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00:02 | This is lecture 14. And as explained we're actually going to cover the |
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00:07 | system today. Instead of the taste smell that is listed on the |
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00:13 | So this will be covering the endocannabinoid and this first slide actually doesn't show |
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00:19 | the endocannabinoid system that shows you what talked about in the last couple of |
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00:25 | . And what we really did is walked through one of the major sensory |
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00:32 | in the C. N. It's a visual system and we understood |
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00:36 | components in the retina and the components the lateral gene Nicollet nucleus All the |
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00:45 | through the primary visual Cortex in the v. one. And we understood |
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00:51 | in this area v. one is you we are capable of generating the |
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00:59 | sketch of this visual world because of properties of certain properties of the cells |
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01:07 | the primary visual cortex and receptive fuel . And so this shows you the |
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01:15 | system would have system, it has components. There is a sensory photo |
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01:23 | , it needs to be activated. information is conveyed by retinal ganglion cells |
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01:29 | L. G. N. There's at the level of the thalamus and |
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01:33 | ventricular nucleus. Before that information goes primary visual cortex and this is where |
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01:40 | kind of a stop. But in the visual information is tied with other |
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01:46 | And visual information further from area V divides into two mainstreams. The dorsal |
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01:56 | pathway that targets the posterior parietal So this is would be area V |
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02:03 | which is area 17 on broad most V Two. Area 18. Then |
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02:10 | you get even further remember these are primary, secondary tertiary. And then |
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02:17 | have to enter into the association So you have to start associating that |
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02:23 | primal sketch with other things and other for example that are indicated by this |
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02:31 | . So as you can see this , the posterior parietal cortex pathway through |
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02:37 | area M. T. Is going be concerned about depth processing about motion |
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02:46 | about four. And there is a pathway that is targeting the inferior temporal |
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02:55 | . It's the ventral inferior temporal And if we follow through that |
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03:02 | the bulk of what that pathway is about is the color in the |
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03:11 | So as we always talked about there parallel streams there's redundancy that means that |
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03:17 | level the color is primarily dominating in cortex. But if you're looking at |
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03:23 | form which is more important than color basic rudimentary human survival, it's more |
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03:32 | to process the form. And you see that the form processing and also |
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03:36 | depth processing is is redundant and you find it along this two different bath |
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03:46 | . So when you talk, when talk next lecture about the taste and |
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03:51 | or faction uh and in particular we talk about another two sensory systems in |
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04:00 | C. N. S. Now other thing to remind ourselves is that |
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04:09 | of the components in the brain in C. N. S. Are |
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04:16 | throughout the central nervous system. So as amino acids neurotransmitters, glutamate and |
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04:22 | . They will be expressed throughout in parts of the cortex of cortical tissue |
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04:28 | the cerebellum in the spinal cord. you'll find these neurotransmitters everywhere, the |
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04:36 | much that synthesize those neurotransmitters, you find them everywhere and they are primarily |
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04:45 | for the major excitation glutamate in the and inhibition Gaba in the brain. |
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04:54 | we discussed these other modular tutorial neuromodulation substances and I've used this analogy that |
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05:02 | excitation as plus an inhibition as minus black and white. Then these neuromodulation |
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05:09 | molecules such as the means such as such as serotonin, they add the |
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05:16 | the grayscale or color in general to activity of excitation and inhibition. They |
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05:22 | localized the selma's that produced these neurotransmitters localized in the specific brainstem nuclei such |
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05:29 | Locusts, Aurelius, for norepinephrine and nuclei for sartre ona and they will |
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05:36 | this molecules throughout different parts of the so as in above the major information |
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05:45 | the sensory system for example from the into L. G. And that's |
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05:50 | be conveyed with glutamate with excitation. you recall in the L. |
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05:55 | N. You have this sheet a of particular nucleus which is inhibitory. |
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06:00 | there's excited or inhibitor circuits with them and then again these long range projections |
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06:07 | are excited to our projections. The sauce from the thalamus will carry that |
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06:12 | into the cortex. And of course of these areas will also be receiving |
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06:20 | all of the cortical areas will be these other modular torrey inputs from the |
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06:27 | systems if you recall, they're very and not only modulating the activity but |
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06:34 | important and plasticity. And in particular looked at how spike timing dependent plasticity |
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06:43 | can be changed and modulated by introducing amino neurotransmitters and neuro modulators. So |
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06:54 | are different systems. There are chemical and there are neurotransmitters within these chemical |
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07:01 | that are found throughout the cns are systems that are confined two nuclei in |
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07:08 | brainstem but their projections are wide throughout cns. Okay. And then this |
