| 00:00 | Recording in progress lecture routine of cellular . And they will be discussing in |
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| 00:09 | cannabinoid system. Before we get to , the cannabinoid system, I want |
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| 00:13 | to think about different things that you already learned about the brain function. |
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| 00:20 | different cellular aspects in the brain for of circus circuits is built uh nuclei |
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| 00:29 | build cells that become a part of larger system. So we disgusted visual |
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| 00:37 | in great detail, the visual The reason why it's a system is |
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| 00:43 | have many different areas involved in creating visual percept of the outside world |
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| 00:55 | which is a retina processing of that information. OK. Converting the light |
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| 01:07 | electrochemical signal, chemical signal inclusive. it goes into the primary visual cortex |
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| 01:17 | we saw that different circuits and arrangements producing different perceptive field properties and sell |
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| 01:30 | properties in the way. And so ended up with the primary visual cortex |
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| 01:34 | the primal sketch. We talked about retina sees and how this retina |
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| 01:41 | And the center concentric center surround the is the same role and how that |
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| 01:48 | more complex and the primary cortex. is a classical sensory system uh |
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| 02:02 | we looked at another sensory system which olfactory system. And we talked about |
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| 02:15 | components of the factory system. we talked about how there is an |
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| 02:25 | that organ in this case is is nose that contains the epithelium factor is |
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| 02:35 | helium. And so this is where interaction of the odor of molecules takes |
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| 02:43 | and you have a conversion of the here. So in this case, |
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| 02:49 | protium receptors that we described are chemo in a way they're reacting to different |
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| 02:59 | and binding different wagons as chemicals or in particular. But then we talked |
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| 03:05 | how from there in order for us have the perception of smell, that |
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| 03:12 | goes through a number of stops, tertiary and from thin was going into |
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| 03:19 | cortex where we also talked about the and bypass tham also a sensory system |
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| 03:30 | uh say classical uh sensory system and could talk about hearing and then |
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| 03:38 | You would have cochlea and you have cells and that's where the transduction of |
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| 03:44 | and movement, mechanical movement. So have songs that are sensitive to mechanical |
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| 03:52 | , it's also sensory system. So different sensory systems, an auditory, |
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| 03:57 | stimulus you have is light in the stimulus you have is chemical and |
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| 04:06 | . Uh and and and visual it's live and auditory sound, it |
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| 04:11 | factory its cameras. Uh It's a of sensory, it's touch. |
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| 04:19 | So it's a matter of sensor sensor for your body. Uh-huh, that's |
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| 04:27 | classical census. And then we, we talked about neural transmission, we |
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| 04:37 | about he here, the nuclei it's not connected to epoch, it's |
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| 04:48 | connected to retina, not connected to epithelia. So there's the system and |
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| 04:56 | system of immune signaling. In this , none from locus Aurelius or serotonin |
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| 05:03 | ray nuclei. The system is very chemically in mediating our different states of |
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| 05:14 | our behaviors in modulating the brain rhythms modulating the plasticity that the cells have |
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| 05:23 | each other, including the spike, dependent plasticity that we discussed. |
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| 05:30 | are they, are they reacted to or in any stimuli? Well, |
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| 05:37 | , you'll have more of an effort in your brain and the fight or |
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| 05:41 | response. But it's other organs and systems that will do the perception of |
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| 05:48 | visual threats coming at you or factory , nearing you or any of that |
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| 05:56 | to put you in a fly So, so do would be associated |
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| 06:07 | , with different behaviors and impairments in neurotransmitter systems. And the means are |
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| 06:16 | with different disorders. So almost if you have epilepsy and we'll talk |
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| 06:22 | a lot about epilepsy you'll have in brain, we saw you have this |
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| 06:27 | of excitation and inhibition. You have excitatory inhibitory circuits controlling each other for |
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| 06:33 | forward feedback, inhibition, um lateral , you have excitatory lateral connectivity and |
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| 06:44 | it's kept within a certain what we ballad. So you wanna call it |
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| 06:51 | steady state. And that steady state be when the brain is very |
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| 06:57 | performing certain functions on the, when brain, steady state of the what |
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| 07:03 | discussed as the Sentinel state, what is the brain is doing anything when |
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| 07:10 | brain is when you're not actively involved a particular described Sentinel. One of |
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| 07:18 | definitions of a soldier on duty, duties, typically standing or sitting, |
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| 07:28 | it doesn't mean they're not doing they're actually potentially waiting to do |
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| 07:35 | somebody coming in to visit or potential of attack or something like that. |
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| 07:41 | now, so you have this exci balance and a lot of neurological |
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| 07:46 | And we study neurological disorders. You have excitation, especially in epilepsy. |
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| 07:52 | classically described by a balance of excitatory , usually too much lutin and too |
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| 07:59 | inhibition. These systems that are immune . We refer to them as modulatory |
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| 08:08 | because they typically have a longer lasting . They typically with the exception of |
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| 08:14 | Coline, which has ionotropic metabotropic all the and or they function only |
