A Re-Evaluation of Cannabis | Muralikrishnan Dhanasekaran & Manoj Govindarajulu | #SangamTalks

Cannabis has been completely banned, but you might have heard so many things and so many stories about cannabis, marijuana. The moment the word marijuana comes to your mind, only the narcotic aspects, drugs and all those things and materials and parties and all these things come to your mind. Basically, I will let you know. Guess what can be in common between the sages of your Himalayan sadhus, psychosomatic diseases, illnesses, as well as the evolution of mammals to some extent related to this common thing. And also you can see now it's so common about modern degree parties. So you can see a canvas from one end to another end and the single word answer is connects. Cannabis is nature's most hardy or among the hardiest plants. It does not need your cajoling, singing to it, dancing with it, or saying Lila to grow it. It grows on. So you can see the diversity of this one. Now what we are talking in this series is basically on the basis of science, not on the basis of testimonials or hearsays or traditions, but we are talking about the hardcore scientific facts. Based on scientific facts, we are taking on the medicinal aspects first. The first two days, the first two parts will be the medicinal aspect. The remaining one will also talk about maybe on the fifth, fourteenth perhaps, will be more on a sustainability aspect of it. It is also called as my book, it has just come out. The other book which is coming maybe in a day or two online is about cannabis for medicinal or rather healthcare medicinal aspects. So today we are going to talk about the most important aspect of it, which is on medicine. There are several thousands of patents, I can say there are more than 15,000 patents on cannabis in just the last 20 years. You can see the growth of this area. The total market of this one is now expected to be around 75 billion in the next five years in the global market, and if India and China open up the market for cannabis, it can go into half a trillion. The medicinally active psychoactive ones are called cannabinoids, and I think no person can be better than Dr. Murali Krishnan to talk about this. He has been working on this area for the last several years, he has published four books on medicinal botany. So over to Dr. Murali Krishnan.

