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00:04 This, this lecture, 24 of . And we, we were discussing

00:12 lot, couple of lectures really. had an introduction into medical cannabinoid when

00:17 talked about epilepsy. And then we about pharmaceutical cannabinoids and medical cannabinoids.

00:24 we'll maybe expand on that a little more so that everybody understands that

00:29 What I mean is that these are approved drugs. And in the United

00:34 , we discuss that there are two delta nine T H C and 10%

00:39 D and it's only for two conditions well. Two, this one is

00:45 mg, DH C and it's appetite and anti nauseating, antibiotic for chemotherapy

00:52 . Terminally ill patients wasting syndrome, . Um Now CD D is for

01:01 . It's anti seizure drug, anti medication. And this DH C and

01:07 D mixture is for sin and pain and multiple sclerosis. But this one

01:14 not FDA approved. Therefore, it not available in the United States,

01:17 it's available in other countries around the . This is synthetic and these are

01:24 derived. What do you mean by the rock? It's like when you

01:29 we talked about this technique called H L C. So when you have

01:35 from the plant, like a mixture the plant here, you can not

01:40 detect it and measure it using H L C. You can also isolate

01:46 ingredients. You can extract from the and isolate those individual ingredients. So

01:51 can isolate T H C, you isolate CV D. You can also

01:59 it from other chemical ingredients in the . So we talked about that and

02:08 hear a lot about medical cannabis and . 4 20 was last Thursday and

02:14 were a lot of celebrations, there a lot of discussions on TV,

02:18 the radio, uh warnings coming from , psychiatry people. And uh why

02:28 there still so much discussion? And the main reason is that cannabis and

02:35 nine T H C that you're seeing and other cannabinoids are on schedule Wong

02:43 a schedule Wong Drum to be on one means that that substance or that

02:51 has no medicinal value is addictive and be dangerous. So, while we

02:59 that, we actually also have drugs Delta nine T H C that are

03:07 medications. So that's why it's it's a misnomer, right? You

03:12 have something on schedule one. Delta T H C say it has no

03:16 value and you can also have an approved drug to treat medical conditions,

03:24 drugs that are planned derived and one them that is intoxicated. So that's

03:32 laws sometimes don't agree with science or not make scientific logic, right?

03:42 you'll see that my scientific logic, cannabis doesn't even produce delta nine T

03:49 C. It produces delta nine T C acid which is non intoxicated.

03:55 that's, that's another uh misnomer, and mistreatment of this plant. And

04:02 why I ended with this slide well, they got all of these

04:06 people, the National Academy of Science and Medicine. They review all of

04:12 literature, all of the clinical all of the pharmaceutical data and tell

04:16 is there uh substantial evidence that these work for other things than just spasms

04:24 other things and the seizures. And concluded that there is substantial evidence that

04:30 2017. So that's six years ago there's a lot of uh interesting research

04:36 has happened since, but it conclusive that it has for treatment of chronic

04:42 in adults, cannabis itself. So doesn't say that it is for anti

04:47 medication. It doesn't say it's for Matic uh medication. If you are

04:54 chemotherapy, it says it helps from pain who doesn't have an older adult

05:01 their family or themselves that actually have pain. Ok. So it's a

05:09 vast condition that applies to many different . Uh especially elderly anti medics and

05:18 of chemotherapy and vomiting oral cannabinoids, patient reported multiple sclerosis, plasticity,

05:24 , oral cannabinoids. And then there's and limited evidence for a lot of

05:28 , moderate evidence for sleep apnea, , chronic pain and multiple sclerosis.

05:34 , while there is conclusive evidence, also limited evidence for chronic pain.

05:39 that's because there's different interpretations, different with different uh subjects and models.

05:46 from animal models to, you human subjects and and and so

05:51 But this is what these smart people there is medicinal value and what we

05:57 about uh last time we talked about cannabis. And I said that the

06:03 phyto cannabinoids that you find in the or Delta nine T H C or

06:09 D and CD G. And actually learn that it's an acidic versions of

06:16 cannabinoids that are naturally occurring. And you will see in this world that

06:22 surrounded by different other cannabinoids and you see advertisements on the gas station

06:34 convenience shops, uh smoke shops, eight, delta eight T H C

06:44 sold here. Delta 10 T H is sold here. H H C

06:57 Komal is sold here. And those derivatives typically from CV D.