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| 08:21 | a metro signal. They are also systems. That to me is that |
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| 08:29 | projections are rather broad and nonspecific and haven't been really correctly replicated and completely |
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| 08:37 | where they end up projecting different A lot of times is a system |
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| 08:46 | means that the sprinkler is pointed to piece of wall, but it doesn't |
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| 08:52 | and boos may be a little there's a wind this way, it |
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| 08:55 | mean that the same amount of water always drop along the pathway of |
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| 09:01 | of that Sprinkle wall. And that how these immune systems are in. |
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| 09:10 | if you upset i immune system, you have dysfunctions, lower, lower |
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| 09:17 | serotonin or dopamine, you will have neurological disorders that are associated that can |
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| 09:27 | subsequently lead to exci inhibitory imbalance even dysfunction of the immune systems. And |
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| 09:38 | again, you will see, as study neurological disorder, some of these |
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| 09:43 | have been impaired and we'll start, believe with epilepsy action section. So |
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| 09:50 | you think about amino acid neurotransmission, you think about glutamate, I think |
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| 09:57 | fast neural transmission. When I think a mean transmission, with an exception |
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| 10:03 | Acey Cole, I think of a mode transmission module authority because to activate |
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| 10:12 | protein coupled receptor of downstream of factors was the channel open the channel? |
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| 10:19 | will be a difference of about 2040 102 100 milliseconds and amino acid faster |
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| 10:27 | the tropic neural transmission. The synoptic only uh a few milliseconds before you |
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| 10:34 | a response by optic. So amino systems that function through an electro means |
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| 10:42 | also fast, really fast. Metabotropic are slower. Amino acids will have |
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| 10:49 | own metabotropic, like uh metabotropic cypress will also be slow serotonin. |
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| 10:58 | C cola means are all acting through protein couple. So they're all |
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| 11:03 | So it tells you something about temporal and communication. But also it tells |
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| 11:09 | something about, well, if these are acting through G per couple |
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| 11:13 | So that means that they're activating something changing something inside the cell cellular signaling |
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| 11:22 | , which may have a longer impact the cell itself. So maybe they're |
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| 11:28 | to respond to chemicals coming in these . And there are a couple of |
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| 11:34 | and uh and their pathways, but also may have a longer lasting |
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| 11:41 | So now today, we're gonna talk then the cannabinoid system and then the |
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| 11:49 | system, it's different, I guess it's not a sensory system and uh |
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| 11:59 | not expressed and the molecules are under cannabinoids or the receptors or in particular |
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| 12:10 | cannabinoids, they are not expressed in very confined nuclei like with los |
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| 12:17 | it contains only several 100,000 neurons. mean, it's only several 100,000 neurons |
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| 12:24 | . No. So if you were literally carve out buus from the |
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| 12:31 | that will not be more just by out that small, it was amino |
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| 12:39 | as we saw are distributed widely and throughout all of the cells in the |
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| 12:45 | . Of course, you know, get it through the glutamate but |
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| 12:49 | So you'll find cy glutamate sauce and cortex of the, and the |
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| 12:56 | And uh and the same with Gavi in the spinal cord is fly |
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| 13:04 | be a lot of cells but they're everywhere. So you'll find them |
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| 13:07 | . There isn't like one place that can take out and there's no more |
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| 13:12 | . You have to take all of out to, you know, stop |
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| 13:16 | production because all of the cells So that tells you something about the |
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| 13:20 | that's important to know. Where is synthesized? Is it everywhere spatially |
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| 13:26 | Is it confined and it's confined? does it go from there? What |
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| 13:30 | of systems? Very precise 1-1 communicating its neighbor or this kind of system |
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| 13:36 | a spring bus system. So just sure the yard is wet. So |
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| 13:42 | when you look at the endocannabinoid the system contains endo cannabinoid molecules. |
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| 13:50 | two dominant ones and accepted ones are or A E A and two are |
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| 13:58 | Glycerol or two A G. So are the molecules that are produced in |
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| 14:02 | like glutamate just like just like but it turns out that and the |
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| 14:10 | and their respective receptors, C B cannabinoid receptor, one and CV, |
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| 14:17 | canid receptor two are expressed everywhere throughout brain And certain organs are dominated by |
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| 14:26 | of one sub type of receptor with other such is the case with the |
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| 14:32 | which is dominated with expression of CB receptors. And you'll see later that |
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| 14:38 | B one receptors are expressed dominantly and in neurons. CV two receptors are |
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| 14:44 | found in the brain and neurons will CV two receptors but they're dominating and |
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| 14:50 | song Other organs throughout the body will expressing CB one and CB two |
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| 14:58 | So the the, the point of slide is that you have naturally occurring |
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| 15:04 | under geno those naturally occurring molecules are everywhere synthesized. Everywhere you talk about |
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| 15:11 | brain very widely synthesized throughout the So also neurons and That they interact |
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| 15:19 | the endogenous receptor CB one and CB receptors. And that this system is |
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| 15:27 | emerging as one of the most important and regulatory brain and body systems. |
