The Peter Attia Drive - #81 - Debra Kimless, M.D. & Steve Goldner, J.D.： Cannabis

00:00:00.000 Hey everyone, welcome to the Peter Atiyah drive. I'm your host, Peter Atiyah. The drive

00:00:10.880 is a result of my hunger for optimizing performance, health, longevity, critical thinking, along

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00:00:33.000 and other topics at peteratiyahmd.com. Hey everybody, welcome to this week's episode

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00:04:05.320 find value in the content I produce, please consider supporting us directly by signing up for a

00:04:11.020 monthly subscription. My guests this week are Dr. Deborah Kimlis and Steve Goldner. I'm not going to

00:04:15.700 say much about them by way of background because I opened the interview by asking them to introduce

00:04:20.440 themselves because their backgrounds are so relevant to the discussion we have. I sought out both Deb and

00:04:27.040 Steve because I wanted to have a discussion that would frankly first inform me, but obviously provide

00:04:33.220 the necessary and relevant background information to all of you as listeners on a topic that frankly it confuses

00:04:38.860 me to no end, which is the entire morass of THC, CBD, hemp, cannabis, that whole landscape. And truthfully,

00:04:48.860 I've never fully been able to understand this in part because I think it's just very confusing in part perhaps

00:04:54.780 because I haven't put enough effort into it. But you know, preparing for this podcast was a great exercise in

00:04:59.640 doing just that. In this episode, we talk about a lot of things, but we start frankly with some of the

00:05:04.660 semantics. You know, what is the difference between THC, CBD? Where do these things work? How do they

00:05:10.360 work in the body? What's the difference between what it's doing in the brain and what it's doing

00:05:13.740 elsewhere? And how do molecules work that aren't neat and clean like designer drugs where one molecule

00:05:21.020 hits one receptor? As you'll see, cannabis, it works very different from that. We also then get into some of

00:05:26.620 the safety issues. At the time of this recording, which was in late October 2019, there is obviously

00:05:32.980 an epidemic or at least a perceived epidemic around the dangers of vaping. We touch on some of the

00:05:38.040 reasons why that may be the case, but really for the past three years, we have been witnessing both

00:05:43.540 a market evolution, a scientific evolution, and certainly a policy evolution, which may be the most

00:05:50.000 important as it pertains to this subject matter. And again, I think as you'll see in the first few

00:05:54.820 minutes, Deb and Steve are really great people to have this discussion with because collectively

00:06:00.900 between them, you have a medical, a pharmacological, and a regulatory expertise that is brought to bear.

00:06:08.320 Now, it's worth pointing out that both Steve and Debra are involved in a company. Steve is the founder

00:06:13.320 and CEO of Pure Green, and Deb is the chief medical officer. And I point that out to say everything must be

00:06:20.220 interpreted with a grain of salt. And obviously, Steve and Deb have a commercial interest in this

00:06:24.920 space. Now, I will tell you that after spending two hours with them, or slightly more than two hours

00:06:30.000 during this podcast, also spending another hour with them off mic, getting into stuff that we just

00:06:34.560 weren't comfortable talking about on mic, I come away thinking very highly of them, very highly of their

00:06:39.120 work, and believing that their intentions here go far beyond just the commercial intentions of people

00:06:45.300 involved in this space. This is a confusing topic, and I won't represent that this one podcast is going

00:06:51.200 to answer every possible question you have. The good news is it might not matter if it did, because

00:06:56.840 frankly, this is an area that is evolving so much. And I suspect this is a topic that I will need to go

00:07:01.760 back to probably a year from now. So without further delay, please enjoy my conversation with Steve

00:07:07.900 Goldner and Deborah Kimlis. Deborah, Steve, thank you so much for making time to come and talk about

00:07:16.440 this stuff today. This is kind of an unusual podcast in that we weren't introduced through anybody. I sort

00:07:22.000 of organically reached out to you guys on the basis of so much demand and so many questions about this

00:07:28.220 topic, which is something, you know, as I've alluded to, I'm completely ignorant of. So this is a topic I've

00:07:35.560 been really looking forward to learning about, because patients ask me about it constantly.

00:07:40.700 I think the implications are only becoming more significant as we watch the evolution of the legal

00:07:45.920 environment. So having a physician and a lawyer to talk about this is perfect. Deb, can you give me a

00:07:53.140 bit of background on your interest in this? You're an anesthesiologist. I know you specialize in pain.

00:07:57.780 Tell me what drew you to this specifically. So what drew me to this is that my mom was dying from

00:08:03.900 a complication from a pharmaceutical drug. And because of that, I started really thinking about

00:08:10.380 what we learned in medical school, how we were trained, and what else could there have been for

00:08:15.240 my mom as an option other than a pharmaceutical. And as she lay dying, my significant other who's an

00:08:23.700 Israeli said, you know, they're studying medical cannabis in Israel. And unfortunately, my mom didn't

00:08:29.660 have an opportunity to try medical cannabis as a pain reliever because she died. But I spent really

00:08:34.960 since 2013 until now, studying and investigating the veracity of whether or not cannabis truly is

00:08:43.760 a medicinal molecules. Steve, how did you guys meet and how did you get involved in this?

00:08:49.500 Well, I've been involved in pharmaceutical formulations as a scientist for almost 50 years now.

00:08:55.980 As a forensic toxicologist at the New York Medical Examiner, I worked on 18,000 autopsies.

00:09:02.280 So I developed and formulated the drug, liquid drug methadone about 47 years ago because friends

00:09:10.000 of mine were coming back addicted from the Vietnam War. So that worked out pretty well. I developed that

00:09:17.780 formulation. Methadone's done very well of helping people around the world. And I went on to become a

00:09:23.840 FDA attorney working in the pharmaceutical industry, but always working in this arena. I became interested

00:09:29.860 in cannabis as a medicine almost 45 years ago. A friend of mine came back from the Vietnam War

00:09:38.000 with PTSD. And he asked me to develop a drug that would help cure him of that. And I noticed that when

00:09:46.420 he smoked marijuana, he felt much better when he drank or got pills from the VA, he did not.

00:09:53.700 And so I realized that cannabis could be a medicine, but it just wasn't legal at the time. And I wasn't

00:09:59.300 that right kind of lawyer to get that legalized. Now I have that opportunity to be able to do it.

00:10:05.360 That's what brought me into it. He also, my buddy who's passed away of cirrhosis of the liver about seven

00:10:11.580 years ago, made me vow to do this. So developing methadone at the beginning of my career was a

00:10:19.320 first bookend. And now developing all these formulations to help people with cannabis is

00:10:25.820 the second bookend on my career. And how did the two of you meet?

00:10:31.120 So I lecture around the country and around the world, and I present studies that I have done on my

00:10:37.180 own. These are case studies. I treat over 400 patients free of charge, a bad business model.

00:10:42.720 But what I've learned from these patients is tremendous using diet-changing cannabinoid

00:10:47.620 medicines. And I share them with colleagues so that they too can understand cannabis is a medicine.

00:10:54.180 And Steve and I met two years ago in Cologne, Germany, I think it was, at IACM, where I was presenting

00:11:01.540 a poster and he tracked me down and we had our first conversation there.

00:11:06.240 And together, you guys are part of a company. We'll probably hear a little bit about that company

00:11:10.880 today. But the aim of this company, I assume, is to create sort of what you perceive to be the

00:11:17.580 safest, most efficacious form of delivery of cannabis. Is that a fair assessment?

00:11:23.000 Yes, that's exactly it.

00:11:24.800 I think to understand why you guys do what you do, we have to understand a whole bunch of things that I

00:11:30.780 don't understand right now. So let's just start with some history. How long has cannabis been

00:11:36.220 consumed by humans to the best of our knowledge?

00:11:39.500 Historically, it's been used as a medicine for over 5,000 years. I mean, this is crazy. It's new

00:11:45.500 for us now, but it's not a new medication. In Asia, the king fancied himself a pharmacist and he was

00:11:52.800 treating people for all sorts of disorders from gout to absent memory, believe it or not, even though

00:11:59.800 people are like, dude, where's my car? Here he was, you know, helping people with memory loss with it.

00:12:05.140 You know, the ancient Greeks used it topically on their horses, which is why I do know that the acid

00:12:12.600 forms of the cannabis medicine actually work because they love their war horses. They applied

00:12:19.720 the cannabis leaves to the horse's bodies to reduce the swelling, inflammation, and infection after a war

00:12:27.580 or a battle. Historically, when did it sort of fall out of favor, back in favor, et cetera? I mean,

00:12:34.160 for most people, when they think about marijuana, they sort of think of the 60s and 70s as this era

00:12:39.500 in which the public sort of got to know it and it became then sort of demonized. When was it actually

00:12:45.200 scheduled, Steve? I think that was the beginning of around 1930 or so. That is, there were a number of

00:12:54.020 individuals who thought that this was just a completely inappropriate drug to be allowed out, a

00:13:01.740 recreational drug, and there was a lot of movement towards controlling people's appetites in many ways,

00:13:09.880 including drinking alcohol that have floated in and out through America and across the world.

00:13:15.460 So it began then with an idea of prohibition, and it was really given a much more emphatic push

00:13:24.900 under the Nixon administration for, it's often said, for their own political purposes of being able to

00:13:33.940 disenfranchise people who would utilize marijuana, young people or people of color. And that became

00:13:43.240 essentially the war on drugs policy that was promulgated through the United Nations and around

00:13:49.440 the world because the United States often was the funder of those activities. That's continued for

00:13:56.360 quite some time, but is now, as everyone knows, dramatically, dramatically changing.

00:14:01.940 Now, unlike the sort of psychedelics, which were actually scheduled only about 50 years ago,

00:14:07.800 you're saying marijuana was scheduled in the 30s. I mean, this is before the FDA?

00:14:11.400 Well, FDA has been around for at least that long, and the originally scheduling of this

00:14:18.500 was under DEA as a narcotic drug, and therefore it would not be allowed. And DEA really had much more

00:14:28.220 of a law enforcement orientation. While FDA does have a staff of essentially policemen working with

00:14:35.340 them, they're not organized in that manner. So they're much more organized towards what is a

00:14:40.460 medicine, what's a food, and how to be able to keep our American health policies the best possible for

00:14:47.480 people. You talked a moment ago, Deb, about topically applying this. How did people do that?

00:14:54.260 Was that an oil? And what was it? I mean, not that you were there at the time, and we could go back and

00:14:58.160 figure it out. But to the best of our understanding, what is it that was being applied to, for example,

00:15:02.420 a horse? Or how was it being used medicinally 5,000 years ago?

00:15:05.300 It varied depending upon the indication and what they wanted to do. But the horse example was they

00:15:10.680 were actually applying leaves to these horses, the actual fan leaves or regular leaves. There are

00:15:18.520 small amounts of trichomes on those leaves with cannabinoids in them. So of course it would work.

00:15:25.980 It was really interesting. In India, they would mix it with heat and milk and make something called

00:15:31.840 bong, B-H-A-N-G, and they would drink it as an anesthetic for people. So it really did vary.

00:15:41.360 It was very interesting that people apply these things in different ways.

00:15:45.520 So today when people think about marijuana, the thing they probably have in the back of their mind

00:15:51.860 is more related to the properties of THC. Is that correct?

00:15:55.080 Yeah. I think that most people, when they think of cannabis, think about it as THC, intoxication,

00:16:02.080 and smoking.

00:16:03.540 So let's talk a little bit about that. So you've used the funny reference of dude,

00:16:08.060 where's my car? So Jeff Spicoli falling out of the van, big plume of smoke coming out after him.

00:16:15.380 He is taking a leaf. He is smoking that leaf. I mean, he's broken pieces of it rolled up into a joint

00:16:22.560 and being smoked.

00:16:23.620 Right. So cannabis as a plant is very interesting, right? So when it grows in nature,

00:16:27.540 it grows as a flower. The leaf does have some cannabinoids in it or some of those medicines in

00:16:34.120 it, but really the most bang for your buck, it comes from the flower where that's what it is. So

00:16:39.260 Spicoli was probably buying off the street and maybe he's getting some leaf, but he's hoping for

00:16:44.080 some flower because that's where the majority of the medicine is. And drying it out and rolling it up

00:16:50.680 and then combusting it. The interesting thing is you can eat the cannabis plant all day long.

00:16:55.540 You may get a bellyache from all the fiber, but you won't get that intoxicating feeling

00:17:00.960 because it's chemical constituents are not in a way that can get you intoxicated.

00:17:07.140 I see. Okay. So let's talk about how that intoxication works. What does THC stand for?

00:17:13.420 Tetrahydrocannabinol.

00:17:13.940 And what does it do in the brain?

00:17:16.880 So our brains have these sort of docking stations called receptors and chemicals act on different

00:17:24.060 docking stations or receptors in order to affect a change. So THC works on these docking stations in

00:17:31.780 our brain and our peripheral nervous system known as CB1 receptor, cannabinoid one receptor. Wasn't

00:17:38.000 very interesting name for it, but that's what they call it. And there are also cannabinoid two

00:17:42.400 receptors or CB2 receptors were found peripherally predominantly on immune cells, but also on other

00:17:47.540 tissue as well and in other organs. And so THC has this really unique ability to activate or sit on

00:17:54.660 these CB1 and CB2 receptors.

00:17:57.660 And did you say both CB1 and 2 are peripheral?

00:18:00.600 They can be. CB2 predominantly is peripheral. CB1 is predominantly in the brain and then other nerves,

00:18:07.640 so the peripheral nervous system.

00:18:08.840 And what is the next chain of events? So once THC binds to these receptors, what happens inside the

00:18:16.120 cells?

00:18:17.400 Oh gosh. So depending upon where in those receptors are located will determine what happens. So for

00:18:24.940 example, if it's in the hippocampus, it may stimulate areas in that area that will help you

00:18:32.320 extinguish memory. So for people with PTSD who cannot stop thinking about certain things,

00:18:39.600 that area of the brain extinguishes memory and help somebody with PTSD maybe to get some sleep.