07:06 And these, this group are semisynthetic although they come from CBD, which

07:19 a phyto cannabinoid or CBD A that found in the plants extracted isolated from

07:25 plants. There's a lot of CBD a lot of it gets converted through

07:31 known means and changing the bond from 9 10 into a nine carbon

07:43 Remember these are long carbon chains. you already you have 10 carbons,

07:49 , 12, 13, 14. . They're, they're long carbon

08:05 Now. Delta eight, what it is C B one receptor binding and

08:13 H C delta nine T H C a high affinity for delta or CV

08:17 receptor binding. CV D has low , which means it doesn't really prefer

08:23 bind to a CV one receptor. , it actually prefers to bind to

08:31 receptors. Remember the function of CV receptors in the brain recall that presynaptic

08:42 had Vesico release and we had calcium and pre optically, we also had

08:53 B one receptors of neurons that were protein coupled and that they would inhibit

09:02 close voltage gated calcium channels. And would control here the release of glutamate

09:11 Gaba. So if you recall endo are made optically, the endo

09:23 they are made optically and they travel gradely combined CV one receptors and have

09:30 effect of controlling neural transmission by blocking gated calcium channel. So phyto can

09:39 of those like T H C delta will have a high binding affinity to

09:46 if you want them. So it mimic the effects of end of the

09:52 . In addition, glial cells in microglial cells contain CV two receptors.

10:03 CV one receptors are going to affect of a neural transmission CV. Two

10:09 are going to affect more of a function, microglia, inflammation repair of

10:17 brain immune response generation in the So it will affect slower processes like

10:28 and maybe even synthesis if it's affecting synthesis of glutamate, for example.

10:36 , so these pinto cannabinoids delta line H C CBD and C B

10:41 they will all have different relationship with one receptor that we'll review in a

10:47 . But in general speaking, we understand the delta A delta 10 and

10:53 H C effects on C B one . And a lot of times we

10:58 talked about synthetic cannabinoids. But a of times people say, well,

11:02 a second, how come the semi or synthetic cannabinoids? It's, it's

11:08 same molecule. How come it, affects people? It's not the same

11:13 . So, first of all, convert it CBD into delta eight or

11:16 10. And second of all, these semisynthetic anana, but there are

11:23 synthetic Annabi that we talked about that be full agonists. What does that

11:30 ? That means that if these phyto are partial agonist of C B one

11:35 , so they bind the C B receptor and then they dissociate and broken

11:42 . It's partial agonist, the full can bind to CV one out and

11:46 stuck there for a week. A of times we don't know because we

11:52 know what has been synthesized. And are different conversions that are taking place

11:58 through acid dots of, uh, of this double bond to put it

12:04 eight and 10 and put it between and 11 carbons that we don't know

12:10 . So, while we understand that and Delta nine T H C have

12:15 researched a lot and there are real that are pharmaceutical medications derived from Delta

12:23 and from CBD, we don't know about these other guys, the semi

12:29 . So we don't know how they're and we're not quite certain how well

12:32 tested that are available in the So buyer beware many different cannabinoids in

12:40 plants. T H C CBD are major also C B G, they're

12:46 major because there's a lot of So the plant will produce a lot

12:50 them. But then there are other like CDC canna bechromate or CV D

12:57 can be. And those are called or rear cannabinoids. And that's because

13:04 plants, cannabis plants don't generate, express high levels of those cannabinoids.

13:11 not all strengths of these plants have minor cannabinoids. So they're harder to

13:17 , they come in smaller amounts in plant naturally and therefore they are minor

13:23 rare cannabinoids. And it's gonna be deal of investigations. I think looking

13:28 a lot of these minor cannabinoids as as some asthe cannabinoids for good and

13:36 reasons. Uh and, and the with full agonist and in general,

13:42 danger with, with cannabis is typically Delta nine T H C. So

13:48 intoxicating effect, the light addicting the cannabis use disorder is alkaline T

13:54 C but it is often not attributed these other cannabinoids like CD D that

14:00 now being researched to be as an addictive drug or antipsychotic. So,

14:08 complexity of this plant is beyond understanding it in two lectures or

14:14 it has over 1000 of different uh that it expresses and certain chemicals have