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| 15:36 | we'll, we'll learn more about this . Now, on the right |
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| 15:39 | you have PTO cannas, vito, are molecules that are synthesized or produced |
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| 15:47 | cannabis plants. Phyto means plant, a lot of semi synthetic or synthetic |
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| 15:55 | . But spino cannabinoids are the ones plants have the mechanism to synthesize T |
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| 16:03 | C T line T H C DH A tetra hydrolic acid CPD, |
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| 16:12 | A acid. So there are a of phyto, dozens of them that |
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| 16:20 | available on the on the cannabis Uh Some of them are considered major |
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| 16:30 | as Delphine T H C or CBD there's a lot of the cannabinoid that |
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| 16:36 | plant produces so many different cannabis strains produce a lot of T H |
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| 16:41 | Others will produce a lot of Other cannabinoids are produce as minor such |
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| 16:46 | T H CD, which is And that is because there isn't much |
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| 16:53 | it in nature and plants don't synthesize lot of that in animal. So |
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| 16:57 | called. But our focus is really the endo cannabinoid system. So what |
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| 17:04 | the bio cannabinoids have to do with end? The system is the fact |
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| 17:08 | that bio cannabinoids interact with cannabinoid So just like the endo cannabinoids interact |
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| 17:17 | phenomenon receptor C B one CV the phyto cannabinoids also interact with C |
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| 17:24 | one but not all phyto cannas will with any other receptors in the brain |
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| 17:33 | the body. So what do you to, to, to, to |
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| 17:41 | what are the components in order for to have the cannabinoid system? You |
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| 17:46 | to have synthesizing and degrading enzymes. you have synthesis and degradation, you |
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| 17:54 | to have liens or chemicals in the that are being synthesized by these synthesizing |
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| 18:03 | and then getting broken down by these . Just like we saw with other |
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| 18:08 | , they need to be synthesized, need to be broken down and you |
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| 18:13 | receptors C B one and C B . So, binding of cannabinoids to |
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| 18:19 | receptors which are G protein couple, all metabotropic signaling. They're about |
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| 18:25 | these receptors will initiate a physiological and and motor response to our body. |
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| 18:35 | whenever you think of the body, have to think there's an enzyme that |
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| 18:40 | the molecule, it has to be of it and there's target receptor in |
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| 18:47 | um and it's not just in the , it can be in the plants |
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| 18:54 | . If the plant has a synthesizing will produce that molecule and that molecule |
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| 18:59 | likely interact with the receptors on, , on that plant or it could |
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| 19:06 | interacting with another plant or another insect something CB one receptors in the |
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| 19:16 | As we talked about, They're very , they're primarily expressed the neurons. |
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| 19:22 | as you can see, they're dominant , it says an abundant CB one |
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| 19:28 | in red And moderately abundant CB one in black. So you have in |
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| 19:37 | hippocampus, our favorite structure, both memory stress mediation, emotional responses |
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| 19:49 | So it's interesting how smells must trigger memories through this pathway to the |
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| 19:57 | It's loaded with a CV ware. , so hippocampus is also responsible for |
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| 20:04 | term processing of memory and recall. basal ganglia commission learning emotional response, |
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| 20:13 | control, prefrontal cortex, executive cerebral cortex, higher cognitive functions, |
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| 20:21 | just depends where the cerebral cortex. throughout you know, perception, vision |
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| 20:27 | uh association areas, sara Oscar. now, there are a lot of |
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| 20:35 | areas in the brain where it is but to a much lesser extent. |
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| 20:43 | of interesting ones, I'd like to out is per gray that is involved |
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| 20:50 | analgesia stimulating the receptors are gray, area causes analgesic like response. Uh |
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| 21:08 | of the solitary tract is sensation, , vol. There's a lot of |
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| 21:14 | one receptor II download but it's a of in brain stem. As you |
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| 21:20 | CD receptors are expressed in area that responsible for sleep, arousal, temperature |
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| 21:29 | and motor control. This is important brainstem is responsible for vital, a |
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| 21:40 | of vital functions of the brain and . And this is also one of |
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| 21:47 | explanations. Um why people cannot effectively or die from phyto cannas. Everybody |
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| 22:01 | overdose from everything but die from phyto and consumption because it may screw up |
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| 22:10 | memory, their posture, uh or their cognitive function, their learning, |
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| 22:19 | commands memory in the brain, stomach deregulate their temperature, but it's not |
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| 22:26 | to affect the heart rate, affect breathing Although they are expressed within in |
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| 22:35 | brain. This is this is the control subject or CP one receptor in |
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| 22:39 | heart. So it will affect the rate by binding to the receptor. |
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| 22:43 | from the brain, now, this important because opioid opioid receptors are expressed |
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| 22:51 | the parts of the brain stem that responsible for vital functions such as heart |
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| 22:57 | . And so if there is binding opioids to the brain stem here, |
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| 23:02 | actually has very strong controlled heart rate breathing and it's very easy to overdose |
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| 23:11 | pharmacological opioids and illicit street opioids is . Uh The horrible things going |
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| 23:20 | So we'll talk about this, overdosing little bit later. It's important to |
