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00:02 | This is cellular neuroscience. Election And what we discussed last lecture where |
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00:10 | medications that are available that our pharmaceutical cellphone nine THC synthetic one made a |
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00:18 | nine THC. And CBD cannabidiol CBD specific conditions specific symptoms in specific |
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00:29 | Then we talked about how there is lot much more evidence that Canada's and |
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00:35 | can help with other conditions that are listed on the specific pharmaceutical cannabinoid list |
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00:44 | that there is this uh decision was by a group of very talented |
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00:51 | Now it would be about five years . Since then there is even more |
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00:57 | information that's emerging on their therapeutic potential capabilities of. Mhm. We talked |
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01:05 | how in cannabis plants naturally you have production of Delta Mind THC because there |
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01:14 | a Delta mind th C. That gets produced in the plant. |
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01:20 | it's a civic version of DELTA nine A. That gets produced in the |
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01:25 | and this is the neutral version of of latitude and this is Finding two |
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01:33 | 1 receptors and interacting With the receptors the brain. And we talked about |
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01:39 | the we TV one receptors will control neural transmission and CB two receptors which |
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01:45 | not shown in Lisbon infographic are controlling of the slower processes such as inflammatory |
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01:54 | immune responses and mostly mediated by glial . We talked about cannabidiol CBD as |
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02:02 | of the major cannabinoids together without the THC also C. E. |
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02:07 | A specific version of it. And we discuss that there is delta eight |
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02:16 | or delta eight THC. It's typically from CBD in a semi synthetic |
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02:23 | So it is not made by the . And it has sort of a |
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02:29 | falls within the medium range of binding to CB one receptor than ACB one |
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02:37 | is responsible in the brain for causing intoxicating or the highest facts. Then |
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02:46 | 88 c. It's very likely essentially A certain high level of intoxication as |
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02:58 | . What we don't know about Delta actually was not well studied and anecdotally |
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03:05 | users don't process that plane as fast the process of natural daughter of |
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03:11 | The other warning on the market that where the anatomy of the solvent including |
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03:18 | is that there is no standard way producing. If there is a standard |
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03:23 | we know that cannabis plant contains the THC a cannot be the C. |
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03:29 | . D. A. We there multiple ways by which there is a |
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03:36 | of this double bomb shifting of this bond from 9 10 to minus |
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03:44 | And it's a har chemical prices and are not certain about the contaminants and |
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03:53 | that might be left over. So is a great debate right now. |
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03:59 | ongoing in the state and probably will be on a better level how How |
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04:08 | Delta eight, there's also another version Delta 10 THC. That would have |
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04:14 | double bond between 10 of carbon town here. So we don't know the |
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04:22 | term of facts and we do not much information on the position of the |
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04:26 | And in this situation here when we about the music effects of cannabis and |
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04:31 | we're typically talking about THC and THC CBD and when we say THC capsules |
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04:39 | least in this text here it is nine THC. Not that the versions |
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04:46 | it. Canada's plans. As I , it comes in many different unique |
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04:54 | just like when you go to the store for example, you can pick |
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04:59 | the variety of the apples, granny apples and some golden crisp apples and |
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05:09 | banana, crisp yellow apples whatever all the different apple trees, apple strains |
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05:19 | we have. And so those we all know they look like apples |
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05:24 | they are different, they taste they smell even different. But we |
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05:29 | know that apple. These are different of apples. Just the same way |
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05:35 | are different varieties of cannabis and what different about different varieties of cannabis is |
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05:41 | expression levels and combinations of servant phenomenal terrapins that are produced in the tri |
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05:51 | and terrapins. And these aromatic molecules cannabis is known for expressing a fairly |
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06:01 | variety, dozens of different Karpin's and of these carbines are quite dominant in |
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06:10 | sense that there will be significant concentrations one to several percentages in total mass |
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06:19 | Canada's plant of these turkey wings Such Lemon 18 and then a curious feeling |
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06:27 | carrier fill in is actually a selective two receptor agonist. So some of |
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06:36 | therapy ins like carry a felon are can have been mathematics. They imitated |
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06:44 | mimic activity of cannabinoids by binding to receptors to carry a filling in particular |
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06:52 | can be found in clothes and hops binds to CB two receptors, it's |
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06:59 | selected CB two receptor agonist. And why not? And so these terrapins |
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07:08 | in different fruits and vegetables and herbs plants and they're also expressed by cannabis |
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07:18 | . And if cannabis plants are dominated CBD for example and Lyman ian it |
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07:25 | have a certain the fact that it be a certain strain genetically that produces |
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07:33 | and it's typically produces this lemon flavor the CBD dominant strain. And if |
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07:40 | strain for example is dominated by THC by Lionel. So then that cannabis |
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07:50 | will have a different effect because THC CBD will interact differently with CB one |
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07:56 | . So the psychotropic effect is going be different from these Canavan ons. |
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08:02 | also the accompanying effect. These therapy can influence how that THC is processed |
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08:10 | with lina low and how winnable would give Canada strains that are dominated by |
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08:18 | . You see for example the lavender smell. So now you have different |
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08:24 | of cannabinoids and Turpin's and uh while made this funny image uh this is |
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08:34 | you walk through a Canada's garden and a hemp garden and hemp gardens, |
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08:40 | an hour outside the Houston here federal . You will smell in some parts |
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08:46 | that garden like lemon and some parts that garden will smell like skunk animal |
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08:53 | , lavender and other parts will smell gasoline and blueberry. And quite often |
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09:00 | Canada strength when they named they could incorporate or do incorporate the dominant |
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09:09 | So there's blueberry this and blueberry that of the cannabis strength, there's also |
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09:15 | strengths that are called skunk because of particular uh now that reminds people of |
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09:23 | skunk smell when you drive on the . Um and you smell skunk or |
