Ep. 369: Dr. Shauli Lev Ran

Cannabis Economy Podcast
Ep. 369: Dr. Shauli Lev Ran

Ep. 369: Dr. Shauli Lev Ran

Shauli Lev Ran elaborates on the benefits of increasing research methodologies: “If we’re talking about 4,000 people smoking daily, they may be smoking hundreds of different strains with very different combinations. And we’re kind of making conclusions or sometimes jumping to conclusions that it is associated with higher or lower levels of THC. But like I said, we don’t actually know that. One of the exciting things about the modern era in terms of cannabis research, is that there’s no real reason from a research perspective that in a few years time we won’t have that data.”

Transcript:

Shauli Lev Ran: My name is Shauli Lev Ran. I'm a psychiatrist. I'm Deputy Director of [inaudible 00:00:52] Tel Aviv University.

Seth Adler: Saul or Shauli?

Shauli Lev Ran: So in Hebrew Shauli is from the biblical King Saul. So when I'm in the States and Canada, abroad then it's usually Saul.

Seth Adler: All right. Well, we're here at your office, and thank you for having me. So I'll call you Shauli for-

Shauli Lev Ran: Shauli.

Seth Adler: Shauli.

Shauli Lev Ran: Yeah.

Seth Adler: This is what I'll call you for the time being.

Shauli Lev Ran: That would be great.

Seth Adler: All right. Let's talk about a little mental health Shauli.

Shauli Lev Ran: We shall.

Seth Adler: And how cannabis effects that and how it doesn't and what this all means. So just, why don't you start by giving us a broad overview of the research that you've done.

Shauli Lev Ran: Okay. So I do mostly epidemiological research looking into what can be perceived as psychiatric outcomes of cannabis use. What that means is that individuals who use cannabis particularly regularly, what I'm interested in is in focusing a few years later, after initiating let's even say intensive use for daily use, do they suffer from more depression or less depression? Are there any special characteristics to that depression? Do they suffer for more or less anxiety, et cetera? Does it affect individuals with ADHD different than individuals without?

Shauli Lev Ran: So, the different various combinations between cannabis use and psychiatric disorders and I'm focusing on long term effects. Because the fact that if I smoke a joint now, I may be more anxious in 30 minutes if I tend to be anxious and obviously depending on what strain I smoke, et cetera. Or if I have a tendency to become psychotic because a genetic predisposition, et cetera.

Shauli Lev Ran: My name is Shauli Lev Ran. I'm a psychiatrist. I'm Deputy Director of [inaudible 00:00:52] Tel Aviv University.

Seth Adler: Saul or Shauli?

Shauli Lev Ran: So in Hebrew Shauli is from the biblical King Saul. So when I'm in the States and Canada, abroad then it's usually Saul.

Seth Adler: All right. Well, we're here at your office, and thank you for having me. So I'll call you Shauli for-

Shauli Lev Ran: Shauli.

Seth Adler: Shauli.

Shauli Lev Ran: Yeah.

Seth Adler: This is what I'll call you for the time being.

Shauli Lev Ran: That would be great.

Seth Adler: All right. Let's talk about a little mental health Shauli.

Shauli Lev Ran: We shall.

Seth Adler: And how cannabis effects that and how it doesn't and what this all means. So just, why don't you start by giving us a broad overview of the research that you've done.

Shauli Lev Ran: Okay. So I do mostly epidemiological research looking into what can be perceived as psychiatric outcomes of cannabis use. What that means is that individuals who use cannabis particularly regularly, what I'm interested in is in focusing a few years later, after initiating let's even say intensive use for daily use, do they suffer from more depression or less depression? Are there any special characteristics to that depression? Do they suffer for more or less anxiety, et cetera? Does it affect individuals with ADHD different than individuals without?

Shauli Lev Ran: So, the different various combinations between cannabis use and psychiatric disorders and I'm focusing on long term effects. Because the fact that if I smoke a joint now, I may be more anxious in 30 minutes if I tend to be anxious and obviously depending on what strain I smoke, et cetera. Or if I have a tendency to become psychotic because a genetic predisposition, et cetera.

Seth Adler: Right.

Shauli Lev Ran: Those are kind of short term effects that have at least in part been studied quite well. So I focus on the long term effects.

Seth Adler: Okay, and before we dive in on long term effects, I want to make sure that we are highlighting the fact that we're talking about THC. Only one of the cannabinoids in the cannabis plant. Is that fair to say? If we remove THC and only focus on CBD or CBG or CBC, does that change the conversation?

