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00:01 | This is Lecture 25 we discuss this called voltage sensitive dye imaging technique, |
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00:10 | is abbreviated VSD or VSD. I I come back to this image to |
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00:16 | you that it's an important technique. an experimental technique, and if you |
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00:22 | , these voltage sensitive dies that these molecules that change their entry point into |
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00:29 | membrane change their confirmation. And as dyes air improve, great impregnated in |
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00:35 | brain to show in the brain slices in a living animal brain, you |
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00:40 | observe variations off large spaces in the , and you can observe them with |
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00:47 | high resolution, where one of the pixels represents activity from several cells. |
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00:53 | so both the sensitive dye imaging technique used and was used to describing the |
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01:02 | columns. Uh, in the primary cortex and the experimental set up for |
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01:08 | would be just like is indicated in slide. The other thing is actually |
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01:16 | that these techniques are experimental techniques, in fact what what is uh, |
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01:23 | interesting about this is that these experimental are advancing all the time, and |
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01:31 | this case, what we're seeing is seeing the fact that image ing, |
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01:36 | we discussed from very early on, can do it multiple different levels and |
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01:42 | these experimental techniques from impregnating the brain sure the slices with the dies, |
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01:48 | can also have genetically, um, voltage indicators. They're called jeffy. |
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01:56 | coded voltage indicators or genetically coded voltage dies. In this case, it's |
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02:05 | something that is encoded genetically, but slide I'm gonna include. And I'm |
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02:11 | in the review because their view talks how to take these techniques. Imaging |
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02:17 | vaulted sensitive dye genetically coded it died and translate them into riel practical |
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02:25 | And as you think about image ing understanding different levels of the brain, |
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02:32 | leads us back to where we started that there are so many different |
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02:37 | You can study brain activity in macroscopic and you're observing population activity where different |
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02:47 | of cells are communicating between different You can observe it at a |
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02:56 | Aske opic level eso. In this , you can increase the magnification and |
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03:04 | can start, uh, segmenting the into blue and and read, and |
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03:13 | those blue and red cells or different subtypes. You can address it |
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03:20 | and you can start looking at not how the cells are activated in different |
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03:26 | or in this case of one specific , but also how these cells form |
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03:32 | circuit that means now you're talking about and communication of the level off the |
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03:40 | , and then you can take it further. You can look at the |
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03:44 | level. What is individual cell and den drives on that sellers doing compared |
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03:51 | the Selma and some cellular level? , now you can look at individual |
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03:57 | and interactions between then drives the critic and accents or external batons that are |
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04:04 | , that are the external synapses that formed in passing from these axons from |
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04:11 | neurons. And so this is very diagram, because are y stands for |
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04:19 | of interest and modern imaging techniques allow to select the region of interest. |
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04:25 | this shows you a cellular and sub localization, where you can select soma |
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04:30 | compare activity in soma to the two that air circled here or outlined by |
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04:39 | and read off lines. And then could look at that did it in |
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04:44 | a single spine to which is sub . So again, the multiple scales |
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04:52 | organizations in the brain, from some to cellular to circuit connectivity Thio entire |
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05:00 | , interconnected circuits on the macroscopic the whole brain level is Well, |
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05:06 | include the references Thio this, very interesting articles. And I will |
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05:13 | these articles from the folder for you well. Uh, there will be |
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05:18 | reviews posted on this topic, as just indicated, um, on Cove |
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05:24 | 19 and the brain. So let's to understand. Let's try to understand |
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05:31 | phenomenon. Let's try to understand the of physiology, how it affects the |
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05:37 | and let's try to spend now the let's say, 20 minutes toe half |
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05:45 | lower discussing the facts of coded 19 the brain. I think that some |
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05:52 | you may be graduating. Is undergraduates into graduates? Fear may be looking |
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05:58 | , um, different professional experiences and , and I think that this area |
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06:05 | over 19 is gonna present a very area prime for investigations prime for new |
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06:15 | off the facts of the viruses on brain as well as the new therapeutic |
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06:21 | . Um, drugs developed. And , as you can see. Coming |
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06:26 | . Um um, Aziz we see recently. So how do these viruses |
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06:36 | ? How does coded 19 enter into CNN s? And we know that |
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06:44 | in the droplets. So when you when you speak, when you |
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06:51 | it is being put out into the the atmosphere into the air. But |
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07:00 | that virus toe, enter into the . N s. Well, one |
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07:05 | that he can enter into CNN s through nasal cavity. Back of the |
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07:11 | is that if you look at the factory system, which is the system |
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07:16 | smell, you have all factory nerve thes air olfactory nerve endings that are |
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07:24 | and inside our nasal cavities. Okay, this this nasal cavity here |
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07:32 | these olfactory nerve endings actually penetrate through skull. This is a picture off |
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07:40 | we call the crib reform plate shown a CFP. And this is an |
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07:47 | , um, skull, That As you can see, this is |
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07:50 | piece of skull the crib reform plate located right underneath the olfactory ball with |
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07:55 | of these nerve endings. going into nose that are responsible for the sense |
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08:00 | smell that there's physical demonstrations, physical wholesome openings that allow with these nerve |
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08:09 | toe enter into the CNS direct So therefore, viruses and things that |
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08:18 | into the nose can actually penetrate through crew. Perform. Play directly into |
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08:25 | CNS through this loose, essentially in way, loose anatomical structure. |
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08:31 | so that's nasal cavity is interest through nasal cavity. So if you have |
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08:36 | in the nasal cavity and you are a mask but you haven't covered your |
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08:45 | , then you're not wearing a Scientifically, your virus lives in nasal |