14:23 properties, but they also have intoxicating . They may have addictive properties and

14:28 effects as well. And not for not every person reacts to different chemicals

14:35 different plants and molecules the same not every condition can be addressed just

14:41 T H C or just with cannabis knowing what's inside. Because different strains

14:47 cannabis, some strains will produce T C only, some strains will produce

14:53 , only some strings will produce five phyto kommen, others, 15

14:59 67 in different variations and different So there's a variety of different plant

15:07 just like you have different color roses each, each color has AAA gene

15:14 has to uh to be present in for a rose to have that

15:17 So you have a variety of changes in genetic composition and also the phenotypic

15:25 and the final chemical output of this . And in addition to cannabinoids,

15:32 some of them are positive and a of them have unknown properties.

15:37 In addition to cannabinoids, we also plants produce turkeys that we also

15:42 When we talked about the olfactory we smell different odors and we said

15:49 odors for from essential oils or turps . And so cannabis and cannabinoids were

15:57 long molecules. They are in long chains and we cannot perceive them through

16:04 olfactory system. And so cannabis expresses variety of different turkeys, limine that

16:12 comes in lemons carrier filling that can found with cloves and hops. In

16:17 , hops is the closest genetically planned cannabis plant li that is found in

16:24 . All of these turps will be expressed by different strains of the

16:30 And this is what stimulates our olfactory . It's not the cannabinoids when people

16:36 they either say, oh it smells or it it it's it or it

16:40 stinks, you know. Uh but it comes from the combinations of

16:45 turbines and cannabis plants we'll be expressing that we will be smelling right.

16:54 uh why is this significant? And we have turkeys and lemons and we

17:01 clothes and don't we eat this in diets anyways. So think about

17:07 I always told you, how do take things in? Right? We

17:11 about medications, we talked about how act through the digestive system, through

17:16 skin, through the suppositories through You guys are really smart. So

17:22 of the time, what do you with turps that are found in your

17:26 fruit and vegetables? For example, eat them. But what do people

17:33 ? Mostly with cannabis? They inhale now. So, so think about

17:40 . So actually it the effect of thins a different route of injection versus

17:50 will have a different effect on the and on the brain as well because

17:55 doesn't get digested, it doesn't get and and so on and so

18:00 And so it's not only smell but also potentially certain effect that is coming

18:07 turbines and it doesn't come when you the lemon. But my as

18:12 if you were to inhale the Lamon in this case, uh Turpin that

18:17 found in uh in lemon, but is expressed in the plant that people

18:21 to inhale. And this is sort a, a fun image that I

18:26 a while back. So cannabis plants smell like lemons and blueberries and

18:32 but also like gasoline like earth also skunk. So different strains will give

18:41 plants a different smell because of the subset of turkeys that they would be

18:49 . And these turkeys they have their physiological and medicinal properties. There's a

18:56 of information here, but I want to pay attention to this guy

19:01 Alpha ping and it is a Cetalol . Do you remember when we talked

19:11 acetylcholine inhibitors? We talked about Alzheimer's . We talked about how this is

19:17 most common Alzheimer's medication that uh the cellular level and chemical neurotransmitter level,

19:26 is a loss and reduction of So by blocking acetylene inhibitor, you're

19:33 the bi availability of acetyl code and the synapse and off of is an

19:40 inhibitor and it affects memory and there studies that are ongoing with alpha pine

19:49 it will be found in a lot coniferous plants. So a lot of

19:53 pine trees, pine woods and uh Christmas trees and such uh in

20:00 , there's even such a thing as wood, wood forest therapy where people

20:05 for walks and they claim that it's of the air and turps that they're

20:14 and they're smelling that, that enhances changes their, their mood and changes

20:19 has a beneficial effect in general. . So what do we have around

20:27 world is we have in addition to pharmaceutical programs which are these international

20:35 Marinol C T E at the some, some CD D we talked

20:38 . So I said it's present like over 25 different countries at the

20:43 Also uh these drugs are international So the health insurance subsidized, the

20:50 have medical canoes are not pharmaceutical. those are national, not always international

20:57 national. So Germany has a medical program I marked international because the import

21:04 medical cannabis from Colombia, from from Portugal and they're starting to grow

21:10 than in Germany. But this is cannabis program in Germany cannabis flour.

