Cannabis, the Gut, & CBD vs THC

I’m hopeful that Kevin and I will be able to navigate this successfully, help you understand what you can and should do, know what might just be marketing BS (that people who are trying to sell a product are trying to leverage, in order to get you to buy said product), and really give you that balanced view on this topic. So Kevin, you’ve got some big expectations to try to deliver on here.

Dr. Kevin Spelman: No problem, Dr. Ruscio. Thanks for having me.

DrMR:   Yeah, it’s a pleasure to connect. Before we get into some of the particulars, can you tell people just briefly about your background and how you got involved with interest in cannabis?

DrKS:   Sure. So academically, I’m trained as a molecular biologist. I did a postdoc at the National Institutes of Health. That’s actually where my interest in cannabinoids started, because I started working on CB1 and CB2 signaling there. I saw the writing on the wall.

I left NIH in 2010, I believe, and I wanted to start a CBD company. I’m really glad I didn’t, because I would have gone bankrupt. It was too early. But that’s some of my background. I also co-founded a Master of Science program in Clinical Herbal Medicine back in 2000. That program just went defunct, unfortunately, at Maryland University of Integrative Health, but it lasted quite a long time.

I’ve been a medicinal plant specialist. If you look me up on Medline or PubMed, you’ll see that in almost all my research, I’ve been really fortunate: I’ve been able to work on medicinal plants from clinical trials to molecular biology and that sort of thing. I feel pretty blessed, I’ve had a fun, good time, and had a stint there where I advised the White House commission on complementary and alternative medicine during the Clinton years. I actually just spent the day on the Hill yesterday lobbying for cannabidiol in dietary supplements and getting multivitamins into the SNAP program (for people that are on food stamps or just lower income so that they can improve their health). Never been a lobbyist before, so that was quite an experience.

DrMR:   I’m sure. Now, one other question. It’s fantastic that you’re involved in research and especially in clinical trials. Are you also working or have you worked in a clinical setting where you’re face-to-face with patients? Or are you purely in the research avenue?

DrKS:   Well, I have. I actually spent 20 years in clinical settings and was literally face to face with patients practicing a blend of ayurvedic medicine and clinical herbal medicine. Naturopathy, if you would, but I’m not an ND.

DrMR:   Gotcha.

DrKS:   I probably shouldn’t use that word, but this was shoulder-to-shoulder with a physician, so if I needed help, he was there, and if he needed help, I was there. It was great. So during that time, working with medicinal plants for patients was really wonderful, because I could actually order labs and look at biochemical changes in peoples’ conditions as I was giving them plants. So I was really blessed there as well, to be able to take a very evidence-based approach and watch biochemical changes in people as they progressed in their therapies.

Cannabis Myths and Misconceptions

DrMR:   Love it. As we wade into the topic of cannabis, do you have any high-level remarks? I’ll just throw out a few maybe to stoke the flame here. As I alluded to a moment ago, it seems unquestionable that right now there’s a huge boom in demand. We can probably label interest in CBD to be a bit of a fad. I don’t mean that in any disparaging way, but it’s something that is of high interest right now. That’s both good and bad. The bad of that is it will have people making unsupportable marketing claims. It’s certainly going on, where people are looking for CBD only, to cure every ill. That should be juxtaposed with what we can actually say it does and some caution. I’m trying to toe that line. Do you have any things that frustrate you, as you look out into this landscape on the internet and what have you? I’m sure there is some good and some bad. Do you have any high-level commentary as we start into this topic?

DrKS:   Yeah, I’ve definitely got some stuff that frustrates me. Let’s start with just what happens to a product—or in this case a medicinal plant product—once there’s money behind it. So for me, cannabis, hemp, and THC cannabis is all cannabis. And it’s all cannabis sativa. There’s still a belief out there that there’s cannabis sativa and cannabis indica. A recent DNA analysis (that was based on proving species) showed that there is no cannabis indica. There is cannabis sativa subspecies indica and there’s cannabis sativa subspecies sativa, but there’s not enough difference in these plants for them to actually be separate species. So that’s one frustration, this whole indica/sativa argument. That one’s for clearing your head and one’s for more of a body experience, I think is mostly a lot of hot air. Now there is a difference in the terpene profiles and that’s really what that feel—that body feel and head feel—is about, the terpene difference, not the cannabinoids. So there’s that piece of it.

