Just four years ago, pediatrician Dr. Orit Stolar was dead set against using cannabis to treat the autistic children under her care. “I would say, ‘you’re off the wall — this is a dangerous drug, it’s illegal.'”
Today, she is running one of the only clinical trials in the world looking at how cannabis can help autistic children, and seeing results in her clinic.
So what changed?
“One kid,” she explained on The Cannabis Enigma podcast. One of her patients came for a periodic visit vastly improved. “I was very sure it’s not something I did, so I asked the mother, ‘what did you do?’ And she quietly said, ‘you know, I’m giving him cannabis.’
Dr. Stolar stayed up all night that night looking for medical research on cannabis and autism. She couldn’t find any, so she set out to create it herself.
One of the biggest problems she faces in using cannabis as a treatment, she explained, is that it’s extremely difficult to know if the plant, or oil extract in her case, is staying consistent over time.
“That’s what’s happening in my clinic. A family starts and says, wow, this really, really helping my child. And then the next month they say, oh my God, it’s gotten really, really bad. And I don’t know if it’s gotten bad or if it’s the bottle that is changing,” she said.
Dr. Stolar thanks all of her colleagues on her study: Dr. Dedi Meiri of the Technion, who analyzes the blood, Prof. Ilan Dinstein of Ben-Gurion University and his team, who do the sleep analysis and EEG, her team at Assaf Harofeh — for everything.
Edited and mixed by Michael Schaeffer Omer-Man. Produced by Michael Schaeffer Omer-Man, Elana Goldberg, and Matan Weil. Music by Desca.
Elana Goldberg: Hi Orit, thanks for being with me today.
Dr. Orit Stolar Hi, thank you for having me.
Elana Goldberg: Sure. Um, so when we’re talking about uh, when we’re talking about children with autism, uh, with autism spectrum disorders, uh, I hear a lot of talk about cannabis treatment and how it relates to the endocannabinoid system. So I’d love it if you could start off by explaining what the function of the endocannabinoid system is in uh, ASD.
Dr. Orit Stolar Okay. First of all we have to talk about what it is in the whole, in everybody. Basically it’s a new, it’s-it’s and old system that we had within our body but we just discovered it in the past 20 years or-or so … a little bit longer. It’s an amazing system, I must say, because that system has the ability to basically cause homeostasis, to balance everything in our body.
It balances our sleep, our eat[ing], our pain reaction, our moods and it also has an important role in brain development. Which for pruning, it’s the ability to, there’s a lot of synopsis that’s happening while the brain is developing and it’s part of the process of deciding what is going to be chopped off and what is going to be left in.
And it has a very important role because otherwise the brain is over-wired, which is a problem. It also helps us forget things, which is kind of cool because when you go to a place where there are thousands of faces, for example in a subway, you don’t need to remember all this data. This is data that is irrelevant and is not important. So it’s like a control-alt-delete that you do on your computer and you download that information because it doesn’t help you for anything. It’s the same thing as remembering the number of the room you’re staying in in a hotel, it doesn’t help you for anything.
And you will see children with autism, that suddenly when you talk to them they remember all those very useless data. Like they would say to me, oh, I went to this and this hotel and I stayed in room 531. And you say to yourself, why do you have to tell me this and why do you remember this? And then you ask, when was this trip? And they say like 10 years ago.
And you say to yourself, why they need to remember that information. Nobody ever showed any relationship between those two things and that’s one of the things that I really want to-to show. That maybe there is a relationship between the system and the memories of all those details.
Dr. Orit Stolar The other thing that we see is a lot of parents report their kids have sleep problems. They either have a hard time falling asleep or staying asleep. And we know there’s a lot of things that influence if we sleep or not, but the endocannabinoid system is part of it. So maybe that’s the cause at least in some of the kids.
Temperature is a very interesting thing, there are parents who swear that their kids’ communication abilities improve when they have fever.
Dr. Orit Stolar And they asked me once, I have a few parents who come to me and say, can you always have my child have 38-degree fever? And I always ask them why. They say, oh, when they are sick they are the cutest, the nicest, the most communicative ever. So maybe that’s related to that, we never were able to explain that relationship — he ability to balance our mood.
I believe that children are good and children with autism are definitely not dangerous or mean. But sometimes their response is with violence. But it’s not because there’s intention, but they’re scared of something. I’ll give an example of another amazing thing about this system. This system can study— it learns, it improves. And for example, if you hear a very loud noise, your first reaction is to — you stuttered.
