friends in police forces who are EMTs and firefighters, first-line responders who frequently have a great deal of anxiety in their life, and frequently a great deal of pain. Just straightforward physical pain aside from everything else, that their personal experience with selected, extracted, purified cannabis has completely changed their thoughts about what they have for generations thought was completely inappropriate behavior. Now they say, oh, she gets rid of my pain

and I don't feel so bad and they are still able to function perfectly well. They're not stoned at all, not in any way at all, well, they're not stoned at all, not in any way at all, partly because the drugs are relatively easy to self-try. Yeah, I know I suggested a lot. I'm not suggesting that one can't see improvements in those things, but I do sort of bristle against the notion that there are people with stage 4 cancer that are being sold a bill of goods that says, take your metastatic pancreatic cancer and in two weeks you're cured with this. I'm waiting to see the first documented case of that. And I'll continue

to be an incredible skeptic of that sort of logic, which is not to say that a patient with cancer wouldn't benefit immensely from really, really, for anxiety or pain. But yeah, I just I have very much. Completely answer remissions. So THC and other cannabinoids have been shown in the laboratory to have a multimodal effect on cancer. So in apoptosis, which is cell death, in migration or metastasis, in neovascularization, it reduces it. So there are actual reasons and rationale behind it.

Your right, is there a double bind or randomized trial of people? I think a doctor would go to jail. If you had somebody who could have XYZ traditional chemotherapy and okay, here's a cannabis concoction that we've come up with, I wouldn't have believed it myself. I can show you pictures afterwards. We can't do it on. I can show you pictures afterwards. We can't do it on a podcast. The story is an eight-year-old girl in hospice. She was on methadone and morphine. Our goal was to just treat her to get her off it so she had a better quality of life before she died. And we transitioned her from hospice to second grade to third grade. What was the underlying pathology? She had a chronic lymphocytic leukemia

and a leptomininial spread. She felt chemo-radiation in a couple of boomeros. She sadly died this past summer. Again, this gets back to the broader point, which is I'd like to see this studied more aggressively because my greatest fear is watching patient. I mean, my greatest fear is safety. I think that's followed with predatory behavior.

Oh, absolutely. And I just, I can't tell you how frustrated I get when I hear stories about people who are spending their last dollars on cockamami schemes that have absolutely no bearing. I mean, and you know, look, there are lots of things that kill cancer in vitro that aren't gonna work in vivo. So we just have to be cautious about it. And yet, I know I definitely remember the pathways of even autophagy and apoptosis and all these things where the cannabinoids play a role. So again, I think this all just speaks to the idea

of kind of loading the boat to more effectively study this. And of course, I mean, the criticism is you have a conflict, right? The criticism is how can you be fully objective? And again, this is something that the maps people can get away from because MDMA has no IP associated with it, right? Merck developed this drug in the 20s. Now there's an interesting business model,

which is how would you incentivize people to study something where there is no profit center at the end? My view is you should be able to pursue this. I mean, I want to be clear. I'm not suggesting that you guys aren't sitting here with the purest of intentions. It comes across very clearly, and I hope the listener can tell, but I can tell how pure your intentions are and that creating a company is just a vehicle through which to pursue more research. But as I think about the broader objective, which is broader than just your

company, again, I'll come back to this idea of creating a research initiative around this that even exceeds the reach of your company. Because remember, the number of questions here is harder, right? Like I'd like to hear from you guys what question you're most interested in knowing the answer to in five years. It would be great that the NIH could carry some of that burden, right? It would be great that independent MROs, medical research organizations could carry some of that burden because no one's retirement account should be depleted in an effort to hold a promise true to a friend, which is a, in some

ways, a part of what started this for you, what the sort of this journey for you. It is. Exactly. Tell me a couple of questions. Like, what do you not know the answer to today that you want to know the answer to with respect to THC, CBD, and its associated products in five years? What would make the world a better place? For me, I've made a vow that I will find a formulation that will relieve PTSD. I made a vow to do that for people who were heroin addicts and, you know, a method don't may not be the

best of all formulations, but that's what I did when I was 23 years old. And I got a little better as I went along. So that is the driving force for me to be able to do this. And then my goal is to be able to discover as many of these disease conditions, psychological or physical conditions, as we can extract value from these stunningly non-toxic molecules. Steve, are there INDs affiliated and associated with these molecules? Like, are you in that phase one pipeline now?