Good evening everyone. Today we are going to talk about cannabis. So the first question we are talking about is: currently in the society, it's always a kind of issue, you're asking whether it is having any protective effect or a toxic effect. So when I use the word toxic, does it have any poisonous effect? So that's the most important question that we want to know. From way back, before Christ, one is wine, the other one is cannabis. So you go to any literature, that's what I'm going to talk about. So wine is one of the substances or a natural product, it has been there, well documented, has been used globally. Similar to wine, cannabis also has been used globally. So now the question is: why is it still in use historically? Then let's look into it in a very simple way. How can we generally classify it? When we say cannabis, at least for the audience, it can be of two aspects. So let's educate ourselves: how do we classify cannabis? What are the basic concepts we should know? The concepts have changed within a few years. So are we going to adapt? Are we not going to adapt? If not us, somebody is going to take over. So the question is, as a general audience, you should know a little bit of basic concept about it. And let me conclude by saying: is it toxic or non-toxic? I'm not going to make a decision here. I'm going to let the viewers, the audience, decide. But as a scientist in this field, I just want to answer this question: is it poisonous or non-poisonous? Is it toxic or non-toxic? So with this background, let me start. I'm from Auburn University, I'm from Auburn, Alabama. Alabama is a state which is very close to Atlanta, Georgia. We are in the South, it's a very beautiful city. Cannabis is a substance of abuse, we all agree. So what do you mean by substance of abuse? I'm going to use the word: they are harmful, they are hazardous, they are psychoactive. The word psych means mind; they activate the mind or they modify the action of the mind, so that is the reason it is called a psychoactive substance. A psychoactive substance for us can be alcohol or any other. So this is the definition given by the World Health Organization for the word psychoactive. Psycho means mind, substance affecting the mind or behavior. Illicit means it is forbidden by the law. So in general, that is substance of abuse. So now what is the problem of substance of abuse? Let's start with the simplest addictive substance known to us. I'm going to start with caffeine. Okay, so definitely we all agree in some form we need caffeine every day in the morning. So we have been addicted. Because of addiction, what happens? You become dependent. Whether you're flying in an aircraft or you're in a train, when you get up in the morning at 5:36, you have somebody serving your tea. So definitely we become dependent. Is there toxicity associated with that? Yes, in acute and long term, but we don't know. When I say toxicity, I'm again going to bring this word toxic. Yes, caffeine can be toxic, but it depends upon how much we consume. It's the dose, the dosage form, the duration. The same thing goes with nicotine, which we know. But marijuana is also a substance of abuse. So now I just want to make sure that we understand what is marijuana. Cannabis refers to all products coming from the Cannabis sativa plant. Under cannabis, there are three particular plants only: sativa and indica. But Cannabis sativa is the most potent one. They have approximately 540 bioactives. This particular word bioactives is a common word now used in the current scientific community to say the chemicals or substances present in a botanical. Bioactives: 540. Marijuana refers to some product from Cannabis sativa and usually they contain... it's called hemp, industrial hemp. Hemp has a significant psychoactive potential and they can induce addiction. So now we are clear. What the source was saying about hemp: when we say that, the amount of it depends upon the amount of THC. The amount of THC is considerably, significantly less in hemp as compared to the other product. So that is the first concept we want to make sure we clear. And then again I want to make sure that we understand that when you think about hemp and marijuana, it basically depends upon the THC content. Legality—there are three aspects that differentiate hemp from marijuana. One is grown because of the less THC, the other is illegal. So now the second term I want you to make sure we understand is cannabinoids and THC. CBD and THC—both are derived from Cannabis sativa. CBD does not have a psychoactive aspect, whereas THC has a significant psychoactive property. So that is the most important thing. CBD does not affect the brain; however, THC significantly affects the brain. Both of them act by the same mechanism; they both act by binding to a receptor, CB1 and CB2. It's not a big word. When you think about lock and key in your house, a chemical has to bind to a receptor to elicit an action. So that is the whole thing. So now, the concept is as we started: you think about any religion, any culture globally, we have literature to show that people have been using it for thousands of years. So we cannot deny the fact that cannabis has been used, is used, and will be used in the future. We can't stop them. So as a scientific community, what are we thinking? Why is it still used? So that is the fact that it is being used. Now, I'm going to just show the legal use of cannabis before I answer the question. Cannabis in the USA has been used for medicinal purposes, for recreational adult use, and in certain states it has not yet been legalized. Eventually they are going to be legalized. So in the US, we have gambling. In certain states gambling is legal, we have lottery tickets, scratch cards. Very similar to India, we have a lot of tickets here. And seven states have it, certain states do not. In certain states we have casinos. So now cannabis is also under that. We are using it for medicinal use, we are using it for recreational use. Some states have legalized it, some states are not. So the question to ask is: is it religion or is it science that is dictating the use of cannabis? Again, I'm making sure that we understand. If you are a religious person, why are we still using cannabis? If it is a scientific person, why are we still using cannabis? Yes, religion and science have not completely banned the use of cannabis. So the first take-home message for today's talk is: religion or science, they have not completely banned the use of cannabis. So that is the take-home message. Now the question becomes: why? So we have been using it for religious, commercial, medical purposes. We all agree that it has an addiction potential. Why are we still in use? Because they are not... So what are the ways that we can classify cannabis? When somebody is talking to you, what is cannabis? Cannabis can be classified through three ways: endocannabinoids. Endo means within the body; they are naturally present. So the first concept is they are naturally present in the body, whether we agree or not. Two are arachidonoyl glycerol (2-AG) and anandamide. The word anandamide is derived from Sanskrit: anandam, meaning happiness. So these are chemicals that are produced in the body to make you calm, to cause a bliss, to make happiness. So definitely they are present in the body. They are endocannabinoids. These are natural substances present in botanical—they are called phytocannabinoids, present in the plant THC. And now the problem: we are going to develop more potent cannabinoids, they are called synthetic. So these are the general classification: endo, present within the body; phyto, from the plants; and synthetic. So when I say the word anandamide, it is a bliss molecule. Some people call it a runner's high. They are mainly mood enhancers, they can reduce pain, they have anti-anxiety effects. So that is well proven. They play a very vital role in mood, appetite, memory, and fertility. Currently, cannabis has been used for recreational purposes. You've got a lot of religions using it for spiritual purposes, commercial purposes as Rajiv was telling, going to be half