Shauli Lev Ran: Well, it probably changes the conversation. One of the complexities are is that we don't know exactly to what extent it changes a conversation because you did mention to cannabinoids, which are particularly different one from another-

Seth Adler: THC.

Shauli Lev Ran: Cannabinol.

Seth Adler: Right.

Shauli Lev Ran: For example, Cannabinol has been shown particularly off late to be effective in various neuro developmental disorders, neuro degenerative disorders versus THC, which has been shown to be neurotoxic. So if you take the THC away, and you only had Cannabinol, that'd be one conversation. But you're going to be left with over 100 cannabinoids inside. So, it's probably more complex than that.

Seth Adler: Okay, fair enough. And that is why we're having this conversation with you. Because we like to ... since there is so little information out there, we kind of gravitate to whatever information we have. And so you've got a little bit more of a nuanced conversation around how cannabis affects the brain. So the let's talk about this long term effect and we'll include THC, because that's what when you say you're smoking a joint, that's what you're feeling.

Shauli Lev Ran: Yeah, right.

Seth Adler: That's the cognitive response.

Shauli Lev Ran: It is but you're already touching upon one of the huge in major methodological challenges when we're trying to determine what the psychiatric outcomes of cannabis use are. Because let's say that we're doing an epidemiological study following up on 4,000 individuals using cannabis. Were it to be a medication, then we'd know what molecule they're actually consuming, right? Or what combination of molecules and to what concentration. Even if it's nicotine, just look at the studies back from the 70s, 80s. So, you know what individuals are using and if you break it down, the same can be said for alcohol, you can actually be very precise.

Shauli Lev Ran: Because let's say we're both drinkers and just for the conversation even though most of us are occasional drinkers.

Seth Adler: Sure.

Shauli Lev Ran: And we want to follow up on the long term effects of alcohol on the brain or on the liver or on something else. I can ask you what you're drinking and based on what you tell me, whether it's Budweiser or wine or whiskey, or vodka, et cetera. I can actually break it down, if I know the quantity. And if I know the percentage of alcohol in your drink, I can break it down-

Seth Adler: Precisely.

Shauli Lev Ran: Precisely.

Seth Adler: Right.

Shauli Lev Ran: So going back to what you said, we're talking about THC. Well, not only. So if we're talking about 4,000 people smoking, let's say daily, they may be smoking hundreds of different strains with very different combinations. And we're kind of making conclusions or sometimes jumping to conclusions that it is associated with higher or lower levels of THC. But like I said, we don't actually know that. One of the exciting things about the modern era in terms of cannabis research, that there's no real reason from a research perspective that in a few years time we won't have that data.

Seth Adler: Right.

Shauli Lev Ran: Because you can actually ask a lot of individuals, so what are you smoking, et cetera. We'll still have other problems because most individuals don't only smoke one strain and the fact that as opposed to other substances for example, alcohol, when two different people smoke, they take different volumes of inhaling and obviously different metabolism. But even just thinking about smoking versus drinking, two very different things. So that was just touching upon me out of the various methodological challenges.

Seth Adler: And also as these labs that are testing the cannabis which are online in the US and are coming online in Israel get more and more advanced, there'll be able to tell us precise breakdown of the percentage of THC versus the other cannabinoids within the plant.

Shauli Lev Ran: They will. I sure hope they have good guys working or good women working on the analytics. Because it's going to be a lot of big data, and it is a lot of big day.

Seth Adler: Sure.

Shauli Lev Ran: Just like we mentioned beforehand, we're talking about hundreds of cannabis laws. And, that's not even including the Tropines, et cetera. So, you can just imagine thousands of people, even, let's say you're talking about medical marijuana, thousands of people, hundreds of disorders, and each strain with a different concentration and hundreds of different molecules. So very big data. So those are probably, this is true throughout research in general in 2018.

Seth Adler: Sure.

Shauli Lev Ran: Those are the important guys nowadays. Accumulating data is one thing.

Seth Adler: Yeah.

Shauli Lev Ran: Analyzing data is a whole different thing.

Seth Adler: All right. And so, we will continue to converse with folks like Steep Hill labs, which I've spoken with Jmîchaeĺe Keller. That's a global lab and they're doing great things as far as analytics are concerned, but we got to keep our thumb on, is what you're saying. We got to keep pressing to make sure that we get pure information as far as the information that you've received, how long term can your data be, as far as the evaluations that you've made? Please share.