The other piece that’s just driving me crazy—now, I agree about the CBD labeling, but I’ll get to that in a second, and this actually concerns the labeling—is the idea of full-spectrum. Let’s be honest here. Full-spectrum is not isolate. I’ve seen isolates out there that were just straight CBD, that were called full-spectrum. It’s basically a buzzword. It’s a marketing department wanting to catch that buzzword and get peoples’ attention.

DrMR:   Is what you’re saying that if you see a CBD-only that’s claiming to be a full spectrum, that that’s a misrepresentation of the term?

DrKS:   Absolutely. If you’re seeing something that’s CBD isolate and they’re calling it full-spectrum, then I think it’s a misrepresentation of the term.

DrMR:   Does that also include hemp? Because from what I’ve heard, there’s no THC, or such a small amount in hemp that someone could claim a full-spectrum CBD from hemp.

DrKS:   So now you bring us to another area that’s misunderstood. Hemp does have THC in it. To find a hemp chemovar… and I’m not going to use the word strain, because strain is a microbiology term, not a botanical term. When we talk about varieties, we say chemovars, chemovarieties, or chemotypes, or just variety. Look at the brassica family, which is broccoli. You’ve got over seven, depending on how you count, up to a dozen different varieties of broccoli, including kale and broccolini and all these different ones. So the same thing for cannabis. You have these different varieties. A lot of that variety is a difference of terpenes.

But when it gets to full-spectrum, I was going to say that distillates are also being called full-spectrum. When you get to a distillate, you’re upwards of 70-plus percent of just cannabinoids. So when I think of medicinal plants, which has been my career, I do not think of something that’s concentrated at 70% in one family of constituents. So that’s been a bit of a frustration for me as well. That’s a labeling issue.

One of the frustrations I also see is that in terms of the market, there’s a clear pathway with dietary supplements right now where you have to follow GMPs, you have to follow FTC (Federal Trade Commission) labeling laws, as well as the FDA labeling laws.

By the way, just for your listeners out there, most of you docs are saying, “There’s no regulation on dietary supplements.” That’s absolutely not true. We are regulated by two different government agencies, the FDA and the FTC. I’ve had people argue with me about that. Just go online, go to the FDA, go to the FTC, and look it up. We are regulated.

DrMR:   I’m learning that firsthand, as we’re doing more with our own line of dietary supplements. Yeah, it is not a free-for-all, there are definitely regulations out there.

DrKS:   Yeah, there really are. So when it comes to cannabinoids, the cannabis industry didn’t know that. Most of the industry didn’t know that. So you saw really faulty labeling, you saw companies not following good manufacturing practices. And that’s really bothered me. That’s been a huge frustration. The Canadians have got it together, they’re just about pharmaceutical grade in terms of their GMPs. I’ve toured several of those facilities, some of the bigger ones. But in the U.S., we’re still learning. I have to admit, it is a little bit of a wild west. There are some companies doing it right, because they’ve had to, but it’s time for us to get on board and really follow the FDA rules.

Hemp, CBD & What to Know

DrMR:   Gotcha. Well, I definitely want to ask you in a little bit here what products or companies that you like. But I want to circle back to the hemp question, just because I know this is something that people are going to be inundated with. I think most people are probably using a hemp-based CBD product, because in many states they can’t get any actual cannabis. I do want to ask you…. I’ve got a CBD right here that claims full-spectrum CBD from hemp. It’s your view that with the hemp products, that is a meaningless claim? Or is it more justifiable there? I wasn’t clear on how you meant your previous response.

DrKS:   This has changed recently because of the 2018 Farm Bill, where basically Congress thought they had created an avenue for CBD to be a dietary supplement, and the FDA has stalled there. That’s another story. In terms of hemp, what you’ll see is that by legal definition—not necessarily botanically—hemp is under 0.3% THC. However, having run a facility and having seen a number of different chemovars come in from different farms, it is really rare to find something—they exist, but it’s rare—that’s under 0.3% THC.