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08:51 | , so if you are a carrier you could be asymptomatic, remembers |
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08:56 | asymptomatic carriers, and you think that so cool because your nose is hanging |
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09:01 | or you see somebody else with their hanging out is just the same is |
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09:05 | wearing in that. So wearing a prevents this inhalation through nasal cavities to |
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09:14 | just X elation but inhalation through nasal . Wearing a mask prevents escalation from |
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09:20 | mouth. Very mia, which is in the blood, reaches CNS through |
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09:28 | blood eso one is entering through the cavity directly. Another one is virus |
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09:33 | the blood. Remember that you can infected by touching. You can get |
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09:39 | through fluids. You can get infected wound. You can get infected |
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09:44 | uh, sexual intercourse. This is is all of the things the fluid |
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09:53 | , anything that penetrates that goes into bloodstream potentially through wounds for three little |
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10:00 | in the skin or stays on the . And then you're touching your |
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10:04 | your mouth, you know, potentially , swallowing and some of it. |
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10:11 | the second or the third enter into CNS is we think it happens because |
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10:16 | the hypoxia damage, so that there a damage and hypothesis is lack of |
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10:22 | . There's no damage to the brain damage just blood, brain barrier and |
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10:28 | things that you might be hearing Is that the entry? How does |
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10:33 | virus? Okay, so it entered the nasal cavity, entered into the |
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10:37 | . Somehow there is a hypoxic damage entered into the CNS. It has |
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10:41 | hang on to something. The first it does it hangs onto a stew |
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10:46 | , Which is this? A cell receptor and your angiotensin converting enzyme two |
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10:54 | . This receptor is located throughout the , so you will find it in |
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10:58 | heart kidney lungs. It was also in the CNS and PMS perform nervous |
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11:06 | . So virus enters has got toe into the south that uses this case |
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11:12 | receptor to penetrate into the south upset whole whole system. Subsequently, a |
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11:24 | receptors in the C n s. will find them in the end, |
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11:28 | lining between the blood capital, Aries the brain. Remember, you have |
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11:33 | endothelial cells, you have the parasites then you have the glial cells. |
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11:37 | Astra sites. There's some a stew on glial cells and neurons. So |
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11:44 | it enters into CNN US if if goes through this lining and the fuel |
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11:49 | lining or if it's in the uh, interstitial spaces now it can |
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11:54 | targeting glial cells and neurons invading the . And also infection year on the |
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12:05 | cell levels is gonna compromise the blood barrier. Infection of the exercise is |
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12:10 | to compromise the blood brain barrier. you compromise, the blood brain barrier |
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12:15 | now loose. Now, if you . It's a double kind of a |
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12:20 | sword that you have infection. Now have compromised blood brain barrier, which |
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12:24 | let him or infection into the causing more neurological damage potential. |
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12:34 | so if you if you think of c N eso review and called in |
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12:41 | and next day this PMS overview of 19 let's try to understand some of |
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12:46 | general concepts. How is it transferred droplets? Direct contact with an infected |
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12:54 | indirectly for my surfaces? When is path of physiology viral? Enter into |
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13:01 | brain adverse immune responses and respiratory It's the logical significance you have these |
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13:12 | dense areas in computer tomography, so damage to the brains, and there's |
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13:18 | in the brains. Main symptoms would headache and vertigo. Initially, major |
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13:26 | would be stroke, meningitis and something is called acute necrotizing and so |
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13:31 | With the type one. It is a very rare type of brain disease |
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13:37 | occurs in viral infections. They're rarely sometimes with flu, but also with |
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13:45 | other viruses, which sets off a chain of reactions and causes encephalitis and |
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13:52 | philosophy the which is inflammation of the , which is delusions, which |
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13:58 | uh, hallucinations and quite often, that can last for weeks because of |
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14:08 | viral infection in the brain, there no conclusive treatment. So paracetamol or |
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14:18 | inflammatories as being, uh said to headache and vertigo relief without worsening |
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14:26 | So if you're talking about headache and , maybe that's the treatment. But |
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14:30 | you're talking about stroke, meningitis, and hemorrhage information or blood clots and |
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14:37 | of blood, then then then, , it's very serious. And the |
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14:45 | accordingly. Eyes hospitalization, potential intensive unit overview. Peripheral nervous system, |
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14:56 | droplets, direct contact with an infected and directly for my surface chemo sensor |
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15:03 | is the first thing. So what think is happening is the hair like |
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15:09 | on olfactory tissues on these old uh, tissues, their hair like |
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15:17 | and they get damaged on. So get a naz mia. You get |
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15:23 | blindness. Andi, if it starts the senses of taste and you get |
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15:30 | Shia, which is loss of um, these air the main |
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15:36 | So even in early stages of co with the flu temperature and, |
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15:47 | fatigue you may also be experiencing and me on a goose er, people |
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15:52 | experiencing just losing completely drinking coffee and tasting anything. And coffee? |
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15:59 | that may return, and it does with time. It's the ending nerve |
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16:07 | endings for the smell pathways on the pathways. Major symptoms is Guillain Barr |
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16:16 | Miller Fisher syndrome, which we don't need. Thio discuss. I have |
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16:21 | definitions that will provide for you, there's no conclusive treatment Nasal spray being |
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16:26 | for medication delivery. Okay, so , pretty grim situation. Good thing |
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16:35 | have vaccines coming out. This is nice diagram that has a that the |
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16:39 | of central member system manifestation from So viral enter to the brain adverse |
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16:45 | response, which is the reaction and stress. This is all path of |
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16:52 | , things that can go bad. in the periphery you have the |
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16:56 | sensory dysfunctions, that virus and factory Mucosa. That inflammatory response You have |
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17:04 | me and Negussie a symptom resulting in periphery in the CNN s. If |
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17:09 | virus reaches the brain and olfactory or if it goes through Vira |
