The Science of Cannabinoids & Health: What You Need to Know
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Is there any more buzzworthy (and polarizing) health topic under discussion right now than cannabinoid-based substances? As a biochemist in the 60s, Dr. Jeff Bland watched the science unfold in real time and living (psychedelic) color. James Maskell is a millennial, a world traveler, and the parent of a young child growing up in the era of legalization. How confident are you about your knowledge of cannabinoids and the endocannabinoid system within the body? You might be surprised by what you learn!
James Maskell: 00:07 Hello and welcome back to the Big Bold Health Podcast, making health personal in a world of disease. Today, we are going to be talking about something that may or may not be legal depending on where you’re listening, but it is legal where we’re sitting right now. So, we’re going to get into it. We’re going to be talking about cannabinoids. And you know, when I got an understanding of the history of the natural health industry in America, I was alerted to the fact that, you know, this conversation really led to sort of like the beginning of people coming together saying, “Hey, can natural compounds really do something?” And, and sort of bringing that into the public discourse, and the physician discourse in the 1960s. And Jeff, I know you were there or thereabouts, so what were you doing in the ’60s?
Jeffrey Bland: 00:53 Well, not all that’s fit to print, but let’s talk about that, which might be interesting. So, in ’67 I was a graduate student, PhD student in Chemistry, and I had the pleasure of meeting at a seminar that was given for our department by a Dr. Raphael Mechoulam. And Dr. Mechoulam in 1963 or between ’63 and ‘5 had been the person to discover the chemical structure of the cannabinoids. And so, he was credited as being kind of the father of the chemistry of the various members of this family, of which tetrahydrocannabinol or THC, the psychoactive component of cannabis sativa, marijuana was a member.
Jeffrey Bland: 01:37 But, he was also a person who knew and had discovered many, many other members of this plant family of cannabinoids, of which there are more than a hundred different members of that family. And so, when I was hearing him speak in ’67, it struck me that there was a very interesting thing that he had thrown out— just as a throw away in his talk—about the fact that the test that was used back in 1967 to arrest people on marijuana was a test called the Duquenois test. And, that he found that the chemistry of the cannabinoid family was such that it overlapped in this test with a variety of other herbs and spices.
Jeffrey Bland: 02:15 And I thought, “Boy, that’s kind of interesting,” because there were a lot of young men and women that were being arrested for marijuana and I wondered if that was really a valid arrest based upon the non-specificity of the test. So, I went back to my lab, I played around and was able to demonstrate that I could show a positive Duquenois test in a whole series of routine spices and herbs. And so, then I became an expert witness and that expert witness was successful in getting out many, actually hundreds of people that had been arrested for marijuana based upon the Duquenois test, out of their arrest.
Jeffrey Bland: 02:52 Well, that then led me, back in the ’60s, ultimately to be interested in this whole family ever since. So, that’s a lot of years ago. We can probably do the math, and I followed Dr. Mechoulam, who’s now a professor emeritus. He’s in Israel and he’s continued to be very active and actually in the 1990s, early ’90s, he then discovered the cannabinoid receptors in the body which are the ways that actually members of the family bind to these receptors and activate these cannabinoid receptors that induce things like hunger and mood and so forth. And, there are two major receptors, CB one and CB two, cannabinoid receptor one and two, and different members of the family of cannabinoids have different affinities for those receptors. Now, the interesting thing about this is that it was that discovery then that led further investigators to discover that our body produces its own native cannabinoids, that are called endocannabinoids, right?
Jeffrey Bland: 03:55 Endocannabinoids have names like anandamide, which are produced by the body that bind to what were called the cannabinoid receptors, but obviously our body didn’t develop receptors for cannabinoids. They developed receptors for these internal molecules that regulate mood, and appetite, and tone, emotional tone. And so, one then started to say, based upon the fact that our body makes these, you know, cannabinoids, could the defects in that system relate to some of the conditions that we’re seeing in our population like depression or chronic pain or mood problems or sleep disturbances? Maybe there’s an interruption in the endocannabinoid system for which when you give these cannabinoids externally, you’re kind of filling the gap for what the body is not able to do on its own. And, that then reframed the whole nature of these compounds, these cannabinoids as being kind of mimics of the body’s own natural endocannabinoid systems, which change it from being like this dangerous drug family to being maybe biological modifiers of natural processes.
Jeffrey Bland: 05:00 Now, I find this very interesting because when you examine other members of the cannabinoid family, it’ll take you into members that have chemical similarity in structure to that of tetrahydrocannabinol, but they do not produce the psychoactive components. The principal one is called cannabidiol, and that has now gotten to a huge point of interest right now. And, it’s one that we are very interested in knowing more about and studying. And, I think it is setting a revolution as you said, James, into redefining how natural products can modulate function in a favorable way without posing risk and producing addiction and other things. So, I’m really fascinated to watch how this is playing out right now.
