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00:04 | This, this lecture, 24 of . And we, we were discussing |
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00:12 | lot, couple of lectures really. had an introduction into medical cannabinoid when |
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00:17 | talked about epilepsy. And then we about pharmaceutical cannabinoids and medical cannabinoids. |
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00:24 | we'll maybe expand on that a little more so that everybody understands that |
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00:29 | What I mean is that these are approved drugs. And in the United |
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00:34 | , we discuss that there are two delta nine T H C and 10% |
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00:39 | D and it's only for two conditions well. Two, this one is |
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00:45 | mg, DH C and it's appetite and anti nauseating, antibiotic for chemotherapy |
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00:52 | . Terminally ill patients wasting syndrome, . Um Now CD D is for |
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01:01 | . It's anti seizure drug, anti medication. And this DH C and |
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01:07 | D mixture is for sin and pain and multiple sclerosis. But this one |
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01:14 | not FDA approved. Therefore, it not available in the United States, |
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01:17 | it's available in other countries around the . This is synthetic and these are |
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01:24 | derived. What do you mean by the rock? It's like when you |
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01:29 | we talked about this technique called H L C. So when you have |
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01:35 | from the plant, like a mixture the plant here, you can not |
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01:40 | detect it and measure it using H L C. You can also isolate |
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01:46 | ingredients. You can extract from the and isolate those individual ingredients. So |
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01:51 | can isolate T H C, you isolate CV D. You can also |
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01:59 | it from other chemical ingredients in the . So we talked about that and |
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02:08 | hear a lot about medical cannabis and . 4 20 was last Thursday and |
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02:14 | were a lot of celebrations, there a lot of discussions on TV, |
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02:18 | the radio, uh warnings coming from , psychiatry people. And uh why |
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02:28 | there still so much discussion? And the main reason is that cannabis and |
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02:35 | nine T H C that you're seeing and other cannabinoids are on schedule Wong |
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02:43 | a schedule Wong Drum to be on one means that that substance or that |
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02:51 | has no medicinal value is addictive and be dangerous. So, while we |
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02:59 | that, we actually also have drugs Delta nine T H C that are |
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03:07 | medications. So that's why it's it's a misnomer, right? You |
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03:12 | have something on schedule one. Delta T H C say it has no |
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03:16 | value and you can also have an approved drug to treat medical conditions, |
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03:24 | drugs that are planned derived and one them that is intoxicated. So that's |
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03:32 | laws sometimes don't agree with science or not make scientific logic, right? |
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03:42 | you'll see that my scientific logic, cannabis doesn't even produce delta nine T |
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03:49 | C. It produces delta nine T C acid which is non intoxicated. |
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03:55 | that's, that's another uh misnomer, and mistreatment of this plant. And |
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04:02 | why I ended with this slide well, they got all of these |
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04:06 | people, the National Academy of Science and Medicine. They review all of |
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04:12 | literature, all of the clinical all of the pharmaceutical data and tell |
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04:16 | is there uh substantial evidence that these work for other things than just spasms |
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04:24 | other things and the seizures. And concluded that there is substantial evidence that |
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04:30 | 2017. So that's six years ago there's a lot of uh interesting research |
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04:36 | has happened since, but it conclusive that it has for treatment of chronic |
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04:42 | in adults, cannabis itself. So doesn't say that it is for anti |
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04:47 | medication. It doesn't say it's for Matic uh medication. If you are |
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04:54 | chemotherapy, it says it helps from pain who doesn't have an older adult |
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05:01 | their family or themselves that actually have pain. Ok. So it's a |
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05:09 | vast condition that applies to many different . Uh especially elderly anti medics and |
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05:18 | of chemotherapy and vomiting oral cannabinoids, patient reported multiple sclerosis, plasticity, |
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05:24 | , oral cannabinoids. And then there's and limited evidence for a lot of |
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05:28 | , moderate evidence for sleep apnea, , chronic pain and multiple sclerosis. |
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05:34 | , while there is conclusive evidence, also limited evidence for chronic pain. |
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05:39 | that's because there's different interpretations, different with different uh subjects and models. |
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05:46 | from animal models to, you human subjects and and and so |
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05:51 | But this is what these smart people there is medicinal value and what we |
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05:57 | about uh last time we talked about cannabis. And I said that the |
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06:03 | phyto cannabinoids that you find in the or Delta nine T H C or |
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06:09 | D and CD G. And actually learn that it's an acidic versions of |
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06:16 | cannabinoids that are naturally occurring. And you will see in this world that |
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06:22 | surrounded by different other cannabinoids and you see advertisements on the gas station |
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06:34 | convenience shops, uh smoke shops, eight, delta eight T H C |
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06:44 | sold here. Delta 10 T H is sold here. H H C |
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06:57 | Komal is sold here. And those derivatives typically from CV D. |
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07:06 | And these, this group are semisynthetic although they come from CBD, which |
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07:19 | a phyto cannabinoid or CBD A that found in the plants extracted isolated from |
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07:25 | plants. There's a lot of CBD a lot of it gets converted through |
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07:31 | known means and changing the bond from 9 10 into a nine carbon |
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07:43 | Remember these are long carbon chains. you already you have 10 carbons, |
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07:49 | , 12, 13, 14. . They're, they're long carbon |
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08:05 | Now. Delta eight, what it is C B one receptor binding and |
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08:13 | H C delta nine T H C a high affinity for delta or CV |
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08:17 | receptor binding. CV D has low , which means it doesn't really prefer |
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08:23 | bind to a CV one receptor. , it actually prefers to bind to |
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08:31 | receptors. Remember the function of CV receptors in the brain recall that presynaptic |
