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00:01 This is Lecture 25 we discuss this called voltage sensitive dye imaging technique,

00:10 is abbreviated VSD or VSD. I I come back to this image to

00:16 you that it's an important technique. an experimental technique, and if you

00:22 , these voltage sensitive dies that these molecules that change their entry point into

00:29 membrane change their confirmation. And as dyes air improve, great impregnated in

00:35 brain to show in the brain slices in a living animal brain, you

00:40 observe variations off large spaces in the , and you can observe them with

00:47 high resolution, where one of the pixels represents activity from several cells.

00:53 so both the sensitive dye imaging technique used and was used to describing the

01:02 columns. Uh, in the primary cortex and the experimental set up for

01:08 would be just like is indicated in slide. The other thing is actually

01:16 that these techniques are experimental techniques, in fact what what is uh,

01:23 interesting about this is that these experimental are advancing all the time, and

01:31 this case, what we're seeing is seeing the fact that image ing,

01:36 we discussed from very early on, can do it multiple different levels and

01:42 these experimental techniques from impregnating the brain sure the slices with the dies,

01:48 can also have genetically, um, voltage indicators. They're called jeffy.

01:56 coded voltage indicators or genetically coded voltage dies. In this case, it's

02:05 something that is encoded genetically, but slide I'm gonna include. And I'm

02:11 in the review because their view talks how to take these techniques. Imaging

02:17 vaulted sensitive dye genetically coded it died and translate them into riel practical

02:25 And as you think about image ing understanding different levels of the brain,

02:32 leads us back to where we started that there are so many different

02:37 You can study brain activity in macroscopic and you're observing population activity where different

02:47 of cells are communicating between different You can observe it at a

02:56 Aske opic level eso. In this , you can increase the magnification and

03:04 can start, uh, segmenting the into blue and and read, and

03:13 those blue and red cells or different subtypes. You can address it

03:20 and you can start looking at not how the cells are activated in different

03:26 or in this case of one specific , but also how these cells form

03:32 circuit that means now you're talking about and communication of the level off the

03:40 , and then you can take it further. You can look at the

03:44 level. What is individual cell and den drives on that sellers doing compared

03:51 the Selma and some cellular level? , now you can look at individual

03:57 and interactions between then drives the critic and accents or external batons that are

04:04 , that are the external synapses that formed in passing from these axons from

04:11 neurons. And so this is very diagram, because are y stands for

04:19 of interest and modern imaging techniques allow to select the region of interest.

04:25 this shows you a cellular and sub localization, where you can select soma

04:30 compare activity in soma to the two that air circled here or outlined by

04:39 and read off lines. And then could look at that did it in

04:44 a single spine to which is sub . So again, the multiple scales

04:52 organizations in the brain, from some to cellular to circuit connectivity Thio entire

05:00 , interconnected circuits on the macroscopic the whole brain level is Well,

05:06 include the references Thio this, very interesting articles. And I will

05:13 these articles from the folder for you well. Uh, there will be

05:18 reviews posted on this topic, as just indicated, um, on Cove

05:24 19 and the brain. So let's to understand. Let's try to understand

05:31 phenomenon. Let's try to understand the of physiology, how it affects the

05:37 and let's try to spend now the let's say, 20 minutes toe half

05:45 lower discussing the facts of coded 19 the brain. I think that some

05:52 you may be graduating. Is undergraduates into graduates? Fear may be looking

05:58 , um, different professional experiences and , and I think that this area

06:05 over 19 is gonna present a very area prime for investigations prime for new

06:15 off the facts of the viruses on brain as well as the new therapeutic

06:21 . Um, drugs developed. And , as you can see. Coming

06:26 . Um um, Aziz we see recently. So how do these viruses

06:36 ? How does coded 19 enter into CNN s? And we know that

06:44 in the droplets. So when you when you speak, when you

06:51 it is being put out into the the atmosphere into the air. But

07:00 that virus toe, enter into the . N s. Well, one

07:05 that he can enter into CNN s through nasal cavity. Back of the

07:11 is that if you look at the factory system, which is the system

07:16 smell, you have all factory nerve thes air olfactory nerve endings that are

07:24 and inside our nasal cavities. Okay, this this nasal cavity here

07:32 these olfactory nerve endings actually penetrate through skull. This is a picture off

07:40 we call the crib reform plate shown a CFP. And this is an

07:47 , um, skull, That As you can see, this is

07:50 piece of skull the crib reform plate located right underneath the olfactory ball with

07:55 of these nerve endings. going into nose that are responsible for the sense

08:00 smell that there's physical demonstrations, physical wholesome openings that allow with these nerve

08:09 toe enter into the CNS direct So therefore, viruses and things that

08:18 into the nose can actually penetrate through crew. Perform. Play directly into

08:25 CNS through this loose, essentially in way, loose anatomical structure.

08:31 so that's nasal cavity is interest through nasal cavity. So if you have

08:36 in the nasal cavity and you are a mask but you haven't covered your

08:45 , then you're not wearing a Scientifically, your virus lives in nasal

08:51 , so if you are a carrier you could be asymptomatic, remembers

08:56 asymptomatic carriers, and you think that so cool because your nose is hanging

09:01 or you see somebody else with their hanging out is just the same is

09:05 wearing in that. So wearing a prevents this inhalation through nasal cavities to

09:14 just X elation but inhalation through nasal . Wearing a mask prevents escalation from

09:20 mouth. Very mia, which is in the blood, reaches CNS through

09:28 blood eso one is entering through the cavity directly. Another one is virus

09:33 the blood. Remember that you can infected by touching. You can get

09:39 through fluids. You can get infected wound. You can get infected

09:44 uh, sexual intercourse. This is is all of the things the fluid

09:53 , anything that penetrates that goes into bloodstream potentially through wounds for three little

10:00 in the skin or stays on the . And then you're touching your

10:04 your mouth, you know, potentially , swallowing and some of it.