a trillion dollars globally. We are using it for... in a few years we may be consuming cannabis. So definitely it has multi-use. So before Dr. Gondra takes over, why can it be used in the U.S.? The connection is cannabis can be absorbed, distributed, metabolized, and eliminated in our body. So when you think about a drug or a chemical, it can be absorbed through the nasal route, through skin, through eyes, through oral route. So cannabis can be absorbed in the body by different routes. It can be distributed throughout the body. It has to be metabolized and eliminated. And as I told you, like a lock and key, it binds to certain receptors CB1 and CB2. So that's the action. So absorbed, distributed, metabolized, and eliminated as I told you. It's a simple network how cannabis acts. They talk this way; we call this neurotransmission, how two neurons talk to each other in the body. So it can do that message communication and can be administered. So from a medicinal point of view, cannabis can affect other drug actions in the body. I'm not going to go into details here. In a big product, if you're taking some cannabis product and if you're taking any other medicines or drugs, cannabis can affect the action of other drugs in the body. So that is the concept we are trying to bring. So in brief, cannabis has been used for commercial purposes, for agriculture purposes, for recreational purposes, for cosmetic value, and like vitamins, when you say nutraceutical like multivitamins, cannabis also has nutraceutical value. So you can see that various products of cannabis have been used to protect against a lot of diseases. We have cannabis in capsule, tablet, lotion, and cream formulation. I come from a pharmacy background, so it's a miracle here. Whatever dosage form you think about, tablets, pills, cream, lotions, we have cannabis product. It has nutritional value, cannabis has cosmetic value. We have so many skin formulations, moisturizers, lotions, creams, serums, soaps. So when you think about the effect of a substance in the body, as the dose increases, the effect in the body increases. You are tired, you drink one coffee, sometimes you are not yet recovered from the fatigue. What do you do? In another 15-20 minutes you take another coffee. So you are stimulating your body. As you increase the dose, the effect increases. So that's the first concept. So now based on that, anything... When somebody asked Buddha what is poison, he said everything in excess in life is a poison. So now when we say about cannabis, the most important thing that I'm going to tell you here is it is the dose, the dosage form, that we are... religions, various cultures. The immediate question that we are now asking is why suddenly is there a burst of interest? Because it's a trillion-dollar market. It's a trillion-dollar market. So now the question becomes: is it toxic or non-toxic? Whether we like it or not, we have use for agriculture, recreational, medicinal, cosmetic, nutritional. And now, to conclude, I just want to say it is the dose, what amount of that a person is addicted to, that will dictate whether it is toxic poison or non-poison. So today's outline of the talk is: I'll be just giving an outline of what are the different endocannabinoids which are present, which is already discussed by Dr. Murali, and just talk about potential medical uses. And finally I would like to discuss about the controversies: whether medical cannabis or marijuana versus THC or CBD-based medications are more effective. So Dr. Murali has already described what is cannabinoids. So any compound which actually acts on those receptors is defined as a cannabinoid. So there are three types of cannabinoids as Dr. Murali has already discussed. One is the endocannabinoids, which means that these are actually synthesized within the humans or in any animal world. So the most important thing about these endocannabinoids is it is synthesized on demand. So it is required for some normal physiological functions in the body and that's why it gets released. So in a broad term, these endocannabinoids are characterized as: eat, sleep, relax, forget, and protect. So these are the generalized terms we call when these endocannabinoids are released. So the general term is these are chemicals which are released to calm a person and just rest. The two chemicals which Dr. Murali had already discussed are anandamide, which is defined as AEA, and 2-arachidonoylglycerol, which is defined as 2-AG. There are also phytocannabinoids present in these plant-based products, and there are 400 different compounds which are being researched. And finally, there are certain things called terpenes which give the fragrances. For instance, caffeine has a different smell; if you smoke, there is a different smell; and cannabis, if you are a person who is smoking cannabis, has a different odor or smell. And these are mediated by terpenes, and these terpenes are also currently in research for different pharmaceutical benefits. The third one is the synthetic cannabinoids, which are synthetic materials formed by humans, which are not medically approved. So the point here is that whatever the different types of cannabinoids, these cannabinoids basically act on receptors as Dr. Murali mentioned: the lock and key. The chemicals which are either present in the body or given externally go and bind to the receptors. So there are two types of receptors basically we classify: one is the CB1 receptor, or cannabinoid 1 receptor, and the second one is cannabinoid 2 receptor. So when these chemicals bind to these receptors, they elicit a biological action, and there can be a lot of actions which happen throughout the body. It depends on the ligand which is binding and where these receptors are located. If these cannabinoid receptors are present in the brain, we have differential effects; present in the heart, we have a differential effect. So it depends on the dose and the location of the receptors to mediate the action. So we just look at where these receptors are located. We usually classify it as CB1 and CB2. The most precise way to tell in a short way is the CB1 receptors are predominantly located in the nervous system, and the CB2 is located predominantly in the immune cells. Immune cells meaning these cells are important for maintaining the immune system. There is something showing where these receptors are located. For example, in the neuron, there is something called a presynaptic and postsynaptic. And I'll be talking in the next line how this cannabis works at a molecular level. We'll just consider an example of a neuron. In the neuron, we have a presynaptic neuron and a postsynaptic neuron. For the sake of understanding, think of it as neuron number one versus neuron number two, or a cell number one and cell number two. What actually happens is the information from one cell goes to the second cell, and that's how everything is communicated within the cells or in the nervous system. So when this happens, these cannabinoids inhibit the release of these chemicals. So basically, this is a kind of a brake system to make sure that everything is moderated at equal amounts and in maintaining normal homeostasis. So what we have to understand here is that these endocannabinoids, either the endogenous cannabinoids or the synthetic or the phytochemicals which we take, modulate how the cell communicates with each other. The predominant function of these compounds is to inhibit the communication in a smooth way. So in a nutshell, cannabinoids, whether endogenous or exogenous, reduce the neuronal signaling in the brain or in the body. So whenever there is a condition where there is excess activity in the brain or in any part of the body, these cannabis-based compounds or the endogenous cannabinoids will be beneficial. For instance, let's take an example of a seizure. What they do is they show a lot of electrical activity in the brain, and instantly there are endogenous cannabinoids which are released just to contract them and stop the electrical activity which is happening inside the neuron. Similarly, pain—the pain is actually when there is excess