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RHR: A Deep Dive into CBD, with Will Kleidon


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The CBD industry is booming—and misinformation is growing as a result. In this episode of Revolution Health Radio, CBD expert Will Kleidon clears up misconceptions about CBD and explains more about how these products work, our history with hemp, and how to get the dosage right for your body.

Revolution Health Radio podcast, Chris Kresser

In this episode, we discuss:

  • What is CBD?
  • The legal and regulatory environment around CBD
  • The health effects of CBD
  • Choosing a CBD product and determining dosage
  • How the CBD industry is changing and what’s next for Ojai Energetics
  • Topical uses for CBD

Show notes:

Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week I’m really excited to welcome Will Kleidon on as a guest. Will is an award-winning pioneer and futurist in the cannabis industry. He’s known for cracking the CBD code by creating the most effective and clean CBD-rich hemp products on the planet. He’s been featured in Cheddar, Forbes, Money, Entrepreneur, and the LA Times and is a regular keynote of the cannabis forum and BevNET. He is a subject matter expert when it comes to the art, science, and technology of cannabis, the history of hemp, and what it means to our future. And I’m really looking forward to doing a deep dive with Will on CBD, or cannabidiol.

I’m sure many of you have heard of it. It’s a powerful medicine for a lot of different conditions and situations. I use it extensively in my clinical work with patients and it has a lot of applications. At the same time, there’s a lot of misunderstanding and confusion about it. It’s really exploded as an industry and whenever that happens, you get a lot of unsavory entrance into the market, a lot of BS claims and a lot of hype.

So I want to sift through all that and just get to what the research says and also talk about the most important things to consider when you’re choosing a CBD product, how to dose it properly, etc. So I’ve been excited about this conversation. I hope you enjoy it, and let’s dive in.

Chris Kresser:  Will, thank you so much for joining the show. I’ve really been looking forward to this.

Will Kleidon:  Thanks for being here. Me as well.

What Is CBD?

Chris Kresser:  I want to start with the absolute basics here. I mean, pretty much everybody who is listening to this, I think, has heard of CBD, or cannabidiol, at this point. But I have a feeling that there’s still quite a bit of confusion about what it actually is. So, what is CBD?

Will Kleidon:  So, CBD is a, what’s called a phyto-cannabinoid. It’s a fat-soluble compound that is a byproduct of the cannabis plant. It’s one of over 400, or one of over 114 cannabinoids, and there’s over 418 compounds that the cannabis plant produces, and it’s one of them. It’s probably got the most coverage currently, other than THC. And when I talk about CBD, I’m always referencing CBD in a phyto full spectrum or broad-spectrum complex. Some people are isolating the molecule. It’s kind of like the trumpet section. And in reality, what our bodies really need is the trumpet section with the symphony orchestra of all the other cannabinoids and bioflavonoids and terpenes, etc.

Chris Kresser:  Right. And we’ll get into more detail on that because that’s something you and I both agree on. As an herbalist myself, that’s one of my pet peeves is this allopathic idea of isolating a specific nutrient or compound and amplifying it. And then expecting that we’ll have the same therapeutic effect and no side effects that you often get with the whole plant. But it’s obviously not that simple. And we’re going to dive into that further.

One of the first things that comes to mind for my patients sometimes when I recommend CBD if they’re not familiar with it, I see a look come over their face when I say this is from a cannabis plant or cannabinoid. And they say I’m not interested in that. Then I need to explain that there’s not the same psychoactive properties with CBD as there is with THC. So, again, for the person who’s not very familiar, can you tell us a little bit about how this works?

Will Kleidon:  Yeah, so it is completely, you do not get high at all from it. In fact, through some indirect mechanisms in the body, that actually counteracts the psychedelic component of THC, and some of the other psychoactivity effects from THC.

Chris Kresser:  I think in a previous conversation you mentioned you’ve been exploring this as a sort of antidote to feeling high.

Will Kleidon:  Yeah, so it’s half of it.

Chris Kresser:  Right.

Will Kleidon:  It gets rid of the, so THC agonizes, so our bodies have these receptors called endocannabinoid receptors. We know two, and now three. The third has been discovered. There’s going to be more in all likelihood.

Chris Kresser:  Right.

Will Kleidon:  THC directly fits like lock and key into one called CB1, and that’s throughout our brain and nervous system, predominantly. And then it also, they found that there’s serotonin receptor sites that couple with the CB1 receptor. And the THC will agonize that serotonin receptor, and it’s the same receptor that other psychedelic compounds like DMT or LSD or psilocybin agonize, and that can attribute to the psychedelic edge of THC. Now CBD binds to that serotonin receptor and selectively down regulates allosterically the THC action and shuts that part of it off and can bring the psychedelic edge down.

And then there’s another compound, pregnenolone, which we produce in our brain, that binds to the CB1 receptor and selectively shuts down the agonization of THC at that site. And so combined, it’s a complete antidote and completely sobers the user up. And we have the patent issued for that.

Chris Kresser:  That is a neat trick.

Will Kleidon:  Yeah.

Chris Kresser:  And actually, it has therapeutic, many therapeutic benefits, as you and I have discussed before. Some people find, and we find in our work with patients, that THC is a medically useful compound above and beyond just the recreational use. And people taking it to get high, it has some properties, therapeutic properties, that CBD doesn’t have. And for some people it can be really helpful, particularly with inflammatory bowel disease and sleep issues. But they don’t want to wake up or deal with any of the psychoactive properties. So, it’s really useful to have that tool in the bag, so to speak.

Will Kleidon:  Because it’s only going to be on the CB1 and CB2, or CB1 and the serotonin site doesn’t get shut down, and then the THC will still be active on other receptors and CBD2 receptors of the body.

