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Kenneth Sharlin, MD, is a neurologist with over 30 years of experience in the medical field, specializing in Parkinson’s disease and other brain disorders. He graduated from Emory University in 1992, where he trained under pioneers in Parkinson’s disease, including Drs. Mahlon Delong and Ray Watts, famous for their work... Read More
Colonel Philip Blair, MD, (USArmy retired) is a Family Physician and consultant in cannabis medicine in the Northwest. He graduated from West Point 1972 and University of Miami School of Medicine 1978, trained in Family Medicine and served as combat physician in 1991 Gulf War. Since 2014 Dr. Blair has... Read More
- Understand how the NLRP3 Inflammasome contributes to Parkinson’s and what you can do about it
- Learn about the endocannabinoid system’s role in Parkinson’s and other neurodegenerative diseases
- Learn how beta-caryophyllene can manage symptoms like pain, anxiety, and sleep issues
- This video is part of The Parkinson’s Solutions Summit
Related TopicsAdvanced Glycation End Products, Autophagy, Cannabidiol, Cb1 Receptor, Cb2 Receptor, Cb2 Receptor Role, CBD, Dopamine Depletion, Dopamine-producing Neurons, Endocannabinoid System, Exosomes, Glycation, Gut-brain Axis, Immune Cells, Inflammation, Inflammatory Signals, Misfolding, Neurodegenerative Problems, Neuroinflammation, Nlrp3 Inflammasome, Parkinsons Disease, Ppar Receptors, Prion Particle, Proteus Degradation, Restoring Endocannabinoid System, Thc, Therapeutic Events, Trp R1 Receptor
Kenneth Sharlin, MD
Welcome to the Parkinson’s Solutions Summit. I’m your host, Dr. Ken Sharlin. I hope you’ve been enjoying the many wonderful interviews we’ve had so far. This happens to be your first day or the first day of the summit. Well, we’ve got a lot in store for you today. I’m interviewing or visiting Colonel Dr. Philip Blair. He’s on the West Coast in the North Pacific Northwest. He is a family physician, a consultant, and an expert in cannabis medicine. I know he’s going to tell you more about what he does and his background. Today’s presentation is a little more formal. We’re going to show some slides. I know you’re going to enjoy them. then hopefully, toward the end, he and I will have an opportunity for a little bit of a discussion. Dr. Blair, welcome to the Parkinson’s Solutions Summit and take it away.
Colonel Philip Blair, MD
It’s a pleasure and an honor to be associated with you, with this group, and with this summit taking place. I’ve got some impressive slide presentations I’d like to share. I want to get to that right away. This is the title of my talk: Cinnamic endocannabinoid modulation and a treatment for Parkinson’s disease. I’m focusing on the endocannabinoid system as the modulator for this problem. My history goes back to my graduation from medical school. In 1978, I became a family physician. I was a U.S. Army colonel. I retired in 1996. I entered a disease management program in 2001, and I learned about cannabidiol in 2014. Since then, I’ve been working with patients and developing other products, including beta-caryophyllene, which I’ll tell you about a little bit later on. I’ve also written a book, Medicinal Cannabis and CBD and Mental Health Care, and that’s available as well. It’s a focus on cannabinoid therapies for the treatment of mental illness, and it’s stellar work. It dug me into a great deal of the science behind mental health issues and CBD, as well as caryophyllene. When we’re talking about Parkinson’s disease, I know there are some causes, but I’ve broken it down into these major categories: protein degradation, neuroinflammation, auto autophagy, endoplasmic reticulum, stress, and this is where the stress is most focused: on the body and in the cells, mitochondrial function, oxidative stress, and exosomes.