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| 23:24 | of understand, I think she know depiction of what these different areas in |
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| 23:32 | brain are responsible for. So if recall, this is the ex |
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| 23:40 | partly descriptions, but um these are of the parts of the brain that |
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| 23:47 | involved in the end the canna Now, how does that uh the |
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| 23:53 | system work or what are some of differences from the systems that we studied |
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| 23:58 | learn about? So, first of , when there is exocytosis of glutamate |
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| 24:04 | gap, but let's use glutamate there's going to be influx of a |
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| 24:10 | of calcium and that can be through receptor sample, it can be through |
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| 24:17 | channel and this calcium and this poop will turn on the production of an |
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| 24:29 | and two A G and anandamide comes from the precursor molecules, phospho ethanolamine |
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| 24:40 | pe and Alaine name that then allow the production of and I'm the two |
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| 24:54 | G plus AOL and diace glycerol by precursor. So endo canna sorry endo |
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| 25:03 | synthesizing enzymes that produce two A So we actually are not even mentioning |
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| 25:10 | the the precursor mo in this Now, so there is a certain |
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| 25:16 | of then the cannabinoids that's produced, produced optically. But when there is |
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| 25:24 | levels of activity, a lot of of calcium and the cannabinoid synthesis is |
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| 25:30 | the followed by demand. And more cannabinoid molecules are synthesized but they're not |
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| 25:35 | in the organ else, they're not in vesicles, the lipid soluble. |
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| 25:41 | they will cross through the plasma membranes C B one receptors are located predominantly |
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| 25:47 | neurons presyn optically. So, binding endogenous to C B one receptors through |
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| 25:53 | protein coupled signaling will reduce calcium And if you remember, presyn calcium |
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| 26:01 | necessary for the release of the neurotransmitters . So this is a negative feedback |
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| 26:09 | . A lot of activity, increased of endo cannabinoids, retrograde. This |
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| 26:15 | referred to as retrograde signaling from S B one receptors and closure of calcium |
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| 26:24 | through G and complex. Therefore, the release of glutamate, you have |
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| 26:31 | lot of glutamate. If you have lot of calcium and you don't have |
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| 26:35 | feedback mechanisms through the cannabinoids or other you can get the system into excitotoxic |
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| 26:43 | where cells with too much glutamate and much calcium will start dying. |
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| 26:50 | and the cannabinoids again here are positioned nicely in balancing the amount of excitation |
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| 26:57 | this excited toxicity that could be produced the system because there's the more excitation |
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| 27:03 | is here, the more depolarization there here, the more of the phenomenons |
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| 27:08 | going to be produced and then they try to tame this presyn optic neurotransmitter |
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| 27:14 | . So a lot of con refer depolarization, induced suppression of excitation, |
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| 27:21 | , induced, a lot of depolarization its own suppression of excitation. But |
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| 27:29 | is a uh simular control of inhibitory by endo can. So this is |
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| 27:36 | unique to glutamate. It also applies gag synopsis and there it's too much |
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| 27:44 | too much um inhibition and synoptic activity to Gava that produces more of |
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| 27:53 | So, this system was discovered in , Just discovered the endo cannabinoids and |
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| 28:03 | receptors in 1990s. So we don't some things about it is because it's |
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| 28:07 | fresh. No TV, tourist doctors located in and uh if they astrocytes |
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| 28:20 | are involved in synaptic transmission and synaptic , but if they're not like |
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| 28:27 | they're involved in other processes like inflammation cytokine release and cytokine regulation. So |
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| 28:34 | talk about this for a second. CV, one receptor, if you |
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| 28:39 | about it are affecting fast neural controlling glut and Gava a dominant in |
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| 28:48 | over glia. And by that virtue faster in its response CB one |
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| 28:58 | although it's still g protein couple but it's faster because it is regulating |
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| 29:08 | processes. Ok. It's reg regulating faster response processes between neurons and not |
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| 29:15 | transmission CD two receptors. A lot them are expressed on microglia microglia are |
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| 29:24 | in inflammation regulation. Uh neuro IUN in the brain and CV two receptor |
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| 29:34 | regulates the amount of cytokines that are released by leon sales. And in |
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| 29:41 | , because they're acting through real they're concerned more with the slower response |
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| 29:51 | . Think about CB one, more faster neural transmission regulation. CP |
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| 29:56 | more about control of slower mechanisms that last people, hours, days, |
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| 30:03 | , inflammation, cytokine. So even this metabotropic system, you have two |
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| 30:12 | scales from regulation. As I one is when you're regulating faster |
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| 30:17 | that one when you slower processes uh then the cannabinoid system gets |
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| 30:31 | I'm gonna come back to the previous gets engaged with stress trauma, hyperexcitability |
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| 30:37 | inflammation. The response of then the system is eat, it makes you |
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| 30:49 | . And the cannabinoid production kicks in early and it actually encourages uh newborn |
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| 30:54 | from mother's breasts. As mothers with babies start producing higher uh levels can |
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| 31:03 | milk. So it generates their appetite . And this is one of the |
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| 31:09 | functions of stimulating the cannabinoid system is eat. The other known function is |