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07:16 | a summary of the neurotransmitters that we them, you know, assets and |
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07:22 | mean neurotransmitters and today we're going to about the endocannabinoid system. An endocannabinoid |
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07:30 | was discovered in the 1990s. It a group of Israeli scientists led by |
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07:37 | national um that discovered different components of endocannabinoid system. But as we know |
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07:46 | we know of the endocannabinoid system today that we have a reason to believe |
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07:53 | it is one of the major homo and regulatory brain and body systems and |
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08:04 | are different components of the endocannabinoid These are the major components of the |
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08:12 | system. You have this synthesizing and enzymes. Again you have these small |
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08:20 | that synthesize undo cannabinoids that are as here, the two major into cannabinoids |
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08:28 | our bodies are to our aka donald , often abbreviated as to A |
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08:37 | And and undermined anandamide and nanda and means a bliss. So it's a |
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08:48 | molecule, that's what anandamide is named These and other cannabinoids that are synthesized |
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08:57 | our bodies. They target cannabinoid receptors one And CB two and binding of |
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09:05 | ominous to CB one and CB two in the brain and then the body |
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09:10 | cause physiological and also psychological responses. just like with other molecules, glutamate |
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09:21 | re synthesized reintroduced into the glutamate So you can adenoids, they get |
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09:28 | and they get reintroduced back into the . Now, components of the endocannabinoid |
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09:36 | are distributed widely throughout the brain and body And what this poster is showing |
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09:44 | that CB one receptors, cannabinoid one are dominant in the brain. |
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09:53 | the C. N. S. are CB two receptors and we will |
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09:58 | at where those receptors are expressed on their function is But CB one is |
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10:05 | the brain. CB one is also a lot of the digestive system |
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10:12 | Okay. and high expression of CB receptors in the heart as well but |
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10:21 | every cell in the body. And brain produces under cannabinoid molecules or has |
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10:30 | of the endocannabinoid system which is the the molecules and the target receptors, |
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10:38 | are cannabinoid molecules and CB one receptors important. Cannabinoid receptors in the brain |
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10:47 | the most abundant G protein coupled receptors the brain. That's significant. If |
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10:56 | told you that serotonin receptors five hT Ahmedabad tropic are the most predominant you'll |
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11:03 | wow that must be important. Serotonin play important roles. So wow that |
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11:08 | be important of CB one receptors cannabinoid in the brain that a G protein |
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11:15 | and metabolic tropical signaling inducing receptors, the most dominant, the most prevalent |
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11:24 | the expression levels in the cns CB receptors Are dominating in other organs over |
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11:34 | brain. However, you will find two receptors in the brain as well |
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11:38 | we'll discuss today with CB two receptors be dominant in the organs such as |
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11:47 | . Find it in the bone marrow general, the organs that are responsible |
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11:54 | amassing and regulating the immune response In brain. CB one receptors are distributed |
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12:07 | . It's very abundant. The most but as you know different parts of |
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12:12 | . n. s. serves different . So this is a really good |
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12:19 | that actually tells you about some of major parts of the brain and what |
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12:25 | parts of the brain are responsible for four effects of endocannabinoid molecules or cannabinoid |
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12:34 | in different parts of the brain on receptors can affect and modulate all of |
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12:42 | listed functions that you see here now is primarily focused on CB one |
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12:50 | CB one receptor was always the first for neuroscientists and in fact it was |
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12:58 | in the brain looking that discovered the of under cannabinoids because CL one receptors |
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13:06 | the brain are responsible for inducing the effect and this high effect is what |
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13:12 | reported with cannabis or marijuana plants that cannabinoids or phyto cannabinoids. So there |
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13:19 | always an interest to figure out While one receptors are located especially in the |
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13:28 | , the ones that have high expression are abundant here are the structures that |
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13:35 | labeled in red. So you can that prefrontal cortex which is responsible for |
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13:42 | function, basal ganglia which is involved cognition. Learning emotional response and motor |
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13:50 | . Motor command controls cerebral cortex. cognitive functions also primary sensory functions in |
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13:59 | ways hippocampus which is concerned with learning and stress and sarah balham which controls |
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14:09 | are 12345 parts of the brain here are highlighted, They've contained high levels |
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14:18 | CB one receptors therefore effects of endocannabinoid CB one receptors would be dominating in |
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14:26 | particular areas of the brain. as you can see the other areas |
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14:32 | the brain and amygdala which processes emotional of fair hypothalamus, temperature regulation. |
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14:39 | balance, reproductive function, energy Perrier aqueduct alegre that is important involved |
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14:48 | analgesia nucleus of solitary tract visceral nausea and vomiting brain stem which |
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15:00 | arousal, temperature regulation motor control and the spinal cord of course, you |