Exosomes are kind of a peculiar thing, and I’ll tell you about that a little bit later. First off, in terms of inflammatory modulation, one of the things that we know is that the NLRP3 inflammasome seems to be a key factor in inflammation leading to Parkinson’s. I’ve noted in some different studies here that NLRP3 is a protein that plays a vital role in the activation of inflammatory processes in the body. And in Parkinson’s, the activation triggers neuroinflammation and a degeneration of dopamine-producing neurons in the brain. In addition, there’s a CB2 receptor that is also present and has low levels of presence in the normal brain, but it becomes highly activated in a disordered brain with neurodegeneration. Now, one of the processes is this molecule, this protein molecule, that gets misfolded along the way. Part of that process is alpha-synuclein. so that this particular molecule goes through a process of improper folding. That process may be generated by a glycation element. In this particular slide, I’m demonstrating the glycolic defense system for methylglyoxal as an unavoidable byproduct of the catabolic processes. This particular molecule generates a significant amount of glycosylation, and it forms the advanced glycation end products.
That leads to problems with misfolding. Then, once this forms, it has problems with the release of this particular molecule. It has ubiquitination and the proteins that are proteus degradation and autophagy. These are all powerful product processes for elimination. But in fact, the glycation of alpha-synuclein impairs the clearance of these particular pathways, and so it impairs the release, the proteus degradation, and the autophagy. It has been shown that advanced glycation end products have increased in our synuclein brains, and they are detected in the periphery of a Lewy body. It’s an active, ongoing function, and it’s worthy of note. Now this particular study was done looking at the alpha-synuclein, and they found that the mechanism was through the gut. When the gut forms different types of molecules, alpha-synuclein forms in the gut and is passed up through the vagus nerve. This is a unique pathway, and it leads to the assumption that there is something like a prion particle that causes some seeding of the gut of the brain in terms of the degradation products.
In this particular study, they did vague automation, and they got to me through the clients. So the image on the left is of a normal individual, and then the one in the center is where they have induced a Parkinson ‘s-like syndrome. On the right, it shows the disruption of that by doing what they got to me, so the point is that what they got to me limits the exposure to the molecule by blocking the pathways and the transference of this molecule up the chain from the enteric nervous system. Now, this process is quite involved, and it occurs through the exocytosis of alpha-synuclein from the enteric and sympathetic neurons into the extracellular space and the psychosis from the neighboring neurons, resulting in retrograde transport into other neurons. Alpha-synuclein acts as a seed for the aggregation of these molecules in the brain and other tissues. It now functions as a misfolded protein that impairs the mitochondrial complex. It’s impairing mitochondrial function at all levels, and it causes oxidative stress. Now it is particularly sensitive in certain areas of the brain; the substantia nigra and the dopamine receptors are particularly susceptible to the sensitivity of these aggregates. The conventional treatment of Parkinson’s has to do with dopamine stimulation, antidepressants, cognitive enhancement, substances, awareness, and anti-tremor medications. Now they haven’t stopped the progress of this disease at all. It tends to be relentless in terms of its progression, leading to its demise. many of the physical effects and quality of life effects that are encompassed. Parkinson’s disease. Now, what about the endocannabinoid system? The endocannabinoid system could be an answer and could be a target for this particular disease entity.
The endocannabinoid system is a complex system of regulation of different neurotransmitters as well as metabolic and immune functions in the body. It relies on several receptors, endocannabinoid substances, ligands, enzymes, and transport molecules that deliver these particular molecules. It’s involved with almost all of our processes, whether it’s gut, neurologic, cognitive, mood, diet, or nutrition. It has a lot to do with inflammation, cell growth, and proliferation. It is the master controller of these complex systems we have within our bodies. We’ve just gotten into the depths of learning about it. But this could be an answer for many of the problems that we’re facing with Parkinson’s disease. Now I’m going to talk about the major dysfunctions in the endocannabinoid system with Parkinson’s disease, as well as other neurodegenerative problems. The CB1 and CB2 receptors, the GPR55, which is now considered part of the endocannabinoid system, and the TRP R1, which is another important receptor that handles a great deal of pain and neurologic function, are discussed. We’re going to talk about restoring the endocannabinoid system as a whole. We know that the endocannabinoid system directly interacts with doping in the glutamic and GABA energetic systems.