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08:42 | had Vesico release and we had calcium and pre optically, we also had |
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08:53 | B one receptors of neurons that were protein coupled and that they would inhibit |
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09:02 | close voltage gated calcium channels. And would control here the release of glutamate |
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09:11 | Gaba. So if you recall endo are made optically, the endo |
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09:23 | they are made optically and they travel gradely combined CV one receptors and have |
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09:30 | effect of controlling neural transmission by blocking gated calcium channel. So phyto can |
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09:39 | of those like T H C delta will have a high binding affinity to |
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09:46 | if you want them. So it mimic the effects of end of the |
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09:52 | . In addition, glial cells in microglial cells contain CV two receptors. |
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10:03 | CV one receptors are going to affect of a neural transmission CV. Two |
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10:09 | are going to affect more of a function, microglia, inflammation repair of |
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10:17 | brain immune response generation in the So it will affect slower processes like |
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10:28 | and maybe even synthesis if it's affecting synthesis of glutamate, for example. |
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10:36 | , so these pinto cannabinoids delta line H C CBD and C B |
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10:41 | they will all have different relationship with one receptor that we'll review in a |
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10:47 | . But in general speaking, we understand the delta A delta 10 and |
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10:53 | H C effects on C B one . And a lot of times we |
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10:58 | talked about synthetic cannabinoids. But a of times people say, well, |
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11:02 | a second, how come the semi or synthetic cannabinoids? It's, it's |
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11:08 | same molecule. How come it, affects people? It's not the same |
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11:13 | . So, first of all, convert it CBD into delta eight or |
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11:16 | 10. And second of all, these semisynthetic anana, but there are |
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11:23 | synthetic Annabi that we talked about that be full agonists. What does that |
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11:30 | ? That means that if these phyto are partial agonist of C B one |
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11:35 | , so they bind the C B receptor and then they dissociate and broken |
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11:42 | . It's partial agonist, the full can bind to CV one out and |
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11:46 | stuck there for a week. A of times we don't know because we |
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11:52 | know what has been synthesized. And are different conversions that are taking place |
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11:58 | through acid dots of, uh, of this double bond to put it |
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12:04 | eight and 10 and put it between and 11 carbons that we don't know |
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12:10 | . So, while we understand that and Delta nine T H C have |
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12:15 | researched a lot and there are real that are pharmaceutical medications derived from Delta |
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12:23 | and from CBD, we don't know about these other guys, the semi |
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12:29 | . So we don't know how they're and we're not quite certain how well |
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12:32 | tested that are available in the So buyer beware many different cannabinoids in |
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12:40 | plants. T H C CBD are major also C B G, they're |
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12:46 | major because there's a lot of So the plant will produce a lot |
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12:50 | them. But then there are other like CDC canna bechromate or CV D |
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12:57 | can be. And those are called or rear cannabinoids. And that's because |
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13:04 | plants, cannabis plants don't generate, express high levels of those cannabinoids. |
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13:11 | not all strengths of these plants have minor cannabinoids. So they're harder to |
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13:17 | , they come in smaller amounts in plant naturally and therefore they are minor |
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13:23 | rare cannabinoids. And it's gonna be deal of investigations. I think looking |
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13:28 | a lot of these minor cannabinoids as as some asthe cannabinoids for good and |
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13:36 | reasons. Uh and, and the with full agonist and in general, |
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13:42 | danger with, with cannabis is typically Delta nine T H C. So |
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13:48 | intoxicating effect, the light addicting the cannabis use disorder is alkaline T |
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13:54 | C but it is often not attributed these other cannabinoids like CD D that |
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14:00 | now being researched to be as an addictive drug or antipsychotic. So, |
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14:08 | complexity of this plant is beyond understanding it in two lectures or |
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14:14 | it has over 1000 of different uh that it expresses and certain chemicals have |
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14:23 | properties, but they also have intoxicating . They may have addictive properties and |
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14:28 | effects as well. And not for not every person reacts to different chemicals |
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14:35 | different plants and molecules the same not every condition can be addressed just |
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14:41 | T H C or just with cannabis knowing what's inside. Because different strains |
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14:47 | cannabis, some strains will produce T C only, some strains will produce |
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14:53 | , only some strings will produce five phyto kommen, others, 15 |
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14:59 | 67 in different variations and different So there's a variety of different plant |
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15:07 | just like you have different color roses each, each color has AAA gene |
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15:14 | has to uh to be present in for a rose to have that |
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15:17 | So you have a variety of changes in genetic composition and also the phenotypic |
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15:25 | and the final chemical output of this . And in addition to cannabinoids, |
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15:32 | some of them are positive and a of them have unknown properties. |
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15:37 | In addition to cannabinoids, we also plants produce turkeys that we also |
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15:42 | When we talked about the olfactory we smell different odors and we said |
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15:49 | odors for from essential oils or turps . And so cannabis and cannabinoids were |
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15:57 | long molecules. They are in long chains and we cannot perceive them through |
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16:04 | olfactory system. And so cannabis expresses variety of different turkeys, limine that |
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16:12 | comes in lemons carrier filling that can found with cloves and hops. In |
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16:17 | , hops is the closest genetically planned cannabis plant li that is found in |
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16:24 | . All of these turps will be expressed by different strains of the |
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16:30 | And this is what stimulates our olfactory . It's not the cannabinoids when people |
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16:36 | they either say, oh it smells or it it it's it or it |