Now, there’s no danger to the consumer there. If the THC content is below about 1%, you’re really not going to experience any sort of euphoria or high from that. I have to say that it’s my belief that with a lot of hemp products that have somewhere between 0.3% and 1% THC in it, essentially you’re microdosing with THC. So that in itself has a profound effect. Now, it’s not enough to feel it from a euphoric standpoint or a high, but it does have pharmacological activity.

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Now, GMP you feel to be something that the consumer should be looking for on all of the labels? Because the other thing here is—and there’s just so many questions that I have—it seems like right now one of the things companies are trying to do in terms of marketing is, “We’ve got the cleanest, the purest.” This just goes on and on and on. It’s hard for me to discern, where is the line where we’re hitting a level of quality that we need? And then when is this just marketing smoke and mirrors, where you’re just trying to make your product look better than the other product by making even more elaborate claims about purity or what have you? So what are you looking for? What should people be looking for? Then what is just superfluous marketing jargon?

DrKS:   Yeah, so there’s a lot of it. I would have to say the whole, “This product is clean,” is, in many cases, marketing spin. That’s not to say… I really do not believe there are a lot of dangerous products out there. However, I do believe that there are products out there that have pesticide levels in them that would probably pass an EPA standard (and of course that’s another whole conversation in terms of what’s happened at the EPA). It’s going to take us a couple of decades to recover from the protective role that the EPA was playing. A lot of that’s been washed away now, but like we said, that’s another story.

So both pesticides and heavy metals need to be checked. Now, hemp is a crop that’s been used to reclaim land that’s been polluted. In other words, it’s really good at picking up heavy metals. So you want to check for that.

Let’s face it, if you’ve got a crop that’s super valuable and you get some sort of a bug infestation or a parasite infestation, you’re probably going to use pesticides. The pesticide testing is a little curious, because with the cannabis labs, which are where you’re going to have to send hemp—it can’t go to a regular pesticide lab because of its status—what you’re going to find is that not all labs check the same pesticides.

So one of the things that’s actually of interest to me is to look at which lab has said that you’re clear for pesticides. I’ve known facilities where, if they got a hemp shipment in that tested positive for pesticides, they would send it to another lab that did another set of pesticides in their test. Because we’re not talking about one or two pesticides, most of these labs will do a dozen or more pesticides. But they’re not all the same pesticides. So you can select the lab that’ll show your stuff is clean, depending on which lab you’re using. So I think that’s a little bit of an issue here as well. And that I’m aware of, a lot of hemp companies aren’t even checking heavy metals at this point.

DrMR:   Gotcha. Okay. Now is there something that someone should be looking for on the label? Are there specifics there? Does some term guarantee that there would be an adequate level of pesticide and heavy metal testing?

DrKS:   No. Because the FDA has not touched hemp yet. In the eyes of the FDA, they’re now thinking it’s a drug, because of Epidiolex, and that’s another issue. Epidiolex is a product put out by GW Pharma in the UK. This is 98% CBD with some terpenes in it. And this is what’s being suggested for epilepsy and other seizure conditions that are non-remitting.

So we want to be really clear that CBD, in my opinion, should be a dietary supplement. It’s another medicinal plant. It’s not anything more than that. Like I say, there’s a lot of hype around that. And I do think that there’s a very significant placebo response right now to CBD because of all the hype and because of the price people are paying. With any other medicinal plant, you take a one-ounce bottle of liquid of some sort of tincture, and I cringe at paying 20 bucks for something like that. With hemp, it might be $100. So I think there’s a very significant placebo response because of the hype and the price.

DrMR:   I agree. That’s why I definitely want to come to some of the research later. Again, for the audience, remember that the average placebo effect in randomized control trials that are designed to mitigate the placebo effect is 45% in IBS research. So it’s likely that we could see well over a 50%—you could even argue perhaps 75%—placebo effect from the CBD because people are being so inundated with the message that it’s vastly helpful, which is why I’ve been cautious in not just jumping on this bandwagon.