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| 31:18 | rest or sleep. The other one forget because memory you can remember, |
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| 31:26 | also it's also good to forget things that is uh part of our emotional |
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| 31:34 | response protect. So if that there's much excitation, it's gonna in the |
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| 31:40 | , it's gonna have neurotransmitter control, gonna have neuro protection, it's gonna |
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| 31:47 | excited, obesity, calcium, obesity, it's gonna balance excitation and |
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| 31:59 | , but also throughout the body, gonna regulate balanced. That's what homeostasis |
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| 32:05 | . Sort of a balanced state, state. Even if it goes out |
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| 32:11 | its or to the bottom of this range, it still gets balanced, |
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| 32:16 | back in. So those are all the ways that you get engaged in |
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| 32:22 | cannabinoid system. And those would be different functions that it serves because it |
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| 32:28 | expressed in so many different brain So many body orients, there's no |
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| 32:33 | to really say that this is what does, this is what it |
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| 32:36 | it makes you hungry, it makes sleepy and does a lot of different |
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| 32:40 | because of its wide distribution. And interestingly, these uh reenters are the |
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| 32:51 | predominant G couple receptors are the most there. Most of those Sarus expressed |
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| 33:01 | the brain compared to either or So it, it's, it, |
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| 33:06 | is meaningful. It has a really strong impact. I wanna talk a |
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| 33:12 | bit about um marijuana and the munchies we just talked about the olfactory |
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| 33:24 | So what we have and the so C delta nine T H C will |
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| 33:31 | B to C B one receptors and known effect of consuming cannabis or consuming |
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| 33:38 | , consuming T H CS and it people hung. It's not only, |
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| 33:42 | only a known fact, it's also lot of medicines, pharmaceuticals including that |
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| 33:48 | developed out of this knowledge and it's around for thousands of years. So |
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| 33:59 | what is the circuit here? It's familiar circuit or factor receptor neurons that |
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| 34:03 | discussed that goes into the um will evolve. OK. In the olfactory |
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| 34:15 | , you have the second order olfactory and carry that information to a factor |
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| 34:23 | . Eventually it's simplified back to the . You have the cell which is |
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| 34:33 | cell maternity, excitatory cell that contacts inhibitory granu cell here. This inhibitory |
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| 34:43 | cell inhibits the secondary order neuron. when cortex or factor cortex activates this |
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| 34:57 | onto the inhibited gradual cell, you some smell down regulates your perception, |
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| 35:07 | . And one of the things that alluded to last lecture is I said |
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| 35:13 | sense of smell is not just what inhale into the nasal cavity, but |
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| 35:21 | would you ingest into the oral cavity as you ingest food and you hm |
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| 35:31 | on it. Mastic the turbines and odor molecules will rise to the top |
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| 35:42 | the nasal cavity and it will give flavor. So a chocolate chip cookie |
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| 35:49 | not just taste sweet, have a of chips and dough, but it |
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| 35:56 | actually taste like chocolate and vanilla, sugar. And what else is in |
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| 36:05 | . So a lot of what we and the flavor that we receive is |
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| 36:11 | of the factory system. Now, is also known that when you consume |
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| 36:19 | or marijuana. It makes it gives munchies. The story behind. It |
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| 36:25 | really interesting. So medical marijuana is prescribed or illegal. It means to |
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| 36:30 | , this is an old book by . It means to stimulate appetite in |
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| 36:33 | with chronic diseases such as cancer and compound that inhibit C C B one |
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| 36:43 | was also developed as an appetite However, human drug trials had to |
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| 36:48 | discontinued because of the psychiatric side effects a lot of suicides. People. |
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| 36:54 | reasoning behind it, OK. If stimulate CD one receptor, it gives |
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| 36:59 | munchies Get too hungry, you gonna more, you lose, you gain |
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| 37:06 | weight. It be awesome if we an obesity drug and block CB one |
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| 37:14 | and they had to drop out of trials because of the psychiatric uh suicide |
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| 37:19 | on on participants. That's because it's over the great structures. So it's |
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| 37:28 | just in the society centers, it's , you know, just in a |
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| 37:33 | system that we discussed, but it's , right? So we have to |
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| 37:38 | now. Uh Where in the brain one receptor actually stimulate appetite, not |
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| 37:45 | , C21 receptor is associated with parents many regions. Surprised to learn in |
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| 37:54 | that appetite stimulation comes from enhancing the of smell. It's actually pretty uh |
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| 38:05 | in uh stimulus, you walk by around around lunch time and just want |
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| 38:14 | put something in your mouth, you that's what smell. So, so |
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| 38:18 | know that, so that that means if you enhance the sense of |
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| 38:24 | you're gonna be more hungry, So uh we discuss how small activate |
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| 38:34 | factor evolve and turn the information to factor cortex. The cortex also sends |
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| 38:40 | projections to the bulk and sign So to to engineers bulk stuff. |
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| 38:44 | this is really cool, right? you don't have projections from cortex back |
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| 38:50 | the retina, but you have projections . Well, you don't have projections |
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| 38:56 | the factory receptor neurons, but you projections into the second record neurons, |
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| 39:03 | . So this would be like an of maybe uh you know a secondary |