Chris Kresser:  Still has a therapeutic effect without producing the psychoactive properties. Yeah, that’s phenomenal.

Will Kleidon:  And our bodies certainly need, in reality, trace amounts of THC. The best, and I consider cannabinoids, particularly the ratio that is found predominantly in our non-psychoactive varietals of high CBD, low THC, but some THC presence, and the other cannabinoids to be micronutrients in reality. That’s the hypothesis. Given the anthropological record of usage, it’s one of the oldest plants domesticated, if not one of the first.

And we have evidence of pre-Neolithic cultivation and usage in Japan. And then around, right when we went to, from hunter–gatherer to agricultural, in the Chinese record, it’s one of the first plants recorded to be domesticated. Then the Scythians and the Steppe people took it and brought it. Anywhere that they went, they brought it to the Greeks who brought it to the Romans. And then anywhere Rome colonized, they brought cannabis. They brought it to the British and then anywhere the British colonized, they brought cannabis.

And the first cannabis laws in the U.S. colonies where you would be fined if you didn’t grow it. And the oldest cookbook that’s recorded and printed is a Roman cookbook. It’s around 300 BCE, that it contains a recipe of cooking with cannabis flowers. And so, there’s documented direct intake. The Scythians used it through combustion. And then there’s the direct recipe of Romans of cooking with it. But the primary intake would have been through feeding it as fodder to the animals. And there’s record in Pennsylvania pre-prohibition being fed to chickens and then all the way back there’s older historical record of some islands as well.

But a prelim study in Colorado, post-2014 Farm Bill, they did hemp-fed chickens, and they found that when homogenized, there is up to 1 percent CBD content per egg. It would have been CBD-A, the acid form, per egg. Which is substantial. That’s like 250 milligrams of CBD.

Chris Kresser:  Yeah, in the eggs.

Will Kleidon:  Right. One egg. Right?

Chris Kresser:  Wow.

Will Kleidon:  And so, pretty early we were consuming substantially high numbers of CBD molecule. And then when we cook the eggs, we would decarboxylate it and get CBD. When we cook the chicken or the cow, we’d decarb it and get the CBD. But then when we drink the milk products, we’d be getting the CBD acid form. So, our bodies for millennia likely have had a regular supply of high CBD, low THC, decarbed with then a less constant, but still frequent supply of the acid form of the cannabinoids.

And I believe that’s why the data shows, particularly Israel has been leading the game in terms of clinical research for decades, just because of prohibition in the United States, the strong data demonstrates you need right around 500 milligrams of the fat-based CBD or the equivalent of a fat-based daily minimum to turn the endocannabinoid system on functionally. The data really starts to kick in of real effect in the body. And so, I think the reason that that number is so high is if we look at the dietary historical intake, the picture really kind of starts to come together.

Chris Kresser:  Right.

Will Kleidon:  A lot of people are taking nowhere near enough in reality.

Chris Kresser:  Yeah. We’re going to get into dosing later, and we’re going to have a separate webinar, I think, where we talk about, where we’re going to do an even deeper dive on all of these particular topics on how to dose it properly and what you should look for in a product. And there’s so much confusion out there on this topic and it’s such a potent therapeutic modality that I just really want to give people all the information that they need to make good choices about it because it’s been such a game-changer for me personally, and also for my patients. So, I mean, that’s really fascinating about the history. As I studied Chinese medicine and I remember learning about the emperor and pharmacologist, Shen Nung—

Will Kleidon:  Yep.

Chris Kresser:  Yeah, who famously used cannabis, and learning about the early history of it, it’s used for gout and rheumatism and even malaria. Pretty, pretty fascinating.

Will Kleidon:  Isn’t it?

The Legal and Regulatory Environment around CBD

Chris Kresser:  Coming back to just some of the basics, like, so, it’s, it’s not psychoactive like THC. And this is why it is legal in all 50 states. So, let’s, why don’t you cover just briefly the legal and regulatory environment. Because I think people are concerned about that as well.

Will Kleidon:  Yeah, and there’s actually a few states, and it’s rapidly shifting for the benefit, but it’s at a state level where they have not updated, and CBD is not so friendly. And at the federal level, it’s completely legal. In the majority of states it is, and we can go over those states. But yeah.

Chris Kresser:  Yeah, how many states? I actually wasn’t aware of that. I’m glad we’re having this conversation.

Will Kleidon:  It flickers. Unfortunately, bureaucratic decisions don’t always pace with logic.

Chris Kresser:  Right. Yes. Because you can order it, like, it’s federally legal. You can order it online.

Will Kleidon:  CBD, and the Farm Bill stipulates that states cannot block the intrastate transport of hemp and its derivatives, including cannabinoids such as CBD. However, at a state level, they can ban it.

Chris Kresser:  Interesting.

Will Kleidon:  That now all of those states, because they’re realizing that the one, health importance, two, market size, they’re missing out on massive tax.

Chris Kresser:  Tax revenues. Yeah.

Will Kleidon:  And jobs.

Chris Kresser:  Follow the money.

Will Kleidon:  Yep. So, they’re, so Idaho is probably the most famous and then you’ve got, it was the Dakotas. North Dakota has flipped. I know they can grow it in North Dakota now, almost certain cities now are friendly there. South Dakota currently is a no-go. Texas was on there, but now it’s golden.

Chris Kresser:  That’s okay, we can put a full list on the show notes so that everyone can see. And another thing is travel. So awhile back it used to be that the FDA didn’t really have a clear position about whether you could fly on a plane with CBD and take it on the plane with you. Recently, if I remember correctly, they issued an update that was basically like, go ahead, that’s legal. Is that right?

Will Kleidon:  Yep, the TSA said that it’s 100 percent legal to travel with CBD oil.

