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00:02 This is lecture 22 of Neuroscience on endocannabinoid system and medical cannabinoids. And

00:12 , this is me and it's not A I picture I'm standing in the

00:18 of hemp plants in Europe and hemp uh cannabis plants. So besides being

00:28 professor here, I I also have an interest in having more understanding on

00:37 hemp, having more scientific research and on hemp and cannabis in general and

00:44 this could be applied for various pharmacological conditions and applications in general. So

00:52 have entrepreneurial side to myself and uh of the links I may have in

00:58 folders is a TED talk I gave 2015 and that TED talk changes the

01:02 trajectory the way I think not just as a scientist, but also as

01:06 person who tries to understand the reality outside the lab on the reality of

01:13 marketplace, the reality of business And so being actively involved since 2012

01:21 with the Bauer School of Business for few years and helping their executive M

01:26 A s program. So I have vested interest in in just learning about

01:30 myself and I learned a lot and have to tell you that even as

01:33 scientist running the lab, you're sort like a business person because you're managing

01:38 , you're managing the accounts, the , you're asking people for money,

01:42 is you're writing grants. This is you have to think about. You

01:46 the academic career is a professor. can be just a teacher if you

01:52 to, you can be an academic just a teacher or you can do

01:56 be a teacher and do research. when you do research, that means

02:00 have to get money, that means have to count money and spend it

02:05 . You have to hire people, people and so on and having some

02:09 experience. Now in the business actually, I understand how inefficient a

02:17 of academia is actually in handling and handling, especially the resources that are

02:23 a lot of times. So one by grant pieces of equipment that uh

02:28 around for 10 years being used a of times. So there's virtue in

02:34 , there's virtue in business, there's in the world in general.

02:38 the way we shape our understanding of is still really stigmatized. So if

02:43 called everybody, we wanna talk about , we we gonna talk about

02:47 medicinal marijuana, medicinal cannabis. People say, is this legal in

02:53 Like to talk about it? Uh to use it. There's a

02:57 program in Texas that we'll talk about general in the world. There has

03:03 in opening and liberalization of how we and how we access and use cannabis

03:09 medicinal purposes, but also for adult or recreational purposes. Historically, the

03:16 why we have so much stigma on and marijuana is because of the Reefer

03:24 campaign that was started in 1930. shortly after alcohol prohibition ended at some

03:31 , this country prohibited the use of and you had all of these gangs

03:35 boozers running alcohol from Canada across the , right? Al Capone, um

03:45 and the whole subculture of illegal alcohol until it was legalized. Again,

03:50 condition was lifted and shortly after cannabis criminalized and it was criminalized on no

03:57 ground but political and special interest In other words, the medical community

04:03 not asking the government to criminalize The medical community was using medicinal corporations

04:10 cannabis, cannabis, tinctures, cannabis , cannabis ointments that contained cannabis uh

04:19 pharmacies in the beginning of the 20th would contain a lot of these kind

04:23 a botanical extracts and preparations. Granted lot of them were unsafe because there

04:28 no standardized ways of preparing them. at the time, we really didn't

04:33 what are the active ingredients in these botanicals and plants including cannabis.

04:39 the government turned against cannabis and decided criminalize produce a lot of agents.

04:45 had detrimental consequences to reefer madness, just on the stigma, but on

04:54 criminal aspect, on the racial aspect criminalization of cannabis, of how it

05:00 up putting mostly uh brown and black behind the bars because of these

05:07 Although this didn't mean that those ethnicities those Racists used cannabis more so than

05:13 white people did. So it was in that respect. It was supported

05:18 special interest. This campaign anti cannabis very influential American companies that were helping

05:25 the legislatures at the national level that involved in chemical injustice, petroleum industries

05:33 lumber industries because Hamp could have replaced of the paper that was made and

05:39 is made from trees. And if have a lot of interest in lumber

05:45 in making paper from trees and the factories built for that, well,

05:50 you may want to go against another industry such as Ham or cannabis,

05:56 the reality of things the way this works. So reefer madness comes out

06:01 these statements that if you smoke cannabis use marijuana, women cry for

06:08 So you get addicted, men die it. So they get aggressive and

06:12 each other and kill each other. It's for adults only this movie of

06:17 Madness. Uh Burning question dope created avalanche into frightful perversions, makes beasts

06:27 men and women. Uh There are racial aspects here where if a white

06:37 is gonna smoke marijuana, she is have an interracial uh relationship. And

06:42 also negative. So we're talking about thirties. Now, the repercussions of

06:47 campaign has persisted for almost 100 And what happened in the United States

06:53 this campaign has followed a lot in countries and at the level of the

06:58 Nations and international laws without really clear for why this is such a dangerous

07:06 frightful substance, why it should be as such. And that stigma from

07:13 thirties created campaign started being uh alleviated the seventies when the flower Children came

07:21 in this tree huggers. Uh and were going to all of these rock

07:26 and uh using cannabis and it started up and that's where decriminalization of cannabis

07:34 was in 19 seventies on the west in Oregon. So cannabis and marijuana

07:42 still placed on schedule one by the government and schedule one means that this

07:50 a substance or, or drug that dangerous, that is addictive and has

07:56 medicinal values or applications officially. So we know, laws are always behind

08:01 the federal level, on the state , you're like, wait a

08:05 there's medical cannabis, you told us the state of Texas and in and

08:08 Colorado and everywhere around this country for most part. So how is that

08:14 from the state? Laws from state are different from federal laws while they

08:18 , we all know. Again, is the reality we live in is

08:22 federal law for abortions or a lack . And there are state regulations and

08:28 for abortions as well. I'll do two co exist. This is the

08:32 States of America. The matters are and the federal government is typically lagging

08:38 of anything that is emergent or And the states like on the west

08:43 are typically the ones leading the then they're joined by north east coast

08:48 the Middle America fills in eventually. the laws change as the case is

08:53 Canada, for example, that is now. So now we criminalize cannabis

09:00 the thirties, but we really don't what we criminalize. We just know

09:03 when people smoke marijuana, they get and when they get high, they

09:08 a different effect from that uh cannabis or if they ingest a tincture,

09:15 get high, but then they get and then they go to work and

09:18 they get high and it's a and a drug that doesn't kill people,

09:22 we don't understand what's in it until is this technique that's invented high performance

09:29 chromatography or H P L C, analytical chemistry technique used to separate,

09:34 and quantify each component in the So the way it works is that

09:40 example, if you are and the times were preparing any tinctures and you

09:47 so dissolve something, you dissolve some substance, you put some leaves and

09:52 alcohol and you swish it around and you wanna know what have you extracted

09:57 those leaves. So you would put component, whatever you extract it.