Dr. Orit Stolar What happened in your body, the cortisol level is going up and, but some also endocannabinoid is being released. The second time you hear that noise, the balance, the amount of cortisol that is going up is a little bit lower and the endocannabinoid system is sending more signals and releases more anandamides to balance it. And the third time you don’t even hear it almost, you just hear the sound and it just goes by you. And probably part of the reason is that the cortisol level is going lower and the endocannabinoid is going higher. So again, it’s kind of balancing — homeostasis is our word here. So if you think about a child with autism, any time you’ll see them doing this all the time, every time they hear a noise, it’s like they’re not learning — there’s no process. Maybe it’s the system that is having a problem and therefore. But this is all theories because nothing was proven yet.
Elana Right. Okay, there’s many things you’ve just covered there that I wanna go back to. So first of all for our listeners that can’t actually see you and can only hear you when you say doing this, can you explain the kind of behaviors that you’re seeing in children?
Dr. Orit Stolar They put their hands on their ears as they hear very, very loud noises, as a response to crowded places, to sudden noises and so on.
Elana Okay. And going back to what you were saying before about memory. So you mentioned that in children with autism often they’re retaining all of this information that they don’t need to retain. What’s the downside of that, like what does that affect, the fact that these memories weren’t deleted or erased as they should have been?
Dr. Orit Stolar I think they occupy their thoughts. They are constantly repeating that information and it’s basically not allowing them to be free to communicate with us or to be in an interaction. Because it’s like the same thing as if you have something that bothers you — you have to, I don’t know, to do laundry and you’re always thinking about it: oh, I have to get the laundry out. I have to get the laundry out, you know? It’s like it’s always there.
So if all you life there is always those noises and those thoughts that are there, it’s overloaded and you, I think it affects your freedom to communicate.
Elana And have you been able to see in your — kind of moving away from the ECS, I suppose — into your clinical practice, have you been able to see situations where less of that unnecessary information is retained and so therefore the patient is calmer?
Dr. Orit Stolar What we see… What I do these days I’m not talking about the medical cannabis, but in my more conventional practice when I have a kid, for example, who has very high anxiety, I can give a medication, like I will give SSRIs that will decrease the anxiety or the obsession — those repetitive thoughts. And by doing so the kids become more communicative.
Dr. Orit Stolar There are very good papers, for example, on risperidone that is the only basic, this and uh risperidone, are the two drugs that were approved by the FDA for, specifically for autism. They’re the only ones. And-and when you look at those studies, they talk about risperidone and they say, oh, it increases the kid’s IQ in some cases. I don’t believe it’s true. I think what it does — it lowers their self-stimulation, the stereotypical movement, the restlessness, and therefore they’re more free to show us, eh, what they know. And then therefore they will perform better on those tests, it’s not like it increases their IQ.
So I think that if I can control a little bit those memories and make it more — make sense out of it a little bit, there will be more of a, it will be easier for them to communicate and show us what they know.
Elana Right, makes sense.
Dr. Orit Stolar Yeah.
Elana So let’s talk about cannabis treatment.
Dr. Orit Stolar Okay.
Elana What are you seeing? What’s working? What do we know?
Dr. Orit Stolar We don’t know anything.
Elana Okay [laughing].
Dr. Orit Stolar We haven’t done enough work. [laughing]
Elana Okay, so why don’t we establish what don’t we know.
Dr. Orit Stolar Okay, what we do know. We know first of all I must say that everything we know is only from the last, the past two years. So it’s new. In fact a child who just learned, he just stood up and started doing his first steps.
Dr. Orit Stolar We have to be very careful and modest about what we claim that it does. And it definitely, what I can say for sure… First of all, I can say that I don’t know enough. Second I can say for sure that it’s not a magic treatment for everybody. It doesn’t cure autism. It doesn’t work for everybody. And even the people that it helps, there’s a lot of problems with it. It’s not constant, sometimes it works, sometimes it doesn’t. And I have more questions than you even can imagine, but I can give you the data that we have as of today.
We know a few things. We know that children with autism have — statistically in two studies that were published — have lower levels of anandamides which is the endocannabinoids that the body produces. And then, if you have lower levels it makes sense that you have to give it.
It’s the same thing as if you have low level of growth hormone then you give growth hormone. If you don’t have insulin then you give insulin. So if you don’t have anandamides, you should give anandamides. We don’t have anandamides yet, so maybe the way to give it is through the medical cannabis.