Chris Kresser:  Yeah. Which made a lot of my patients happy, I can tell you that.

Will Kleidon:  I mean, it’s crazy, right? It’s a vegetable that, Jefferson was quoted saying the most patriotic thing someone can do for the country is to sell hemp seeds. The Articles of Confederation and the first draft’s written on hemp. The first flag made by Betty Ross was made out of hemp.

Chris Kresser:  Right.

Will Kleidon:  Anyways, the reality is the prohibition was a blip in historical human usage. For the majority of the time, it was the most commonly grown plant, one of, right? And so basically the definition of hemp, it’s actually not a botanical distinction. It’s a legal distinction. And a Canadian doctor in the ’70s was tasked with drawing the line from industrial needs. So, the term canvas, the etymology of canvas, it comes from cannabis.

And so, you had industry and naval and demand. And so, after the prohibition, they said okay, let’s draw a line at 0.3 percent THC unless that is hemp, and anything above 0.3, that is not hemp. And the guy who did it, he stated that this is an arbitrary line. Actually, recently he’s expressed regret, thinking he should put it closer to 1 percent. Certain countries in Europe have that 1 percent threshold because anything above 1 percent is when the THC becomes psychoactive in ratio.

Chris Kresser:  Right.

Will Kleidon:  So, the U.S., any cannabis plant, because THC is below 0.3, so it’s not psychoactive, is legally hemp.

What makes some CBD products more effective than others? What’s the optimal dosage? And how does CBD oil work? Check out this episode of RHR with CBD expert Will Kleidon for answers to your questions on CBD. #optimalhealth #chriskresser #unconventionalmedicine

The Health Effects of CBD

Chris Kresser:  Okay, that’s helpful. So now that we’ve kind of got those basics out of the way, let’s dive into what CBD’s properties are from a medicinal standpoint. And starting with the mechanisms: anti-inflammatory, analgesic, antianxiolytic, what are some of the other things that it does in the body?

Will Kleidon:  Yeah, so our bodies have a system called an endocannabinoid system, endo being “internal,” cannabinoid coming from the cannabis plant and system. And so, this system, it turns out, it has receptors in every single other system of the body, including at a cellular level. And the primary functionality of this system is to maintain homeostatic balance for every other system. So, it’s got receptors in:

  • The nervous system
  • The digestive system
  • The skeletal
  • The dermal
  • Reproductive
  • Cardiovascular
  • Respiratory

Literally every system has these cannabinoid receptors and it’s like the conductor of the body symphony, monitoring, that all these systems are playing well together at the right times and the right levels. And if one of them goes out of balance, its job is to deploy cannabinoids to then go in and bring that system back into harmony with the entire body. And one of the ways that it does this is through buffering oxidative stress. So, oxidation is like rust for our cells.

Chris Kresser:  Involved in every chronic inflammatory modern disease that is killing us every year.

Will Kleidon:  Right, and so we live in, so if we look at humans who have been consuming these cannabinoids for millennia, and what’s fascinating is each epoch, kind of the cannabis plant actually drove technological advancements in society. So, it was used for all the nautical sails and rubs. It’s antimicrobial, antifungal, it’s the strongest fiber on the planet, which led to expansion, and then going into the beginning of the first industrial era, it was the lubrication, the hemp seed oil was the lubrication, the diesel engine was designed to run off of hemp seed oil.

It led to plastics. But with each of these events comes an increase of oxidative stress. And the plant simultaneously provided an expansion and at the same time, the micronutrients to feed our bodies’ endocannabinoid system, its fuel for the system. So, these cannabinoids in the full complex are like fuel for the endocannabinoid system and enabled us to buffer the oxidative stress or help buffer the oxidative stress associated with living and the changes.

Chris Kresser:  Right.

Will Kleidon:  And what, so now we go to the ’40s. We’ve got an, for the first time, really, we prohibited this plant, artificially created this endocannabinoid deficiency by cutting the nutrients out of the diet and simultaneously entered an era of more oxidative stress than ever before. The saber-toothed tiger’s gone, but going to a grocery store and needing to pick between more than six options, they did a study and it shows that it creates a notable oxidative stress response. So that’s like the least of our modern stressors. So, we one-two punched ourselves essentially. We cut out our fuel for the endocannabinoid system and ramped up the stuff that the oxidation which the fuel is needed to buffer.

Chris Kresser:  Right.

Will Kleidon:  When we have an oxidative stress response, it increases this compound called FAAH, and that enzyme actually degrades one of our internal cannabinoids called anandamide. So, when you go through a stress event, the body is going to try and deploy the anandamide, but this FAAH enzyme increases and destroys it. So, we put ourselves in this negative feedback loop artificially.

When you take CBD, it actually modulates the levels of FAAH in the body and enables anandamide to last longer in its half life and circulation in our body. And so that’s why when we put the cannabinoids and fuel back in our system that we’ve artificially idled, all of a sudden, the system lights up and all of a sudden driving in rush hour traffic, people go, “Oh my goodness, normally I would be freaking out, and I feel totally collected and present in it.”

Chris Kresser:  So, it’s got a regulatory effect on the antioxidant defense system, the oxidative stress. It has antianxiolytic, or antianxiety, effects for many people via the endocannabinoid system as well.

Will Kleidon:  Yep. And it has direct action on the vanilloid receptors, which modulate pain and inflammation response.

Chris Kresser:  Right. I was going to say then pain and inflammation are other major uses, particularly at those higher doses that you talked about. So, I mean, if we’re talking about pain, inflammation, oxidative stress, then it’s no wonder why CBD has been shown to have an impact on so many different conditions. Because those are, pain, inflammation, and oxidative stress basically characterize every chronic modern inflammatory disease from headaches to migraine to Crohn’s and ulcerative colitis, to arthritis, to cardiovascular disease to depression, which is now considered to be an inflammatory condition. I mean the list really goes on and on.