10:06 if you pass it through these OK. It's liquid solvent containing the

10:13 through a column, fill with a absorbent material. And from this

10:19 it goes into this H P O column and each component in the sample

10:24 slightly differently with absorbent material in this , causing different flow rates for the

10:31 components or active ingredients, chemicals in mixture and leading to the separation of

10:39 active ingredients as they flow out of column. And then we have a

10:44 in the sixties and and and Uh it would be like a little

10:49 that would print this. Now it in digital on the computer and what

10:54 tells you is that each one of peaks is a certain substance, a

10:59 chemical, certain active ingredient and it you also the amount a percentage of

11:07 active ingredient within then whatever mixture you're . So a lot of analytical chemistry

11:17 that study botanical preparations, safety metal contaminations, pesticides, herbicides will

11:24 using this type of techniques. There's mass spectroscopy that would be added on

11:29 , for example. But this technique botanicals will produce and you will hear

11:35 word for products that are especially for , cannabinoid products, CVD products,

11:42 products and some other botanicals like If you are buying some turmeric extract

11:49 something, it may have what is the C A, which is a

11:53 of authenticity or a certificate of which says that a certified analytical lab

12:01 tested this preparation and has found certain of chemicals in it at certain concentrations

12:07 hopefully found no contaminants, no metals such. So the point being is

12:14 we have this technique and this technique 1964 is being used by Rafael

12:20 Doctor Rafael Maul passed this year about month and a half ago. In

12:25 nineties, Rafael Masullo uses uh uh chromatography and isolates him correctly describes the

12:34 of delta nine T H C or nine tetra hydro Komal. OK.

12:43 nine T eight C. And it's , there's a wonderful movie online about

12:48 discoverer about Rafael Shula that he discovers H C. And of course,

12:54 any good scientist before he tries to any experiments on animals or on

13:01 He takes some of that T H home and invites guests and his wife

13:06 uh bakes a chocolate cake and there eight slices and each slice has 10

13:13 of Dolphin line THC. There's eight , eight guests and this is in

13:20 and they have this chocolate cake. this is 19 sixties nobody really knows

13:24 is an active substance, one we're not talking about cannabis,

13:29 So he sees a different the fact a couple of people are laughing their

13:34 off. A couple of people are and talking and then somebody's having a

13:40 attack and anxiety attack and they're withdrawn the group. And to this

13:44 we know that Delta Nine T H has a different effect in different people

13:49 has a negative effect on a portion people. It also has negative consequences

13:54 use of cannabis or Delta Nine T C as well. So now Rago

14:01 does that, he also does some with monkeys, does some experiments with

14:06 and then a lot of the research is beneficial that shows beneficial effects of

14:12 H C or any cannabinoids or cannas marijuana becomes systemically suppressed and you cannot

14:19 funding for it. And this is fact too, this is just the

14:24 . So if in the eighties, wanted to apply for a grant and

14:27 saw a positive effect from cannabinoids, agencies would ask you to articulate.

14:32 you prove that it has a negative instead and then you are more likely

14:37 get funding. So there's this bias is, you know, going through

14:42 through the government and goes into the agencies and affects all of the academia

14:48 all of the research. And to date, we can get schedule one

14:54 . Water on Sigma Out Bridge is catalogs that will get shipped in and

14:59 put it on the shelf and we 50 different vendors trying to sell different

15:04 one substances that are synthetic including Delta IC. But to this date to

15:11 in a cannabis plant, a marijuana to study in the lab to do

15:16 in humans. Despite the fact that is vastly prevalent through these different programs

15:21 date, it's still very, very , very, very restrictive. So

15:27 had very limited access to federally approved that are allowed to provide this cannabis

15:35 for research plant. Now for synthetic H. So you go out and

15:39 any catalog off the shelf with any chemical company and and they will be

15:44 them. So again, this still , the stigma coming out is

15:50 we're still not done with 100 It's going to be another 10,

15:53 years before all of this kind of more implemented into, into reality.

16:00 since there's a discovery of natural T C and that T H C is

16:04 from cannabis extract, he actually takes from the police station and isolates T

16:11 C from hashish because people are using and it's not a different drug.

16:15 just a concentrated form of marijuana, concentrated form of cannabis and he isolates

16:21 C from that. So now we that in the plant in that concentrate

16:25 the plant is in ingredient Delta Since then, there's pharmaceutical preparations to

16:31 synthetic Delta nine T H C navi . Typically 2.5 mg T H C

16:39 you ingest for IZED stimulation, it's anti and also anti wasting and

16:48 and radiation therapy. Typically in advanced of cancer and terminal illnesses. And

16:55 is really interesting that this came out the eighties because the hippies discovered this

17:00 the sixties, late sixties and seventies California and Oregon. And they discover

17:06 because there is an uh there's AIDS going on, there's HIV. And

17:15 don't know how to deal with that and AIDS is deadly and this is

17:20 auto, uh it's an immune deficiency disorder. Uh eventually it's so difficult

17:29 person that has advantages of AIDS, go through what is called wasting

17:35 They, they are nauseous, they wanna eat and they're losing a lot

17:39 weight. And what people saw on west coast in Oregon and California is

17:45 they give some of these cannabis, tinctures and concentrates and even inhalation products

17:53 these patients is that their appetite would , they would eat a little bit

17:58 therefore they would live a little bit . Uh-huh. So, you

18:03 of course, the pharmaceutical agencies and that had money saw that capitalized on

18:10 and patented a medication from THC, THC. And that's how typical it

18:17 , right. Somebody's grandmother, grandmother some concoction with mint and lemons and

18:22 else. And it's been around for years and then some scientist picks up

18:27 , you know, has some pain says it help me from pain.