We are well aware of it. With this incredible integration, there’s got to be connections here with the endocannabinoid ligands and with phytocannabinoids, as well as some of the receptor systems that are involved. We know that there’s a doubling of the primary endocannabinoid, which is AEA levels, and we know that there are compensatory mechanisms to alleviate dopamine depletion that go through this system. We also know that dopamine lesions are reversed by dopamine, ECS receptors, and ECS inhibitors. We know that the CB1 receptor is downregulated early on, but it’s upregulated later on. We’ve got CB2 upregulation occurring in this situation.
Now what about the endocannabinoid role in Parkinson’s? Well, we know that there’s crosstalk between the CB1 and CB2 and the TRPV1 receptor systems, and we know that there is a complex with GPR55 that potentiates the neuroprotective capability in Parkinson’s disease. We also know about TRPV1, GRP55, and other connections, and we also know about the PPAR peroxisome proliferator-activated receptors and the neuroprotective effects of Parkinson’s disease. We know that this has a lot to do with this pathology. We also know that CB2 receptors are very keen on the rectification of this disorder and many of the symptoms that go along with it. Now, first off, on the CB2 receptors, which control every one of our immune cells, every immune cell has a CB2 receptor, and it controls the inflammatory signals that cells give off. It has the purpose of shipping the metabolism and immune system to the end of the healing phase of the inflammatory system from the pro-inflammatory phase. CB2 receptors are located on all inflammatory cells and in our immune cells, including macrophages, and everywhere in the body. Oftentimes, it’s left out if the CB2 receptor has a great deal of connection with the neurologic system. The central nervous system, where it orchestrates ion currents where the transmitter is released, has post-synoptic reception expression and post-synoptic currents that have to do with membrane potential. Another key factor here is the PPAR alpha receptor and the PPAR gamma receptor. I’m going to focus on the immune system. It’s a nuclear receptor system on each of our nuclear membranes that controls in detail the immunologic system in a cascade fashion. It’s not just one function; it has a host of different functions, and it’s key and important in the inflammation cycles that go on within the body. What are CBDs?
I’m going to jump to cannabidiol right away, and I’m talking about cannabidiol’s actions on the endocannabinoid system. This has the potential for a major benefit in the body in that cannabidiol blocks the CB1 receptor and blocks TRPV1 and the GPR55, and that has major therapeutic events in Parkinson’s. It increases the arachidonic ethanol mean, which is AA, which is the key ingredient in our endocannabinoid system. It activates the PPAR receptors, and it includes an exosome inhibitor. I’ll get to the exosome inhibition in a moment because what we talked about earlier was a little bit of the migration of the molecule alpha-synuclein into the brain, and it goes by an exosome mechanism, and this is a pathway that CBD can block, and it has a weak modulation of the CB2 receptors, adding anti-inflammatory effects in specific. There have been several clinical trials with cannabidiol, but they haven’t been successful. This is in contrast to an uncontrolled randomized study and clinical practice data collected from patient charts in a randomized controlled trial. The randomized controlled trial did not see any specific benefits.
