Cannabis & Tourette Syndrome: The Evidence, The Promise, & The Perils

0:04 Good evening and welcome. 0:06 Thank you so much for joining us for tonight’s webinar, Cannabis and Tourette Syndrome, The Evidence, the Promise, and the Perils, presented by Dr. Elia Abidjaoudai. Hopefully I don’t butcher that. 0:19 My name is Katie Delaney, and I’m the Family and Medical Outreach Coordinator for the New Jersey Center for Tourette Syndrome and Associated Disorders. I will be your facilitator for this evening. 0:29 Before I introduce our presenter, I want to go over some housekeeping notes. 0:33 The audience is muted. 0:34 If you are attending the live webinar, questions can be submitted in the questions box at the bottom of your screen. 0:41 During the live Q &A, the audience will gain access to unmute themselves. 0:44 We will stop recording right before this. 0:47 At the top right of your screen, you’ll see a paperclip icon. 0:50 Ooh, excuse me. 0:52 At the top right of your screen, you’ll see a paperclip icon. 0:57 There you will find a copy of the slides and upcoming events. 1:01 At the bottom of your screen, you’ll see a react button. 1:04 To the right of it is an arrow. 1:06 When you click the arrow, you will see a few emojis appear, such as heart, thumbs up, et cetera. 1:11 Throughout the webinar, feel free to use this feature to let our presenter know how they’re doing. 1:16 Give me a thumbs up, you guys, if this sounds good. 1:22 Beautiful. Thank you, thank you. 1:25 Okay. So, for those viewing the webinar recording, you will not have access to these features. 1:32 However, any questions you have for the presenter can be submitted through the chat box to the left of your screen. 1:38 The presenter will answer those questions on our webinar blog located on our website, njcts.org, under the programs tab. 1:46 This blog will be monitored until Tuesday, February 4th. Any personal information will not be included in the post. 1:53 Real quick, for Q &A section for the live. 1:56 In addition to the audience getting access to be able to verbally ask their questions, also feel free to manually submit questions in the questions box in the upper right hand of your screen. It’ll be a box with a question mark in it. 2:13 So we’ll be answering those as well. 2:16 The New Jersey Center for Tourette Syndrome and Associated Disorders, its directors and employees assume no responsibility for the accuracy, completeness, objectivity, or usefulness of the information presented on our site. 2:30 We do not endorse any recommendation or opinion made by any member or physician, nor do we advocate any treatment. 2:45 You are responsible for your own medical decisions. 2:48 Now it is my pleasure to introduce speaker for this evening, Dr. Elia Aby-Jaude? How did I do? Good, awesome. Dr. 2:59 Aby-Jaude is the medical director of ambulatory psychiatry at Toronto’s Hospital for Sick Children, where he leads the Provincial Pediatric Tics and Tourette Clinic. 3:11 I’m struggling with these words today. 3:13 He holds an MS in neuroscience from McGill University in Montreal, an MD from the University of Manitoba and a PhD in Cognitive Neuroscience from the University of Toronto. 3:26 Dr. 3:26 Abhi Jaude also works at the Tourette Syndrome Neurodevelopmental Clinic at Toronto Western Hospital, oh my goodness, specializing in developmental neuropsychiatry. 3:40 His research spans neurobiology, psychopharmacology, cannabinoids, and function-like tick behaviors. Oh my gosh, that is a mouthful. I love it though. 3:54 So, Dr. Abhi Chaudhary, the floor is all yours. Oh, you are currently muted. 4:07 All right, can people hear me now? All right. You are all good. 4:11 Okay, and can people see this in presentation mode, my slides? 4:17 Can I get either a thumbs up or a yay from you, Katie? 4:20 Yeah, we’re getting a whole bunch of thumbs up. You’re good to go. 4:24 Okay, great. Perfect. All right. Well, thank you very much, Katie, Brianna, for this invitation. 4:33 And I would like to acknowledge and thank the New Jersey Center for Tourette Syndrome for the opportunity to present to you about this topic. 4:45 And thank you all for being here to listen to this and allow me to share some of my experiences with this on this, I think, very exciting topic. 5:00 And I want to thank my collaborators and colleagues that we’ve worked together for over 15 years now in this area. 5:11 And I especially want to thank the patients. 5:13 This is very much been a patient-driven endeavor. 5:18 As you’ll see when I get into more details about it, I got into this because patients talking about it and first clinically, then we’ve, and then subsequently, we’ve done some research on it. 5:33 I do think cannabis is promising, but I think we have to be cautious, okay? 5:40 As you’ll see, as I go through this, that, you know, the quality of the evidence is variable and the whole thing is very new, okay? 5:49 So, again, this is something we have to be very careful about. 