18:29 I'm gonna take it to the I'm gonna research it, find some

18:33 . Usually most of the pharmaceutical drugs we had 80 85% of all of

18:38 formulations that derived from botanicals and then size uh in the lab from

18:45 So they're not plant derived, but don't have planned derived cannabis derived medications

18:51 2005, which is Delta nine T C and CD D. It's a

18:56 to 12.7% T H C 2.5% The vix, it's produced in UK

19:04 a British company and it is still available in the United States. It's

19:10 in over 25 different countries, especially Europe. And it's a buckle

19:16 Buckle spray is a cheek spray. why would you want to spray medicine

19:23 the cheek? Because if you take tablet and you swallow something, it

19:29 falls into P H 3.5 and the juices and start getting digestive. So

19:37 a fraction of it goes into the system and then it gets absorbed through

19:43 digestive system into the blood. And way of effectively getting active ingredients through

19:50 consumption is through the cheek, the of the cheek, sublingual under the

19:56 and upper seal esophagus regions. This where you have the highest abor absorption

20:02 many of the active ingredients. So , pills that you swallow actually not

20:08 effective as some of the oral preparations will prolong the time of that active

20:15 in the mouth or would expose directly lining of the cheek to a spray

20:21 basically, you know, breaks it into smaller molecules in the air.

20:26 use this anti spastic and anti anti spastic spasms and multiple sclerosis.

20:33 we talked about multiple sclerosis. It's autoimmune disorder, demyelination. One of

20:39 mutations and chromosomes and bone. We about chromosome 18, right. You

20:45 to have two bad. All it diagnosed typically in the thirties, symptomologies

20:51 if you'll have tremors, you will spasms and you will have pain is

20:55 have C N S demyelination. you can put it together with what

21:00 example, Rama Chadron talked about how have Sonatas, senses system plasticity.

21:06 you have demyelination of the of the parts of the neurons and motor complexes

21:12 basal ganglia, different areas of the . And that will result in poor

21:18 . Let's say if it's in the system, motor cortex, a matter

21:21 sensory, poor gait, poor poor motor coordination, abnormal signals from

21:28 motor cortex may cause lock up and of the muscles and spasms can be

21:34 and they don't always have to be in the arms or limbs. They

21:38 also be in the diaphragm, which be deadly because you need diaphragm to

21:43 and relax in order for you to . So, it's an anti spastic

21:48 anti pain and multiple sclerosis and a medication that was produced by the same

21:54 companies that 10% can have a dial CV D and CBD is the second

22:00 prevalent phyto cannabinoid. So, these synthetic cannabinoids, both of delta C

22:07 these are phyto cannabinoids, which means they are extracted or derived from the

22:13 plant that um for the um is the pathway that you learned last unit

22:23 it um does uh a negative feedback this side as well? We're in

22:34 . It's a very good question. you know that most of the drugs

22:37 the pharmaceutical level? They don't even exact mechanisms of action for drug to

22:43 on the market? You don't really to know the exact mechanism of action

22:46 because there are disorders, for like depression, what you need to

22:51 is that the drug is safe and and you do that through a number

22:56 clinical trials. So you start with research and your typical in rodents and

23:02 you do clinical trials. And if show in humans that certain combination like

23:07 to 1 T H C to CV anti spasms. You don't really have

23:11 show the mechanisms by which it alleviates spasms. And there are some,

23:16 you will see some short term mechanisms phyto cannabis can act like endo

23:21 So they can regulate neurotransmitter release. can regulate potentially over excitation and too

23:28 of the glutamate release. Maybe that's you're going. But it can also

23:31 slower processes such as inflammation and inflammation also contributing to abnormal neuronal activity and

23:40 and potential lockup of these muscles and . And of course, if you

23:44 something bucky, it's systemic. You , of course, MS is the

23:50 nervous system disease, but the consequences be still systematic throughout the whole

23:56 And here is a substance that is systematical. It will have an effect

24:01 the brain through this buckle absorption into bloodstream into the brain, but also

24:06 the whole body too. Now, 10% CD D is an oral solution

24:14 , tincture, that's anti convulsive or seizure medications for Dr syndrome and Len

24:21 . So if you recall, we this concept of medical cannabis when we

24:28 about Dr syndrome. Last lecture, a mutation C N one A gene

24:34 mutates voltage gated sodium channel that causes I severe my chronic epilepsy of

24:41 which is also a syndrome. So is the medication for drive A syndrome

24:48 Leonard gestal epilepsies, which are also form of very severe childhood epilepsy.

24:56 , and that's all folks. So uh 64 it's gonna be 60 years

25:02 2024 uh millions of people have used and cannabinoids around the world. Hundreds

25:12 millions, there's states, 37 or states that have medical cannabis programs in

25:20 , they're alone. It's a very program, but it's over 50,000 patients

25:24 Texas alone. But from pharmaceutical you basically have two choices T H

25:34 synthetic in this country, synthetic PC CBD. So for, you

25:41 chemotherapy treatments, terminal illness or for intractable severe forms of and that's

25:51 So we'll see what the next uh years, 30 years brings because in

25:57 development, we quite often see what called the first generation, second

26:01 third generation drugs. And there's a of breakthroughs that happen. And I

26:05 believe this is an unprecedented opportunity for community to start understanding what the dispensaries

26:13 the cannabis companies are preaching that you to take this 1 to 13 to

26:18 , 15 to 7 and you're gonna , it's gonna help you from pain

26:22 you're gonna do this. There's no for these specific formulations, there's a

26:27 of evidence of positive effects, but is also evidence of negative effects.