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17:15 | which is overall coming from the blood the brain hanging onto these a stew |
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17:22 | . Then what it does. It and causes leaking in the blood brain |
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17:29 | , which causes cerebral um, Dema , which is causing cerebral swelling. |
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17:37 | the same time, the inflammation that on viral load easier starts causing |
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17:45 | death of cells of the brain, leads to increased intracranial pressure, and |
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17:53 | of the cerebral oedema and then cerebral of this inter cranial pressure buildup and |
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18:02 | of the brain build up. Now can start compressing brain stem. And |
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18:07 | you remember, brainstem contains your vital , control centers for respiration and for |
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18:14 | trade. Damn. So now you ones, in fact, that this |
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18:19 | in here, causing massive swelling in brain and inflammation. That swelling now |
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18:26 | affecting your brainstem region so you can . Breathe barely, and you don't |
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18:32 | control or breathing. And heart rate , plus your lungs are also in |
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18:37 | , that through the respiratory stress the stress. You will have lots of |
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18:43 | in the lungs. Multi system organ , including the brain. There is |
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18:48 | neural injured in the brain. If go off oxygen, some of the |
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18:52 | susceptible south to damage in lack of or hypoxia. Our neurons, two |
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18:59 | and they're done two minutes without oxygen neurons die in euros. We generate |
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19:06 | so they don't regrow like the nerves the periphery. They don't regrow like |
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19:12 | nerve endings and the olfactory or the things do it. Once you kill |
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19:16 | , their synapses. Without us, done. Adverse Immune response. Violent |
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19:23 | could trigger CIDA Conover abundance and sidle storms Those air pro inflammatory molecules. |
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19:30 | also can cause a lot of coagulation hemorrhaging in the brain. So both |
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19:38 | on the philosophy. I'm sorry. so fill Itis are acute, the |
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19:46 | and philosophy. Now we're encephalitis leaking of the blood. And now |
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19:54 | have a recipe for calculation formation off blood clots and, uh, plugging |
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20:02 | of the blood. That's all swish can lead to other problems like like |
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20:07 | , for example, So neurological abnormalities cove In 19, 30% of patients |
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20:17 | required hospitalization have neurological abnormalities, 45% those with severe respiratory illness with |
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20:30 | So if you get into the situation you have compromised your respiratory, |
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20:39 | organs okay, with severe respiratory illness 85% of those with acute respiratory |
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20:52 | So if you start affecting the lungs the breathing, that means you are |
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20:56 | even more significant damage to the If you were just hospitalized, one |
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21:03 | three will have neurological damage. But you're hospitalized with respiratory syndrome or acute |
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21:12 | disease, that number goes up to to 85% of neurological damage. Good |
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21:23 | . Well, not so good, mostly neurological symptoms, mostly confined to |
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21:28 | specific abnormalities. So just dizziness, , loss of smell, taste |
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21:36 | You may experience similar things with some the, um, influenza cold viruses |
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21:44 | . I actually had a loss off about three years ago. It was |
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21:52 | strange. That lasted for about two , when I had a pretty severe |
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21:58 | . So seriously, Neurological complications, mean reported with Mild Cove in 19 |
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22:07 | , of course, severe complications with bill patients and associated with much |
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22:16 | significantly higher mortality. It's a philosophy again Viral infection can cause cell |
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22:26 | delusions, coma, ischemic stroke. is you have the blockage. You |
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22:35 | the blockage off the blood vessels. epoxy is you don't have enough |
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22:43 | You also have post infectious neurological and so you can hear about people |
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22:50 | are long haulers and that these neurological may be significant with persistent headaches and |
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22:59 | for months following testing negative cult in . And in addition to that, |
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23:06 | a mental health aspect to a very indications for anxiety and depression associated with |
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23:14 | haulers of coded 19 intensive care by intensive care related neurological manifestations. So |
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23:23 | get, and to intensive intensive care means to have respiratory failure. You |
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23:28 | other things and treatments that are happening you that again could be indirectly not |
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23:35 | directly due to the virus but trying contain the virus in order. So |
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23:45 | include some or of these descriptions here a slide for you that you can |
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23:51 | . But I think that this is , very important that we start understanding |
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23:57 | that you put all of the things you learned into perspective of what is |
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24:02 | on the big problem that is happening now right in front of us. |
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24:08 | , so when somebody tells you that don't need to wear a mask because |
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24:14 | does not do anything to you. , please send me those references. |
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24:19 | masks don't do anything on guard. than that, I think that you |
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24:27 | by looking at this anatomy, just duh. The virus. Anderson to |
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24:33 | virus enters into here. Exits from exits from here. Uh, I |
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24:37 | probably cover my nose and my And if I cover my mouth, |
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24:42 | I might not as well cover And, you know, besides just |
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24:48 | own belief, whatever it may uh, motivated by individual freedom, |
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24:56 | standing, uh, partisan affiliation, , you have responsibility to others. |
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25:05 | your peers. You have responsibility to elders. You have responsibility, |
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25:11 | the whole society and the whole You are not alone. And so |
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25:19 | each other is the key here. they keep talking about this because this |
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25:25 | an unfolding story. It's unfolding. of physiology were cracking the code off |
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25:34 | by covert. 19 were cracking the of what is happening in the brain |
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25:39 | the processes. And you should be Thio really understand much better. What |
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25:47 | scope it may have on the brain you have taken this course during the |
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25:56 | during the pandemic. So this last half an hour, this last lecture |
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26:05 | a spend talking about them, the system and you already learned about |
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26:13 | They're cannabinoids is neurotransmitters that regulate excited and inhibitory neuro transmission. We studied |
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26:21 | Canavan us when we studied neural Uh, the cannabinoid system was discovered |