5:54 And in recent years, there’s been an explosion of interest, and particularly in Canvas, for all sorts of things. 6:01 And, again, I think we have to be careful. 6:04 You know, any new treatments, there’s a famous quote from William Osler, who’s considered the father of modern medicine. 6:11 And he says, when a new drug comes out, you should use it as fast as you can before it stops working. 6:18 And what he’s referring to here is that when something first comes out, we are all excited. 6:24 It seems like a panacea, it works for everything. 6:26 And then it’s only a matter of time before we realize, well, it’s not so perfect and maybe not a great idea at all. 6:34 So anyhow, while I do think that cannabis is promising, I think we have to be cautious and without further ado, I’m gonna get into things and I’m gonna speak a little bit fast Just because I have a lot to share that I want to share and I want to make sure that there’s a good amount of time For Q &A, but hopefully not too fast. 6:52 And if it is too fast, I’m happy to slow down I could even skip over stuff, you know, not everything has to be covered in like excruciating detail, but We’ll keep you posted on the speed. 7:03 Perfect, thank you, thank you. 7:05 All right, I have no financial conflicts of interest to declare. 7:09 And the other thing is I’m going to use this into laser pointer. 7:13 Okay, so in terms of our objectives for today, what I’m hoping is by the end of this session, that you’ll be able to describe the current evidence for cannabinoids in the management of ticks, okay? 7:23 And evidence, you’ll see there are different kinds of evidence And what the results are will differ depending on the type of evidence we’re talking about. 7:33 So, we’re going to go over this. 7:35 The other thing I want to point out is I use here the term cannabinoids. 7:39 Okay? So, cannabinoids is a term that includes cannabis, which is the plant, the herb. 7:44 But it includes other things, pharmaceuticals that work on the cannabinoid system in the brain. 7:51 Okay? So, it’s kind of a very general term. 7:53 So, we’re going to talk about the evidence for cannabinoids in the management of ticks. 7:58 You will know when to consider cannabinoids in the management of ticks for adults with Tourette syndrome. 8:05 You’ll be able to describe the potential benefits and harms of cannabinoids, okay? 8:10 So, a lot of the times we’re focusing on the benefits and we forget about the harms. 8:14 It’s not just for cannabinoids, it’s for all of our treatments, okay? 8:18 And this is something not to forget this part of the equation. 8:21 And then, lastly, I’m going to touch on practicalities around administration of cannabis, okay? 8:31 And it has, and here specifically cannabis, it has its own kind of complexities when it comes to how do you administer it, and we’ll go over that, okay? 8:41 All right, so first, just kind of the first couple of slides are going to be kind of more introductory to introduction to Tourette syndrome kind of slides. 8:50 It’s really just one overview slide and then one just on medications for Tourette’s Syndrome, just to make sure everyone’s on the same page. 8:58 Just a quick summary, what do we do for Tourette’s Syndrome? 9:03 So, first of all, Tourette’s Syndrome is a condition defined by motor and phonic ticks. 9:07 That’s what characterizes it, but the majority, as we know, have comorbidities as well. 9:12 And that’s what defines Tourette’s Syndrome. 9:14 There’s a typical course that ticks tend to follow. 9:19 They tend to start early childhood and then even as they fluctuate, they tend to peak around early puberty, so around ages 10 to 12. 9:28 And then for most people, there’s a gradual decrease thereafter, such that by early adulthood, the large majority outgrow their ticks. 9:37 But not everyone, okay, a good quarter roughly give or take do not outgrow their ticks and continue to have significant ticks as adults. 9:46 What do we do in terms of managing Tourette’s syndrome? 9:50 For a lot of patients, well, for everyone, education and reassurance and talking about what ticks are and aren’t and what to do and what not to do is a big part of what we do. 10:00 And I put this in red because it’s really very important, we often overlook it, and, you know, adjusting, dealing with the environment in terms of the environment’s reactions to the ticks, whether it’s the home environment, the school environment, the work environment, et cetera. 