00:18:46.960 How do you think it acts with respect to pain?

00:18:49.420 It's a multimodal different way of doing it. So centrally it does interfere with periaqueductal

00:18:56.000 gray areas. These are areas of the brain that conduct pain signaling where a brain actually

00:19:01.780 understands this also works perfectly on immune cells to decrease inflammation and reduce cytokine

00:19:08.960 expression. So it works in a whole host of different ways. We're used to thinking in medicine actually

00:19:14.740 as an allopath of a single molecule, single target. But what you really learn is that that's a great

00:19:22.120 way of understanding how a drug could work, but that's not how it works in a biologic system

00:19:27.700 known as a person or an animal.

00:19:29.920 And so contrasting this with what you talked about with respect to your mom's care, for example,

00:19:34.380 she was probably being prescribed opiates, I'm assuming?

00:19:37.380 So my mom actually died from fracturing to death from a pharmaceutical known as a bisphosphonate

00:19:42.480 from Fosamax. The weird thing about my mom is that she was one of the 20 to 30% of people who,

00:19:49.140 when they took opiates, had an enhanced response to pain, not a decreased response to pain. So basically

00:19:56.120 she was, you know, using acetaminophen and non-steroidals to try to reduce her pain, which

00:20:01.780 when she spontaneously blew out her pelvis, you know, didn't really help that much. So we were

00:20:08.380 just hoping that since medical cannabis works in different methods for pain relief, it could have

00:20:14.920 been an option for her. Wouldn't have cured her, but could have helped her.

00:20:19.120 Now, one of the other effects of inhaling marijuana for many people seems to be an increase in appetite.

00:20:25.600 Do we have a sense of why that's the case? And that's, I remember certainly in medical school,

00:20:29.280 that was even something that we talked about a lot was patients that had, you know, wasting

00:20:33.020 syndromes either with cancer or AIDS. This would be a great way to help them eat.

00:20:37.440 Exactly. So there are areas of the brain that control appetite and nausea and vomiting as well

00:20:42.560 in the area in the medulla. And those areas is replete with CB1 receptors. So when those areas

00:20:49.300 are stimulated, your appetite is stimulated and you actually have a desire to eat, which you're right,

00:20:55.280 is life-saving for somebody who has wasting syndrome or who has chemotherapy-induced nausea

00:21:02.900 and vomiting. There's this other thing that now people talk about a lot called CBD. I probably hadn't

00:21:08.280 even heard of this until maybe four or five years ago. I mean, Steve, how long has CBD been understood

00:21:14.280 as a distinct part of this equation? So this is a truly revolutionary new molecule to come out into

00:21:24.100 the public consciousness so quickly. It's always been in the plant and available to use, but it's

00:21:31.940 because people were so entranced with the idea of let's get stoned or then let's do some science on

00:21:41.200 this stoning aspect of THC that that drew most of the attention. It's just really in the last two or

00:21:50.600 three years that CBD, because of its non-hallucinogenic effects, has become interesting to people because it

00:21:59.160 appears to have, it does have so many medicinal applications and at the same time, it doesn't

00:22:05.580 get a person stoned. How is that possible? What is it doing chemically to create that distinction?

00:22:11.660 So different than THC, CBD does not sit directly on CB1 receptors or CB2 receptors, but works either

00:22:21.420 indirectly activating the endocannabinoid system or it works on completely different receptors.

00:22:27.500 And so together it has a synergistic effect with THC or all the other molecules that live in the

00:22:34.840 cannabis plant or by itself is pretty effective as a medicine.

00:22:40.100 Now in nature, do they come lockstep one in one for every molecule of THC is one CBD coming with it,

00:22:47.620 or how does that work?

00:22:48.780 So in nature, it doesn't exist at all, right? It isn't until you apply time and temperature

00:22:53.260 and get rid of that acid form, that carboxyl group on either THC or CBD or any of the other

00:23:00.200 cannabinoids. So that's kind of interesting as a baseline anyway. But CBD, there are cultivars or

00:23:07.540 plant strains as known in the street, can grow in higher concentrations in certain cultivars.

00:23:13.480 It can occur as a one-to-one, one molecule to one molecule. It depends upon the strain that you're

00:23:18.520 growing. The legal definition of hemp is something that's higher in CBD-A and less than 0.3% THC.

00:23:29.120 I'm glad you brought that up. Tell us a little bit more about the difference between

00:23:32.280 hemp and cannabis specifically, and again, using the CBD-THC delineation.

00:23:37.300 So the legal definition is for a hemp cultivar is to have less than 0.3% by weight of THC or THCA,

00:23:47.660 actually, compared to the rest of the biomass or the rest of the molecules in the plant.

00:23:52.800 Technically, that would make anything hemp that doesn't have THC in it, right?

00:23:56.300 Exactly. So people use cannabis plants and just crossbreed so that THC is less than 0.3%

00:24:05.540 so that they can grow it. But the term of industrial hemp back in the day when our constitution was

00:24:13.300 written and sales were being made out of hemp, it's a totally different plant as it is today,

00:24:19.120 just because of crossbreeding and farming the way we're doing it.

00:24:24.340 Steve, the Farm Bill brought this to the forefront recently. Tell us about the Farm Bill and why that's

00:24:30.520 relevant. I want to come back to this, but just while we're on the topic of hemp, it's important,

00:24:34.240 I think, for people to understand this distinction. The Congress decided, pushed forward by several

00:24:40.080 legislators who had large numbers of farmers, that this would be a really good cash crop for them.

00:24:47.600 When you think of it, these products are selling for thousands of dollars a pound compared to 50

00:24:54.040 cents or a dollar a pound for lettuce or tomatoes. So if you're a farmer, you'd much rather grow

00:24:59.860 something that you can get thousands of dollars for. The idea was put forward that this should be

00:25:07.060 something that's allowed now. We can see across America that people really are interested in it,

00:25:13.460 that medicine can be developed from it. So it was with this idea that a number of legislators,

00:25:20.540 particularly Senator McConnell, had a number of farmers in his jurisdiction, wanted to be able to help them

00:25:29.140 in their businesses and in their personal lives to be able to develop this. Otherwise, these products

00:25:36.640 are imported from overseas, and we'd like the American population to be able to have a good,

00:25:43.160 well-regulated source of product here. I think that was the entire idea behind it,

00:25:48.720 was that we would bring the U.S. Department of Agriculture, as well as other scientific bodies like

00:25:54.680 FDA, to be able to begin to study these products and help the growers. All of the growers that have

00:26:02.240 worked on cannabis hemp products have had to do this for generations without having someone like

00:26:09.660 the USDA around to tell them what pesticides were appropriate to use, how to grow it, how to have good

00:26:16.720 growing conditions for it. So this has really helped, I think, to be able to advance it.

00:26:22.260 Was the Farm Bill basically just an economic package that made it more attractive, or was there some

00:26:29.320 legalization that was previously not there? The Farm Bill really provided legal cover

00:26:35.920 for farmers to be able to grow the hemp and then to be able, for processors, then to be able to

00:26:45.280 process it into oil and be able to turn it on into other products. So it started out as something to

00:26:54.080 just aid farmers, but now it is moving through the economic distribution chain. And that's why we can

00:27:01.920 see it now in nearly every drug store or big box store as finished goods on the shelf.

00:27:09.240 What are some of the products that come from the hemp plant?

00:27:12.980 There are vape cartridges, certainly, although they're not at the moment, not all that perhaps

00:27:19.500 professionally done, except by those who are licensed to be able to do it. There's a very large

00:27:24.980 gray or black market in it, but there are lotions, creams, ointments. You can find CBD products

00:27:34.200 in ice cream and tea. Soon it'll be in coffee and nearly every other consumer product that's available.

00:27:44.060 Is the idea that there are certain hemp products that do not contain CBD and certain hemp products

00:27:49.120 that do? Or is the implication that all hemp products are containing CBD?

00:27:54.940 So I think what you're asking is about the industrial uses of hemp beyond the cannabinoid.

00:27:59.580 And so you can put that flower into seed and make hemp seeds from it, which has a wonderful

00:28:05.600 profile of omega-3 to omega-6, probably better than anything, and a wonderful source of protein

00:28:10.900 as well. The fiber that it comes from, hemp fire, has a tensile strength of steel or greater than

00:28:17.220 steel. Where you see plastic goods, you can actually substitute for hemp. It's just really

00:28:23.720 expensive machinery for now until they figure it out.

00:28:27.560 And it displaces the petroleum in plastic? Or what is it displacing?

00:28:30.740 Yes, it displaces the petroleum in plastic. So you can make a credit card out of hemp fiber.

00:28:35.580 You can make hempcrete. So instead of concrete, you can actually use it, make it to make it concrete.

00:28:41.240 You can, there are BMWs right now that are using parts of their door panels and dashboards using hemp.

00:28:49.120 You can make cloth. You can make clothing. You can make sailor's sails.

00:28:53.760 Do you have a sense of, you take all of the biomass that's being produced in the United States from a

00:28:58.300 hemp crop today, how much of it is being used for all of these industrial uses and how much is being

00:29:03.480 used just for CBD? I assume the latter is a tiny fraction of it?

00:29:08.120 Oh no, I think CBD is the lion's share of it because that's where the money is right now.

00:29:14.160 You know, the decortication machine, the machine that is required to break down the stock, which is

00:29:19.260 incredibly fibrous and tough, is very expensive right now. But, and I think that, you know, there's

00:29:25.120 such a huge interest, at least in the United, well, everywhere, but especially in the United States

00:29:30.580 for CBD as a potential medicine or tonic, that's where the money is. So it's a lot easier to extract

00:29:37.800 and make derivative products than it is to create a lot of these other iterations that I just described

00:29:43.680 as an industrial use.

00:29:45.800 But let me just interject that some of these other uses are just remarkable and have been around for

00:29:51.460 a long time. Henry Ford personally was very proud of having developed a hemp mobile. And he actually

00:29:59.860 built, had built a car that ran and its fuel was fueled by hemp oil. So the entire car in the 1930s

00:30:10.160 could have been put out on the road and they had to shelve that project because suddenly hemp was

00:30:17.260 illegal because it was, came from the marijuana, marijuana plants. When did CBD become federally legal?

00:30:26.760 I assume it is federally legal today or is it still state regulated?

00:30:30.520 Well, it certainly is state regulated and each state has its own regulations. The federal

00:30:36.940 regulation of it is continuing to unfold. The farm bill has legalized hemp itself. It has not directly

00:30:49.520 said that CBD is okay to put into products. Rather, there's been an intense push on the Food and Drug

00:31:00.000 Administration whose responsibility it is to regulate those kind of consumer products that they should

00:31:07.820 move expeditiously. And actually, Deb testified before FDA about five months or so ago on the safety

00:31:17.340 and effectiveness of CBD to help them in their data gathering.

00:31:23.180 So when you spoke to the FDA, Deb, what were the main points you tried to get across?

00:31:27.380 The main points that we discussed was about a clinical trial that we ran using a water-soluble

00:31:34.100 iteration of CBD for mild to moderate pain in a 16-patient cohort and the results of it. And I wanted

00:31:43.660 to share that with safety, efficacy, and our results.

00:31:47.820 Let's talk a little bit about that. So you said 16 patients that had mild to moderate pain,

00:31:52.540 meaning what was the etiology of their pain?

00:31:54.740 So it was multifactorial. I didn't just stratify to one condition because I just wanted to see. It

00:32:01.040 was a proof of concept trial. And I actually didn't think it was going to work. Steve was kind enough

00:32:06.480 to let me formulate an ultra-low dose, five milligrams of CBD with some curated terpenes

00:32:11.800 in a water-soluble tablet. I gave it to 16 patients who had mild to moderate pain for which

00:32:19.060 they were treating their pain with an over-the-counter medication. And we ran this trial for two weeks,

00:32:26.700 and we had statistically significant decrease in pain across all 16 patients.

00:32:35.200 How do you control for the placebo effect there? Was there a control in that study?

00:32:39.380 There was not. Again, it was a proof of concept study to see if this ultra-low dose of CBD would

00:32:45.060 even work, and it did. There's no control for placebo, really for anything. I mean, I know lots of patients,

00:32:51.760 I'm sure you do as well, that seem to really respond to a whole host of medicines, whether

00:32:56.560 it comes from a double-blind randomized trial or not.

00:33:00.600 How does CBD, in your mind, differ from THC? We know, obviously, how it does from an intoxication

00:33:07.820 standpoint. How do you think it differs in the remainder of the profile?

00:33:12.500 It works in different mechanisms of action. So for example, CBD doesn't sit on a CB1 receptor,

00:33:20.520 but what it does is it interacts with the breakdown products of our naturally occurring

00:33:27.060 endocannabinoids, which does sit on a CB1 receptor. So by enhancing that, that's one pain-relieving

00:33:34.480 mechanism of action. You know, it interacts with dopamine, norepinephrine, epinephrine-type

00:33:42.520 receptors, and enhances those chemicals as well. So it works in a multimodal way, just like all of our

00:33:50.040 other medications. I'm trying to, in my mind, wrap this idea around a Venn diagram of THC and CBD,

00:33:56.940 where does that make sense, where you have certain things that they both do, and then things that are

00:34:02.840 unique to each of them. Does that make sense to think of it that way?

00:34:05.960 It does and it doesn't. So I understand, as an allopath physician, that that's how we like to look

00:34:12.080 at things. That's a very reductionist view of it. And I think it's, this is really botanical medicine.

00:34:19.320 We really have a lot of different constituents within it. There's over a hundred different

00:34:24.060 cannabinoids, over 80 plus terpenes, flavonoids, and probably constituents we're not smart enough yet

00:34:30.800 to even have figured out.

