Twenty 4:20 | #2 Understanding Research Studies
June 14, 2019
Welcome to episode 2 of our bonus series featuring cannabis expert Curt Robbins. In this episode we start by exploring the types of research studies; look at how different dosages and cultivars of cannabis can affect us all in different ways; consider the amazing ways in which cannabis compounds mimic substances we produce in our own bodes; and look at how we've really just scratched the surface in terms of our knowledge of how our bodies interact with this plant.
It's episode 2 — we're just getting started! Listen, learn and share!
Welcome to Twenty 4:20 the bite-sized educational podcast from Tom at Kannaboomers and Curt Robbins, author of more than 500 articles about the science of hemp and cannabis. We're giving 20 cannabis topics 20 minutes each to help you get smarter about terpenes, cannabinoids, cultivars and much, much more. And our show starts now.
Welcome back to Twenty 4:20 the special bonus series of podcasts from Kannaboomers and Curt Robbins, who is really knowledgeable about this topic. Our first episode was a primer on the endocannabinoid system. Today we're going to do a deep dive into how we know about the efficacy of cannabis. Curt's going to talk about some foundational studies. We've got a lot of ground to cover, so let's jump right in.
Curt Robbins: (00:52)
And Tom, thanks for having me.
You bet. We're going to talk more about the basics and understanding research studies.
Curt Robbins: (00:58)
You know, there's a lot of talk and a lot of controversy about the efficacy, the medicinal efficacy of hemp and cannabis and cannabinoids and terpenes that we talked about in episode one. And we talked about the endocannabinoid system, this network of cellular receptors that are these microscopic receptors on the cell membrane surface and they're basically neurotransmitters. And so these molecules from herbs like hemp and cannabis enter our body through ingestion or inhalation and they plug in and almost a literal lock-and-key binding mechanism with that receptor network throughout the body. So we have all these claims of, of medical efficacy, how, you know, how do we get to that? How do we know that, oh, there was a child having, you know, hundreds of seizures per week or per month. They uh, consume certain cannabinoids and terpenes and now they have two seizures, go from 400 seizures a month, two seizures a month, or possibly no seizure activity whatsoever.
That's getting into like miracle territory, right? And then there are understandably people who, and I think this is a good thing, who are cynical about that. Good question. It because there are claims of miracles. And we really, I know you had Mara Gordon on as, as a guest a few weeks back, and she says, look, this is not a panacea. This is not a miracle. This is chemistry. That's a science. And you know, we have to make sure we don't get into a position where we're kind of worshiping in this plant. So how do we get this information and make a conclusion why cannabis reduces seizures, cures cancer, or maybe helps reduce tumor size? Let's try to be careful with the word cures, right? And we have two routes. We have formal research studies, and we have anecdotal evidence. Now, anecdotal evidence can be anything. It can be an article in a lifestyle magazine for someone saying, I had cancer, the doctors gave me three months to live, so there's nothing we can do. And I started taking this oil, this hemp oil, and it's saved my life. That's not science. That is an anecdotal report. And that doesn't mean that there's no validity to it, but that's not hard science.
So let's look at the research side because this is where we're going to convince any cynics of, you know, the reality of the science. There's basically two categories in vitro and in vivo. And this is Latin in vitro is basically petri dish experiments. Okay. Laboratory not involving living creatures and these are the least reliable, but we sometimes get very good data and some, you know, amazing findings from these studies. So we don't want to discount them too much, but they do not involve living creatures. And that's the next level. Those in vivo Studies, now there's different levels of those two. Sometimes it's a rat study or a mouse or another animal.
Curt Robbins: (04:02)
They have endocannabinoid systems also. In fact, the ECS is in all vertebrates, not just all mammals. So this is why we see products aimed at dogs and cats, but all vertebrates have an ECS. So there is a lot of validity. People who say, Oh, well you did that study on a rat, not a human. So that's true. But when we get down to the science of it, when some of these, uh, when the ECS shows some very similar characteristics in these creatures, we can get some valid data that way. But the gold standard is a human trial. And in fact, it's a certain type. It's a placebo controlled double blind human research trial.