26:33 that's why doctors would still recommend pharmaceutical because they safe in applications as far

26:38 the negative effects of cannabinoids and cannabis talk about it in a second,

26:45 the reason why we have such I don't know, affinity or strong

26:54 also from cannabis or cannabinoids into our . Then through the ages and cannabis

27:02 because we have other phenomenal system. talked about CV, one receptors and

27:06 two receptors in the brain. But a much larger system that is a

27:11 system is one of the major body brain homeostatic and regulatory systems and uh

27:21 , major components. There are two leuco, there are other leos,

27:27 the two major ones are an anam two A G and two major cannabinoid

27:35 . So CD one and CD And apart from being expressed in the

27:40 , C B one and C B receptors will be expressed throughout the

27:45 C B, one receptors in the are dominant in neurons and C B

27:50 receptors are dominant on glial cells in microglial cells. Now, this is

27:57 endocannabinoid and this is the phyto cannabinoid nine T H D. So you

28:02 see that there's structural resemblance and just endo cannabinoids interact with the CD one

28:09 CD two receptors, phyto cannabinoids. there's a variety of phyto cannabinoids.

28:14 C DH C A CD D CD A CD G, CD D

28:18 CDC CD G. There's a whole of phyto cannabinoids. Most of them

28:25 we know are called major phyto DH C CD D and CD

28:30 But then there are minor phyto That means that they're not as abundant

28:35 nature or rare PTOs. Uh There's whole uh slew of them and we

28:43 don't understand uh a lot about a of their functions or interactions or different

28:49 of how it interacts to cause any effect. However, I look a

28:55 gets activated, really earned early on a newborn has to start suckling uh

29:08 milk, mother's human milk increases the of endo cannabinoids. In particular in

29:16 , think about it if T H or smoking cannabis or consuming T H

29:22 makes people hungry, that's what was from wasting syndrome, right? I

29:27 it will increase appetite and let people a little bit anti nausea. So

29:34 and amide acting, the CD one is not only controlling CD two

29:38 not only controlling that neural transmission, it also is encouraging promoting hunger so

29:46 the so that the person could so the person could eat basically and continue

29:53 . It gets activated with pain and . So it's a modulatory system for

29:59 and stress. So endo cannabinoid production newborns with suckling with pain and stress

30:07 immune function. CD. Two receptors predominantly expressed in the parts of the

30:14 , bone marrow spleen that are going a massive immune response and uh sorry

30:27 you have a response to to Of course, memory, it can

30:35 memory and it will actually help us things. So, and the cannabinoids

30:41 forgetting things endogenously is an important mechanism survival. Because if you lose somebody

30:52 you love so much, you are this overwhelming state of grief. But

30:59 a few months later, a few later, people are no longer in

31:04 state. And part of that is forget things because if we didn't forget

31:09 , especially negative or bad things, distressing things, we could possibly not

31:16 about our life in a normal So it's a normal protective mechanism.

31:22 so and the cannabinoids will be kind a regulating in a way the forgetfulness

31:28 the forgetting in memory. But it's important in the plasticity and encoding uh

31:35 , of the information. Uh it's activated with inflammation. So CD two

31:43 and marco glia release cytokines, they the immune and inflammatory response in the

31:50 . It's also involved in thermal regulation has other effects. So these are

31:56 cannabinoids and because phyto cannabinoids will interact the same system, end the cannabinoid

32:03 , they also have similar effects of , stress modulation, appetite, memory

32:11 , inflammation, and so on. how you consume medicines. I've talked

32:20 this from the very beginning because I that some of you are going to

32:24 on and develop really smart pharmaceutical neuroprotective preparations, anti neurodegenerative drugs because

32:33 taking my my course and you love . So some of you will pursue

32:39 to always tell you to think about . You know, you ingest anything

32:43 talk about. If you ingest anything is the effect immediately you have a

32:50 or you have pain in some joint something and you take a couple of

32:54 , you know, it's not like seconds later, the pain is going

32:58 . You know, the doctors will you wait 15, 20 minutes,

33:05 ? And so if you ingest cannabinoids any cannabinoid preparation, the reason why

33:11 talk about that is because you will about these things called the gummies.

33:17 heard about the gummies, right? is in the gummies. Now,

33:21 and beetroot is in the gummies and is sold in the gummies too,

33:27 medicinal way of delivering substances. Uh nonetheless, it's oral and Josh.

33:35 it's better if you instead of chewing swallowing because this is what you do

33:39 gummies. It's similar to the the tablet you put in your mouth

33:43 table. What you swallow with gummies 12345 chew and you swallow it with

33:52 . They get distributed throughout your buckle sublingual areas. So it's a better

33:58 of delivering. But unfortunately, there that many of these format products in

34:05 either pharmaceutical world or in medical cannabis . Another uh way that is very

34:13 is topical aluminum. So creams there are CV one and CD two

34:21 on the nerve endings. That we . Remember the soma of sensory motor

34:26 endings that are there, there are , one CD, two receptors in

34:30 nerve endings. So it has to a transdermal preparation has to cross the

34:37 . And if you're making a product a cream and it doesn't cross to

34:41 these canna receptor swab, we're not what effect it's having. But there

34:46 a lot of topical preparations uh out from cannabinoids, but there's also no

34:52 preparations on the CV S shelves that 10% menthol with count four. You

34:57 , if you have an injury in knee, rub it on, you

34:59 , it keeps it cool, keeps warm, it helps, it really

35:02 . You know. So there are things there, but we don't understand

35:06 on the side of the cannabinoids, we do know that it will control

35:11 and can control pain too. Now, if you have oral ingestion

35:19 lot of times with cannabinoids and with pharmaceutical medication, people will say start

35:25 , go slow, which means take . Advils don't take 16 and wait

35:30 15, 20 minutes. If the is still excruciating, maybe take a

35:34 more, but then lay off for hours. You come on because it's

35:38 affect your metabolism. It's gonna affect bla now you're taking something potentially like

35:43 that is DH C that causes a effect. So you have to start

35:48 , go, slow, start, , go slow. It has a

35:51 fact, it depends on your Some things, you know, most

35:55 the time the Ibuprofen preparations are standardized you're taking a anti analgesic, you

36:02 , and you'll feel in the fact 10, 15 minutes, a lot

36:04 the products that are on the medical cannabis market, vitamin gummy

36:10 we don't know that there's no standardized of prepa preparing these different gummies.