Yes. We are. We have three files. We actually just met with FDA three weeks or so ago. Over one of them, and we are pursuing that very, very actively. So each time you reconstitute something, it's a new IND. That's right. Okay. Explain to folks because you're the expert on this. Explain to folks what an IND is, and how important this is in this regulatory pathway.

In order to sell a drug in the United States, you have to have an approved new drug application. That's called NDA from the Food and Drug Administration. So what do you do before you get that? You have to go investigate that drug. So that's what an IND is. It's an investigational new drug exemption from all of the rules that say you have to have this approved drug. So you go and meet with FDA, we provide them with data and the documents that we have available and say, dear FDA, we would like to run the following clinical trial.

And here's all our evidence, and do you folks agree with us? And in the course of hashing that out, they will come back and say, we'd like you to do a little more work in with an animal model, or we'd like you to do some additional studies in humans in a particular way. And so we are in the process of doing that

in three different therapeutic indications. What are those three besides PTSD? One of them is an animal model, that is for pet dogs who have pain from osteosarcoma and the other osteoarthritis. Ostratoarthritis to the knee and then PTSD. Right. So those are pain in dogs, pain in people, particularly osteoarthritis, pain, as well as PTSD, which I think of as a combination of anxiety and pain, it presents in a number of ways, mild, moderate, severe, etc.

Again, for the listener to make sure to understand the distinction, there are currently products you are legally selling in Michigan that do not require an IND. They're currently grass products. They're not basically pharma grade products. Is that safe to say or is that it? No, these are pharma grade products simply because this is the space that I live in. I have always thought that that was the only appropriate way to make products. It's called meeting good manufacturing practices. It's a couple levels higher than any of the states require for safety or efficacy. And so we just make products to meet FDA

specifications because to me that's just easier. In other words, you're a, this is gonna sound crass. So excuse it and you can clarify it. But you're like a supplement company that adheres to GMP practice. I don't think of us as a supplement company. You make a supplement to a GMP, this product, for example, like something that you can sell currently today without a prescription. Right. We work within the medical, legal rules in Michigan, but those rules do not mandate GMP manufacturers. And you hold yourselves to that standard. That's the one I'm trying to make.

Yeah, that's exactly. I'm trying to pay you a compliment with that. And I'm making it sound backwards, but yes. And this is, as most everyone knows, doing an adequate amount of testing to go through the FDA process is very expensive and very time consuming. And let's put some numbers to that. I average it's about a decade and a billion dollars to create a new drug. Yes, that's exactly right. Let's say that again, you want to make a new drug from IND to approval is order of magnitude 10 years and one billion dollars. Yeah, that's right. I don't think your retirement account is that big.

That's correct. So anyone out there? Ooh. This is going to turn into a telethon. Let me ask why have you not pursued a product yet on sleep? Because I, again, I think anecdotally what you've said resonates with many people, the power of CBD,

including probably very inferior products compared to what you've said resonates with many people, the power of CBD, including probably very inferior products compared to what you're capable of making with your IP, is the view that you don't need to go down the IND pathway to produce that, or is it just a matter of resource allocation? It really is resource allocation. Truthfully, we have 14 indications that we are going for, and you have to prioritize, as everyone does with everything in your life, and we looked at them and said, which ones are easier or faster or less expensive to test and be able to prove, sleep studies, frankly,

are very expensive. And they are variable just in the methodology of it, whereas it's a lot easier to be able to measure pain, and there are scoring systems that are more reliable in that way. Tell me a little bit about what you can sell in Michigan and how does a business work that can only limit itself to one state? So it's quite challenging. We drove at getting a first license, and we were successful in getting the first license in Michigan to be a processor. That is, we can take in cannabis that's been grown within the state and turn it into an extractive and then turn that into tablets.