activity which is happening inside the brain—anxiety, and muscle spasticity disorders. These are all some of the conditions where these compounds are very useful. I'm not going to talk a lot about the receptors, but the take-home message is that these compounds are useful in any condition where there is hyperactivity. So what effects do these compounds have? As Dr. Rob Murali has already talked about, two different compounds: one is THC, which is called delta-9-tetrahydrocannabinol, and the second one is cannabidiol, which is termed CBD. So THC, because it is reaching the brain in high quantities, is also termed a psychoactive compound. And CBD is usually considered non-psychoactive because it does not reach the brain in substantial quantities. This is the generic way of telling it. But looking at the mechanism, THC directly fits into the receptor, and then the person will start having various effects ranging from relaxation, altered sensation that may be pain relief, they feel hungry and they start eating more, and after sometimes they sleep. So these are all some of the normal effects of THC. Again, it's a dose-dependent effect. And if you take in more quantities, you start having euphoria, hallucinations, and things like that with THC compounds. The most important thing about CBD is it is non-psychoactive. The question is why? If you can see, CBD does not actually bind to the receptor just like THC, but it modulates the receptor. It does not bind to the receptor; it just modulates the receptor and basically it does not allow THC to come and bind. That's the reason why it is not having any psychoactive component. So which means the CBD can also behave in a certain way. And it has more of an anti-anxiety effect. It is shown to have anti-epileptic effect and anti-psychotic effect. It also is a good pain-relieving agent. It is more of an anti-inflammatory, and some studies are showing it could be a neuroprotective agent as well. So the take-home message here is whether it is THC or CBD, the more likelihood is that the drugs being developed are more likely to be used. So based on the previous religious aspects, is it proven to be scientific? So let's look at what are the effects of the cannabinoids: pleasure or relaxation, memory, coordination, pain control, appetite or vomiting reflex. So what medical problems do you think this can be helpful for? This is the most important question we actually take from all the historical aspects. And then moving forward, based on what it is showing, is there any benefit in terms of treating a medical disorder? So some of the potential research which is conducted and shown evidence for these evidence-based medicines is that these products can reduce nausea and vomiting, and also it reduces convulsions. So these have scientifically been proven to be beneficial, and more importantly, without any adverse effects, not much severe adverse effects. So these are some of the ongoing clinical trials which are happening currently for marijuana and marijuana-based medications. There's a huge list of medications; I've selected a few, but just to understand that the trend towards these medications getting into the approval stage or maybe into the market stage are high, considering the therapeutic potential of these compounds. So again, coming back, there are different kinds of cannabis-based medicines which have already been discussed. One is the whole plant-based medical marijuana. It offers various therapeutic benefits. We have synthetic-derived medications which are FDA approved in the United States. One is dronabinol, which is usually given for patients who have nausea and vomiting after taking chemotherapy for cancers. So these patients have an extreme amount of nausea and vomiting, and dronabinol has been shown to be therapeutically useful for decreasing this nausea and vomiting. We also have nabilone, which is again FDA approved for chemotherapy-induced nausea and vomiting. And there are also these medications approved for anorexia associated with weight loss in patients with HIV-infected patients or AIDS. So based on the reports they have generated from a long time, other medications which are not available in the US but are approved elsewhere are Sativex. These are a combination of THC and cannabidiol; it's a mouth spray, and it's useful for pain relief and muscle spasms. And currently the FDA in the United States is investigating its therapeutic benefits. The other one is rimonabant, and these are used for obesity and nicotine dependence. It's a selective cannabinoid receptor blocker; it's not a drug which goes and binds and activates it. It just goes and blocks the activity, which I have not discussed in the previous slides. The last one is Epidiolex. CBD is used for various types of seizures: one is Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. So basically, this CBD component is beneficial for seizures, as I said, or any conditions where there is high activity of a cell or high activity of a neuron; these compounds are really beneficial. The advantage of CBD is that it is not psychoactive, so it does not induce any behavioral responses. The abuse potential is extremely low. And there are various research which has been conducted with CBD with respect to various other disorders which have high activity, like some neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, multiple sclerosis, and so on. So the controversy again comes back to whether you use medical marijuana or medical cannabis versus THC- or CBD-based medications, and which is better among these two. This is the controversy that has been going on for the past few years. So we just look at what are the pros and cons of these two medications. The THC medications are also having psychoactive effects compared to the medical marijuana or maybe even high because it's a restricted molecule and these are chemicals. In medical marijuana, there are chemicals that moderate psychoactive effects. However, these chemicals are not present in the medications. Smoked marijuana can give effects within minutes, whereas the medications take over a long time, maybe an hour or two. Instant feedback allows users to take more if needed for relief, and due to rapid relief, may consume less smoke. So again, I'm talking about some of the benefits of medical cannabis. When swallowed, THC absorption is more erratic and less concentrated. THC effects are more unpredictable and variable and possibly less effective. However, the problem with medical marijuana is that it is not FDA approved. FDA approval assures that medications are effective, safe, and properly labeled. FDA cannot evaluate medical marijuana as it is a plant with inconsistent composition. There's no way to know if medical marijuana is pure; it can be contaminated by pesticides, mold, fungus, depending upon the region where it is grown, how well the quality is taken care of. And it's always difficult to approach something which is smoked as a medicine. Some of the negative effects of smoking can also be there, and depending upon the type of marijuana, it can undergo different types of chemical changes when burnt. There is no standardized measurement of dose; inhalation varies by individuals, unlike a constant way of taking pills. So in a nutshell, the advantages of medical marijuana are that it has chemicals that moderate THC's psychoactive compounds; however, they are naturally derived, meaning they are extremely safe, apart from a few side effects. These are standardized medical formulations; they are pure, they are not smoked, and they have a standardized dosing. And in the United States, according to federal law, marijuana is still considered illegal. And that's the reason the hypothesis is: can marijuana still be used as a medicine when it is illegal? That's the question we are trying to ask. So the last part of the question that Dr. Murali asked is: is this compound toxic or non-toxic? Toxic by definition means can it cause death? Whether it's an opinion or is it a fact? Cannabis has not even caused a single death as of now just because of overdose. However, the point here is that...