00:34:32.800 What do the terpenes do?

00:34:33.760 Terpenes occur in nature, in all kinds of plants and foods that are giving the taste and the scent

00:34:42.960 to all kinds of things. And they're anti-inflammatory. They're actually secondary

00:34:47.800 metabolites like the cannabinoids as well. And it's used for the plant, not for our benefit,

00:34:53.340 but for its benefit as a natural pesticide, a antioxidant. And it works that way in our bodies

00:35:00.460 as well. I want to come back to sort of the THC side of the equation. Let's start talking about

00:35:07.400 some of the health risks and or benefits. And let's start with the risks. What do you think are

00:35:12.580 the most important risks to understand from THC use?

00:35:17.180 So I think everybody is different. We're all an N of one and we all respond differently to the same

00:35:23.700 type of thing. So if I give one person an aspirin, their headache may go away. Somebody else may die of,

00:35:29.560 you know, an allergic reaction to it. In some people who are very sensitive to THC,

00:35:35.400 they may not just feel intoxicated, but they may feel so much anxiety and panic that they are

00:35:42.500 incredibly uncomfortable. And some is dose dependent, but some experience that even with

00:35:48.460 a small amount. Some people experience a feeling of wellbeing with a little bit of THC. Some people

00:35:54.740 have a rapid heartbeat and their blood pressure shoots up and have an uncomfortable experience.

00:36:00.660 How much of that do we think is setting dependent? So if you took the same person,

00:36:05.320 administered the exact same dose by the same route, but under different settings, either the actual

00:36:11.240 physical setting they're in or the emotional state they're in, how much can that impact the response?

00:36:15.820 I think anytime you're dealing with something that plays around with neurochemistry, set and setting

00:36:21.760 is always a huge important thing. You know, same thing with alcohol.

00:36:26.020 I think there's one part of this is while we're talking about the safety or potential adverse events

00:36:31.440 from this that we should also address. In my experience, this has the lowest toxicity potential

00:36:40.120 of any pharmaceutical, nearly of almost any product I've ever seen. That is in the course of history,

00:36:48.180 we really do not have any deaths or truly serious events that are attributed to THC or CBD at all.

00:37:00.120 It is so less toxic than what are common over-the-counter drugs, aspirin, Tylenol, et cetera.

00:37:08.820 And certainly far and away compared to alcohol, which is truly toxic.

00:37:15.240 What is the reported LD50 of THC?

00:37:19.040 So there really isn't, and you cannot dose.

00:37:22.080 I guess maybe explain to people what LD50 is.

00:37:24.100 Okay, so LD50 is the lethal dose that it takes in order to kill off 50% of a population,

00:37:34.100 usually in mice or rats. With THC and CBD and all of these cannabinoids, it has never been possible

00:37:45.120 to dose them with enough to be able to do it so that there is just a simple cutoff generally that

00:37:54.060 it's something more than five grams per kilogram. So that's a tremendous, absolutely tremendous amount

00:38:02.560 of cannabis to be able to take on.

00:38:05.620 In the 70s, an attorney for the DEA actually was writing in support of de-scheduling cannabis,

00:38:14.240 said that the lethal dose 50, it would take a 75 kilogram man to smoke 1,500 pounds of cannabis

00:38:22.640 flour in 15 minutes in order to die. And he wouldn't die from a cardiorespiratory effect from cannabis.

00:38:30.340 It would be from probably carbon monoxide poisoning.

00:38:33.080 Did Willie Nelson try this?

00:38:34.200 I think so.

00:38:34.980 Okay, but he wasn't able to do it.

00:38:36.380 He's still alive, right?

00:38:37.500 He's still alive, yeah.

00:38:38.060 So it's interesting what Steve was saying is that the receptors, those docking stations,

00:38:42.860 there are no CB1 receptors, or very few, in the cardiorespiratory centers of our brain,

00:38:48.740 different than the opioid receptors, the mu receptors, where you overdose because that docking

00:38:54.740 station gets activated by heroin or Percocet or OxyContin and you slow down your respirations and

00:39:01.460 you stop breathing and your heart slows down and your heart stops beating and you die. That doesn't

00:39:07.220 happen with cannabinoids because those receptors don't exist in those areas of the brain where that

00:39:13.840 would happen. And so literally to this day, you can over consume cannabis and you may feel like

00:39:21.220 you want to die with this incredible anxiety or psychotic event, but you're not going to.

00:39:28.060 So it's sort of like LSD in that sense where it really doesn't have a known upper limit of

00:39:33.340 toxicity from a pure cardiorespiratory standpoint. By comparison, Steve, you worked in the medical

00:39:39.920 examiner's office for so many years. What's the LD50 of ethanol?

00:39:43.800 That's a great question and I can't remember the answer right offhand. However, I do remember

00:39:49.600 that the level at which people are intoxicated by this, and generally we all know to be one or two

00:39:59.140 shots of alcohol or wine or beer, and that it very quickly becomes a disorienting drug with just a

00:40:09.220 second one. Particularly the problem is that people don't think they're disoriented by it and that they

00:40:15.500 are actually under control. It's a very different situation with cannabis. Usually as people take

00:40:23.160 on these substances within their body, they actually know that they're stoned and have a sense of it and

00:40:32.920 are able to be able to rectify their own behavior. Usually it's called just sit on the couch and watch TV

00:40:40.120 or something like that. Yeah, there's another point here I think on the toxicity that probably is worth

00:40:44.780 mentioning, and you could probably speak to this with more accuracy, but it's sort of how I explain

00:40:48.420 toxicity to people. It's not just what the LD50 is, it's how far the LD50 is from the use dose.

00:40:55.700 Consider acetaminophen. You'll very easily go and take a thousand milligrams of acetaminophen.

00:41:01.860 I don't know what the LD50 is. It's probably between 10 and 20 grams.

00:41:05.500 That's not that far away. That you could be, that you could only miss the dose by 10X and kill someone

00:41:13.100 is amazing. I'll tell you a ridiculous story. This is, I don't know why I'm getting it, but it's just

00:41:18.740 an illustrate this point. I remember in residency once during our internship, a guy accidentally wrote

00:41:25.040 a prescription for one gram of Ativan instead of one milligram of Ativan. So he wrote for a thousand

00:41:31.700 times more of the dose, which is a clerical error that came from his just being careless. Unfortunately,

00:41:38.820 the nurse working that day was very new and she took the order as one gram of Ativan. And to make

00:41:48.060 matters worse, the pharmacist on call that day was also new and realized in the Pixis system,

00:41:54.980 there's only, we only have 20 milligrams here. So that's, you know, 21 thousandths of what you've

00:42:01.540 ordered. I'll send it up right now and go and get the remaining 980 milligrams. That patient was

00:42:07.300 actually administered 20 milligrams of Ativan and of course had a respiratory arrest. That's toxicity.

00:42:13.160 Right.

00:42:14.260 So they, they look at that.

00:42:15.420 That's a lawsuit.

00:42:16.300 Right. That's a therapeutic index. And so they say for over-the-counter drugs, it's,

00:42:20.640 it's like, you know, one to 20, you take, you know, two aspirin and your headache goes away 40

00:42:26.720 and you're going to be in the hospital for something like, you know, Valium or, or, or Ativan.

00:42:33.140 It's usually a one to 10.

00:42:34.700 Yeah. But look at alcohol. That's my really, my point I wanted to make. Look at the therapeutics

00:42:38.700 index of alcohol. Three drinks shouldn't kill anybody. 30 would kill anybody.

00:42:44.420 Right. Exactly. And they say that for the therapeutic index for cannabis. So one to 20 is

00:42:50.060 over the counter. One to 10 is like Ativan or Valium. It's one to 20,000 to one to 40,000

00:42:57.300 is a therapeutic index. So the greater that second number, the bigger the safety profile.

00:43:02.460 You know, we call it a therapeutic window. I call that a therapeutic garage door.

00:43:06.820 Right. There are certain drugs that are simply just narrow therapeutic index drugs and need to be

00:43:12.560 very, very cautiously prescribed. I should point out for anyone who's listening that there really

00:43:17.820 isn't a therapeutic reason to dose alcohol. As far as I know, unless you're rubbing it on an insect

00:43:25.000 bite or something like that. Alcohol is not really recommended for curing any particular disease.

00:43:32.020 I want to just kind of go back to something that I forgot to ask you earlier because I got distracted

00:43:35.400 in my thinking about the next thing I was interested in. Why do you think during the prohibition era,

00:43:40.580 alcohol was brought back into favor and marijuana was not? Because I think it would be very difficult

00:43:47.960 to make the case that alcohol is less toxic than many things. I mean, alcohol is about as toxic as

00:43:56.100 it comes and yet it is completely accepted societally. Why do you think it was, I mean, this is again,

00:44:02.080 just speculating on. My sense of it was it's the sociology at the time. We live in very difficult

00:44:10.840 times and certainly they were very difficult at those times. And it seemed that people really need

00:44:17.520 to have a release from the tensions of the day. The idea of creating the prohibition of alcohol

00:44:27.260 was pretty quickly recognized as not successful. That is, it simply drove it underground. People

00:44:35.060 continued to imbibe it. And what happened was there was no control. There was no tax stamps.

00:44:41.340 There was no health inspections that went along with it. And the people who were utilizing it were

00:44:47.540 demonized even more than they were before. So it was sort of a contraindication for the society,

00:44:55.060 although it certainly came out of people in their heart thinking they could make their fellow man

00:45:01.180 better by not having them be allowed to drink. Then cannabis was not brought back. I think at the

00:45:10.840 time it was societally, it was a bridge too far for people to be able to reach. And it was apparently

00:45:19.920 not a plant or an intoxicant that was used by, frankly, the people who were in control of writing

00:45:27.260 the rules and the laws. But the legislators felt pretty comfortable drinking and they didn't think

00:45:34.380 they knew anyone who smoked marijuana. A lot of people talk about the idea that marijuana is a

00:45:40.280 gateway drug. What is the state of the evidence of that argument? In other words, what are the pros and

00:45:46.300 cons of that argument to the best of our understanding? So it's an interesting question.

00:45:50.580 I always say that cannabis is a gateway more towards health than to other drugs. And in fact,

00:45:56.940 NIDA, the National Institute of Drug Abuse on their website has agreed with that statement and no longer

00:46:02.860 considers cannabis as a gateway drug. But I think what people are looking at or concerned about is

00:46:09.960 young people participating in the intoxicating effects of cannabis or alcohol or high fat and

00:46:19.840 sugar foods, just like anything else, can be leading to other addictive behaviors. But there really

00:46:27.100 isn't anything that proves that cannabis is a gateway drug.

00:46:32.160 We sort of have natural experiments that have gone on with the legalization in the states that

00:46:37.060 were at the forefront of this. Are there data that we could take from, I guess, Colorado would be

00:46:43.220 first, Washington state would be second. Are there data we can take from those states that could point

00:46:49.820 to either a rise or fall in the utilization of drugs beyond marijuana that have either gone up or down

00:46:59.180 since the legalization? It depends on how you're spinning this question. If you're saying

00:47:03.540 saying to this question that as a gateway drug, Colorado has shown proof positive that there is

00:47:10.240 not an enhanced utilization, at least of cannabis from the black market in young people who shouldn't

00:47:18.060 be taking it unless it was for medicinal purposes only. If you're referring to the opioid epidemic,

00:47:25.360 for sure, you know, Bakhuber has looked at states with medical legal programs with patients that have

00:47:33.400 access to dispensaries. There has been a statistically significant reduction in opioid prescriptions in

00:47:41.220 patients for those, for people have access. Do you think there's an association? I mean, again,

00:47:46.580 I don't know this literature, so I'm not asking a loaded question. I'm, but I sort of know these

00:47:52.080 arguments, right, which is nobody takes heroin without first taking marijuana is the argument.

00:47:58.200 Therefore, heroin, the precursor to utilization of that is taking marijuana, which of course is a

00:48:04.000 silly argument, even if it were true. I don't know that that's entirely true, but it's a silly argument

00:48:08.360 because you don't know what the denominator is on the other side of that equation. How many people

00:48:12.320 would take marijuana and not go on to use cocaine or opiates or other things like that? So A is

00:48:17.860 correlated with B does not mean A causes B and A precedes B does not mean A causes B either.

00:48:24.520 Is there any argument though, that one would make from a cautionary perspective about certain

00:48:31.240 individuals who are predisposed to addiction, who if in the presence of marijuana are more likely to

00:48:39.140 take on harmful addictions? I'm not sure that either Deb or I are that well qualified in figuring out

00:48:47.100 who could potentially have addictive behavior, nor have I really seen any studies that are able to

00:48:55.980 talk to this. My sense of it though, as having grown up here in America for quite some time

00:49:03.720 with children myself and even growing up here in lovely New York City, is that as people move

00:49:12.020 through their teenage years, they experiment with lots and lots of things, lots of behaviors that

00:49:18.380 are important, interesting, and sometimes risky behaviors. Marijuana is generally more available

00:49:27.160 than any of these other perhaps hardcore drugs. So it may appear that people are starting with

00:49:35.180 marijuana, but frankly you can get cigarettes on every street corner. So therefore I think we should

00:49:42.140 blame cigarettes more for beginning this inappropriate behavior that is sometimes addictive. I don't think

00:49:51.960 that marijuana itself, cannabis in any way, causes or leads people on into, let's call it more

00:50:00.740 hardcore drug addiction. And I just have not seen data to be able to prove it or disprove it one way

00:50:07.920 or the other. How addictive is THC? Like using formal definitions of, you know, rats, you know,

00:50:14.620 pressing levers and things like that compared to things where the addictive potential seems to be

00:50:18.720 very high. Cocaine, opiates seem to have a very high addictive potential. LSD seems to be the exact

00:50:23.500 opposite, right? They'll never push that lever again. Where does THC fit on that spectrum?

