Edge of Cannabis Medicine
Matthew Myro and Mark Mangieri
I am seeking out experts and innovators all across the medical cannabis/ marijuana industry in order to bring you, all the very best information possible. Todays guest is Mr. Mark Mangieri. Mark works for a company called Hemp Synergistics and they have created a really innovative process of taking raw hemp oil and converting it into a powder, in a way that nobody has ever done before. So it’s five times as strong, has no taste, it can be mixed in really easily and used for creating different formulations. It’s super cool and we get really deep into the details of how this works. It was just really fun talking to Mark, hes a great guy with some really great experience with the nutraceutical industry. Please enjoy this episode with Mark Mangieri.
I am Matthew Myro and this is the Edge of Cannabis Medicine podcast. Today’s guest is Mark Mangieri. Mark started in the nutraceutical industry in 1998 and started product formulation in 2000. He has launched 6 brands, including his own brand in 2005. By 2015 that start-up product reached the shelves of every GNC and Vitamin Shoppe around the country. And from there mark transitioned to creating functional foods and fortifying snacks which led directly into his current role as director of sales and product development at Hemp Synergistics. Your product isn’t so much a product as a new way to process cannabis and I thought it was fascinating. So maybe we can backtrack a little bit and you can tell us how you made the jump from your previous careers to the hemp nutraceutical industry?
Sure. You hit the nail on the head right off the bat, we see that CBD and the other cannabinoids, not necessarily as an industry, but we see it as an ingredient. That can be used functionally in a variety of ways. And that’s how it became a good fit for me. So backing up, in my college years I was really into training and all that that entails. I got really into sport supplements as a part of the culture and wondered how to increase my performance and got engrossed in how they work and why they work for me specifically and the science behind it as well. At the time I was at Penn State, I was an agriculture and food science major so it kind of played into a lot of the topics that I was actively learning about. It was one of the pioneering universities to first study createmonohydrate on the baseball team. So it was very specific to me and specific to what I was doing and it grew from there. After graduating I found myself back in Pittsburgh, that’s where I’m from, working for a contract manufacturer of nutraceuticals. And my fascination and general curiosity kept growing. And by 2000 I become part of a product development team. I started a few brands and by 2005 I started my own brand called Bio Rhythm and we did pretty well. It was a slow process and along the way, if you remember from the 90s, in the news there’s always some new ingredient that’s making the headlines. I don’t even remember them but you’ll usually see a spike in popularity and then a drop off. So when CBD and the different cannabinoids started becoming more popular, I payed attention to that because that’s where I came from. But it maintained it’s popularity and it kept growing. And it keeps growing at a point where its superseding any other previous popular ingredient. But this one was different in that all the products coming to the market were only or significantly built around CBD or the Phyto cannabinoids. And that was the strange thing that struck me as a product designer. Why it just was the singular ingredient? Why not couple it with other ingredients? And just being in the industry and being in the area, I came across the group Hemp Synergistics and got a behind-the-scenes look for the first time of what’s going on. I spoke to farmers. I spoke to processers. What we do here is we’re the last stage remediators. We take it from a crude oil to something extremely refined and ready for consumption. And so I learned about that process. And the idea of all these products in stores and companies built around this one ingredient struck me as something that was going to change really soon. And my conversation with the management here was that I see this as an ingredient. If I come on board, here’s my angle. Initially it was about making a brand and using CBD as one of the ingredients. But the reason why there’s not many products out there with significant support ingredients, in these tinctures or soft gels, is because CBD is very hard to work with. Its very viscous and sticky and goopy, it’s prone to oxidation and sometimes you’ll see darker spots or brown spots. Sometimes you’ll see tinctures or gummies packed with darker materials in order to protect the CBD from oxidation. So our goal as a team was to turn that into something that’s more durable, more functional so it can be used in different applications, and more affordable as well. And that’s another component. The pricing is still very high. Because the technology to bring it to a finished good, a lot of hands have to touch it, a lot of expensive equipment is used. And that’s what keep the price so high for CBD. So what we developed was a way to turn that sticky, viscous hemp oil into a very dry and free flowing powder that’s protected from oxidation. This powder won’t turn dark. It’s not affected by sunlight or open air. So the product we developed is called Bio Dry and it’s sister product is plainly named CBD Bake Mix. The Bio Dry has a CBD concentration of 50% and the CBD bake mix, which is much more durable for obvious reasons, has a CBD content of 20%. Again, the reason why we’re excited is because it’s an industry first. We see it as a change, and not only with how CBD is taken but also with how its perceived. I lead with CBD but the other minor cannabinoids are equally important. The same science in refinement techniques apply to all the cannabinoids. Long story short, turning it into this powder gives formulators and users the freedom and flexibility. It give formulators the ability to put this powder into a hard shell capsule and then couple it or compliment it or accentuate the effects with other ingredients. So its going to open the doors to a wide variety of possible benefits.