Shauli Lev Ran: So what we're doing, we're analyzing data from two waves of a study conducted by the National Institute on Alcohol Abuse and Alcoholism in the States, one of the NIH institutes and it's probably the largest epidemiological study on substance use and psychiatric disorders called the NESARC, two waves three years apart. So analyzing a lot of data pertaining to individuals who use cannabis and then trying to determine what we actually mean by frequent use versus infrequent use, because you're taking a continuous variable, so to speak, like height or weight, and you're categorizing it very artificially.

Seth Adler: What did you mean in the study? I guess.

Shauli Lev Ran: So in a lot of our studies, we started out by dividing cannabis users into three categories, into very occasional users which use less than once a week, which we expected to find not substantial associations between that level of use and psychiatric disorders. Perhaps aside from individuals with a very strong genetic predisposition. Individuals who may have already suffered from a psychiatric disorder. Individuals who use weekly but less than daily or almost daily. So people use a couple or a few times a week.

Seth Adler: That's the second group.

Shauli Lev Ran: That's the second group and third group are individuals who use daily or almost daily which is six, seven times a week.

Seth Adler: Okay.

Shauli Lev Ran: So, can I stand behind that 100%? Of course not. For example, our recent studies refer to two categories. Individuals using three times a week or more. Excuse me more than three times a week. So using more often than not.

Seth Adler: Right.

Shauli Lev Ran: Versus individuals using less. So, I'm author on both kinds of studies, which means that there is no real discrete categorization. But it is particularly important because one of the things that we've known ever since, I think it was probably the 50s. Sir Bradford Hill English Epidemiologist constructed a set of rules that ... Yeah, you should stand by before determining causality between an exposure variable and an outcome variable, between cause and effect. One of them is dose dependency.

Seth Adler: Okay.

Shauli Lev Ran: Which means that what we expect for example, let's go back to the example of alcohol and liver disease, I would expect that if our alcohol is associated with liver disease, the more alcohol I consume, the more severe my liver disease will be and the higher the risk for developing that diseases is. So we expect the same from cannabis.

Seth Adler: Right.

Shauli Lev Ran: That the higher the dose, the higher the risk for psychiatric disorder or the more severe the psychiatric outcome will be. But then we have to ask ourselves, "Okay, what do we mean by dose? Do we mean frequency? Or do we mean for example, number of joints per day?" Two very different variables. You and I can smoke a joint daily.

Seth Adler: Mm-hmm (affirmative)-

Shauli Lev Ran: I may be smoking small joint in the evening. You may be smoking morning till evening. We're going to be in the same category in terms of frequency.

Seth Adler: So, for the study, what did you focus on?

Shauli Lev Ran: So, for the study, we focused on those three groups. Analyzing-

Seth Adler: And as far as dosage, what did you focus on? How did you define it?

Shauli Lev Ran: We defined it as frequency.

Seth Adler: Okay.

Shauli Lev Ran: What we're working on now is trying to establish a measure which takes into account both.

Seth Adler: Mm-hmm (affirmative)-

Shauli Lev Ran: A bit like we do for cigarette smoking. Cigarette smoking we have a term called pack years, which is the multiplication of the number of years I've been smoking times the number of packs I smoke per day. A pack is 20 cigarettes.

Seth Adler: Right.

Shauli Lev Ran: So, we're trying to construct a similar kind of term in cannabis taking count both frequency and dose. So we focused on frequency. And what we expected to find when we studied the association between cannabis and depression, is that if there would be or if their were an association, then the higher the frequency of use, the stronger the association with depression will be. So we weren't surprised that we didn't find it among very occasional users. Because, like I said, no real reason to think that, that would induce depression.

Seth Adler: Okay.

Shauli Lev Ran: But we didn't find it among those who use at least weekly and we didn't find it among daily users either. So, three years later, individuals who are using cannabis continuously don't have ... and we excluded all individuals with depression at base line. So we're only talking about individuals who never had a severe-

Seth Adler: Right.

Shauli Lev Ran: Major depressive episode.

Seth Adler: Okay, great.

Shauli Lev Ran: Three years later.

Seth Adler: Yeah.

Shauli Lev Ran: Using cannabis even daily, they don't have a higher risk of developing depression than their counter part.

Seth Adler: Okay, am I to receive that as I think good news? Can we check that box? As far as depression is concerned, at least for the time being based on the research that's been done?

Shauli Lev Ran: We may.

Seth Adler: Okay. I'll take it.

Shauli Lev Ran: No, yeah. So we may. One of the issues that caused us a bit of concern, is that the second question we asked ourselves-

Seth Adler: Okay.