That's what the process of processing is. We could also make it into gummy bears and vape cartridges and we sell those also. And then we are able to ship those to just state authorized dispensaries. Historically, people in Michigan needed to have medical marijuana licenses in order to get into those stores, but

now, like many states, it's called recreational or adult use. You only need to show that you are 21 years of age to be able to go into those stores and buy. So that's how we started, but now we have grown to have, we have liaisons with subsidiary companies or affiliated companies where we're growing about 5,500 plants, bringing it to our facilities, doing the extraction, and we have relationships with all of the 70, 80 dispens restores throughout Michigan. That's how that business has grown and that's to a large extent so far what's been able to fund our research studies.

But once again, this is a telethon, folks, you can call in. How large is your team? So we have overall about 100 employees working in various aspects of production and sales and administration for the company in terms of the research team. Deb is our chief medical officer and then there are about another 10 or so direct people

working on it and then another 30 to 40 consultants who come in and out of the projects to be able to work on those. What will be required from a legal standpoint for products like this or similar products to be sold across state lines? Does that only happen with at the federal level? Yeah, that only happens at the federal level. We think that the first number of indications that we've picked and worked on with FDA are going to go through fast track approval. And that's without getting down into the weeds

of all of the legalities of that, that frequently allows a product to get through the FDA process in somewhere between two to four years. In the space of drug development, that's the blink of an eye. And at the same time, we're beginning our international aspect. Debeni will be in Berlin presenting our data at an international meeting of cannabis physicians. So that this activity is very, very quickly spreading not just here, but across the country and across the world.

I was lucky enough to be able to be at the United Nations in 2016, testifying and telling the UN that they should change the war on drug policy from incarceration and retribution to medication and treatment. And while things move slowly through the political process, we see that that is taking hold in country, after country, that this war on drugs policy is changing dramatically to, as countries are able to see the medicine and science for themselves, it's very, very encouraging. How often do you get invited to speak at medical conferences that are not about THC or cannabis? In other words, how often is the Innociology Society saying, hey, come and give us a talk

on pain and the use of this because as physicians, we're seeing that our patients are using these things and we're ignorant. Right, sadly, not often enough. I do lecture to grand rounds for individual physicians and groups and Departments that have heard me speak or seen me on YouTube and said wait, we need to have her come in. I'm actually lecturing in Detroit next month to a group of actually lecturing in Detroit next month to a group of scientists and engineers and bio pharma developers who are interested in what we do. And so that's sort of a unique space, but I am actually hoping to target in California at the end of Q2 for 2020 that I'm going to speak with the Society of Pain. So I'm looking forward to that.

I have this might sound like a dumb question, but if you have a state like Colorado or California in which you have the same legal framework basically as Michigan, why can your product not ship from one state to another state? Because I have to leave Michigan and pass into another state before I get to Colorado. Even if I shipped next door to Illinois or Ohio for a micro second, it will be in federal land as it goes from state to state. It's called interstate commerce.

And there was a very classic law case on this 150 years or so ago, that defined what is interstate commerce and it's essentially just stepping over the border and sometimes even more than that, just being on a federal highway. What does the, if you had to guess, I know you don't have a crystal ball, but if you had to sort of think about what the legal framework is going to evolve into, do you believe that cannabis will always be illegal at the federal level, or do you think that it will have a change in legal status?