As I’ve mentioned before on the podcast, I am assessing this in a controlled fashion as I do with new things. It’s too early for me to report in just yet, but we want to be careful. New does not equal good, new does not equal better. Certainly at a high price point, we want to be careful that we’re not using a very expensive placebo. So more to come here in the discussion in a moment on the research studies and what we can defend.

But Kevin, are there certain companies that you like, that people should be looking to get their products from?

DrKS:   Boy, that’s a tricky question. There are a couple of companies that I trust above some of the other ones. I’m feeling a little uncomfortable, actually, doing that on the air.

DrMR:   Okay. So let me ask you this then. Would you be willing to provide a list afterwards, or do you just want to avoid making any recommendations altogether?

DrKS:   Yeah, I’m feeling like because of some financial interests I have, I need to pass on it.

DrMR:   Sure, I can understand you don’t want to incriminate, haha. Unfortunately, right now with how people are looking at these claims as being so important, I can appreciate that.

Benefits of Terpenes

So, okay. Terpene content. You mentioned that this is something that can dictate the response. There is one company that I’ve been looking at called dosist. They are making different vaporizer pens with the cannabis oil in them preloaded. They’re looking at the terpene content as a way of distinguishing. One is purportedly supposed to help with sexual arousal, one is supposed to be more anti-inflammatory, one is supposed to be better for feeling happy. How far along are we with the terpene research? Are those specific claims kind of a reach? Is there some evidence supporting this? What can people do with the information regarding terpenes?

DrKS:   Well, let’s face it, all your listeners’ ears perked up when you said sexual arousal, so why don’t we start there? I certainly don’t know of a terpene that’s going to increase libido or have a Viagra-like effect, but…

So the terpene research is, I would say, maybe a little ahead of the cannabinoid research. Terpenes have been around such a long time. It’s the largest family of plant chemistry that we know of. I think we’re looking at over 40,000 terpenes at the last count that I saw. That number could have grown.

But there are terpenes that will relax you. So for example, linalool in lavender. There are actually clinical trials on just inhaling linalool. Now, one thing to remember about terpenes is that they’re volatile. You’ll hear things like essential oils (which are mostly terpenes), or volatile oils, same difference. We call them volatile oils because terpenes are so light—especially the monoterpenes and the sesquiterpenes—that they’ll go into a gaseous form. Plants use them to communicate with each other, so how they communicate is by passing these messages that are in molecules. You can just inhale these compounds and actually have an effect. So linalool would be a relaxant.

Myrcene. By the way, most cannabis chemovars out there are myrcene-dominant. It’s pretty hard to find something that’s not. They definitely exist, but generally if you’re just searching the market, you’re going to find myrcene-rich cannabis varieties. Ethan Russo says about myrcene that it’s responsible for the couch lock effect. The couch lock effect is when somebody takes a big hit of cannabis that’s THC-rich and they can’t get off the couch, supposedly. Well, that’s not the THC, Ethan says. He says that this is actually the myrcene.

Myrcene is an incredible sedative, but it’s also via opioid receptors. Not direct activation, but indirect activation. It has a really profound effect on pain. So if you’re using a myrcene variety of hemp or THC cannabis, this is probably going to be pretty good for pain and for sleep.

DrMR:   Now, let’s say you go to your local dispensary or you’re shopping online for a CBD. Is this something that’s readily available on the ingredient label? How do you determine that?

DrKS:   In some dispensaries, yes, it’s available on the label in THC dispensaries. And with CBD now, I think you’re seeing more and more companies essentially boasting about the terpene profile. So yeah, you may see that.

But what some companies are starting to do is what we used to call in the dietary supplement industry, “spiking.” Now it’s become an acceptable behavior, but the idea of spiking was adding a particular constituent or family of constituents to make your product test better in analytical tests. In this case, the spiking means that people are adding specifically lavender essential oil to their hemp or their THC cartridges, or adding citrus reticulata or tangerine for that limonene effect (which, by the way, is a fantastic antidepressant and has an effect on the adenosine receptor system in the brain).