10:11 the second or the third enter into CNS is we think it happens because

10:16 the hypoxia damage, so that there a damage and hypothesis is lack of

10:22 . There's no damage to the brain damage just blood, brain barrier and

10:28 things that you might be hearing Is that the entry? How does

10:33 virus? Okay, so it entered the nasal cavity, entered into the

10:37 . Somehow there is a hypoxic damage entered into the CNS. It has

10:41 hang on to something. The first it does it hangs onto a stew

10:46 , Which is this? A cell receptor and your angiotensin converting enzyme two

10:54 . This receptor is located throughout the , so you will find it in

10:58 heart kidney lungs. It was also in the CNS and PMS perform nervous

11:06 . So virus enters has got toe into the south that uses this case

11:12 receptor to penetrate into the south upset whole whole system. Subsequently, a

11:24 receptors in the C n s. will find them in the end,

11:28 lining between the blood capital, Aries the brain. Remember, you have

11:33 endothelial cells, you have the parasites then you have the glial cells.

11:37 Astra sites. There's some a stew on glial cells and neurons. So

11:44 it enters into CNN US if if goes through this lining and the fuel

11:49 lining or if it's in the uh, interstitial spaces now it can

11:54 targeting glial cells and neurons invading the . And also infection year on the

12:05 cell levels is gonna compromise the blood barrier. Infection of the exercise is

12:10 to compromise the blood brain barrier. you compromise, the blood brain barrier

12:15 now loose. Now, if you . It's a double kind of a

12:20 sword that you have infection. Now have compromised blood brain barrier, which

12:24 let him or infection into the causing more neurological damage potential.

12:34 so if you if you think of c N eso review and called in

12:41 and next day this PMS overview of 19 let's try to understand some of

12:46 general concepts. How is it transferred droplets? Direct contact with an infected

12:54 indirectly for my surfaces? When is path of physiology viral? Enter into

13:01 brain adverse immune responses and respiratory It's the logical significance you have these

13:12 dense areas in computer tomography, so damage to the brains, and there's

13:18 in the brains. Main symptoms would headache and vertigo. Initially, major

13:26 would be stroke, meningitis and something is called acute necrotizing and so

13:31 With the type one. It is a very rare type of brain disease

13:37 occurs in viral infections. They're rarely sometimes with flu, but also with

13:45 other viruses, which sets off a chain of reactions and causes encephalitis and

13:52 philosophy the which is inflammation of the , which is delusions, which

13:58 uh, hallucinations and quite often, that can last for weeks because of

14:08 viral infection in the brain, there no conclusive treatment. So paracetamol or

14:18 inflammatories as being, uh said to headache and vertigo relief without worsening

14:26 So if you're talking about headache and , maybe that's the treatment. But

14:30 you're talking about stroke, meningitis, and hemorrhage information or blood clots and

14:37 of blood, then then then, , it's very serious. And the

14:45 accordingly. Eyes hospitalization, potential intensive unit overview. Peripheral nervous system,

14:56 droplets, direct contact with an infected and directly for my surface chemo sensor

15:03 is the first thing. So what think is happening is the hair like

15:09 on olfactory tissues on these old uh, tissues, their hair like

15:17 and they get damaged on. So get a naz mia. You get

15:23 blindness. Andi, if it starts the senses of taste and you get

15:30 Shia, which is loss of um, these air the main

15:36 So even in early stages of co with the flu temperature and,

15:47 fatigue you may also be experiencing and me on a goose er, people

15:52 experiencing just losing completely drinking coffee and tasting anything. And coffee?

15:59 that may return, and it does with time. It's the ending nerve

16:07 endings for the smell pathways on the pathways. Major symptoms is Guillain Barr

16:16 Miller Fisher syndrome, which we don't need. Thio discuss. I have

16:21 definitions that will provide for you, there's no conclusive treatment Nasal spray being

16:26 for medication delivery. Okay, so , pretty grim situation. Good thing

16:35 have vaccines coming out. This is nice diagram that has a that the

16:39 of central member system manifestation from So viral enter to the brain adverse

16:45 response, which is the reaction and stress. This is all path of

16:52 , things that can go bad. in the periphery you have the

16:56 sensory dysfunctions, that virus and factory Mucosa. That inflammatory response You have

17:04 me and Negussie a symptom resulting in periphery in the CNN s. If

17:09 virus reaches the brain and olfactory or if it goes through Vira

17:15 which is overall coming from the blood the brain hanging onto these a stew

17:22 . Then what it does. It and causes leaking in the blood brain

17:29 , which causes cerebral um, Dema , which is causing cerebral swelling.