21:17 bugs that we discussed would be sold the pharmacies. So you would get

21:21 prescription recommendation, a prescription from your and you go to the pharmacy to

21:26 a little white jar that has your flour and that's health insurance subsidies.

21:34 uh it's uh it's cheaper state cannabis medical cannabis that we have. Uh

21:42 is Massachusetts, example is Texas. have a limited medical cannabis program.

21:47 of the time patients don't get any , there's no health insurance, they

21:51 save on certain percentages of tax. if the program, for example,

21:57 a state like Massachusetts has a medical , an adult or recreational program,

22:04 medical patients can be exempt for this tax, sales tax and they can

22:11 different products and the recreational users will to pay full tax and they'll be

22:19 a lot of times in the amount products that they can, they,

22:22 can purchase recreational or adult use is correct way. Now, typically full

22:30 in the United States, it's state . So Colorado has recreational, New

22:37 has recreational uh the whole west uh most of northeast Michigan and so

22:44 um, I think over maybe 20 , almost 30 states have a recreational

22:50 . 20 states have recreational program. , and then you have national recreational

22:56 . So adult use programs. So Canada it's province specific. So if

23:01 are on the east coast with Quebecois Quebec, in Montreal, it's state

23:10 . So the state of Quebec has shops, they're government owned shops.

23:14 open at nine and close at Yeah. And I think the purchasing

23:20 is uh 18, then you go a different province in Canada and they

23:25 their own laws. And if you to the west coast, for

23:28 you are in Vancouver, British Columbia there you'll have the shops with dispensers

23:35 20 hours or 18 hours a long and they're privately operated and their different

23:43 . Now also such a program exists the world and other countries. Uh

23:51 has a different uh law that just in Germany for recreational cannabis. It's

23:58 the clubs, both social clubs. You knock on the door and say

24:03 , I'm a, I'm a club and then you can consume cannabis and

24:08 will allow one person to grow three . So already those people that are

24:15 to grow plants, they are signing their cousins and their grandmothers to be

24:20 of their residence so that they can three more, three more, three

24:24 plants uh to supply the social That's what happens usually when there is

24:29 no open regulation for these. So will like do it on your

24:34 But it's an interesting market space. this is what we have. It's

24:38 full taxation, state regulated uh medical programs, as I said, that

24:45 in Germany exist in um Canada, . So it's really spreading throughout the

24:55 . This is a map. It's map. It's 2021 December 2021.

25:01 lot of things are changing but the , the green color that means the

25:07 has both adult and medical use regulated . So in other words, the

25:13 , so the shops are there and can come in as a patient with

25:17 medical card or you can come in a partier and, and, and

25:22 your supply that way. Texas has limited program that we'll talk about in

25:27 second when typically a person comes into dispensary or even a hemp shop here

25:37 CBD products or something else. They don't know what they need if they

25:44 looking for a medical condition and this usually becomes their savior and helper,

25:55 , retailer. Uh, but tender the dispensaries they have different names.

26:03 . And so I need something from . Oh, and then that person

26:08 give their biased opinion about the sleep this or the other. And these

26:16 , they, they have jobs, have to sell products. So if

26:19 doesn't sell, they recommend something that will help you sleep, that they

26:23 to sell because it's a business Ok. And worst of all,

26:29 no standard and there's no standards in the products presenting the products and how

26:39 semi synthetics are derived and are in open health market. There's no standard

26:45 what should be on the label. when people go and look at the

26:50 , they're like, they think they found something that helps them. We're

26:54 talk about it from me additional right? And then they go to

26:58 state and that brand or that product that company may not have a license

27:05 a different state. It's a state state license program. So they go

27:10 another state and once again, they to ask this person, they

27:15 but I had this and, and they have to try to find something

27:19 even if they find something, the , the label is gonna be

27:23 there's gonna be a lot of confusion hopefully they will find a, you

27:28 , a matching product that can help while they're on vacation in, in

27:32 , away from New Mexico and So this is being fixed, standards

27:38 being sort of established. It's a fragmented market, medical cannabis market because

27:45 state owned state, uh state not state owned, but hopefully there

27:51 be some standards and I think that guys are gonna be much smarter than

27:56 but tender or any person behind the and you can ask them questions

28:01 Oh yeah. What ratio of CBD C B G? Uh where is

28:05 C O A for this product? H P L C did you do

28:10 mass? Right? Oh It's gonna you sleep. Really? Is gonna

28:14 you sleep? Is it stimulating a or or what a Damien receptors?