36:15 some of them may have an effect , 20 minutes later, some of

36:19 half an hour later and some people hours later. And the fact once

36:24 is through consumption is for cannabinoids is 6 to 8 hours. It's a

36:30 effect. And most of the poisonings most of the da danger from these

36:36 uh ingestible cannabis products comes from when land at Denver airport and where is

36:42 dispenser? It's a very popular Google in Denver, where's the nearest dispensers

36:46 the airport? And they go through and they get their gummies and they

36:50 back in the Uber, you to go to the conference or to

36:53 to the hotel or something like that they, you know, take a

36:58 and then, you know, they in the car and Uber and

37:02 you know, so it's another half hour and 15, 20 minutes,

37:06 know, they ask their friend, you feel anything? No, I

37:08 do anything. Do you feel No, I don't do anything.

37:10 take another one. So, and where issues begin because then they take

37:15 one. But then at the same the first one starts acting and it

37:20 oxidized T H C gets oxidized in liver. Delta nine into the 11

37:24 , 11 0 H T C which has a intoxicating or high causing

37:30 So now we getting a double whammy the first gun is starting to act

37:35 an hour into it. And you're get another wave of that second one

37:40 was swallowed maybe 15 or 20 minutes , it could be an additive effect

37:44 it causes problems. Now, this also the most common way that Children

37:49 poisoned because the products are prepared to like rice crispies and you know,

37:54 gummies and such and when adults use and leave them unattended and pro in

38:01 storage gives good hold of these gummies set the, you eat them.

38:05 get poisoned. You can overdose from from cannabinoid. They go into

38:10 into the hospital, they get their washed out, you could pass out

38:14 a night and they go to school following day. But it's a traumatic

38:19 , you know, especially if they very young Children to go through all

38:23 this. So the whole marketplace and have to be a lot more responsible

38:29 things that you know, look and like they're made for Children, but

38:32 really more adult, you know, or intoxicating uses like alcohol. You

38:38 be leaving, you know, little bottles that look like Squire juices

38:44 kids, you know, uh to take on the way to school

38:47 their lunch boxes. That's just, know, the way it is so

38:52 to be responsible. The market has be responsible. Now is that the

38:57 way to get the canal in the populous is done is the second most

39:01 still is in the use of cannabis marijuana is in relation to smoking and

39:06 vaporization. The difference between smoking and is in smoking, the the matter

39:12 being burned. So it's typically 400 and above to 1000 centigrade and vaporization

39:19 are built so that the heat, temperature below 400 centigrade, they heated

39:25 about 303 150 C. And that's a lot of active substances from

39:31 cannabinoids and also turbines will evaporate without combustion without burning the matter. So

39:38 really a safer way is vaporization. the millennial generation is the first one

39:45 is using more the vaporized products and rather than the smokable or uh combustible

39:52 preparations from, from, from cannabis from tobacco as well. So

39:59 it's, it's, it's also uh modern way of thinking that uh there's

40:04 lot of harm from combusting and And uh we really need to know

40:11 the benefits and the harm from the ingredients that we can either extract or

40:16 without burning. Suppository uh is another way of getting cannabinoids into the

40:23 Why is inhalation or suppository grade? when you inhale something, it goes

40:29 your lungs, it goes into your vessels, it goes into your

40:34 it's not going into your stomach, not going into your digestive system and

40:37 going into the blood. Ok. suppository AOL or vaginal suppository is the

40:44 way. There's a huge blood uh supply in those areas, huge sensitivity

40:50 delivers it directly into the blood And so it bypasses the liver metabolism

40:56 you would have through the digestive So you have to think about,

41:02 know, how different preparations are used this, just not just with cannabinoids

41:08 any pharmaceutical preparations. And that's something you should think about also. And

41:14 as you pursue anything in the health field, let's talk about some basics

41:20 cannabis. I call this cannabis and is one oh one. We have

41:25 legal hemp. So United States federal allows for the growth production, processing

41:32 sale of what we call hemp or hemp, which are typically these tall

41:38 , although they don't have to be they, they by way, 0.3%

41:43 H C in this country or So T H C is still viewed

41:47 it's an intoxicating canna. We understand industrial purposes, we don't want any

41:53 substances in there. We're gonna keep and most of Europe is a 0.2%

41:58 H C Italy decided it is going be 0.6% T H C in

42:04 Switzerland says it's gonna be 1% Czech said it's gonna be 1%. So

42:10 does that mean? Is a real separation between industrial harm? He plants

42:18 medical marijuana. There isn't, there's regulatory separation. The regulators in the

42:25 States said that it's 0.3 regulators in said it's 0.6, it's country by

42:33 and that's why it makes things even complicated because there's international trade, there's

42:38 trade to it in this country as . So it's a complicated matter.