Oh, it's absolutely going to change. Absolutely going to change. No question about it. It's so clear how long do you think this could take? Well, we see that it is beginning. That is hemp right now is part of that story. It is the nose of the camel in the tent to be able to move this forward. At this point, we have more than half the states have said that these products are just fine for their patients, for their

population. And FDA is currently very, very actively involved in this. I was fortunate enough to be part of a task force that started some years ago. To be able to move this forward, FDA is struggling to find literally a legal pigeonhole to put this into my suggestion for any of the FDA officials who might be listening to this podcast, and I hope it's all of them, that there's the over-the-counter drug review that has been used for many, many years to be able to take products onto the shelves of drug stores, to be able to use this based on the fact that people could self-prescribe some medications for themselves. They didn't need a physician to write a script.

So we think that many of these products have sufficient safety that they are self-prescribable. And I think we see that because, frankly, there's about 30 million, 40 million people using these on a regular basis right now. And other than the vaping crisis, they're not filling up hospital wards due to toxicity from these products. They're able to use them.

Okay. So do you think that the Farm Bill is really the single most important thin end of the wedge because it was the first piece of federal law that decriminalized the first part of the value chain here? Yes. law that decriminalized the first part of the value chain here? Yes, absolutely. It really was. I think that that will continue actually for many of the cannabis business people who are struggling in this area because the tax

laws are incredibly burdensome and require a lot of dancing in order to be able to just simply run a business, but we see ourselves a year and a half ago, I had to switch bank accounts four times in one year. For if anyone ever tried having to switch your bank account where your bank suddenly closes out on you every three months. That's terrible, especially as you're just trying to run a business and pay bills. Now though, we have completely solid, reasonable banking relationships, we're able to get insurance, everything is becoming normalized. normalized and we do not see patients or consumers acting foolishly in any way, quite to the contrary, they often are reducing their amount of smoking of cigarettes and alcohol

use and are becoming more law-abiding citizens and less. What concerns, if any, do you have about what this industry looks like? I mean, I can't go more than a week without getting pitched some CBD THC hemp company. I mean, there must be more companies sprouting up some and some part of this value chain than than any other industry. I mean, this is from an investment standpoint, this is an area where people are very excited. I just don't imagine most of the people bring the expertise that your team is bringing, which is why I wanted to talk with you guys as

opposed to every other person out there who's peddling a cause. But do you see that as being a concern? In other words, can a few bad actors set the stage back? Yes, especially in the stigma area for patients. That's my major concern, is patient safety. You know, there are a lot of people out there that see a gold rush or green rush, and they just want to make products sell them to people and get out of Dodge and enrich themselves. And that's a concern to me. You know, when patients, unfortunately, are not understanding that just because you can buy something off the shelf

of a big box store or from an online source that it's tested and it's safe, because there's no guarantee to that. And so, you know, my recommendation, patients is if you live in a legal state, you should buy from a legal dispensary, ask for their certificate of analysis, take a look at it, make sure that there's no adulterance to the best of our knowledge and the science right now. This is why I'm happy to work with Steve because this is his passion as well, because we really don't want to hurt people. I mean, that's the thing that kills me. That's the reason why actually it should be descheduled.

I mean, so it'll allow for robust testing, a standardized testing. I mean, just because there's testing in states, doesn't mean they all use the same methods. That's sort of something you guys brought up today that was news to me, which was the inability of the states to rise to the level of federal testing. And so in many ways, the decriminalization state by state is not a great approach. You can't just run that out to its natural conclusion without decriminalizing it at the federal level to get the full muscle of the FDA and the protocols behind testing. Absolutely. I mean, from laboratory to laboratory, there are no standards. And the problem is there's no guidance because it's been illegal.

And so the sources that laboratories would use to go to to say, well, where do we get our standards from? And what are the methods of extracting from this gummy bear or this brownie in order to test the potency or test the microbials or to test any of it? Don't exist. So look, there are people listening to this in 49 states that are not Michigan, not to mention people that are listening to this outside of this country. What would be your playbook for them to protect themselves as they go into their local dispensary or purchase online, you know, you can buy CBD across state lines if it's pure enough? How would you give people a sort of instruction list of things to do, to first inform us, protect themselves? Right, so this is a human rights issue. You'll