10:16 For a lot of patients with mild to moderate tics, this is enough, okay? 10:20 If the tics are not causing any problem, then this is all that’s needed. 10:24 That’s the intervention. 10:27 But if the tics are causing problems and they need to be targeted, and as we know, tics can cause problems. 10:33 They can be, can impact function. 10:35 They can cause physical pain, discomfort, even injuries. 10:38 Socially, they can be very problematic. 10:39 And if they need to be targeted, excuse me, the first line treatment is behavioral therapy, in particular, in the form of habit reversal training, okay? 10:48 There are quite a few clinical practice guidelines out there for Tourette’s syndrome. 10:52 They’re generally all good, and there’s some variability across them. 10:56 However, they all agree on one thing, which is that behavioral therapy should be the first line targeted treatment for TICS. 11:04 If medication is required, then our mainstay treatments are the alpha-2 agonists and antipsychotics, in particular, the higher-potency antipsychotics. 11:15 And these are our main state treatments. 11:17 There are other options, but these are the main ones, okay? 11:19 The other aspect in terms of the management of Tourette’s syndrome is the comorbidities, as I mentioned earlier. 11:25 So, in particular, OCD and ADHD, anxiety, rage, outbursts, and a whole slew of others. 11:30 And sometimes those are more problematic than the ticks themselves. 11:33 Sometimes they interact with the ticks, and then it takes some negotiation to figure out what’s how best to start, and et cetera, okay? 11:41 So, this is kind of just the overview. 11:44 What about the medications? 11:45 Let’s get into a little bit more detail there. 11:48 As I mentioned, there are a number of clinical practice guidelines out there for Tourette’s syndrome. 11:52 My favorite ones that I think are really good in terms of how they were done, how they evaluated the evidence and everything are the American Academy of Neurology Guidelines. 12:02 They were led by Tamara Pringsheim, who’s a neurologist in Calgary. 12:05 And they they what they do is they make recommendations they they with different strengths the recommendations Okay, they call it level and the the strengths are level a B and C Level a is you must level B is you you you should and level C is you may okay? 12:25 This is how they recommend so this is the in terms of their right how strong their recommendations are and then they also give an assessment of the evidence for any intervention. 12:36 Do they have a moderate, based on how strong the evidence they evaluated was, they might say it’s low or moderate or high level of evidence. 12:48 So in the case of the alpha-2 agonist medications, it’s the level B recommendations, meaning they’re telling clinicians, you should offer this as an option to patients, okay? 12:58 And the evidence there is low to moderate. 13:01 remember depending on the medication, okay, in terms of how good the evidence is, in terms of how good these treatments are for the test. 13:10 When it comes to the antipsychotics, there’s more confidence in the evidence. 13:14 It’s moderate, actually, but the recommendation is a level C, meaning you may give this recommend this for patients as an option. 13:24 And the reason is because the adverse effects of the antipsychotics can be quite concerning. 13:31 So, this is not something, at least in North America, we tend to jump to right away. 13:37 In terms of adverse effects, it’s level A. 13:39 That’s the one thing that gets a level A recommendation. 13:42 If you must talk to patients about the adverse effects, you must monitor them, et cetera, et cetera. 13:47 So, as I said, these are the two mainstays, but there’s a whole slew of others and of other agents and including, in particular, cannabis, okay, or cannabinoids. 13:59 And in particular, THC, tetrahydrocannabinol, which is one of the main active ingredients in cannabis. 14:07 And specifically for adults, okay, and they give a level C recommendation, meaning you may talk about it to patients. 14:16 Their level of confidence in the evidence was low, okay? 14:19 Mind you, this was, these guidelines came out in 2019. 14:22 The evidence would have been evaluated from a year before. 14:25 So there’s been more evidence since that I will go over with everyone today. 14:29 All right, poll question. 14:32 When you think about cannabis for ticks, what comes to mind? 14:37 It’s a fad that will eventually pass. 14:39 It can be helpful for some people. 14:42 It is being pushed by companies that profit from it. 14:46 Give a minute for people to put in their answers. 15:04 Okay, we’re just going to give it a couple more seconds. 15:15 Okay, so we had a hundred percent say that it can be helpful for some people. 15:21 Wow, a hundred percent, okay. 15:26 We had someone do a clapping emoji. 