Will Kleidon:  And so, we did a, we have to be careful with what we say. On our supplement end we have substantial IP on medical sides.

Chris Kresser:  Yeah, I understand.

Will Kleidon:  But we did a preliminary 60-day blood panel study with Quest Diagnostics. A doctor from, a cardiovascular surgeon from UCLA, he was monitoring it. And we looked at three different inflammation factors, along with other things like lipids. But the homocysteine, C-reactive protein, and one of the other major markers. And Dr. Brandman said he had high hopes, given all three combined, to see across the board, around a 3 to 4 percent  reduction would be fairly substantial. After the 60 days, he came back at 12 to 14 percent reduction.

Chris Kresser:  Wow. Yeah, that doesn’t surprise me, but I’m sure it was pretty shocking for the investigators. Because you don’t see those even with a lot of significant pharmacological anti-inflammatory drugs.

Will Kleidon:  Exactly.

Chris Kresser:  Yeah. Yeah and I’m not under any of the same restrictions you are, so I can talk a little bit about my own experience using CBD in clinical practice and some of the conditions that I think about it for. And to be honest, at this point, I’m using it. It kind of stands out when I don’t recommend it for a patient, just because I’ve found it to be so effective for so many different conditions. And so well tolerated. It doesn’t have the side effects typically that most other medications and even supplements have.

And as we’ll talk about later, there are some interesting dose–response curves and things that happen when you’ve been taking it for a while that mean you don’t actually tend to build up significant tolerance. And sometimes it’s the opposite. So, I don’t really believe in, oh, I hadn’t believed in miracle cures and panaceas that help everybody. But I mean, this is, and I’m kind of allergic to hyperbole. But this is, yeah. This is about the closest that I’ve seen in 10 years of clinical practice, especially when you get the form and the bioavailability and the dosage correct and you’re making sure to choose a product that’s not full of pesticides and other contaminants. Which again, we’re going to talk about later.

But just for me in the quick list would be, like, again, anyone with any kind of inflammatory conditions. So, we’re talking about all the inflammatory bowel diseases, including any irritable bowel syndrome, any GI issues, because the endocannabinoid system is highly represented in the gut.

Will Kleidon:  Yes.

Chris Kresser:  So, I definitely think about it for that. Mood disorders, behavior disorders, and anxiety because of the, what you just described with the, how it works in the brain and the oxidative stress system and the relationship between inflammation and all of those conditions that we now, has now been well established. Any kind of pain, whether it’s from an injury, musculoskeletal pain, and it can be used topically that way or internally.

Or from like chronic inflammatory conditions like arthritis or rheumatoid arthritis. Autoimmune conditions, because it has remarkable amino regulatory effects, what I’ve seen. Certainly nausea, that’s probably one of its most famous uses for people who are undergoing cancer treatment. I’ve actually seen a phenomenal antimicrobial effect too, both internally as part of, like, antimicrobial protocols and also on the skin for any kind of skin bacterial or fungal issue. I mean, those are probably the things, the ones that I think of most. But it’s just amazing to me.

Will Kleidon:  Yeah, and it keeps going.

Chris Kresser:  We’re still discovering so many uses of this compound.

Will Kleidon:  And it, despite like, knowing like, okay, if you are providing fuel for the system whose primary purpose is to regulate homeostasis for every system of the body, like the functionality of it checks out, right?

Chris Kresser:  Yeah.

Will Kleidon:  It still is profound.

Chris Kresser:  Yeah.

Will Kleidon:  I think it’s also because we artificially idled this system for almost a century now, until just now, right? And so, the data and the medical science didn’t realize that essentially and so, with it turning back up online, all of a sudden, we’re seeing all these, just these almost panacea-like results, and it’s, like, okay, well, we’re feeding the system that regulates every other system and it makes sense. Yet it’s still never not, for me at least, profound to see what it does.

Chris Kresser:  Yeah. For me as well. And especially the more familiar I become with it and the more skill I gain in using it therapeutically, I think that’s a big issue. And maybe this is a good segue because I often have seen when patients come in and they have their first appointment with me, and we start talking about stuff that they’ve tried. And I always ask them, have you tried CBD? And they say, yeah, it didn’t work.

You’re laughing because you know what my next questions are going to be. What form did you take? What was the dosage? How did you use it? Because so often people will just buy some that they heard about or their friend told them about. And they’ll take a few drops in a dropper or something, and they won’t really notice any difference. And that’s the end of it. And it’s a shame because, because it’s so potent, and it has so much therapeutic potential, but there’s so much misinformation out there about it now. I mean, I don’t need to tell you that. You’re always beating this drum.

And it’s like, because there’s so much money being made now and there’s just so many unsavory entrants coming into the marketplace just to make a quick buck and they don’t really care about the purity of the product, they don’t know even one hundredth of what you know about the plant and how it works. They’re just basically trying to make money.

Will Kleidon:  Yep.

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Choosing a CBD Product and Determining Dosage

Chris Kresser:  And consumers, patients, they’re suffering from this, and practitioners are too. Because I know a lot of doctors in my training program are always asking me, like, “What do you recommend here? It’s overwhelming. Like, I don’t have time to research four thousand different CBD products on the marketplace and try to figure this out.” So, for someone who, either a practitioner or a consumer is trying to get into this, what are the most important considerations when they’re choosing a CBD product?

