Professor Greg Gerdeman on brain science, the neurobiology of stress, and how the discovery of the endocannabinoid system has liberated cannabis from the drug abuse paradigm.
Project CBD: We’re speaking with Greg Gerdeman, a neuroscientist and professor of biology at Eckerd College in Florida. Greg Gerdeman is one of the few professors that we know of who actually teaches classes on something called the “endocannabinoid system.” What is the endocannabinoid system? Why do you teach classes on that, and what’s its significance?
Greg Gerdeman: The endocannabinoid system is an area of research that’s been my focus for 20-some years. It was discovered by understanding how cannabis works. So cannabis works at the endocannabinoid system. It’s a broad way to speak about it. But partly what’s so exciting is that as scientists have studied the endocannabinoid system to understand cannabis, we’ve really come to learn a tremendous amount more about how our brains, our bodies work. How we work, not just how cannabis works. So to the education piece, I’m a neuroscientist and now teaching about how the brain works and processes information, how different circuits work in the brain, endocannabinoids are such an integral part of that, that it should be part of neuroscience curriculums, let alone a course in and of itself.
Project CBD: So what do we specifically mean by endocannabinoid system?
Gerdeman: Well, it means, first and foremost I think the receptors by which THC and other cannabinoids act. So, the targets of how cannabis works and an intrinsic set of neuromodulators called endocannabinoids that are released by cells and act at the receptors. So, although the system is distributed throughout the body, I tend to think about the brain and it’s very highly utilized by the brain. And, as an example of how the brain works with endocannabinoids, a given neuron – a cell within the brain receiving thousands of different inputs – will release endocannabinoids, these small signaling molecules, to fine-tune the strength of their own synaptic inputs. So the endocannabinoids are signaling molecules that are created and broken down by enzymes in the body. They act at cell surface receptors that change the activity of cells. And all of this – the signaling molecules, the enzymes that make them and break them down, the receptors that exert the effects of the compounds – are bundled up into what we call the endocannabinoid system.
Project CBD: So when you talk about “endocannabinoids,” you’re talking about molecules that exist in our own brains and bodies.
Project CBD: Would it be correct to say they’re marijuana-like molecules? How do they relate to THC and CBD, or other components of the plant, these endocannabinoids in our own body?
Gerdeman: In some ways, it’s fair to say that. And people say it’s like the body’s own marijuana. A structural chemist they might take some objection to that because the structures [of the molecules] don’t look that much alike. But functionally, which is what a physiologist thinks about, the physiology of how anandamide binds to and changes cellular activity binding a cannabinoid receptor is actually quite similar to THC.
Project CBD: Anandamide is an endocannabinoid.
Gerdeman: That’s right. “Endo” is short for endogenous cannabinoid, molecules within our own body. They primarily are represented by anandamide and a compound called 2-AG. There are probably several others. We know there are other endocannabinoid-like molecules that are released in an entourage sort of way. And, regulate in a concerted way a great many cellular functions. It’s quite variable, but it seems to be a system that promotes homeostasis well being, keeping the body within an optimal set range. The endocannabinoids modulate the body in that way.
Lee: So you talk about homeostasis and about other crucial functions that the endocannabinoid system plays in the body; homeostasis balancing physiological systems is one. What other aspects of human physiology and biology is the endocannabinoid system affecting or interacting with?
Gerdeman: Well, it certainly interacts with processes of learning and memory and how we integrate sensory, motor information. In a way, as a physiologist, I can think of that all as homeostasis. Like if you’re hungry and go get cues through your body to seek food, that’s a complex process of homeostasis – the human organism is sensing deficit and seeking to restore balance by eating food. And the endocannabinoid system in fat tissue and the hypothalamus of the brain, in the brain pleasure centers (as they get called) that motivate behavior – they’re all being choreographed, sort of orchestrated by endocannabinoids.
Project CBD: In your own research, I know you’ve done work on exercise and how physical exercise affects the endocannabinoid system or the cannabinoid receptor signaling. What drew you into that research? What did you find essentially?
Gerdeman: Well I got drawn into that because, being a cannabinoid brain guy, I had an interaction with an anthropologist named David Raichlen and we started teaming up because he has a long interest in what drove endurance running behavior as an evolutionary force in human evolution. And, so the question of why do people engage in distance running, anthropologists get caught up on the notion that it’s energy intensive, it has risk of damage to your body, and to make what can be kind of a long story short, we started investigating what others had already seen, that with aerobic exercise, anandamide (not 2-AG), anandamide goes up in the blood in humans. We found it in dogs, another group of animals that have evolved to run distances. And we relate it to sort of the runners joy, the runners high. When you get a sense of wellness, elevated mood, wellbeing, the kinds of things that make exercise a good compliment to just healthy lifestyle and well being, the endocannabinoids are related to this. We think that the anandamide levels that go up with exercise are really important for how running and other forms of exercise helps to maintain a robust, resilient physiology – resilient to stress and disease.
Project CBD: So it’s kind of like a feedback loop. It gives you kind of a pleasure, like the runners high, you’re saying, and that’s related to the endocannabinoids in our body, you specifically mentioned anandamide.