It can cause death because of its indirect effects. It means that you consume cannabis and you start driving a vehicle, you go on it because you are actually in a kind of a sleepy mode, or you are with a group of people and you are trying to hallucinate and then you try to jump from somewhere and fall and get killed. So these are the indirect effects rather than the direct. So these are one of the cases where a person actually fell to death after eating marijuana. He was actually hallucinating, he said that he can fly suddenly and he went to a cliff.

Brain different parts of the brain, whether it binds the cerebral cortex and causes altered thinking, causes impaired memory, or increased appetite, slow reaction time, or if there is loss of balance and incoordination when you consume because it acts on certain regions of the brain which causes certain functions. The most important thing about this cannabis, whether it's an endogenous or exogenous given compounds, is that this cannabinoid receptors which I talked about in the previous slides is not present in the brainstem. What does that mean? This brainstem is a region in the brain which is important for respiratory center and the patient can eventually die because of an overdose. So that's part of the system which actually controls respiration and cardiovascular centers. In cannabis, the receptors for these compounds are not present or less scarily present in brainstem, so there is no CB1 or CB2 receptors in the brainstem. Hence, even if you consume a little bit more dose, the patient might have different effects but he will not die. That's the concept we wanted to tell. So the ending point here is, irrespective of the dose, it is not going to cause a direct dose-related death to the individual. So it can be still considered as a non-toxic.