Thanks for diving into that, I have a lot of questions. We’re going to get real deep into all of this. I’m going to start with the other minor phyto cannabinoids. This is something that grabbed my attention about the product is that it doesn’t work as an isolate, it is working with full-spectrum. When talking with other specialists about isolates and full-spectrums, there seems to be a 100% agreement that full-spectrum is far more effective. Do you mind talking more about these minor cannabinoids?
I think in one of your podcasts you talk about the need for more research. Currently, CBD and other cannabinoids, theres about 22000 studies done in the last two years. Now that might sound like a big number, but by comparison its pretty small. There still needs funding and more research done on it. These other minor cannabinoids like CBG, CBN, THCV, which is what I’ll be keeping my eye on, THCV has the potential of helping people with blood sugar problems. Early studies are showing that it’s extremely effective at helping regulate blood sugar. Most of the minor are really expensive. Because of the extraction techniques and the low volume in which they exist naturally, it has to be refine multiple times. In general, these things are costing 20 to 60 thousand dollars a kilo. Each one of these minors are a super star for helping with a variety of issues. PTSD. Sleep disorders. Anxiety. Blood sugar problems. In general, they’re too expensive, although the pricing has come down a little bit over the past few months. We haven’t dug too deep into the minors. We want them present and we know they exist. There’s something call the entourage effect, and we want the user to have the entourage effect and in our broad spectrum products, we have a few minors detectable but that’s it however. The next popular besides CBD is probably going to be CBG or CBN. Right now the best form is the tinctures.
I spoke to Dr. Jeffry Black who is an expert on endocannabinoid system and one of the things that he is a massive supporter of is moving away from the term entourage effect and moving to the term ensemble effect. They all work together, rather than focusing on CBD as the big proponent and everyone else just hanging out.
I’ll switch out my verbiage from now on and it’s a good point too because THC, CBD are the most prominent cannabinoids. But CBG and CBN have a far greater effect at much lower dosages. So juts because they exist at 1/10 or 1/20 the concentration of CBD, does make them 1/10 or 1/20 as effective. They aren’t tag-alongs, they’re also part of the show as well. That’s a good point and I’m switching to saying ensemble now.
Also, the two cannabinoids that you mentioned, CBG and CBN are also really interesting because they’re age related. It’s fascinating that these two molecules are growing more and more popular and it’s cool that we’re sort of able to control the amounts of them depending on the age of the plant.
The fact that they exist that way, speaks to the way that they exist post-harvesting. They’re both more sensitive than CBD. More sensitive to heat, to light. It makes it a more difficult product to manufacture. It makes the storage conditions more strict. Which gives us all the more reason to aim for more standardization. That’s what this is all about, standardization. It highlights the need for us to standardize its existence.