Shauli Lev Ran: Is well, maybe it's the other way around. Maybe people who are depressed who've touched cannabis are at a higher risk to initiate cannabis use as a form of self medication.

Seth Adler: Understood.

Shauli Lev Ran: And then the answer was significantly yes.

Seth Adler: Sure.

Shauli Lev Ran: So even if you take into account the large number of background variables which can confound our results, you still see the same pattern that individuals who are depressed who have never touched cannabis are at higher risk to initiate probably but this is already interpretive is a form of self medication, which led us to the next question, so is it helpful? The self medication is an attempt of consuming a substance in order to feel better.

Seth Adler: Right.

Shauli Lev Ran: The question is, is it done effectively? And that's where we were a bit more surprised, because in the next study, we analyzed what happens to depressive symptoms among those individuals who have depression and started using cannabis. So are the better off than their counterparts who have depression who aren't using cannabis? And the answer to that was, no, they aren't.

Seth Adler: They are not better off.

Shauli Lev Ran: They are lot better.

Seth Adler: Okay. And are they worse off?

Shauli Lev Ran: To a very small degree.

Seth Adler: Okay.

Shauli Lev Ran: In very specific, A, in terms of how worse off they are very, little.

Seth Adler: Okay.

Shauli Lev Ran: I mean, so very small differences significantly from a statistical point of view, but very small in terms of the effect. So it's not a very big effect, but it's statistically significant.

Seth Adler: Okay.

Shauli Lev Ran: So the domains were particularly things like psychomotor activity, weight, some sleep disorders. So, again, on the one hand, we didn't see any differences in terms of suicidality, not for the better not for the worst.

Seth Adler: Okay.

Shauli Lev Ran: In terms of functional outcomes. In terms of by proxy measures, which indicates severity, like hospitalizations, going to the ER, receiving medication, et cetera. So no more of that.

Seth Adler: Okay.

Shauli Lev Ran: Slightly less better off in terms of sleep, psychomotor, et cetera. But for the most part, not a lot of effect.

Seth Adler: Okay.

Shauli Lev Ran: Neither direction, so that surprised us.

Seth Adler: So this is depression. Let's put depression away for a second if you would, Professor if you don't mind, and let's move on to a next kind of condition. Where would you go next? I guess. I don't want to guide to. You tell me.

Shauli Lev Ran: So I'd go domain pain.

Seth Adler: Okay, let's do that.

Shauli Lev Ran: Which is a big one.

Seth Adler: Yes. Because we all feel like we're on the same page as far as pain. Go ahead.

Shauli Lev Ran: And I think we are, and we should be.

Seth Adler: Okay.

Shauli Lev Ran: Particularly because you always have to assess the perils and advantages of a substance in comparison to other alternatives for the same disorder.

Seth Adler: Understood.

Shauli Lev Ran: So, particularly in the States, but not only Western Europe, Australia, Canada, opioid epidemic. When you think about pain-

Seth Adler: Yes.

Shauli Lev Ran: It's irrational to compare cannabis users to non-users. One of the more important things is using the comparison of individuals with chronic pain using opioids.

Seth Adler: There we go.

Shauli Lev Ran: And that's what we've explored quite a bit.

Seth Adler: Roll your sleeves up. Let's do.

Shauli Lev Ran: So I think some of our findings are not surprising but extremely important, and I don't think they've been stated as such.

Seth Adler: Okay.

Shauli Lev Ran: So the first thing we explored is among individuals with chronic pain who use opioids versus those who use medical marijuana, what percentage develops addiction. So we found substantial significant differences there. Among individuals, for example, with chronic pain who use opioids, even using the most conservative measures over 16% developed opioid dependence.

Seth Adler: 16%.

Shauli Lev Ran: 16, yeah.

Seth Adler: Okay. All right.

Shauli Lev Ran: Or a form of problematical opioid use, depending on the tools we use.

Seth Adler: Yep.

Shauli Lev Ran: But that is the most conservative. The least conservative, if we just went according to psychiatric DSM diagnosis was about 50%.

Seth Adler: Uh-huh.

Shauli Lev Ran: So I tend to be conservative when I state my results.

Seth Adler: Fair enough.

Shauli Lev Ran: Let's say at least 16%.

Seth Adler: Right.

Shauli Lev Ran: Versus those who use medical marijuana who have chronic pain which only in the quotation marks about 10% developed a problematic marijuana use or marijuana dependence.

Seth Adler: And so now we're going to put a pin in that and take that tangent because I am from the understanding and I don't know where I got this, so I'd love for you to turn me wise. That cannabis is mentally addictive, yet not physically addictive. Does what I just said mean anything?