So there are a number of ways to go here with this. Pinene has been suggested—because it’s pro-acetylcholine—to be somewhat of a remedy to the brain-numbing effect of THC. So there are companies essentially exploiting this idea of adding particular terpenes, and they’re not necessarily from the hemp plant or from the cannabis plant.

DrMR:   Interesting, okay. Was it citrolene or a different C word there for mood?

DrKS:   Yes, I was talking about citrus reticulata. So there’s a bunch of citrus species, but citrus reticulata is one of the richest in limonene. So limonene is the compound you were looking for, I think.

Anti-Inflammatory Terpenes

DrMR:   Gotcha. You mentioned one for pain there, via the activation of the opioid receptors. Would that be the same for inflammation also? And this is kind of a bridge into the topic of gut health. Is there a certain terpene or a couple of terpenes that you like for an anti-inflammatory effect?

DrKS:   One of the interesting things about terps in general is, if you look at most medicinal plants that have been used for the gut, I’d say at least half, and maybe even 75% of them, are terpene-rich. In other words, early people using plants as medicines (which were the original medicines), learned that if the plants had a particular odor to them, that they could have a pretty profound effect on the gut.

So these terpenes can be anti-inflammatory. Very commonly, they’re antispasmodic. This is why, for example, drinking a cup of mint tea can settle people’s stomach if they’re having spasms. Very, very common effect. Now, the same thing happens in terms of getting to the urinary tract. The way that you metabolize terpenes, generally speaking, is you either blow them out through the lungs or you pee them out through your kidneys. So these antispasmodic effects will follow that, but they also tend to be very commonly antimicrobial. So this is one of the ways that lung remedies and urinary tract infection remedies have worked, is by moving terpenes through to those tissues.

DrMR:   So are there a handful that you would say, maybe for this profile that is gut-friendly, meaning they’re anti-inflammatory, antispasmodic, antimicrobial? Are there too many? What would you say? If I’m a person with these vague gastrointestinal symptoms of different sorts, what would be a good place for me to start, in terms of something that may help?

DrKS:   So here’s the thing about hemp, in terms of CBD and the various terpene profiles you’re going to get. You basically can’t go wrong with the anti-inflammatory effects of hemp. It’s a number of different models—now, these are all pre-clinical—but whether it’s COX, PPAR or gamma, adenosine, there are a number of anti-inflammatory effects here. So there are very strong indications there, not just for joints, lower back, headaches and that sort of thing (although for headaches I’d probably choose another herb), but really very specifically for the gut.

DrMR:   Okay, so is what you’re saying that any kind of CBD-derived hemp product would work? Or do you drill down into… For someone looking for any more specifics, I ask these detailed questions. Because I’m assuming most people know very little about this, and so they’re walking into a store or an online store knowing almost nothing. We need to give them a few hooks to grasp for, or else they may just end up in the bottom of the ditch with a crappy product.

DrKS:   Haha. Yeah, it’s true. Certainly there are a ton of varieties out there, so it’s hard to pin it down. Menthol is pretty reliable as an antispasmodic. I would say that myrcene is pretty reliable for pain. Pinene also has some pretty significant anti-inflammatory effects. I’m just trying to think off the top of my head. I mean, almost all of them have some anti-inflammatory activity.

DrMR:   Okay, so would perhaps an easier way for someone to come at this be to find a company that’s following GMP, that is making some claims about testing for both pesticides and heavy metals when they looked at their quality insurance page? As long as those boxes are checked, they’re looking at a CBD that’s hemp-derived, and hit all those quality assurance claims, would that be a decent place for most people to start with some self-experimentation?

DrKS:   I would say so. I think that the wilder the claims get—which is going to really attract consumers—the more likely that they’re not true, and the more likely they’re not following GMPs, because they don’t know how to label. I’m not saying GMPs are just labeling. I’m really concerned about safety here of the consumer.

But another terpene that’s particularly known as an anti-inflammatory, which is found in clove and cinnamon and a number of different spices, is caryophyllene. Beta-caryophyllene is very strongly anti-inflammatory. That compound itself binds CB2 receptors. It’s a strong agonist, a high affinity agonist for CB2 receptors. And CB2 receptors are usually found on immune cells, although you do find them in the brain as well on some of the microglia. But very strong dampening effect in terms of the inflammatory process.