There’s a lot of steps in the process to get to the point where you get to do what you do. There’s the growers and they have to harvest it and then they have to get that product over to the processors to get the oil and then you guys take that oil and then do your processes on it in order to make it this powdered product. Now traditionally I understand that there is this nano emulsifying procedure that is how you traditionally go from the oil to the powder. But what you guys have done is something totally new, a game changer in this industry. Make you can talk a little more about how you got to where you are now with that whole process?
Yeah, it is a game changer because the of the freedom of flexibility and the increased stability. The good thing is, is that I didn’t come from the cannabis industry or the hemp industry. When I walked in here, I didn’t know much about the science of it. The nano emulsification, in addition to the normal process of turning a hemp oil into a tincture is that it is already really laborious. Again, there is a lot of expensive equipment used. You then have to bring that into a sonicator, in order to nanoemsulsify it. And that takes a lot of time and it produces an enormous amount of heat. When you nano-emulsify you have to pack the product that you’re emulsifying and you can emulsify any oil. But you have to pack it in ice. I guess my point is, when you put a product through a nano-emulsification, the product is at risk. It’s at risk of being denatured, it’s at risk of being changed into something else. You also add a lot of time and you also add a lot of cost. After you nano emulsify that product, and you want a powder, you then have to do this spray dry process. Currently, if you want a CBD powder, you have to then get that emulsification and then do that spray dry. And again, it involves pressure, and it takes a long time. So that’s whats keeping the pricing so high. That’s what makes the drinks so expensive is because it takes so much work to get to that point. With the Bio Dry process it’s a much more lighter process and it’s a patent pending process. And it’s a simple combination of poly saccharide which is a root starch and a fiber. At our highest concentration, the hemp oil is about 55% percent of the volume of the product by weight. And so if you’re looking for a high CBD content, we can get it as high as 50% by weight. Because those broad spectrum distillates are 90% CBD by weight. And of course the other minor cannabinoids are present. And so the process is more of a food science project than a chemistry project. And the thru-put and the scalability is far greater than the nano process. We’ve successfully produced several batches and our official launch is the beginning of next month. And we’re confident that we can meet any demand. It’s an easily duplicated system, with minimal investment on a production side. And that’s where a lot of my history is, is production, sellability and monitoring that retail price. Because the lower the price, the more people will be able to use it. And so this whole process speaks to that. And that’s one of the reasons why this is a cool new process and product. It’s checking all the boxes that we need.
Yeah. Speaking of checking those boxes, in terms of bio-availability, that’s a big box that you guys are checking. I was digging around a little bit and there’s this nasty enzyme called SYTOCHROMEP4503A4 or CYP3A4 and this tends to block a lot of the efficient uptake of these endocannabinoids because the stomach and the guts are producing all this. So what have you done to get around that in order to increase the bio-availability?
So bio-availability, backing up a little bit, simply means the rate at which an ingredient makes it into your blood stream. So let’s say you take 100 mg of CBD by tincture. Your best case scenario is to absorb into the bloodstream somewhere in the mid-teens, like 14% , 15%, 16% of that will get in. Soft gels are lower, in the single digits. Versus smoking, which is the highest, about 40%. Again, a lot more research is needed on the condition for creating the best possible scenario for you to absorb things. A lot of products say to take with food or take with something fatty, that seems to help. But your real roadblock is our own body’s reaction to a foreign body. I don’t care how natural an ingredient is, there’s a reaction whenever you put something in your body. These cannabinoids are no different. So specifically with the Bio Dry, the cannabinoid has two enemies. Number 1 the mouth: your body can produce something call amylase, and that begins the digestion process in your mouth. You swallow it, it goes into your stomach, and of course you have a very acidic environment. That can also harm the cannabinoid. Specifically Bio Dry and the bake mix, that poly saccharide, that root starch full incases the hemp oil molecule. It protects that cannabinoid. It protects it from sunlight, it protects it from acid. Acid cannot penetrate this polysaccharide. No matter what. So the absorption of the cannabinoid begins in your small intestine. That’s