17:37 the same time, the inflammation that on viral load easier starts causing

17:45 death of cells of the brain, leads to increased intracranial pressure, and

17:53 of the cerebral oedema and then cerebral of this inter cranial pressure buildup and

18:02 of the brain build up. Now can start compressing brain stem. And

18:07 you remember, brainstem contains your vital , control centers for respiration and for

18:14 trade. Damn. So now you ones, in fact, that this

18:19 in here, causing massive swelling in brain and inflammation. That swelling now

18:26 affecting your brainstem region so you can . Breathe barely, and you don't

18:32 control or breathing. And heart rate , plus your lungs are also in

18:37 , that through the respiratory stress the stress. You will have lots of

18:43 in the lungs. Multi system organ , including the brain. There is

18:48 neural injured in the brain. If go off oxygen, some of the

18:52 susceptible south to damage in lack of or hypoxia. Our neurons, two

18:59 and they're done two minutes without oxygen neurons die in euros. We generate

19:06 so they don't regrow like the nerves the periphery. They don't regrow like

19:12 nerve endings and the olfactory or the things do it. Once you kill

19:16 , their synapses. Without us, done. Adverse Immune response. Violent

19:23 could trigger CIDA Conover abundance and sidle storms Those air pro inflammatory molecules.

19:30 also can cause a lot of coagulation hemorrhaging in the brain. So both

19:38 on the philosophy. I'm sorry. so fill Itis are acute, the

19:46 and philosophy. Now we're encephalitis leaking of the blood. And now

19:54 have a recipe for calculation formation off blood clots and, uh, plugging

20:02 of the blood. That's all swish can lead to other problems like like

20:07 , for example, So neurological abnormalities cove In 19, 30% of patients

20:17 required hospitalization have neurological abnormalities, 45% those with severe respiratory illness with

20:30 So if you get into the situation you have compromised your respiratory,

20:39 organs okay, with severe respiratory illness 85% of those with acute respiratory

20:52 So if you start affecting the lungs the breathing, that means you are

20:56 even more significant damage to the If you were just hospitalized, one

21:03 three will have neurological damage. But you're hospitalized with respiratory syndrome or acute

21:12 disease, that number goes up to to 85% of neurological damage. Good

21:23 . Well, not so good, mostly neurological symptoms, mostly confined to

21:28 specific abnormalities. So just dizziness, , loss of smell, taste

21:36 You may experience similar things with some the, um, influenza cold viruses

21:44 . I actually had a loss off about three years ago. It was

21:52 strange. That lasted for about two , when I had a pretty severe

21:58 . So seriously, Neurological complications, mean reported with Mild Cove in 19

22:07 , of course, severe complications with bill patients and associated with much

22:16 significantly higher mortality. It's a philosophy again Viral infection can cause cell

22:26 delusions, coma, ischemic stroke. is you have the blockage. You

22:35 the blockage off the blood vessels. epoxy is you don't have enough

22:43 You also have post infectious neurological and so you can hear about people

22:50 are long haulers and that these neurological may be significant with persistent headaches and

22:59 for months following testing negative cult in . And in addition to that,

23:06 a mental health aspect to a very indications for anxiety and depression associated with

23:14 haulers of coded 19 intensive care by intensive care related neurological manifestations. So

23:23 get, and to intensive intensive care means to have respiratory failure. You

23:28 other things and treatments that are happening you that again could be indirectly not

23:35 directly due to the virus but trying contain the virus in order. So

23:45 include some or of these descriptions here a slide for you that you can

23:51 . But I think that this is , very important that we start understanding

23:57 that you put all of the things you learned into perspective of what is

24:02 on the big problem that is happening now right in front of us.

24:08 , so when somebody tells you that don't need to wear a mask because

24:14 does not do anything to you. , please send me those references.

24:19 masks don't do anything on guard. than that, I think that you

24:27 by looking at this anatomy, just duh. The virus. Anderson to

24:33 virus enters into here. Exits from exits from here. Uh, I

24:37 probably cover my nose and my And if I cover my mouth,

24:42 I might not as well cover And, you know, besides just

24:48 own belief, whatever it may uh, motivated by individual freedom,

24:56 standing, uh, partisan affiliation, , you have responsibility to others.

25:05 your peers. You have responsibility to elders. You have responsibility,

25:11 the whole society and the whole You are not alone. And so

25:19 each other is the key here. they keep talking about this because this

25:25 an unfolding story. It's unfolding. of physiology were cracking the code off

25:34 by covert. 19 were cracking the of what is happening in the brain

25:39 the processes. And you should be Thio really understand much better. What

25:47 scope it may have on the brain you have taken this course during the

25:56 during the pandemic. So this last half an hour, this last lecture

26:05 a spend talking about them, the system and you already learned about

26:13 They're cannabinoids is neurotransmitters that regulate excited and inhibitory neuro transmission. We studied

26:21 Canavan us when we studied neural Uh, the cannabinoid system was discovered

26:28 the 19 nineties, so it's relatively sistemas. We understand it. And

26:34 phenomenal system, therefore, is only 30 years old. And what we

26:42 about this system is developing. But I choose to talk about this is

26:48 I think that this system is grossly studied. I believe the system is

26:58 important in the overall homey, a body regulation and homey a static regulation

27:08 the brain functions. I think it's system that's very intricately involved with other

27:15 in the brain and potentially gets, , activated before some other neurotransmitter systems

27:22 active. So given this, that the cannabinoid system is a system that

27:30 every animal in nature has, including of the very primitive animals that live

27:37 the bottom of the ocean and given fact that recent regulatory changes, including

27:44 the last selections, have brought out changes in the cannabis laws and regulations