Is this what's meant by a clinical trial?
Curt Robbins: (04:45)
Yes. And they're expensive. They're multi million dollars. Typically they happen over years. Uh, typically federal funds are tied to them. So on the political side, it's a lot of red tape and very difficult, and then you've got to use the government cannabis and it's very low quality. There's, there's all these big headaches that we won't get into those details right now. But basically we've got research and we've got anecdotal reports and we need to understand the differences there. And when it is research, you know, we see a lot on social media, right? Research study says what kind of research study, you know, we need to dig just a little deeper. And also on the human trials, it's a matter of how many participants. So the more participants, the better. In theory, if you have 12 participants versus 300 participants, you're going to get some better, more detailed data from the 300.
Right. And I don't want to go deep into this, but pharmaceutical companies do this routinely, right? With new products. But for a plant growing in your backyard there, there hasn't been the budget or the will to do this?
Curt Robbins: (05:52)
Right. Yeah it went underground in the teens, the 19 teens, not if we didn't have to wait until 1937 individual cities and states began outlawing cannabis. El Paso, Texas was the first in 1914. So it's been well over a century where we're, we're making up for lost time with this research, if you look at different systems within the body, okay, right now we're considering the endocannabinoid system and the molecules that plug into that. But if you look at, uh, other systems, they've been researched relatively thoroughly. They were at the stage that we are now with the ECS and cannabinoids and terpenes. A hundred years ago, 150 years ago. Just kind of learning about these basic mechanisms.
We have a lot more science, scientific tools and techniques to uncover what's really going on.
Curt Robbins: (06:44)
Yeah. And again, we get into the political controversies. So anytime there's federal funding attached to that, there's going to be problems, right? So again, if you have a human clinical trial that cost $2.6 million and is conducted over 28 months, you know, there has to be a lot of cooperation to make that project happen. And unfortunately there's just a ton of roadblocks, which, okay. The good news is there is excellent research going on in Israel and there's terpene research in China and the Canadians are doing a lot of research and getting ready to do a lot more research. There's American companies who are saying, Oh yeah, you're going to put roadblocks in our way. And so they're doing the research in a different, some outside the U.S and a place like Canada. So in the next few years, you know, some writers have referred to the period we're entering as a golden age of medical cannabis research because of what we're about to see.
That's exciting. You mentioned Israelis and um, you know, Dr. Raphael Meshulum was a foundational figure in all this doing his work in Israel, right?
Curt Robbins: (07:47)
Yes. In fact, he was, he and his team were involved in something we want to talk about now called the entourage effect. In 1998, Rafael Meshulam and his team published a paper and it was called An Entourage Effect and Endogenous Fatty Acid Glycerol Esters, Enhanced Cannabinoid Activity. This coined the term entourage effect. No one had, you know, this dialogue did not exist prior. Yeah, it was really advanced. Uh, this idea of an entourage effect, and it is a theory, uh, was advanced in 2011 by American Dr. Ethan Russo. He published another research paper and these are easy to find online and, and folks can do their own research and get into the details. It was called Taming THC, Potential Cannabis Synergy and Phytocannabinoid Terpenoid Entourage Effects. And this paper really took our understanding of a potential entourage effect even further. So let's talk about what it is. It is the idea that we've got 113 cannabinoids, 200 terpenes. Now they don't all manifest in a particular cultivar of hemp or cannabis, their potential they're the genome, and they can manifest just like in humans, not everybody gets blond hair or blue eyes or long legs or whatever characteristic it might be, and that's called a profile, a cannabinoid profile and a terpene profile and an individual sample of hemp or cannabis has these profiles and we can look at those profiles. If we analyze a sample from a laboratory, right, it's called a Certificate of Analysis or COA, and that can show us exactly what's what's going on in there. Well, depending on the exact composition and ratios, this is important, the ratios of those molecules. Okay. I might have a bunch of THC and a bunch of CBD. What's the ratio? 20 to one three to one? And we can determine that when we formulate products. So it gets even more complicated.