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| 39:07 | station secondary area when you send the back. And what it does is |
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| 39:13 | if you inhibit, if you excite inhibitory cell, this inhibitory cell inhibit |
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| 39:19 | order or bacter neuron, they inhibit uh so they inhibit these cells and |
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| 39:26 | can reduce the size of spine. these cells, these, these neurons |
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| 39:33 | optically gluon cells, they contain C one receptors. So when T H |
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| 39:40 | is consumed, which is the major high or euphoria causing and also um |
|
| 39:49 | stimulating molecule. So when T H , when the person is exposed to |
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| 39:55 | H C ingested or whatnot, It CD one receptors on glutamatergic cells and |
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| 40:03 | reduces glutamate release by reducing glutamate It reduces the inhibition by reducing the |
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| 40:13 | , it enhances the perception of. this is the circuit behind the |
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| 40:24 | So let's think about that. That that if you're producing a lot of |
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| 40:29 | , you're also gonna have potentially really appetite, It stimulates CV one |
|
| 40:43 | enhancing a sense of smell and you know, and so a really |
|
| 40:49 | outcome, good way to gain That's not something usually people look |
|
| 40:54 | And typically, you know, there all of these programs and offices for |
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| 41:00 | too loss recently. Everybody's people that, that sense, they won't |
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| 41:07 | low, they won't see and then started losing weight. It's one of |
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| 41:11 | side effects. You may lose That was enough, right? That |
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| 41:16 | enough for, you know, replication . And, uh, see if |
|
| 41:21 | can treat just, uh, overweight obese people necessarily having diabetes. It's |
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| 41:30 | big, big, big trend now , for these, uh, weight |
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| 41:35 | and, and tablets legally approved. , the caveat there is, is |
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| 41:42 | if you stop, if you eat than what you have now. |
|
| 41:50 | that's perfect system. Right. The company. Genius. I don't think |
|
| 41:54 | forever now. Sorry. Oh, . I mean, that's just, |
|
| 41:58 | so loud. They are, you'll , you know, like commercials for |
|
| 42:04 | something like that and it's like join billions that are taking this, you |
|
| 42:10 | , you really need it, you , it's action call. That's, |
|
| 42:16 | pretty interesting. So, people who diabetes can't get it or, or |
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| 42:21 | expensive or, you know, there's a whole business aspect of somebody's |
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| 42:26 | more versus somebody who's paying less, sell it or to the providers to |
|
| 42:31 | it for, like, he, , he got like, a coupon |
|
| 42:36 | the Olympic but, like, they realizing how much money they made for |
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| 42:40 | weight loss stuff. So, he ended up like, the, |
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| 42:43 | is getting run around from all the like, oh, like, |
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| 42:46 | we don't take this coupon anymore but it was for so many years and |
|
| 42:51 | he ended up just having to get because he couldn't even get his bill |
|
| 42:53 | he's not some bills that doesn't work good. So it just kind of |
|
| 42:57 | up, you know how they, there's one that you can um There's |
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| 43:06 | injectable the cost up to $1,000 but are, yeah, people say that |
|
| 43:12 | don't have a factor's coupon or something that. That anyway. So this |
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| 43:21 | not gonna help with losing weight, it's gonna help with the gaining |
|
| 43:26 | Now, the story that it, the Cancer and Aids and HIV, |
|
| 43:32 | a very interesting story and this is it really came about. Uh So |
|
| 43:39 | see if I wanna, let's talk evidence a little bit later. I |
|
| 43:43 | to show you um that slide that, that, that is important |
|
| 43:49 | us to, to understand them getting is three um things, uh three |
|
| 43:55 | four slides that are from this specific is not activated right now. Um |
|
| 44:01 | most of the, we're gonna talk neurological disorders. We're gonna talk about |
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| 44:04 | . We're gonna talk about drugs. not a really a drug expert, |
|
| 44:08 | I'm learning about well, how this kind of works and how it comes |
|
| 44:12 | that little in medieval times really. we do have some cool technologies and |
|
| 44:18 | of them that came about in the is called high performance of HPLC. |
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| 44:24 | an analytical chemistry technique used to identify quantify each component in a |
|
| 44:31 | And why is that important? Because medieval times and even before that in |
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| 44:36 | times, medicine and formulations of medicine botanically based. So somebody a shame |
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| 44:45 | medicine man, whoever you know, leader would put some concoctions together and |
|
| 44:52 | would know this concoction helps from this you not Uh it wasn't methodically |
|
| 45:00 | there wasn't signs behind it. But you worked in the pharmacies in the |
|
| 45:04 | States in the 19 06, you would find the tins, you |
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| 45:10 | find the botanical extracts or medicines. was rarely uh uh a pill that |
|
| 45:17 | being uh sold that a lot of sts contained things that were not good |
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| 45:23 | were harmful or were killing people or were drugging them too much. And |
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| 45:28 | many instances they were very helpful, people still didn't know what are the |
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| 45:32 | active ingredients. So the big breakthrough H P L C is that it |
|
| 45:36 | a Good and reliable technique and later very affordable where I don't know how |
|
| 45:43 | HPLC machines. We have a I would probably guess 100 or |
|
| 45:47 | maybe 50, but uh 30,000, for this whole setup. So what |
|
| 45:54 | does it takes that. So, typically when you extract the things in |
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| 45:59 | medicine, then you put some let's say a cannabis plant or lavender |
|
| 46:04 | . It's something and that something was water or alcohol, some salt. |
|
| 46:12 | then you extracted this green mixture and like, oh wow, this is |
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| 46:16 | green mixture. Now you have the to put the salt in containing the |
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| 46:20 | mixture through a column filled with an . So you have a P so |
|
| 46:26 | so delivery system that pumps it into B L C column. There are |
|
| 46:31 | columns and they have certain properties and uh sizes and all of these |
|
| 46:37 | there's a lot of specifications, but it passes through this column, what |
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| 46:41 | does each component, the sample interacts differently with absorbent material that was called |
|
| 46:48 | different flow rates. So different like , so large molecules would be very |
|
| 46:55 | moving and they get stuck. Uh molecules will move faster and then they |
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| 47:01 | further leading to the separation of the as they flow out of the. |
|
| 47:07 | as you basically force is make sure keep the like the fastest component, |
|
| 47:12 | smallest component shows up first, another that goes into the detector that |
|