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15:07 | , it's peripheral sensations including pain but also motor commands through the spinal |
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15:13 | So it's everywhere in the brain. a significance for the fact that you |
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15:19 | CB receptors in the center in the stem the processes pain which is |
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15:27 | And so these are some of the properties of endocannabinoid is there are involved |
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15:34 | pain response and analgesia and also in control of the spain through the brainstem |
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15:43 | . The other important thing to know that although cannabinoid receptors are expressed in |
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15:50 | brain stem, the areas where they expressed in the brain stem are not |
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15:59 | for vital body functions such as heart and breathing. And that's the difference |
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16:09 | and the cannabinoids and opioid receptors. receptors actually are located in the brain |
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16:17 | centers that control breathing and heart rate that's why opioids are so much more |
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16:26 | . Then cannabinoids that are externally Okay, But this is an important |
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16:33 | here. So again different parts of brain are responsible for different functions. |
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16:43 | post rima that was mentioned is involved nausea and vomiting and this is also |
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16:50 | known function of that cannabinoids, including and phyto cannabinoids, cannabinoids found in |
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16:59 | , they control vomiting and nausea. in the brain circuits. If we |
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17:08 | at the tripartite synapse between neurons and . We have the following information that |
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17:16 | already familiar with. You have action which will de polarize external terminals. |
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17:22 | is going to be an influx of through volt educated calcium channels. This |
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17:29 | will allow for the fusion of the and the release of the neurotransmitter, |
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17:35 | release of the neurotransmitter. For example it is glutamate will cause excitation post |
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17:43 | aly by binding to glutamate receptors. it binds to the NMDA receptors is |
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17:48 | to be a significant influx of calcium sodium there's gonna be significant deep polarization |
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17:55 | optically and rises of calcium post synaptic and with very high levels of |
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18:02 | Endocannabinoid molecules will be synthesized on demand synaptic lee. They're not going to |
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18:12 | stored in the vesicles thereby they will diffuse through the plasma membranes. Travel |
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18:20 | lee to the pre synaptic side where bind to the CB one receptors and |
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18:26 | one receptors are G protein coupled receptors will actually close this calcium channel and |
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18:36 | calcium influx. So through this neuronal and the cannabinoids can really regulate the |
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18:44 | of glutamate release and that is very . So the endocannabinoid synthesizing enzymes that |
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18:51 | shown here as possible. Title Anomie. Uh An NSL Foster |
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18:59 | ethanol, amine, nape and I. Which is prospect title in |
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19:04 | hospital and D. A. Which is diacetyl glycerol which are necessary |
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19:11 | to produce to A. G. you remember something about the absolute |
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19:24 | The divergent pathway and glutamate signaling formidable glutamate signaling. It diverges into |
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19:32 | P. Three from P. P. Two and membrane bound |
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19:36 | A. G. So glutamate activation metabolic tropic receptors would actually contribute to |
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19:44 | levels of D. A. As well. What I'm saying is |
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19:48 | there are mechanisms that will be induced up regulated calcium and phosphate synaptic deep |
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19:56 | . There are mechanisms that are gonna induced through already measurable tropic receptor |
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20:03 | And the inter cellular mechanisms cascade mechanisms as D. A. G. |
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20:07 | can now serve as the necessary enzyme the synthesis of to A G. |
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20:13 | raise the levels of that to A . On demand. Then this negative |
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20:18 | loop can control the release of It's negative feedback because if there is |
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20:24 | lot of glutamate, if there is lot of influx of calcium and a |
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20:28 | of deep polarization, what happens is neurons can go through what is called |
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20:35 | or calcium excited toxicity. They get up with so much calcium. There's |
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20:41 | much active. There's so much glutamate neurons start dying slowly. They're |
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20:49 | It's called hyper excitability and neurotoxic So by activating CB one receptors now |
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20:59 | can regulate the levels of glutamate that being released. Glutamate is not the |
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21:05 | neurotransmitter that is regulated by the end cannabinoids. Gaba can also be regulated |
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21:12 | endo cannabinoids? So endocannabinoid through CB regulation pre synaptic Lee has a really |
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21:22 | influence of being able to modulate and the amount of both excitation and inhibition |
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21:32 | these neuronal communications. So now as can see glia cells and in particular |
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21:40 | glial cells will be abundantly expressing CB receptors. And obviously the glial function |
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21:49 | you're talking about astrocytes then they are in your restaurants that are cycling like |
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21:55 | . But if you're talking about micro , what is the involvement of endocannabinoid |
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22:01 | CB two receptors and micro glia CB receptor controls neural transmission and you can |
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22:08 | about it as a faster system because having neurotransmitter release glutamate, post synaptic |
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22:14 | polarization action potentials CB two receptors in in particular michael glia. They are |
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22:23 | in regulating inflammation and immune response. glia, one of the functions is |