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16:40 | stinks, you know. Uh but it comes from the combinations of |
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16:45 | turbines and cannabis plants we'll be expressing that we will be smelling right. |
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16:54 | uh why is this significant? And we have turkeys and lemons and we |
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17:01 | clothes and don't we eat this in diets anyways. So think about |
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17:07 | I always told you, how do take things in? Right? We |
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17:11 | about medications, we talked about how act through the digestive system, through |
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17:16 | skin, through the suppositories through You guys are really smart. So |
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17:22 | of the time, what do you with turps that are found in your |
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17:26 | fruit and vegetables? For example, eat them. But what do people |
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17:33 | ? Mostly with cannabis? They inhale now. So, so think about |
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17:40 | . So actually it the effect of thins a different route of injection versus |
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17:50 | will have a different effect on the and on the brain as well because |
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17:55 | doesn't get digested, it doesn't get and and so on and so |
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18:00 | And so it's not only smell but also potentially certain effect that is coming |
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18:07 | turbines and it doesn't come when you the lemon. But my as |
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18:12 | if you were to inhale the Lamon in this case, uh Turpin that |
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18:17 | found in uh in lemon, but is expressed in the plant that people |
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18:21 | to inhale. And this is sort a, a fun image that I |
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18:26 | a while back. So cannabis plants smell like lemons and blueberries and |
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18:32 | but also like gasoline like earth also skunk. So different strains will give |
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18:41 | plants a different smell because of the subset of turkeys that they would be |
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18:49 | . And these turkeys they have their physiological and medicinal properties. There's a |
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18:56 | of information here, but I want to pay attention to this guy |
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19:01 | Alpha ping and it is a Cetalol . Do you remember when we talked |
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19:11 | acetylcholine inhibitors? We talked about Alzheimer's . We talked about how this is |
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19:17 | most common Alzheimer's medication that uh the cellular level and chemical neurotransmitter level, |
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19:26 | is a loss and reduction of So by blocking acetylene inhibitor, you're |
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19:33 | the bi availability of acetyl code and the synapse and off of is an |
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19:40 | inhibitor and it affects memory and there studies that are ongoing with alpha pine |
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19:49 | it will be found in a lot coniferous plants. So a lot of |
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19:53 | pine trees, pine woods and uh Christmas trees and such uh in |
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20:00 | , there's even such a thing as wood, wood forest therapy where people |
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20:05 | for walks and they claim that it's of the air and turps that they're |
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20:14 | and they're smelling that, that enhances changes their, their mood and changes |
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20:19 | has a beneficial effect in general. . So what do we have around |
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20:27 | world is we have in addition to pharmaceutical programs which are these international |
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20:35 | Marinol C T E at the some, some CD D we talked |
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20:38 | . So I said it's present like over 25 different countries at the |
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20:43 | Also uh these drugs are international So the health insurance subsidized, the |
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20:50 | have medical canoes are not pharmaceutical. those are national, not always international |
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20:57 | national. So Germany has a medical program I marked international because the import |
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21:04 | medical cannabis from Colombia, from from Portugal and they're starting to grow |
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21:10 | than in Germany. But this is cannabis program in Germany cannabis flour. |
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21:17 | bugs that we discussed would be sold the pharmacies. So you would get |
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21:21 | prescription recommendation, a prescription from your and you go to the pharmacy to |
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21:26 | a little white jar that has your flour and that's health insurance subsidies. |
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21:34 | uh it's uh it's cheaper state cannabis medical cannabis that we have. Uh |
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21:42 | is Massachusetts, example is Texas. have a limited medical cannabis program. |
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21:47 | of the time patients don't get any , there's no health insurance, they |
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21:51 | save on certain percentages of tax. if the program, for example, |
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21:57 | a state like Massachusetts has a medical , an adult or recreational program, |
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22:04 | medical patients can be exempt for this tax, sales tax and they can |
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22:11 | different products and the recreational users will to pay full tax and they'll be |
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22:19 | a lot of times in the amount products that they can, they, |
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22:22 | can purchase recreational or adult use is correct way. Now, typically full |
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22:30 | in the United States, it's state . So Colorado has recreational, New |
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22:37 | has recreational uh the whole west uh most of northeast Michigan and so |
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22:44 | um, I think over maybe 20 , almost 30 states have a recreational |
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22:50 | . 20 states have recreational program. , and then you have national recreational |
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22:56 | . So adult use programs. So Canada it's province specific. So if |
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23:01 | are on the east coast with Quebecois Quebec, in Montreal, it's state |
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23:10 | . So the state of Quebec has shops, they're government owned shops. |
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23:14 | open at nine and close at Yeah. And I think the purchasing |
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23:20 | is uh 18, then you go a different province in Canada and they |
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23:25 | their own laws. And if you to the west coast, for |
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23:28 | you are in Vancouver, British Columbia there you'll have the shops with dispensers |
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23:35 | 20 hours or 18 hours a long and they're privately operated and their different |
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23:43 | . Now also such a program exists the world and other countries. Uh |
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23:51 | has a different uh law that just in Germany for recreational cannabis. It's |
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23:58 | the clubs, both social clubs. You knock on the door and say |
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24:03 | , I'm a, I'm a club and then you can consume cannabis and |
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24:08 | will allow one person to grow three . So already those people that are |
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24:15 | to grow plants, they are signing their cousins and their grandmothers to be |