Shauli Lev Ran: Well it means what we used to think. That's basically what it means in terms of ... first of all substances by definition, which are addictive, are psychologically addictive. I mean, so I'll have

Seth Adler: I could be psychologically addicted to chocolate, for instance.

Shauli Lev Ran: Yeah, particularly to caffeine.

Seth Adler: Okay. That's a different. I meant chocolate and as opposed to coffee, because I know that I'm both physically and mentally addicted to chocolate.

Shauli Lev Ran: Right.

Seth Adler: I don't think that I'm physically addicted to, excuse me to coffee. I know that I'm physically addicted to coffee. I don't think that I'm physically addicted to chocolate, although it tastes oh, so good.

Shauli Lev Ran: It does indeed.

Seth Adler: So do you see the distinction I'm drawing?

Shauli Lev Ran: Yeah, yeah.

Seth Adler: So, where does cannabis-

Shauli Lev Ran: Well, I'm going to refer to the DSM.

Seth Adler: Okay. Please. Yeah.

Shauli Lev Ran: The Diagnostic and Statistical Manual, which is a kind of the code book for psychiatric diagnosis.

Seth Adler: Yes.

Shauli Lev Ran: So I'm going to refer to that for a second because it does make some sense in terms-

Seth Adler: Please.

Shauli Lev Ran: What substances are included in the chapter on substance use disorders and addictive disorders.

Seth Adler: Okay.

Shauli Lev Ran: First of all in general there are three domains that determine addiction. There's the physical aspect, which a lot of times is determined by either developing tolerance. So I need increasing doses to get to the same effect or withdrawal symptoms, which means that if I stop abruptly, I'm going to suffer from ... now we tend to think of withdrawal as heroin withdrawal. That kind of junkie-

Seth Adler: Yeah.

Shauli Lev Ran: "Withdrawal" from the movies and Burroughs, et cetera.

Seth Adler: Sure.

Shauli Lev Ran: But withdraw can be being more agitated or sleep disorders.

Seth Adler: Yeah.

Shauli Lev Ran: Having kind of mood swings, a lot of things that you can definitely see with cannabis. And those are part of the cannabis withdrawal criteria in the DSM.

Seth Adler: I thought we were talking about coffee. Because in all seriousness, if I don't get at least two cups of coffee in the morning, the whole thing is a mess.

Shauli Lev Ran: So, I'm with you. We met this morning. First thing I did was tell you, "Hey, I'm going to come back."

Seth Adler: Grab a cup of coffee.

Shauli Lev Ran: So I'm the same as you. And that's why caffeine is included as one of the substances in the DSM under the addictive substance category.

Seth Adler: And DSM sees cannabis the same as coffee?

Shauli Lev Ran: Well, the same as coffee and the same as cocaine. They're all in one category.

Seth Adler: Oh, okay. Well that's problematic.

Shauli Lev Ran: Yeah, but it's not a it's not like the legal schedules. It's just something saying, you have a variety of substances which have a greater tendency to be addictive.

Seth Adler: Where's the spectrum? I guess is my point it I understand. Okay, fine. We think that cannabis could be construed much like coffee is construed in the human body.

Shauli Lev Ran: Right.

Seth Adler: Where is the spectrum as far as the DSM is concerned? It doesn't sound like there is a spectrum.

Shauli Lev Ran: There's a spectrum for each substance based on the number of symptoms and individual has, which means that if you have a substance use disorder, which doesn't, by the way mean anyone using cannabis.

Seth Adler: Yeah.

Shauli Lev Ran: The majority of people using cannabis don't have a cannabis use disorder. But those who do a can have a mild, moderate or severe. So the spectrum is it within the disorder.

Seth Adler: And within each?

Shauli Lev Ran: Yeah, with the each substance. I do have to say that as critical as a lot of us, even as psychiatrists are with the DSM, more with a parallel ICD, International Classification of Diseases or disorders, it's important to remember that it's also a key for access to care. So we're always in a tricky zone there because the lower the threshold is for a disorder on the one hand you're designating and individual's having a disorder. On the other hand, chances are that if he needs treatment, he's going to be reimbursed by his insurance coverage. So it's also an act of compassion. It's a bit tricky in that aspect.

Seth Adler: Okay.

Shauli Lev Ran: Because there was a lot of sociology and economics going into those diagnosis.

Seth Adler: Anyway, getting back to the 16% to 50% of opioids, versus what was a 10% for cannabis?

Shauli Lev Ran: Right.