00:50:28.700 On the low end of the spectrum, for sure. It's below alcohol, I believe.

00:50:32.760 It's below alcohol. Tobacco is probably one of the higher percentages than heroin, believe it or not,

00:50:38.720 below tobacco. And I think they say the studies are 9%. You know, remember these are recreational

00:50:45.440 markets or using animals at high doses, lever pressing. So it doesn't really reflect real world

00:50:53.540 behaviors. To take that a little bit further, there are medical centers right now that are running

00:51:00.260 clinical trials utilizing CBD and sometimes CBD with THC as dosage forms to move people off of other

00:51:11.340 addicted substances. So that's to move people off of methadone, to move people off of heroin. So it may

00:51:19.820 very well be that THC and CBD are truly an exit drug, not an entry drug.

00:51:26.800 What do we know about the effect of THC on a developing brain versus a more developed brain?

00:51:32.380 So the three of us sitting here presumably have done most of our brain development,

00:51:37.240 but the 15-year-old is still probably in the throes of developing. What do we know about differences

00:51:43.220 under those circumstances?

00:51:44.480 So what I say to patients and other physicians is that I don't think we're advocating using any

00:51:51.680 kind of chemical substance on a developing brain unless they need it.

00:51:56.940 But do we have actual data? Because I know that I did try to look into this about a year ago,

00:52:02.100 maybe two years ago at the request of a patient. And what I found difficult at the time,

00:52:06.960 and I'm hoping maybe you have better data, is that we just didn't have great studies because

00:52:12.640 everything was confounded by recreational use without control. So even though at first principles,

00:52:19.060 it seems illogical that a 15-year-old is going to benefit from using marijuana, it wasn't really

00:52:27.460 clear from the data what the case was. So two years later with legalization in some states or

00:52:34.180 decriminalization, can we say any more than that?

00:52:37.380 Not really. Unfortunately, there haven't been the robust double-blind randomized trials in people.

00:52:42.640 But when you talk about the 15-year-old and should cannabis be used, again, people think of

00:52:47.300 cannabis as inhalation. So let's, you know, take that off the table for a second. Let's think

00:52:53.060 about it as a medicine. So if this 15-year-old has a seizure disorder and there are constituents in

00:53:00.260 this plant that can help with that, that makes sense to use. If this 15-year-old has attention

00:53:07.120 deficit or anxiety or depression and other medicines are not working, or maybe the risks of those other

00:53:14.180 medicines are a lot greater, I think these are reasonable tools in our medical toolbox that can

00:53:20.300 be used. I mean, people think about just THC as a very high, you know, intoxicating chemical. It

00:53:28.280 doesn't have to be. You have to have the receptor. You have to have the drug that sits on that receptor.

00:53:32.840 And you have to have enough of that drug to sit on those receptors to get that intoxicating effect.

00:53:38.920 So let's go back to something we talked about a little while ago, which is the different modes

00:53:42.400 or routes of administration. So we talked about the Spicoli route. And I guess the advantage of

00:53:49.320 that route is it's relatively quickly. The active ingredients become engaged with the receptors,

00:53:54.640 both peripherally and within the CNS in a very short period of time. I'm guessing one of the

00:53:59.800 drawbacks of that route of administration is dose-to-dose consistency, and presumably you're

00:54:07.040 inhaling other things that might not be too good for your lungs. Is there data on that?

00:54:11.680 So you're correct. So your bioavailability in an inhalational method is fast and furious. You miss

00:54:18.920 the whole GI tract, which is great. So if you're somebody with MS and has muscle spasm that's acute,

00:54:24.040 inhalation method could be a godsend for them, for sure. You're right that the length or duration of

00:54:30.820 action is a lot shorter than other methods of administration. So if you're somebody with a

00:54:36.500 chronic pain issue, that's probably not your method of administration that you want to employ.

00:54:41.880 Yes, you get products of combustion. So if you're smoking plant material, you have a whole bunch of

00:54:46.460 other things, no differently than tobacco, that can cause some issues. There have been no studies.

00:54:51.640 In fact, Dr. Tashkin has shown that there has not been an association between

00:54:56.260 lung cancer and smoking cannabis, flowers.

00:55:00.020 Yeah. Why do you think that is, by the way? I'm sort of surprised by that.

00:55:02.920 Me too.

00:55:03.020 Do you think it's a dose effect or-

00:55:04.920 Or maybe it's the anti-inflammatory effects of the cannabinoids themselves that sort of are

00:55:10.500 kind of pretreating it. I don't know. I'm not smart enough to know that. That was one study.

00:55:15.080 Maybe we need to look at other studies. I can't answer that. What I can say though is we do know that

00:55:21.160 heat does cause cellular change. So for that reason, I'm always concerned about it. And for

00:55:27.760 my patients that I treat, I don't recommend inhalational method at all.

00:55:33.380 Any inhalational method?

00:55:34.520 I don't. Only because I don't understand how to help them titrate because inhalation is different.

00:55:41.440 A small inhalation gives you one dose. A deeper inhalation gives you a different dose. Your

00:55:46.940 inhalation is different than somebody else's.

00:55:49.220 Thinking about this as an anesthesiologist from a clinical perspective, outside of anesthesia,

00:55:56.500 where we're totally controlled, we don't like to give drugs or we don't know the dose.

00:56:01.840 I think patients who are really sick want their hands held in a way that they can wrap their head

00:56:08.120 around it as much as I can. So if I say, use X, Y, and Z, and they come back to me and say,

00:56:14.360 it works, then we understand what they should take. If I say, take X, Y, and Z, and maybe it doesn't

00:56:20.380 work or it only does part way, then we have an understanding as to how to go, how to pivot from

00:56:25.340 that point. Inhalation doesn't allow me to do that.

00:56:29.060 Is there anything else, Steve, from a chemical perspective? So when I think of inhalation,

00:56:34.020 I guess I think of two vehicles. I think of the sort of bong joint method where the temperature

00:56:41.340 is like literally from the flame burning the material, combusting it, that then gets inhaled.

00:56:47.700 And then you think of sort of the vaping method where, well, tell us how vaping works actually.

00:56:54.080 Vaping works at a lower temperature than the pyrolysis that goes on when you use a bong.

00:57:02.680 And some people even take it a little bit further and heat up a substance using an acetylene torch

00:57:08.540 on a nail and then inhaling it. That's really hot. The vaping goes on at a much lower temperature

00:57:17.320 and there are other dosage forms that are going to come out soon that are simply inhalers like

00:57:24.480 bronco inhalers where there won't be any temperature gradient at all and the product will be brought

00:57:32.400 into the lungs through an inert carrier gas. So that will allow a much more controlled dose.

00:57:40.080 Those just aren't really on the market very effectively yet.

00:57:43.220 There's been a lot of talk about vaping lately and this is both from the lens of the use of THC

00:57:50.160 and nicotine itself totally separately. What do you guys know about this as it pertains to safety?

00:57:56.160 Let's start with that. That's an interesting question. I don't think anyone really can put

00:58:01.680 a finger on a specific reason for this problem that these vape partries are causing.

00:58:06.960 Tell people what the problems are that we're seeing.

00:58:08.800 So it looks like an acute respiratory distress syndrome. So it almost looks like a chemical burn

00:58:13.720 to a lung where people have a respiratory failure that requires a huge amount of support in the

00:58:21.900 intensive care unit including intubation and ventilation and other support measures. So it's

00:58:27.620 pretty severe and pretty significant. When you extract cannabis, it comes out as a thick,

00:58:33.800 goopy oil and you need to refine that oil in order to put it into cartridges. And those methods of

00:58:40.880 getting the right viscosity for that oil to be put in that cartridge is done in a whole host of

00:58:48.740 different ways. And I don't think it was done intentionally to hurt people. I think people

00:58:53.100 thought, oh, let's thin this oil out using PG or PEG because it's a grass ingredient generally

00:59:00.300 regarded as safe. But it's generally regarded as safe if you eat it. And no one really understood

00:59:05.800 what happens when you combust it. For those two things, I think it's formaldehyde gets created when

00:59:12.140 you combust or heat up PG or PEG. Other people are using, we're using vitamin E acetate. Again,

00:59:19.820 generally regarded as safe if you ingest it, not if you heat it up to a vapor or steam. And so-

00:59:25.300 Does the FDA not require a reanalysis? So if the FDA says substance A has a grass designation

00:59:33.640 and substance A has historically been consumed at room temperature and subject to a first pass effect

00:59:40.320 in the liver, can anybody come along and say, I'm going to burn said substance and it still

00:59:45.960 maintains its grass designation? How does the FDA think about that?

00:59:49.500 The FDA allows something to be grass, generally recognized as safe for particular uses, either

00:59:57.140 as direct food ingredients, indirect food ingredients, part of packaging. But once the product is out there

01:00:03.780 in the marketplace and available to use, it's America. People will do whatever they wish with it.

01:00:12.260 And that brings us to part of the issue here is that this is, while this is a regulated environment

01:00:20.300 within the States, there are many actors, many producers who are not yet regulated. It's kind of

01:00:28.000 like alcohol was legalized. And then there were still bathtub gin being made for many, many years. There

01:00:37.600 were hundreds, thousands of deaths from it. On this vaping issue in particular, I had some experiences

01:00:46.040 at the New York Medical Examiners some years ago on a syndrome that came to be called SIDS, sudden

01:00:52.900 infant death syndrome, where we had to look at the lungs of a number of infants that had died in this

01:00:59.520 way. And so something similar is happening here. We're in the midst of a quiet, slow-moving,

01:01:07.600 epidemic, where there are now thousands of people in hospital. I think we have over 34 deaths

01:01:16.120 directly attributed to it. And week by week, the toll continues to mount. It's just not been brought

01:01:24.600 out all that widely. It does look like these are chemical burns within the lungs, but then the lungs

01:01:33.160 seem to be not regenerating themselves, but the wounds are getting worse.

01:01:39.120 So does it behave like ARDS?

01:01:41.320 That's what it sounds like. It's a lot of cellular recruitment, and then oxygenation doesn't occur,

01:01:47.360 but they're not 100% sure.

01:01:49.560 Are they getting edema as well?

01:01:51.620 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

01:02:00.900 health organizations are trying to find epidemiologic locuses where events have occurred.

01:02:09.160 In a couple of cases, they've been able to identify that there were individuals who made

01:02:15.740 some vape cartridges where there is a higher proportion of people who have been hurt

01:02:21.920 from other vape cartridges, but there is just no clear-cut etiology so far.

01:02:28.080 So if I'm understanding you correctly, we have no idea if the uptick in these acute toxicities

01:02:35.940 is potentially manufacturing-related, loci-related, diffuse. We don't know any of those things yet.

01:02:43.920 That's exactly correct. From having worked in this industry for a long time, I'm very familiar with

01:02:50.160 every time a new product. Even if it's something as innocuous as a lipstick is changed,

01:02:59.380 there is a slight uptick in adverse events. Even from just changing the coloration in a lipstick or an

01:03:06.920 eyeshadow, because there are millions of uses of it, you're able to see what happens in products like that

01:03:15.540 that are where people are using them external to their body. It's a slight irritation. And the person

01:03:23.400 simply decides, I won't use that eyeshadow anymore or that lipstick anymore. And they self-select out of

01:03:29.040 the population. Here, this is a sudden onset of a serious nature. But even with all of these numbers of,

01:03:39.080 well, a terrible amount, more than 30 deaths and hundreds, thousands in hospital, this is against

01:03:47.240 millions and millions of uses. And there just doesn't seem to be a clear-cut cause that we're

01:03:53.020 able to find so far. You said something a moment ago, and I want to make sure I understand it because

01:03:57.200 it seems staggering to me. The FDA, if you go down to the grocery store or the corner store and you buy

01:04:03.640 a bag of, I don't know, jelly beans, and they come in a plastic container, does the FDA have

01:04:10.280 oversight into the plastic that holds the jelly beans? Yes. Yeah, they do. And the FDA says this

01:04:16.740 plastic is grass. Yes. That the individual chemicals that went into making that, they don't

01:04:23.720 look at the overall plastic bag, but rather the individual polymers or monomers or the colorants

01:04:29.960 have all gone through extensive testing. Now, let's say I'm an idiot and I decide to create a

01:04:37.240 new product, which is I'm going to take the plastic, I'm going to take those constitutive elements in that

01:04:42.900 plastic bag that holds the jelly beans, and I'm going to combust it for inhalational use. So new use

01:04:50.620 of previously agreed upon grass constituents. Does the FDA say, Peter, you can't do that? Or does the

01:04:59.680 FDA say, well, gee whiz, each of those things were safe to be touching jelly beans, therefore you can

01:05:04.940 be burning them? The FDA actually would be very annoyed at you. What's the legal recourse? Oh, the

01:05:10.860 legal recourse was if you had turned that into a business, is they would come and shut you down.

01:05:18.880 Okay. So the FDA still has their pants on and they would still be looking out to protect people

01:05:23.620 from me doing that. Yes, absolutely. But not in the cannabis world. Why? Because it's federally

01:05:29.360 illegal and the FDA is not a participant. So you're saying that the fact that cannabis is still

01:05:36.020 illegal federally means this entire discussion is moot and it would be at the state's discretion to

01:05:43.460 police this type of use switching? Exactly. That's exactly correct. And that is part of the difficulty

01:05:51.760 right now is that state agencies are not used to having the scientific horsepower or the manpower or

01:06:03.140 womanpower is much better to be able to figure out which of these ingredients can or cannot be added

01:06:11.420 to it. And on top of that, the producers of the products are not required to test them for safety

01:06:20.700 or efficacy before they start shipping the products, which is very different than products sold under FDA

01:06:28.900 auspices where you have to demonstrate at least safety for foods products and for drugs. You also have

01:06:36.720 to prove efficacy before you can make it and ship it. Prior to the explosion of these acute events of

01:06:44.160 toxicity, I was much more personally curious about chronic toxicity. Let's take tobacco as an example.