28:19 it will be like, I don't , just buy this. So uh

28:27 to help you buy there, uh are called unicorns companies that are valued

28:32 billions of dollars. One of them Duchy was valued $4 billion or

28:39 They're doing a lot of transactions. marketplace is bigger than tobacco marketplace in

28:44 United States right now. And so a lot of technology and sales and

28:50 menus like shopping like almost on Amazon a 30 minute delivery to your

28:57 And if you're in one of these robust developed states that have these adult

29:03 medical programs, so, but no for most of the things. And

29:10 , from medical perspective, it's not the standard, it's not only the

29:15 but it's also the regimen. I chronic pain versus I have peripheral neuropathy

29:21 I have spasms from a mask versus have, I have some disease that

29:26 been approved by FDA. OK, have Crohn's disease. How much should

29:32 take of T H C or When should I take it?

29:35 Most of the people will say, , Ibuprofen, you know, start

29:38 mg, you know, maybe it hop half an hour, we can

29:41 another 204 100 but then don't do for 34 hours. Let your system

29:47 . It doesn't exist really. But just emerging in Texas. It's an

29:52 program. T H C in medical is limited to 1% of T H

29:59 . The products are only ingestible or edible so, oils or tinctures,

30:05 they contain 10 mg of P H per gram. And that's because of

30:11 T H C limit 1% by Good. The hemp farm bill,

30:18 are hemp products. And remember I you those tall plants, they said

30:22 can contain up to 0.3% T H by law, but by weight,

30:26 law, 0.3% T H C is mg of T H C per

30:33 Let me tell you two problems here that when you do it by weight

30:37 that, let's talk about medicinal OK. First of all, you're

30:45 me ingestion products. I cannot I have a tube feeding tube,

30:52 can swallow, I'm out. I I'm, I can have one

30:58 the conditions that we'll talk about. a lot of qualifying conditions. Parkinson's

31:04 . Uh A lot of neurological conditions not good. So what do these

31:11 need? Maybe inhalation, maybe right? But currently it's not

31:18 The other thing is I need 200 of T H C for my

31:25 200 mg of T C I can have 10 mg of one g.

31:31 many grams do I need to What that does? 20 g or

31:36 mL of product? So the whole bottle has to drink. So do

31:43 take medications in such amounts? Like pharmaceutical medications where you are like,

31:48 know, adjusting spoonfuls with your you know, not really, it

31:54 work. So right now, the law is to strike this by weight

32:00 in medical program and that's going to a lot of the patients. So

32:06 if there's no weight limit, that you can have a small grain of

32:10 that weighs 50 mg and that can 10 mg if you're active, which

32:16 delta nine T H C. Now may be asking a person to consume

32:20 a half a gram or a gram something. The most of these products

32:24 not very healthy either. Gummies, know, think about it. It's

32:29 what goes into making. It's like , you know, it's like a

32:33 , I know you got lots of and that I citric acid and you

32:39 , not, not the best. , so this is a medicinal

32:44 right? The medicinal end. Let's about this the open market for hemp

32:51 . So if you're not on medicinal and you want to get a lot

32:56 T H C Delta nine. if you can have three mg and

33:01 g, that means you can have five g hunk of gummy five g

33:10 three is 15 mg of T H . So now you have access through

33:16 hump market to doses 15 mg You can look around the coffee shops

33:22 here and everywhere. You can have single dose of 25 mg of delta

33:27 T H C. No, I'm even talking about semi synthetics natural delta

33:30 T H C because I'm derived in in a big format product. So

33:38 again, it doesn't make sense because only need like a $300 license to

33:44 as a hamp operator retailer and you a $500,000 license, the renewable fee

33:51 two years to operate A T H business and deliver door to door around

33:55 state. So now the other interesting in Texas, we have institutional review

34:03 . So they put this into law they will allow those products. Remember

34:08 told you that we can order as and scientists and medical doctors, synthetic

34:13 H C, synthetic CD D from to be shipped into the university,

34:18 we cannot work with real products, plan from the dispensary and real products

34:23 the dispensary. This may allow for research to be done with medical schools

34:29 hospitals, large hospitals with actual products you buy here in the dispensary,

34:33 a dispenser in the Heights on Houston in Texas by one of the

34:38 It's very limited operations in Texas. so this is very interesting. It's

34:43 hopeful in two years. Nobody has able to execute on that. But

34:47 is what I'm interested in. Can bridge what is on the marketplace?