Seth Adler: Okay.

Shauli Lev Ran: So A, we have the physiological domain, then we have the psychological domain, which is a requirement or a part of every diagnosis of a substance use disorder. So that is a psychological aspect of preoccupation, or pathologically pursuing a specific feeling or let's say a feeling of reward.

Seth Adler: Okay.

Shauli Lev Ran: That's kind of a neurobiological term. And the third aspect is continuous use despite negative consequences. So these are the three domains. So we're not going back to Cannabis. So looking at the physiological effects, I think there's no doubt physiological effects of opioids are substantially greater. And when they said that you have to think of real life comparison between two substances, aside from driving which data there is quite clear, there's no comparison between the risk for death, let's say between opioids and cannabis that side effects, adverse effects, the sedating effects that, overdose doesn't happen with cannabis, literally almost impossible. So driving is one thing, but that's a huge difference between the two.

Seth Adler: And the number today is the same as it has been, since the beginning of time. Zero deaths from cannabis explicitly.

Shauli Lev Ran: Exactly.

Seth Adler: Right.

Shauli Lev Ran: So, that is extremely, that that should in many ways, or maybe perhaps should be the end of the conversation. Because one, it's very risky, the other is not risky. And probably from what we see, at least in chronic pain effective to the same extent, if not more, so to speak. So it was so that's one aspect that we saw. Second aspect that we saw is that those individuals who are using medical marijuana and have chronic pain had less anxiety and less depression.

Seth Adler: Mm-hmm (affirmative)-

Shauli Lev Ran: So this may be attributed to a few things. A, we know that opioids are depressants to the central nervous system. So, makes sense that they're more depressive, and B, that especially those which metabolize rapidly, part of a what happens when the body metabolizes an opioid is that you get into these short withdrawals part of which may be experiencing anxiety. So it may make sense. The other part is that there may be antidepressant and anxiolytic properties to cannabis.

Seth Adler: Right.

Shauli Lev Ran: So those are findings which are extremely important because, country is different, states different within the US, as to what is considered first line, second line. For example, in Israel, at least up till recently, first line for treating pain was opioids.

Seth Adler: Yep.

Shauli Lev Ran: If you fail, then you go on to get well. I think that kind of research raises question is that the right order?

Seth Adler: Yeah.

Shauli Lev Ran: Shouldn't it be the other way around?

Seth Adler: What about cannabis solving, opioid abuse and opioid addiction?

Shauli Lev Ran: That's actually trickier in a way. Data is not conclusive.

Seth Adler: Fair enough.

Shauli Lev Ran: There's been some evidence indicating that states in which medical marijuana is legalized, they have less of an opioid probably.

Seth Adler: Yes.

Shauli Lev Ran: Versus others studies coming out which don't show exactly the same thing.

Seth Adler: Okay. That one's up for grabs. As far as you're concerned.

Shauli Lev Ran: It is up for grabs. And again, I think we have to differentiate between long term prevention and treating an existing epidemic. Those are probably two different things.

Seth Adler: Understood.

Shauli Lev Ran: And there is an important focus that I think should be mentioned in that is the way the message is conveyed to teams and to very young people.

Seth Adler: Mm-hmm (affirmative)-

Shauli Lev Ran: Because one of the things that has happened with the legalization of medical marijuana is that anything designated as medical is perceived as good. It's healthy kind of by default and by definition.

Seth Adler: Mm-hmm (affirmative)-

Shauli Lev Ran: We should be concerned about very young people about teen, and that's where we have to think about ... There are studies showing that places in which medical marijuana is legal, the perceived harm among very young people is substantially lower.

Seth Adler: We've also seen numbers that say that teen use is actually down because it's legal.

Shauli Lev Ran: That also happens. I think where we have to get our message straight.

Seth Adler: Yeah.

Shauli Lev Ran: Well I think the message should be things along the lines of postpone it a bit.

Seth Adler: Yeah. Yeah.

Shauli Lev Ran: Postpone it a bit, which I think is a responsible message just like a lot of other things.

Seth Adler: Absolutely.

Shauli Lev Ran: We do that for driving.

Seth Adler: Hang out until you're 18.

Shauli Lev Ran: Exactly.

Seth Adler: My brother in law, the neuroscientist will tell you that the child's brain is not developed really until 18 and mine's still going. So, I'm 42, right. And you're 42 too I think.

Shauli Lev Ran: 45 already.

Seth Adler: Oh, my goodness.