27:52 by state, where overwhelming majority over off population United States have access to

28:00 cannabis or the forms of fighter there's a cannabinoids that come from the

28:08 mhm. Given these two things, think that there's a lot of future

28:14 drug development for science development program as this is an emergent field,

28:21 so as it is emergent, with in 19 might be also interactions between

28:28 field and studies on, and the that are being developed for covered 19

28:36 well. So two very relevant topics cannabinoid system than we know consists of

28:44 receptors under cannabinoid molecules, and these receptors remain. One C B one

28:50 C D. Two are expressed very throughout the body in many different

28:56 observing different functions in these organs major in the cannabinoids that we discussed our

29:04 Mind or Eric Adonal Phenolic mine and a G or two or $2 glycerol

29:15 CB one receptors, cannabinoid receptors, are dominating in the brain, but

29:22 one receptors are also very highly expressed the intestinal organs. Heart,

29:29 kidneys, stomach CB two receptors on other hand, arm or confines.

29:40 organs like bone marrow like spleen are involved in regulating and amassing

29:51 an immune response in the body. you have this very complicated and do

29:57 system where you have cannabinoid and the molecules cannabinoid receptors there synthesizing and there

30:06 enzymes throughout the body and in the as we saw it serves a very

30:12 function, very important function off regulating transmission in the brain. You also

30:19 expression of CB two receptors. Center in control of inflammation in the

30:24 as well as the release of these inflammatory side of cons. And and

30:30 mind and the cannabinoids are introduced into human system very early on with a

30:38 and the production of a human milk has increased production and synthesis of Ananda

30:45 and and a mine or Ananda stands bliss. What happened? Molecule blissful

30:54 , newborn suckling is thought to be by the president's off the cannabinoids because

31:01 the cannabinoids in the newborn's themselves, just in the human milk but also

31:07 the newborn's, promote feelings of hunger also feelings of satisfaction. It's a

31:15 that gets activated with pain and stress trauma. It's in law than the

31:22 function. It regulates appetites, so cannabinoids, regulate levels of appetite.

31:28 affects memory, inflammation, thermal regulation many other different functions in the

31:34 So these end of cannabinoids like Ananda very similar in structure to Fido

31:41 and you have over 120 different phyto that are found mostly in the cannabis

31:49 . An example of such phyto The Steptoe Hydra Canavan, all delta

31:55 THC DHC, just like Ananda Mind be interacting with cannabinoid receptors as well

32:03 other receptors and pathways in the body the brain. If we look at

32:11 CB one receptor expression, you will that there is abundance CB one expression

32:18 here in red and then read. have a lot of CB one receptors

32:23 the hippocampus, which is responsible for memory and stress in basil ganglia,

32:31 is emotional response. Motor command the memory, cognition, learning prefrontal

32:39 , which is the executive function in cortex, which is higher cognitive

32:45 as well as in the cerebellum, controls the posture. So there's high

32:51 of CB one receptors that are expressed these brain structures in here. And

32:57 you recall what those brain structures they're for, then you will understand now

33:04 the end of cannabinoids but also how fiddle cannabinoids can have an effect on

33:09 and memory, like THC can have effect on posture can have an effect

33:15 executive or emotional functions. In the . We have CB one receptor that

33:25 moderately abundant in the specific areas of brain, so you'll find them in

33:29 hypothalamus, which is length again to regulation. In the making, the

33:35 is linked emotional response and it's very in the brainstem cannabinoid receptors again think

33:44 what under economic noise can then or the final economic noises that in

33:48 brainstem CB one receptors are located and Aqueduct gray area and nucleus of the

33:54 track. So in the brain which we know control, sleep

33:59 temperature regulation on motor control, the receptors, or CB one receptors more

34:06 are not involved in breathing, are involved in regulation of the heart

34:13 The opioid receptors that are found in brain stem would be responsible for the

34:19 body. Organ controls and the opioid in the opioid overdoses happened because the

34:27 dose of opioid is this big and lethal goes of opioids is only three

34:33 or four times effective. Does with lethal dose can affect the vital respiratory

34:39 heart rate centers, causing an opioid and death. So in United

34:45 we have tens of thousands of overdoses opioids, and we have an opioid

34:55 , um, epidemic going on in States, tens of thousands of deaths

35:01 opposed thio cannabinoids that are in the plant. The effective those maybe 1

35:10 of cannabis or one joint of cannabis the lethal does is about 1000 times

35:18 joints that have to be consumed in 15 20 minutes. And in the

35:25 of THC, which isn't intoxication, no deaths. There's a recovery over

35:31 period of ours from overdoses of and it does not affect the vital

35:37 and therefore you don't have the deaths to candidates in THC. This should

35:46 look really cool to you guys because understand everything. This is what I

35:52 medical doctors. I also have a entrepreneurial string inside of me. And

35:58 of this entrepreneurship, uh, endeavors teaching medical doctors, nurses and healthcare

36:06 about the endo cannabinoids under cannabinoid system medical candidates. So what happens?