DrMR:   Okay. By the way, for the audience, I’ll link to a few companies that have come highly recommended from previous interviews and some of my research, so I’ll try to provide people with some specifics in terms of, “Okay, there’s a thousand places trying to market you a product. Here’s a handful that we’ve looked into and seem to be okay.” Not being a cannabis expert, but certainly having spoken to a few now, we’ve accrued a couple different resources for you.

View Dr. Ruscio’s Additional Resources

Cannabis Research in Humans

But Kevin, tell us more about the research. When we were chatting before we started the recording, you were saying that it doesn’t seem that the positive gut effects are discussed enough, even though there are some clinical interventional studies. I said, “Yes, I believe there’s maybe two in IBD and one in IBS, roughly.”

We discussed this on the podcast a while back. There was a systematic review looking at cannabis research. And there are a handful of well-done clinical trials in humans. A few of those are in inflammatory bowel disease, and I believe one in IBS. This is using THC, so the whole plant. But tell us a little bit about what’s been published in terms of clinical data, and then what you see in terms of pre-clinical. And if you want to distinguish between CBD versus the entire plant along the way there when able, that would also be very helpful.

DrKS:   Yeah, I’ll try to distinguish between these. So first, let’s start with the idea of the obstacles to clinical trials in the United States. Because cannabis has been scheduled, and even hemp at one point now… Again, the 2018 Farm Bill was supposed to solve that issue. But the DEA is still under the illusion that hemp is still a Schedule I, which means that the CBD would be Schedule I. Schedule I basically means that there’s no medical value, that the stuff is toxic, and that there’s a high potential for addiction. None of those are true about cannabis.

Certainly people can get THC addictions, but they’re usually minor. THC in itself has really made a huge difference in terms of opioid abuse and opioid deaths in the states that have implemented a medical marijuana law. Generally speaking, the stats you’ll see are—somewhere around this depending on the state—25% opioid use decline, and you see about 25% deaths decline, due to opioid overdoses in states that put forward a medical cannabis law (in other words, THC). So that in itself, I think, speaks volumes to the fact that we’re using something that is actually quite safe.

Nobody has ever died from a THC overdose. Now, people have done stupid stuff on THC and possibly died from the stupid stuff they did, but in terms of the pharmacology and the toxicology, nobody has ever died from THC or CBD, for that matter.

And CBD has been used up to about 1500 milligrams in clinical trials, for safety tests or phase one tests, and comes out smelling very clean. The thing that bothers me about some of the THC research, and I’m going to rely on Dr. Ethan Russo again here for this… I’ve had the opportunity to do a bunch of teaching, training physicians in cannabinoid therapeutics. And one of the things he tells physicians that I find really fascinating, and I agree with, due to a chronic pain experience I had, was that if you’re getting high from taking medical cannabis, you’re having an adverse event. In other words, you’ve taken too much. He points out that the pharmacology is such that you should be able to get most of the effects that you’re looking for, depending on what condition you’re treating, except for maybe very serious pain. You should be able to get an effect without getting high.

And I actually had this experience in my own life. I live with chronic back pain. I had an exacerbation, it lasted a number of months, and I finally, out of desperation—I’m not an opioid fan—I finally went to a THC tincture and found that I could find a dose where I was fully functional and wasn’t high. So it killed the pain, and I was able to actually go to work and perform my job. My job, generally speaking, is cognitively demanding, so I don’t want to be high at work by any means.

So I think we need to keep in mind that a lot of the trials that are out there, that have been done on THC, are using ridiculous doses of THC. I saw a trial on 20 milligrams of THC, for people that were THC naïve.

DrMR:   That’s a lot. That would cause me to want to jump out of my skin.

DrKS:   Exactly, yeah. It’s way too much. But even 7.5 milligrams tends to be too much. 5 milligrams to someone who’s THC naïve is going to feel that. Some of them are going to be really uncomfortable with it, depending on the SNPs they have in their endocannabinoid system. Somewhere around 1 milligram, most people aren’t really going to feel that. Somewhere around 2.5, you may start to feel that (milligrams, that is). So I think we need to look at our trials and reconsider the dosing we’re using.