What you're describing sounds like two very foundational studies in, you know, at the top you talked about in vitro and in vivo where these petri dish experiments or how did they begin to kind of corral the complexity of all, all these different compounds and ratios and all that?
Curt Robbins: (10:09)
Some of the most valuable studies are actually literature reviews where they review everything that's been done prior, so they might not be doing a human trial themselves, but they can be analyzing the data obtained from other human trials. And really what these studies did is they were from respected professional, serious researchers who were saying for some of the first times in our history, hey, this looks like we've got efficacy here and here's some numbers to back it up, right? We know cannabis and hemp had been used for thousands of years going back five, 6,000 probably 10,000 years. But we don't have a whole lot of science behind those mechanisms at work and modern life and people like the FDA and cynical consumers. We want science behind it. We want to know how it works and why it works, and the entourage effect helps explain that. So basically it says that all of these molecules co-mingling, offer an efficacy that is greater than the sum of their individual efficacies. They start to buffer and boost and change the efficacy of each other. And we get new efficacies.
For example, if we just have this single molecule called an Isolet, it might increase appetite or decrease pain or reduce inflammation and swelling or something like that. When combined with a different molecule, the efficacy might be significantly different. For example, the molecule THC increases appetite. Okay? It has a molecular cousin, it's barren version called THC V. And THC V reduces appetite, which would be good for somebody with type two diabetes or obesity and other conditions like that. Whereas you know, they don't want to do THC because that's their issue. They don't want to increase their appetite.
There's another wrinkle that I know you've researched and I've heard you mentioned before, and that's the, the biphasic response that some of us have.
Curt Robbins: (12:14)
Uh huh. And this is where it starts to really get a little complicated, right? Because we love to make blanket statements. We're a newsfeed society. We'd like to say, you know, cannabis is good, cannabis is bad. That's kind of ridiculous because again, we've got these hundreds of molecules, terpenes and cannabinoids and flavonoids floating around them. They're so too talk about that set of molecules as just a single thing that's either good or bad is a, is kind of ridiculous. But THC is a great example. The biphasic response for means that in low quantities, low doses, a molecule has a certain efficacy, but in high dose as potent doses, it has a different efficacy and sometimes that efficacy is polar opposite. And that's what's a little frightening about this because now we can't even say, oh, THC is good for X, Y, Z, what's the dosage? And we're not even taking subjective efficacy into account pair, right? So with anxiety specifically, THC reduces the anxiety in low doses, the mellowing effect, right? Let's, let's chill n' Netflix kind of thing. Right? In high doses, especially for new consumers, people not acclimated. Their endocannabinoid system is not acclimated to consuming these molecules and in high doses it can increase anxiety, lead to disorientation, quote unquote spun out, you know, as the kids say and even blatant panic attacks, you know, people show up in the emergency room because they had two brownies and they should have had half a brownie or however it works.
Right. So it's another layer of complexity on top of the, the entourage effect. Another aspect of it too is the idea that you could be deficient. I mean as we talked about in the first episode, we have this endocannabinoid system, we have endogenous cannabinoids and phytocannabinoids, but can you talk about the possibility of being deficient and how you might supplement your, your body with phytocannabinoids?
Curt Robbins: (14:16)
Back to Dr. Ethan Russo in 2004 he published a research paper called Clinical Endocannabinoid Deficiency or a CECD: Can This Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and Other Treatment-Resistant Conditions. I know it's kind of a verbose title, but accurate nonetheless, right? Yeah. And basically, again, this is a theory as as, uh, Mara Gordon pointed out on one of your previous episodes, what Russo observed was that if have a mental model of a deficiency in the ECS, why would it be deficient? Well, we don't get enough exercise. We have poor diets with a lot of processed food. Uh, you know, we're all stressed out about rush hour traffic. Uh, we might have genetic issues, you know, all of us have imperfections in our code and our physiology, right? We have pros, we have pros and cons. And uh, so, so we have all these potential causes of this deficiency in the ECS.