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24:20 | of their residence so that they can three more, three more, three |
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24:24 | plants uh to supply the social That's what happens usually when there is |
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24:29 | no open regulation for these. So will like do it on your |
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24:34 | But it's an interesting market space. this is what we have. It's |
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24:38 | full taxation, state regulated uh medical programs, as I said, that |
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24:45 | in Germany exist in um Canada, . So it's really spreading throughout the |
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24:55 | . This is a map. It's map. It's 2021 December 2021. |
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25:01 | lot of things are changing but the , the green color that means the |
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25:07 | has both adult and medical use regulated . So in other words, the |
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25:13 | , so the shops are there and can come in as a patient with |
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25:17 | medical card or you can come in a partier and, and, and |
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25:22 | your supply that way. Texas has limited program that we'll talk about in |
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25:27 | second when typically a person comes into dispensary or even a hemp shop here |
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25:37 | CBD products or something else. They don't know what they need if they |
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25:44 | looking for a medical condition and this usually becomes their savior and helper, |
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25:55 | , retailer. Uh, but tender the dispensaries they have different names. |
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26:03 | . And so I need something from . Oh, and then that person |
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26:08 | give their biased opinion about the sleep this or the other. And these |
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26:16 | , they, they have jobs, have to sell products. So if |
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26:19 | doesn't sell, they recommend something that will help you sleep, that they |
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26:23 | to sell because it's a business Ok. And worst of all, |
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26:29 | no standard and there's no standards in the products presenting the products and how |
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26:39 | semi synthetics are derived and are in open health market. There's no standard |
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26:45 | what should be on the label. when people go and look at the |
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26:50 | , they're like, they think they found something that helps them. We're |
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26:54 | talk about it from me additional right? And then they go to |
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26:58 | state and that brand or that product that company may not have a license |
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27:05 | a different state. It's a state state license program. So they go |
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27:10 | another state and once again, they to ask this person, they |
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27:15 | but I had this and, and they have to try to find something |
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27:19 | even if they find something, the , the label is gonna be |
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27:23 | there's gonna be a lot of confusion hopefully they will find a, you |
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27:28 | , a matching product that can help while they're on vacation in, in |
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27:32 | , away from New Mexico and So this is being fixed, standards |
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27:38 | being sort of established. It's a fragmented market, medical cannabis market because |
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27:45 | state owned state, uh state not state owned, but hopefully there |
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27:51 | be some standards and I think that guys are gonna be much smarter than |
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27:56 | but tender or any person behind the and you can ask them questions |
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28:01 | Oh yeah. What ratio of CBD C B G? Uh where is |
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28:05 | C O A for this product? H P L C did you do |
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28:10 | mass? Right? Oh It's gonna you sleep. Really? Is gonna |
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28:14 | you sleep? Is it stimulating a or or what a Damien receptors? |
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28:19 | it will be like, I don't , just buy this. So uh |
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28:27 | to help you buy there, uh are called unicorns companies that are valued |
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28:32 | billions of dollars. One of them Duchy was valued $4 billion or |
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28:39 | They're doing a lot of transactions. marketplace is bigger than tobacco marketplace in |
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28:44 | United States right now. And so a lot of technology and sales and |
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28:50 | menus like shopping like almost on Amazon a 30 minute delivery to your |
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28:57 | And if you're in one of these robust developed states that have these adult |
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29:03 | medical programs, so, but no for most of the things. And |
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29:10 | , from medical perspective, it's not the standard, it's not only the |
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29:15 | but it's also the regimen. I chronic pain versus I have peripheral neuropathy |
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29:21 | I have spasms from a mask versus have, I have some disease that |
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29:26 | been approved by FDA. OK, have Crohn's disease. How much should |
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29:32 | take of T H C or When should I take it? |
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29:35 | Most of the people will say, , Ibuprofen, you know, start |
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29:38 | mg, you know, maybe it hop half an hour, we can |
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29:41 | another 204 100 but then don't do for 34 hours. Let your system |
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29:47 | . It doesn't exist really. But just emerging in Texas. It's an |
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29:52 | program. T H C in medical is limited to 1% of T H |
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29:59 | . The products are only ingestible or edible so, oils or tinctures, |
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30:05 | they contain 10 mg of P H per gram. And that's because of |
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30:11 | T H C limit 1% by Good. The hemp farm bill, |
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30:18 | are hemp products. And remember I you those tall plants, they said |
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30:22 | can contain up to 0.3% T H by law, but by weight, |
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30:26 | law, 0.3% T H C is mg of T H C per |
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30:33 | Let me tell you two problems here that when you do it by weight |
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30:37 | that, let's talk about medicinal OK. First of all, you're |
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30:45 | me ingestion products. I cannot I have a tube feeding tube, |
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30:52 | can swallow, I'm out. I I'm, I can have one |
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30:58 | the conditions that we'll talk about. a lot of qualifying conditions. Parkinson's |
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31:04 | . Uh A lot of neurological conditions not good. So what do these |
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31:11 | need? Maybe inhalation, maybe right? But currently it's not |
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31:18 | The other thing is I need 200 of T H C for my |
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31:25 | 200 mg of T C I can have 10 mg of one g. |
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31:31 | many grams do I need to What that does? 20 g or |
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31:36 | mL of product? So the whole bottle has to drink. So do |
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31:43 | take medications in such amounts? Like pharmaceutical medications where you are like, |