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09:29 | walk through the woods and and you smile itself. Now these turbines, |
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09:35 | have their own physiological and therapeutic They're being studied and they have been |
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09:43 | , I'm not saying that they're accepted pharmaceutical medication. I'm saying that there's |
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09:49 | lot of indications and evidence that these et Merci finding and line a little |
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09:57 | are some of the most dominant therapy that you will find um including better |
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10:03 | film but they have their own properties what's interesting for example, is lying |
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10:13 | the end has anti carcinogenic and Elliptic immuno stimulation properties in humans Morrison |
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10:22 | anti inflammatory analgesic realistic, which is relieves anxiety. Now interestingly out of |
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10:29 | is a cyclical industries you give So when we talk about all these |
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10:34 | disease, I'm going to talk about common education and the common medications for |
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10:39 | disease are colonists, terry's inhibitors and alba pining which is present in |
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10:46 | Also counteract memory deficits that can be by THC. So all of these |
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10:53 | Turpin's, you will not have to exactly what they do. But it |
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10:57 | be important for example if you remember better carry opulent as a cannibal magnetic |
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11:04 | in that seem to be too selective . That would be important to know |
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11:08 | the test. It would be important milk with a task that uh different |
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11:14 | of cannabinoids and Turpin's determined what what call the final output chemical outfit of |
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11:21 | plant. And it depends on the , it depends on the growth |
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11:26 | In the end, if you have , it's genetics for a certain strain |
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11:31 | will express or supposed to express a phenomenon such as CBD and certain turkeys |
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11:38 | environment. So that's important to It's I think important to remember this |
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11:45 | Alba p. 19 is a silver colonoscopies inhibitor because that will come up |
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11:50 | the following election. So now we different medical programs. We have national |
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11:56 | international programs that these are pharmaceutical programs of duty calls all health insurance |
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12:03 | We have national cannabis and international cannabis have in Germany and pharmacies that's marijuana |
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12:10 | is solved in Germany pharmacies and it's from other countries. Also, health |
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12:15 | is up to Saddam has to have regulated cannabis in the United States. |
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12:20 | example in Massachusetts with many states Louisiana is another example in the states. |
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12:26 | they have both medical and recreational programs medical patients will be getting a tax |
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12:32 | of 20 that they don't have to but adult users they have to |
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12:37 | Also, the distinguishing features is for , an adult use of recreational |
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12:44 | It's also state regulated in the United . But also there are countries that |
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12:50 | international levels such as Canada. But specifics of that free available cannabis. |
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12:58 | is province specific and provinces have their rules for selling tobacco for somebody |
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13:04 | And in this case in Canada for Canada's as well. Canada and |
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13:11 | So for adults uses is typically full that's particularly controlled at the local level |
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13:18 | can even be controlled by a city be controlled by quality. Uh and |
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13:24 | far as what can be sold or facilities can be operated is very much |
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13:29 | very complicated web out there. This the current state. This is December |
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13:35 | . So it's not really current You can see dark, you have |
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13:40 | and medical use regulated program everywhere you light like in texas, you have |
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13:45 | and low TSC program. So we'll what you have in texas with a |
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13:49 | we have green, you have comprehensive cannabis program. So you can see |
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13:55 | I would say maybe half of the if you take Northeast New Jersey, |
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14:01 | want adult actually. So New Jersey not dark, dark green too. |
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14:07 | , and I think pennsylvania and Ohio to be soon anyways, if you |
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14:12 | the Northeast michigan Illinois, this is recreationally or about these cannabis. And |
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14:19 | in the west coast California, the states and but about half of the |
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14:26 | , maybe not quite 45% of the has adult in medical use programs. |
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14:34 | then you can see that there are states like Idaho, Nebraska and |
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14:41 | which is also changing maybe even South that they don't allow any access to |
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14:49 | at all. So what's happening is is no federal program for medical |
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14:54 | The only federal program exists for So there are all of these different |
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15:01 | and then all of these different state , you have different products. So |
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15:06 | when you talk about them, they have a word system that you learned |
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15:10 | . It's a vast system. Let's out the distributed throughout the body. |
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15:15 | you inhale something which is smoking of authorization. The effect is immediate because |
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15:22 | of cannabinoids or turkey means and so the lungs very quickly distributes hysterical into |
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15:27 | blood. Now everything that is ingestible . Oral ingestion. So just sublingual |
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15:34 | and swallowing oils and gummies that actually about it, you swallow half of |
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15:40 | it goes into the digestive system, exposed to very low ph gastric |
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15:46 | parts of the broken balance start getting and enters into the digestive system where |
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15:52 | starts being observed, observed. And this oral ingestion rod can be a |
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15:59 | effect. The onset of the fact you're talking about psychotropic onset for medicinal |
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16:06 | concert from cannabis plants and turbines can half an hour. And some instances |
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16:12 | the person has flown metabolize, we take you up to two hours for |
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16:16 | effect to start showing also the fact something injustices prolonged and when something is |
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16:23 | , it gets through the secondary And one of these is oxidized in |
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16:30 | liver to produce delta nine THC seem . That produces 11 0. |
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16:37 | THC. And that is also psychotropic intoxicating molecule. So some of them |
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16:43 | , some of the economic metabolized and the have a psychotropic, the fact |
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16:48 | the adjustable products or very status laws christmas cookies, you never know what |
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16:53 | states we're going to find when you about ratio ratio to see 1 to |
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17:02 | . What does that mean? That that there is 10 mg of THC |
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17:06 | 10 mg of CBD in the service too long means that there is if |
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17:10 | THC dominant for times of the THC if there's one time of the THC |