Will Kleidon:  Yeah. So, the reason why like most people haven’t felt anything, is due to the poor bioavailability of the fat-based cannabinoid complex. Like I stated earlier, the data really shows you need a minimum of, like, 500, minimum of 500 milligrams of a fat-based equivalent of a CBD molecule. Most bottles, that’s the entire bottle. And then you start seeing these higher number of bottles around like $1,000 to $3,000. Those are always going to be spiked with isolate 99.9 percent of the time. And even then, that 500 milligrams, that’s the minimum amount needed.

Chris Kresser:  And just to be clear for my listeners, I want to make sure they don’t miss this point because it’s important. When you say spiked with isolate, that means it’s spiked with an isolated CBD, not the full-spectrum CBD compound.

Will Kleidon:  Exactly.

Chris Kresser:  Just to bring up the dose that they can say is in there on the bottle.

Will Kleidon:  Exactly. And isolates being made with hexane and sometimes …

Chris Kresser:  Which is a pretty harsh, yeah, I mean there’s some, yeah, let’s talk more about that in a second. So spiked …

Will Kleidon:  Even at the $3,000, that’s six doses.

Chris Kresser:  Yeah.

Will Kleidon:  Right? And so, what’s happening is you have people who are getting placebo, which is great.

Chris Kresser:  Yeah, nothing wrong with that.

Will Kleidon:  Yeah. However, proper engagement of the cannabinoid system is vastly different from a placebo response and I think there’s also, which warrants more discovery, is trace amounts … so THC, it’s metabolite when it gets digested through first pass digestion. It goes from delta-9-THC and it becomes 11-hydroxy-delta-9-THC. Now, the 11-hydroxy form is actually substantially potent in the body at very small amounts, which is why some people, a lot of people have terrible experiences taking edibles where they …

Chris Kresser:  Right, oh boy. Yeah.

Will Kleidon:  It’s substantially more psychoactive, it lasts longer in agonization. And so, I think there’s, it warrants, there could be some anti-inflammatory response with this trace amount of THC in these products. However, to really get to see what CBD can actually do, no one’s really getting enough unless they’re taking a more bioavailable form.

Chris Kresser:  So, what are, most of the CBDs come in a fat-soluble form.

Will Kleidon:  Right. In MCT or, which, and there’s issues with MCT, as you’re aware.

Chris Kresser:  Yeah.

Will Kleidon:  Again, hexane. But you can’t make an organic MCT … But so, adding some fat to it enhances the bioavailability, but nothing substantial enough. We’re talking about maybe not even close to 1,000 percent increase. So, what happens is when we eat the fat, our bodies have to, and any type of fat, not just cannabinoids, it has to nano-encapsulate it in the stomach through bile secreted by the liver that basically nano-encapsulates it around 40 nanometers in these little bubbles of water, and that’s how it can get into the bloodstream. So, our bodies have evolved having this water layer to keep fat out of the blood immediately. So, it can sit in the gut, and that’s where the body is determining, okay, is this toxic? Or do I want this to get let into the blood? Because once it lets a fat into the blood, then it can travel anywhere.

Chris Kresser:  Yeah.

Will Kleidon:  And so this process is very inefficient with cannabinoids. So, the data shows on average, if you eat 20 milligrams of CBD, 90 percent of it is lost and only two milligrams of CBD actually makes it into the blood. And it takes about 30 to 40 minutes for it to get nano-encapsulated and then it’s brought into the bloodstream. And so, 20 milligrams is nowhere near enough to really, to functionally engage it at its, properly turn the system on.

So, let’s say you eat 500 milligrams. That’s a lot of fat to eat. And so historical-wise, how we were getting it is we would be eating the byproducts of the animals and the animals. So, what you can do is, we actually figured out in 2014, how to nano-encapsulate the cannabinoid complex in a water bubble, essentially, without using anything synthetic or synthetically modified, at the same nanometer size that our gut does it.

And so, this process enables it to get directly into the bloodstream the second that it comes in contact with the mucosal membrane. And so, our formulations, the users can actually get a functional dose. So, all the time, we get people, and I’m sure you’ve seen it directly within your practice—

Chris Kresser:  Yes.

Will Kleidon:  Is people go, “I thought CBD didn’t work, and oh my goodness, it actually works.”

Chris Kresser:  Right, right. And I don’t have to buy 14 bottles to get the necessary dose, which is, yeah.

Will Kleidon:  Exactly.

Chris Kresser:  Yeah. So how does it break down, like with a bottle of Ojai Energetics, which is your product? What is the, you mentioned 500 milligrams with the fat-soluble form, how does it break down?

Will Kleidon:  Initially, we’re looking at around a 20-times increase. Subsequently looking, so this delivery system is called, and there’s different types of encapsulation techniques. And ours is called, it’s a colloid. And so, this formulation, it has repetitively been demonstrated to increase bioavailability by over 100 times.

Chris Kresser:  Wow.

Will Kleidon:  For fat-based compounds like cannabinoids, like curcuminoids, curcuminoids have almost identical PK profiles in terms of ratio responses. They basically have the same molecular weight, very similar. When you take a liposomal encapsulation, which is not the best way to do it, and you cannot do it without synthetically modified compounds for cannabinoids, it tends to have, your curcuminoids have an eight-times bioavailability.

Same for cannabinoids. When you take it and you nano-size the particles without encapsulating, it gives a three-times for curcuminoids, it gives a three-times for cannabinoids. And when you do a colloidal of curcuminoids, you get over 100 times and we’ve seen this with following through with CBD, and that’s what we use for our formulations. Conservatively 20, but …

Chris Kresser:  It does say 20 times. And how does that actually, without me having to do the math, like how many doses would that be in a bottle typically?

Will Kleidon:  So, 5,000 mgs, but the reality is it’s, and you’ve seen it …

Chris Kresser:  Yeah, probably more.

Will Kleidon:  It’s closer to 25,000.

Chris Kresser:  Yeah, okay.