36:12 potentials arrive. You have deep Calcium influx through voltage, gated calcium

36:19 , fusion of neurotransmitter vesicles, a membranes, extra psychosis. Let's say

36:25 . In this case, binding of glutamate receptors increased deep polarization postion optically

36:31 through Boston optic, both educated calcium . Due to the deep polarization this

36:37 influx now turns on. The production on the end of cannabinoids synthesizing enzymes

36:44 year, and those under contaminants emphasizing produce on demand Ananda mine into a

36:53 . They're not packaged in the but remembering soluble will traverse through these

36:59 . Will retro greatly travel and blind one receptors pre synaptic lee on the

37:07 and CB two receptors, which are dominant and glial cells. When the

37:12 of cannabinoids bind to the CB one , the G protein coupled signaling they

37:19 reduce calcium influx. It will also the sodium influx and deep polarization.

37:26 by reducing calcium influx and deep they will control the Exocet Telesystem Balance

37:33 psychosis in this case of ex Editori . But it also is done with

37:39 inhibitory synapses with inhibitory GABA. our transmitter, so CB one receptors

37:47 the brain are also responsible for the effect. That euphoric effect can be

37:55 with endo cannabinoids. And one of best ways to stimulate in the cannabinoid

38:01 is not only through negative stress but through exercising, which in a way

38:08 a repeated stress. You demand more . You demand mawr, sugars and

38:15 to the cells that are active. breathing your blood is circulating. You

38:20 a lot of other cannabinoids, and we know is the runner's high people

38:28 feel blissful feeling and very happy. there running especially long distances because there

38:35 an increased production and release of under and demand that this runner's high and

38:41 feeling this good feeling is because of end of cannabinoids, the cannabinoids we

38:46 inside our bodies, Sam there's no no such things as endogenous morphine molecules

38:56 endorphins. But there are such things Endo cannabinoids of science. Off This

39:03 high meditation induced, blissful nous is attributed and is now thought is a

39:12 that acts through the end of cannabinoid and activation of the cannabinoid receptors.

39:19 besides this, under CA nominal is final cannabinoids. THC can also bind

39:26 CB one receptor. By binding, can cause the euphoria or the high

39:32 . So the high effect that you're comes from TC binding in the CB

39:38 receptors. So the higher fact that from the brain okay doesn't come from

39:46 two receptors. It comes from CB receptors and potentially activation of other receptors

39:53 under cannabinoids and phyto, cannabinoids will to other receptors. So this this

40:01 of high that's mediated by CB one . Also, the CB one receptors

40:06 this fast neural transmission. So it's alterations and fast neural transmission. That

40:13 the fact that and our final Kannapolis to CB one receptors CB two receptors

40:20 glee are not concerned. This this fast synaptic transmission but mawr with

40:26 responses. Calcium regulation with pro inflammatory of kind release and so, in

40:33 way, to cannabinoid receptors that have modes of activity. One is fast

40:39 with synaptic transmission and another one a , which is regulating more of the

40:44 process essentials. Inflammation. We're Response in the brain. Okay,

40:52 and the cannabinoids do that, then cannabinoids do that as well, and

40:57 cannabinoids mostly bind to C B one CB two receptors. But guess

41:04 They also bind to serotonin. So say, Wait a second told the

41:08 transmissions. Cortona. This promise There's molecules that bind to different receptors

41:16 so challenging your understanding. Now what learned about neural transmission. Then the

41:22 combined the serotonin receptors in the Pfizer allergic signaling, which you know is

41:27 . It's appetite, and so Combined the trip down a Lloyd

41:31 which are involved in pain mediation. proliferator activated perception, which is involved

41:37 inflammatory and pro oncological pro cancer can also affect ion channels and directly

41:45 channel sodium channels and the cannabinoid Or maybe it's different systems because you

41:52 these receptors that expressed in the spleen the bone marrow, and they do

41:58 very different function. They don't cannabinoid contaminated. Binding to bone marrow doesn't

42:05 you feel have a euphoric effect does cause the higher fact it does something

42:11 . So impairments associated with impaired under signaling a cannabinoid receptors is associated with

42:20 different responses. You have impairment, then the cannabinoid system and cannabinoids that

42:25 being used for epilepsy and you have and then get under cannabinoid system the

42:32 that are being used for cancer. is the common mechanism? Potentially,

42:39 common mechanism couldn't be the inflammatory Inflammatory process is linked to the improper

42:48 function or immune dysfunction and improper immune . So let's talk about cannabis

42:59 And the first thing that I have explain to you is that you have

43:02 realize that you live in the state gross cannabis. Texas gross low

43:09 cannabis. There is low THC cannabis . It's a low THC, cannabis

43:14 law countries like China. I've been home for decades. Canada has been

43:22 home for decades. Most of this hamp is very tall plants. It's

43:29 sativa plants or Canada's Rudar LS. contains low percentages of THC tetrahydrocannabinol.

43:38 is the molecule advanced to CB one and causes euphoric, high like

43:45 And so most of these strains over decades most of these hemp strains that

43:50 non psychotropic they don't talk cause a effect. Most of these strengths have

43:57 grown for fiber have been grown for . They grow very tall every

44:04 It can grow up to 5 m . All of this is great

44:09 great conductivity materials, building block materials the male plants will contain a lot

44:16 seats that are rich in omega three six. I mean Assad's oils,

44:23 oils and IT Z um also rich pro team so Hampus federally legal Hampus

44:32 and regulated by each state, and everywhere in the United States and most

44:37 the countries around the world. And you goto the store, you can

44:42 em seed oil. And now, Texas, another big way and big

44:48 off cultivating Hampus for another active ingredient is called cannabidiol, or CBD.