James Maskell: 05:45 You know, one of the things that I’ve advocated for and that many people in this community have is this, the concept that I’m sure you’re very familiar with, which is this idea of the therapeutic order, right? Using the least costly, least invasive interventions first. And, if you look at the mental health, sleep, all of these areas, we’re using very expensive and, you know, interventions that should be further up the tree, first. You know, I just saw a study the other day with something like Ritalin that may cause psychosis in children and yet, you know, Ritalin is like first line therapy for things that you know, may be much easier treated with something like CBD that has no, you know, no effects that are negative to children and can be supportive.
James Maskell: 06:30 And you know, I’ve taken it a step further in my own life and actually, you know, I have a five year old and there are moments—anyone who’s a father here knows that—moments of overtired or situations where you know, you’re having a different environment than you’re used to where you know, kids are bumping off the wall, and to be able to use a tool where it’s just a lot less of a, a less costly intervention, a less invasive intervention that works unbelievably quickly makes a lot of sense. And, I just feel that, you know, maybe everyone’s head is getting a little better screwed on as towards you know, what we should be using and what order to deal with these pervasive issues in society.
Jeffrey Bland: 07:18 Well, I think you just said a huge payoff for anyone that’s listening to this podcast. And so, let me if I can, just amplify, and underscore, and exclamation point what you’ve said. We have to ask ourselves, and I apologize, I’m gonna wander just briefly here into the world of pharmacology. We have to ask ourselves, how are drugs produced, where do they come from? And, the way that drugs are generally produced is by looking for a condition that you want to modify and then looking for a target in the biology of that condition that you can block or inhibit with a specific synthetic molecule. So, you say, “Okay, let’s find what the condition is. Then let’s find a target in the biology of that condition from what we understand of its cause that we could find a molecule that would inhibit that function to block it so it doesn’t produce that particular effect.”
Jeffrey Bland: 08:16 Now, in doing that, you as a medicinal chemist producing and involved with that process of developing that drug for that condition, you’re going to screen, and make and screen maybe hundreds of thousands of different molecules to see what one might best arrest that function. And, the assumption is the more powerful the molecule, the better the drug will be and so you screen against your assay, this target, the hundreds of thousands of molecules that have, you know, maybe similar structure, until you find the molecule that has the highest potency. Then, you hope that that molecule highest potency is also safe and so what you do is you say, “Well, I’m going to have to go through various kind of safety studies,” but those safety studies are generally studies of what we would consider short duration relative to maybe that drug being used in a person for years or maybe even decades.
Jeffrey Bland: 09:15 Maybe a safety study would be done for months to a year at most. And, if it passes muster or marginally passes muster on the safety studies, then you say, “Oh, I have an active compound that blocks that function.” It has a high affinity for that target and it has no ambiguity, doesn’t care about the genes of that person. It doesn’t care about the other environmental conditions because it’s such a potent drug that it’s gonna override any of those other conditions and it’s got only one heat-seeking activity, which is go in there and do that job and it’s going to do it hopefully safely. And if all goes through the FDA with whatever the various processes are and it gets approved, it ends up in the market. Now, how is that different from something that may have an affect upon that same disease or condition that we’re talking about, but it is much more mellow, much more mild, much less target affinity?
Jeffrey Bland: 10:08 It has higher affinity, but maybe its safety has been proven by the most lengthy study ever done on safety, which is called natural selection, right? Yeah. What are the safest compounds of all? Things that have been eaten in our diet or exposed to humans for hundreds of thousands—if not millions of years—in which our genetics are compatible with that, and it has a wide-ranging safety. Now, its activity may be lower than the drug, but its safety has been demonstrated by the biggest study ever done, which is evolution, natural selection. And so, now we say, okay that what you call, the mellow approach, may not have the immediate effect that you would have with a hard hitting, high affinity drug, but it will have an effect that allows hormesis to occur. Hormesis means low level exposure gives a long-term high-level effect. And so, we then see over time that having a beneficial effect when we compare activity to adverse side effects.
Jeffrey Bland: 11:17 That’s a whole different pharmacology. Now, it turns out that the bioactive compounds found in much of nature or found in foods often fulfill this criteria. In foods they had to, because think of what happened if our foods had drugs in them, we’d be whipsawed around horrible every time we ate it, like eating high sugar diets. That’s maybe-
James Maskell: 11:37 The closest thing that we have to it in modern nutrition.
Jeffrey Bland: 11:40 Exactly. So, these compounds that are found in natural products in foods have had this safety of history going on to their advantage. So, when we talk about CBD, it is a material that doesn’t have a high affinity for the target. It has multiple orchestrations; it would be like saying it touches all sections of the orchestra, the strings or woodwinds, the brass and the percussion, but it touches it lightly. It’s like the conductor using the baton very gently versus a drug that might go in and just tell the first violinist how to play and that’s all it does.
Jeffrey Bland: 12:19 And so, CBD has a mild effect, which means that its activity in severe cases might not be active enough to treat a disease, but in milder cases it might be really the agent of choice for long-term safety and effectiveness. This construct that I’m describing with CBD is—you can see, as a thought or as a strategy that could be employed for many other conditions that relate to things like mood variations, like stabilizing insulin, and changing inflammatory pathways—that there are things in foods and spices that might have just the right activity that we don’t have to depend upon hard-hitting drugs who have black box warnings on the package inserts because they’re overly strong and produce adverse effects. So, I think that the CBD story is a very, very interesting story from that perspective.