Gerdeman: Anandamide. 2-AG doesn’t seem to go up. And that’s part of the new and emerging complexities of the endocannabinoids – what’s the difference between these two. But in the biology, in studies of the neurobiology of stress, it’s interesting that keeping a solid anandamide tone, having a healthy level of anandamide, at least within certain brain areas, seems to be very important to one’s resilience to stress. And the neurobiology of sensing fear and perceiving fear is related to that anandamide level transiently dropping. This is work by Matt Hill. When an organism senses fear, anandamide levels in the amygdala drop, and that triggers the fight or flight immune response. And it also triggers sort of higher level coding of the fearful experience. Higher anandamide levels – and this could be oversimplified – but higher anandamide levels or a healthy anandamide level seems to be, in some very mechanistically clear ways. This is high-end scientific research, related to resilience, to stress, and overcoming and forgetting stress and stressful cues that provoke anxiety from past trauma, for example.
Project CBD: And what do we mean by “stressful cues” in this instance, because so many different things can act as stressors in the body. Are there only certain kinds of stress, like psychological stress, that the endocannabinoid system will mediate in some ways? Or would that be a plethora of different stressful cues that the endocannabinoid system in some way will be involved in helping the organism cope?
Gerdeman: Well, I think more the latter. Because I look at it as a brain scientist, and the neural circuitry involved in perceiving stress, sensing it, responding to it, communicating to the body to elevate the heart rate, the whole suite of stress sensation, responsing, remembering -- those are complex neural circuits and they regulate themselves on a moment-to-moment basis with endocannabinoids. So the system is involved. Now, as far as real close investigation, real fine investigation of stress, the best evidence is for what in jargon you might call homotypic stress, the kind of repeated day-in, inescapable stress that describes some people’s conditions in life that lead to chronic anxiety.
Project CBD: Stress is understood to underline many different diseases or aberrant medical conditions. In general terms or in broad terms, the advances that have been made in understanding brain science through studying the endocannabinoid system -- what are the implications just in terms of understanding disease and health and how we function? What light does studying the endocannabinoid system, or what light has it shed on these basic challenges that we confront in life, on a day-to-day basis? Because most people aren’t scientists, we don’t think it terms of molecules and these things, it’s just we want to improve our health. What does the endocannabinoid system tell us about that?
Gerdeman: Well, I mean, I think we’ve learned enough to say it’s incredibly promising and fascinating focus to look into. The endocannabinoids are implicated in so many different disease states. And it fits in with the whole area of cannabis as medicine, and botanical cannabis products tweaking or interacting with the system in a way that there’s just so much potential for, you know, pain states and stress states and chronic disease. Part of what fascinates me, as a neuroscientist that looks at how endocannabinoids like allow cells to fine tune their own inputs, I can think of how this relates to motor control, for example. And there’s really high-level research showing that endocannabinoids are related in Huntington’s Disease and Parkinson’s Disease, different kinds of tremor. But these same molecules that interact with these electrical neurocircuits are like controlling tumor growth and are signaling in the gastric, the intestinal cell lining, to regulate healing and scarring. There’s so much we don’t know yet. But it’s fascinating that this system acts at so many different levels that are related to health and wellbeing.
Project CBD: So the implication would be that if cannabis interacts with this very subtle and important physiological system, the endocannabinoid system, that it could be used to improve health, to bring the system back into balance if there are some deficits in our own physiology, that for some reason this particular plant interacts in a very profound and deep way with our own physiology and to understand that relationship somehow the endocannabinoid system in crucial.
Gerdeman: Yeah, like no other. The endocannabinoid system, sort of crystallized by the cannabinoid CB1 and CB2 receptors, the evolution of these genes that appeared at sort of the base of the vertebrae tree of life, they weren’t there before, these receptors. And now you look at human animals and we’ve got this extraordinarily complex brain, extraordinarily adaptive immune system, that really fine tunes itself all the time with endocannabinoids, the endocrine system that works with endocannabinoids, something really works with endocannabinoid signaling. And the cannabis plant interacts with it in such incredibly diverse ways, surprisingly subtle ways. You know the notion that you don’t get more serious side effects from using a medicine that interacts at such an integral level with your neurocircuitry, is pretty amazing. It’s pretty amazing.
Project CBD: Opens up whole new vistas, it seems, to understanding human biology with great implications for medicine.
Gerdeman: It does. And that’s why different avenues of research – I mean, when I got into it, the National Institutes of Health really only funded endocannabinoid research under the National Institute on Drug Abuse. Nobody – if you told people, hey you’re interested in the circuitry of the amygdala and fear, learning, and stress, what do you think about endocannabinoids because they’re all over that circuit, the response among scientists would still be kind of like well I don’t study marijuana! I don’t study drug abuse. They didn’t get yet. But now, I like to say that the scientific discovery of the endocannabinoid system has, in some important ways, liberated cannabis from the drug abuse paradigm that’s been locking it in for so many, several decades here – which in the long span of cannabis as medicine is a short period of time – but it’s been enormous. And the endocannabinoid system has liberated cannabis more into the biomedical health and wellbeing – not just for terminal illness, not just as a last resort – but there’s so much value to researching the endocannabinoids and cannabis-derived botanicals as medicines for wellness and resilience.
Project CBD: Well fortunately there are some scientists such as yourself who are not simply operating within the drug abuse paradigm, but have been really doing cutting-edge research that has advanced our understanding of health and disease. And hopefully that can be used to make a better life. Thank you, Greg Gerdeman for speaking with us at Project CBD.
Gerdeman: Thanks Martin.