44:55 , the deal can have a dialogue more prevalent and hemp plants, and

44:59 THC is only sub 1%. CBD be up to 10 or 15% this

45:06 ingredient in total massive to find that plans that can have a dialogue this

45:12 THC is on the drug schedule. so you have to have a different

45:17 for cannabis, medical, cannabis or THC cannabis, but can have a

45:22 on. CBD is regulated around the , including the states and state of

45:28 , and you can process help. you can produce cannabis products with cannabidiol

45:34 long as you are registered with the of Texas and have certain permissions to

45:39 process or sell industrial hemp. This different from high THC cannabis, and

45:46 you hear recreationally marijuana or adult use or when you hear medical cannabis for

45:53 marijuana, you have to understand that in marijuana is the same thing.

45:58 is a derogatory word that is, has a lot of racial connotations in

46:04 past that came about in this in reality, is cannabis Plant with

46:10 cannabis plant as different variations. Cannabis , cannabis indica and most of the

46:17 plants across is between Steven Indica, they can contain after now 35% off

46:25 in the plant. So these are THC plants. They're usually grown

46:30 up to 3 m in length. very heavy and THC, but they

46:37 have other cannabinoids like CBD that C g like individual. And this is

46:43 we refer to as adults use or cannabis for medical marijuana. But

46:48 you should stay away from marijuana term really focus on medical cannabis.

46:54 so this is This is what's allowed it's regulated. State by state and

46:59 state of Texas has a compassionate use that allows for low levels of

47:05 I believe up to 5% only in products. If you qualify under one

47:11 the medical conditions, it is not approved. Medical cannabis is legal,

47:16 most of the states in Texas it's to very confined, uh, set

47:22 patients conditions, but also product But that will very likely change was

47:30 legislative sessions in the next year or on the right. You have stuff

47:36 you hear all about Is synthetic street , Kush spice synthetic marijuana, synthetic

47:46 , Synthetic Canada's does not exist. cannot synthesize the plant from chemicals.

47:52 can synthesize chemical molecules that look here white powder there hundreds, sometimes 1000

47:59 more potent than cannabis of phyto It is dangerous. It gets implanted

48:06 all of this crap bio materials from , some stuff and sold in the

48:12 shops. And it is deadly. Houston, we had hundreds of people

48:17 from synthetic cannabinoids that especially sold on streets very dangerous. And they're not

48:24 their illegal. And the system cannot up with them because the synthetics keep

48:29 reinvented in Asia and Eastern Europe and over here under different formulations and sold

48:36 evil scientists and evil salesman. So to do you cannot synthesize a

48:43 Stay away from synthetic Anomalous has nothing do with anything medicinal, regulated at

48:50 . Huge distinction that can never be together Come low THC, cannabis,

48:59 THC, cannabis, which is medical adult use. And then there was

49:04 deadly stuff. Synthetic cannabinoids, Nothing that resembles the plant.

49:13 there's a lot more problem than You're smarter than that. And when

49:19 smarter than that, you want to a lot more about this plan.

49:23 , lot more about the active ingredients where they're located. So the big

49:30 right now is on the try combs these plants. Cannabis plants that have

49:34 glandular opera to shins and these try . These glandular protrusions that look here

49:40 of a like mushroom like structure and they're not unique. Tricon's.

49:44 not unique to Canada's plan, so , when you have okra blooming in

49:48 garden, look the beautiful Tricon's have . Okay, so you'll find the

49:55 offs on cannabis plants. And the thing that these try combs, where

50:03 of the active ingredients cannabinoids and other ingredients of volatile Europeans that have very

50:10 smell get very strong smell of a are located in these strike homes.

50:16 all these different parts of the but the active ingredients are in these

50:21 chrome molecules, and we know that know that. 1964. Dr Rafael

50:31 This is a little bit of a day history off medications, cannabinoid

50:37 the isolated THC, a great documentary to you to watch. It's called

50:44 Scientist. The doctor, Raphael goes to police station in Israel and

50:53 up block of hashish. And, , he thinks that that's used thio

51:03 and and he isolates THC. So did that her shoes come from?

51:11 is a concentrated form off cannabis. cannabis resin that is produced from these

51:19 comes from accumulating These try cons. it's a concentrated resin that is called

51:24 sheesh that's produced its not a different , a lot of different that comes

51:27 the same cannabis plant but is These glandular opera to tions that are

51:33 into resin is a Raphael Meshulam Goes the Health Ministry is a great,

51:40 episode. Drink some coffee. Let go to the police station, talks

51:45 the police officer, drink some coffee give him a kilo of Ashish,

51:50 puts it in his bag, goes , system this bus going back to

51:55 university bus going through Israel, and whole bus is smelling like crazy,

52:02 Canada's marijuana. Everywhere everybody is everybody's looking. Of course, it's

52:07 from his bank. So funny part that he's the only person that seems

52:13 have confiscated. She's from police to back into the lab and isolated

52:22 What else did Michelle um do when isolated THC? He gave that THC

52:27 monkeys, and they became very Was like Oh, that's the high

52:30 that made them sleepy. It is experiments that were squashed. They we're

52:37 people from Apple FC, and they seeing really positive results from cancer.