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17:16 | for serving or totaling a product. that's very important that we consumers to |
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17:21 | because THC has negative side attacks. And CBD can can reduce some of |
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17:30 | negative side effects. And for THC can evoke is not recommended and |
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17:38 | make problems worse with people that have , psychosis, schizophrenia or have those |
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17:47 | of mental psychiatric disorders. Maybe the in most cases by health care practitioners |
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17:56 | be to focus on CBD rather than of course they have top of those |
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18:02 | , sounds chopsticks patches, depends what you're in or development in the state |
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18:08 | texas. These are the two product that are allowed adjustable products and topical |
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18:15 | flour, which is cannabis flower, buzz basically it's both the product and |
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18:22 | commodity because you can have a final that you're selling out of this |
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18:27 | not in the state of texas. you can have a commodity which these |
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18:31 | and gummies and oils that come from . And so it's a commodity that |
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18:37 | being sold for somebody else to make product. And I'm telling you a |
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18:41 | bit now that the market, which interesting and some of the opportunities that |
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18:44 | may actually be a part of in future, that's what your interests |
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18:51 | So THC CBD cannot influence up to and the plants that can be produced |
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18:59 | one g of high THC cannabis without . Pre rolled joint with, let's |
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19:05 | 20% of these, he contains 200 of THC. So Typace one joint |
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19:15 | being shared dependent on the concentration we're on the person's tolerance of medicinal |
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19:25 | But 200 mg it sounds like a . But if you ingest it, |
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19:30 | it and immediately it also gets metabolized processed faster than the adjustable. Um |
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19:39 | not the case with the adjustable and not the case with the doses for |
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19:43 | . So in most cases doses for would be when you talk about delta |
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19:48 | THC is about 10 to 20 And the fact like I said, |
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19:54 | delayed, it's longer and it could stronger and that's the reason for it |
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19:58 | it goes through the justice system of tabloids. And then when you talk |
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20:03 | concentrates that are available in different concentrates. Traditionally we discussed how William |
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20:13 | used hashish and Rosalind resin essentially, was either pressed or it was alcohol |
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20:20 | . And then there are different variations these products on the market shattered battered |
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20:26 | when new variations coming up And they're concentrating too. seems CBD or other |
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20:35 | from natural Kwan's up to 90 and many instances there is an argument. |
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20:45 | why do you need such strong ah of THC and if you have such |
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20:54 | concentration, that's true. But most the people that are problems with Canada's |
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20:59 | for with adjustable and would concentrate. because they don't understand that the difference |
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21:07 | Canada's flour is 20 and cannabinoids and concentrate up to 90 and the way |
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21:16 | body processes, it adjusted the way interacts with every step tourists, it's |
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21:22 | at the same time. If you about medicinal delivery of something that you |
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21:28 | to have concentrates because you want to as much as possible with as little |
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21:35 | as possible when people inhale plant which is flour, There is remnants |
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21:43 | everything else and the leaves that are and it's actually heated temperature. And |
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21:50 | there's a lot of plant matter that not gonna happen. Cannabinoids are only |
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21:56 | and then concentrates the plant matter essentially it's being removed. So for medicinal |
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22:03 | , therapeutic purposes concentrates are going to gained popularity as well as they're going |
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22:09 | be properly. Micro does the micro , so people use them responsibly to |
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22:16 | the medicinal effect without getting themselves into panic attack in the emergency room. |
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22:24 | , what's interesting about Canada's market in United States is that in general and |
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22:30 | talk actually gonna give these talks, business colleges and a master's programs at |
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22:38 | Business University. So you want to about the entrepreneurship and business aspect. |
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22:44 | interesting in cannabis is that there are that are basically plant touching companies, |
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22:53 | plant touching companies, if they're they're operating under the federal law and |
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22:58 | they still need to abide by state because if there in South Dakota it's |
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23:05 | no go even with them. But they're in marijuana, they have to |
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23:12 | to the state regulators and follow all the regulations very closely and rules and |
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23:19 | there is a mistake on this the fines are millions and millions of |
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23:26 | in funds. So it's very very regulation and security around the marijuana high |
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23:33 | cannabis plant touching businesses, manufacturing, , manufacturing, producing the products. |
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23:42 | there is non plant structuring businesses and anything, it helps the plants grow |
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23:49 | helps the extraction. So non plant businesses and cannabis can be microscopes that |
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23:57 | at the tri cones and predict something tri cones that their online technologies and |
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24:07 | , they are delivery services. They're plant touching a little bit but they're |
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24:13 | not touching the product, they're just it. There's a lot of medical |
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24:20 | around medical patients. Uh there's a of research is going on. Um |
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24:27 | is a lot of white extraction solvents, fertilizers, cleaners, everything |
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24:41 | related to basically this massive agricultural One of the interesting things that's popping |
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24:49 | of these companies which is uh, jame or dutchy or what is this |
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24:56 | for. And if you don't know website it is, maybe we'd laps |
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25:02 | . Yeah, these are tech companies companies, Non planning budgeting companies. |
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25:09 | has become accompanied and I believe $4 dollars valuation within two years because they |
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25:17 | a technological solution for the consumers and businesses. Some of these companies analyze |
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25:24 | lot of data and they know how use the data in order to drive |
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25:31 | sales. It's a whole complete subset he technology, the whole complete subset |
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25:38 | marshaling online marketing, social media, , influence of marketing. It's a |
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25:45 | world of cannabis. Um There is standard, there's no standards products, |
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25:53 | no standard of labels. You can from colorado to California and you will |
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26:00 | find the same product. You will know if you find the same |
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26:04 | you don't know what is labeled. th CSR just delta nine THC. |