Well, we should talk a little about endocannabinoids versus phytocannabinoids, which I know we talked about a bit in the first episode, but if the endocannabinoids become deficient, it's like taking vitamin C because your body is not producing. We produce a lot of our own medicines. I know it's a crazy concept and western medicine doesn't embrace it, right? So we have these endocannabinoids, like anandamide and 2 AG, and we're producing our own medicine basically when, when we have those, well if we have deficiencies in those levels, it turns out that molecules from plants like hemp are memetic molecules and they evolved after the endocannabinoid system. So the plants are inviting themselves to our party, but it's our party, not their party. Hm. Plants evolved molecules like CBD and THC and limonene and pinene and all the terpenes and flavonoids after the Mammalian endocannabinoid system. So it's really cool concept called mimetic molecules. So THC mimics and anandamide and CBD from what we understand right now mimics 2 AG and kind of a rough model there, but there's just so much. We don't know. There's other, you know, there's receptor types. We have the CB one and CB two right now, but there's receptor types that are both theorized and not even theorized yet. We just don't even know they're there.
That's really fascinating. I mean, the relationship between this plant and anybody with an endocannabinoid system, there's sort of a synergy going on here, I guess.
Curt Robbins: (16:55)
Turns out this as a really critical system because, well, we all know someone who's got arthritis or fibromyalgia or Crohn's disease or cancer or one of these conditions that Dr Russo is saying can be prevented if we achieve a state in the endocannabinoid system called homeostasis. And it's just a fancy word for balance. Okay. But as Mara Gordon pointed out in an earlier episode, it's not so much that we're trying to balance the ECS. It's we want a healthy ECS because it balances all the other systems immune response. How important is your immune response? I mean, holy cow, right? So healthy immune response that ECS is in charge of that. That's what we've learned over the last couple of decades.
That's some mind blowing stuff when you consider how long we've neglected this plant and how crucial it is to balance.
Curt Robbins: (17:45)
Yeah, I know we're all busy and that's one thing we're trying to do with this series is not talk for two hours. Talk for 20 minutes. Right? And let people learn as efficiently and easily as possible. But the reality is this is complex science. You know, for me the epiphany moment was the bi phasic response curve where I'm like, wow, we just cannot make definitive statements. Especially when we start considering different use case scenarios. A six year old child with Dravet syndrome epilepsy versus an 87 year old with osteoporosis. Those are very different scenarios.
And each consumer has to be involved themselves. Test and learn, see what works. There's no blanket statement you can make about this plant.
Curt Robbins: (18:26)
Yeah, just, just dosing alone is a, I don't want to call it a game, but it is an activity or exercise and trial and error, especially difficult for, let's go back to the child patients where they're growing, right? Their physiology is changing. Uh, maybe they're entering puberty or you know, hormonal levels are changing, but regardless, so dosing can be a real headache for parents of special needs. Children who are using CBD or cannabis and hemp products, uh, because the child's physiology is changing literally on a weekly basis, uh, and they have to go through, the dosing determination. Again, it's a, it's a moving target.
Well, it requires a lot of attention and care on, on the side of anybody who's using this plant. And that's why we're doing this series. And, and uh, hopefully this episode was useful to people who want to know about the efficacy of the plant and we'll be continuing this series uh, for 18 more episodes. But that's about it for today. And I want to thank you, Curt, for taking the time. We look forward to connecting on the next episode.
Curt Robbins: (19:31)
Thanks Tom, let's do it again.
You've been listening to Twenty 4:20 a special edition podcast series from Kannaboomers and Curt Robbins. Want to learn more and help grow the cannabis movement, spread the word and follow us on your favorite podcast platform at kannaboomers.com.