52:41 that research was squashed in the sixties seventies and eighties, and it was

52:47 squashed to study the plant. It is very difficult to study. Cannabis

52:53 . You can study synthetic and avenues are produced by chemical labs, not

52:59 or illicit labs, but it's still difficult to study. The actual plan

53:05 is very difficult, while other countries are opening up these avenues Israel,

53:12 , they're going ahead in this game the drug development and understanding these active

53:19 . As Meshulam is a scientist, have to realize that if you believe

53:23 something, you have to test it yourself. So he takes it

53:27 gives it to his wife and his , makes a chocolate cake, and

53:31 piece of chocolate cake has 10 mg THC, and it was about seven

53:36 at the party. We eat each a piece of chocolate cake, 10

53:41 of THC. Two of them are . Another one kind of stopped

53:49 Yeah, another one is having bad and anxiety and scared and paranoid until

53:57 day. We know the THC will with your body system differently will interact

54:02 these different receptors. But this is Marshall I'm dead about. 20 years

54:08 , we had a Nabilone system and that was synthetic THC. In 85

54:14 John Nominal or Marinol, that's developed THC tablets for appetite, stimulation and

54:21 nausea, especially in chemotherapy treatment. it's a synthetic drug that's in the

54:27 . Proof is being out there. then finally, in the 21st

54:31 we come back to something that people been doing for centuries. We know

54:39 plant based cannabis plant based medications have around in recorded human history for over

54:46 years for different conditions specific conditions. in 85 you have production off 1

54:53 1 Delta, nine THC and which is cannabidiol medication. It's a

54:59 spray that means to sprayed on the . It's 2.7% THC, 2.5% CBD

55:06 to 1 ratio and it is for and pain and multiple sclerosis. So

55:13 exists is prescription, and over 30 . It was made by UK

55:20 It's probably throughout Europe. It still not approved. In United States

55:26 the same company comes up with a preparation, which is 10% cannabidiol preparation

55:35 drop form. It's the aural solution , and it is anticonvulsant er to

55:42 seizure activity in Dravet syndrome or in Gastaut Epilepsy. Dravet syndrome is a

55:50 childhood epilepsy, where you are either epileptic drugs, traditional pharmaceuticals do not

55:59 and drive. And Alana's guest star also, uh, infantile spasms is

56:07 condition that this is the treatment And so, as of last

56:12 the dialects or cannabidiol is, FDA approved medication. This is different

56:17 the CBD that is derived from help is not studying under the safety Africa's

56:23 system that comes in this different home . So now you can see that

56:28 would like for you guys to continue stable with your innovations with cannabinoid medicines

56:37 helping very diverse conditions is you're seeing . Chemotherapy, spasm, Spain

56:48 What I'm interested in is also the that in the raw plant, these

56:55 and C d g A. Is the mother of all cannabinoids. Other

56:59 . That's just THC A and C d a synthesized from c b d

57:03 c b g a. But all the cannabinoids in cannabis plant come in

57:09 city form and th CIA is actually psychotropic. It doesn't cause the high

57:18 C d A. Doesn't either. neither the CBD a so that tells

57:22 that cannabis plant itself does not have properties. What? Yes, Canada's

57:31 does not produce. THC produces THC . That's where hydrogen of Manali casted

57:37 that if you consume THC, A not cause the higher fact. And

57:42 a lot of the drug development a of the potential. I think a

57:46 of the treatments, especially for could be coming from these acidic cannabinoids

57:51 are now emerging as effective potential in of some of these conditions as their

57:57 . Our box elated versions so th turns into THC with heat or deacon

58:03 elation with aging process with heating with and extraction. So you have to

58:10 the plant that you have to turn plant into the psychotropic or or intoxicating

58:16 by heating and deacon Box Elation in becomes an agonist two CB one

58:25 so the plants that have C B A M THC, a synthesis will

58:31 THC A. And then you can THC, the plants that are dominated

58:36 CBD. A synthesis will produce CBD , and this will be the source

58:41 CBD and C B D A becomes a the same way through heating or

58:47 card box elation. They're moving off c o H group. What is

58:53 B? D. Do can have dialogue dampened CB one activity. It's

58:57 negative al hysteric modulator. That means it binds to different Seidman THC,

59:05 it actually dampens activity of the C wondrous suffered instead of activating it more

59:12 B G. Now, if the doesn't have CBD, a synthesis or

59:16 synthesis will produce mostly C B, and C B G will act in

59:21 CB one receptor as an antagonist. , it will inactivate CB one receptor

59:29 an antagonist of CB orders up. now you're trying thio and seeing that

59:35 is complexity and the plant there's a of cannabinoids have produced as a city

59:42 and is it converted in their neutral ? They can target the same receptor

59:46 the cannabinoid system but have a different on that receptor. Somebody had a

59:52 from the earlier in the semester. C B. Do not do anything

59:56 the sound. Of course it Remember the cannabinoids buying two CB

60:01 So you're modulating C B receptor already the endogenous system if you're adding

60:09 but as of course is this medication 1 to 1 THC and CBD and

60:14 of THC and CBD potentially interacting at one receptor, different binding size of

60:20 two receptor is I prefer treatment, for specific conditions. Now, in

60:29 to these different cannabinoids THC, CBD see beyond CBD gonna be a kind

60:35 be the Vyron C B D G be chrome in CBC and so

60:41 Canada's plants also contain Turpin Caesar, molecules that give cannabis distinct smell.