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31:48 | know, adjusting spoonfuls with your you know, not really, it |
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31:54 | work. So right now, the law is to strike this by weight |
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32:00 | in medical program and that's going to a lot of the patients. So |
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32:06 | if there's no weight limit, that you can have a small grain of |
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32:10 | that weighs 50 mg and that can 10 mg if you're active, which |
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32:16 | delta nine T H C. Now may be asking a person to consume |
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32:20 | a half a gram or a gram something. The most of these products |
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32:24 | not very healthy either. Gummies, know, think about it. It's |
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32:29 | what goes into making. It's like , you know, it's like a |
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32:33 | , I know you got lots of and that I citric acid and you |
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32:39 | , not, not the best. , so this is a medicinal |
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32:44 | right? The medicinal end. Let's about this the open market for hemp |
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32:51 | . So if you're not on medicinal and you want to get a lot |
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32:56 | T H C Delta nine. if you can have three mg and |
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33:01 | g, that means you can have five g hunk of gummy five g |
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33:10 | three is 15 mg of T H . So now you have access through |
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33:16 | hump market to doses 15 mg You can look around the coffee shops |
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33:22 | here and everywhere. You can have single dose of 25 mg of delta |
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33:27 | T H C. No, I'm even talking about semi synthetics natural delta |
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33:30 | T H C because I'm derived in in a big format product. So |
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33:38 | again, it doesn't make sense because only need like a $300 license to |
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33:44 | as a hamp operator retailer and you a $500,000 license, the renewable fee |
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33:51 | two years to operate A T H business and deliver door to door around |
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33:55 | state. So now the other interesting in Texas, we have institutional review |
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34:03 | . So they put this into law they will allow those products. Remember |
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34:08 | told you that we can order as and scientists and medical doctors, synthetic |
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34:13 | H C, synthetic CD D from to be shipped into the university, |
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34:18 | we cannot work with real products, plan from the dispensary and real products |
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34:23 | the dispensary. This may allow for research to be done with medical schools |
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34:29 | hospitals, large hospitals with actual products you buy here in the dispensary, |
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34:33 | a dispenser in the Heights on Houston in Texas by one of the |
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34:38 | It's very limited operations in Texas. so this is very interesting. It's |
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34:43 | hopeful in two years. Nobody has able to execute on that. But |
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34:47 | is what I'm interested in. Can bridge what is on the marketplace? |
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34:51 | what the reality is I say versus the catalog is and chemical with |
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34:57 | with the real clinical studies with the conditions like for Crohn's disease, all |
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35:02 | of colitis for spasms, for cancers and so on and so forth, |
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35:08 | disorders. Now the state of just like politicians banned the use of |
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35:16 | and said it's gonna be prohibited with rear Agnos. Now, the politicians |
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35:20 | saying, OK, we're gonna allow , we're gonna allow recreational. And |
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35:24 | politicians first said in Texas only epilepsy be treated with medical cannabinoids. In |
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35:30 | , started in 2017. In there was a whole list of conditions |
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35:36 | was added. A L S Alzheimer's cancer. Look at how many of |
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35:41 | are neuro degenerative neurological conditions. C cancer can affect the brain autism. |
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35:48 | A L S Parkinson's peripheral neuropathy is to peripheral nerves in your fingers or |
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35:54 | hand or your arm and no feeling numbness, posttraumatic stress disorder, seizure |
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36:00 | , spasticity, which is typically could MS it could be peripheral. Also |
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36:05 | specificity, diabetic neuropathy, dementia, M SS, we're talking at another |
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36:14 | incurable neurodegenerative disorders. So just like 100 years ago, politicians said, |
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36:20 | no, the s cannabis is we should ban it. They didn't |
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36:23 | medical doctors, the politicians a lot times in the States, they consult |
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36:29 | doctors, the medical doctors don't know and they now have all of these |
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36:34 | that are open to treatment um with cannabis in the form of a |
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36:40 | So how do you get to Obviously, you have to have a |
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36:45 | , the disease, then you contact of the doctors in what is called |
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36:50 | compassionate use program. They have a number of doctors like 600 or |
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36:55 | The program has over 50,000 patients now Texas and it's probably gonna be over |
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37:01 | in a year. It's gonna be to half a million in a couple |
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37:05 | years. So it's, it's, , it's gonna grow. Uh So |
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37:09 | call one of the doctors, you the documentation you have this condition, |
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37:14 | the doctor will actually talk to you the doctors in Texas. It's different |
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37:18 | other programs in other states. That's Texas kind of uh has a real |
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37:23 | program with the possibility of that institutional boards to make it really clinical medical |
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37:29 | the reason why, because in other and a lot of other states, |
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37:34 | have a contact with a cannabis physician cannabis certified physician and you say you |
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37:40 | a headache, so you don't have present any diagnosis. They, they |
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37:45 | you right there and they give you card and you, and, and |
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37:49 | core called medical card, they give a card, medical cannabis card and |
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37:54 | never see you again. Maybe two you have to renew and then you |
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37:59 | back to say, how's your I still have it. They're really |
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38:03 | and you, you use it for years again in Texas. It's, |
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38:09 | , it's interesting. The doctor will with the patient that has a |
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38:14 | talk to them for about half an and prescribe them, not recommend, |
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38:21 | prescribe them on a state level, treatment, a regimen for that |
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38:26 | So you take this oil, you these gummies. I want you to |
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38:29 | with this. I want you to it in the morning. I want |