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26:11 | your C. D. G. ? And you test for C. |
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26:15 | . I don't know I just do spectrum, full spectrum refers when there |
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26:20 | an extraction or concentrate made, contains full spectrum of all of the |
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26:27 | Where's my CBD products? That's that's that's online with the CBD shop or |
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26:32 | the gas station? Where do you by your medicine? Who's advised? |
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26:40 | you gonna trust? What labels are going to understand? What brands are |
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26:48 | going to be able to find the location? I want to talk about |
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26:53 | and I'm talking about CBD other strange believing and if you can find it |
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26:59 | across the States and can you find international. So the community is setting |
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27:05 | standards on these products are very much in finding the solutions to these problems |
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27:10 | myself. The technological level. what we have in the state of |
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27:15 | is 1% THC level, which is mg THC program, Home Farm |
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27:21 | which is helped 0.3% THC three mg THC program in a finished appliance |
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27:30 | And also in the tropical products. a lot of edible products of three |
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27:36 | per gram of THC. And you do the math. If you have |
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27:40 | five grand products, you can have 15 mg THC does intend to hand |
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27:44 | Bill and that was not intended by regulators. So this problem, 0.3% |
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27:50 | nine THC. And now the problem Delta and Delta 10 th these are |
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27:56 | to have to be sold and in , there's a bill that hasn't been |
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28:02 | yet, institutional review board, which that there is going to be allowed |
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28:07 | and medical schools and hospitals on the cannabis products that are sold in texas |
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28:14 | if once that goes through, once is an alignment of the medical schools |
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28:19 | hospitals and some sort of a federal that says, okay, we won't |
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28:23 | everybody in medical schools and hospitals doing with dummies because only 20,000 people in |
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28:30 | Vietnam. Uh, then at that in texas could become a leader and |
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28:36 | cannabis research, But right now the is in 1% Texas has legislature every |
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28:43 | years and so 2021 is one of last Round of Laws was acceptance of |
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28:51 | . It's going to be a new of the laws in texas. It |
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28:56 | not called the medical cannabis program. is called texas compassionate use program. |
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29:01 | traditionally, not surprisingly because it's a long history recorded history. The first |
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29:08 | and the first program that opened in allowed only intractable seizure disorders. Intractable |
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29:18 | to be treated with these very low THC preparations and in 2017 that concentration |
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29:25 | even lower. Now these conditions, you can see the list protects us |
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29:30 | fashion abuse program is all neurological conditions cans but most of them are |
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29:39 | Parkinson's peripheral neuropathy. Of course it's the periphery dementia, Annapolis. This |
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29:45 | . S. Uh seizure of art is um cT And plus over |
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29:56 | incurable neurodegenerative disorder. So in the of Texas is the Texas state of |
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30:03 | . We have a partner of public texas DPS which are, you will |
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30:09 | them on the highway as texas, troopers but they do a lot of |
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30:14 | in the states like they teach people to paddle their kayaks and they also |
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30:20 | Canada this program that's what we have texas now you've learned enough and I'm |
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30:28 | to pause the supporting for the second to the next section. So now |
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30:35 | we learned about epilepsy and medicinal historical uses of cannabis and cannabinoids. |
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30:42 | even the historical use of medical Canada's in texas for treatment of epilepsy. |
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30:51 | you started Migraines are don't believe on list that I just showed you. |
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30:58 | on that other 100 uh neurological disorder so Migraines is probably the correct way |
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31:09 | saying it because typically people have more one and they repeat. It's a |
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31:18 | debilitating brain disorder characterized by recurring attacks moderate to severe headache is often a |
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31:24 | by other neurological symptoms. They can enhanced sensitivity to sensory stimulation such as |
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31:34 | , sound touch or all factories. there are different subtypes of migrating with |
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31:41 | but also distinct critical features. A of the people that experience migraine experience |
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31:51 | aura and so we talked about aura precedes seizures and there is an aura |
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31:57 | precedes migraines and what that means is the severe headache is preempted by some |
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32:09 | of sensory disturbances or motor disturbance and commonly a person that has migraine. |
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32:21 | now we can speak from personal I suffer from migraines and my migraine |
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32:30 | us are visual and what happens is start seeing little floaters, meaning that |
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32:40 | cannot keep focused like see blurry parts the visual field in several areas and |
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32:49 | typically starts in the same part of visual field, which indicates that it's |
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32:55 | typically originating in the same circuit someplace communicating that information to divisional circuit and |
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33:05 | that typically minutes there is an answer of pain and that pain can be |
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33:18 | for other people. It's tactile sensations much sensitivity. They become too sensitive |
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33:25 | touch. That's the hora. There be motor speeds, disturbance is actually |
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33:32 | first migraine and the most severe migrants I have. I cannot properly |
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33:40 | So I start either speaking in cyclically repeating the same thing or I |
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33:48 | to stop speaking and very selectively select word and say followed by another word |
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33:56 | saying otherwise. They kind of communicating items. So in the 19 forties |
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34:04 | three hour dr milner proposed that the unified migraine aura may be secondary to |
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34:12 | propagating quarter for formalin on that's called spreading depression before depression. Clinical depression |
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34:18 | real. The slowest fraud and cortical of neuronal and glial decolonization followed by |
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34:26 | of the community. You guys are smart to understand everything I understand. |
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34:33 | this is the schematic schematic representation of cortex and in relation to this trigeminal |
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34:46 | pain talk would which reminds me I have a uh huh. It's slightly |
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34:56 | presentation here that I wanted to insert few spies and activation during migraines the |
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35:10 | and neurons they don't have pain receptors so the pain is explained through this |
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35:20 | complex and try to grab them at vascular pathway and we'll look at this |
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35:26 | when we talk about the war on we talked about cortical spreading depression, |