60:47 Canada's plan smells like lemons. Other like lavender, and it's a very

60:53 diversity of these. Terrapins expressed a high degree. And so when the

60:59 cannabis planned medications are prepared, they multiple cannabinoids and multiple Turpin's. And

61:08 interactions between these cannabinoids and Turpin sometimes to it as cannabinoid anti garage affect

61:15 entourage of the molecules not just one , synthetic molecules or one CBD

61:22 But the entourage of molecules that comes the whole plant, we think,

61:29 be more beneficial, especially when you at the holistic treatments of the body

61:36 isolated molecules. All of these isolated and different molecular preparations of contaminants,

61:43 contaminants of Turpin's have their right respectable are due for our scientific investigation have

61:50 through it have conclusive evidence of some them inconclusive and others. But the

61:57 plant will contain this whole complexity of . And this is simplified complexity,

62:03 I'm showing Oh, boy, what this? Oh boy. Now let's

62:09 to put everything together. You have . You have Gabba. You have

62:12 . Europeans have a city cannabinoids. have neutral cannabinoids, THC and

62:19 You will not be responsible for this , but what I'm showing in this

62:25 when I'm illustrating by showing this diagram the complexity you consuming preparations from the

62:33 plant. This preparations will contain acidic cannabinoids, Turpin's and the target CB

62:42 receptor trip receptor serotonin receptor Gpr 55 receptor CB to a Dennison receptor is

62:51 target of CBD very complex system, it's not just easy to understand.

63:00 other phenomena is this is actually very to understand the interactions between the whole

63:05 extracts in this very complex systems. why sometimes isolated molecules can be off

63:12 as well. So it's not that making this all up. It's actually

63:18 dated, I believed in 2017. health effects of cannabis and cannabinoid is

63:24 current state of evidence and recommendations and National Academy of Sciences, Engineering and

63:32 . There's a conclusive or substantial evidence cannabis not talking about synthetic THC.

63:38 plant or cannabinoids are effective treatment of pain and adults cannabis, but there

63:47 no medication except for Sativex that can used. Sativex can be used for

63:57 and clenching pain from spasms that people . But other than that, there

64:04 no cannabinoid medications for pain there now clinical trials. Cannabis also in clinical

64:14 . Certain strains of cannabis, anti in the treatment of chemotherapy induced nausea

64:20 vomiting. Orel Cannabinoids Improving patient M s multiple sclerosis Spasticity symptoms.

64:27 Cannabinoids. Moderate evidence for sleep outcomes sleep apnea, fibromyalgia, chronic

64:37 multiple sclerosis. Limited evidence from many conditions for which cannabis is being

64:45 Enlisted. But in my opinion, is happening is a major disconnect between

64:53 repression of the plant and the ability study the plans and then saying that

64:59 have all of this limited evidence for plant that could do all of these

65:05 . And you have hundreds of thousands patients that are going through medical candidates

65:11 . That's not FDA approved. That a recommendation by medical doctor that is

65:19 recommendation by neurologist to treat epilepsy. neurologist to treat post traumatic stress

65:31 This is non federal system. This not a D approved. How many

65:37 you know somebody using Medical Canada's have themselves using the Medical Canada's Yes,

65:45 , you have to keep in mind there is addiction to cannabis. It's

65:50 just all hunky dorey. It's bad the young brains unless it's used this

65:54 because it can affect the plasticity of brain. Development in the developing brains

66:00 do so. An adult or aging and addiction level for Canada's is one

66:08 nine. So this this this cannabis disorder is like into addiction or candidates

66:17 disorders observed in one of nine users it starts affecting their performance or starts

66:22 their life. And if you talk them, they'll say, That's actually

66:28 my life and just a synesthesia. learned this prevalent seven or eight times

66:36 among artists and poets. Um, be surprised at the cannabinoids or

66:43 Use this and eight times higher amongst and poets as well, because there's

66:50 avenues for creativity. There's certain avenues concentration, but there's negative effects.

66:57 , THC and cannabis use can cause can cost para lawyer it cost panic

67:04 and panic attacks are not fun. called the panic attack. Oh my

67:10 ! Something's panic attack. Somebody is a serious panic attack. They don't

67:15 live. They don't want to get . They don't wanna just go about

67:20 day they're done. I'm tired of like this. Don't wanna do

67:24 And I feel like I'm gonna So I might as well just kind

67:28 like die. You can get even People rushed the hospital of panic attacks

67:33 that they cannot breathe. This is by THC and high high concentrations of

67:40 , mostly mhm. So you have be cognizant of all of these things

67:45 to be very cognizant of water said synthetic cannabinoids as well. And so

67:50 is what's happening in this country. is from the national cannabis,

67:56 society. This is Texas Low CBD and low THC program. Everywhere

68:03 see dark green, you have adult recreational and medical use. Cannabis.

68:10 , uh, west Northwest, Illinois, Michigan, South Dakota just

68:17 to have adult use one of the conservative states. But don't use

68:25 um and so I believe that this is gonna be dark green map within

68:34 next three years completely when it is to be through the federal programs or

68:39 the states. Just self determination. establish their own, uh, cannabis

68:47 locally and regulate from a swell. . This is Texas Compassionate use

68:55 So in Texas, the Medical Canada's run by state troopers. Texas Department

69:06 Safety. Public Safety. Okay, . That's what they decided to

69:15 The low THC cannabis program, and will probably improve it and will probably

69:21 to educate a lot of that. Department of Public Safety folks and affiliates

69:28 this plant, about different aspects of . And it's gonna be you doing

69:35 , some of you during it, extent in some near

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