However, in the trial with medical charting in a non-randomized fashion, they had an 87% improvement in some symptoms related to Parkinson’s disease. Now, this makes it very difficult to get to the detailed science of what’s going on, and is it a real benefit? This was a quality-of-life study that was done that showed none of the movement disorders had any statistical benefit. But look at the quality of life improvements here, where you had mobility increasing by four times, emotional well-being increasing considerably, stigma, social support, cognition, communication, physical discomfort—all these things improved immeasurably with the cannabidiol in this particular group. Quality of life issues appear to be very significant, and a short-term study like this may not see the results of correcting or reversing some end-stage Parkinson’s disease symptoms. Next, I want to get into caryophyllene. Caryophyllene is a phytocannabinoid. It is a substance that connects to the endocannabinoid system very directly and hits all the targets that we have already talked about with CBD. It’s an essential oil common in many spices. It alleviates pain, inflammation, anxiety, and metabolic disorders. It’s found in hundreds of plants, has high concentrations in 36, and has over 3000 articles that have been published on it. But there haven’t been very many human studies. It is FDA-approved as a food flavoring, and it has no toxicity or significant drug interactions. Now, how does caryophyllene work? Caryophyllene works across this range of targets, including cytokines, enzymes, genetics, and signaling molecules over to the receptors, the CB2 receptors and the opioid receptors, as well as the key parts, PPAR-gamma and PPAR-alpha, and the TLR receptors.
Not only that, it’s signaling the nuclear factor Kappa Beta. It’s signaling for autophagy in the mTOR and that whole list of combined connections there. It’s got over 75 different connections on it, all for the benefit of the individual, and it’s got huge potential for everything. Now, because of this potential, we’ve only been able to target several different substances and connections to disease. But across the board, it has been effective for many different problems in pre-clinical studies for ulcerative colitis, chemo-genic pain, dyslipidemia, nephropathy, and so the list goes on but includes pain and cerebral ischemia as well as neurodegenerative conditions. The focus here is on Parkinson’s disease with beta-caryophyllene, and I want to get into that right away. These are the human studies that have been done on beta-caryophyllene. They don’t amount to much. There are less than ten human studies that have been done on beta-caryophyllene, and yet we’ve known about it for 20, 30, 40 years. We haven’t entered into any significant dialogue with it. You can’t rely on human studies.
We can only rely on the pre-clinical work on animal models and cell culture programs that have been going on. Based on these, beta-caryophyllene has magnificent effects on regulating the endocannabinoid system. It promotes neurogenesis; it shifts the microglia from the M2 to the healing type of immune function that restores the blood-brain barrier. It’s anti-inflammatory, it regulates proteasome stasis and autophagy, and it prevents tau tangles and neurodegenerative amyloid beta. But we don’t know about synuclein, and it increases mitochondrial formation and function. That’s very important; it restores mitochondrial function in all of these neurodegenerative diseases. We’re dealing with mitochondrial failure in many cases. I mentioned before that CB2 has two avenues of approach. It works on the glial cells for the inflammatory signals and reduces inflammation, but it also coordinates for neurotransmitters and ion channels, ligand receptors, and synaptic functions, as well as on neural networks and neural functions. All of these have a great deal of bearing on neuropsychiatric and neurologic diseases and neurodegenerative diseases, in particular.
Now, this is very interesting. There is dysregulated microglial polarization in alpha synuclein-induced synaptic pruning, and this is related to the CB2 receptor. If the CB2 receptor is removed from the body and becomes incapacitated, then there are increases in the amount of synaptic pruning that occurs, and that’s going to lead to a pro-inflammatory phase and a major functional problem within the body and Parkinson’s disease, specifically. I get to the point of what actions beta-caryophyllene has on neurologic and pain syndromes. First of all, it’s targeting the CB2 receptor and activating it. It’s affecting the microglia and astrocytes, reducing neuropathic pain. It’s also reducing neuroinflammation and promoting brain-derived neurotrophic factors for improved memory and function. On the left, it is working on an impressive effect on mast cells. I’ve seen this time and again where it has an anti-allergy effect on mast cells that tend to have a lot of connections with our neuropathy and many other function malfunctions as well. I want to keep that as a key factor. On the amyloid beta, it’s handling these misfolding mechanisms that are going on.