42:41 typically these plants have grown for many purposes, really all and skinny I

42:47 H C calendars can contain up to 36% T H C by weight in

42:53 flour uh and typically grown smaller or least bushier and shorter to increase the

43:02 of the production of what are called here for the cannabis flowers and they're

43:08 concentrated, you know, female flowers ham. It's typically mixture, female

43:14 male flowers. Because for him, will grow for seeds because seeds will

43:19 a lot of really good oil and oil and a lot of protein in

43:23 . Ok. So, and you do that with this because you don't

43:26 it, you typically drug meats or products and you're trying to drive the

43:32 H C level for intoxicating or medicinal because active ingredients can do both just

43:38 antiepileptic drugs that can make a person stop the seizure through activation. It

43:45 make them intoxicated, feeling like So the same is with, with

43:50 preparations, the high concentration, if a psychotropic molecule, intoxicating molecule,

43:57 higher intoxicating effect but potentially a a medicinal effect also and also a higher

44:04 effect potential as well. This is natural cannabis and can, this is

44:12 . This is going out of fashion little bit because these other things,

44:15 delta eight T H C and delta T H C came into the market

44:21 well as hexahydrate, Cannavino H H and they're semisynthetic cannabinoids. But just

44:28 few years ago, this is fake chemicals that are produced synthesize that are

44:34 synthetic cannabinoids. And the difference is the binding properties. So natural cannabinoids

44:40 they bind to CV one receptor. CV, one receptors will regulate calcium

44:47 , presynaptic through metabotropic signaling. So binds to CV one receptor and

44:52 it's called a partial agonist, binds and then it it dissociates from

44:58 receptor. This is a natural You know, when you synthesize something

45:03 synthetic, it can be a full , which means it binds to that

45:09 won't leave it alone for two So when we're talking about these effects

45:14 for 6 to 8 hours through ingestion inhalation is typically 33 to 4 hours

45:20 cannabinoids, phyto cannabinoids. Then you're about cool agonist that may have an

45:25 for two weeks for three weeks. means it's gonna change potentially permanently brain

45:31 and even the wiring of some of neuronal networks and could cause chronic mental

45:37 , especially with synthetic annoy. So is danger from consuming mostly high levels

45:43 T H C. And it is recommended for people that have psychological problems

45:49 have psychosis that are psychosis prone. it is, you know, adult

45:57 or recreational is available in many different States and countries around the world,

46:02 few countries around the world. So can tell adults what to do.

46:06 for medicinal purposes, you want to a medical supervision and you want to

46:12 sure that you're consuming the molecules that been analyzed through H P L

46:17 So you understand what are the active ? What are their concentrations that your

46:21 understands that that is being used for purposes and even for recreational purposes because

46:26 consumers are becoming way more aware of active ingredients, right? Way more

46:33 of natural vegan. Uh No, GMO. Your generation, you guys

46:41 for different symbols of products whether it's products or food products that,

46:47 for, for a lot of it has to check off some

46:50 No GMO vegan. I'll take you know, or others, you

46:54 , organic, it's fine. I'll that, you know. So now

47:00 synthetic substances are typically applied on the matter. They're dangerous. They can

47:06 pros psychotic, they can induce schizophrenia by a single or two time

47:12 So, a lot of synthetic stuff just horrible. We can regulate natural

47:19 that stinks and everybody knows what it . Our lives would be really better

47:25 there's a lot of synthetic stuff right . It's fentaNYL. Minute amounts,

47:32 mg, no smell, some something somewhere you're dead one time

47:40 Ok. So this is, this really dangerous stuff when people start

47:45 when humans start synthesizing, when humans that there's an effect that we can

47:50 somebody even more addicted to this version fentaNYL. Now, that's pure evil

47:57 the, the reason why people don't from people buy a lot of

48:02 The people, why, why people die from cannabis or economics is the

48:09 mic range of any system. And is my best explanation is that for

48:16 , if you're taking opioids, let's even talk about fentaNYL, which is

48:19 very small dose is lethal for I believe it's two mg of

48:24 Well, let's talk about regular opioids the regular opioids have an effective

48:33 What is an effective dose? And do you use opioids from pain?

48:38 . It's typically from pain or analgesia effective dose is, is small.

48:46 means effective dose is, is gonna the pain or alleviate the pain at

48:51 partially or to the extent that it . Now, if you triple or

48:57 that small dose in opiates, it's lethal dose. So when a patient

49:05 taking something from pain or they have opioid pump that they can access to

49:10 they can inject themselves more opiate then if they triple or quadruple this

49:17 , the effective dose that dose is and that's because uh in the brain

49:26 receptors are found in the brain stem the areas that are controlling vital bodily

49:33 , the heart rate and the So we've increased just a few times

49:41 the effective dose. Opioids are lethal a lot of synthetics and fentaNYL is

49:47 same way they're lethal. So why it with, with cannabis? Cannabis

49:54 dose? Well, many different it's different dose. But let's say

50:02 a joint is an effective dose for to either have a medicinal effect,

50:08 marijuana cigarette joint, whatever or has high causing effect. Sometimes it causes

50:16 people to get high, sometimes it's parcel. But let's say one is

50:20 effective dose for either medicinal effect or the high effect to put cannabis to

50:27 a lethal dose, you have to about 1000 joints in about 15 to

50:32 minutes and not even snoop doggy dog do. So. The point is

50:38 this system has a very wide dynamic of the lethal dose is very hard

50:45 achieve. I think if you tried hard with concentrates that are concentrated preparations

50:51 T H C and if you, know, had high heat and were

50:56 , there would be other problems from , from consuming heat from other

51:02 But the fact of the matter, system and the cannabinoid system, cannabinoid

51:07 activation has a very wide dynamic You can, you can use an

51:12 of the rubber band. You know happens when the rubber man gets

51:18 you stretch it a little bit and breaks right. So that's sort of

51:22 like it doesn't have much of a range. So that's the opioid

51:26 it has an effective range, you it a little bit, it

51:29 you die. All right. With cannabinoids and cannabinoid phyto cannabinoid activation,

51:36 have a very broad dynamic rate. you can stretch that rubber band,

51:41 comes back three or four hours later it can be stretched again. There's

51:46 . So for medicinal purposes, people have a small dose of cannabis.