I call it black market hangover, because everybody was using cannabis to get high, not necessarily for medicine. So there’s this belief that getting high is part of the medicine. I have to say, nothing could be further from the truth.

I think there are two exceptions. I think those exceptions are very acute pain—mild to moderate pain, I think you can get away with not getting high—and if people are really, seriously using THC for cancer in a chemotherapeutic way, they’re going to be using really high doses that are going to basically flatten them in the way that conventional chemotherapy would.

CBD Dosing

DrMR:   Now if you’re using a CBD-only product, how are you dosing the CBD?

DrKS:   This is a great topic and I’m glad you brought it up. If you look at the clinical trials, most of the clinical trials are using over, let’s say, 200 milligrams to get an effect. If you look at what’s happening in the marketplace… if you were taking 200 milligrams of CBD a day—and that’s just one dose, some of these trials are 600 milligrams a couple times a day—you would bankrupt yourself pretty darn quick, because of the price of these products.

So what you’re seeing is that, in my opinion, a lot of people are sub-clinically dosing. I have to say that, now whether it’s placebo or not—I appreciated your remarks on placebo very much—it may be placebo, or maybe some people are getting effects at 20-50 milligrams, but most of the doses out there are somewhere between 10 and 40 milligrams on a product. And you can take that multiple times per day, but people don’t want to because they don’t want to pay another $100 for a one-ounce tincture!

DrMR:   Right. So is what you’re saying is that people can get away with far less of a dose? Because I’ve heard something along the lines that someone may need a dose of up to 300 milligrams per day, which, with a tincture, looks like 2-3 full tincture fulls per day. So where do you like people to start with, the CBD only? Sorry if I missed that there in your description.

DrKS:   No, it’s okay. I’m going all over the place here, kind of stream-of-consciousness. So where do I like to start? One of the rules that Dustin Sulak and Ethan Russo put forward, that I completely agree with, is to start low and go slow. So in other words, what you’re doing is starting really low dose. And if you elevate the dose, you’re going really slow about it, you’re taking your time.

I think this is a brilliant way to do any medicine, because essentially, it’s the difference between physiological dosing and pharmacological dosing. And with pharmacological dosing, essentially what you’re doing is you’re using a big dose. You’re just hitting something over the head with a hammer. And with physiological dosing, you’re finding just that amount that gives you the effect you’re looking for.

Now as healthcare providers, we usually don’t do that, because it takes a lot of attention for both the physician, or the caregiver, as well as the patient. But there is something to be said for using just the right amount of medicine. If you look at the history of dosing in medicine, it’s very common that drugs come out on the market, and then suddenly ten years later, people are like, “Oh yeah, we can use half of what we used to suggest.” So, not uncommon.

The other piece of this is, the endocannabinoid system tends to have a high inter-individual variability. So there are SNPs from CB1 to CB2 to FAAH (fatty acid amide hydrolase, which breaks down anandamide), to MGL, to all these enzymes that synthesize and break down the endocannabinoids, which also may have an effect on the breakdown of THC or the response to THC in the case of the receptors. There are SNPs all over the place. So this is part of the issue. That’s why you want to start so low.

Dustin Sulak (the physician Dr. Sulak), tells this great story about a kid who came into see him with seizures. Dustin got so frustrated with all the medicines on the market that he actually put a lab into his clinic, an analytical lab, so he could actually test stuff that people were bringing in. You have to say that’s great commitment as a physician to be that committed to really doing this right. I really appreciate him for that.

But he found this child had come in, and they tried all these CBD products, and nothing had worked. They found a product that worked. He tested it. He said, “Great, give it to me. Give me some of it and I’ll test it.” They took it to the lab and they tested it, and they found that what it was actually THCa. So not THC, but the raw form of THC, which still had a carboxyl group on it. It’s an acidic group, so it’s tetrahydrocannabinolic acid. And THCa doesn’t get you high because of the acidic part of it.