34:51 what the reality is I say versus the catalog is and chemical with

34:57 with the real clinical studies with the conditions like for Crohn's disease, all

35:02 of colitis for spasms, for cancers and so on and so forth,

35:08 disorders. Now the state of just like politicians banned the use of

35:16 and said it's gonna be prohibited with rear Agnos. Now, the politicians

35:20 saying, OK, we're gonna allow , we're gonna allow recreational. And

35:24 politicians first said in Texas only epilepsy be treated with medical cannabinoids. In

35:30 , started in 2017. In there was a whole list of conditions

35:36 was added. A L S Alzheimer's cancer. Look at how many of

35:41 are neuro degenerative neurological conditions. C cancer can affect the brain autism.

35:48 A L S Parkinson's peripheral neuropathy is to peripheral nerves in your fingers or

35:54 hand or your arm and no feeling numbness, posttraumatic stress disorder, seizure

36:00 , spasticity, which is typically could MS it could be peripheral. Also

36:05 specificity, diabetic neuropathy, dementia, M SS, we're talking at another

36:14 incurable neurodegenerative disorders. So just like 100 years ago, politicians said,

36:20 no, the s cannabis is we should ban it. They didn't

36:23 medical doctors, the politicians a lot times in the States, they consult

36:29 doctors, the medical doctors don't know and they now have all of these

36:34 that are open to treatment um with cannabis in the form of a

36:40 So how do you get to Obviously, you have to have a

36:45 , the disease, then you contact of the doctors in what is called

36:50 compassionate use program. They have a number of doctors like 600 or

36:55 The program has over 50,000 patients now Texas and it's probably gonna be over

37:01 in a year. It's gonna be to half a million in a couple

37:05 years. So it's, it's, , it's gonna grow. Uh So

37:09 call one of the doctors, you the documentation you have this condition,

37:14 the doctor will actually talk to you the doctors in Texas. It's different

37:18 other programs in other states. That's Texas kind of uh has a real

37:23 program with the possibility of that institutional boards to make it really clinical medical

37:29 the reason why, because in other and a lot of other states,

37:34 have a contact with a cannabis physician cannabis certified physician and you say you

37:40 a headache, so you don't have present any diagnosis. They, they

37:45 you right there and they give you card and you, and, and

37:49 core called medical card, they give a card, medical cannabis card and

37:54 never see you again. Maybe two you have to renew and then you

37:59 back to say, how's your I still have it. They're really

38:03 and you, you use it for years again in Texas. It's,

38:09 , it's interesting. The doctor will with the patient that has a

38:14 talk to them for about half an and prescribe them, not recommend,

38:21 prescribe them on a state level, treatment, a regimen for that

38:26 So you take this oil, you these gummies. I want you to

38:29 with this. I want you to it in the morning. I want

38:31 to take it in the middle of day. I want you to take

38:33 at night. I don't want you take it. Uh Don't take this

38:38 that. Uh So it's, it's really fully medically supervised and it

38:44 started where you had to talk to physician every six months. Think about

38:49 . You don't talk to your primary physician every six months, you're lucky

38:52 you talk to them once a So, but they want it six

38:56 now. They're down to a But so this is really kind of

39:00 medically supervised program and they give you limit. So the physician says this