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35:32 | talking about this cortical spreading depression that's from as was described away from the |
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35:39 | organizations. And so the mechanism behind the cellular mechanism is that there is |
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35:47 | rise at least. Professor Rist Edie's from brazil explain this by saying that |
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36:02 | is an accumulation of the castle just selling the potassium and low ph in |
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36:09 | extra salary would space. Okay. reach peel arachnoid on durable surfaces and |
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36:18 | the dairy in vascular sensory appearance of trigeminal ganglion teaching neurons, signals are |
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36:27 | . Men in general know susceptible know of pain receptors are related to the |
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36:35 | nerve processing. So trigeminal nervous and nerves that will process it's a sensory |
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36:45 | motor nerves but sensory it will process a receptors of the pain from the |
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36:53 | but also know susceptible which are pain . The dye germinal cervical complex which |
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37:02 | TCC it's situated in the medial aspect cerebral cortex. Okay sorry. In |
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37:11 | brain style. And then from TCC goes into the thalamus and from thalamus |
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37:21 | you know it goes into cc which the singular cortex also referred to singular |
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37:29 | salt off of the Singulair vortex and in emotional and effective processing the season |
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37:39 | ptolemy's in several regions of the frontal the temple for attacks. Yeah. |
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37:48 | this is sort of that wave of . The surprises in fantastic with the |
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37:54 | in ph activates neurons, neurons deep . If you increase expressivity of potassium |
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38:03 | , remembering potential of neurons is going go up it's going to be |
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38:08 | it's going to start firing action for shells, there's going to be a |
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38:13 | sink for me. And this wave cortical spreading depression is a slow wave |
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38:21 | so it is thought and typically that have for example visual disturbances the primary |
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38:28 | cortex and the visual cortex in general located in that exhibit a world. |
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38:35 | these cortical spreading depression wave fronts can in the exhibit a love that can |
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38:41 | from the border of occipital parietal. could originate in that motor areas or |
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38:48 | standing in motor areas rather than traveling them and therefore the fact is going |
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38:54 | be more on the border areas. Professor is the one that described this |
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39:02 | and I actually followed up on some his work experimentally and my students also |
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39:09 | studying cortical spreading depression and it is phenomenon that cellular mechanism about phenomenon, |
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39:17 | expression of that phenomenon. It is similar to the mechanisms that you see |
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39:24 | seizures and epilepsy but there are also . So the headache phase activation of |
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39:31 | trigeminal vascular system that conveys those accepted from the men energies. Central brain |
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39:39 | of cortex you may have a transient in Egypt, you know what global |
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39:46 | is. We there there are different of the media expressive receptive global |
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39:53 | This is a transient global amnesia. each may temporarily forget everything. You |
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40:00 | temporarily not be able to recognize the , forget your phone number, forget |
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40:05 | to dial 911. So this is cortex it is not clear if it |
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40:14 | but it modulates and amplify sensor Two if the hypothesis is that there |
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40:21 | some sort of a hypersensitivity sensory inputs and mind you pardon? The migrants |
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40:28 | often are also a consequence of stress . And it could be also a |
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40:36 | of other things. So it is clear. But if it's a sensory |
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40:42 | in other words, if there is parliament, there's hypersensitivity, the visual |
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40:54 | or to the auditory impact. Then those could be the sides war. |
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41:03 | could go through the salon of circuit uh singular cortex other circuits in my |
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41:11 | path of physiology. So I'm a type of environment, brainstem, trigeminal |
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41:20 | , all of the stops here. llama cortical okay hypothalamus. The hypothalamus |
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41:26 | be involved brainstem because of the trigeminal here, trigeminal ganglion this is the |
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41:35 | is that they're typically there's no self even following severe and prolonged migrants but |
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41:46 | of neuro degeneration. What you have you have this massive, massive metabolic |
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41:53 | on the brain. So the brain consumes 20% of your total body |
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42:00 | Now as you're experiencing these particles starting waves and the pain and the |
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42:07 | it's a huge metabolic drain of neurons it's also a huge physical drains a |
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42:13 | of times when people undergo an attack migraine attack and they come out of |
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42:20 | whether they're at home with the medication doing something or getting called from the |
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42:26 | room, they typically feel that their have been beaten up with with the |
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42:35 | bat and quite off of their bodies well. So there is this depression |
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42:41 | that follows cortical spreading depression and this waves to speak in the pain. |
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42:48 | lessons to the responsive Itty in the . Look at the cellular, we're |
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42:55 | in business for this. Here is description. Trying to explain to you |
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43:02 | trigeminal nerve vascular activation disease. These cascade of signaling events is depicted on |
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43:08 | cortical surface following cortical spreading depression and transient opening of the national panics and |
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43:17 | and this connections and foreign accents. junctions. So gap junctions and the |
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43:25 | of these slaves. A lot of is implicated to the gap junctions. |
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43:32 | . So side of teens across the that are released from real cells across |
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43:36 | real limit mints to reach sensory axons discharge appeal and dural try general axons |
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43:43 | are carried centrally to the trigeminal ganglion trigeminal nucleus for Dallas T. |
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43:49 | C. CS. Ds do induced inflammatory response and mast cell degranulation within |
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43:58 | inches plus reflex violation of physical Rbb of great satisfaction. So this |
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44:05 | this metabolic burden causes a certain this of the pro inflammatory molecules. And |
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44:13 | could potentially be that we're not sure this is actually the chicken or the |
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44:19 | . Maybe there is over in just of some of these uh frosted wind |
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44:24 | some side of kinds that that we're about. Um But you can see |
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44:30 | neuronal real processes with this leo cortical depression. Wave split wheel wave migration |
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44:40 | basically releases the floral inflammatory molecules um group protein one B one. And |
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44:50 | we can one be one. Doesn't . I will not ask you the |
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44:53 | but there's a pro inflammatory molecules. . And then you have the release |