Different with respect to the TCPT. You might have most of the people might have heard and read in the recent past about the Bollywood stories, the drug stories called CBD containing. People are taking CBD. CBD is a remedy for THC because both of them are from US. What is the status of India? Just one minute, I will tell them. The cannabis definition means only a ganja, that is the flowering top of the flowers.

Definitions. Now just like in alcohol, the states can certainly ban it or allow it. Just like in Gujarat the alcohol is banned, but here it is the same with the heart. Can also be legally sold in several states like Uttar Pradesh, Bihar, Rajasthan, and few more, but not anywhere else. So these are state related things. However, one is less psychoactive than the ganja, and the reason... These are the status as far as India is concerned. Now the cultivation of hemp which is less...

And ingestion, what we call these are two different methods. Inhalation is more for recreation purpose because it floods your brain with the CBD. It immediately, instantly within minutes, you will get the high, but that is not very good because health wise it is also very clear that it can certainly flood the system and blood in very very short time, that the neurons and the whole CB1 receptors get flooded and you make that some difference. But as far as the condition is concerned, digestion goes through the digestive system, it takes an hour or so, it's a sort of slow release, so you get a more soothing.

What happens? This THC gets converted into a corresponding metabolite, an acid which is much more, three to four times more effective as the psychoactive. So it takes care of the psychoactivity overall, but it is more smoother. In India, yesterday I was talking to a buddy and I told about the series. He says in Ayurveda, he himself is using more than a few tons of energy garage leaves every year for the formulations for Ayurveda, because this is the basis for the populations and Ayurvedic products. It has 51 names in the Sanskrit scriptures. So having said that...

