November 6, 2019

An Update on the Clinical Applications of Cannabidiol

Sponsored by CV Sciences, Inc.

Michael Lewis, MD, FACPM, FACN, is the president of the Brain Health Education and Research Institute, which he founded in 2011 upon retiring as a Colonel after a distinguished 31-year career in the US Army. In this interview, Lewis provides listeners with an overview and update on the clinical applications of cannabidiol (CBD). In addition to discussing recent research, Lewis describes mechanisms of action, safety, and dosage of CBD in clinical practice.

Approximate listening time: 24 minutes

About the Expert

Michael Lewis

Michael D. Lewis, MD, FACPM, FACN, is an expert on nutritional interventions for brain health, particularly the prevention and rehabilitation of brain injury. In 2012 upon retiring as a Colonel after 31 years in the US Army, he founded the nonprofit Brain Health Education and Research Institute. He is a graduate of the US Military Academy at West Point and Tulane University School of Medicine. Lewis is board-certified and a Fellow of the American College of Preventive Medicine and American College of Nutrition.

He completed postgraduate training at Walter Reed Army Medical Center, Johns Hopkins University, and Walter Reed Army Institute of Research. He is in private practice in Potomac, MD, and is a consultant to the US Army and Navy as well as several nutrition companies around the world. A highly sought-after speaker, Lewis has done hundreds of radio shows, podcasts, medical conferences, and television appearances and is the author of the Amazon best-selling book, When Brains Collide: What Every Athlete and Parent Should Know About the Prevention and Treatment of Concussions and Head Injuries.

About the Sponsor

CV Sciences is on a mission to improve the well‐being of people and planet. We believe that the future of hemp is unlimited. Through innovative and responsible application of science, we strive to enhance the prosperity and health of our employees, customers, and communities. We are committed to pioneering the CBD evolution as the leading producer of quality hemp CBD products under the PlusCBD™ Oil brand. For more information please visit


Karolyn Gazella: Hello. I'm Karolyn Gazella, publisher of the Natural Medicine Journal. Today I'll be talking with Dr Michael Lewis about the clinical applications of cannabidiol, or CBD. Before we begin, I'd like to thank the sponsor of this topic, who is CV Sciences Incorporated. Dr Michael Lewis is the president of the Brain Health Education and Research Institute, which he founded after retiring as a colonel in the US army. Dr Lewis, thank you so much for joining me.

Michael Lewis, MD, FACPM, FACN: Oh, it's a great pleasure to be with you today.

Gazella: So before we begin, I'm always curious about why physicians are interested in what they're interested in. So, as a physician, what draws you to the use of CBD in clinical practice?

Lewis: Well, the easy answer is because it's effective, but of course there's always a longer story. How did I fall into this? I mean, I spent 31 and a half years, my entire adult life in the army. And cannabis is not something that's a particularly ... It's rather frowned upon as, as you might guess. And so I really had no experience with cannabis or cannabidiol at all, but I've always been open to nutrition, and in the last 10, 15 years more much more open towards is there ways we can use targeted nutrition or nutritional therapy to ... I was in the army, so I was looking at it for helping people, helping soldiers recover from traumatic brain injury or concussions. So it really started out of fish oil and omega 3s, because the brain's made of fat. And then it kind of ... As I started to learn more and more, there started to be this interaction with the CBD industry. I finally, after I retired from the army, took a good look at it, and, more importantly, started to get great experiences with my patients using the combination of fish oil and CBD.

Gazella: Yeah. And you focus a lot on brain health, so that makes sense, the connection between a traumatic brain injury. So what conditions ... In addition to, I'm assuming traumatic brain injury, what conditions do you feel that CBD works well for either as a primary or adjuvant treatment or even as proactive prevention?

Lewis: Well, the biggest thing is as far as any specific one thing I would have to say anxiety, for sure. So 100% of my patients have issues with anxiety, and pretty much there's lots of anxiety just in today's society, with a 24-hour news cycle and all the craziness that's going on in the world. So it's about balance, and CBD, it interacts with our cannabinoid receptors and it's really about kind of achieving that balance. Not so much like that pharmaceutical model where you kind of hit something and you shut off a process and relieve the symptoms. The use of CBD is really much more about achieving a better balance, and nowhere has that been more important for my patients than in the world of anxiety. Helping calm that voice down in the back of your head. But I also find that it helps with chronic pain, particularly headaches. Can help decrease it. It doesn't always eliminate them, but I can tell you without a doubt, anxiety is my number one reason, whether you have a head injury or just dealing with anxiety.