The second thing we know is that when you look at people who died, and you look at people with autism that died, and you look at their brains as part of their postmortem investigation or status, whatever you say the word, I forgot. You see that they have less receptors for, CB1 receptors that are the receptors for the endocannabinoid system, so that also raise a question, maybe there is something wrong — a dysfunction in that system in children with autism or people with autism.
And we also know that oxytocin ,which is the the love hormone — the one who helps us balance interaction, social interaction, love and so on, and makes us feel good also is related to this system. So there is all kind of clues on the way that kind of make it reasonable to believe that medical cannabis can help.
What we know about studies? As of now there are a few studies that are based on a parent’s report. There is one… There was a big problem because in medicine,in our world we usually start with animal models and then we go to people. But what happened with cannabis is the people are taking it and now I’m studying it and I’m making animal models-
Dr. Orit Stolar … to study it, so the pyramid is upside down. So when we ask parents what they know and what it helps them with, we got some interesting data from that. I’m not the only one who published a paper like this, there were a few others. And what we see is that parents report that it helps in hyperactivity, it helps in anxiety in some cases, it helps in sleep problems and mainly in rage attacks and self-injury and so on. There are a few papers, similar results, the numbers are not so important. Those papers, I have problems because they’re based on parents’ reports.
Dr. Orit Stolar And parents want their kid to do well. And when they are brave to give medical cannabis, they really want it to succeed. So the placebo effect is probably very high, but I must say that I believe that some of this report, it is right. So we-we need to figure it out. There is a study that was done um, the first medical clinical study was done in Jerusalem by Dr. Adi Aran, and he didn’t publish yet his results, but he’s a friend of mine and I know that he got nice results that show that it helps. I must say also that he also reports a very high placebo effect.
Dr. Orit Stolar So we’ll see. And I just started a study that hopefully next time we meet I will be able to tell you what I found out.
But what we’re doing is basically we’re taking the children with autism that have severe comorbidities, meaning rage attacks, anxiety, restlessness ,and we do a full evaluation before. We check the severity of the autism. We check their cognition abilities. We do EEG to all of them. We do blood work. We do sensors under their mattresses. And then we give them a lot of questionnaires, standard questionnaires.
And then we give them the cannabis.
If you talk about cannabis, there’s another problem with it. We know that when you give a bottle of cannabis, of medical cannabis, it’s not for sure that the second bottle will be exactly the same.
Elana Right. Of course.
Dr. Orit Stolar And then we’re in a miss — because that’s what’s happening in my clinic. A family starts and says, wow, this really, really helping my child. And then the next month they say, oh my God, it’s gotten really, really bad. And I don’t know if it’s gotten bad or if it’s the bottle that is changing. So in my study I’m making sure that they get the first bottle and the last bottle will be the same.
I taking samples. I send to independent lab to make sure that really it’s as stable as possible. I’m sure it won’t be stable 100%, but at least to a certain extent.
So there’s a lot of problems when you talk about medical cannabis because the question is, what you’re giving exactly? When you say medical cannabis, what do you mean? It’s like saying I’m giving medicine. What kind of medicine are you giving? Nurofen? Are you giving Tylenol? Those are very different drugs.
Dr. Orit Stolar Both will reduce your fever, but they’re working on a very different mechanism. And when you give cannabis you have to make sure, we need to do some standardization to make sure that people get the same exact [product] as much as possible whenever you can get they are the same exact medicine or treatment.
Elana Right. And what are you expecting to find or hoping to find, I suppose, from this study in terms of the the reports from their parents?
Dr. Orit Stolar What do I want to hear [laughs]?
Dr. Orit Stolar I would love to get… There’s a few things that I really would love to see. I would love to see that the kids that have lower level of anandamides and 2-AG, the endocannabinoids, will react in a specific way that I can — later on in life when the study will be over, it will be really nice if I can predict who are the kids who can benefit from medical cannabis.
And if I will be able to show that the kids who have lower levels of whatever in that system, specific thing, eh, will benefit from a specific treatment, that will be really a nice contribution. Mainly to myself because I’m frustrated, and with the parents — I don’t know what to tell them.
Dr. Orit Stolar But it would be really nice, that’s one thing. Second, I would like to be able to define better who can, who is the one that are benefiting from it and really what does it do? It has side effects, by the way. We know of some of them that are reported but none are, seem to be uh, really uh severe and most of the things that people report, like somnolence, change in appetite and weight are things that are reversible.
So I hope that we will stay in that ballgame because my study’s longer than all the other studies that were, the only one study, clinical study that was done, eh, they did only three months and I’m doing six months.
Dr. Orit Stolar So I hope to see that really it’s stable for the whole period.