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45:00 | the side of kinds and the press noise and then you have basically accusations |
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45:07 | the uh of the trigeminal ganglion and activation of moses receptors which now produces |
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45:16 | perception of pain through the trigeminal But that is again community communicated back |
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45:25 | the cortex. So this is actually conditions better there are larger. So |
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45:39 | is the spreading depression the wavefront of and spreading depression. Then you have |
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45:47 | massive deep polarization. This is extra recording here. Okay and this is |
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45:54 | potassium concentration. K plus concentration. can see that there's a rise in |
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45:59 | concentration. You can see that there a drop and sodium and chloride as |
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46:08 | drop in calcium and there's a rise glutamate. And so these are all |
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46:15 | the electro physiological and ironic features that the dendrite and Selma's recorded extra salary |
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46:25 | to face these organizations. And if record and for cellular early you will |
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46:30 | this from the resting membrane potential about 65 68 syllables have this massive |
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46:37 | You see at the beginning of this polarization you have a few spikes that |
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46:41 | produced But the rest of it is very prolonged you see this as 20 |
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46:47 | Timescale. Their prolonged in bed slow beds were reporting from one cell this |
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46:54 | was going to move over this one in one minute it's very slowly |
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47:00 | Gonna move to Mexico Mexico Mexico Mexico that's why it's very painful. So |
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47:11 | you can have high potassium injections and producer of this particle spreading depression. |
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47:18 | and one of the models to replicate models to replicate spreading depression is to |
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47:26 | and increase the extra set of the concentration. You can also change as |
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47:34 | sell the concentrations capacity sodium chloride. because because we just discussed so when |
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47:43 | talked about seizures and we talked about and we talked about cellular mechanisms and |
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47:48 | said oh look there's this synchrony and . G. And there's abnormal brain |
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47:56 | . And then I said oh look these traces from neurons and these neural |
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48:01 | them and these new inspire them. and word is kind of a was |
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48:08 | and discussed on the electrophysiology and cerebral . When we talk about the period |
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48:16 | the actual seizure activity which is referred as efecto activity and the activity that |
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48:24 | between the procedure advance, which is indirect activity and what we looked |
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48:33 | And we looked at seizures and We looked at the X. Selectivity |
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48:37 | we looked at the interplay of excited the industry sells during the collectivity. |
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48:44 | is a trace of a recording where have a wholesale reporting uh produced by |
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48:51 | and an extra sound recordings And these repetitive seizures. This is a time |
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48:57 | of 30 seconds. So there are 40 some seconds 45, maybe 60 |
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49:03 | in duration. You can see there's deep polarization, a lot of action |
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49:08 | . This is a parameter all And this activity that you can see |
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49:13 | the single south is also recorded extra . So we already talked about how |
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49:20 | . G. Except activity through the and extra cellular electorate picks up activity |
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49:27 | outside of neurons and it represents a of an average activity of that neuronal |
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49:34 | . And you can see that these advance or it'll enhance our very much |
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49:40 | in the extra several recordings. That that there is a significant synchronization of |
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49:44 | number of parameters all cells producing these potentials and visualizations at the same time |
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49:52 | between these equal advance, you have events and these interregional events are much |
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50:01 | duration birth. So instead of 40 60 seconds in duration, these bursts |
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50:09 | anywhere From 70 to 200 to few milliseconds in duration and just want a |
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50:16 | action potentials. And often they may even be picked out by the exercise |
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50:23 | recording traces because there might not be synchrony in the network to be reflected |
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50:32 | exercise recordings. In other words, a few cells may be synchronized to |
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50:37 | and Tariq traverse, but much much numbers of cells need to be synchronized |
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50:44 | order to produce these efecto. She really about, this is for |
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50:51 | it is before seizure. We looked this excitatory cells here in the |
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50:56 | This is an inventory, sell, a neuron, this is the pre |
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51:02 | phase and you can see that in predictable phase. This into neural was |
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51:07 | , I think the peripheral cells were now during the battle phase. The |
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51:13 | neurons went into this what we call polarization block. So this is different |
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51:18 | cortical spreading depression. This is a polarization block. During seizures and then |
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51:24 | have this interplay of gloom and his fails excited to ourselves. Fire. |
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51:31 | when the seizures then is finished. after that you have a bursting activity |
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51:37 | that bursting activity in this case persists inhibit their self but not an excitatory |
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51:43 | and this is post victim first So basically immediately before seizure is predicted |
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51:51 | after seizures. Post Picton during seizure perfecto and longer duration periods in |
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52:00 | Such exchangers are incorrect and this is happening during seizure than some parameter |
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52:08 | With these parameters themselves be polarized and a few action potentials. They sit |
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52:13 | and be polarized for a very long . This is a one minute time |
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52:18 | . So this is 1, 3, 45 minute duration of that |
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52:24 | a single south and also in the salary recording and the extra cellular our |
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52:33 | here and the way that these experimental spreading depressions were induced were with application |
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52:41 | potassium chloride. So if you remember potassium levels go up and they |
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52:50 | cortical spreading depression. These are the mechanisms of cortical spreading depression and to |
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53:02 | the cortical sparkles group depression who reproduce experimentally, we can apply potassium chloride |
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53:11 | will basically raise exercises the potassium concentration we produce these very slow moving events |
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53:20 | you can see just produce a few for tom Charles son, there is |
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53:25 | and co essence the rest of the . So this is the dynamics are |
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53:32 | spreading depression are different. If you define very clearly predictable pixel plastic tile |
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53:39 | rectal in seizures and cortical spreading You have this phase of globalization firing |
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53:47 | it's very slow and there's really no little activity. Now this is important |