Gazella: Yeah. That makes a lot of sense. Now you're talking about balance and that speaks to potential mechanisms of action, how CBD actually works in the body. Can you expand on that a little bit more? How much do we really know about how CBD works in the human body?

Lewis: Well, the interesting thing is we've known about CBD and its uses medicinally for thousands of years. Every major culture in the history of the world has used cannabis for medicinal purposes. So we know a lot, but yet we don't. Because of the issues with prohibition and then the war on drugs … we really kind of missed this golden era of clinical research, scientific research where we're really able to understand the mechanisms. Whereas in for thousands of years it was used because we just knew it was effective. Now we have a much better way of understanding why, and the why is really ... The why and the how is really it turned out that we have these indigenous cannabinoid receptors throughout our body and principally in our brains, CB1, or cannabinoid type one receptors, CB1 receptors in our brain associated with neurons and, and neuronal function and CB2 type receptors more closely associated with our immune system.

So when you're out of bounds and you think about you're out of balance on your immune system, you're more susceptible to colds and viruses and infections and stuff like that. So it's about this homeostasis, this balance, not just with your immune system but with our brains, with how we're thinking. And the really neat and interesting thing is ... One way to try to describe it is the CB1 receptors in particular, we have these chemicals that are in our bodies. I mean, we know about serotonin and therefore you have serotonin reuptake inhibitors, for example, SSRIs for antidepressant medicines. Well, we also have these internal cannabinoids that we now know about. One in particular, anandamide ananda meaning bliss, or an anandamide bliss molecule, and it's an on-demand thing.

So we used to call them endorphins. That runner's high, we would say that's an endorphin rush. We now know that that's our own body making on demand this stuff called anandamide that interacts with these receptors that keeps us happy, keeps us calm, keeps us thinking more clearly. And you can imagine, as somebody that's struggling with brain health issues maybe from concussion or from chemotherapy or just chronic stress in life, that can really make a difference. Whether or not somebody's happy and functioning in life is whether their cannabinoid system is working internally, but nature also gives us a way to interact with that through the cannabis plant, and as well as diet and exercise.

Gazella: Yeah, it does seem like we're learning more and more about the endocannabinoid system and the fact that that system in the body has such wide-reaching health effects, and I'd like to talk a little bit about the research. I understand what you're saying that we lost some opportunities in researching this plant because it was, frankly, hard to get and illegal and researchers had difficulty in doing really highly organized research. However, it does seem like the research is increasing. Now recently I read a study that was presented at the International Society of Sports Nutrition conference specifically on CBD. Can you tell us a little bit about that study?

Lewis: Well, I wasn't involved in the study. I'm only somewhat familiar with it, but it was a placebo-controlled randomized clinical trial and it was really looking at healthy people and to see if CBD versus a placebo would make a difference in everyday life events, such as quality of sleep and perception of how clear am I thinking, how am I doing throughout the day, energy levels and so on. And there was a ... It hasn't been published yet, but there was a, I'll say, statistically significant difference, particularly, my understanding is with the quality of sleep that those people that were put on the active CBD versus the placebo had a much greater reported quality of sleep, using very standardized sleep quality indexes that are used in research every day.

Gazella: Yeah. That's what drew me to this study is the fact that it was done on healthy people and it did in fact impact sleep quality, because that's a huge issue. And somebody can be deemed as being healthy and yet still struggle with sleep. So I really liked that about that study. Now, what else does the previous published research tell us about the efficacy of CBD? Have there been a lot of studies on efficacy and CBD?

Lewis: There's not been ... Relative to a lot of other things, whether you're talking omega 3s, fish oil or pharmaceuticals, there's not been a lot of research, published research. So it's really just because we're kind of coming out of this prohibition era, there's lots of research starting to get done, and there's some issues on how to actually go about doing some of the research, because your cannabis plant and my cannabis plant may not be the same.