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22:32 | , release their pro inflammatory molecules that called cytokines. So we've learned a |
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22:38 | bit about micro glee and we said microglia are the scavengers and they're the |
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22:44 | mobile glial elements of the brain that responsible for damage cleanup and repair in |
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22:50 | of traumatic brain injury or chemical So but michael, we are also |
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22:59 | for cytokine release and these cytokine molecules inflammatory molecules it's a normal response to |
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23:09 | inflammation in case of injury in case toxicity in case of infection. |
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23:17 | And it's important to have that inflammatory and start generating an immune response to |
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23:23 | . For example infection, it can a covid infection in the brain. |
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23:29 | if those cytokine levels are unchecked let's it was a very strong trauma, |
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23:35 | was a very uh strong viral load infection in the brain. Then you |
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23:43 | upset the side of kind balance and those upset cases there's too much of |
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23:50 | release its uncontrolled and so CB two that cytokine release in the ways modulating |
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23:58 | slower processes that are involved with inflammation are involved with immune response. Now |
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24:07 | have the endocannabinoid system That can through one receptors can control the fast neural |
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24:16 | And regulate the balance of excitation and plus and minus and through CB two |
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24:23 | than the cannabinoids can control the slower that are involved in the inflammation immune |
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24:31 | and as well as repair uh in cns. Yeah, so they know |
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24:44 | gonna talk about the oh factory system because it's uh a cool system to |
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24:53 | . And and it's also relevant for things. For example when you smell |
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25:03 | that smell enters into your nasal cavity in that nasal cavity you have nerve |
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25:11 | that are hanging out there like sort a little nerve endings hanging out that |
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25:16 | uh shown here, these are the factory receptor cells and their nerve endings |
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25:24 | actually hanging out through this what is all olfactory epithelium. Okay, so |
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25:32 | are not the only cells that you'll the olfactory epithelium there's a whole collection |
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25:38 | cells like supporting cells which will find too. But these are the receptor |
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25:45 | just like we had the photo receptors the retina. These are the nasal |
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25:50 | . So these are the olfactory receptors the structure of the skull in this |
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25:57 | is weird because it has these very openings, very small cavities or administrations |
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26:07 | the skull. It's called the crib plate. And these little administrations will |
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26:14 | the site where you can see you the olfactory receptor cells that will have |
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26:20 | peripheral nerve ending that's concerned with smelling and nasal cavity processing that information and |
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26:28 | sending that information through the central axon the olfactory evolve. And more specifically |
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26:38 | the glimmering realist in the olfactory bulb contacts onto the second order of factory |
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26:49 | and the second order of factory neurons send their output to olfactory cortex. |
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27:01 | , so this is how the information into the brain. So the smell |
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27:06 | the odor molecules get detected that way they get processed eventually. The perception |
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27:13 | smell through olfactory cortex. Part of pathway goes through thalamus part of the |
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27:19 | goes directly into cortex. Now, are we talking about marijuana and munchies |
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27:28 | ? When we're talking about the olfaction these circuits because you guys understand these |
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27:34 | excited or inhibitory circuits. You understand CB-1 receptors how they can control excitation |
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27:40 | inhibition. So a well known consequence marijuana intoxication or I guess getting high |
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27:51 | of appetite and effect known by users the munchies. The active ingredients in |
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27:59 | is Delta nine tetrahydrocannabinol THC, which neuronal functions by stimulating a receptor called |
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28:08 | receptor CB one. So then the molecules that bind to CB one receptors |
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28:15 | also the CB one receptors are also too. Exogenous molecules of phyto cannabinoid |
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28:25 | . So the exogenous cannabinoid molecules can with the endogenous system. So there's |
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28:32 | molecules like DELTA nine THC which comes cannabis plants, interacts with the cannabinoid |
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28:41 | , it interacts with other systems and receptors but it interacts with cannabinoid |
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28:47 | CB one receptors are abundant throughout the . So it is overly simplistic to |
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28:53 | these receptors of serving only appetite regulation we just talked about. Nevertheless, |
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29:01 | marijuana is often prescribed were legal as to stimulate appetite in patients with chronic |
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29:08 | such as cancer and AIDS. So enough, When Cannabis was placed on |
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29:18 | one which means it doesn't have any purpose and it is highly addictive and |
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29:25 | . It was done in the 70's the same time. There was AIDS |
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29:35 | problem that was happening and there was way of treating patients that had AIDS |
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29:45 | these patients would go through what is the wasting syndrome, they wouldn't |
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29:51 | There's no appetite a lot of times were subjected to very heavy doses of |
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29:58 | or radiation therapy which caused a lot nausea lack of appetite, immobility, |
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30:07 | and weakness of the patients would literally wasting away their bodies. And the |