Will Kleidon:  So that’s why people get response with less than a dropper. The first time they take it, they actually feel it. Because also the system is upregulated. The receptors, because it’s been in this drought, so to speak.

Chris Kresser:  Yeah.

Will Kleidon:  And so, you need to prime the pump and do a loading dose to really kick it in. And most people are never even coming close to that …

Chris Kresser:  Right.

Will Kleidon:  And so, we’ve found that most people, at most it’s two droppers, and they feel it in under 30 seconds.

Chris Kresser:  So, and is that one time a day, twice a day, three times a day? Or is that just the full daily dose?

Will Kleidon:  Yeah, most people find a single dose in the day is more than sufficient to get the results they’re looking for. Now, it depends on the individual. And so, what’s really interesting is that CBD has multiple bell curves of efficaciousness. Meaning that a higher dosage can be substantially less effective than a slightly lower dosage amount.

Chris Kresser:  Yeah.

Will Kleidon:  Curve of efficaciousness. And there’s more than one of these peaks. And so, it actually, it doesn’t stay static that way. It actually modulates depending on oxidative stress of the day. So, it’s a moving target. It tends to trend downwards with inverse tolerance. So, I liken THC to be, like, a scalpel. THC, you build tolerance. With high CBD, low THC, you actually lose tolerance and need less over time, because you’re downregulating the receptors and the system becomes more efficient.

Chris Kresser:  I think you might’ve accidentally said that backwards. So, let me rephrase that just to make sure people are understanding. With THC, you need to take more and more over time because you develop a resistance. But with CBD, the opposite can actually be the case, where you take less over time. Because your body becomes more sensitized to it.

Will Kleidon:  Yeah, yep. And that’s on average. However, if you then get on a plane and you get jet lag, the oxidative stress from that will bump the bell curve chart back up higher.

Chris Kresser:  Interesting.

Will Kleidon:  So, a moving target.

Chris Kresser:  All right, so anything that happens, like, if someone has autoimmune disease and they have a flare, they might need to go back up on the dose curve during those times.

Will Kleidon:  Correct. Depending on whether, like, what’s going on and what they’re doing in their system, if there’s a more systemic issue, the bell curve and dosage amount downregulating tends to take longer for that to occur.

Chris Kresser:  Right.

Will Kleidon:  It typically happens around two months.

Chris Kresser:  And is there a scenario earlier on where they do need to increase initially. Like I know, you said there’s a kind of a loading dose up front. Is it, well let’s actually back up. Because we had some back and forth via email on this when I started using the product and was, initially, had phenomenal results. And then after a period of time, those started to become less evident. And so, I reached out to you to get some tips on dosing it properly.

And of course, all of my own research that I do on myself, I get to share with my patients and all the practitioners I train and the health coaches I train. So, it’s multipurpose. So yeah, why don’t we walk through that. Because there’s a whole way of dosing that you talk about where you put some drops in your mouth and you taste, you wait and see how it tastes and then you make decisions based on that. So, let’s talk about how that works.

Will Kleidon:  Yeah. So, the, because of the encapsulation technique, it gets so rapidly into the body. It actually will modulate our sweet receptors of the tongue, depending on where it’s at in the efficacious ratio. And so, it will literally, as you titrate dosage, we recommend titrating a quarter dropper at a time. It will go from quite bitter to sweeter and sweeter and sweeter. And when it’s halfway up the curve of efficaciousness, it will be like sweet, and then bitter.

And then all the way to like cloyingly sweet, almost too sweet at a peak, and then if you keep going and will actually start getting more and more bitter again as it goes down in the efficaciousness curve. And then as it approaches the next efficacious dose range, it gets sweeter and sweeter and sweeter to fully sweet, like honey again at a peak.

Chris Kresser:  Right.

Will Kleidon:  And these peaks, so the endocannabinoid system operates running, like, in triage. And so, it’s determining which system is, it deems most out of balance and deploys the cannabinoids to those systems on its order of priority accordingly. And so sometimes in predominantly the, and the cannabinoid system is going to prioritize vision as well as nervous system and as well as inflammation response.

Chris Kresser:  Right.

Will Kleidon:  And that makes sense biologically, right? Like if our vision goes, we have some problems.

Chris Kresser:  Right.

Will Kleidon:  He can’t see the saber-toothed tiger. But once it kind of takes those checklists, sometimes what we think is most our number one issue and we’re consciously aware of, sometimes the body doesn’t prioritize that. And it’s, what we found is if the first sweet spot doesn’t take care of what we think is number one, and maybe it prioritizes the gut over our headache. The second sweet spot range of efficaciousness, majority of the time what we’re consciously aware of, that makes the triage cut list. And so, each bell curve peak, the more you go up, that means the more systems the body can pull into balance at once.

Chris Kresser:  So, I’ve had the benefit of talking to you directly about this. But for people who haven’t seen the dosing video you sent, let’s get even a little more in the weeds on this. So, they open the bottle. This is a fairly thick fluid. So, when you say a quarter of a dropper, I mean one thing I’ve noticed is the dropper doesn’t always fill up all the way. So, do you mean like a quarter of a full dropper or how many drops are you talking about with a quarter of a dropper?

Will Kleidon:  Basically, the quarter of a dropper is just above where the pipe hat begins to taper.

Chris Kresser:  Okay.

Will Kleidon:  And yeah, we’ll pull up to, a milliliter is about three quarters of the way all the way up to the pipe hat.

Chris Kresser:  Okay.

Will Kleidon:  And so.

Chris Kresser:  And then they put that, where in the mouth do they put these drops so that they can assess the sweetness?