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38:31 | to take it in the middle of day. I want you to take |
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38:33 | at night. I don't want you take it. Uh Don't take this |
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38:38 | that. Uh So it's, it's really fully medically supervised and it |
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38:44 | started where you had to talk to physician every six months. Think about |
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38:49 | . You don't talk to your primary physician every six months, you're lucky |
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38:52 | you talk to them once a So, but they want it six |
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38:56 | now. They're down to a But so this is really kind of |
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39:00 | medically supervised program and they give you limit. So the physician says this |
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39:05 | should consume this much. And so the next year, they have a |
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39:10 | , you know, of 20 g everything. If they order it over |
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39:14 | next year or something, and if exceed that limit, that means that |
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39:18 | uh oh, they're exceeding the they exceed that limit. They have |
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39:22 | go back to the position and look, I needed to increase my |
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39:26 | or something and be like, you're giving it to your friends and |
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39:28 | giving you a bigger subscription than You know, it's enough, you |
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39:33 | , whatever the situation is. but this is potentially truly medical program |
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39:39 | we have here rising in Texas and child laws change in Texas every two |
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39:44 | in case you didn't know the legislators every two years. So 2023 now |
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39:51 | gonna be 2025. So whatever changes made are gonna be made. And |
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39:55 | the governor signs them into law, you know the political system, it's |
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40:00 | interesting. Somebody proposes a bill on committee level, they approve the |
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40:04 | they put it to Congress, congress . Yay, they put it to |
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40:09 | Senate Committee reviews the bill Senate Say yay, they give it to |
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40:15 | Governor Dan Patrick and they give it the governor and they say no, |
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40:22 | not doing two years. Boom. two years again, people that are |
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40:28 | for whatever changes, laws, regulations against something, they have to wait |
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40:34 | . So it's multiple, multiple steps get something through in this country. |
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40:40 | see it play out all the time front of our eyes. Ok? |
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40:45 | this is our very last lecture that talk about. Um COVID-19 infections. |
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40:52 | lot of us have been affected by . A lot of us have lost |
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40:57 | sense of smell and it's not going in the sense that I have students |
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|
41:03 | come up to me. And they're , you know, my brother had |
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|
41:06 | two years ago still can't smile things . So it depends, it depends |
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41:13 | several things. We know that the can have a different impact on each |
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|
41:19 | , on each body. But most depends on the viral load and the |
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41:23 | response and the location of the And typically the location is where the |
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41:30 | response is weak. So it's almost a virus that is meant to identify |
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41:36 | weak spot. Uh-huh, get his , you know, get the lungs |
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41:40 | , ok? Get some other, the nose, you know, respiratory |
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41:45 | . So it's, it's identifying these thing. It's exacerbating almost some |
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41:52 | issues or um uh conditions that may be there that you have experienced while |
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41:59 | have other infections or uh another type disease or problem. So, we |
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42:04 | that we are most concerned about how virus enters into the brain. We |
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42:09 | that the virus can enter into the through the blood vessels. We know |
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42:15 | the virus can enter through inhalation into cavity or inhalation, air passages that |
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42:23 | into the nasal cavity through the ruber , plague through these demonstrations in the |
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42:30 | and will be used by the olfactory , the primary olfactory receptor neurons, |
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42:36 | neuro carrying information into the olfactory And of course, you can have |
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42:44 | . So if you have uh hypoxia of oxygenation, that hypoxia and uh |
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42:52 | damage compromised blood brain barrier and allow for the Andrew of the virus. |
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42:58 | doesn't have to have a very high load, but it can have a |
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43:03 | blood brain barrier for the virus to the C MS. We also learned |
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43:08 | it has to bind to something. , h two receptors and tens and |
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43:13 | enzyme to they're found in neuronal They're also found throughout the body. |
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43:21 | once it attacks the A two uh it now can invade the cells |
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43:29 | it can kill the cells. Basically over the cell, the host and |
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43:32 | the cells. These uh we'll discuss these two receptors are expressed. Their |
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43:39 | is mostly to control blood pressure with attention in converting enzyme too. |
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43:47 | So there's a couple of articles that included if you wanted to look at |
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43:52 | detail on what's going on. But we discussed that cul receptor neurons that |
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43:58 | these cell hanging out there in the layer that are smelling things but also |
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44:02 | subjected to the viruses. They have h two receptors. But these cells |
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44:08 | green that are called sustentaculum cells. yellow cell is a micro villa |
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44:15 | This is CYA cells, these green that have these two receptors and they're |
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44:20 | right there, watering the mucus So any invasion through any of these |
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44:25 | fest administrations into the mucus layer now the cyst cells uh susceptible and most |
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44:32 | infected first in this epithelium factor, helium from there. It's very likely |
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44:40 | there is trans cellular migration or trans invasion from one cell to the next |
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44:48 | by proximity and also progenitor cells here you're seeing that also have a two |
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44:55 | . And once they enter into the receptor neurons, it can climb |
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45:00 | Now into the order centers into the B, for example. So if |
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45:10 | recall, you have different glial we just were talking about microglial cells |
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45:16 | CD two receptors, astro glial one of their functions is to have |
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45:22 | feet to form the blood run And if you have an infection in |
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45:28 | blood with COVID-19 or SARS COV Uh Technically, right now, if |