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30:15 | in California noticed that if they give patients marijuana or candidates, if they |
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30:22 | that and boost their appetite, it their appetite and it also reduces the |
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30:29 | at the same time. So those cancer patients and those with AIDS |
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30:35 | And so in the 70s, about same time as cannabis by the federal |
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30:44 | , FDA Food and Drug agency placed on this most severe schedule of drugs |
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30:51 | you find heroin. Uh there was very significant movement, I would |
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31:00 | And also facts that people are observing in legal states mostly, but also |
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31:07 | illegal where cannabis was illegal. So compound that inhibits CB one receptors, |
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31:15 | Bond was also developed as an appetite . So the idea was that if |
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31:23 | stimulate CB one receptor CB one receptor mm Promotes appetite. So if you |
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31:32 | CB one receptor with an antagonist, then you would reduce appetite and people |
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31:42 | oh my God this is great because this is like you know, weight |
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31:46 | pill, people just won't be We just need to block it. |
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31:52 | , human drug trials had to be because of the psychiatric side effects. |
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31:59 | goes to the same problem that we've discussed different things and different look functions |
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32:06 | located in different parts of the although they have the same receptors, |
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32:09 | responsible for different functions. So you're one problem but you're also causing another |
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32:18 | . So like psychiatric problem. And drug was removed from the market very |
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32:22 | actually it was causing suicide and some . So although this finding underscores that |
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32:30 | that these receptors do much more than the munchies, it is still still |
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32:36 | of interest to know where in the . CB one receptors act to stimulate |
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32:41 | . Not surprisingly, CB one receptors with neurons in many regions of the |
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32:46 | that controlled feeding such as the hypothalamus some of the direct psychogenic effects of |
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32:54 | are related to changing these activities of neurons, appetite stimulating or exit |
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33:00 | However, neuroscientists were surprised to learn 2014 that much of the appetite stimulation |
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33:06 | from enhancing the sense of smell at in mice well, but you don't |
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33:14 | to make that argument for mice. , you can say that it is |
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33:18 | same for humans. Uh Covid has us that when you lose a sense |
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33:24 | smile, you really don't want to that much and whatever you eat doesn't |
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33:28 | that great. So you just do not because you're enjoying it just to |
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33:33 | over and not to, you start. So we know that for |
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33:40 | and part of what we taste is much about what we smell too. |
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33:47 | collaborative research conducted by neuroscientist Frances spain incidentally known for the appreciation of good |
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33:54 | and smells revealed that activation of CB receptors and olfactory bald increases odor detection |
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34:02 | it's necessary for the increase in food , stimulated in hungry mice by |
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34:09 | So in Chapter eight We didn't discuss how smells activating neurons. But let's |
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34:16 | at the circuit here. The brain under cannabinoid are synthesized under fasting conditions |
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34:24 | they inhibit glutamate released by acting on one receptors on cortical funeral axon terminals |
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34:33 | granule cell activation by glutamate in the has the net effect of enhancing the |
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34:37 | of smell. Let's look at the here. So what is happening in |
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34:42 | circuit right here, the secondary order olfactory neurons, you can see that |
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34:47 | have an inhibitory granule cell and from cortex which you get you get excited |
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34:54 | glutamate release. So this is the when you smell something I guess it's |
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35:00 | negative feedback to control that sense smell . So you release glutamate on the |
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35:05 | cell. Okay. And that inhibitory then if not inhibits the smell modulates |
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35:12 | amount of smell sculpts that smell the inhibition but you can say that |
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35:18 | controls and it's very important especially if are surrounded by something that smells really |
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35:25 | and imagine if your hands are tied you just have to smell something |
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35:30 | really horrible. So this mechanism would basically like okay it's a lot of |
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35:35 | now calm down calm down. You're gonna be processing the smell as much |
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35:40 | the secondary neurons CB one receptors, just saw the CB one receptors will |
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35:46 | glutamate release. So if you activate one with endocannabinoid you blog glutamate release |
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35:53 | blocking calcium influx. So activation of one buy and sell cannabinoids or activation |
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36:03 | CB one by phyto cannabinoids like delta THC. With them reduce glutamate reliefs |
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36:12 | the inhibitory cells and will reduce the of the second order neurons. By |
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36:20 | this inhibition. These secondary order neurons be enhanced so there would be smelling |
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36:27 | . And that is I guess you make an argument then when there is |
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36:31 | increased production of endocannabinoid, it stimulates smell and it stimulates the appetite. |
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36:41 | just by stimulating the appetite centers but just by stimulating the smell. That's |
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36:48 | important. One of the features of systems and the increased production of under |
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36:56 | happens during early postnatal days when a child starts suckling and the mother increases |