Shauli Lev Ran: Yeah. 45 and going. Look at me. So I think that it's complex, but I think an important message which I think from a lot of teens that I meet will be better received than the just say no message, because you get that look. I sit across from teens they give you that look saying, "Okay, you got another old geese who doesn't know anything about anything."

Seth Adler: Exactly. Well and then there's also the distinction for young people that have epilepsy that cannabidiol absolutely is helpful in bringing down the number of seizures.

Shauli Lev Ran: Well Cannabidiol in general there's a huge question should we even talk about Cannabidiol in the same sentence as cannabis at large.

Seth Adler: This was my initial point.

Shauli Lev Ran: Being [inaudible 00:27:23] you're protective.

Seth Adler: Right.

Shauli Lev Ran: Studies coming out, a systematic review coming out indicating that it may be beneficial for treatment resistance because of Frenia. Who would have thought cannabis [inaudible 00:27:35] schizophrenia, et cetera. Alzheimer maybe potential, autism. So have a lot of things and places, countries looking at legalization of Cannabidiol alone. Saying maybe we should think about that differently because that is, no indication that that's harmful or has any psychoactive activity on it's own.

Seth Adler: You bring up because I know that you're focused on mental health that you brought up schizophrenia and I've heard now a couple of different sides of that equation. And I think what you are saying is with Cannabidiol, maybe there's potential help as far as schizophrenia is concerned. Where I've heard, be careful, just like the depression thing, be careful if you've got a history of schizophrenia or schizophrenia in your family with utilizing THC.

Shauli Lev Ran: Which is a very big difference.

Seth Adler: Yeah.

Shauli Lev Ran: I mean, first studies came out. Well, to be honest, a lot of my clients and I think that's where a lot of the research into the short term effects started. Clients, individuals coming in saying, "Listen, man, after I smoke, I'm a bit more paranoid. There's a knock on the door I think maybe it's the police, et cetera. So I'm a bit more paranoid."

Seth Adler: Of course. Right. These are the side effects. You might get hungry. You might get paranoid.

Shauli Lev Ran: Exactly. So that's something that you talk to anyone who's smoked, they'd tell you it may happen.

Seth Adler: Yes.

Shauli Lev Ran: It's kind of an extreme form of anxiety of sorts.

Seth Adler: But where does that paranoia go? Medically, what are we actually talking about?

Shauli Lev Ran: So, if you take healthy subjects, and if even if you infuse THC intravenously, within-

Seth Adler: My goodness.

Shauli Lev Ran: Exactly.

Seth Adler: No thank you.

Shauli Lev Ran: Not for you.

Seth Adler: Not at all.

Shauli Lev Ran: You'll stay yeah old fashioned ways.

Seth Adler: That's exactly right.

Shauli Lev Ran: So four hours later symptoms have subsided. But for healthy individuals if you ask them to or if you interview them with a structurized interview or structurized questionnaires looking at psychotic symptoms, you'll see an increased. Healthy individuals getting a THC infusion and they'll subside within 240 minutes just about so.

Seth Adler: Okay.

Shauli Lev Ran: So that's acute and it'll subside.

Seth Adler: Sure.

Shauli Lev Ran: But for individuals who do have a predisposition like you mentioned, there are already quite a lot of studies and probably the latest and most important meta analysis, 11 years old from 2007 indicating that cannabis users are at about a two fold risk for developing psychotic disorders. Not a two hour uneasy feeling but rather psychotic disorder. And this is also important because it touches upon the way messages and scientific messages are conveyed.

Shauli Lev Ran: The prevalence of schizophrenia in the general population is about 1%.

Seth Adler: Okay.

Shauli Lev Ran: Something a bit of a statistical trick now, but not very crude, if the risk among cannabis users is two fold, so let's say that brings it up to 2%. I can phrase the same by saying that over 7% of individuals who use cannabis won't suffer from psychotic outbreak. Both will be true.

Seth Adler: Yes.

Shauli Lev Ran: Scientifically-

Seth Adler: Right.

Shauli Lev Ran: Kind of depends what story I'm trying to tell, what narrative I'm trying to tell. But that did bring about a lot of concern among mental health professionals as to people's schizophrenia and cannabis. And I think that's been changing when studies about Cannabidiol came out. So that's why a lot of individuals are calling for, a lot of professionals are calling for talking about it kind of in a category of its own.

Seth Adler: There we go.