51:51 may need a higher dose. there is a tolerance increase in use

51:56 cannabis. But in, in general substances, they are either full

52:02 they're dirty, they're dangerous combined to cannabinoid receptors in white and end the

52:09 system. The cannabinoid activation has a dynamic range. Therefore, it's non

52:14 but surely you can overdose from cannabis T H C. Uh cannabis parts

52:21 bio active molecules. There are different to cannabis plant. I really like

52:26 plant because the stems uh can be for production of cellulose. It also

52:36 a conductor, very highly conductive uh materials that are even more conductive than

52:43 than graphene. Actually, uh the will not have any cannabinoids, but

52:50 very rich in essential fatty acids. 35% whether these omega three or omega

52:59 . This is what your doctor tells . You have to take olive

53:02 you have to take the Omega So, hemp seed oil that's prepared

53:07 hemp seeds and you buy it anywhere the grocery store. And Amazon has

53:11 of the best ratios of omega three omega six. I can't remember now

53:15 direction, but I just know that's good ratio. I give it to

53:19 dog and I put it on my hemp seed oil and my dog loves

53:23 when I put it in, in her food, um, seed

53:28 has this other substance called camp and and in general there's a whole culture

53:35 sprouts and microgreens, right? You to the grocery store, you can

53:40 a big bag of potatoes for three . Or you can buy a really

53:45 container of microgreens for eight bucks. this was going to be like small

53:50 greens, the bean sprouts, alfalfa like all of these things. And

53:55 reason why is because they're small, typically they have very high levels of

54:00 molecules, very high levels of Ok. So they're babies, but

54:05 are like super rich in nutrients and And this is anti inflammatory that come

54:11 sprout. So don't be surprised uh the west coast, it already

54:15 but don't be surprised that will be , microgreens in the grocery store near

54:19 pretty soon. And uh cannabinoids that talking about T H C CD D

54:26 G, they are produced in cannabis and they're produced in these granular

54:35 And also that's where the smell of comes from because there's a lot of

54:40 that are produced in these glandular So this is what they look

54:47 This is the anatomy where you have cola of the plant, you have

54:51 here, the pistol. And if zoom in typically on the flowers or

54:58 the buds on the cos of these , you'll have these trico that are

55:03 protrusions here and they are biochemical factories for producing cannabinoids and producing tur they

55:12 a specialized anatomy and most of the ingredients are gonna be uh located in

55:19 centralized metabolize droplet where you will have lot of cannabinoid synthesis. So,

55:27 enzymes that will synthesize cannabinoids as well urines, can navigate intermediaries and synthesis

55:36 are located in these disc cells below central metabolite droplet. So there's a

55:42 beautiful anatomy. This is a single uh uh trico and they range typically

55:49 I believe 50 to about 150 micrometers size. So you need about four

55:56 to 10 X magnification to see their , to see their structure properly.

56:00 40 X magnification. And this is cannabinoids are produced. Uh The major

56:07 that are produced by cannabis plan are even T H C CBD or CD

56:12 cannabis plant does not produce T H . It does not produce delta nine

56:16 H C. So it's not it produces T H C A or

56:23 hydro of acid. So if you cannabis plant raw called, you're consuming

56:30 H C A, there was no effect from T H C A.

56:35 the government placed a can on this that produces T H C A doesn't

56:39 able to produce T H C. schedule one, it actually placed a

56:44 plant, a substance that produces nonintoxicating on schedule one, how this DC

56:51 become a neutral form of T H is through the process of heating or

56:58 with T H C A will have coo H group and you basically eliminate

57:04 acid group and turn it into a phenomenon. The plant cannot do that

57:11 . Cannabis plant can burn itself, itself up, put itself through some

57:17 process, through some bath and turn into a T H C. So

57:22 you can see how a lot of the logic behind the loss is driven

57:29 something else than science. It's driven myth, money, special interest.

57:40 unfortunately, that's the situation. I think that these acidic cannabinoids,

57:45 C A CD G A CD G is I used to call it the

57:50 of all cannabinoids, the mother of major cannabinoids, DH C A and

57:54 D A. There's a huge therapeutic to the cytic cannabinoids. And that's

58:00 I wanted to talk to you about . Well, you consume medicine that

58:03 a positive effect means that it calm your seizure inflammation but you are

58:09 Well, yeah, if you consume , you still stop the seizure,

58:12 still high benefit versus harm. And what your doctor decides, benefit versus

58:19 . Now, here these molecules don't the high effect. So you eliminate

58:25 potential, you know, uh associated of a person feeling intoxicated.

58:32 you have the potential of developing pharmaceutical , pharmaceutical anna, but they're not

58:38 stable. You heat the temperature or changes. So the storage to convert

58:44 neutral kommen, they have to come with the different ways of treating these

58:48 cannabinoids versus neutral, can all three them CD G A, DH D

58:54 and CD D A with hero decarboxylate turn into neutral form C H C

59:00 B G C DB. And let's at our C B one receptor.

59:04 if you recall C B one receptors located presynaptic, right? And they

59:12 this, this synoptic, you have P one receptor, an activation of

59:18 B one receptor will typically inhibit calcium . OK. So it blocks calcium

59:26 and it blocks the circular release here the synapse. So, so if

59:34 activate CV one, you control neural . So end of cannabinoids, we

59:40 they were agonous of C B one they activate C B one, they

59:45 G protein cascade and they activate and this case, they shut down the

59:50 of excitatory or inhibitory neurotransmitters, Everybody remembers that from neural transmission

59:57 OK. Good. So T H will act as an uh C

60:04 One result. C B G is antagonist on CV one. So and

60:15 is negative allosteric modulator. So if antagonist inactivates CD one receptor, then

60:22 allosteric modulator dampens CDC D one So what does that mean?

60:30 that means again that we have in plant, the plant itself produces precursors

60:37 as CD G A that can become G that have a completely opposite effect

60:42 delta nine T H C one is agonist that causes a height of

60:48 C B G is an antagonist in moment. So it, it

60:54 it, it doesn't seem right that of them would also, you

60:57 schedule one if one is the bad to see them as potentially almost like

61:03 antidote or something that regulates T H A activity at C B one receptor

61:08 the opposite direction. Physiological direction. general, cannabis has sometimes it's called

61:17 , a plant of 1000 molecules. has at least 500 plus compounds.