Elana What’s the split in the study of low-functioning and high-functioning children?
Dr. Orit Stolar It’s interesting because initially when we started the process I insisted to take in only the low-functioning children with autism. The process to get, uh, the permit to do all the paperwork to get the license to do the study took almost two years. In that time I started seeing in my clinic patients that are high-functioning who are getting cannabis and I said, it doesn’t make sense anymore to limit it to only the low-function.
So now I’m taking in kids, low and high-function, it doesn’t matter, but mainly what’s important to me is that they have severe comorbidities. That the comorbidities is the one who affect their quality of life and I would like to hope that medical cannabis will improve that.
Elana Is it, this is an assumption, I wonder if you can tell me if this is right — that that would be more common among the lower-functioning children, the comorbidities?
Dr. Orit Stolar Um no, that’s not a true statement. A lot of people believe that but I don’t believe it’s true. I see a lot of kids that are high-functioning and the anxiety is basically ruining, for example, their life because the anxiety is managing themself instead of them managing their anxiety.
Dr. Orit Stolar So it’s not always true. However, rage attacks and self-injury is more common a lot of times in the low-functioning although that’s not even a correct statement either because there are high-functioning that are so frustrated they can not communicate it, so they will bite their hands or bang their head. Um, so there are no rules. You see one child with autism, you saw only one, the next one will look very different.
Elana Right. I mean, it’s a spectrum.
Dr. Orit Stolar It is a spectrum.
Elana Yeah. So we’re talking all the time about children with autism, what about adults?
Dr. Orit Stolar I’m a pediatrician [laughs]. I’m a pediatric neurologist, so I can’t talk about them. I don’t see a lot of adults.
But the studies, there’s no studies on them. That’s the next stage. The truth is that I took in my study up to the age of 25, so I’ll have young adults a little bit. But I don’t know much about cannabis and older adults.
Elana Back to the study again, what formulation are you using?
Dr. Orit Stolar We’re giving 20:1 of CBD to THC. The reason is, like I was asking myself why I’m giving this? I don’t have a good answer. I will say this: traditionally it started because that’s what was available. You couldn’t get in Israel CBD, pure CBD initially, and that’s what they were using. And in the market in Israel that’s the most available format that you can get. It’s harder to get pure CBD.
Now on a different level. In a clinic the few patients that, for example, have epilepsy and get pure CBD like Epidiolex or CBD, I see less improvement. I think that you need a little bit of the THC and it makes sense physiologically that to have a little bit of THC, but I’m terrified because the THC is my enemy, I’m scared of it, especially when you’re talking about kids. THC, theoretically, can affect their cognition, their brain development, he’s the one who’s responsible for most of the pruning that we talked about initially at the beginning. It can cause a psychotic effect, attack. So I’m afraid of it, but a little bit I think is safe.
I must say one second, I say one-one more thing.
Dr. Orit Stolar When you talk about children with autism and medical cannabis, in my study I’m giving only 20:1, I have two growers that are giving me the oil. Each kid gets the same oil for the whole period of time. But in my clinic, sometimes when the 20:1 doesn’t work or doesn’t work as well, or in the morning it works and at night it doesn’t, I sometimes go to higher concentration of THC.
Like I would give like 15:3 or whatever, or 5:1. So I can switch, but in the study we’re doing only 20:1. That’s the only thing I’m checking.
Elana And you’re seeing positive results with that switch in the, in your clinical practice?
Dr. Orit Stolar Sometimes. Sometimes yes, sometimes no. Sometimes it’s wonderful at the beginning when you have this patient that was, I mean, he’s 18 years old and he was doing, um, not so well.
The truth is, he was on risperidone and one day the mother sent me pictures of, uh, him destroying the house. Basically taking the furniture and taking them apart. Taking the door, em-
Dr. Orit Stolar … frame off the door. And she said to me, you know, “Help.” And she said, “Increase the risperidone, do something.” And I said, “You know what, why don’t we try the cannabis?” She thought I’m off the wall. She was like, “What are you doing?” I said, “Trust me, why don’t we try?” And after the first or second week already, she sent me pictures of the family sitting down and having dinner. She called me up and she was crying. She says, “18 years we didn’t have a family dinner and this is amazing.”