Gazella: So Dr Lewis, you were just talking about the variance between the plants, the cannabis plant, like one plant can be different from another plant. So when we're dealing with any botanical, the way that we extract the active compounds is so important. Tell us about the extraction process that's used for CBD oil.

Lewis: Well, so the extraction is really important, but it actually starts way before that. If you want a consistent product at the end, you've got to have consistency all the way through. And one of the things about Plus CBD Oil that I really like is ever since they even began, when they started to import ... And they're the largest importer of European hemp. It's grown in the Netherlands, it's processed in Germany. But ever since the very beginning, they've only used 2 strains of the cannabis plant. And so the seeds are highly controlled, always using these 2 strains, and so you get consistency all the way from the seed through the entire process. If you're buying hemp left and right from Colorado and from California and from Europe and from Kentucky, you're not going to get that kind of consistency. And I would hope that that's what people want in a product.

Certainly one of the things that I think sets Plus CBD Oil apart is that consistency. And then when it's extracted from the plant, it's not using solvents and alcohol or other things that can adulterate the plant. And we certainly see that with some of the cheap brands that are out on the market. But what we use is a CO2 extraction. So you're not getting that issue with solvents and other things that can adulterate it. And so consistency is really, really important. Not just to me, but to the product and hopefully to the consumer, all the way from the seed to the end product that sits on the shelf.

Gazella: Yeah, that makes a lot of sense. Consistency from seed to extraction. Now, is there anything else that you look for when choosing an effective CBD product?

Lewis: Well, one of the things of course is good documented third party testing. So as an example, there's a barcode or what's the ... QRS code? I always forget the name of those little square codes, but they're on the label of every product and you can scan that and actually pull down that third party certificate of analysis of what's in that particular lot of that particular bottle of that product. And so you're able to look at that and that's really, I think, very important to know what it is that you're taking. One of the concerns is the cannabis plant is widely varied. Everything from how much THC content to CBD content to the turpines to the flavonoids, to the minerals and so on, and different strains, different products are going to be widely varied and so you really want to know what you're going to consume. It's helpful to have that kind of a third party analysis that's right there available to anybody that wants it.

Gazella: Oh, I agree. And the convenience factor alone is great for our healthcare professionals who want to look at that third party testing. That's great. Let's talk a little bit about dosage. So what dosage do you recommend for CBD, and more importantly, does the dosage vary based on if you're using it for proactive prevention or if you're using it for treatment, and if you're using it for treatment for anxiety versus dramatic brain injury? Talk a little bit about dosage and how it's used in clinical practice.

Lewis: Well, it's one of the greatest challenges, I think, that we face as practitioners is knowing what dosage to use because everybody's different. And here's the problem is that your dose and my dose may be very different. And so we've got to start somewhere. And I've got a pretty typical way that I like to start with patients, but I'm always ... It's all about educating the patient and to emphasize that you've got to find your individual dose.

So if we look at the Plus CBD Oil products, I think the thing that's made the biggest difference for me and my patients was about 3 or so ... 3 or 4 years ago, they came out with little soft gels, tiny little pearl-sized soft gels. That to me may make all the difference in the world. I mean, tinctures and drops under the tongue and lysosomal and all these different ways to do and deliver CBD are great, but patient compliance is so much better when it's just a tiny little pill, and you know, for example, the gold soft gel, you're getting 15 milligrams of CBD as part of the whole plant, broad-spectrum hemp complex. But you know every soft gel you're getting 15 milligrams, and you can look at the certificate of analysis and third party studies by consumer labs and so on to know that they're always dead on, and there that's not necessarily the case with a lot of other products. They're widely varied.

So I think that that is really important. I like 2 different products and the 3 main lines, they have soft gels, they have a red label, which is for their raw product and that's actually mostly CBDA, the acidic form of the cannabinoid, of CBD and the other cannabinoids. And then it's gently heated because you have to decarboxylase the CBDA and the other cannabinoids to make them active, which is why in terms of marijuana you have to smoke marijuana or bake it because you have to activate it for it to be active for it to cross the blood-brain barrier and do the job on the brain that you want to use THC for. But with hemp of course we're only dealing with trace amounts of THC, virtually none, but still trace amounts. So I actually ... The function of CBDA in their raw product is very different than the CBD.