where most of the absorption occurs. Of any food or nutrient you put into your body. So by the time it goes through your mouth and down into your stomach and reaches your small intestine, it is 100% intact, the Bio Dry that is. I’m not saying you get a 100% absorption, but by that point you’ve gotten a 0% loss. So that alone is a huge win for bio availability, right? And after that, your body releases these defenses. These enzymes as you called them. The P450 enzyme group is a very common group of enzymes. If you’ve ever gotten a prescription before and it says, do not take with grapefruit juice, the reason is, grapefruit juice has an ingredient, I believe it’s called bergamottin, it inhibits a very specific enzyme. And that very specific enzyme is known to attack a lot of different foreign entities. How I became aware of it was back in the nutraceutical world. So these enzyme are on a mission to destroy these ingredients. Specifically any hormone altering ingredients. When that phyto-cannabinoid reaches your small intestine, these P450s are released and get instruction to destroy that cannabinoid. And that’s where probably 80% to 90% of the loss occurs. So again, speaking to the very concentrated nature of the powder, if you put it in a pill and add other ingredients in there, you can add other ingredients that can counter-act those enzymes. So we put together a group of ingredients in there called Canna-Boost that are designed to temporarily inhibit those P450 enzymes that are known to attack the cannabinoid. And they’re ingredients like black pepper extract, curcumin, and those ingredients are great anti-inflammatory ingredients on their own, lots of people just take those alone. But specifically when you couple them with a CBD or CBG or CBN or any cannabinoid they’re there to increase the bio-availability by temporarily inhibiting those enzymes from attacking this cannabinoid. It’s well established science on how this works and for some reason it just hasn’t been addressed in this industry yet. So we’re real excited we have a capsule product called on the market to sort of demonstrate that these two ingredients work really well in concert together and that these two groups of ingredients produce accumulative, very positive, biological effect.
Yeah, I was so excited to see that. I’ve been using biopren for a long time just because I want to get the most out of my turmeric. And seeing how they can work together and specifically seeing curcumin in a formulation of CBD because I don’t know too more anti-inflammatory products that exist on the planet. So seeing them together and boosting by the biopren was really cool. So you have two thumbs up from me on that one. Good job.
Thank you. And Biopren is produced by a company called ________ and it’s been in the industry longer than me. They’re producing it at a very high level. They’ve done their own studies specifically and the biopren increases the absorbability of the curcumin which increases the absorbability of the CBD. So it’s this nice ensemble of ingredients that really and truly compliment each other in every way possible.
Yeah. Very cool. It’s very cool. So I wanted to backup just a little bit. So you guys claim that the Bio Dry has 5 times the concentration of these other nano emulsified powders. So number one, how are you able to prove that’s the case and number two what is it that you’re doing that allowing you to do that?
Well the short answer is is that it’s a different process. We started doing this Bio Dry before we understood what nano emulsification was. Which is a good thing. One way to keep an open mind about any process is to not really dive too deep into what the standard is. And not to throw shade on the standard, it’s just sometimes that it can sway you in the wrong way. And let me go off track, real quick, before I started with Hemp Synergistics I made functional foods. I had this idea to make an almond butter keto truffle. And I said to myself, do not learn how everyone else makes a truffle, just figure it out yourself and when you got it down, go back and look. So I did it and it literally took me two months to figure it all out, exactly how to do it. And then I went to look at how it’s made on youtube just to see what they do, and they do it the exact same way that I figured it out. So sometimes that can come back and waste time but now I’m so intimately familiar with every step of the process and I knew it backwards and forwards and I just didn’t have to follow instruction. So that’s what we did with the bio dry and we just did it intuitively and calculated it should be and that’s how we got 50% concentration. Now looking back and fully understanding this nano-emulsification process, there’s a lot of steps to where if your goal is to have a concentrated powder, there are steps that are unnecessary. Nano-emulsification exists so you can put a concentrated liquid into a larger vat and then dilute it out and have this CBD drink that the powdered version of it was an afterthought. In my opinion. So they got this concentrate liquid and then they spray dry it. And