01:06:52.940 Very few people have acute toxicity to tobacco use, but by the middle of the 1960s, it was abundantly

01:06:59.700 clear what the chronic toxicity was from tobacco use. Alcohol is an interesting one. Alcohol has

01:07:06.700 lots of acute toxicity. You could kill yourself in a moment with alcohol. That's a very easy thing to

01:07:12.020 do. But I don't know if your friend who died of cirrhosis had complications of alcohol use or whether

01:07:17.660 it was hepatitis, but certainly the chronic toxicity of alcohol in this country is the longest, fattest,

01:07:24.160 widest tail we see along with tobacco perhaps. Maybe fatter actually. What do we think is the chronic

01:07:30.860 toxicity or do we believe that there's any evidence of or against chronic toxicity from vaping?

01:07:36.700 Things that we just haven't, it hasn't been around long enough and we don't know, but you're sort of

01:07:42.480 playing with fire, that logic. I mean, that's a feeling because it really hasn't been available

01:07:48.120 as widespread as it is now. Remember, 2014, 2013 was when really other states started really coming

01:07:57.100 on board. I mean, California was the first in 2009. There was nobody vaping then. People were,

01:08:02.020 you know, using cannabis as a flower to smoke. People were using it in foodstuffs to eat,

01:08:09.040 but nobody was using this vaping thing. I don't think it was until the popularity of the vaping

01:08:15.220 through the e-cigarette market when the cannabis market turned and went, hmm, this is an interesting

01:08:20.700 business, an interesting mode of administration, no products of combustion, so people will feel a lot

01:08:26.640 better about it. And I think people honestly and truly thought it was a better mousetrap.

01:08:32.500 Do you know what the people who favor that approach will argue in their defense?

01:08:36.480 So there's a couple of arguments. One is it's better than smoking and getting products of

01:08:40.860 combustion. Two, it's helping me get off nicotine, so I'm vaping instead. So that's better. And three,

01:08:47.620 people who have an acute pain issue or a muscle spasm feel like the instantaneous nature of the

01:08:56.320 effects of this is what they require. I think that manufacturers of cannabinoid medicine are

01:09:03.920 looking to do things with the cannabinoids. I know we are, and I don't want to push our product,

01:09:09.300 but we are looking at changing the solubility from a fat-soluble to the water-soluble method of

01:09:15.260 administration makes the bioavailability a heck of a lot faster. It's just not available across

01:09:20.880 the country because we have a state license in Michigan, and we can't sell it across state lines.

01:09:26.280 Yeah, I want to come back to talk a lot about your product because when you said that a moment ago,

01:09:30.420 Deb, I couldn't understand how you were talking about water solubility of this. So let's, between

01:09:35.400 the three of us, remember to park that and come back to that because I could use the chemistry lesson.

01:09:39.160 Going back to the toxicity point, we talked briefly about edibles earlier. We didn't,

01:09:45.940 we sort of indirectly did. You said that if Spicoli ate that flour, he might've got a belly

01:09:51.760 upset, but he wouldn't have got high. Why is it that when people consume edibles, they get high?

01:09:57.040 Because it's a different constituent. They're not using the raw plant. They're heating those

01:10:01.980 chemicals. So when people are making brownies, yes, the batter's yummy, but they generally bake it at a

01:10:07.540 certain temperature for a certain amount of time. And there are actual curves that show when THC in

01:10:14.660 its acid form, in its raw form, gets converted to, or some people call it activated form, into THC.

01:10:21.420 So it takes time and it takes temperature before you make that conversion. And at that point when

01:10:27.200 you eat it, that's when you can, those chemicals can sit on the receptors that make you feel high or

01:10:32.980 intoxicated. So it's, again, it's very unlikely you'll make two batches of brownies identically

01:10:38.200 because time, the area under the curb is almost always going to be different. So everybody gets

01:10:44.140 a different brownie. Now, when you get the candies or things like that, is it the extraction of the THC

01:10:49.140 required heating to get the active ingredient into these commercial edible products?

01:10:53.840 So it depends on what you're making. I mean, there are medicinal-

01:10:56.100 Chocolates or candies and stuff.

01:10:57.760 But there are medicinal properties in the raw form as well as the heated form. So if you're making it

01:11:03.360 for the direct purpose of intoxication, you're going to heat the starting material first,

01:11:09.800 you know, the active ingredient first, the THC, and then you're going to put it into your chocolate.

01:11:14.440 So this might be a bad analogy, but you know how anytime you make coffee, you're basically

01:11:19.600 running hot water across a bean. But if you're a real coffee snob, you'll do a cold brew so that

01:11:27.280 you can extract the flavor without the temperature and you avoid the bitterness. It seems to me that

01:11:33.800 whether you're talking about smoking a joint, lighting a bong, vaping, or eating a candy or

01:11:38.560 chocolate or a brownie, heat always seems to be required if you're going to get this active

01:11:45.080 ingredient out. Is that the case? If you're trying to get THC-

01:11:48.700 For intoxication.

01:11:49.540 Right, for intoxication. So the answer is yes. You have to apply time and temperature

01:11:54.480 in order to make THC. And then you put that THC as your starter ingredient into whatever it is.

01:12:01.540 And the variables for the edibles is not just the preparation of the food, but that our digestive

01:12:11.120 process varies hour to hour, person to person, as well as our body mass and how we feel about

01:12:21.300 things and what the time of day is and the circadian rhythm. So it's almost impossible to expect out of

01:12:28.160 eating any food that contains THC or CBD to expect that you will get a reliable, repeatable dosage

01:12:36.800 experience from that. Even if the label is completely correct and completely accurate.

01:12:43.180 And that's a big if.

01:12:44.780 It's huge.

01:12:45.340 Yes, it is. The legitimate laboratories in cannabis have gotten better and better and better all the

01:12:51.760 time. But still, when you make a batch of a thousand brownies and you just sample one or two of them,

01:13:00.800 there's an awfully good chance that the batter may not have been mixed appropriately. Pharmaceuticals

01:13:07.400 sort of solve that because of the consistency by which we make things in a pharmaceutical way. But

01:13:14.300 foods are not quite that precise. And, you know, you can buy a brownie at a store one day and then

01:13:21.780 buy a homemade brownie the next day and it can taste very different.

01:13:25.440 How many strains are there of cannabis that are commonly used?

01:13:28.580 From what I've heard, there's over 800, but people are crossing and back crossing all the

01:13:32.800 time. But back to the edibles thing that I think is even more important is that when you eat

01:13:38.460 something and it goes through your stomach and it goes to the liver and gets cleared, it gets

01:13:42.320 chemically converted. And so therefore, you're really not even ingesting THC anymore. You're ingesting

01:13:49.100 its metabolite. And that metabolite is even more intoxicating than THC itself. So there are people

01:13:56.680 who are experienced in inhalational methods of THC that do it all the time that say they can't even

01:14:02.640 eat a THC brownie or a gummy bear or, you know, drinking a soda with it in because it's far more

01:14:11.020 intoxicating.

01:14:12.160 Do you think there are any appropriate, might be the wrong word, but just call it, what are the best

01:14:16.960 use cases for edibles?

01:14:18.620 I think the best case use edibles are for somebody with a chronic pain. So let's take example,

01:14:23.160 somebody with a chronic pain that can't sleep at night.

01:14:25.740 Let's take an extreme case. Somebody with cancer that's spread to their bones.

01:14:28.900 Right. And they literally can't sleep. So what I would do with a patient is I would trial them on

01:14:33.800 a certain edible or something that I believe is consistent. It wouldn't be held within a food

01:14:38.680 stuff. It would most likely be in a capsule or a tablet because it makes sense. Again, remember we

01:14:44.420 talked about wanting to understand the dose and wanting to understand what it is. We would dose it in a

01:14:49.560 way that it would be the same time every night for this, this patient. And we would see how they

01:14:54.020 would sleep. The bioavailability takes about 60 to 90 minutes in the best case scenario. You only get

01:15:00.460 about 8% of whatever it is that you're taking, but it can last up to eight to 10 hours.

01:15:06.440 We haven't talked about tachyphylaxis or tolerance. How does the body respond to repeated

01:15:10.820 administration of THC?

01:15:12.480 That's really interesting. THC sits on these docking stations known as receptors, and there

01:15:18.100 are chances of over-consuming THC and down-regulating these receptors that actually can be reset very

01:15:26.720 quickly by just stopping for a couple of days. But there's an interesting study out of the

01:15:32.000 Netherlands, since they've had a medical program for a very long time, I think since 2012 or something

01:15:38.460 or 10, where they looked at patients, the average patient only takes 750 milligrams of cannabis a

01:15:47.900 day. And you would imagine if there was so much tachyphylaxis, you would have seen an increase or

01:15:52.440 rise in that, and you didn't. It seemed like they stabilized at 750 milligrams, and that was it,

01:15:58.180 which is contrary to what I just said.

01:15:59.800 So explain the opposite. Talk about opiates. You've obviously, as an anesthesiologist,

01:16:04.640 had lots of experience with them. What typically happens to a patient who is prescribed opiates for

01:16:09.920 pain?

01:16:10.420 That's the problem with opiates. Opiates sit on these, their own docking station, and they do

01:16:15.780 down-regulate very quickly, which means that you require more and more for the same effect. And then

01:16:21.340 it does something really strange. It flips. And after a certain amount of opiates, your pain gets

01:16:29.700 enhanced, not decreased. And it's called hyperalgesia. It's a strange phenomenon.

01:16:34.840 And you said 20% to 30% of people experience that?

01:16:37.340 No, actually 20%, 30% of people experience that from the beginning, where they experience an opposite

01:16:42.680 reaction to pain relief. But I'm saying people who traditionally get pain relief, who require more

01:16:48.500 and more and more for the same amount of pain relief, suddenly they are experiencing a hyperalgesia,

01:16:53.980 an increase in pain. Whereas before, a month ago, you know, two months ago, they were actually getting

01:17:00.020 pain relief. Nobody talks about that.

01:17:03.800 So we don't think that this is necessarily happening with THC and the CB1 or CB2 receptor?

01:17:10.620 No, we're not seeing that yet, as of now.

01:17:13.760 Hmm. Let's talk a little bit about how THC mixes with other drugs. What happens when THC is combined

01:17:21.200 with alcohol, for example? Alcohol is a known depressant of the central nervous system.

01:17:27.100 I still don't really understand what THC is doing in the CNS. I'm still confused by

01:17:31.620 the intoxicating versus non-intoxicating effects. I know that I can tell what you're thinking,

01:17:36.540 which is, Peter, that's the point. It's a plant. It's complex. It's doing many things, but...

01:17:40.480 It's multimodal, actually. So a little bit of THC won't cause any intoxication. You need the

01:17:45.360 receptor, you need the drug, and you need enough drugs sitting on all those receptors in order to

01:17:50.580 express those things. And I joke with Steve and say I like to be called the queen, basically,

01:17:56.000 but the queen of microdose, which means I like to use very small amounts of cannabinoids to activate

01:18:02.240 things on a cellular level so you actually don't feel the intoxicating effects because most patients

01:18:07.440 don't want to be sidelined by their pain, and they don't want to be sidelined by their pain

01:18:11.520 medicine. So that's kind of off topic.

01:18:14.840 Is that the majority of your personal focus? I mean, I want to come back to, obviously,

01:18:19.820 what your company, Pure, does. That makes sense there. But what about people who actually want

01:18:26.560 some of the intoxicating effects because, well, let me unpack that a little bit more. I was about

01:18:31.440 to say because of things like anxiety or stress, but you could make the argument that if one has

01:18:36.840 their anxiety and stress reduced without intoxication, that might be just as beneficial.

01:18:41.600 Have you thought much about the particular demand, the consumer demand? What is it that people

01:18:47.340 actually want from THC?

01:18:49.080 My sense of it is that they would actually like relief. That is, over and over again, I did an

01:18:55.880 extensive survey of, in Michigan, we have over 400,000 people with medical marijuana cards.

01:19:03.940 And of people who were going into cannabis dispensaries, two-thirds of them were really

01:19:09.640 there for medical reasons, not to get stoned. They had learned over the course of their lives

01:19:16.500 that they could reduce their pain, often chronic pain from very serious accidents or operations.

01:19:25.720 They could reduce their anxiety. And they had learned that they could find strains of marijuana,

01:19:33.000 marijuana, and they were using them and smoking them because it was all that they had available

01:19:38.800 to them. So these are people generally who were just looking to live happy, normal lives like all

01:19:45.860 the rest of us, and that they have found that this is a relatively inexpensive and pretty harmless

01:19:51.620 way to manage what are otherwise very, very severe symptoms. So that if, going back to your question

01:20:00.740 about utilizing alcohol at the same time, there are some people who utilize alcohol regularly in order

01:20:09.960 to, frankly, numb the pain, even without listening to any Frank Sinatra songs about the heartache and why

01:20:17.960 we're all still in a bar at 3 o'clock in the morning, it's for pain relief or it's psychological and

01:20:25.220 sometimes straightforward physical pain relief. Once people discover that they can achieve that

01:20:32.380 by using a small, relatively easy titration form, people who utilize cannabis smoking or vaping are

01:20:43.060 readily able to titrate themselves, which is just remarkable to be able to do that. Certainly I did when

01:20:50.920 I was smoking cigarettes. I could learn how to accelerate my heart rate or relax by just puffing

01:20:58.080 in a different way. I gave up that addiction myself.

01:21:02.920 Interesting. I don't think I appreciated that you could have that distinction from, presumably from the

01:21:08.020 nicotine, depending on the speed at which you take on that nicotine.

01:21:12.900 I could either excite myself to be able to get up for something or you could use it to calm down and

01:21:21.140 relax by just simply dosing in a different manner. Do you think there are certain medical conditions

01:21:27.740 that are contraindicated from the use of THC? For example, I'm making this up, I have no idea.