So it was wow, really wow. And his brother took him to run this little marathon and the whole family function was improving and the quality of life of everybody was amazing. But the story is not such a happy story all the time, because after a few months, I think it was about six months of this honeymoon, things started to get sour and it didn’t work as much. And I started changing the medic-, you know, the cannabis and I tried trying this this and that. Now he’s not taking anything, we took a break. We said that we are stopping because it’s not working and I’ll try again in a month or so, eh, we’ll try something different. So we had this wonderful six months but, you know, sometimes [laughs] as the mother said, you, “I left with that taste that it can happen.”
Dr. Orit Stolar And now it’s not working. So, it works and it should be part of my arsenal of treatments that I’m offering patients, but I need more data. I need more research. I need to understand better. I need to learn why it works and why it stopped working. I have so many questions.
Elana It sounds like obviously you’re treating uh children with ASD, but a lot of your work uh, you say you don’t see adults but you have a lot of parents in your clinic.
Dr. Orit Stolar Yes.
Elana How do they respond to this idea of giving medical cannabis as a treatment to their children?
Dr. Orit Stolar The ones who come to me, they want it.
Elana So they already know.
Dr. Orit Stolar I’m on the opposite side. Iit’s a trend, you know, and people believe that it’s magical. There are a lot of myths out there. It’s funny because a lot of times people say, oh, I don’t want any medications, but just medical cannabis because it’s natural. And I always say, natural is not always safe, you know, we have some samples of like, for example, if you opioids is also a plant and it’s not so safe.
Dr. Orit Stolar So nothing that, not all the things that are natural are safe and we have to be careful. Another thing, it’s not for everybody. I hhad this patient come with a two-year-old and they yelled at me that they wanted me to give them cannabis. And I said, “I’m not giving a two-year-old cannabis.”
Dr. Orit Stolar “I think it’s malpractice.”
Dr. Orit Stolar I also, three I think it’s too young. I wouldn’t give anybody under five, definitely not. Five it’s very, still not comfortable for me. The brain is developing in a very high rate. I’m not feeling comfortable that it doesn’t cause any harm eh, to give it. So, the people who come in, they usually want the cannabis.
I have a few patients that I offered and some of them didn’t want it. They said, “You do your studies on other kids and then let us know.”
Elana So it was only a few years ago that you thought that the idea of treating children with cannabis was a crazy idea too, right?
Dr. Orit Stolar Absolutely. Four years ago, it’s not so long ago. Patients would come in and say, oh doctor, what do you think about cannabis? I would say, oh, you’re off the wall, this is a dangerous drug, it’s illegal. Go, [laughs] you know?
Elana Right. So what happened?
Dr. Orit Stolar Get off this boat.
Elana What changed your mind?
Dr. Orit Stolar One kid, like always. That one child that used to walk into my clinic and always renovated every time he came to visit me that I had to, after he left, to redecorate it. Um, he came and he sat down on the chair and I was very sure it’s not something I did so I asked the mother what did you do? And she quietly said, you know, I’m giving him cannabis.
Dr. Orit Stolar So I said, what? She says, yes. I said, okay. So that was the night that I stayed up and I looked for data and I couldn’t find anything, none, no article. I went into Pubmed, I went into Google, nothing was reported. And it was only four or five years ago. And then I turned to look for help. So I went to my partner, a good friend of mine, one of the best doctors I know, um, Professor Mati Berkovitch, from Asaf Harofeh, now we call it Shamir Medical Center,, and I said, he’s a pediatrician. He’s not specializing in autism but he’s a pharmacologist.
So I went to him and I said, “You know Mati, what do you know about cannabis? He said, “I don’t know that much.” So I said, “Come, we’re on the boat together now.” And we’re starting this journey and I must say that it’s lovely. It’s, he’s amazing and we are finding or way through this thing.
And it’s challenging because there’s a lot of money in it. And a lot of business people, I’m not used to it. I’m a doctor, I’m, you know, I work usually with patients and with labs, and stuff like that. And suddenly we start having all those companies coming to us and asking all of those information and wanting to do business. And it’s a challenge to always, um, it’s not so hard because we both, Professor Berkovitch and I are very much the same and we always stay focused- and say, okay, we don’t care about the money, we want to get answers.
Dr. Orit Stolar So, um, it’s an interesting journey, it’s fun-
Elana Yeah, it sounds like it.
Dr. Orit Stolar … to be part of it, yeah.
Elana Really fascinating.
Dr. Orit Stolar Thank you.
Elana So please be in touch with us when you get the results of this study-
Dr. Orit Stolar I will.
Elana … we’ll do another interview.
Dr. Orit Stolar [laughs] Okay.
Elana We’d love to hear about how it all went and thank you so much for joining me today.
Dr. Orit Stolar We’d love to share. Thank you.
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