Will Kleidon:  Yeah. So, they put it under the tongue, and it’s about 10 droplets. And then you roll your tongue over it kind of like you would like a wine and wait about five seconds. Notice whether it’s sweet, or bitter or bittersweet, and then repeat. And you take another quarter dropper, put it in and do the same thing. And it should be sweeter. Now some people, their bell curves are just tighter packed, and it tends to be if they’re using high THC.

Chris Kresser:  I see.

Will Kleidon:  Which is interesting. So, in theory, you could be just skipping the bell curve peaks, but majority of the time you would not using this method of titration. And it will go sweeter and sweeter, and then when it’s almost 100 percent sweet, then you just do single droplets under the tongue and then roll it around, and it should be very sweet, and you swallow. And so, you don’t have to wait long in between taking the quarter droppers. Just a couple seconds to taste it and get a sense of where you’re at in these bell curves.

Chris Kresser:  Okay.

Will Kleidon:  And we have more information online as well.

Chris Kresser:  Right, right. Yeah, we can direct folks to that. Okay, so, 10 drops at a time, you do what you just described, this process, to find the right dose and that can vary depending on what’s happening in your life, how much oxidative stress is present, etc.

Will Kleidon:  And sometimes, normally most people don’t find, it’s like their first time. Average person will take maybe two full droppers, and it will be fully sweet. And then after that, it can be, like, half a dropper.

Chris Kresser:  Right. Once they get, after they …

Will Kleidon:  After the first loading, yep.

Chris Kresser:  Right, okay.

Will Kleidon:  And then sometimes then you keep titrating and it’s just staying bitter and bitter and it’s not changing, almost always it’s very unlikely that you’re just skipping over the peaks of the efficaciousness. It means that something kind of acutely is going on in the body.

Chris Kresser:  Yeah.

Will Kleidon:  And it will, almost, the majority of the time it will be six full droppers, and then it’s fully sweet like honey.

Chris Kresser:  Yeah.

Will Kleidon:  And then, so that’s the only other, which is pretty interesting. It’s just amazing that our body has this intelligence feedback and it turns out the endocannabinoid system is responsible for sweet modulation of the tongue as well.

Chris Kresser:  Right. You sent me the study to look at, which is fascinating. I definitely read it.

Will Kleidon:  Yeah.

Chris Kresser:  Okay, so that was my next question, actually. I obviously work with patients who are quite sick in many cases, complex chronic illness. Sometimes people dealing with pretty intense pain and inflammation and a lot of oxidative stress. And so, this doesn’t necessarily apply to the general population, but in those, I wanted to ask you, like, is there a maximum or what number of droppers can people feel safe going up to if they’re in an acute flare type of episode.

Will Kleidon:  Yeah, so most people will never need to exceed eight. And that’s, like, really the top of the board. For the study we did with Quest, they were taking three droppers, and that had a 12 to 14 percent. That’s where most people in most situations with greater needs will find substantial effect.

Chris Kresser:  In that three-dropper range?

Will Kleidon:  Yep, and then six is like something, that’s some serious—

Chris Kresser:  Really full significant issue.

Will Kleidon:  Or a quick short term, like, you’ve got a cold. Like, cold season, when people tend to need six for one day, and then they feel much better the next day.

Chris Kresser:  Yeah, okay. Great. And when they’re taking six to eight, this kind of goes back to the question before, is there any reason to break those into more than one dose? Or is that also still just one time of day is no different?

Will Kleidon:  At that dose range, no. It’s typically just once, and it’s sufficient for what’s going on. Now, like, the body will let you know, like, kind of like a craving, if you need it. If you’re having a particularly stressful day, like, I’ll take less than a dropper, typically, in the morning. And then if I’m really traveling a lot, or it’s just a packed day, I’ll end up taking around two throughout the course of the day of, like, a quarter to three quarters at a time.

Chris Kresser:  Right. Just dosing it based on your need and what’s happening, yeah.

Will Kleidon:  Exactly.

Chris Kresser:  That makes sense.

Will Kleidon:  Like, sometimes also, like, the body can deploy the cannabinoids and work on one system and then feel that it’s got it to a sufficient level, and then move next on the triage list. But, like, you, personally, as, like, our human does not. It’s, like, no it’s still irritating. Then redosing, it will almost always take continue to work on that and prioritize it.

How the CBD Industry Is Changing and What’s Next for Ojai Energetics

Chris Kresser:  Cool, this is so helpful. I know people are going to get a ton out of this and I really hope that folks who have been curious about CBD, but a little hesitant to try it because understandably, they’re totally confused. They don’t know what products to look for, what to try, how to dose it. There are a couple …

Will Kleidon:  CMA, right?

Chris Kresser:  Yeah.

Will Kleidon:  Like, people will say they’re doing, when you want third-party batch testing, not in-house for transparency and quality checks. And then additionally, per batch, not just one, a lot of companies will do one test result.

Chris Kresser:  Right.

Will Kleidon:  And then they’ll never post another test result.

Chris Kresser:  Then it’s all downhill from there.

Will Kleidon:  Yeah. So, we pioneered, you’re the first, and I still haven’t found another company that’s doing the full battery of tests per batch available on the website. And I don’t know, I hope more people are doing it now. But we test for pesticides, herbicides, volatile organic compounds, heavy metals, microbial, as well as terpenes and cannabinoids. So, you know exactly what you’re putting in your body every single time.

Chris Kresser:  Yeah, this is critical. It’s 100 percent organic ingredients. Hemp is a heavily sprayed crop.

Will Kleidon:  It can be, and it also has a dynamic accumulator. So, it’s going to pull up any nasty contaminants in the soil. So, it’s wonderful for cleaning up toxic soil. I mean it’s a crazy plant because it’s such a, we’re talking about the nutritional and then also the medical side of the plant. But on, like, an industrial level, you can make plastic out of it. We actually figured out with a Stanford PhD how to make scalable supercapacitor batteries and graphene.