hit that now on the head. I mean, that's a huge problem. For me, as a physician, to guide patients, which I do, I guide over 400 patients privately, free of charge, because I'm a terrible business person. But for me to guide them and have to understand their state in order to help them access certain medicines is just horrific to me. But what I would say to them is, good will equal state, become certified as a patient, meet with a physician there, and get the guidance from that and buy from a legal dispensary. Do you think that's enough? So, I mean, a physician in another state, do they have the expertise to help them navigate

through the dispensary? There are a society called Society of Cannabis Clinicians where they have a list of doctors by state who actually are, you know, experts in cannabinoid medicine for which they can go seek out and help themselves. I mean, this is a nascent industry. It's still federally illegal, which allows for all of these hoops to have to be jumped through. I would recommend not buying

online. I would recommend not buying off the street. I mean, we tell our children, don't take candy from strangers because you don't know what it is. Why would our medicine be any different? So I don't know that it's widely known, but I developed the actual assay methods to detect LSD, marijuana, cocaine, and fetamines, and I published those results when I was 21 and 22 years old. So I really have a pretty solid sense

of what these laboratories are able to do. That was, well, almost 50 years or or so ago and it was my first scientific publications The labs are capable nowadays because I just recently set one up a few years ago of doing remarkably accurate and precise work on all of these cannabinoid products and to be able to do it. But the state rules vary and the states are still learning. What should the pesticides be that are allowed or allowable? What are the levels of heavy metals, etc. So from state to state,

the rules vary and they are getting more learned as the work is done. So this is a great developing field. Some labs are better than others to be able to do it. So that's why is to echo Deb's recommendation for people who want to utilize these products, they really need to ask for the certificate of analysis, see if they can become educated enough to be able to do that. Certainly physicians should. I know that these systems and the cannabinoid systems were not taught in medical schools. They certainly weren't taught in the chemistry schools that I went to. And this is a remarkable societal experience in allowing non-toxic substances to be used and self-prescribed. I think it's a challenge for the physicians to catch up because you are alerted intermediary to help patients be able to do this. And I hope out of this podcast, that's why we're here,

is to help encourage all of these educational programs, because frankly our hands are full enough just running the clinical trials and being able to run a business. So we're going to have to leave that part of it up to you. Well, I'm not, guys, I want to thank you very much for coming down here today and for making time and for sharing kind of all your insights. And for the work you're doing, I'm not, guys. I want to thank you very much for coming down here today and for making time and for sharing kind of all your insights. And for the work you're doing, I mean, I think this is, I don't know, I've got to be honest

with you. I think I'm still somewhat confused about all of the different permutations and combinations of these molecules. And it's complicated by the fact that interstate commerce prevents easy access of higher quality products to individuals. So, I guess the thing we can all hope for is that, and I guess I would say this, frankly, even if you are still undecided on the safety or efficacy of these, everyone still seems to benefit from the decriminalization of this because it allows far more rigorous testing and it destigmatizes so much of the research funding that goes into this

that I think one way or the other we get answers quicker and that's probably what we're kind of missing at the moment. Right. This is a process that's unfolding in a very, very short length of time. I was at a meeting with FDA, DEA, and Department of Defense just four and a half years ago, and NIH, where I brought up the idea, hey, fellas, you're the federal regulators, and it looks like cannabis is going to get approved state-by-state. Why don't we try and set some federal health policies here around that? And just four and a half years ago, everyone in the room except me said, are you kidding? That's never going to happen. And now we see it actually has. And so the people who are in a role to be able to bring these forces

to bear are trying to play catch up and do it and more power to them. And I think that everyone should just try and continue to do just as you are doing here, allow folks like us to bring our thoughts to bear and happy to hear from anybody. We're not certain we have all the best right answers. We have a particular predilection towards medicine and the idea that above all else do no harm. First, we're kind of pushing about it though. Thanks very much guys. I really appreciate it. Thanks for having us. Thank you. We're kind of pushing about it though. Thanks very much guys, I really appreciate it. Thanks for having us.

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