39:05 should consume this much. And so the next year, they have a

39:10 , you know, of 20 g everything. If they order it over

39:14 next year or something, and if exceed that limit, that means that

39:18 uh oh, they're exceeding the they exceed that limit. They have

39:22 go back to the position and look, I needed to increase my

39:26 or something and be like, you're giving it to your friends and

39:28 giving you a bigger subscription than You know, it's enough, you

39:33 , whatever the situation is. but this is potentially truly medical program

39:39 we have here rising in Texas and child laws change in Texas every two

39:44 in case you didn't know the legislators every two years. So 2023 now

39:51 gonna be 2025. So whatever changes made are gonna be made. And

39:55 the governor signs them into law, you know the political system, it's

40:00 interesting. Somebody proposes a bill on committee level, they approve the

40:04 they put it to Congress, congress . Yay, they put it to

40:09 Senate Committee reviews the bill Senate Say yay, they give it to

40:15 Governor Dan Patrick and they give it the governor and they say no,

40:22 not doing two years. Boom. two years again, people that are

40:28 for whatever changes, laws, regulations against something, they have to wait

40:34 . So it's multiple, multiple steps get something through in this country.

40:40 see it play out all the time front of our eyes. Ok?

40:45 this is our very last lecture that talk about. Um COVID-19 infections.

40:52 lot of us have been affected by . A lot of us have lost

40:57 sense of smell and it's not going in the sense that I have students

41:03 come up to me. And they're , you know, my brother had

41:06 two years ago still can't smile things . So it depends, it depends

41:13 several things. We know that the can have a different impact on each

41:19 , on each body. But most depends on the viral load and the

41:23 response and the location of the And typically the location is where the

41:30 response is weak. So it's almost a virus that is meant to identify

41:36 weak spot. Uh-huh, get his , you know, get the lungs

41:40 , ok? Get some other, the nose, you know, respiratory

41:45 . So it's, it's identifying these thing. It's exacerbating almost some

41:52 issues or um uh conditions that may be there that you have experienced while

41:59 have other infections or uh another type disease or problem. So, we

42:04 that we are most concerned about how virus enters into the brain. We

42:09 that the virus can enter into the through the blood vessels. We know

42:15 the virus can enter through inhalation into cavity or inhalation, air passages that

42:23 into the nasal cavity through the ruber , plague through these demonstrations in the

42:30 and will be used by the olfactory , the primary olfactory receptor neurons,

42:36 neuro carrying information into the olfactory And of course, you can have

42:44 . So if you have uh hypoxia of oxygenation, that hypoxia and uh

42:52 damage compromised blood brain barrier and allow for the Andrew of the virus.

42:58 doesn't have to have a very high load, but it can have a

43:03 blood brain barrier for the virus to the C MS. We also learned

43:08 it has to bind to something. , h two receptors and tens and

43:13 enzyme to they're found in neuronal They're also found throughout the body.

43:21 once it attacks the A two uh it now can invade the cells

43:29 it can kill the cells. Basically over the cell, the host and

43:32 the cells. These uh we'll discuss these two receptors are expressed. Their

43:39 is mostly to control blood pressure with attention in converting enzyme too.

43:47 So there's a couple of articles that included if you wanted to look at

43:52 detail on what's going on. But we discussed that cul receptor neurons that

43:58 these cell hanging out there in the layer that are smelling things but also

44:02 subjected to the viruses. They have h two receptors. But these cells

44:08 green that are called sustentaculum cells. yellow cell is a micro villa

44:15 This is CYA cells, these green that have these two receptors and they're

44:20 right there, watering the mucus So any invasion through any of these

44:25 fest administrations into the mucus layer now the cyst cells uh susceptible and most

44:32 infected first in this epithelium factor, helium from there. It's very likely

44:40 there is trans cellular migration or trans invasion from one cell to the next

44:48 by proximity and also progenitor cells here you're seeing that also have a two

44:55 . And once they enter into the receptor neurons, it can climb

45:00 Now into the order centers into the B, for example. So if

45:10 recall, you have different glial we just were talking about microglial cells

45:16 CD two receptors, astro glial one of their functions is to have

45:22 feet to form the blood run And if you have an infection in

45:28 blood with COVID-19 or SARS COV Uh Technically, right now, if

45:38 have infection here, it can bind H two receptor and endothelial cells,

45:45 lining. And if it penetrates crosses the blood brain bar, it can

45:51 infect both neuronal populations, as well glial populations. Both will contain a

45:57 receptors. So they could have a of the whole brain and the major

46:04 types of all of the cells that infected. So we know this route

46:13 SARS called two entering into the nasal and potentially infecting the factory valve and

46:22 the brain through that route. And are three theories that are described here

46:30 I included a figure legend, although have this paper, but I included

46:34 figure legend, if you want to it, there are three ways in

46:40 we believe this virus gets from the into the brain. First is through

46:46 trans cellular migration. So, in , then infecting these endothelial cells that

46:52 part of blood brain barrier and then endothelial cells because they're touching on to

46:59 uh astrocytes and the parasites surrounding they get infection into the glial cells

47:07 into the neuronal cells as well. is neurons, neurons, microglia and

47:14 that are have their feed on the very badly. The other one is

47:21 migration where potentially due to hypoxia due inflammation, the tight junctions become not

47:29 tight, they become loose and they filter all of the foreign subjects.