| 47:18 | Uh actually, even before the uh uh computer set ups, they would |
|
| 47:27 | uh print a little graph. And , now it's displayed in the what |
|
| 47:34 | called the chromatogram and it shows you peaks and each one of these peaks |
|
| 47:40 | different chemical. And the size of peak typically represents the amount of that |
|
| 47:45 | relative to other or in total to was found in the mixture. So |
|
| 47:55 | will hear this word product C O s which stands for certificates of |
|
| 48:02 | food products and ingestible product, even products, it doesn't have to be |
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| 48:11 | to cannabis. They will all have O A. So we'll measure the |
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| 48:15 | in them. And this could be to a really serious analytical level, |
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| 48:20 | the chemicals, you could measure contaminants a lot of different things. But |
|
| 48:26 | technique is very important. And so technique was used by this brilliant |
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| 48:35 | Doctor Rafael Maul in 1964 Doctor Rafael just passed two weeks ago in Israel |
|
| 48:44 | his 90s, but in 1964, uses HPLC. The story is really |
|
| 48:53 | intriguing. Uh if you get a to watch a movie online called the |
|
| 48:59 | . But so he's a young scientist Israel. He decides to go police |
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| 49:06 | and get a chunk of hashish from and take it to the lab to |
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| 49:10 | what's in them because he has H L C or penal C before it |
|
| 49:16 | high performance. So he takes it and he claims that I'm the only |
|
| 49:25 | that confiscated the issues for police the way around. So the story is |
|
| 49:32 | funny because he discovers DH C he it. He's the first one to |
|
| 49:37 | the structure, the right one. all of the time when people were |
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| 49:41 | cannabis preparations, the stings in the in the 1920s, 30s, they |
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| 49:47 | know what that ingredient was. They that this plant can do this, |
|
| 49:51 | plant can do. This is a . Maybe that we float. This |
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| 49:54 | looks like this. This is it has the ingredients in it. |
|
| 49:59 | now we have that molecule. And at the same time, what's going |
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| 50:06 | 1981 was the first synthetic and open HC pharmaceutical that's produced everything I don't |
|
| 50:17 | , OK, I don't think I'm not gonna say that 80 plus |
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| 50:21 | 90% pharma materials. If we have about this way, we knew that |
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| 50:27 | plant does something and somebody took it this, this, this, this |
|
| 50:32 | ran it for anxiety. They ran , they ran for this, they |
|
| 50:36 | it for sleep. Yes, it . Then what's next? It's much |
|
| 50:43 | than sourcing some plant from some place , isolating, purifying the ingredient, |
|
| 50:50 | it. It's much easier to And that's what most farm is. |
|
| 50:54 | all of this knowledge, history that's drawn from shamans and medicine and that |
|
| 51:01 | being looked upon actually contributed to brain for us to synthesize these molecules. |
|
| 51:11 | , what's going on in the if you know a little bit about |
|
| 51:14 | culture, 19 sixties and seventies, are these flower Children, there are |
|
| 51:19 | tree huggers, this Woodstock going Uh historically, the United States puts |
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| 51:29 | cannabis and marijuana on schedule one, is the drug schedule, which states |
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| 51:36 | this is a dangerous drug has uh properties and has no medicinal use. |
|
| 51:43 | . Yeah, all of that. puts it on schedule one in 1973 |
|
| 51:50 | decriminalized as cannabis in 1974 just like . So, Oregon just legalized uh |
|
| 51:59 | aside. So that is 30 years now, 30 years from now. |
|
| 52:08 | why, why, why do people that? They just all you |
|
| 52:13 | there's a whole history there that sure draft Dodgers, they're dodging the draft |
|
| 52:18 | Vietnam. They don't want to So they run from the United States |
|
| 52:21 | they run to Vancouver, British Columbia all these strains called BC Buzz. |
|
| 52:27 | is all going on before this drug a synthetic pharmaceutical is developed. |
|
| 52:34 | while these guys are starting to experiment California and along the west coast, |
|
| 52:40 | were growing different strains because they finally to get seedless strains from Mexico that |
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| 52:46 | called. So there's a very famous uh guy that worked for cartels that |
|
| 52:55 | came up with seedless uh plants. so they started experimenting with a lot |
|
| 53:02 | strains. And also at the same , you have HIV and A I |
|
| 53:08 | epidemic that's starting and you have uh that when they go into uh severe |
|
| 53:18 | response, they go into wasting, have nausea, they vomit, they |
|
| 53:23 | no appetite there. Uh They're basically shedding and losing weight and dying |
|
| 53:31 | So those hippies started giving these patients cannabis extracts. That was their first |
|
| 53:38 | because it uh simulated their appetite, nausea. And by that, they |
|
| 53:44 | a more wait longer and lived a longer with AIDS or terminal cancers. |
|
| 53:51 | , United States, pharmaceutical companies and were smart and they synthesize T H |
|
| 53:59 | and in the form of 81 85 grana, it's tablets 2.5 mg |
|
| 54:09 | T H C an appetite stimulant, . And to this day, it's |
|
| 54:14 | available medication for uh chemotherapy associated But people don't like uh uh Marinol |
|
| 54:23 | much. They, they just it's, it's a synthetic phenomenon and |
|
| 54:27 | prefer to go to naturally drive Canons natural preparations that's just being reported by |
|
| 54:35 | not by. So and that's because causing some of other things. |
|
| 54:41 | it's, it's when you change the of the molecule, although it looks |
|
| 54:44 | same, it's synthetic, it has binding properties to the receptor. If |
|
| 54:49 | has different binding properties or penetrated properties different parts of the brain, it |
|
| 54:54 | cause a different effect than the natural natural. So 1985, so from |
|
| 55:03 | observation was when he discovered THC, first took a hole And he asked |
|
| 55:10 | wife who made a cake and invited six other or three other couples who |
|
| 55:15 | eight of them invited the cake in piece is 10 mg for a piece |
|
| 55:20 | THC and most of the people had . One person had a panic |
|
| 55:26 | another person just once, you So it's known because it will affect |
|
| 55:33 | differently. So because we're slight variants each other, right? In connectivity |
|
| 55:38 | expression, maybe you have too many one or something in there. One |
|
| 55:43 | without it, it makes you super , but it's just the opposite. |
|
| 55:48 | get it. Now in 2005 and , we saw the development of Phyto |
|
| 55:58 | medications as a plan arrived. DH and CV D will talk about Spasms |
|
| 56:08 | multiple sclerosis. It's anti static, a spray, it's a buckle |
|
| 56:13 | it's ATHC and so 2.7 um milligrams tea C M 2.5 mg of CV |
|
| 56:22 | per spray. And that's available And plus some countries around the world, |
|
| 56:29 | in Europe. It's the UKK or sclerosis produces spasm is by and also |
|
| 56:37 | by pain. Yeah. What's the in terms of cremation, synthetic versus |
|
| 56:45 | based? They're both made in a , right. What's that? What |
|
| 56:49 | the difference between how they like? does plant based mean? Exactly in |
|
| 56:53 | of like based? it's mean, not like synthetic is I took this |
|
| 56:59 | and I took this solution, I it together and I have a new |
|
| 57:04 | uh plan derive is you actually take planned and you take it to a |
|
| 57:10 | , Boil It, you put in alcohol, you put it in co2 |
|
| 57:14 | , you put in them something else gives you that solvent based preparation from |
|
| 57:21 | solvent based preparation. You can isolate molecules with H P L C for |
|
| 57:27 | , but there are ways that you isolate so much that you get a |
|
| 57:30 | chemical, which is 99.9 or 100% , but it comes from the |
|
| 57:38 | Was it like a technology thing that took? Like that's kind of a |
|
| 57:42 | gap. Uh I think not necessarily alcohol has been around for a |