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37:08 | levels of the endocannabinoid and the breast . And if you think about these |
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37:13 | basic rudimentary functions then that endocannabinoid will the child's sense of smell, Make |
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37:22 | more hungry. Will make that child likely to survive. Okay, so |
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37:31 | why not everything can be substituted with with powders with baby powders because there |
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37:39 | certain physiological elements that potentially like I'm sure they're probably not present. |
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37:48 | the milk. Baby powders potentially precursors the cannabinoids which are omega three and |
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37:57 | six uh fatty assets are important and would be present and in child |
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38:08 | So there you go. This is the munchies would happen within the |
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38:15 | With exogenous use of cannabinoids, consumption THC would also reduce inhibition and promote |
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38:23 | sense of smell um and make you hungry. So in the central nervous |
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38:34 | you have neural transmission Controlled by CB , a faster response and the slow |
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38:44 | . The cytokines, inflammation, Michael cell activity modulated by CB two receptors |
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38:54 | the cannabinoid system can get engaged to more endocannabinoid wants. That means that |
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39:03 | certain base level of under cannabidiol is our bodies but you can raise those |
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39:09 | and other economic rewards. They get with stress. They also get raised |
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39:16 | repeated exercise activity, repeated exercise activities as long distance running or hiking or |
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39:28 | else is the low level of cellular stress, normal stress. Remember |
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39:38 | stress that cannot be handled and stress is necessary to push our systems to |
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39:43 | them more dynamic and to handle things . So for a long time there |
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39:49 | a thought that runner's high this idea when long distance runners get this happy |
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40:00 | , they just feel good after running sometimes during the middle of their |
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40:05 | They get this overwhelming happy feeling. was always interpreted as endorphins or endogenous |
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40:15 | like molecules but morphine is not a molecules. Exogenous molecule. And the |
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40:26 | scientific research nurse scientific research shows that feeling of the runner's high is likely |
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40:34 | of the increased levels of under Ananda the bliss molecule and activation of |
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40:41 | one receptors and CB two receptors. chama traumatic brain injury, hypoxia lack |
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40:55 | oxygen, death of neurons um hyper , calcium excitability, glutamate excitability which |
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41:08 | everything into the favor of excitation. is when endocannabinoid system gets engaged. |
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41:18 | inflammation. We're focusing on the brain you will see that these molecules and |
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41:26 | they function and inflammation in the brain also they're involved. And as I |
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41:31 | , CB two receptors are predominantly expressed the organs that are involved in the |
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41:36 | response. Once you have this you , very fine balance of excitation and |
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41:46 | of our brains that I really like image because it shows uh somebody standing |
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41:52 | two chairs on top of a high in new york city, It looks |
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41:57 | it's a turn of the 20th the middle of the 20th century and |
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42:02 | can imagine that this is your brain this is the state of your |
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42:08 | It's it's quite fragile. It's it's it's it's stable for most of our |
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42:16 | but it constantly teeters between more more inhibition. Uh it is fragile |
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42:25 | if you have a genetic mutation and of the chairs slips. You can |
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42:32 | , you can fall to either Too much excitation or too much |
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42:40 | So and the cannabinoids seemed to be of the molecules that is really well |
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42:47 | to control this excitation and inhibition, this balance. They're responsible. They |
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42:54 | produced is eat munchies, they make hungry, increase the sense of |
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43:01 | They actually promote rest and sleep too and protected neural protection against excited |
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43:17 | forgetting. Why is forgetting important because you remembered everything and especially if you |
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43:24 | everything bad that happened to you. if you had no ability to clear |
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43:30 | bad memories and bad emotions, you are reducing your your your capabilities or |
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43:40 | , your lifespan potentially to. So an important mechanism for forgetting. What |
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43:46 | that mean? That means that too much of CB one excitation can |
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43:53 | short term memory. Delta nine THC affect short term memory if you have |
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44:01 | levels of endogenous molecules. But then you're adding some something exogenous li like |
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44:07 | nine THC. Oh I'm just can't things as well. I can't remember |
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44:12 | as well because you're pushing the system the address of its dynamic range. |
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44:19 | chemical system in the body. I the analogy of a rubber band. |
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44:26 | has a dynamic range. You can it. It's meant to stretch, |
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44:31 | can stretch it many times. But has it's finite dynamic range and once |
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44:42 | reaches the boundaries of that range. rubber band may snap and then it |
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44:51 | take your body two weeks, 3 , three months, 3 years to |
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45:00 | the enzymes that are involved in the that synthesize molecules. So break down |
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45:08 | to re express the receptors, reinsert receptors in the proper synopsis and the |