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26:28 | the 19 nineties, so it's relatively sistemas. We understand it. And |
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26:34 | phenomenal system, therefore, is only 30 years old. And what we |
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26:42 | about this system is developing. But I choose to talk about this is |
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26:48 | I think that this system is grossly studied. I believe the system is |
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26:58 | important in the overall homey, a body regulation and homey a static regulation |
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27:08 | the brain functions. I think it's system that's very intricately involved with other |
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27:15 | in the brain and potentially gets, , activated before some other neurotransmitter systems |
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27:22 | active. So given this, that the cannabinoid system is a system that |
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27:30 | every animal in nature has, including of the very primitive animals that live |
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27:37 | the bottom of the ocean and given fact that recent regulatory changes, including |
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27:44 | the last selections, have brought out changes in the cannabis laws and regulations |
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27:52 | by state, where overwhelming majority over off population United States have access to |
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28:00 | cannabis or the forms of fighter there's a cannabinoids that come from the |
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28:08 | mhm. Given these two things, think that there's a lot of future |
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28:14 | drug development for science development program as this is an emergent field, |
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28:21 | so as it is emergent, with in 19 might be also interactions between |
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28:28 | field and studies on, and the that are being developed for covered 19 |
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28:36 | well. So two very relevant topics cannabinoid system than we know consists of |
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28:44 | receptors under cannabinoid molecules, and these receptors remain. One C B one |
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28:50 | C D. Two are expressed very throughout the body in many different |
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28:56 | observing different functions in these organs major in the cannabinoids that we discussed our |
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29:04 | Mind or Eric Adonal Phenolic mine and a G or two or $2 glycerol |
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29:15 | CB one receptors, cannabinoid receptors, are dominating in the brain, but |
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29:22 | one receptors are also very highly expressed the intestinal organs. Heart, |
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29:29 | kidneys, stomach CB two receptors on other hand, arm or confines. |
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29:40 | organs like bone marrow like spleen are involved in regulating and amassing |
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29:51 | an immune response in the body. you have this very complicated and do |
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29:57 | system where you have cannabinoid and the molecules cannabinoid receptors there synthesizing and there |
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30:06 | enzymes throughout the body and in the as we saw it serves a very |
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30:12 | function, very important function off regulating transmission in the brain. You also |
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30:19 | expression of CB two receptors. Center in control of inflammation in the |
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30:24 | as well as the release of these inflammatory side of cons. And and |
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30:30 | mind and the cannabinoids are introduced into human system very early on with a |
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30:38 | and the production of a human milk has increased production and synthesis of Ananda |
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30:45 | and and a mine or Ananda stands bliss. What happened? Molecule blissful |
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30:54 | , newborn suckling is thought to be by the president's off the cannabinoids because |
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31:01 | the cannabinoids in the newborn's themselves, just in the human milk but also |
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31:07 | the newborn's, promote feelings of hunger also feelings of satisfaction. It's a |
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31:15 | that gets activated with pain and stress trauma. It's in law than the |
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31:22 | function. It regulates appetites, so cannabinoids, regulate levels of appetite. |
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31:28 | affects memory, inflammation, thermal regulation many other different functions in the |
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31:34 | So these end of cannabinoids like Ananda very similar in structure to Fido |
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31:41 | and you have over 120 different phyto that are found mostly in the cannabis |
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31:49 | . An example of such phyto The Steptoe Hydra Canavan, all delta |
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31:55 | THC DHC, just like Ananda Mind be interacting with cannabinoid receptors as well |
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32:03 | other receptors and pathways in the body the brain. If we look at |
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32:11 | CB one receptor expression, you will that there is abundance CB one expression |
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32:18 | here in red and then read. have a lot of CB one receptors |
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32:23 | the hippocampus, which is responsible for memory and stress in basil ganglia, |
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32:31 | is emotional response. Motor command the memory, cognition, learning prefrontal |
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32:39 | , which is the executive function in cortex, which is higher cognitive |
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32:45 | as well as in the cerebellum, controls the posture. So there's high |
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32:51 | of CB one receptors that are expressed these brain structures in here. And |
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32:57 | you recall what those brain structures they're for, then you will understand now |
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33:04 | the end of cannabinoids but also how fiddle cannabinoids can have an effect on |
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33:09 | and memory, like THC can have effect on posture can have an effect |
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33:15 | executive or emotional functions. In the . We have CB one receptor that |
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33:25 | moderately abundant in the specific areas of brain, so you'll find them in |
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33:29 | hypothalamus, which is length again to regulation. In the making, the |
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33:35 | is linked emotional response and it's very in the brainstem cannabinoid receptors again think |
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33:44 | what under economic noise can then or the final economic noises that in |
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33:48 | brainstem CB one receptors are located and Aqueduct gray area and nucleus of the |
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33:54 | track. So in the brain which we know control, sleep |
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33:59 | temperature regulation on motor control, the receptors, or CB one receptors more |
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34:06 | are not involved in breathing, are involved in regulation of the heart |
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34:13 | The opioid receptors that are found in brain stem would be responsible for the |
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34:19 | body. Organ controls and the opioid in the opioid overdoses happened because the |
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34:27 | dose of opioid is this big and lethal goes of opioids is only three |
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34:33 | or four times effective. Does with lethal dose can affect the vital respiratory |
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34:39 | heart rate centers, causing an opioid and death. So in United |
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34:45 | we have tens of thousands of overdoses opioids, and we have an opioid |
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34:55 | , um, epidemic going on in States, tens of thousands of deaths |
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35:01 | opposed thio cannabinoids that are in the plant. The effective those maybe 1 |
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35:10 | of cannabis or one joint of cannabis the lethal does is about 1000 times |
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35:18 | joints that have to be consumed in 15 20 minutes. And in the |