Hopefully, it could prevent the misfolding of the alpha-synuclein and inflammation. The key factor here is the CB2 receptor, but it also connects up with an endocannabinoid, palmitoylethanolamide, and oleoylethanolamide. They activate the PPAR alpha receptors. This has a great deal of reduction in pain and inflammation, and it targets tumor necrosis factor-alpha, interleukins, and interferon-gamma. It’s doing this very effectively, and it’s going through PPAR gamma. It also affects the immune system and vascular inflammation by interfering with nitric oxide synthase and promoting that as a mechanism for decreasing vascular inflammation. It sort of has its effects on the heart, the brain, the gut, the airways, and the enteric circulation. About inflammation, I want to point out once again that the action of beta-caryophyllene is to switch the body from the M1 type of activated microglia to the M2 healing-like glia, and it compensates by reducing all those inflammatory markers that I have listed there. What’s the evidence for Parkinson’s? Well, again, it’s not human evidence; it’s animal models. But beta-caryophyllene attenuates oxidative stress, inflammation, and glial activation and salvages dopaminergic neurons in a rat model of Parkinson’s disease, generating neuroprotective effects against dopaminergic neuron injury. It ameliorates a model of Parkinson’s disease in this MPTP cytotoxicity model and upregulates CB2. It upregulates the amount of CB2 in Parkinson’s disease patients specifically. Now, CB2 agonists have reduced L-dopa dyskinesia as effectively as amantadine in some cases, and beta-caryophyllene inhibits
LRP3, inflammation, and the nuclear factor Kappa beta signaling pathway are extremely important factors for inflammation and disease entities. Now I assure you this picture of Parkinson’s, but I want to emphasize the quality of life issues here with these types of problems. All kinds of social and lifestyle problems occur, and the emphasis here on the use of cannabinoids is going to be on the quality of life. As we saw from the earlier study that I mentioned, anxiety, depression, beta-caryophyllene, and cannabidiol can significantly reverse anxiety, stress, and depression. Now, a particular point I want to make here is that this particular study was evaluating obesity-associated airway responsiveness, but it gives you some mechanisms that are involved with beta-caryophyllene and why it works this way. It converts macrophage repolarization to the M2 phase. That’s understood, but it also reduces food intake by decreasing appetite, and it upregulates GLP-1. That’s an important factor that we found that has a great deal to do with neurodegenerative problems as well as diabetes and obesity and upregulates the uncoupling proteins, switching the body from white fat to brown fat through energy conservation.
It increases mitochondria but decreases reactive oxygen species, probably from its antioxidant nature, and it downregulates inflammatory nuclear receptors. It protects the gut magnificently. This is important, particularly in Parkinson’s, because there is up to an 80% rate of constipation that occurs. There are probably issues with the leaky gut, the problems that can occur, and the inflammatory molecules that can arise from the gut into the brain. Beta-caryophyllene has been fabulous for improving sleep quality. I’ve got a couple of testimonials there where these people have slept better and more effectively without any ill effects the next day.
What about CBD versus BCP? Am I comparing them? How am I comparing them, and is it one or the other? Well, it turns out that they both work in combination, and it’s the most effective arrangement when they are combined. In this particular study, there was a comparison between CBD and BCP, and when they were combined, there was a synergy that occurred. For analgesia, that’s certainly the case. But it’s also true in ischemic disease, and this is a stroke model where the combined effect reduced the infarct area significantly with a narrower and shallower range of damage, and both directional effects are protective changes mediated by different mechanisms.
They work together, and they work in a blended fashion. My recommendation for you is that we should combine CBD with beta-caryophyllene to reach the maximum potential of stimulating and balancing the endocannabinoid system. Beta-caryophyllene is a natural herbal food substance. It’s all around us; we just don’t get enough of it, and we don’t get it delivered in a bioavailable fashion. It’s a broad-spectrum cannabinoid that has not been recognized by the medical profession or naturopathic professionals, for that matter. It’s FDA-accepted, it’s low-dose, and it’s got few adverse effects. It’s synergistic with CBD, and it’s an alternative to cannabis products. If a person can’t take or is reluctant to take a cannabis product like CBD, then they can take beta-caryophyllene. It’s just a food, a natural food herb, that they can use effectively. For people who are at risk for urinary drug testing, like athletes, police, military, or medical personnel, you can use this product and don’t have to worry about coming up positive on a drug test because it comes from hops or cloves, which is the main source of beta-caryophyllene in the product. It’s got an established, effective liposomal format and is very effective for many types of problems.