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45:16 | neurons. And and believe this takes lot of time. Now, what's |
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45:22 | about the endocannabinoid system and it has pretty vast dynamic range in contrast to |
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45:32 | system and the brainstem that I already to. And that's the problem. |
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45:36 | know, we're actually not even talking much about marijuana or cannabis or what |
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45:42 | does. There's more information I would happy to share with you in the |
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45:46 | lecture if you have questions. But fact of the matter is that there |
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45:54 | negative effects and most of these negative is not from too much running. |
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46:02 | runners can be addicted to the round much that they will prioritize that over |
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46:08 | else. Which is a running use . Uh there is a cannabis use |
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46:16 | , there is an effect on the system that can stretch it, that |
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46:22 | affect the memory that can affect these . Now. The thing is that |
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46:27 | not lethal. So if you're under system is or too much consumption of |
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46:35 | nine THC, you may get intoxicated the point where you may end up |
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46:40 | the hospital, there's a panic There's anxiety attack, heart racing because |
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46:46 | one receptors are also present in the . For Children, it presents a |
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46:52 | in the states where delta nine THC legal and it's an edibles that look |
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46:57 | very colorful pretty gummies and they find on the parents table and consume |
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47:02 | Those kids, they get their stomachs out, they usually sleep it off |
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47:07 | they go to school the following day that's because the cannabinoid receptors are not |
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47:15 | the vital body in the in the of the bracelet that control breathing and |
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47:22 | rate and opioids are. So when hear about opioid epidemic going on, |
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47:30 | many opioid deaths we get This is rubber band theory. Mr rubber band |
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47:37 | , not theory or delta nine THC cannabinoids to have an effective dose, |
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47:47 | say whatever that effective does, it's Gummi or if you're talking about consumption |
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47:52 | cannabis flower, it's one joint, cigarette from marijuana from cannabis, it's |
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47:58 | effective dose because it will intoxicate people . A deadly dose for Canada's is |
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48:05 | 1000 times of that in about 15 . So it's very, it's impossible |
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48:11 | consume that high of a dose even you use very concentrated preparations, you |
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48:16 | pass out or fall asleep before you and then you just sleep so you |
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48:24 | die okay with opioids effective dose is treatment and that effective doses to treat |
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48:33 | typically and the lethal dose is only or four times of the effective dose |
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48:41 | is very easy to achieve. And problem is the opioid receptors are expressed |
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48:49 | the brain stem areas and the centers control breathing and heart rate. And |
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48:57 | the dynamic range of that system, rubber band is like you can't stretch |
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49:02 | far, you stretch it just a bit, boom, that snaps. |
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49:05 | when it snaps you don't fall he dies. Okay, will you |
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49:13 | breathing? So that's that's that's the when we talk about effects of different |
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49:22 | molecules, exogenous molecules. Uh and particular system then the cannabinoid system and |
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49:29 | dynamic range. So this is a bit about cannabis and this is a |
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49:42 | from 2017 which probably was one of very exciting times for the changes in |
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49:53 | laws in this country and internationally. the fact that all of a sudden |
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49:58 | saw marijuana companies on stock exchanges and trading the shares and the value of |
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50:10 | company sort of like blown up out proportion. There was a big |
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50:14 | Like with everything else in the there's a housing bubble, there's Bitcoin |
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50:21 | . This was Canada's bubble butt, was so much excitement. Everybody thought |
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50:27 | was gonna go legal everywhere in United States. Mexico Well it is |
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50:33 | in Canada. We have very different and Canada is federally illegal for both |
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50:42 | adult use and medical use. There medicines that are made from cannabis and |
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50:49 | should actually, maybe I should have those here. Maybe I'll include a |
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50:55 | more slides in there in Germany. have a federal illegal medical cannabis system |
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51:03 | you obtain your cannabis flower or marijuana in a popular language. And the |
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51:12 | where a pharmacist with a white lab explains to you Why you should get |
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51:19 | product or the other one. And insurance covers your medical bills. So |
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51:25 | very different systems in the United What we have is we have state |
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51:30 | systems on a federal level. Canada's delta nine THC molecule remain on schedule |
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51:42 | , which is basically the worst possible , Most addictive, no medicinal |
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51:50 | That's what still the federal government Canada says now in 2017, when |
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51:56 | of these changes were happening. people like me were already observing the |
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52:04 | . And there's two realities. There a reality of not being able to |
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52:08 | research on cannabis on the planet. could do research on synthetic cannabinoids and |
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52:14 | could order one mg of THC pay to michigan came in pharmaceutical, $60 |
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52:20 | one mg, 20 mg, THC and texas costs. I think $10 |
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52:27 | something like that. So you can that synthetic drug. You could have |