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35:25 | of THC, which isn't intoxication, no deaths. There's a recovery over |
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35:31 | period of ours from overdoses of and it does not affect the vital |
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35:37 | and therefore you don't have the deaths to candidates in THC. This should |
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35:46 | look really cool to you guys because understand everything. This is what I |
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35:52 | medical doctors. I also have a entrepreneurial string inside of me. And |
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35:58 | of this entrepreneurship, uh, endeavors teaching medical doctors, nurses and healthcare |
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36:06 | about the endo cannabinoids under cannabinoid system medical candidates. So what happens? |
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36:12 | potentials arrive. You have deep Calcium influx through voltage, gated calcium |
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36:19 | , fusion of neurotransmitter vesicles, a membranes, extra psychosis. Let's say |
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36:25 | . In this case, binding of glutamate receptors increased deep polarization postion optically |
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36:31 | through Boston optic, both educated calcium . Due to the deep polarization this |
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36:37 | influx now turns on. The production on the end of cannabinoids synthesizing enzymes |
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36:44 | year, and those under contaminants emphasizing produce on demand Ananda mine into a |
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36:53 | . They're not packaged in the but remembering soluble will traverse through these |
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36:59 | . Will retro greatly travel and blind one receptors pre synaptic lee on the |
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37:07 | and CB two receptors, which are dominant and glial cells. When the |
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37:12 | of cannabinoids bind to the CB one , the G protein coupled signaling they |
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37:19 | reduce calcium influx. It will also the sodium influx and deep polarization. |
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37:26 | by reducing calcium influx and deep they will control the Exocet Telesystem Balance |
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37:33 | psychosis in this case of ex Editori . But it also is done with |
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37:39 | inhibitory synapses with inhibitory GABA. our transmitter, so CB one receptors |
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37:47 | the brain are also responsible for the effect. That euphoric effect can be |
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37:55 | with endo cannabinoids. And one of best ways to stimulate in the cannabinoid |
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38:01 | is not only through negative stress but through exercising, which in a way |
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38:08 | a repeated stress. You demand more . You demand mawr, sugars and |
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38:15 | to the cells that are active. breathing your blood is circulating. You |
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38:20 | a lot of other cannabinoids, and we know is the runner's high people |
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38:28 | feel blissful feeling and very happy. there running especially long distances because there |
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38:35 | an increased production and release of under and demand that this runner's high and |
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38:41 | feeling this good feeling is because of end of cannabinoids, the cannabinoids we |
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38:46 | inside our bodies, Sam there's no no such things as endogenous morphine molecules |
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38:56 | endorphins. But there are such things Endo cannabinoids of science. Off This |
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39:03 | high meditation induced, blissful nous is attributed and is now thought is a |
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39:12 | that acts through the end of cannabinoid and activation of the cannabinoid receptors. |
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39:19 | besides this, under CA nominal is final cannabinoids. THC can also bind |
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39:26 | CB one receptor. By binding, can cause the euphoria or the high |
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39:32 | . So the high effect that you're comes from TC binding in the CB |
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39:38 | receptors. So the higher fact that from the brain okay doesn't come from |
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39:46 | two receptors. It comes from CB receptors and potentially activation of other receptors |
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39:53 | under cannabinoids and phyto, cannabinoids will to other receptors. So this this |
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40:01 | of high that's mediated by CB one . Also, the CB one receptors |
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40:06 | this fast neural transmission. So it's alterations and fast neural transmission. That |
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40:13 | the fact that and our final Kannapolis to CB one receptors CB two receptors |
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40:20 | glee are not concerned. This this fast synaptic transmission but mawr with |
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40:26 | responses. Calcium regulation with pro inflammatory of kind release and so, in |
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40:33 | way, to cannabinoid receptors that have modes of activity. One is fast |
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40:39 | with synaptic transmission and another one a , which is regulating more of the |
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40:44 | process essentials. Inflammation. We're Response in the brain. Okay, |
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40:52 | and the cannabinoids do that, then cannabinoids do that as well, and |
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40:57 | cannabinoids mostly bind to C B one CB two receptors. But guess |
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41:04 | They also bind to serotonin. So say, Wait a second told the |
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41:08 | transmissions. Cortona. This promise There's molecules that bind to different receptors |
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41:16 | so challenging your understanding. Now what learned about neural transmission. Then the |
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41:22 | combined the serotonin receptors in the Pfizer allergic signaling, which you know is |
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41:27 | . It's appetite, and so Combined the trip down a Lloyd |
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41:31 | which are involved in pain mediation. proliferator activated perception, which is involved |
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41:37 | inflammatory and pro oncological pro cancer can also affect ion channels and directly |
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41:45 | channel sodium channels and the cannabinoid Or maybe it's different systems because you |
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41:52 | these receptors that expressed in the spleen the bone marrow, and they do |
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41:58 | very different function. They don't cannabinoid contaminated. Binding to bone marrow doesn't |
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42:05 | you feel have a euphoric effect does cause the higher fact it does something |
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42:11 | . So impairments associated with impaired under signaling a cannabinoid receptors is associated with |
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42:20 | different responses. You have impairment, then the cannabinoid system and cannabinoids that |
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42:25 | being used for epilepsy and you have and then get under cannabinoid system the |
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42:32 | that are being used for cancer. is the common mechanism? Potentially, |
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42:39 | common mechanism couldn't be the inflammatory Inflammatory process is linked to the improper |
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42:48 | function or immune dysfunction and improper immune . So let's talk about cannabis |
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42:59 | And the first thing that I have explain to you is that you have |
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43:02 | realize that you live in the state gross cannabis. Texas gross low |
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43:09 | cannabis. There is low THC cannabis . It's a low THC, cannabis |
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43:14 | law countries like China. I've been home for decades. Canada has been |
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43:22 | home for decades. Most of this hamp is very tall plants. It's |
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43:29 | sativa plants or Canada's Rudar LS. contains low percentages of THC tetrahydrocannabinol. |
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43:38 | is the molecule advanced to CB one and causes euphoric, high like |