the maximum concentration that we’ve seen is maybe 15%, 16%, 17%. Most of the nano-emulsification powders are 4% or 5%. And the formulas are wonky at best. They have a strong taste. They’ll make you change your recipe. The bio dry and specifically CBD Bake Mix has literally zero impact on taste, literally zero impact on the recipe. You just add it in and it’s so concentrated. It’s not voluminous enough to affect what you’re doing. It’s such a small percentage. And so, how we were able to do that is to not pay attention to the way it was currently made and to sort of soil our thought process and to try and make that process better. We just never learned how to do it in full and just did it our way. How do we know it works? Well we send the product to a third-party lab and have it analyzed, not only in its pure powder form but we put it in a muffin or a capsule and test the ingredient as it sits in a more complex product, just to make sure that it stayed stable through whatever process it went through to get to that final product. And it works. The next is, we partnered with a variety of different partners in different industries, we have a doctor who specializes in rehab therapy who has used some of these ingredients with some of her patients that’s also enrolled into a peer review case study. So we’ll be able to judge the real world efficacy of these ingredients and finished products. And so that’s how we come to the ingredient and that’s how we know the ingredient is going to be effective.
So I saw that you have a partnership with Grimway Farms?
Grimway is a large, organic, and I believe the largest organic farm in the United States. They got into the hemp growing business. And unfortunately for farmers it’s been a tough go in recent years where the bio mass that they produce is not very valuable. It’s not as valuable as…they’ve been sold at one point. And that’s a function of the large number of people growing it and like I said it takes a lot of work to bring it into something valuable. So our partner with Grimway is nice because we have a giant supply of ingredients and they’re very consistent with their grows and we’re not as prone to market fluctuations in price as other companies might be. So you have this agreement that allows us to have a large amount of product at a very consistent price over a long period of time. And if I’m a brand and I’m looking at one of these ingredients, that’s one of the things that I’m concerned about. Over the years you see these shortages and spikes of various commodities. And so the way to lower your risk against that flux is through these long term relationships and we’re real happy with our partnership with Grimway.
The Farm Bill that passed in 2018 opened a lot of eyes and a lot of doors for people in this industry. And one of the things that it made very clear, very quickly was the different concentrations of different cannabinoids in different parts of the plant. So for a long time there was this marijuana part of the plant and the hemp part of the plant and now because of the wording within the farm bill we’re able to use the flowers from the cannabis plant that has extremely low levels of THC to extract the most phytocannabinoids possible from it. Number one, is grimway taking advantage of that? So you’re able to use the flowers as the base for the extract as opposed to the less concentrated leaves and stems and things like that. So I guess we’ll just start there.
Yeah, whenever you’re making an ingredient or whenever you’re making a product, you do have to declare on that label where that active ingredient came from in terms of part of the plant. The arial parts or the flower is where most of cannabinoids live naturally. There’s some in the leaves, there’s some in the stems, and I’m speaking a little bit of out school here because I am not a farmer and I’m not an extract professional but just knowing that in general. So that’s where you get the most for your labor dollar. And that’s kind of how you have to think in my opinion. If you’re able to harvest these buds and put them through the first level of extraction—when we get the product it’s at the crude stage. We’re not dealing with bio mass, there’s a lot of crude extractors out there. Sometimes you get some pieces of plant. Its not a clean product, its not ready for general consumption. But it’s 25% of it down the road. They took it from that first step of taking something that grows out of the ground into an oil. And so the flower is where you get the most bang for your dollar. So that’s what we’re receiving from our Grimway fellows. Even if we go to a local farm, and need something specific from somebody else, that’s where we’re sourcing.
Okay. So you’re in Pennsylvania correct?
And so Pennsylvania has a very robust and growing medical cannabis industry. So you’re specifically working in THC free zones right now, but being in a state where it is legal for THC, do you have any plans for creating extractions along those lines? Because I imagine that this product would be incredible beneficial for that side of the industry as well.