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53:56 | in some instances these inter erectile bursts the bursts that are occurring between |
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54:05 | This is extremely important for clinical purposes for clinical diagnosis purposes. As I |
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54:13 | , the person that has epilepsy and seizures. Their brains will be |
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54:20 | And one of the ways in which can definitively diagnose if the person is |
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54:24 | seizures is to have an E. . Recording of that seizure. But |
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54:31 | a person may spend hours or days that seizure may not happen. But |
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54:35 | may happen in between the seizures is incorrigible bursting activity. And if you |
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54:43 | up, they give them part of brain with the E. G. |
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54:47 | above the electrode. And you're lucky you picked up a circuit synchrony enough |
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54:54 | recognize the directional verse in the G. Signal. That may suggest |
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55:00 | you that this person or certain brain in that person are hyper excitable. |
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55:07 | doesn't say that having seizures. So you saw intellectual burst, it doesn't |
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55:12 | that I saw seizure spread from the 1617-12 and so on. But I |
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55:19 | intellectual burst. And that is also indication of potentially epileptic brain. You |
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55:27 | see that with cortical spreading depression. you put them in june recording. |
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55:34 | wouldn't see much except that wave of polarization that would be very slowly |
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55:43 | So there are two dominant hypotheses on etiology development of csd band harder than |
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55:52 | eliminate hypothesis as a key regulator. is being in the initial D polarizing |
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56:00 | of the csD. The extra celery and aspirated concentrations increase activation of metallic |
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56:08 | is following by csD initiation compromises blood barrier permeability. High permeability of blood |
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56:15 | barrier serves as a major reason for glutamate accumulation during the following CS. |
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56:21 | . And more glutamate can come in the blood. In addition activation of |
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56:25 | M. D. A receptor leads further deep polarization of glutamate release which |
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56:30 | to see as deep propagation the high brain barrier from the ability also exposes |
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56:36 | brains of the world concentration of magnesium is also an NBA receptor blocker if |
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56:43 | remember. So if you lower magnesium you make the brain more prone to |
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56:48 | spreading depression, resolving in further cell deep organization and outward potassium current therefore |
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56:56 | accumulation on the outside of the So it's essentially extra cellular glutamate. |
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57:06 | initial p polarization and then glutamate drives leaky blood brain barrier to allow more |
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57:14 | to activate more than the receptors to the propagating legal activity. And then |
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57:22 | of this deep polarization and self aspiring professional leaking outward and how national concentration |
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57:30 | the second one is graph fest and hypothesis professed and proposed the release of |
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57:35 | amounts of potassium during their own firing most accumulation of potassium extra seven which |
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57:41 | colonized experience causes glutamate release followed by direction of normal excitation extra salary that |
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57:49 | . And Natasha can also be. used the adjacent area. Yes. |
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57:57 | he's saying that maybe that spread and potassium concentration slowly. Maybe even through |
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58:03 | glial network with cause the origination of deep polarizing ways. So glued innate |
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58:12 | versus like Cecelia potassium festo. And think that the truth lies somewhere in |
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58:25 | or all together with potassium Alexa cellular leaky blood brain barrier and an accumulation |
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58:35 | the polarization producing these cortical spreading So cortical spreading depression leaving corona will |
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58:41 | a civilization that's present velocity of at six millimeters. And then at the |
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58:47 | . Well across the federal quarterbacks, violator, physiological cellular live and migrant |
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58:55 | response bottles of cortical spreading depression, potassium floor and application with mermaids. |
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59:05 | manipulation of N. A. Pump. Why is that important? |
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59:10 | does an ak pump do it rebuilds member of potential following the decolonization quality |
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59:17 | action, potential firing. So it works against the concentration radio. It |
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59:22 | needs a teepee. Energy, huge demand during? Mm hmm. |
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59:30 | And what if you shut down the which works with a T. |
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59:35 | What if there is a lack of teepee because it's being used for something |
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59:39 | . And the pump doesn't have enough to a TTP. You now are |
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59:46 | for themselves to be more D polarized the spot came not working. It |
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59:51 | a presentation ingredients so you can manipulate ak pump and reproduce the cortical spreading |
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59:58 | , mechanisms in the brain, electrical for hypothermia. So just like with |
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60:06 | brow seizures, you can use hypothermia these people have seizures, you can |
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60:11 | the tissue in the presence of hypothermic and also induce particles from compression. |
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60:21 | injury can cause cortical spreading depression, frequency electrical pulses to stimulation, electrical |
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60:31 | . All experimental particle spreading an apartment by high exercise at a level of |
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60:36 | and glutamate induced excited toxicity. Wait second if there is glutamate induced excited |
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60:45 | but there is a neuro degeneration, there is a significant toxicity from eliminate |
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60:52 | can actually read. It's about the of neurons at least immediate neural regeneration |
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60:58 | the sentences. All right. So do we see when we look at |
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61:06 | from that trick imaging or functional imaging the brain for the migrants. When |
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61:17 | talk about more For metric imaging, talking about the morphology and the metrics |
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61:24 | that morphology is the shrinkage is the of certain cortex and altered gray matter |
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61:33 | in the fizz Odjick migrant minors versus . So the study the study control |
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61:41 | people that were having migraines, the that were not and they saw that |
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61:48 | a cortical thickness and s warm. other sensory cortex has increased also an |
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61:56 | all middle frontal for the migrant These are uh that bizarre rick |
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62:05 | So but if you look at the versus the exotic migrant knows there are |
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62:11 | differences chronic, the gray matter volume down. So there's a decrease in |
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62:19 | late cortex and singular gyrus to talk frontal, temporal and occipital areas. |
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62:25 | , mostly the motor auditory and visual , but there is a grave matter |
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62:35 | increase and some matter something and the emotional processing attainment, which we don't |
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62:44 | time to discuss the function. But you have varying effects. There are |