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43:45 | And so most of these strains over decades most of these hemp strains that |
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43:50 | non psychotropic they don't talk cause a effect. Most of these strengths have |
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43:57 | grown for fiber have been grown for . They grow very tall every |
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44:04 | It can grow up to 5 m . All of this is great |
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44:09 | great conductivity materials, building block materials the male plants will contain a lot |
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44:16 | seats that are rich in omega three six. I mean Assad's oils, |
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44:23 | oils and IT Z um also rich pro team so Hampus federally legal Hampus |
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44:32 | and regulated by each state, and everywhere in the United States and most |
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44:37 | the countries around the world. And you goto the store, you can |
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44:42 | em seed oil. And now, Texas, another big way and big |
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44:48 | off cultivating Hampus for another active ingredient is called cannabidiol, or CBD. |
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44:55 | , the deal can have a dialogue more prevalent and hemp plants, and |
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44:59 | THC is only sub 1%. CBD be up to 10 or 15% this |
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45:06 | ingredient in total massive to find that plans that can have a dialogue this |
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45:12 | THC is on the drug schedule. so you have to have a different |
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45:17 | for cannabis, medical, cannabis or THC cannabis, but can have a |
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45:22 | on. CBD is regulated around the , including the states and state of |
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45:28 | , and you can process help. you can produce cannabis products with cannabidiol |
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45:34 | long as you are registered with the of Texas and have certain permissions to |
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45:39 | process or sell industrial hemp. This different from high THC cannabis, and |
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45:46 | you hear recreationally marijuana or adult use or when you hear medical cannabis for |
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45:53 | marijuana, you have to understand that in marijuana is the same thing. |
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45:58 | is a derogatory word that is, has a lot of racial connotations in |
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46:04 | past that came about in this in reality, is cannabis Plant with |
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46:10 | cannabis plant as different variations. Cannabis , cannabis indica and most of the |
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46:17 | plants across is between Steven Indica, they can contain after now 35% off |
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46:25 | in the plant. So these are THC plants. They're usually grown |
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46:30 | up to 3 m in length. very heavy and THC, but they |
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46:37 | have other cannabinoids like CBD that C g like individual. And this is |
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46:43 | we refer to as adults use or cannabis for medical marijuana. But |
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46:48 | you should stay away from marijuana term really focus on medical cannabis. |
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46:54 | so this is This is what's allowed it's regulated. State by state and |
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46:59 | state of Texas has a compassionate use that allows for low levels of |
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47:05 | I believe up to 5% only in products. If you qualify under one |
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47:11 | the medical conditions, it is not approved. Medical cannabis is legal, |
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47:16 | most of the states in Texas it's to very confined, uh, set |
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47:22 | patients conditions, but also product But that will very likely change was |
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|
47:30 | legislative sessions in the next year or on the right. You have stuff |
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|
47:36 | you hear all about Is synthetic street , Kush spice synthetic marijuana, synthetic |
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47:46 | , Synthetic Canada's does not exist. cannot synthesize the plant from chemicals. |
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47:52 | can synthesize chemical molecules that look here white powder there hundreds, sometimes 1000 |
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47:59 | more potent than cannabis of phyto It is dangerous. It gets implanted |
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48:06 | all of this crap bio materials from , some stuff and sold in the |
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48:12 | shops. And it is deadly. Houston, we had hundreds of people |
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48:17 | from synthetic cannabinoids that especially sold on streets very dangerous. And they're not |
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48:24 | their illegal. And the system cannot up with them because the synthetics keep |
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48:29 | reinvented in Asia and Eastern Europe and over here under different formulations and sold |
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48:36 | evil scientists and evil salesman. So to do you cannot synthesize a |
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48:43 | Stay away from synthetic Anomalous has nothing do with anything medicinal, regulated at |
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|
48:50 | . Huge distinction that can never be together Come low THC, cannabis, |
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48:59 | THC, cannabis, which is medical adult use. And then there was |
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49:04 | deadly stuff. Synthetic cannabinoids, Nothing that resembles the plant. |
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|
49:13 | there's a lot more problem than You're smarter than that. And when |
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49:19 | smarter than that, you want to a lot more about this plan. |
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49:23 | , lot more about the active ingredients where they're located. So the big |
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49:30 | right now is on the try combs these plants. Cannabis plants that have |
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49:34 | glandular opera to shins and these try . These glandular protrusions that look here |
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49:40 | of a like mushroom like structure and they're not unique. Tricon's. |
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|
49:44 | not unique to Canada's plan, so , when you have okra blooming in |
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49:48 | garden, look the beautiful Tricon's have . Okay, so you'll find the |
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|
49:55 | offs on cannabis plants. And the thing that these try combs, where |
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50:03 | of the active ingredients cannabinoids and other ingredients of volatile Europeans that have very |
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50:10 | smell get very strong smell of a are located in these strike homes. |
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50:16 | all these different parts of the but the active ingredients are in these |
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|
50:21 | chrome molecules, and we know that know that. 1964. Dr Rafael |
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|
50:31 | This is a little bit of a day history off medications, cannabinoid |
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|
50:37 | the isolated THC, a great documentary to you to watch. It's called |
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|
50:44 | Scientist. The doctor, Raphael goes to police station in Israel and |
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50:53 | up block of hashish. And, , he thinks that that's used thio |
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51:03 | and and he isolates THC. So did that her shoes come from? |
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51:11 | is a concentrated form off cannabis. cannabis resin that is produced from these |
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51:19 | comes from accumulating These try cons. it's a concentrated resin that is called |
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51:24 | sheesh that's produced its not a different , a lot of different that comes |
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51:27 | the same cannabis plant but is These glandular opera to tions that are |
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|
51:33 | into resin is a Raphael Meshulam Goes the Health Ministry is a great, |
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|
51:40 | episode. Drink some coffee. Let go to the police station, talks |
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51:45 | the police officer, drink some coffee give him a kilo of Ashish, |