Jeffrey Bland: 13:10 But, it’s also interesting because if you think of where low THC containing CBD comes from, it comes from hemp. So, hemp has very low levels of the psychoactive components of cannabinoids, but it’s much higher, the principal cannabinoid is CBD. So, hemp oil is a very interesting less than 0.3% THC, which fulfills a farm bill of 2019 or ’18 activity, and it then allows for this more mild effect to be realized in modulating functions such as sleep and what they call anxiolytic effects, meaning reducing anxiety. And, the last thing I would say is it’s a systemic or systems kind of approach because what happens to the hemp once you’ve taken the CBD oil out of it? It’s a fiber that has huge numbers of applications in making all sorts of goods out of the fiber.
Jeffrey Bland: 14:15 So, it has an advantage from a fiber perspective. And lastly, where is the hemp grown? It’s often grown on soils that are really good for growing things like tobacco. And so, you have a sustainable organic crop that is replacing a plant for which the human health has been adversely affected, in areas where rural farmers need a cash crop to generate meaningful income. So, it is sustainable, it has multiple uses, and it produces a product that has a mild effect across mood and sleep that is in search of a remedy.
James Maskell: 14:55 It’s interesting that it has such a meta effect, right? So, you’ve got on the body level, you’ve got the sort of systemic improvement and then at the systemic level of how it’s grown and how it’s organized, there’s improvement that relates to regenerative agriculture, to sustainable solutions for farmers, to weeding out poisons that have plagued the human health for generations, if not centuries. How do you see how these kind of tools can be personalized for, because different people react to it differently, and different people have different tolerances for certain different parts, and there’s different parts of the plant that have different effects on different people and sort of like an orchestra, like you’re saying.
Jeffrey Bland: 15:42 Yeah, I think that’s another important part of this story in the natural plant. In the hemp plant, when you extract out the oils, you don’t just get CBD. It is the major component of the cannabinoids, but you also get a variety of other what are called terpenes. And terpenes is a chemist name for what a lot of people would call essential oils, so they could be things like linalool or limonene. These are things that often have fragrances, like essence of rose, essence of lemon, these are the volatile essential oils. But they also, terpenes can be of other families like the sesquarterpenes and the diterpenes, that have effects as well. And these, when they are individually studied— these terpenes that are found in hemp oil—have things like anti-inflammatory effect. They have effects on potentiating cannabidiol’s effect at the receptors to improve its activity.
Jeffrey Bland: 16:40 That kind of synergizing effect. So, if you really talk about a whole hemp oil extract, you’ll find both CBD and you’ll find these, this blend of terpenes. And, the terpenes often is what gives odor and flavor to hemp oil because the cannabidiol itself doesn’t have much odor or flavor. So, when a person says, “Well, I’ve tasted CBD oil and it has kind of a marijuana like flavor or aroma,” those are the terpenes that are present in it. So, the combination of the symphony of these compounds together in nature is what gives rise to these synergistic effects.
Jeffrey Bland: 17:22 And, I think that those individuals who have been herbalists or involved with botanical medicine for years have always talked about the advantage of natural mixtures. That the plant didn’t make all these things because they had nothing better to do, it made these things in combination because they work in combination to help orchestrate certain functions. So, I think that as we move from the pharmacology of one molecule for one disease to the effects of natural products that are mixtures of molecules for functions of variety of chronic nature, it’s a whole different philosophy.
James Maskell: 17:55 Yeah, absolutely. And, what do you imagine, going another meta level, what the impact of, you know, the significant increase of these kind of tools in the population would be for health of the individual and health of the population?
Jeffrey Bland: 18:13 Well, again, I think the answer I’d give you back is why we’re doing the Big Bold Health Podcast, because we’re moving from medicines for the group—and what is the group? The group has been divided historically into diseases. So, if you have diabetes, then you’re labeled by your doctor as a diabetic. You’re not Mr. Jones or Mrs. Smith, you’re the diabetic that happens to be Mr. Jones or Mrs. Smith, and you’re treated with a standard of identity for that disease, diabetes.
Jeffrey Bland: 18:40 As we move to individualization and looking at how we manage health, not just disease, how we can get the maximum functional capability of an individual out of their genes—the white light of good health are their genes—then we look about synchronizing these things that they eat and they’re exposed to. And, as Dr. Sidney Baker has said, “Health is to get rid of the things that are causing you harm and adding back the things that make you better.” And so, that’s what personalized health is all about. And, these symphonic orchestration of our function with these complex mixtures of foods and plant botanical agents is a whole different strategy that we’re seeing to personalize health.
James Maskell: 19:24 Absolutely. Well, it’s a very interesting conversation and certainly if you’re following it as closely as we are, you see that there is going to be no shortage of opportunity for engagement with this incredible plant in all its ways. This has been the Big Bold Health Podcast. We are making health personal in a world of disease. It’s been a pleasure spending this time with you, Jeff, and we’ll see everyone who’s listening and watching next time.
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