Boast to be having so useful. Now as for the next topic is concerned, we will be talking more on the material aspect of it, as well as some sort of traditional aspect and historical aspects we'll be talking about. Like there was some report which said that according to the margin of exposure level, nicotine and alcohol are far more harmful or intoxicating than marijuana. So still it is not legal in many countries and many states. And number two, how does it determine what effect will it have on one?

So if you take a drug A and I take the same drug A, we know we may not be absorbing, distributing, metabolizing, and eliminating the drug the same way. We both are administered 10 milligram or let me not use 10 million, based on our body weight. If a particular drug is being administered, we know we may not be metabolizing the drug the same way. I may have the drug stay in my body longer as compared to you, or you may be eliminating the drug faster as compared to me. So now when you asked about nicotine, alcohol, or any cannabis product, these drugs are definitely being metabolized. So this rate of metabolism completely alters the effect of the drug in the body. So some people will get high immediately.

So it depends upon each individual, that is number one. And that is also again, if you want to go to very basic science, there's a very big genetic aspect to the drug metabolism. The genes that are involved with drug metabolism is not the same. We all have different types of genes. Yeah, just to add to the point, as he said, the two important things are the dose and the second one is the person's genetic things. We call it as a new field which is the pharmacogenomics. We identify each person's genes, how it regulates all the absorption, distribution, metabolism of the drug, and each person varies based on their genetic component. So that's one part. Coming to the second part is the dose of the THC, whether the THC is more, whether the CBD is more, or is the combination, what is the ratio of THC versus CBD which determines the effects. So for everything, the dose of the particular component versus the person's way of handling those compounds determine the actual responses. So we cannot really come to a defined conclusion that this person at this dose, the second person have the same methods. Something similar to that. So hope I answered your question.

See, Avitosh and all of the viewers, it has been found that the largest concentration of these endocannabinoid leakage, which are basically a key which is a very smart key, it finds its lock on its own, that is the beauty. So in the pregnant ladies, basically in the placenta, now the first communication between the fertilized egg and the mother in the mammals, and the research has been done on the... There, if the concentration of the endocannabinoid is not there in the placenta wall, then there is no conception can happen. The egg cannot connect to the wall where the nourishment can start and the growth can start. So that's number one. Second thing is that once the baby is just born, the child is just born, the suckling part of the baby comes from the endocannabinoid system. That means glycerol has to be there in the larger concentration, otherwise the child cannot have the suckling ability of the milk. Presence of endocannabinoid system could have been one of the reason to jump from the birds to the mammalians. This is the evolutionary aspect of this one. So cannabinoids are there, but it has nothing to do with the marriage.

Six months to one year, there are so many regulations for us to get it, number one. So when you are talking about THC, basically how much scientific work has been done is going to be very minimal as compared to CBD, okay? Number two, with regard to yes, there have been with regard to humans, there are a lot of, I don't know about much study carried out with pregnancy and these drugs, but there are animal models that we have studied. At least I'm here in Auburn, Dr. again Brazil and I, we have been part of a group where we have studied about fetal alcohol syndrome, fetal nicotine exposure, and now currently we are trying to do fetal THC exposure. So to answer your question, definitely you can cross the...