01:21:33.060 Someone with schizophrenia or someone with severe psychiatric illness, can it be exacerbated by THC?

01:21:38.980 The short answer is yes, but that doesn't mean that they should not be availed to cannabinoids

01:21:45.460 because again, there's over a hundred different cannabinoids specific to the cannabis plant that

01:21:51.800 could be and has shown to be incredibly useful. So yes, high dose THC alone could stimulate somebody

01:21:59.380 who has schizophrenia to have an exacerbation of those things, but CBD and maybe even a low level of

01:22:07.480 THC along with it could actually be hugely beneficial. Back to your question about THC and

01:22:13.380 other drugs, THC plus opiates has shown that a reduction in opiates with a greater pain-relieving

01:22:21.380 efficacy without that tachyphylaxis or tolerance that we know to be true for opioid use.

01:22:28.820 How much time do you still spend in a hospital setting or an inpatient setting? Do you spend any time there?

01:22:34.380 Zero anymore. Do you have any sense of how long it will be before THC and or CBD make their way

01:22:41.820 into the, for example, post-op surgical patient world? Dranabinol, which is a synthetic THC has been

01:22:48.180 on the market since the 1980s and we as doctors are allowed to write prescriptions for it across the

01:22:54.720 country and patients can travel with it. That's available now and it's being used for chemotherapy,

01:23:01.460 induced nausea and vomiting in some settings. Not very well because straight up THC is really

01:23:07.400 uncomfortable. It does increase your heart rate, does make your mouth dry, does make you feel

01:23:11.400 agitated and uncomfortable. I mean, the rest of the constituents within the plant sort of modulate

01:23:16.660 all of that. I'm glad you brought this up because I was going to ask you about the synthetics.

01:23:20.680 The synthetics have a pretty bad rap. There's sort of the teleologic argument of, you know,

01:23:25.720 nature always packs the right amount of this antidote versus that antidote. I mean, what is

01:23:30.120 your take on synthetics through that lens in particular? That's a complicated answer. I mean,

01:23:35.560 I think what I'm really wanting to focus more about is a single molecule as opposed to looking at many of

01:23:43.300 the molecules within the cannabis plant and try to find utilization. You know, so a single molecule

01:23:49.520 like CBD from Epidiolex from GW Pharma came from a plant, but it is isolated and purified to 99.99%

01:23:59.080 and it requires a tremendous amount to get the effect that GW Pharma wanted to get on two types of

01:24:06.980 seizures. We formulate using isolated cannabinoids, but we join them together along with other constituents

01:24:13.640 so that we use less and we capitalize on the synergistic effects of a lot of the molecules.

01:24:19.960 No differently than what we do in medicine as an anesthesiologist, we just don't push one

01:24:24.240 medication. We push a lot of different medications to lower the bad effects of one particular medicine

01:24:31.180 and capitalize on the good effects of all of them. Say more about the GW CBD for epilepsy. What is the

01:24:38.420 purity of it? You said it's 99. It's pretty high. It's greater than 90%.

01:24:42.400 Tell me about the success and utilization of that.

01:24:45.100 So it's plant derived, but it's isolated. So it's purified and they have it for two particular types

01:24:50.900 of seizures. Those kids with these rare seizure forms that are refractory to multiple other

01:24:57.600 traditional pharmaceuticals. I think they have like a 30% reduction in their seizures, but there's

01:25:05.860 side effects. I mean, there's GI effects, there's liver issues. I mean, there's side effects in high,

01:25:11.100 high doses of, of Epidiolex.

01:25:13.940 What do you think is the potential for CBD and sleep? Something that gets talked about a lot.

01:25:20.520 What is your take on the efficacy of CBD oils? Let's start with the oils, which are very commercially

01:25:25.460 abundant.

01:25:26.580 Well, let me first mention my bias. I took it this morning at one o'clock in the morning, because as

01:25:32.180 usual, I'm up for an hour trying to do something and it's a little noisy in this city and I needed to go

01:25:38.120 back to sleep. So it is in our hands and in our experience, it works. It simply works. That is,

01:25:49.300 people are able to take CBD. We think that taking it as an oil is less effective than taking it in a

01:25:57.800 water-soluble form. But it is certainly effective. We have pharmacovigilance data on several hundred

01:26:07.280 thousand people that demonstrates that they generally go to sleep pretty quickly, have a

01:26:14.180 great night's sleep, and wake up refreshed with no feeling of what other sleep aids give,

01:26:21.100 of grogginess, or anything like that. Most people think it is just fabulous.

01:26:28.600 Do you have any insight into what the mechanism of action is?

01:26:32.300 So remember, multimodal mechanisms of action, so anti-inflammatory, it also activates the GABA receptor,

01:26:39.700 decreases anxiety, and a lot of people have that three-year-old running around in their head at night

01:26:44.500 and prevents them from going to sleep. So we think it is central activation of GABA that would be one

01:26:51.460 of the more potent mediated. There's a molecule out there called phenibut, which is an oral form of

01:26:58.500 GABA that crosses the blood-brain barrier. Now the FDA has not designated it GRASS, so therefore it's no

01:27:04.920 longer available easily. But for something that was for so long over the counter, it was kind of a

01:27:11.940 remarkable sleep aid. So one shouldn't underestimate the potency of CNS GABA activation. Is there any

01:27:19.380 sort of polysom data that talks about staging of sleep with CBD? In other words, it's one thing to say,

01:27:25.700 great, you know, a person can sleep for this many hours uninterrupted, but do we have any sense of the

01:27:32.060 impact of CBD on sleep architecture? I haven't seen any data like that, and your questions are

01:27:38.420 remarkably and remarkably perceptive. You have to realize that at this current time, because of the

01:27:45.860 still illegality of THC and the confused legality about all of the others, that pretty much every

01:27:56.320 university, especially medical universities, do not allow research to be done on the facility unless

01:28:04.080 someone has a DEA license. And even then getting the DEA license is a long drawn out process,

01:28:11.740 so that very little work is able to be done. And there are thousands of medical researchers who

01:28:18.780 would love to work on these problems, but they can't, just like they haven't been able to for 50 years.

01:28:24.120 But is CBD not permitted for research if the THC level is low enough?

01:28:28.960 That's only come about in the last few months. So it certainly takes a lot longer for research

01:28:39.120 protocols to be developed, to move through NIH, to move through whatever funding opportunity there is.

01:28:46.920 And I expect that in the next year or two or three, that there'll be much more research done on that.

01:28:54.740 It's still a highly restricted, highly restrained, and frankly, the university administration in almost

01:29:03.240 all of these schools and universities are very, very worried about jeopardizing their federal funding

01:29:10.620 for billions of dollars of other projects.

01:29:14.320 In other words, it's not that there's a dearth of funding. If a philanthropist came along and said

01:29:18.480 to somebody at the University of Michigan in Ann Arbor,

01:29:21.140 hey, here's $5 million, I want you to study the effect of CBD on sleep duration and architecture,

01:29:29.540 the university would say, well, thank you for that, but I don't want to jeopardize the

01:29:33.260 billion dollars of NIH funding I have. Is that, am I understanding you correctly?

01:29:37.300 Yeah, well, I wouldn't pick on U of M because my wife works in pathology there. So,

01:29:41.440 but it's a great school, terrific school, football's coming back, folks,

01:29:44.600 that any university in these stages will move much more carefully to consider what the research is

01:29:55.160 and who is the researcher simply because of 50, 60 years of illegality.

01:30:02.520 It's just so surprising to see how far behind THC and CBD are when you have a beautiful roadmap

01:30:08.660 from organizations that have been funding so much psychedelic research.

01:30:12.660 I mean, when you look at MAPS, the Multidisciplinary Association for Psychedelic Studies started by Rick

01:30:17.840 Doblin, I mean, he started this organization in 1986. 33 years later, they are now in phase three

01:30:24.960 studies using MDMA, which is, as you know, obviously schedule one. I'm kind of amazed,

01:30:31.300 is there not a comparable group that is advocating for the judicious study of THC and CBD?

01:30:39.260 We are. We run clinical trials regularly. Dr. Kimlis here is running clinical trials right now.

01:30:46.840 And there are others, but they're from, let's call it private sources.

01:30:51.480 So is that the business model of your company is that you have a product that you sell and the

01:30:57.100 proceeds of that help fund the research?

01:30:59.940 Yeah, that's pretty much it. We came up with formulations that we felt would work.

01:31:06.060 And then we ran pilot clinical trials to see how they would do in a small patient population.

01:31:14.640 And once we saw that that was getting a very good response among people, then we were able to

01:31:21.380 distribute the products within the state because we were state licensed to be able to do that.

01:31:26.760 And now we are taking the funds from essentially from that cash flow and scaling up to be able to

01:31:33.460 do studies under FDA office auspices, which are frankly much more expensive to do because of all

01:31:40.640 the controls that go along with it. Talk to me now about this idea that we

01:31:44.340 alluded to twice already, which is the water solubilization of something that I didn't assume

01:31:50.800 could be water solubilized.

01:31:52.240 We have a number of patents on it and a number of them are moving through. So you'll have to

01:31:57.220 forgive me for sort of speaking generically about that. We have one issued patent out of the seven

01:32:04.920 that we've filed for. And that was to figure out, we figured out how to freeze dry cannabis and that's

01:32:12.160 an industrial process and it helps. So that's an awarded patent and anyone can look that one up.

01:32:18.480 So THC and CBD and all of the molecules that are in cannabis that appear to be useful and viable

01:32:27.780 are all oil soluble. They are not water soluble. So if you put them in a glass of water and stir it,

01:32:36.780 you'll have little oil globules on it. So we figured out how to be able to convert that

01:32:43.380 instantly into a water soluble molecule. So that when a person puts a drop of this or a powder of this

01:32:55.700 on their tongue, it doesn't taste oily. It doesn't feel oily and it doesn't act like an oil. And as

01:33:03.540 everyone knows, yeah, you can have some oil and vinegar maybe on your salad, but the body doesn't

01:33:10.200 really like to have a lot of oil in it on a regular basis. Whereas everybody can drink pints and pints

01:33:16.380 of water, gallons of water, perhaps a day. So these molecules are rendered to be water soluble

01:33:25.180 and because they're put into very, very fast, rapid dissolving tablets that disintegrate in about 15

01:33:32.480 seconds or so. Do they disintegrate under the tongue and therefore escape the first pass effect of the

01:33:38.120 liver? That's exactly right. Under the tongue, on top of the tongue, mushed around the tongue.

01:33:43.100 But they're not to be swallowed. They're not to be swallowed. They're called sublingual because it's

01:33:47.620 under the tongue. But what happens is as the tablet disintegrates literally in the mouth, the molecules

01:33:55.940 move towards the tissues of the mouth, the tongue, or throughout the oral cavity. What we see is in about

01:34:06.380 a minute, the molecules have moved into the bloodstream. And for those who are sensitive

01:34:13.660 enough, they can actually feel their toes tingle in two minutes, which teaches us that we have full

01:34:20.280 systemic absorption. Frankly, the molecules have reached a person's toes. And then we find following

01:34:27.900 that, that people are able to experience whatever effect, medical effect that we are looking for

01:34:35.760 in about eight to 10 minutes. So that's the onset of sleep for sleep formulations, the onset of pain

01:34:42.560 relief for anxiety. So that has the advantage. It avoids first pass metabolism. It gets much more of the

01:34:52.860 active drug into the bloodstream and to be distributed throughout the body. So in theory,

01:34:58.100 you could actually lower the levels of drug that are necessary to do, which-

01:35:03.040 How potent is this? Is this a millimolar or micromolar drug?

01:35:06.680 I would say that this is closer to micromolar. That is someone who's, we found very effectively

01:35:16.840 that sleep works in someone who takes 10 milligrams of CBD and one milligram of THC.

01:35:27.920 And that's spread across a body that's maybe 70 kilograms, 80 kilograms of weight.

01:35:35.360 This is really interesting to me, is that the optimal cocktail for sleep may actually have some THC

01:35:40.900 in it as opposed to just pure CBD. It's our experience over and over again that this concept

01:35:48.420 that's called the entourage effect when it's applied to cannabis, but yet this is used throughout

01:35:54.060 medicine. As Deb mentioned, as an anesthesiologist, she used a cocktail of medicine, certainly in

01:36:01.820 oncology. It's very, very common to prescribe multiple drugs at the same time or in some sequence.

01:36:10.900 We found exactly the same effect and did it by clinical trials of seeing how it would be with

01:36:18.780 patients, getting feedback from them, revising the formulations, redosing them, and seeing

01:36:25.620 how those effects changed. Does your company have a 501c3 attached to it that allows people to fund

01:36:32.480 research in the way that MAPS works? No, it doesn't. So far, it's me. I drained my retirement

01:36:38.420 account in order to do this. As you said, though, as you move towards the more and more rigorous FDA

01:36:43.900 studies, it's something you should consider. I mean, I think the public support for this type of

01:36:50.520 research is strong. I think the public's appetite for this is strong. You know, if you think about it,

01:36:55.340 you have a harder problem, in my opinion, to solve than the psychedelic community does because at least

01:37:01.340 there, there's no ambiguity about the molecule. We know what psilocybin is. We know what LSD is.

01:37:06.900 We know what MDMA is. There is no purity concern. I mean, there is if you go to a club or a party or

01:37:13.180 something like that. But from the standpoint of doing clinical research, we know exactly what we're

01:37:17.700 talking about. Whereas you're dealing with, in many ways, a more complicated set of molecules.

01:37:23.080 So you have two issues, right? Which is not just the straightforward safety, efficacy, effectiveness

01:37:31.160 chain of phase one, phase two, phase three. You have a problem that lies beneath the surface of that,

01:37:37.500 which is route of administration, cocktail, chemical composition, all of these other things.