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

47:56 blood into the brain is a Trojan hypothesis. So, macrophage which contains

48:04 virus inside and that macrophage is, a, it's a regular cell of

48:10 body. So it's not being recognized a foreign invader. It passes into

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

48:36 that was gifted to one of the . Mhm It's a wooden horse and

48:42 city thought that this was a gift the city. So they accepted the

48:46 horse and at night, there was army hidden inside the horse that came

48:50 and destroyed the city. So this the the Trojan horse and the army

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

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

49:40 . So, cytokines are also controlled microglia and they're released so that they

49:46 amass immune response because there's infection and inflammation. So inflammation signals immune response

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

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

54:10 those Olfa mucosa inflammatory response, chemo dysfunction. So when you get your

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

61:08 few functions, or if they may just nonfunctional like a kind of

61:15 like a vegetable. And that's lack oxygen and death of neurons due to

61:20 of oxygen. And if you can it with a respiratory infection, lack

61:26 oxygen and swallowing, it would be very serious problem. So, um

61:33 have interesting data here. Talks about abnormalities that are neurological disorder abnormalities are

61:42 30% of all the patients that get . And the more serious infection.

61:48 you have a respiratory illness, if have a respiratory illness or a

61:53 you uh have a greater chance of all of these neurological dysfunctions. So

61:59 have uh potential of encephalic encephalitis, stroke, postinfectious neurological complications as well

62:09 intensive care related neurological manifestations. That if you are in the IC U

62:16 the COVID-19 infection, it's very likely are being intubated, uh you're on

62:22 respirator or being intubated. And if intubated, there's a chance one in

62:28 individuals cannot even survive this procedure. even if you survive, it's,

62:34 tall, is pretty significant, psychological physiological tall with the whole procedure and

62:41 in the IC U takes time to . All right. And so we

62:56 here and we're gonna end here And if you learned anything in this

63:06 I think you learned a lot. one of the things that I hope

63:12 addition to neuroscience and thought, you , is that there's reality in this

63:17 , there's science in this world, regulations, politics. There are all

63:23 these interesting opportunities with pharmacological developments for disease, for particularly Alzheimer's disease.

63:32 we saw that so far, a target is just one molecule inhibitor.

63:40 uh I think you've learned a lot the brain and how neurons interact with

63:45 other. They form the networks, this networks can synchronize their activity and

63:52 certain frequencies, how these frequencies determine behavioral outputs and emotional perceptions and encode

64:01 of the information like memory and recall of that information when you're taking the

64:07 . Uh So you form the view a single neuron from voltage gated sodium

64:16 to potassium channels, producing action potentials chemical neural transmission communication to systems that

64:23 different parts of the brain and how all interconnected. And the more you

64:30 , the more humbled I am about complexity of this organ. But I'm

64:36 very hopeful that maybe some of the that we talked in this course that

64:41 talked about in this course, maybe example, the video that what we

64:47 with Doctor Ramachandran where he devised a box for an individual to get rid

64:53 their phantom limb syndrome. What uh about all of these tools being in

64:58 virtual world in the matter world. about all of these tools, revisiting

65:04 of these stories as you are becoming professional in this area, revisiting some

65:10 these therapies and stories with virtual reality artificial intelligence and helping us solve the

65:17 , ultimately diagnose disorders as early as can as noninvasively as we can with

65:26 best treatment options available from pharmaceuticals to alternatives to uh medical diets, to

65:39 working out and exercising and hopefully being individuals and better society as a

65:45 So with this, uh I will today's lecture and I will see everyone

65:51 more time on zoom on Wednesday. you very much once again for coming

65:56 being here with

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