Shauli Lev Ran: Which I think can be helpful, because it'll lower resistance among mental health professionals and a lot of the good studies coming out in those that ... there's a big study that a, well it's been in the media hasn't been published yet to the best of my knowledge, but it's already been in the media about refractory autism and CBD conducted in Shaare Zedek, Jerusalem. So you have autism, you have epilepsy, neuropsychiatric or neurological disorder, you have enough initial data about schizophrenia. Interesting data about Alzheimer. So all those touch upon the fact that Cannabidiol may be extremely important in psychiatric disorders, and we probably haven't even seen the potential of it.

Seth Adler: That's it.

Shauli Lev Ran: Yeah.

Seth Adler: Yeah. And so we end at the beginning, I guess. I want to keep talking to you, because I'm sure that we didn't bring up many conditions, which you know about, but we don't have that kind of time.

Shauli Lev Ran: Sure.

Seth Adler: At least today. And so Shauli.

Shauli Lev Ran: Yeah, yeah.

Seth Adler: I'm going to ask you the, I'll tell you the three final questions. I'll tell you what they are, and then I'll ask them in order. What's most surprised you in cannabis? What's most surprised you in life and on the soundtrack of your life? One track one song that's got to be on there. But first things first. We've been talking about cannabis here, and you've been really looking at it. And you've been really, you understand it in a different way than many, many, many people. Most people of Earth for that matter. What's most surprised you in cannabis?

Shauli Lev Ran: I think the rapid medicalization of it.

Seth Adler: As we sit here in Israel, getting ready for Cannaan.

Shauli Lev Ran: Exactly.

Seth Adler: The conference that's being put on by the Ministry of Health of Israel.

Shauli Lev Ran: Well, that has to do the fact that, I'll try to be short on this. Because you can say I'm passionate about cannabis. So I'll try to be short.

Seth Adler: Yeah.

Shauli Lev Ran: So, we have this, we have criteria for who can receive medical marijuana. So let's say I have social anxiety, but I don't meet the four criteria, nor am I going to go to for psychiatric evaluation. But man, it helps me. Should I really have to have X criteria out of Y from a Chinese menu kind of diagnostic manual in order to get cannabis or and I think that's where the line between recreational and medical kind of dissolves. I'm not sure I believe in that line. We're on a spectrum-

Seth Adler: It's all wellness.

Shauli Lev Ran: It's all wellness everything. So who's to say that aspect that if I had severe traumatic events but didn't develop full blown PTSD I shouldn't receive it but if I did develop I should because I have one more criteria. So, I'm in a bit of a funny position. I'm a lot more towards legalization than towards only medical marijuana because I think it brings about a categorization which is not true in life.

Seth Adler: Interesting. And based on what you said that's interesting because we are distinguishing between THC and other cannabinoids within the conversation and so what we're saying or if we're saying that it is all wellness, is it does come back to those analytics and making sure that we know exactly.

Shauli Lev Ran: I agree.

Seth Adler: What's in everything, yeah.

Shauli Lev Ran: I like the word wellness because I think, that's what medicine is about generally. It's about increasing wellness.

Seth Adler: Sure.

Shauli Lev Ran: So it's not only about putting down a line saying you should, you shouldn't, and things like in different countries use it differently. In Canada up to late I think one of the criteria was any medical condition which a physician is under the impression that you can benefit which in my opinion makes a lot more sense. It's a kind of holistic general approach, which I think is better.

Seth Adler: Yeah.

Shauli Lev Ran: So I think that's one thing.

Seth Adler: What's most surprised you in life?

Shauli Lev Ran: I don't know if exactly surprised but it keeps on surprising the extent the importance of family. You go about running, trying to achieve a lot of different stuff, and whatever. It can be career, it can be money, it can be sports, it can be, and end of the day, those are the most important people you have around you. So, it keeps on surprising me the extent to which that is-

Seth Adler: The case. [crosstalk 00:34:52]. All right. On the soundtrack of your life, one track one song that's going to be on there.

Shauli Lev Ran: That's probably a tough one. Especially if it has to be in English. Well, hey I know one. Doesn't necessarily have to be the soundtrack of my life. I just, Lou Reed, Magic and Loss is where my mind goes.

Seth Adler: There you go. That's why we asked the question. That's perfect. He's a New Yorker, I'm a New Yorker.

Shauli Lev Ran: Yeah, exactly. [crosstalk 00:35:16]

Seth Adler: Very much appreciate it. Shauli thanks so much.

Shauli Lev Ran: A pleasure.

Seth Adler: We will check in with you down the line.

Shauli Lev Ran: Great. Enjoy your stay here.

Seth Adler: And there you have Shauli Lev Ran, very much appreciate his time. Very much appreciate your time. Stay tuned.

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