61:23 1520 or so phyto cannabinoids, 120 aromatic molecules that are also produced in

61:32 other molecules such as flavonoids and amino in different parts of the plant.

61:38 now these are the effects that have reported on T H C and CBD

61:44 CD G. So with T H , it causes a high effect.

61:48 also a inflator Nero protective analgesic stimulant, anti anti cancer. Does

61:55 mean we have all of these pharmaceutical that I? No? But if

61:59 look at the Texas uh Department of Safety B P S that controls

62:06 the, the Texas, the, Texas program, you know,

62:10 there's cancer there, there's epilepsy there there's over 100 neurological disorders. There's

62:16 again, there's no pharmaceutical drugs, not a federally accepted system, but

62:20 is a lot of it does that that. Yeah, and because it

62:25 not lethal, that's why the local allowed the people to try it.

62:30 side effects you see can cause anxiety panic attacks and it can be bad

62:35 a lot of people can abuse So those, those people, if

62:40 need to use cannabis for medicinal they may not be able to use

62:44 H C at all. There's too paranoia, too much panic and the

62:49 effects uh increases heart rate. It low rate of the tendencies of one

62:56 10, 1 in 11. Uh is called cannabis use disorder, but

63:01 they're functional. So people that have use disorder of defendants in cannabis are

63:07 members of society. Um and uh of them run these multibillion dollar companies

63:15 are on stock exchange, all the publicly traded companies, the CEO S

63:20 those companies that have hundreds of employees such. So there is of course

63:27 different dependency when you talk about when you talk about cocaine, when

63:31 talk about alcohol, which one is dangerous just for depends on an

63:38 you know, addiction or dependency and it's there and how and how people

63:43 with it. It's a very complex hyper syndrome. So high concentrations there

63:49 now these concentrate preparations from cannabis and concentrations of T H C can cause

63:56 neis. It's really painful, it's in the stomach, difficult to

64:00 Uh very uh strong coughing bouts and typically in the morning from the users

64:08 consume high levels of T H So it also has side effects on

64:13 . So T H C and the of cannabis can start affecting short term

64:17 , it can start affecting long term . It's also pro psychotic psychotic because

64:25 it's prone panic attack, pro pro psychotic, you know, so

64:29 person has psychosis bipolar depression. This not the phyto cannabinoid that a supervising

64:36 will probably talk to that person We probably talk about CBD which is

64:41 psychotropic. It's psychoactive psycho non psychotropic it's nonintoxicating. What else is

64:49 Almost everything you consume. Caffeine is . Why is it psychoactive? It

64:54 to the dent of receptor and controls release CBD binds to CD receptors,

65:02 in this case, in a different . Glutamate. Ok. Uh It

65:06 counteract negative effects of T H It can be anti psychotic, not

65:10 protective that all of these positive effects reported from CBD. And I don't

65:16 you to know all of these. just want you to know that there's

65:19 effects and there's also negative effects. mild side effects of the CBD.

65:24 doses of CBD can cause fatigue, and indigestion. But in clinical trials

65:29 in the studies of CBD as pharmaceutical , there's very low rate of withdrawal

65:35 patients from those trials, meaning that , it's not bothering that many people

65:39 it doesn't have that many side effects B G. That's where we don't

65:44 a lot except we know that it CD, one antagonist, partial agonist

65:49 CD two, a lot of these . In fact, CBD also will

65:56 with serotonin. CBD is an agonous serotonin receptor. CV G is an

66:03 and it will interact with other So we don't know much about CV

66:07 which is really the core molecule of cannabis plant. But there are anecdotal

66:12 of uh positive effects of anxiety, and opposing negative effects of T H

66:20 because CV G is an antagonist of B one receptor and T H C

66:23 an agonist of CD one receptor. now you see how this picture is

66:29 complicated with just three major cannabinoids, of these effects and all of these

66:35 conditions that helps and only two drugs that are available for two conditions through

66:41 pharmaceutical prescriptions. Just a reminder we're here in this country, we still

66:49 just this available 10% CD D plan synthetic T H C tablets. If

66:57 want to tell you sea ball or the disk or anywhere, that's,

67:01 maybe um given certain conditions, you get a subscription to it. Uh

67:08 know, this is now a report 2017. Actually, it's a report

67:16 the National Academy of Sciences, Engineering Medicine. We got together the smartest

67:23 , engineers and doctors, together over of them. And they said,

67:27 can you tell us if this cannabis any positive therapeutic effect that this is

67:33 BS? So all of these smart went and searched literature, all the

67:39 , all the resources they had, came up with this report in

67:44 which is now dated 60 years ago . But that report said that this

67:48 of substantial evidence that cannabis or cannabinoids effective with the treatment of chronic pain

67:54 adults antis and the treatment of chemotherapy nausea and vomiting cannabis or can when

68:04 say cannabis, they mean the plant improving patient reported multiple sclerosis specific in

68:13 of oral phenomenons. There's no pharmaceutical for pain for cannabinoids in the United

68:24 . There is only one for spasms pain and multiple sclerosis in UK and

68:32 antia metic anti vomiting, anti chemotherapy, induced nausea and vomiting.

68:39 many people are having chemo, how people having cancer? And there is

68:45 variety of natural phyto Cannavino preparations that pharmaceutical preparations to date. And that's

68:53 this this this pathway is a long . There's moderate evidence on other uh

68:59 such as short term sleep, chronic , uh obstructive sleep apnea, limited

69:06 that are affected for HIV AIDS, syndrome, anxiety symptoms, limited evidence

69:13 this limited evidence of this limited evidence this reducing depressive symptoms. So there's

69:18 lot of evidence, a lot of is limited evidence. Ok. I'm

69:22 end the lecture today here and we'll have to get together on 4 20

69:27 talking about the rest of the, , medical canna. So I'll see

69:32 on Thursday.

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