It's great for inflammation, great for the body. And then I like to combine that with one that's really good for the brain, and that's their more concentrated product, their gold product. So I actually start patients on a gold and a red soft gel, and I start them twice a day, one of both morning and bedtime, and then have to educate. Some people, they don't like how the gold makes them feel during the day and they like to only take it at night. I have patients that take 3 at night and none during the day. I have people that take 2 every couple of hours during the day. So it just really depends on the person. But the easiest thing is start twice a day and adjust from there, either more frequently, or to a higher amount.

Gazella: Yeah, that makes a lot of sense. Because we are very individualized, especially when it comes to a substance like this. So let's talk a little bit about the future. As a clinician, I'm curious as to what you would like to see happen with CBD in the future? What more needs to be done from a research or clinical perspective when it comes to the use of CBD?

Lewis: Well, I think the obvious thing is that it's not widely accepted, and this holds true for a lot of botanicals, but the stigma that cannabis has had for the last 70, 80 years, it's going to take a little bit of time to overcome that. And one of the ways we can overcome that is with good science to prove that it works, but we'd certainly have challenges because the variability in a plant and the variability in products. We always try to boil it down to what's that one thing? And that one thing we always [inaudible 00:19:04] nomenclature we say at CBD ... Well, when we talk about CBD oil, almost always we're talking about not really CBD oil. We're talking about industrial hemp oil that happens to have CBD and has a lack of THC. But that strain and this strain can be very different.

So that consistency among products is really difficult. How do you do research around something that varies so widely? And that's one of the bigger challenges. Well, again, we will always want to boil it down to that one thing and that's why the FDA approved Epidiolex, because it's 99.9% pure CBD, but it misses out on all of those other important things in the hemp plant that make that entourage effect, that synergistic effect between all the different things. And so the safety profile is actually very different compared to something like Plus CBD Oil that has a tremendous safety profile.

Gazella: Yeah, I was actually going to ask you about safety. So are there any patients who should not use CBD?

Lewis: Every once in a while you run into a patient that just is exquisitely sensitive to pretty much anything. And so whether it's Tylenol or Benadryl or other things. Most patients, if you give them Benadryl, it makes them sleepy. That's why I send Tylenol PM or Advil PM, so on. But every once in a while you run into that patient that is a hyper metabolizer, and Benadryl makes them wired. It keeps them awake.

Well, you can have a similar thing with CBD, it's processed through the P450 system in the liver. So genetically some people are just prone to have different effects in medications that are metabolized by the liver. So those are the ones that you have to watch out for. So what I typically do is I drop them way back and start them really, really low dose, like get a dropper, and we just do one drop or one spray once a day and see how they do, and then go to 2 and then 3 and then 4 and build them up so that their body gets used to it. It doesn't mean that they don't need CBD or else I wouldn't be doing this with a patient, but their bodies just need a much slower ramp up to be able to adjust to it.

Gazella: You know, that makes a lot of sense. Because I've heard about the reverse effect with other substances like melatonin, you mentioned Benadryl. It's good to know that if there is that reverse effect that you don't have to just stop completely. You can just do this titration where you start really small and just ramp up slowly, so that's good to know. And you've had good luck with that in clinical practice?

Lewis: Very much so. And those are the patients that ... I'm dealing, again, with head injury patients or concussion patients that have been struggling for months or even years with the symptoms following a concussion and they're the ones that really need it. They really need the CBD. And so I'm not so quick to just say, "Stop taking it." But where I've found the success is, all right, we're going to start back over at ground zero and we're going to step up really cautiously, really slowly. And once you work through that process over a month or so, it is absolutely life-changing for those patients.

Gazella: That's great. That's good to know. And I would agree with you. I think in the future it would be good to see the stigma ... To overcome that stigma, to get some more consistency with the plant and some more human trials associated with the efficacy of CBD. I think those are all really great future goals for this particular substance. Well, Dr Lewis, once again, thank you for joining me today, and I'd also like to thank the sponsor of this topic, and that is CV Sciences Incorporated. Thanks again, Dr Lewis.

Lewis: Oh, my pleasure. Hopefully we can do it again sometime soon.

Gazella: Absolutely. Let's stay in touch. Well, have a great day everyone.

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