So he found that the dose the kid was getting was in the micrograms. In other words, nobody would have ever predicted that this would have actually worked. So he said, “Well, that seems like a low dose. Let’s increase the dose.” The seizures came back. So they decreased the dose and found that he needed just a little nudge, a physiological nudge if you will, to eliminate his seizures.

I think this is something that’s actually more common than we know of in medicine in general, but also with the endocannabinoid system. We need to really be aware that there’s high variability in patients and really start with really minute doses and see what works. So this may be an argument for, yeah, maybe 10 milligrams of CBD really does do something for somebody. I tend to be a little suspicious there, just because of—as we talked about before—the placebo response, but there may be many cases where people really need no more than just a low dose.

DrMR:   Okay. Is there a certain dose that you find most people tend to respond to? I just double-checked, the dose that I’ve experimented with was between 20-30 milligrams per day. It depends on the concentration of the dropper you’re using, but the one I was using was about 2-3 droppers full per day. Make sure you check the concentration of your formula, because that could vary from formula to formula. But would you say the 20-30 milligrams per day—maybe after someone took a few days to start at a lower dose of maybe 5-10 milligrams to make sure they’re okay with that—is a general approximation for most people?

DrKS:   I’d say that most physicians I talk to are starting somewhere in that range, in the 20-milligram-a-day dose and then elevating from there, titrating up if they need to. Yeah, that seems like a good place to start.

DrMR:   Okay, great.

DrKS:   But I think it’s important for your listeners to also know that if it doesn’t work, let’s say, at 50 milligrams or 75 milligrams, that’s still a really low dose as compared to the clinical trials that are out there. So they may need hundreds of milligrams to actually get the effect that they’re looking for.

DrMR:   Okay, some people may need as much as a couple hundred milligrams. And that is a big difference!

DrKS:   That’s a big difference, yeah.

DrMR:   I’m assuming that’s a smaller subset of people who need to go that high?

DrKS:   I’d like to see some data on that. I can’t really say. I can say that in terms of FAAH SNPs, fatty acid amide hydrolase, the compound that breaks down anandamide, in some populations, that SNP is up to 50%.

DrMR:   Wow.

DrKS:   Yeah, so it’s super common. It’s interesting. I spent some time in Nigeria doing work. The Nigerians have a really high FAAH SNP. The type of SNP I’m talking about would be where FAAH is kinetically slowed down. The enzyme doesn’t break down anandamide as quickly, which would mean you would have more of a CB1 signaling effect. So what that would look like in personality would be really chill and relaxed and mellow. When I was working in Nigeria in labs there, I just found everybody to be incredibly relaxed and mellow. I don’t know, but it is interesting.

DrMR:   Yeah. I think it’s an area where we need to clarify a bit from a research perspective, but thankfully with some observation, time, attention, and experimentation, people should be able to sort out what position on the spectrum they’re going to get the benefits from.

DrKS:   Yeah, exactly.

Episode Wrap-Up

DrMR:   Awesome. Well, Kevin, thank you. This has been a great conversation. Is there anywhere you want to point people to on the internet or books or programs you’d want to refer them to?

DrKS:   Let’s see. I think the most prolific author in cannabinoid research is probably Dr. Ethan Russo. I’m completely amazed by how much he’s producing in terms of really quality articles and reviews and research. Dr. Ethan Russo put Sativex on the shelf for GW and left after a while so he could do his own thing. But just look up Ethan Russo on PubMed and you’ll see a huge number of articles. They’re actually accessible for the layperson as well, as long as they’ve got a little bit of science underneath them. So I’d say he’s a great source.

I’m not really a fan of many of the websites that are cannabis-related. I know that’s going to upset some of your listeners probably, but I tend to like to go straight to the research myself and interpret it myself, rather than having somebody else interpret it.

DrMR:   I can agree with you on that, so I totally appreciate that. Well, again, Kevin, thank you so much. This was a great conversation. I appreciate your tempered approach here, and hopefully our audience has taken away a few pearls in terms of how to navigate the landscape of options regarding cannabis and CBD out there. So again, thank you, really appreciate it.

DrKS:   My pleasure, Michael. Thanks for having me, I appreciate it.

DrMR:   Absolutely.