|
| 57:48 | very long time. Uh And people still argue that at all extractions, |
|
| 57:54 | corporations for cannabis and for other botanicals still superior. It's just that people |
|
| 58:00 | want to consume alcohol or high concentrations it together, but it's the best |
|
| 58:06 | to extract mole. And yes, were other technological developments, probably things |
|
| 58:13 | uh holds to two extractions under high that were able to take plant |
|
| 58:21 | It was shredded and on the other to put out some really nice extracts |
|
| 58:26 | also came about like just general agricultural , I think in the sixties, |
|
| 58:31 | , eighties and nineties and still novel and the last one based drug that's |
|
| 58:40 | available in the United States. It not, it came out in |
|
| 58:43 | Originally, it was not, came in 2016. And it's a dial |
|
| 58:49 | is uh trademark ends. Now it's CBD oral solutions. It's actually on |
|
| 58:59 | five, I believe. Now that and is gonna start epilepsy. So |
|
| 59:04 | talk about Dr Syndrome and we'll talk epilepsy and we understand how maybe this |
|
| 59:10 | of this disorder actually changed a lot regulations around the world, not just |
|
| 59:17 | with pharmaceutical companies. So It's pretty that we have this plant for centuries |
|
| 59:26 | we used for the purposes. But some 60 years ago, we discovered |
|
| 59:31 | active ingredients in that and we only these limited medications. But I believe |
|
| 59:39 | with the breakthrough of medical cannabinoids and cannabis and the opening of the research |
|
| 59:45 | that age, a long time, you wrote a grant, you have |
|
| 59:49 | write a grant, it's gonna be , it's gonna cause negative effects. |
|
| 59:53 | if it didn't cause negative effects, people are not gonna get a follow |
|
| 59:56 | on that stuff. So that was institutionalized to basically demonize uh cannabis research |
|
| 60:05 | a long time. Uh And it is a big stigma. You still |
|
| 60:09 | to people and still the uh older , not not you guys because you |
|
| 60:15 | up skiing in Colorado. But so won't get into a lot of details |
|
| 60:26 | . But I wanna uh focus on endogen system today. But I wanted |
|
| 60:35 | tell you this important thing is that of as plants don't even produce T |
|
| 60:40 | C. They produce acidic versions, H C H C I and |
|
| 60:46 | I said, if you uh ingest raw or eat raw cannabis plant, |
|
| 60:53 | can get on. So the government something on the schedule T H C |
|
| 60:59 | cannabis plant, but cannabis plant doesn't T H C. It produces T |
|
| 61:05 | C A but you can do it taking derivatives. So, but |
|
| 61:10 | that's an interesting thing because again, we talked about, I said, |
|
| 61:13 | know, another cannabinoid system, you synthesizing it. So you have delta |
|
| 61:21 | TCA syn, you have delta uh a surveys and then you have a |
|
| 61:28 | of different synthetic variations. They don't the first thing always to ask |
|
| 61:32 | who is synthesizer. So I'm just you that from good to the source |
|
| 61:36 | always the scientists or medical scientists future to the source. We synthesize |
|
| 61:45 | You know, what are the enzymes either if there's no, where does |
|
| 61:51 | come from? That means it may coming from someplace. Maybe it's |
|
| 61:54 | maybe it's semisynthetic, the enzyme uh you from the squirrel. Last thing |
|
| 62:01 | wanted to talk about is this, fine because I introduced the pharmaceutical |
|
| 62:11 | Look, we live in the We have a lot of legal cannabis |
|
| 62:14 | C systems, including tax Texas is to expand its medical counties program. |
|
| 62:20 | legislature, They're gonna include chronic I think they're gonna take the upper |
|
| 62:26 | of TDC off and I think Texas gonna become more like kind of a |
|
| 62:31 | cannabis state. But what do you of other medical can? States? |
|
| 62:35 | Texas has about 45, patients that registered in Texas and a different variety |
|
| 62:42 | conditions is qualified to be a part the medical candidates program. Letter in |
|
| 62:47 | , you have medical candidates focus study The recreational is becoming an international |
|
| 62:55 | 1st. It was Colorado, California it was Canada. Then it's |
|
| 63:04 | So recreational in the United States, still in the state level. There's |
|
| 63:10 | adult use of recreational. There are cannabis programs that are recreational outside of |
|
| 63:19 | United States, but they typically province . So if you're in Canada. |
|
| 63:26 | if you're in Quebec, it all monopolized cannabis stores open and not close |
|
| 63:32 | time. You're in Montreal, it's a lot more privatized and individualized |
|
| 63:40 | stores open for, they want, have a full tax station for the |
|
| 63:47 | for the recreation. You pay you pay full tax to the state |
|
| 63:52 | to the national government. Uh in , you have uh legalization that is |
|
| 64:00 | up the German uh Germany announced that will have adult use camps already has |
|
| 64:08 | . So it's really going to And I'm just, I'm concerned that |
|
| 64:12 | research is lagging behind of what we out of the market that people are |
|
| 64:18 | . I would really like to have research, more hand and more understanding |
|
| 64:23 | of, of, of, of what it does. So on |
|
| 64:28 | medical side, we have Pharmaceuticals So of course, if they're you |
|
| 64:33 | d a group you got in the States, it's produced in the |
|
| 64:36 | you can sell in the United States international trade and you have medical, |
|
| 64:41 | international programs. German Germany is reporting and Colombia. So you have these |
|
| 64:50 | and national medical cannabis companies in for example, it is tax |
|
| 64:58 | So the insurance subsidies. So if buy your cannabis uh flower or buds |
|
| 65:05 | the pharmacy in Germany or Pharmacist, white jars and insurance insurance. And |
|
| 65:14 | the United States medical, it's still level of state an example that I |
|
| 65:20 | in Massachusetts because that's where the most incredible learning institutions are the power, |
|
| 65:31 | example. And so, so Massachusetts both rack and medical. If you're |
|
| 65:42 | medical patient, you're 20% tax From products. So if you have a |
|
| 65:50 | condition, there's other limitations in these . I lived in Massachusetts uh a |
|
| 65:56 | of years ago for over a And in Massachusetts, if you are |
|
| 66:02 | medical patient and you come into the or the store, you don't pay |
|
| 66:09 | tax and you can buy a lot whatever tinctures and products. And if |
|
| 66:19 | are not a patient or part of recreational program, you go to the |
|
| 66:23 | dispensary you combine with And you have pay a 40% tax and this is |
|
| 66:32 | , you know, the states really to understand, is it medical or |
|
| 66:36 | are just using it because they're using because they're having fun and or is |
|
| 66:41 | not harming them? So, of , there are inherent harms with, |
|
| 66:45 | , with cannabis and cannabinoids and Children the ones that get poisoned from edibles |
|
| 66:50 | frequently. Luckily because it's not that kind of the diet now or |
|
| 66:57 | substances. So, but it's we're lacking a lot of information, |
|
| 67:03 | lot of knowledge, we need to up the floodgates of research, I |
|
| 67:09 | because people have used these substances it's already psychedelics. We haven't even |
|
| 67:15 | doing research or understanding that psychedelics are coming out. Uh I didn't have |
|
| 67:21 | chance today. I think a lot time probably. Uh, 5 |
|
| 67:31 | OK. We're almost finished. I'll to tell that to you in a |
|
| 67:34 | of time, but maybe we'll talk it when we start talking about therapies |
|
| 67:39 | neurological disorders and therapies. I want introduce this concept that I haven't discussed |
|
| 67:45 | in any of my classes before called doubts. So I'm doing a little |
|
| 67:50 | on this right now that was inspired deep black chopra. Uh If you |
|
| 67:56 | know his name, find out who person is. And maybe together we |
|
| 68:01 | even look at an episode. We about pharmaceuticals, we talk about chemical |
|
| 68:07 | . Let's look at the power of mind how not. And virtual reality |
|
| 68:15 | actually serve as, as medicine and has no real measurable physiological impact. |
|
| 68:26 | we'll talk about that. Ok. you so much. I will add |
|
| 68:29 | four slides that I talked to them um into your lecture folders. I'll |
|
| 68:36 | everyone online on Monday. Yeah. then your is on Wednesday. All |
|
| 68:42 | . When did you say you had the same questions? I was trying |
|
| 68:46 | do it before Monday. Yeah. |
|