Well, not specifically. And I’m not real familiar with the THC laws in this state here. I know it’s not approved for recreational use and just medicinal, and with my understanding it’s not very hard to get a medical card. Which is good news. But for us, the way we see ourselves possibly interacting with that side of the industry is, this Bio Dry product is actually a process that can be applied to any cannabinoid, including THC. And so, again, changing it from a sticky, viscous, into a Bio Dry form, is how we would interact with the THC community. And we’re open to that. But we don’t deal with THC in house here. I don’t think there are plans to get into it. We have our hands full with what we’re currently working on. But we have talked internally to applying this process to THC oils to make them more accessible and more easily consumed. There’s still a stigma attached to it compared to CBD. So we have a little way to go in Pennsylvania. But I see ourselves working with that side of the industry using this process.
Right. Because it would be so beneficial. Some of the major issues with THC based medicine is that the quickest way to access it is to either smoke it or vaporize it. Which is not ideal or healthy. And then the other side is the edible solution, which has negligible efficacy. But the edibles tend to be filled confections which is not the healthiest way to go. You could have a small amount of a pill with this powder it could real help the process, especially for people with stomach issues. Which THC is very very good for. Anyway, I’m rambling. Anyway, I see a great possibility with you guys.
No you’re not rambling and it is important and I do know about IBS and I have a severely autistic son and he can’t smoke he doesn’t understand the idea of smoking and to force an edible down his mouth, I can’t see that being a possibility or something that I would want to do to him. So being a young adult, which is something that he is going to be soon, if it were a simple pill, that’s much more therapeutic. It falls in line with our version of normal. In the United States at least. And in the pill form, all those same technologies with absorption, you could have a 90 percent absorption rate. That’s the real world benefit of these types of ingredients. And then you widen the audience. That’s the goal here. Make it easier to consume and widen the audience.
Okay, I’m going to make a turn here back to CBD. With the Farm Bill, I think it had a lot of unintended consequences that the government didn’t forsee, like CBD gummy worms in a gas station. I don’t think that they could see that happening with this Farm Bill. But they did open the door for that to be a possibility. Now before all this covid stuff happened, there were some rumblings out of D.C that the FDA was going to take a really strong look at CBD to see if it needs to be reclassified away from a nutraceutical to a pharmaceutical. Do you have any understanding around that being a possibility or any plans to work more in that direction depending on how the FDA chooses to go?
Well the regulatory is the ultimately big unknown variable here. I seriously doubt it. Because it has permeated so many sections of the free market from the gas station to the vitamin shop. I mean literally it’s everywhere and it’s weird. It’s in video stores. It’s strange and here’s what I tell people when they see it in a negative light: it’s because it works. That’s the reason why it’s so popular. The end. It’s also profitable right now, there’s a lot of price gauging going on right now. That lends itself to unscrupable business practices about mislabeled business products or products that don’t meet label claims or silly claims that people make on the label. So what we see regulatory doing is putting and curbing that activities. Putting a high standard on the labeling and the testing. Maybe a higher standard than nutraceuticals. But to completely eliminate it, I think the backlash will be too great and it’s a step too far. And ultimately those government bodies are run by people and people have a human element to all these regulations. I’ve sat down across the table from various FDA administrators over the year, and their goal isn’t to prop up FARMA. It just so happens that there’s this one company that’s been working on cannabinoids since 2003. And really studying it and putting serious money in it and they deserve a cut of what’s going on. So that’s one of big hurdles—how can this ingredient exist both as a nutraceutical or a pharmaceutical. And at the top of podcasts you talked about isolates. And that’s a sure way to attract negative attention from the FDA. Because that’s more the pharmaceutical side. And I’ll give you an example, White Willow Bark. This is the common herb or nutraceutical and the active ingredient is salicylic acid or something like that. If I refine that