Chris Kresser:  Right. Nanotech, yeah amazing. I love how you’re approaching this. And it’s so important to me that the companies that I recommend and support have a social mission and are providing real value to, above and beyond just the product that they’re selling. And when I first learned about Ojai several years ago, and read more about you guys and found that you were the first public benefit corporation in the, I think the entire cannabis industry, right?

Will Kleidon:  Yep.

Chris Kresser:  Yeah. Can you tell the listeners who aren’t familiar with that, what that means?

Will Kleidon:  Yeah. So, we are legally bound to our charter, which we set to be a holistic benefit to all life, including the planet itself, through all of our products, services ventures, partnerships, at an actual legal level.

Chris Kresser:  Not just providing benefits to shareholders, which is the typical corporate charter. But you actually have to provide benefits to society at large.

Will Kleidon:  Exactly.

Chris Kresser:  Yeah.

Will Kleidon:  Because when that happened, when the law changed, companies, almost always, there were four people really got into an understanding of environmental. But there was almost always a social benefit until the ’60s when this legislation was passed, which said no, actually, your primary function is purely to maximize money for the shareholders.

Chris Kresser:  Right.

Will Kleidon:  Which extensively created sociopathic zombie entities.

Chris Kresser:  Corporations. Yeah.

Will Kleidon:  The public benefit corporation injects the conscience back into the vehicle and so that our whole mission and purpose is to provide abundance, starting with the zone zero, our internal environment of health. And continuing to like, what we’re going to open source, like, patents at the right time. And we’re actually actively stepping towards where you can 3D print a battery for your car that runs purely off of renewable energy and hemp power for free from the cloud, from the hemp that’s growing in your local area.

Chris Kresser:  Yeah, that’s amazing. So exciting, what’s possible here.

Will Kleidon:  Steven, and do you know, have you met Steven Kotler?

Chris Kresser:  I don’t think so, no.

Will Kleidon:  He’s a baby. He wrote the book, co-authored with Peter Diamandis, Abundance.

Chris Kresser:  Oh, okay. Yeah, I’ve read that book, but I haven’t met him.

Will Kleidon:  He’s now an advisor to the company. And it’s just, it’s awesome. This plant provides so much benefit and it’s really a privilege to be able to serve it and the planet and the population. Because it’s just an incredible catalyst.

Chris Kresser:  Yes, I agree 100 percent. And thank you for setting the bar high here and doing this in a way that does serve the planet as well as people who are taking this. As I said before, I wish that could be said for all of the companies in this space. But that is unfortunately not true of many of them. And it’s just a relief as a clinician who’s treating patients and the creator of a training program that’s training hundreds of practitioners and coaches every year to be able to confidently refer my patients to this product.

We use it in our family. I recommend it to all my other friends and family when they ask, and to the coaches and practitioners I train. And just feel totally safe and secure and that they know that they’re getting, first of all, the therapeutic benefit that CBD promises. But also, that it’s organic, that what the bottle says is in it is what’s in it. Because that’s a huge problem with not just CBD, with a lot of different supplements. So, yeah, I applaud you guys for taking the high road here and making this available to everybody.

Will Kleidon:  Yeah, yeah. We hope that others follow the standards.

Topical Uses for CBD

Chris Kresser:  Yeah, I do as well. So, for all the listeners, if you want to give this is shot, Will and his team at Ojai have been super generous creating an offer for you to make it easy. So if you go to Kresser.co/CBD, that’s Kresser.co/CBD, you can learn more about it. But they’re offering free shipping if you order a single bottle of the Hemp Elixir. That’s what we’ve been talking about so far. And then if you order three of the bottles of the Hemp Elixir, you get free shipping as well, but you also get a free tube of their CBD pain gel, which we haven’t had a chance to talk about yet. So, let’s talk briefly about this, because this is another use of CBD to use it topically in a gel form for pain, but also, I mentioned for skin conditions as well. What are some of your favorite topical uses?

Will Kleidon:  A lot of which we can’t say.

Chris Kresser:  Right, right. So, let me say. I’ve seen it have an antimicrobial effect on various skin conditions.

Will Kleidon:  I can’t say that we have the patents for cannabinoids, like this for MRSA as well.

Chris Kresser:  Right, so I was just about to say, yeah, MRSA, resistant staph infection for skin. I’ve used CBD in honey, manuka honey, together with good results. But lots of different skin conditions, different pain conditions. I’ve had patients who have GI distress use it both internally and topically on top of the belly with good results.

So, the gel can be super handy to have around, especially for injuries or aches and pains in your neck or back, or things like that. So, the three bottles with the free tube of the pain gel is a phenomenal way to try it out. And so again, Kresser.co/CBD, and what Will and I decided was that after a while, while you’ve had a chance to order it and try it, you’re going to have some questions. And so, we’ll do a webinar where we answer those questions and give you even more insight and feedback on how to use it properly. Because it’s one thing to hear a podcast like this. And then once you start using it, you’ll have probably more questions. I definitely did myself.

So, look out for that in a few weeks after this is published. And yeah, thank you everybody, for listening. Thank you, Will, for joining us and spending time with us. I really appreciate it.

Will Kleidon:  Yeah, it’s a blast.

Chris Kresser:  And for doing this work, and I’ll be seeing you next week. Look forward to that.

Will Kleidon:  Yes.

Chris Kresser:  And everybody, listeners, thank you so much for your time and attention. And I hope you keep sending in your questions at ChrisKresser.com/podcastquestion, and we’ll talk to you next time.

Will Kleidon:  Thanks so much.

Chris Kresser:  All right, thanks, Will.

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