Ma'am, it's a governmental design. When you think about research, number one, it's not about the brain drain. We need funding. Everybody, we all have our ideas, and you want to implement the ideas. That's not a problem. There's no brain drain in India. Just don't tell them. We have a lot of smart people. Yeah, that is not the right thing. Where are we going to get funding? Is it going to be from a private sector or public sector? Public sector, when we say that, it's going to be more on the welfare of the society. If it's a private sector, they are going to fund based on what funding can come back. So I'm going to... This product is an Indian product. If you want to look from a basic product, people have been using in India for thousands and thousands of years. So now how are we going to protect this? Is it indigenous to us? How are we going to... So the commercial aspect or the scientific aspect, who's going to fund? We have all the tools, we have all the technology, we have every aspect of that in India. So what is missing is the funding. How are you going to, without funding, research cannot be done. Let's be very honest with that. You can have thousands of ideas to make sure that we are implementing something. The goals, the objectives, it is money driven. We need economic support. It has to be manpower, it has to be the techniques, it has to be the tools. All these are required, and we need funding. Whatever you want to validate, what the... Like a lot of thousands of people are taking multivitamins. Whether we are going to agree or not agree, in another 10 to 20 years, everybody may be consuming a cannabis kind of form. It can be a gel, it can be a tablet, it can be a chewing gum. We are all going to do that. That is where the current society is. We cannot deny that, we cannot stop it. Think about the cosmetic industry, think about the nutrition. We are there. Who is going to accept it? How are we going to validate it? That's the only thing. But here is an update. I can mention in many minutes or so. In 2018 November, Government of India allowed the research on cannabis for medical, traditional, and research purposes. And they have been a participant in the research. And I maybe wanted that his director or the team can join us for a discussion, but I think they are busy. He is the director of the two labs. So in May, he personally told me that there is no possibility in the May, perhaps sometime later on. And if it happens, we will just bring them some time and have a discussion with him on research done in India and being done, research as well as what are the basic policy related things. We'll be covered in the next stop as I mentioned earlier. So India is also waking up, let me put that.

The two aspects here: one, any threat to a drug company, it's an economical war. Number one, whether we are to... Economical war, we are going to say that yes, we can always claim that for centuries Ayurvedic therapy is far more prophylactic, far more therapeutic, it can prevent, it can treat, we always can, both adverse effects are less. But still, as I told you, somebody has to come out and fund us and then take us to the next stage. So that funding is the most important thing. So whatever you say, we can always say we can validate it scientifically, we can prove it, but unless somebody comes and invests... But one thing that we are not going to deny is in Europe they have coffee shops. They call this as a coffee shop. Then every coffee shop, particularly in Holland if you go, they have cannabis, and people who are above the age of, I think for alcohol was 14, I think for... Socialization in India, whether we deny it or not, if I was a 70s kid, so when alcohol was a condition, it's kind of a very bad thing. People who drink alcohol were not accepted in the society. But now alcohol is part of the social function. Everywhere you go, you have alcohol. And whether we like it or not, in another 20 years we are going to have coffee shops with cannabis products, which we are not going to deny. That's coming, or it has come. So now when we talk about this pharmacology toxicology, as a scientist I'm very excited to talk about it. But in reality, how are we going to overcome the adverse effects? That's the only thing that I'm going to use is the adverse effects associated with these. And we cannot regulate it. These are not regulated products. So when you think about all these things, we cannot regulate any of these substances. So we are not going to have any much regulatory agency, but we are going to have it in the market legally or illegally. Most probably it's going to be legalized the same way what happened to alcohol. If you think about the story of alcohol, all these cannabis is going to be legalized soon. The only problem is from the health science point of view, how are we thinking about the acute and chronic effect? Acute effect, chronic effect, it can be both mental, physical, economical impact. We have to get ready for that. I'm just bringing a very similar alcoholism. Think about if you have been from 70s to 2020 in India, in the last 50 years...

I can say that there is an institute in the next book which we are going to have. They are already doing on the formulations of the higher veg. I have also been personally involved for many years in this Ayurvedic populations and scientific validation of that. The problem in the cannabinoids on cannabis is basically the content of the THC varies from parts of the plants, means leaves to the flowers, the resins differently, and they are very vaguely categorized in the NDPS except for the leaves. But the problem is that even with the leaves, if it is... Like in any formulations you have an alcohol concentration, there must be a methodology developed for the THC concentration or CBD concentration in any formulations. Many things like toffees, or the coffee shops, most of the time in the next decade perhaps or in this decade, you will see even in India the formulations are done. Many three people are developing this particular CBD. You can get CBD from the Indian companies under a simple doctor's recommendation. So things will move. And as very clearly mentioned, there is a problem with the Ayurvedic formulations. Migraine, and I don't think cosmetics are also under the same things by the way. So this is a larger perspective I'm talking about. But principal cannabinoids are concerned, our policy matters, the legal aspects are really the biggest stumbling block.