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51:50 | puts it in his bag, goes , system this bus going back to |
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51:55 | university bus going through Israel, and whole bus is smelling like crazy, |
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52:02 | Canada's marijuana. Everywhere everybody is everybody's looking. Of course, it's |
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52:07 | from his bank. So funny part that he's the only person that seems |
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52:13 | have confiscated. She's from police to back into the lab and isolated |
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52:22 | What else did Michelle um do when isolated THC? He gave that THC |
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52:27 | monkeys, and they became very Was like Oh, that's the high |
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|
52:30 | that made them sleepy. It is experiments that were squashed. They we're |
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|
52:37 | people from Apple FC, and they seeing really positive results from cancer. |
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|
52:41 | that research was squashed in the sixties seventies and eighties, and it was |
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52:47 | squashed to study the plant. It is very difficult to study. Cannabis |
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52:53 | . You can study synthetic and avenues are produced by chemical labs, not |
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|
52:59 | or illicit labs, but it's still difficult to study. The actual plan |
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53:05 | is very difficult, while other countries are opening up these avenues Israel, |
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|
53:12 | , they're going ahead in this game the drug development and understanding these active |
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|
53:19 | . As Meshulam is a scientist, have to realize that if you believe |
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53:23 | something, you have to test it yourself. So he takes it |
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|
53:27 | gives it to his wife and his , makes a chocolate cake, and |
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53:31 | piece of chocolate cake has 10 mg THC, and it was about seven |
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|
53:36 | at the party. We eat each a piece of chocolate cake, 10 |
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|
53:41 | of THC. Two of them are . Another one kind of stopped |
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53:49 | Yeah, another one is having bad and anxiety and scared and paranoid until |
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|
53:57 | day. We know the THC will with your body system differently will interact |
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|
54:02 | these different receptors. But this is Marshall I'm dead about. 20 years |
|
|
54:08 | , we had a Nabilone system and that was synthetic THC. In 85 |
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|
54:14 | John Nominal or Marinol, that's developed THC tablets for appetite, stimulation and |
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|
54:21 | nausea, especially in chemotherapy treatment. it's a synthetic drug that's in the |
|
|
54:27 | . Proof is being out there. then finally, in the 21st |
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|
54:31 | we come back to something that people been doing for centuries. We know |
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54:39 | plant based cannabis plant based medications have around in recorded human history for over |
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|
54:46 | years for different conditions specific conditions. in 85 you have production off 1 |
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|
54:53 | 1 Delta, nine THC and which is cannabidiol medication. It's a |
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|
54:59 | spray that means to sprayed on the . It's 2.7% THC, 2.5% CBD |
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|
55:06 | to 1 ratio and it is for and pain and multiple sclerosis. So |
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|
55:13 | exists is prescription, and over 30 . It was made by UK |
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|
55:20 | It's probably throughout Europe. It still not approved. In United States |
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|
55:26 | the same company comes up with a preparation, which is 10% cannabidiol preparation |
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|
55:35 | drop form. It's the aural solution , and it is anticonvulsant er to |
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|
55:42 | seizure activity in Dravet syndrome or in Gastaut Epilepsy. Dravet syndrome is a |
|
|
55:50 | childhood epilepsy, where you are either epileptic drugs, traditional pharmaceuticals do not |
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|
55:59 | and drive. And Alana's guest star also, uh, infantile spasms is |
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|
56:07 | condition that this is the treatment And so, as of last |
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56:12 | the dialects or cannabidiol is, FDA approved medication. This is different |
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|
56:17 | the CBD that is derived from help is not studying under the safety Africa's |
|
|
56:23 | system that comes in this different home . So now you can see that |
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|
56:28 | would like for you guys to continue stable with your innovations with cannabinoid medicines |
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|
56:37 | helping very diverse conditions is you're seeing . Chemotherapy, spasm, Spain |
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|
56:48 | What I'm interested in is also the that in the raw plant, these |
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|
56:55 | and C d g A. Is the mother of all cannabinoids. Other |
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|
56:59 | . That's just THC A and C d a synthesized from c b d |
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|
57:03 | c b g a. But all the cannabinoids in cannabis plant come in |
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57:09 | city form and th CIA is actually psychotropic. It doesn't cause the high |
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|
57:18 | C d A. Doesn't either. neither the CBD a so that tells |
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|
57:22 | that cannabis plant itself does not have properties. What? Yes, Canada's |
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|
57:31 | does not produce. THC produces THC . That's where hydrogen of Manali casted |
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57:37 | that if you consume THC, A not cause the higher fact. And |
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57:42 | a lot of the drug development a of the potential. I think a |
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57:46 | of the treatments, especially for could be coming from these acidic cannabinoids |
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57:51 | are now emerging as effective potential in of some of these conditions as their |
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57:57 | . Our box elated versions so th turns into THC with heat or deacon |
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58:03 | elation with aging process with heating with and extraction. So you have to |
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58:10 | the plant that you have to turn plant into the psychotropic or or intoxicating |
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58:16 | by heating and deacon Box Elation in becomes an agonist two CB one |
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58:25 | so the plants that have C B A M THC, a synthesis will |
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58:31 | THC A. And then you can THC, the plants that are dominated |
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58:36 | CBD. A synthesis will produce CBD , and this will be the source |
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58:41 | CBD and C B D A becomes a the same way through heating or |
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58:47 | card box elation. They're moving off c o H group. What is |
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|
58:53 | B? D. Do can have dialogue dampened CB one activity. It's |
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58:57 | negative al hysteric modulator. That means it binds to different Seidman THC, |
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59:05 | it actually dampens activity of the C wondrous suffered instead of activating it more |
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59:12 | B G. Now, if the doesn't have CBD, a synthesis or |
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59:16 | synthesis will produce mostly C B, and C B G will act in |
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|
59:21 | CB one receptor as an antagonist. , it will inactivate CB one receptor |
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59:29 | an antagonist of CB orders up. now you're trying thio and seeing that |
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|
59:35 | is complexity and the plant there's a of cannabinoids have produced as a city |
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59:42 | and is it converted in their neutral ? They can target the same receptor |
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|
59:46 | the cannabinoid system but have a different on that receptor. Somebody had a |
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59:52 | from the earlier in the semester. C B. Do not do anything |