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62:48 | interesting more from metric changes that are and the take home message is that |
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62:53 | will have more from metric changes have reported between normal individuals and those that |
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62:59 | migraines. And you'll also have more network changes that have been reported. |
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63:04 | we have decided by the nurse versus migrant workers that have much more |
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63:10 | higher frequency and repetition of this migraine on the functional imaging, you can |
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63:18 | a distinction here in typical predictable than of and when we talk about the |
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63:26 | imaging, I believe this is with , which is blood oxygenation level dependent |
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63:32 | . I because we're still metabolic in hunt. We're tracking, tracking camera |
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63:37 | activity changes and had positron emission tomography is typically based on glucose turnover in |
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63:45 | Tabernacle. But you can see increases one s one temporal power, surprised |
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63:52 | directed activity. That means the migrant haven't increased bold activity signal already. |
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63:59 | there blows a little bit more active like the nurse and this is what's |
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64:05 | on. Um So I'm not going go over all of these differences. |
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64:12 | obviously there is a good and they here. Feel free to discuss and |
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64:17 | important. But also there's a gabba two. If you think about some |
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64:24 | may be between cellular mechanisms of seizures according to spreading depression, you're now |
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64:32 | there is some sort of a shortcut . There's maybe some sort of a |
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64:37 | . This organization sponsored sensor service. affecting certain parts of the brain but |
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64:44 | is also due to this increased potentially metabolic or yawning this regulation you |
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64:53 | an increase with the names and you decreased. Yeah, I want and |
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65:00 | is also where the distance of the and inhibitory balance that we discussed and |
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|
65:06 | we're discussing here. What are some the medications for for we've for |
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65:14 | So what is litigation used to relieve pain or his best when taking the |
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65:21 | sign of an ongoing migraine and sit the sand. Acceptable project to there's |
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65:28 | the reasons for my parents and we'll talk about it is the main reason |
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65:36 | migrants is genetic reasons there is a situation because by the things but I |
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65:45 | it in my family. So my also has my agreements and she has |
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65:51 | whole routine as soon she also gets As soon as she sees these visual |
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65:59 | she drops whatever it may be going because We cannot wait for longer than |
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66:06 | five minutes. You know she starts the same issues of not seeing or |
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66:13 | able to speak properly and you know don't want to be around people didn't |
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66:19 | so drops whatever she's doing. She's a class or she's you know cooking |
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66:27 | or walking her dog and she immediately her pain medications, pain relievers, |
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66:35 | turns all eyes off all sound She puts black hat then cover over |
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66:44 | eyes and she relaxes and a lay position. And if there is situations |
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66:54 | moments actually there are migrating attacks that can stop. Well you don't have |
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67:01 | and you have You have 10:15 minutes get home. You're driving in a |
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67:08 | that that is you know to take medication you know that can be really |
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67:18 | , not recommended to drive for If there is an urgent education's trip |
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67:25 | calcitonin, gene related peptide receptor opioid help campaign and anti nausea drugs do |
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67:37 | people buy it off and also experience that's related to migrants, preventive medications |
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67:45 | migrants. What pressure lowering medications, depressants, anti seizure drugs and that's |
|
|
67:54 | of the old reliable two of the mechanisms simply talk interestingly enough Botox |
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68:02 | That's the regulation of the civil Colin Tony and gene related C. |
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68:09 | R. P. Monoclonal antibiotic So there are several solutions for |
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68:18 | So I don't I think there are cures but some of them are very |
|
|
68:25 | and some of us are treating it pain relievers. There are two energy |
|
|
68:33 | ah bump, a noise are quite ah And alternative preparations. So just |
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68:45 | but just CBD because there is evidence financial resources and mention of campaign. |
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68:53 | yeah so taking medication right away and everything drawing making a salsa quite often |
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69:04 | somebody to. So I've had situations my my migraine attack that's so bad |
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69:12 | I couldn't dial my phone because I see that the dial pad. So |
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69:21 | know if you if I had a to feel it maybe but then you |
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69:26 | sensitivity and numbness. People also feel around her face and that's associated with |
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69:34 | trigeminal ganglion complex that we'll talk about probably not today because I'm running out |
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69:42 | time but we'll come back and review few more slides on on this sparkling |
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69:48 | the trigeminal ganglion complex. Okay but what what happens if you wait too |
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69:55 | then you're helpless You know that because cannot style how so what you do |
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70:03 | you take the medication Surly and actually speaks for whatever attack you're having you |
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70:10 | anxiety attacks. Panic attack. Tremor uh spasm attack because it could be |
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70:18 | spasms or it could be pulmonary spasms will be shutting down or breathing. |
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70:27 | you only have a certain amount of . So typically, and even with |
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70:32 | and people say, oh, it's a headache. Okay, don't go |
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70:35 | er headache. You don't feel like cannot do much, you know, |
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70:40 | hours or sometimes in a day or after. You have a headache. |
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70:45 | not a headache. We don't have us all those 1/3, but |
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70:51 | So you alert somebody. So you yourself in a quiet space century and |
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71:00 | organization. Darkness can call somebody hey, I'm having a migraine |
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71:07 | The detail over at home and I checked on this evening medication should typically |
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71:14 | acting just like with edibles Within 15 , 20 minutes, half an |
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71:20 | That's why when you swallow any you have to wait for it to |
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71:24 | this modern media. Okay, I'm end the lecture here today. We've |
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71:30 | through pretty much all of the I wanted to share with you that |
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71:34 | that I've uploaded. I want to with you also an additional slide on |
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71:40 | causes of the most important emerging cause migrating as uh, as the familial |
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71:48 | . And then moved into Alzheimer's disease COVID-19 and see how much we can |
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71:54 | at that time. So all thank you all very much. And |
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72:04 | hope to see you in person on , I'm |
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