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45:38 | have infection here, it can bind H two receptor and endothelial cells, |
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45:45 | lining. And if it penetrates crosses the blood brain bar, it can |
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45:51 | infect both neuronal populations, as well glial populations. Both will contain a |
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45:57 | receptors. So they could have a of the whole brain and the major |
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46:04 | types of all of the cells that infected. So we know this route |
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46:13 | SARS called two entering into the nasal and potentially infecting the factory valve and |
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46:22 | the brain through that route. And are three theories that are described here |
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|
46:30 | I included a figure legend, although have this paper, but I included |
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46:34 | figure legend, if you want to it, there are three ways in |
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46:40 | we believe this virus gets from the into the brain. First is through |
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46:46 | trans cellular migration. So, in , then infecting these endothelial cells that |
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46:52 | part of blood brain barrier and then endothelial cells because they're touching on to |
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46:59 | uh astrocytes and the parasites surrounding they get infection into the glial cells |
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47:07 | into the neuronal cells as well. is neurons, neurons, microglia and |
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47:14 | that are have their feed on the very badly. The other one is |
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47:21 | migration where potentially due to hypoxia due inflammation, the tight junctions become not |
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|
47:29 | tight, they become loose and they filter all of the foreign subjects. |
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|
47:37 | this case, the virus can cross between endothelial cells through the tide |
|
|
47:45 | And in fact, the brain the third cellular uh infection hypothesis from |
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|
47:56 | blood into the brain is a Trojan hypothesis. So, macrophage which contains |
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48:04 | virus inside and that macrophage is, a, it's a regular cell of |
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|
48:10 | body. So it's not being recognized a foreign invader. It passes into |
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48:17 | brain to lose blood brain barrier and releases the virus in the brain. |
|
|
48:27 | Trojan Horse, if you recall, is a famous story uh of a |
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|
48:36 | that was gifted to one of the . Mhm It's a wooden horse and |
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|
48:42 | city thought that this was a gift the city. So they accepted the |
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|
48:46 | horse and at night, there was army hidden inside the horse that came |
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|
48:50 | and destroyed the city. So this the the Trojan horse and the army |
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|
48:56 | is the virus that comes in and the city. That's why it's called |
|
|
49:00 | Trojan Horse hypothesis. All right. now the the other three most important |
|
|
49:08 | of what we think is going It's a neurological involvement in COVID-19 and |
|
|
49:17 | mechanisms, right? So I really this diagram because it talks about if |
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49:23 | have COVID-19 infection, if you have damage, OK, you have blood |
|
|
49:30 | barrier damage, you have infection of cells and neurons, there's overproduction of |
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|
49:40 | . So, cytokines are also controlled microglia and they're released so that they |
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|
49:46 | amass immune response because there's infection and inflammation. So inflammation signals immune response |
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|
49:53 | that site because typically inflammation is because something like injury or infection and it |
|
|
50:01 | cytokines. But if these cytokines are re re released because of the |
|
|
50:09 | then you have overproduction of cytokines and referred to as cytokine storms in the |
|
|
50:17 | . And that can be also bad , for the brain, the |
|
|
50:23 | And this is immune system activation. other is activation of pro coagulation factors |
|
|
50:29 | the blood. So, a lot people view SARS called two as coagulopathy |
|
|
50:41 | a disease that causes coagulation of the cells. Now, if you have |
|
|
50:48 | , you have thrombosis or thrombus it's blocking the blood vessel. So |
|
|
50:55 | gonna be pressure building up in that vessel and sometimes it can lead to |
|
|
51:00 | rupture of the blood vessel and spillage the blood in the brain. So |
|
|
51:08 | not good. That's stroke. You rupture of blood vessels in the |
|
|
51:13 | You have leakage of blood in the . But what it does is essential |
|
|
51:17 | the blood, it starts coagulating uh forming these co coagulation factors in the |
|
|
51:26 | binding to two receptors. Once it to two receptors, um it activates |
|
|
51:36 | immune system and this is direct viral of neurons, endothelial cells or glial |
|
|
51:44 | . In case of neurons, it neuronal necrosis and neuronal apoptosis. |
|
|
51:49 | neuro degeneration or neuronal cell death. , uh three ways, right, |
|
|
51:58 | of an immune response to the unregulated , thrombus formation through coagulation factors and |
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|
52:08 | a stew binding that basically causes necrosis apoptosis in the cells. We also |
|
|
52:16 | that in the periphery. It, mostly chemo sensory dysfunctions, anosmia and |
|
|
52:26 | that are most common. These are main symptoms we're gonna focus on the |
|
|
52:33 | N S in the C N There are astrologically significant differences in C |
|
|
52:42 | scans. Those are computer tomography You know that and we talked about |
|
|
52:47 | they're x-ray based. They're really good heart tissue, but they will also |
|
|
52:51 | differences in soft tissue. They can cancer, so they can detect more |
|
|
52:56 | that are hyper dense versus hypodense. there are changes in in the anatomical |
|
|
53:02 | of these, the densities in some the anatomical structures in the brain following |
|
|
53:07 | infection in the brain. Main symptoms be headache and vertigo, major |
|
|
53:13 | stroke, meningitis, acute necrotic encephalopathy hemorrhages. No conclusive treatment management and |
|
|
53:23 | . Although there's many different treatments, and recoveries that are now uh being |
|
|
53:30 | in different hospitals, different countries, doctors, depending on individuals, conditions |
|
|
53:35 | other diseases that that person may be from uh while they're being admitted to |
|
|
53:42 | for acute uh for infection COVID-19 And here I spelled any accurate net |
|
|
53:51 | a Phil. Ok. So for , I also have uh another uh |
|
|
54:01 | and the figure in there. So , periphery chemo censor function virus reaches |
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|
54:10 | those Olfa mucosa inflammatory response, chemo dysfunction. So when you get your |
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|
54:18 | such virus infected theia infected and they dying and you lose sense of |
|
|
54:25 | And it depends, it depends how your immune response is. It depends |
|
|
54:29 | kind of a genetic predisposition you may also depends on the viral load. |
|
|
54:35 | typically it comes back, the sense smile comes back in a few |
|
|
54:41 | But I've had people tell me they it for two months. Others tell |
|
|
54:45 | they lost it for two years. one of the students after Thursday class |
|
|
54:51 | , what do you think about the that COVID-19 sits dormant inside of |
|
|
54:58 | I was like, oh, that's of interesting, right? Because uh |
|
|
55:04 | talked about shingles, remember and herpes virus that once it expressed itself its |
|
|
55:10 | pox, it goes in, it's and then it rears its ugly head |
|
|
55:15 | 30 40 years later or more. , is that the case where some |
|
|
55:21 | , they are testing negative, how testing the presence of that, maybe |
|
|
55:28 | the mucosa or the cells and things that, they're not picking up and |
|
|
55:33 | not, don't maybe understand or have good way to understand if this virus |
|
|
55:38 | stay dormant in certain cells, maybe can stay dormant in mucosa and some |
|
|
55:44 | the cells that we were discussing and re express itself. And I, |
|
|
55:51 | , I, I think maybe there a little bit of uh necessity |
|
|
55:55 | to address this because I've experienced loss smell in the last year and a |
|
|
56:03 | now, three times in addition to it when I was diagnosed with |
|
|
56:09 | And before that, I lost my of smell, maybe five years before |
|
|
56:14 | once. So, uh I'm either some condition that's becoming more frequent |
|
|
56:22 | or I think that maybe it has do with the, with this virus |
|
|