I’m trying to create a balance and complement health through this endocannabinoid system, and I want to restore people’s health with this system, not only with these phytocannabinoids but with diet, exercise, proper sleep, rest, and social interactions. Those are all important elements for encouraging and enhancing the endocannabinoid system. But when we’re faced with serious diseases, we may have to use phytocannabinoids to help restore our balance. Thank you.
Kenneth Sharlin, MD
That was excellent and informative. Folks need to understand where we are today with Parkinson’s disease and that, right now, there is no available or commercially available disease-modifying therapy for Parkinson’s. We treat symptoms. There are some papers on neuroprotection, potentially particularly with a family of monoamine oxidase inhibitors such as selegiline. But these are very theoretical, and they may or may not be appropriate for a lot of people because of the enzyme system that they inhibit. We have a very promising compound that is currently available for folks to sample and experience for themselves and see how it works for them. Dr. Blair, if somebody wants to get beta-caryophyllene, how can they possibly do that?
Colonel Philip Blair, MD
Well, they can call; they can go to the website, and that’s my prominent position. We’ve got blairmedicalgroup.com or blairmedicalgroup.shop, and you can buy four different products that are available in caryophyllene forms: the liposomal oral form; the topical tincture; the topical gel; the crunch, which is a small cookie; the edible form; and the dosing, which is highly variable because people have such a variable response to the cannabinoid effects. I generally tell people to start low and move slowly upward, but half a milliliter or 15 milligrams of caryophyllene is an ideal starting dose for an average person. If you’re particularly sensitive to substances, I would start you off with five drops and/or down to a quarter of a mole liter. But I’ve had people take two, three, and four milliliters for serious problems, and they get tremendous benefits from that.
Kenneth Sharlin, MD
Now, in case someone wants to try this, are there any side effects or sensitivities that have been reported that they should at least be aware of before they try it?
Colonel Philip Blair, MD
Well, Ken, this is the most magnificent part of it. There haven’t been any significant side effects from it. There’s no drug interaction. I haven’t encountered any drug interactions with it; it doesn’t have any toxicity. I offer samples. The website offers five milliliters of samples to get you started because this is so new, nobody has any experience with it, and they won’t believe their response. The response occurs within 10 minutes. You get a significant response after taking 15 or 30 drops; you can have an amazing response within 10 minutes, and you can see that you are getting the benefits that you’re looking for.
Kenneth Sharlin, MD
Excellent, so again, the website is www.blairmedicalgroup.shop.
Colonel Philip Blair, MD
Kenneth Sharlin, MD
You have a code for folks who would like to try it and have a little discount on the cost.
Colonel Philip Blair, MD
Right, and we have a code that says THANKYOU23.
Kenneth Sharlin, MD
THANKYOU23. I also have one: it’s okay to use BCPARK23.
Colonel Philip Blair, MD
Yes, that’s probably the ideal code to use because that will give us a little bit more insight as to who’s ordering it and where they’re coming from.
Kenneth Sharlin, MD
Wonderful. Dr. Philip Blair, thank you so much for joining us today at the Parkinson’s Solutions Summit and sharing your unique experience with this emerging compound they hope will help thousands, if not ultimately, over a million people suffering from Parkinson’s disease. This is very important information. Once again, thank you for your time and your effort. I know what it takes to put together a slide presentation. Folks, this is hours’ worth of work that we are bringing to you. Complimentary of DrTalks, Sharlin Health Neurology, and Dr. Philip Blair with the Blair Medical Group. Thank you again.