01:37:44.220 I mean, I generally try not to give unsolicited advice, but my view is I don't know that you want

01:37:49.620 to go alone at this problem because I think the work you're doing is very important. I was at a

01:37:54.240 dinner the other day and somebody at the dinner table was talking about telling a story. And you

01:37:59.600 hear these stories all the time, right? So I think the person is totally well intentioned, and I just

01:38:04.100 sort of sat there silently because I didn't really feel like debating it. But the claim was a friend of

01:38:09.660 my friend's father was in hospice with stage four pancreatic cancer, had weeks to live, and they put

01:38:16.400 them, you know, the family snuck in CBD oil for him. And two weeks later, he was home and cured.

01:38:22.460 And, you know, the problem with those types of stories is not only that they're almost assuredly

01:38:27.400 incorrect, it's that they sort of damage the credibility of a body of research because you

01:38:35.660 start to have absurd claims that are thrown in with sort of legitimate claims. How do you think about

01:38:42.300 the sort of stigmatization of this and trying to manage the hype and the potential?

01:38:49.720 That's a really awfully good question. So I should point out, while there's only two of us here in

01:38:54.500 the room, this is a research team with a great deal of depth and breadth. That is, everyone I've

01:39:00.980 worked with in pharmaceuticals for the last 40 years have said, oh my goodness, please let me work

01:39:06.820 with you on this. And so we have that as well as a number of people who are fairly well-to-do who are

01:39:15.280 looking at this as a business opportunity and an investment, which I really appreciate and my wife

01:39:21.920 is especially appreciative of so I can stop draining our own retirement account.

01:39:26.300 Many of these anecdotal experiences are true. I wouldn't have believed it myself, honestly,

01:39:39.860 except for the fact that we have now sold six, 700,000 tablets to tens of thousands of patients

01:39:50.160 repetitively in Michigan. And I watched, it sounds funny to say, the weak and the lame get up out of

01:39:59.540 their wheelchair and move and say, I don't know how to tell you this, but what the heck is in your

01:40:07.520 tablet? And I just say, well, it's THC or it's CBD in a particular ratio with these terpenes.

01:40:13.500 And families would say, thank God. My husband is living. My mother is living. My child's anxiety is

01:40:26.680 greatly reduced. And I know to classically trained scientists and physicians that in this society at

01:40:36.940 this time that seems damaging or inappropriate, but in other societies, it is not that way. This is a

01:40:49.500 sociologic event that is just beginning to spread. And I know among many of my friends in police forces

01:40:59.000 who are EMTs who are EMTs and fire fighters, first line responders who frequently have a great deal of

01:41:07.540 anxiety in their life and frequently a great deal of pain, just straightforward physical pain aside from

01:41:13.780 everything else, that their personal experience with selected, extracted, purified cannabis has

01:41:23.740 completely changed their thoughts about what they have for generations thought was completely

01:41:30.320 inappropriate behavior. Now they say, oh, geez, it gets rid of my pain and I don't feel so bad.

01:41:37.520 And they are still able to function perfectly well. They're not stoned at all, not in any way at all,

01:41:44.780 partly because the drugs are relatively easy to self-titrate.

01:41:47.880 Yeah. I know I threw a lot.

01:41:50.340 No, no, no. I'm not suggesting that one can't see improvements in those things. But I do sort of

01:41:55.960 bristle against the notion that there are people with stage four cancer that are being sold a bill

01:42:00.200 of goods that says, you know, take your metastatic pancreatic cancer and in two weeks you're cured with

01:42:05.880 this. I'm waiting to see the first documented case of that. And I'll continue to be an incredible

01:42:12.180 skeptic of that sort of logic, which is not to say that a patient with cancer wouldn't benefit immensely from

01:42:17.880 relief of anxiety or pain. But yeah, I just, I very much struggle to imagine cancer remissions.

01:42:24.840 So THC and other cannabinoids have been shown in the laboratory to have a multimodal effect

01:42:32.220 on cancer. So in apoptosis, which is cell death, in migration or metastasis, in neovascularization,

01:42:41.440 it reduces it. So there are actual reasons and rationale behind it. You're right. Is there a

01:42:47.980 double-blind randomized trial of people? I think a doctor would go to jail if you had somebody who

01:42:53.480 could have XYZ traditional chemotherapy and okay, here's a cannabis concoction that we've come up with.

01:43:01.160 I wouldn't have believed it myself. I can show you pictures afterwards. We can't do it on a podcast.

01:43:07.180 The story is an eight-year-old girl in hospice. She was on methadone and morphine. Our goal was to

01:43:12.180 just treat her to get her off it so she had a better quality of life before she died. And we transitioned

01:43:18.980 her from hospice to second grade to third grade.

01:43:22.400 What was the underlying pathology?

01:43:24.360 She had a chronic lymphocytic leukemia and a leptomeningeal spread. She felt chemoradiation

01:43:29.420 in a couple of bone marrows. She sadly died this past summer.

01:43:34.260 Again, this gets back to the broader point, which is I'd like to see this studied more

01:43:37.980 aggressively because my greatest fear is watching patients. I mean, my greatest fear is safety.

01:43:43.420 I think that's followed with predatory behavior.

01:43:45.980 And I just, I can't tell you how frustrated I get when I hear stories about people who

01:43:53.960 are spending their last dollars on cockamamie schemes that have absolutely no bearing. I mean,

01:44:01.100 and, and, and, you know, look, there are lots of things that kill cancer in vitro that aren't

01:44:05.660 going to work in vivo. So we just have to be cautious about it. And yeah, I know I'm, I've

01:44:09.600 definitely remember the pathways of even autophagy and apoptosis and all these things where,

01:44:15.260 where the cannabinoids play a role. So again, I think this all just speaks to the idea of kind

01:44:20.000 of loading the boat to, to more effectively study this. And of course, I mean, the criticism is you

01:44:25.900 have a conflict, right? The criticism is how can you be fully objective? And again, this is something

01:44:30.300 that the maps people can get away from because, you know, MDMA has no IP associated with it,

01:44:36.540 right? Merck developed this drug in the twenties. Now there's an interesting business model, which is

01:44:40.860 how would you incentivize people to study something where there is no profit center at the end?

01:44:46.660 My view is you should be able to pursue this. I mean, I want to be clear. I'm not suggesting that

01:44:52.580 you guys aren't sitting here with the purest of intentions. It comes across very clearly. And I

01:44:56.700 hope the listener can tell that I, I can tell how pure your intentions are and that creating a company

01:45:02.520 is just a vehicle through which to pursue more research. But as I think about the broader objective,

01:45:08.680 which is broader than just your company, again, I'll come back to this idea of creating a research

01:45:15.000 initiative around this that even exceeds the reach of your company. Because remember the number of

01:45:20.760 questions here is harder, right? Like I'd like to hear from you guys, what question you're most

01:45:25.680 interested in knowing the answer to in five years, it would be great that the NIH could carry some of

01:45:31.380 that burden, right? It would be great that independent MROs, medical research organizations could carry

01:45:37.380 some of that burden because no one's retirement account should be depleted in an effort to hold

01:45:43.640 a promise true to a friend, which is a, in some ways, a part of what started this for you, what

01:45:47.800 started this journey for you. It is exactly. Tell me a couple of questions. Like what do you not know

01:45:52.440 the answer to today that you want to know the answer to with respect to THC, CBD, and its associated

01:45:59.280 products in, in five years, what would make the world a better place?

01:46:02.620 For me, I've made a vow that I will find a formulation that will relieve PTSD. I made a

01:46:13.140 vow to do that for people who were heroin addicts and, you know, methadone may not be the best of

01:46:18.920 all formulations, but that's what I did when I was 23 years old and I got a little better as I went

01:46:24.600 along. So that is the driving force for me to be able to do this. And then my goal is to be able

01:46:35.060 to discover as many of these disease conditions, psychological or physical conditions, as we can

01:46:43.520 extract value from these stunningly non-toxic molecules. Steve, are there INDs affiliated and

01:46:51.020 associated with these molecules? Like are you in that phase one pipeline now?

01:46:54.480 Yes, we are. We have three filed. We actually just met with FDA three weeks or so ago over one of

01:47:03.740 them and we are pursuing that very, very actively. So each time you reconstitute something, it's a new

01:47:09.820 IND. That's right. Okay. Explain to folks, because you're the expert on this, explain to folks what an

01:47:14.800 IND is and how important this is in this regulatory pathway. In order to sell a drug in the United

01:47:21.420 States, you have to have an approved new drug application that's called NDA from the Food and

01:47:27.760 Drug Administration. So what do you do before you get that? You have to go investigate that drug. So

01:47:35.180 that's what an IND is. It's an investigational new drug exemption from all of the rules that say you

01:47:42.460 have to have this approved drug. So you go and meet with FDA. We provide them with the data and

01:47:48.620 the documents that we have available and say, dear FDA, we would like to run the following clinical

01:47:53.880 trial. And here's all our evidence. And do you folks agree with us? And in the course of hashing

01:48:00.720 that out, they will come back and say, we'd like you to do a little more work in with an animal model,

01:48:07.980 or we'd like you to do some additional studies in humans in a particular way. And so we are in

01:48:14.120 the process of doing that in three different therapeutic indications. What are those three

01:48:20.040 besides PTSD? One of them is an animal model that is for pet dogs who have pain from osteosarcoma

01:48:29.980 and the other osteoarthritis. Osteoarthritis of the knee and then PTSD. Right. So those are pain in

01:48:39.720 dogs, pain in people, particularly osteoarthritic pain, as well as PTSD, which I think of as a

01:48:48.440 combination of anxiety and pain. It presents in a number, a number of ways, mild, moderate, severe,

01:48:55.120 etc. Again, for the listener to make sure you understand the distinction, there are currently

01:48:59.580 products you are legally selling in Michigan that do not require an IND. They're currently

01:49:04.960 grass products. They're not basically pharma-grade products. Is that safe to say? Or is that-

01:49:10.060 No, these are pharma-grade products simply because this is the space that I live in. I have always

01:49:17.980 thought that that was the only appropriate way to make products. It's called meeting good manufacturing

01:49:24.140 practices. It's a couple levels higher than any of the states require for safety or efficacy.

01:49:32.520 And so we just make products to meet FDA specifications because to me, that's just easier.

01:49:38.660 In other words, you're a, this is going to sound crass, so excuse it and you can clarify it, but

01:49:44.040 you're like a supplement company that adheres to GMP practice.

01:49:48.260 I don't think of us as a supplement company.

01:49:51.260 Meaning you make a supplement to a GMP, this product, for example, like something that you

01:49:55.440 can sell currently today without a prescription.

01:49:58.120 Right. We work within the medical legal rules in Michigan, but those rules do not mandate

01:50:05.880 GMP manufacturing.

01:50:07.680 And you hold yourselves to that standard. That's the point I'm trying to make.

01:50:10.400 Yeah, that's exactly-

01:50:11.460 I'm trying to pay you a compliment, and I'm making it sound backwards, but yes.

01:50:15.420 And this is, as most everyone knows, doing an adequate amount of testing to go through

01:50:23.220 the FDA process is very expensive and very time-consuming.

01:50:27.460 And let's put some numbers to that. On average, it's about a decade and a billion dollars to

01:50:32.060 create a new drug.

01:50:33.100 Yes, that's exactly right.

01:50:35.280 Let's say that again. You want to make a new drug from IND to approval is order of magnitude

01:50:41.020 10 years and $1 billion.

01:50:43.520 Yeah, that's right.

01:50:44.460 I don't think your retirement account is that big.

01:50:46.700 That's correct. So anyone out there who-

01:50:49.560 This is going to turn into a telethon.

01:50:53.200 Let me ask, why have you not pursued a product yet on sleep? Because I, again, I think anecdotally

01:51:00.500 what you've said resonates with many people, the power of CBD, including probably very inferior

01:51:06.620 products compared to what you're capable of making with your IP. Is the view that you

01:51:12.880 don't need to go down the IND pathway to produce that, or is it just a matter of resource allocation?

01:51:18.300 It really is resource allocation. Truthfully, we have 14 indications that we are going for,

01:51:25.140 and you have to prioritize, as everyone does with everything in your life. And we looked at them

01:51:31.380 and said, which ones are easier or faster or less expensive to test and be able to prove.

01:51:38.900 Sleep studies, frankly, are very expensive and they are variable just in the methodology of it.

01:51:46.940 Whereas it's a lot easier to be able to measure pain and there are scoring systems that are more

01:51:52.480 reliable in that way.

01:51:54.360 Tell me a little bit about what you can sell in Michigan and how does a business work that

01:51:57.480 can only limit itself to one state?

01:51:59.120 So it's quite challenging. We drove at getting a license, a first license, and we were successful

01:52:07.540 in getting the first license in Michigan to be a processor. That is, we can take in cannabis that's

01:52:14.460 been grown within the state and turn it into an extractive and then turn that into tablets. That's

01:52:22.280 what the process of processing is. We could also make it into gummy bears and vape cartridges,

01:52:28.320 and we sell those also. And then we are able to ship those to just state authorized dispensaries.

01:52:37.500 Historically, people in Michigan needed to have medical marijuana licenses in order to get into

01:52:44.320 those stores. But now, like many states, it's called recreational or adult use. You only need to

01:52:51.520 show that you are 21 years of age to be able to go into those stores and buy. So that's how we started,

01:52:59.740 but now we have grown to have, we have liaisons with subsidiary companies or affiliated companies

01:53:08.880 where we're growing about 5,500 plants, bringing it to our facilities, doing the extraction.

01:53:15.960 And we have relationships with all of the 70, 80 dispensary stores throughout Michigan.

01:53:24.240 That's how that business has grown. And that's to a large extent so far, what's been able to fund our

01:53:31.820 research studies. But once again, this is a telethon, folks. You can call in.

01:53:37.000 How large is your team?