56:26 | and potentially sticking in our bodies and long haul or, or the long |
|
|
56:32 | . The facts from long haul, people carry it for a long time |
|
|
56:37 | test positive. We don't know if carry it also as dormant virus. |
|
|
56:41 | that's something to but typically anosmia loss smell and the loss of taste. |
|
|
56:49 | , I'll give you that question again no market for a cancer on exam |
|
|
56:54 | . Now, for the type of of the C N S, you |
|
|
56:59 | virus that enters here there, bones enters into the brain and it can |
|
|
57:04 | into these H two receptors. Now neurons and glial cells, you can |
|
|
57:10 | go through the viremia as we talked infect neurons and glial cells affect the |
|
|
57:16 | brain barrier causing cerebral edema or This is interchangeable, bidirectional apoptosis leads |
|
|
57:27 | intercranial pressure and cerebral edema or But this is also possibly using leading |
|
|
57:35 | potential acu Nero of Phil and So, all of this is pointing |
|
|
57:42 | cerebral edema, compresses the brain stem alters respiration. So there's a lot |
|
|
57:48 | basically swelling going on in the brain you have this infection. That's what |
|
|
57:53 | edema is. What does it mean the brain stem and alters respiration. |
|
|
57:59 | you remember that we talked about brain ? And we said that brain stem |
|
|
58:05 | nuclei that control respiration, vital body , respiration, heart rate. What |
|
|
58:13 | these nuclei swell that the whole brain swallowing, everything is swallowing it. |
|
|
58:18 | , it's nowhere for it to It's not like your neck is gonna |
|
|
58:21 | expanding twice the size and the skull gonna start expanding. It's not. |
|
|
58:26 | there's a lot of pressure build up that swelling that swallows the tissue builds |
|
|
58:33 | and more pressure, physical pressure. that pressure now starts interacting with the |
|
|
58:39 | stem cells that are responsible for vital like breathing. So they're not even |
|
|
58:44 | they're in fact infected or because the cannot breathe, but because of the |
|
|
58:49 | of the brain tissue, those centers functioning abnormally. So, adverse immune |
|
|
58:56 | will talk about viral infection triggers cytokine potential a Nero and hemorrhaging respiratory stress |
|
|
59:07 | of oxygen in the lungs, multisystem failure. So, neurons are very |
|
|
59:12 | to loss of oxygen. Two minutes oxygen and neurons start dying. But |
|
|
59:17 | organs can also fail if you have of oxygenation. And a lot of |
|
|
59:24 | when uh a person passes out, don't have PC R, let's say |
|
|
59:31 | not receiving PC R, they don't and they don't have pulse, uh |
|
|
59:38 | will get revived. And one of first few things, people will |
|
|
59:41 | how long was that? How long that last? When the person had |
|
|
59:45 | breathing, no pulse to when they revived? Now, if, if |
|
|
59:49 | person passes out and somebody is doing PC R uh CPR polymer chain |
|
|
59:59 | uh if they're doing CPR, um you know, they're also administering |
|
|
60:07 | So there is some oxygen coming in the heart is still artificially pumping. |
|
|
60:13 | if that doesn't happen, what is time period? And that is important |
|
|
60:18 | a lot of times people in that , if they get revived, they |
|
|
60:25 | to the hospital, they get placed a coma in the medical coma. |
|
|
60:31 | then they're typically brought out of that colum maybe two days later, maybe |
|
|
60:37 | days. It depends on all of organs and how everything is functioning, |
|
|
60:42 | of the indicators. And as they're the person out, they're asking the |
|
|
60:47 | that was with them or the close or somebody responsible for their life. |
|
|
60:52 | long was it for? Because if is longer than five minutes, then |
|
|
60:57 | potentially permanent damage to the brain. really have to watch whether that person |
|
|
61:02 | comes back out of coma. If gonna be a normal functional person missing |
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61:08 | few functions, or if they may just nonfunctional like a kind of |
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61:15 | like a vegetable. And that's lack oxygen and death of neurons due to |
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61:20 | of oxygen. And if you can it with a respiratory infection, lack |
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61:26 | oxygen and swallowing, it would be very serious problem. So, um |
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61:33 | have interesting data here. Talks about abnormalities that are neurological disorder abnormalities are |
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61:42 | 30% of all the patients that get . And the more serious infection. |
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61:48 | you have a respiratory illness, if have a respiratory illness or a |
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61:53 | you uh have a greater chance of all of these neurological dysfunctions. So |
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61:59 | have uh potential of encephalic encephalitis, stroke, postinfectious neurological complications as well |
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62:09 | intensive care related neurological manifestations. That if you are in the IC U |
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62:16 | the COVID-19 infection, it's very likely are being intubated, uh you're on |
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62:22 | respirator or being intubated. And if intubated, there's a chance one in |
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62:28 | individuals cannot even survive this procedure. even if you survive, it's, |
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62:34 | tall, is pretty significant, psychological physiological tall with the whole procedure and |
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62:41 | in the IC U takes time to . All right. And so we |
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62:56 | here and we're gonna end here And if you learned anything in this |
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63:06 | I think you learned a lot. one of the things that I hope |
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63:12 | addition to neuroscience and thought, you , is that there's reality in this |
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63:17 | , there's science in this world, regulations, politics. There are all |
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63:23 | these interesting opportunities with pharmacological developments for disease, for particularly Alzheimer's disease. |
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63:32 | we saw that so far, a target is just one molecule inhibitor. |
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63:40 | uh I think you've learned a lot the brain and how neurons interact with |
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63:45 | other. They form the networks, this networks can synchronize their activity and |
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63:52 | certain frequencies, how these frequencies determine behavioral outputs and emotional perceptions and encode |
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64:01 | of the information like memory and recall of that information when you're taking the |
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64:07 | . Uh So you form the view a single neuron from voltage gated sodium |
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64:16 | to potassium channels, producing action potentials chemical neural transmission communication to systems that |
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64:23 | different parts of the brain and how all interconnected. And the more you |
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64:30 | , the more humbled I am about complexity of this organ. But I'm |
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64:36 | very hopeful that maybe some of the that we talked in this course that |
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64:41 | talked about in this course, maybe example, the video that what we |
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64:47 | with Doctor Ramachandran where he devised a box for an individual to get rid |
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64:53 | their phantom limb syndrome. What uh about all of these tools being in |
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64:58 | virtual world in the matter world. about all of these tools, revisiting |
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65:04 | of these stories as you are becoming professional in this area, revisiting some |
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65:10 | these therapies and stories with virtual reality artificial intelligence and helping us solve the |
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65:17 | , ultimately diagnose disorders as early as can as noninvasively as we can with |
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65:26 | best treatment options available from pharmaceuticals to alternatives to uh medical diets, to |
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65:39 | working out and exercising and hopefully being individuals and better society as a |
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65:45 | So with this, uh I will today's lecture and I will see everyone |
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65:51 | more time on zoom on Wednesday. you very much once again for coming |
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65:56 | being here with |
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