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52:31 | of the experiments in the dish you do. And in reality people were |
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52:37 | all of these plant preparations and there's disconnect so there was a reality here |
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52:43 | you can do this and then there's reality that you cannot do research on |
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52:47 | plant. That still reality is is persistent. That the states just started |
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52:52 | up to that. I mean the the feds just started opening up to |
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52:57 | last year. That was the And at the same time Oregon decriminalized |
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53:08 | in 1974, California legalized medical cannabis 1996. That's almost 30 years |
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53:20 | D. C. I believe 1998 have most of the states in this |
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53:27 | that have medical candidates. What is on and maybe I'll get into the |
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53:34 | between what's happening in the state and state level, What's happening in the |
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53:39 | world and the pharmaceutical level. But as this culture was emerging, the |
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53:45 | , the big business was emerging and of people were using cannabis for various |
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53:52 | reasons. Well it was no longer you know, an a grandma's tale |
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54:00 | could be ignored. Oh it just so and sell, oh just the |
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54:05 | you know, I went to the epilepsy meetings around that time, 2000 |
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54:10 | 15, 16 17, I was Dravet syndrome and the drive a syndrome |
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54:16 | . It's an intractable form of epilepsy talk about it. Which means these |
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54:20 | don't lend themselves to available pharmaceutical Over 20% of them die in their |
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54:28 | because of the medications not working. was going to epilepsy meetings. I |
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54:34 | listening to the to the parents of patients of kids saying they're using cannabis |
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54:40 | . So they're using marijuana, they're their Children even inhale marijuana smoke even |
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54:46 | the pumps and stuff just to stop seizures. And the scientific community didn't |
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54:56 | want to listen to those parents and found it very frustrating and found that |
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55:02 | can we work with synthetic drugs with molecules? Yet we have thousands of |
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55:09 | that are using these plant derived oils preparations that have been around actually for |
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55:16 | of years. Nobody's dying from And what is the disconnect here? |
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55:25 | In 2016, 2017, it was difficult to even speak about this. |
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55:32 | in in in the pharmaceutical scientific It was very frustrating. These people |
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55:39 | together from the National Academy of Sciences and Medicine and you can look up |
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55:43 | article I can post for you and reviewed all of the available data on |
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55:49 | and Cannabinoids. So when they say of the available data, you have |
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55:54 | keep in mind what I've just told the systematic suppression of no data on |
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55:58 | plant. And despite all of there's still some studies and they published |
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56:05 | following this conclusive or substantial evidence that or cannabinoids are affected for the treatment |
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56:10 | chronic pain and adults candidates as anti in the treatment of chemotherapy induced nausea |
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56:19 | vomiting for improving patient reported multiple spasticity symptoms. Oral cannabinoids. There's |
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56:28 | evidence that cannabis or cannabinoids are effective improving short term sleep outcomes and individuals |
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56:33 | sleep disturbance associated with obstructive sleep apnea , Fibromyalgia, chronic pain, multiple |
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56:39 | , cannabinoids primarily in the big So while you have the brightest minds |
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56:48 | the sciences, engineering and medicine telling this is medicine, the federal law |
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56:57 | says this is not medicine. This an addictive drug does not have |
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57:04 | Where is the truth? The truth lies. Somewhere in between? I |
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57:11 | will prepare maybe three or four more for you for our next meeting so |
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57:15 | we can look up and see what acceptable for 95% of medical doctors at |
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57:23 | medical center. As a recommendation of approved cannabis pharmaceuticals, What is acceptable |
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57:32 | 5% of medical doctors that are open openly prescribing medical cannabis. You can |
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57:43 | that there's pain here, anti anti nausea spasticity, maybe sleep When |
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57:53 | come back. We'll see that Texas medical candidates in the state for about |
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57:58 | different conditions. Why who determines How does a regular individual? Who |
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58:08 | not an analytical lab themselves, understand whole world and discrepancy between federal state |
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58:17 | also, I think we should look Delta eight because Delta eight THC is |
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58:22 | advertised a lot of gas stations and shops. And I just wanted to |
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58:28 | you some very basic thing that delta not produced by a plant. That's |
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58:32 | a synthetic molecule. And then it's out there for the consumers and |
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58:38 | of them have difficult time understanding what is most actually, because even for |
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58:45 | and people that are interested in it takes time to figure things |
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58:50 | Okay, so we'll end here. think I'll tag on another three or |
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58:53 | slides onto this lecture when we meet on Wednesday and we'll see how our |
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59:03 | proceeds. Um, most likely I'll into the olfactory and taste systems. |
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59:09 | I'll just do olfactory instead of both . It's most closely related to what |
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59:14 | talked about today. Okay, thank for being |
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