01:53:40.000 So we have overall about 100 employees working in various aspects of production and sales and

01:53:47.400 administration for the company. In terms of the research team, Deb is our chief medical officer.

01:53:55.780 And then there are about another 10 or so direct people working on it. And then another 30 to 40

01:54:06.320 consultants who come in and out of the projects to be able to work on those.

01:54:11.480 What will be required from a legal standpoint for products like this or similar products to be sold

01:54:18.800 across state lines? Does that only happen at the federal level?

01:54:22.540 Yeah. That only happens at the federal level. We think that the first number of indications that

01:54:28.560 we've picked and worked on with FDA are going to go through fast track approval. And that's without

01:54:37.820 getting down into the weeds of all of the legalities of that. That frequently allows a product to get

01:54:44.940 through the FDA process in somewhere between two to four years. In the space of drug development,

01:54:51.660 that's the blink of an eye. And at the same time, we're beginning our international aspect.

01:54:59.640 Deb and I will be in Berlin presenting our data at an international meeting of cannabis physicians.

01:55:05.880 So that this activity is very, very quickly spreading, not just here, but across the country and across

01:55:14.080 the world. I was lucky enough to be able to be at the United Nations in 2016, testifying and telling

01:55:22.280 the UN that they should change the war on drug policy from incarceration and retribution to medication

01:55:29.980 and treatment. And while things move slowly through the political process, we see that that is taking

01:55:36.780 hold in country after country that this war on drugs policy is changing dramatically to as countries

01:55:45.160 are able to see the medicine and science for themselves. It's very, very encouraging.

01:55:50.720 Deb, how often do you get invited to speak at medical conferences that are not about THC or cannabis?

01:55:57.180 In other words, how often is the anesthesiology society saying, hey, come and give us a talk on pain

01:56:01.600 and the use of this? Because as physicians, we're seeing that our patients are using these things

01:56:05.520 and we're ignorant.

01:56:06.280 Right. Sadly, not often enough. I do lecture to grand rounds for individual physicians and groups and

01:56:13.780 departments that have heard me speak or have seen me on YouTube and said, wait, we need to have her come

01:56:19.120 in. I'm actually lecturing in Detroit next month to a group of scientists and engineers and

01:56:26.500 biopharma developers who are interested in what we do. And so that's sort of a unique space. But I am

01:56:33.400 actually hoping to target in California at the end of Q2 for 2020 that I'm going to speak with the

01:56:42.720 Society of Pain. So I'm looking forward to that.

01:56:46.620 Now, this might sound like a dumb question, but if you have a state like Colorado or California

01:56:50.360 in which you have the same legal framework basically as Michigan, why can your product not

01:56:55.660 ship from one state to another state? Because I have to leave Michigan and pass into another state

01:57:02.660 before I get to Colorado. Even if I shipped next door to Illinois or Ohio for a microsecond,

01:57:12.420 it will be in federal land as it goes from state to state. It's called interstate commerce. And there

01:57:20.280 was a very classic law case on this 150 years or so ago that defined what is interstate commerce.

01:57:28.600 And it's essentially just stepping over the border and sometimes even more than that, just being on a

01:57:34.080 federal highway.

01:57:35.440 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

01:57:40.200 about what the legal framework is going to evolve into, do you believe that cannabis will always be

01:57:45.540 illegal at the federal level? Or do you think that it will have a change in legal status?

01:57:48.880 Oh, it's absolutely going to change. Absolutely going to change. No question about it. It's so

01:57:55.880 clear.

01:57:57.100 How long do you think this could take?

01:57:59.000 Well, we see that it is beginning. That is hemp right now is part of that story. It is the nose of

01:58:08.860 the camel in the tent to be able to move this forward. At this point, we have more than half the states

01:58:16.940 have said that these products are just fine for their patients, for their population. And FDA

01:58:24.020 is currently very, very actively involved in this. I was fortunate enough to be part of a task force

01:58:30.500 that started some years ago to be able to move this forward. FDA is struggling to find literally a

01:58:38.080 legal pigeonhole to put this into. My suggestion for any of the FDA officials who might be listening to

01:58:44.480 this podcast, and I hope it's all of them, that there's the over-the-counter drug review that has

01:58:50.840 been used for many, many years to be able to take products onto the shelves of drugstores to be able

01:58:56.460 to use this based on the fact that people could self-prescribe some medications for themselves. They

01:59:02.860 didn't need a physician to write a script. So we think that many of these products have sufficient

01:59:09.800 safety that they are self-prescribable. And I think we see that because, frankly, there's about

01:59:16.340 30 million, 40 million people using these on a regular basis right now. And other than the vaping

01:59:24.100 crisis, they're not filling up hospital wards due to toxicity from these products. They're able to use

01:59:31.520 them okay. So do you think that the farm bill is really the single most important thin end of the

01:59:37.100 wedge? Because it was the first piece of federal law that decriminalized the first part of the value

01:59:43.780 chain here? Yes, absolutely. It really was. I think that that will continue, actually, for many of the

01:59:51.040 cannabis business people who are struggling in this area because the tax laws are incredibly burdensome

02:00:00.880 and require a lot of dancing in order to be able to just simply run a business. But we see ourselves a

02:00:09.860 year and a half ago, I had to switch bank accounts four times in one year for if anyone ever tried

02:00:19.260 having to switch your bank account where your bank suddenly closes out on you every three months.

02:00:24.580 That's terrible, especially as you're just trying to run a business and pay bills. Now, though, we have

02:00:32.580 completely solid, reasonable banking relationships. We're able to get insurance. Everything is becoming

02:00:39.380 normalized. And we do not see patients or consumers acting foolishly in any way. Quite to the contrary,

02:00:51.320 they often are reducing the amount of smoking of cigarettes and alcohol use and are becoming more

02:00:59.280 law-abiding citizens and less. Deb, what concerns, if any, do you have about what this industry looks

02:01:06.940 like? I mean, I can't go more than a week without getting pitched some CBD, THC, hemp company. I mean,

02:01:15.700 there must be more companies sprouting up in some part of this value chain than any other industry.

02:01:22.540 I mean, this is, from an investment standpoint, this is an area where people are very excited.

02:01:28.300 I just don't imagine most of the people bring the expertise that your team is bringing, which is why

02:01:34.180 I wanted to talk with you guys as opposed to every other person out there who's peddling a cause.

02:01:40.280 But do you see that as being a concern? In other words, can a few bad actors set the stage back?

02:01:45.020 Yes, especially in the stigma area for patients. That's my major concern is patient safety. You

02:01:51.900 know, there are a lot of people out there that see a gold rush or a green rush, and they just want to

02:01:57.820 make products, sell them to people, and get out of Dodge and enrich themselves. And that's a concern to

02:02:03.260 me. You know, when patients, unfortunately, are not understanding that just because you can buy

02:02:08.440 something off the shelf of a big box store or from an online source that it's tested and it's safe

02:02:15.700 because there's no guarantee to that. And so, you know, my recommendation of patients is if you live

02:02:21.560 in a legal state, you should buy from a legal dispensary, ask for their certificate of analysis,

02:02:26.320 take a look at it, make sure that there's no adulterants to the best of our knowledge in the

02:02:30.860 science right now. This is why I'm happy to work with Steve because this is his passion as well,

02:02:36.260 because we really don't want to hurt people. I mean, that's the thing that kills me. That's the

02:02:41.880 reason why actually it should be descheduled. I mean, so it would allow for robust testing,

02:02:48.880 a standardized testing. I mean, just because there's testing in states doesn't mean they

02:02:53.280 all use the same methods.

02:02:54.860 That's sort of something you guys brought up today that was news to me, which was

02:02:57.940 the inability of the states to rise to the level of federal testing. And so in many ways,

02:03:04.440 the decriminalization state by state is not a great approach. You can't just run that out to

02:03:10.320 its natural conclusion without decriminalizing it at the federal level to get the full muscle

02:03:16.320 of the FDA and the protocols behind testing.

02:03:19.940 Absolutely. I mean, from laboratory to laboratory, there are no standards. And the problem is there's

02:03:24.780 no guidance because it's been illegal. And so the sources that laboratories would use to go to,

02:03:31.280 to say, well, where do we get our standards from? And what are the methods of extracting from this

02:03:36.860 gummy bear or this brownie in order to test the potency or test the microbials or to test any of

02:03:42.260 it don't exist.

02:03:44.120 So look, there are people listening to this in 49 states that are not Michigan, not to mention people

02:03:48.680 that are listening to this outside of this country. What would be your playbook for them to protect

02:03:53.880 themselves as they go into their local dispensary or purchase online? You know, you can buy CBD

02:03:59.440 across state lines if it's pure enough. How would you give people a sort of instruction list of things

02:04:05.420 to do to first and foremost protect themselves?

02:04:07.520 Right. So this is a human rights issue. You hit the nail on the head. I mean, that's a huge problem

02:04:12.800 for me as a physician to guide patients, which I do. I guide over 400 patients privately, free of charge

02:04:19.480 because I'm a terrible business person. But for me to guide them and have to understand

02:04:25.040 their state in order to help them access certain medicines is just horrific to me. But what I would

02:04:31.740 say to them is go to a legal state, become certified as a patient, meet with a physician

02:04:37.500 there and get the guidance from that and buy from a legal dispensary.

02:04:41.760 Do you think that's enough? So, I mean, a physician in another state, do they have the expertise

02:04:45.980 to help them navigate through the dispensary?

02:04:48.600 There is a society called Society of Cannabis Clinicians where they have a list of doctors

02:04:53.660 by state who actually are experts in cannabinoid medicine for which they can go seek out and help

02:05:00.680 themselves. I mean, this is a nascent industry. It's still federally illegal, which allows for all

02:05:07.440 of these hoops to have to be jumped through. I would recommend not buying online. I would recommend

02:05:13.260 not buying off the street. I mean, we tell our children, don't take candy from strangers

02:05:17.780 because you don't know what it is. Why would our medicine be any different?

02:05:22.740 So, I don't know that it's widely known, but I developed the actual assay methods to detect LSD,

02:05:29.660 marijuana, cocaine, amphetamines. And I published those results when I was 21 and 22 years old.

02:05:35.840 So, I really have a pretty solid sense of what these laboratories are able to do.

02:05:42.380 That was, well, almost 50 years or so ago, and it was my first scientific publications.

02:05:49.340 The labs are capable nowadays, because I just recently set one up a few years ago,

02:05:56.060 of doing remarkably accurate and precise work on all of these cannabinoid products,

02:06:04.500 and to be able to do it. But the state rules vary, and the states are still learning. What should

02:06:10.860 the pesticides be that are allowed or allowable? What are the levels of heavy metals, et cetera?

02:06:16.640 So, from state to state, the rules vary, and they are getting more learned as the work is done.

02:06:26.440 So, this is a great developing field. Some labs are better than others to be able to do it.

02:06:32.540 So, that's why, to echo Deb's recommendation for people who want to utilize these products,

02:06:40.260 they really need to ask for the certificate of analysis, see if they can become educated enough

02:06:47.060 to be able to do that. Certainly, physicians should. I know that these systems,

02:06:53.380 endocannabinoid systems, were not taught in medical schools. They certainly weren't taught

02:06:57.000 in the chemistry schools that I went to. And this is a remarkable societal experience

02:07:06.300 in allowing non-toxic substances to be used and self-prescribed. I think it's a challenge for the

02:07:15.480 physicians to catch up, because you are a learned intermediary to help patients be able to do this.

02:07:23.940 And I hope out of this podcast, that's why we're here, is to help encourage all of these educational

02:07:32.320 programs. Because, frankly, our hands are full enough just running the clinical trials and being

02:07:37.400 able to run a business. So, we're going to have to leave that part of it up to you.

02:07:41.780 Well, on that, guys, I want to thank you very much for coming down here today and for making time and

02:07:45.300 for sharing kind of all your insights and for the work you're doing. I mean, I think this is,

02:07:48.940 I don't know, I've got to be honest with you. I think I'm still somewhat confused about all of

02:07:53.740 the different permutations and combinations of these molecules. And it's complicated by the fact

02:07:59.560 that interstate commerce prevents easy access of higher quality products to individuals. So,

02:08:08.680 I guess the thing we can all hope for is that, and again, I would say this, frankly, even if you are

02:08:14.940 still undecided on the safety or efficacy of these, everyone still seems to benefit from the

02:08:23.900 decriminalization of this because it allows far more rigorous testing and it destigmatizes so much

02:08:31.160 of the research funding that goes into this. But I think one way or the other, we get answers quicker.

02:08:36.640 And that's probably what we're kind of missing at the moment.

02:08:39.520 Right. This is a process that's unfolding in a very, very short length of time. I was at a meeting

02:08:46.920 with FDA, DEA, and Department of Defense just four and a half years ago, and NIH, where I brought up

02:08:56.960 the idea, hey, fellas, you're the federal regulators, and it looks like cannabis is going to get approved

02:09:03.480 state by state. Why don't we try and set some federal health policies here around that? And

02:09:10.600 just four and a half years ago, everyone in the room except me said, are you kidding? That's never

02:09:17.620 going to happen. And now we see it actually has. And so the people who are in a role to be able to bring

02:09:26.240 these forces to bear are trying to play catch up and do it and more power to them. And I think that

02:09:33.780 everyone should just try and continue to do just as you are doing here. Allow folks like us to bring

02:09:42.200 our thoughts to bear and happy to hear from anybody. We're not certain we have all the best right

02:09:48.760 answers. We have a particular predilection towards medicine and the idea that above all else do no

02:09:57.460 harm first. We just, we're kind of pushy about it though. Thanks very much, guys. I really appreciate

02:10:03.480 it. Thanks for having us. Thank you. You can find all of this information and more at

02:10:09.660 peteratiamd.com forward slash podcast. There you'll find the show notes, readings, and links related to

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The Peter Attia Drive - November 25, 2019

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

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