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|
59:56 | the sound. Of course it Remember the cannabinoids buying two CB |
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60:01 | So you're modulating C B receptor already the endogenous system if you're adding |
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|
60:09 | but as of course is this medication 1 to 1 THC and CBD and |
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|
60:14 | of THC and CBD potentially interacting at one receptor, different binding size of |
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|
60:20 | two receptor is I prefer treatment, for specific conditions. Now, in |
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|
60:29 | to these different cannabinoids THC, CBD see beyond CBD gonna be a kind |
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|
60:35 | be the Vyron C B D G be chrome in CBC and so |
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|
60:41 | Canada's plants also contain Turpin Caesar, molecules that give cannabis distinct smell. |
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|
60:47 | Canada's plan smells like lemons. Other like lavender, and it's a very |
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|
60:53 | diversity of these. Terrapins expressed a high degree. And so when the |
|
|
60:59 | cannabis planned medications are prepared, they multiple cannabinoids and multiple Turpin's. And |
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|
61:08 | interactions between these cannabinoids and Turpin sometimes to it as cannabinoid anti garage affect |
|
|
61:15 | entourage of the molecules not just one , synthetic molecules or one CBD |
|
|
61:22 | But the entourage of molecules that comes the whole plant, we think, |
|
|
61:29 | be more beneficial, especially when you at the holistic treatments of the body |
|
|
61:36 | isolated molecules. All of these isolated and different molecular preparations of contaminants, |
|
|
61:43 | contaminants of Turpin's have their right respectable are due for our scientific investigation have |
|
|
61:50 | through it have conclusive evidence of some them inconclusive and others. But the |
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|
61:57 | plant will contain this whole complexity of . And this is simplified complexity, |
|
|
62:03 | I'm showing Oh, boy, what this? Oh boy. Now let's |
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|
62:09 | to put everything together. You have . You have Gabba. You have |
|
|
62:12 | . Europeans have a city cannabinoids. have neutral cannabinoids, THC and |
|
|
62:19 | You will not be responsible for this , but what I'm showing in this |
|
|
62:25 | when I'm illustrating by showing this diagram the complexity you consuming preparations from the |
|
|
62:33 | plant. This preparations will contain acidic cannabinoids, Turpin's and the target CB |
|
|
62:42 | receptor trip receptor serotonin receptor Gpr 55 receptor CB to a Dennison receptor is |
|
|
62:51 | target of CBD very complex system, it's not just easy to understand. |
|
|
63:00 | other phenomena is this is actually very to understand the interactions between the whole |
|
|
63:05 | extracts in this very complex systems. why sometimes isolated molecules can be off |
|
|
63:12 | as well. So it's not that making this all up. It's actually |
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|
63:18 | dated, I believed in 2017. health effects of cannabis and cannabinoid is |
|
|
63:24 | current state of evidence and recommendations and National Academy of Sciences, Engineering and |
|
|
63:32 | . There's a conclusive or substantial evidence cannabis not talking about synthetic THC. |
|
|
63:38 | plant or cannabinoids are effective treatment of pain and adults cannabis, but there |
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|
63:47 | no medication except for Sativex that can used. Sativex can be used for |
|
|
63:57 | and clenching pain from spasms that people . But other than that, there |
|
|
64:04 | no cannabinoid medications for pain there now clinical trials. Cannabis also in clinical |
|
|
64:14 | . Certain strains of cannabis, anti in the treatment of chemotherapy induced nausea |
|
|
64:20 | vomiting. Orel Cannabinoids Improving patient M s multiple sclerosis Spasticity symptoms. |
|
|
64:27 | Cannabinoids. Moderate evidence for sleep outcomes sleep apnea, fibromyalgia, chronic |
|
|
64:37 | multiple sclerosis. Limited evidence from many conditions for which cannabis is being |
|
|
64:45 | Enlisted. But in my opinion, is happening is a major disconnect between |
|
|
64:53 | repression of the plant and the ability study the plans and then saying that |
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|
64:59 | have all of this limited evidence for plant that could do all of these |
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|
65:05 | . And you have hundreds of thousands patients that are going through medical candidates |
|
|
65:11 | . That's not FDA approved. That a recommendation by medical doctor that is |
|
|
65:19 | recommendation by neurologist to treat epilepsy. neurologist to treat post traumatic stress |
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|
65:31 | This is non federal system. This not a D approved. How many |
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|
65:37 | you know somebody using Medical Canada's have themselves using the Medical Canada's Yes, |
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65:45 | , you have to keep in mind there is addiction to cannabis. It's |
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65:50 | just all hunky dorey. It's bad the young brains unless it's used this |
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65:54 | because it can affect the plasticity of brain. Development in the developing brains |
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66:00 | do so. An adult or aging and addiction level for Canada's is one |
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66:08 | nine. So this this this cannabis disorder is like into addiction or candidates |
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66:17 | disorders observed in one of nine users it starts affecting their performance or starts |
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66:22 | their life. And if you talk them, they'll say, That's actually |
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66:28 | my life and just a synesthesia. learned this prevalent seven or eight times |
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66:36 | among artists and poets. Um, be surprised at the cannabinoids or |
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66:43 | Use this and eight times higher amongst and poets as well, because there's |
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66:50 | avenues for creativity. There's certain avenues concentration, but there's negative effects. |
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66:57 | , THC and cannabis use can cause can cost para lawyer it cost panic |
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67:04 | and panic attacks are not fun. called the panic attack. Oh my |
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67:10 | ! Something's panic attack. Somebody is a serious panic attack. They don't |
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67:15 | live. They don't want to get . They don't wanna just go about |
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67:20 | day they're done. I'm tired of like this. Don't wanna do |
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67:24 | And I feel like I'm gonna So I might as well just kind |
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67:28 | like die. You can get even People rushed the hospital of panic attacks |
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67:33 | that they cannot breathe. This is by THC and high high concentrations of |
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67:40 | , mostly mhm. So you have be cognizant of all of these things |
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67:45 | to be very cognizant of water said synthetic cannabinoids as well. And so |
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67:50 | is what's happening in this country. is from the national cannabis, |
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67:56 | society. This is Texas Low CBD and low THC program. Everywhere |
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68:03 | see dark green, you have adult recreational and medical use. Cannabis. |
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68:10 | , uh, west Northwest, Illinois, Michigan, South Dakota just |
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68:17 | to have adult use one of the conservative states. But don't use |
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68:25 | um and so I believe that this is gonna be dark green map within |
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68:34 | next three years completely when it is to be through the federal programs or |
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68:39 | the states. Just self determination. establish their own, uh, cannabis |
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68:47 | locally and regulate from a swell. . This is Texas Compassionate use |
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68:55 | So in Texas, the Medical Canada's run by state troopers. Texas Department |
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69:06 | Safety. Public Safety. Okay, . That's what they decided to |
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69:15 | The low THC cannabis program, and will probably improve it and will probably |
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69:21 | to educate a lot of that. Department of Public Safety folks and affiliates |
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69:28 | this plant, about different aspects of . And it's gonna be you doing |
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69:35 | , some of you during it, extent in some near |
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