15:29 All right. 15:30 And a heart. 15:30 Wow. 15:31 Talk about consensus. 15:32 That’s amazing. 15:33 Okay, so you are all correct. 15:37 I think it can be helpful for some people. 15:39 want to say if someone said it’s a fad that will eventually pass I think that’s correct too and what I mean by that doesn’t mean pass as and disappear but there is a fair bit of hype about it and I hope that that will dampen a little bit because we want to be level-headed and clear-minded about it and then it is being pushed by companies that profit from it unfortunately that is also correct okay so all of these answers are correct but if I had to if I was stuck with choosing just one, I think I would favor the one that everyone chose so they can add me to the consensus. 16:14 It can be helpful for some people. 16:17 And I’m gonna start from the beginning of how I got involved in this. 16:21 And as I mentioned, this was really very much driven by patients. 16:25 So this was really about 15 years ago. 16:29 I was fresh out of my clinical training, working in a Tourette syndrome clinic in Toronto. 16:35 And I see a patient where the reason for referral was specifically for cannabis for ticks. 16:41 Okay? It wasn’t about to evaluate as this Tourette syndrome or the management and such. 16:46 It was specifically one that cannabis for ticks. That’s what this patient wanted. 16:50 And this was a young adult patient. 16:54 And what had happened is he had been to a party and there was a joint being passed around. Joint meaning cannabis joint weed. 17:04 And he he smokes up a bit and then he goes home and his family was like you don’t have any ticks where are your ticks and put two and two together and realizes it was the cannabis that caused decrease in ticks and so he started using cannabis and he found this is quite helpful for the ticks but he was getting it from the street and he didn’t want that he wanted medical cannabis I had very limited experience with this, really. 17:33 I clinically never used it and personally had to try it twice in my life at similar kind of parties. 17:41 And I was uneasy, you know, especially at the time. 17:46 And I was aware that there were two small studies, and I will touch on those two small studies actually, that showed some effect for ticks, but I was also aware that cannabis had risks, had serious risks with it, especially for a young person and especially for using it every day and I started talking about the limited evidence the risks and that kind of thing and the patients tossed me just stop right there I’ve gained 50 pounds on risperidone I slept through high school on clonidine okay risperidone anti-psychotic and clonidine an alpha-2 agonist you’re not going to tell me this is worse this is working for me, like don’t give me your, so it was compelling and we did it. 18:31 I tried to figure out, we figured out together. 18:34 At the time, it was a different process. 18:35 I had to, it was an application to submit to Health Canada, et cetera. 18:40 It was quite a process at the time, but anyhow, got the approval and the patient started using medical cannabis. 18:46 I’d never prescribed before and it was really learning things as I went together with the patient, we were learning together. 18:54 And the patient did very well on it. 18:56 Went back to school while working a part-time job, got a graduate degree, was in a relationship, did very well really. 19:05 And so, you know, over time, I started hearing this more and more from patients. 19:10 You know, I’d be asking, you know, what kind of things make the tics worse? 19:15 What kind of things make the tics better? 19:18 And every once in a while they’d say, yeah, you know, I was at a party, you know, I smoke up a bit and I realized my tics were better with cannabis. 19:25 And, you know, I was hearing this story where people serendipitously, like not expecting it, especially at the time when cannabis, again, now it’s very much in the air. 19:34 But at the time, it’s not something that people were thinking about medical cannabis as much, but, you know, realizing it was helpful for the tics. 19:42 So I started offering it even for patients, all adults, for whom, you know, had failed multiple treatments, okay, behavioral therapy, anti-psychotics, alpha-to-agis, nothing’s working, and they continued to have severe ticks. 19:58 So, I’d say, you know, you want to try cannabis, medical cannabis. 20:02 And so, we’d go there and quite often, there would be a significant improvement in the ticks. 20:10 So, that’s basically been the story. 20:12 And then, at some point, you know, our groups started researching it. 20:16 We figured this was something important worth pursuing and that’s how we got into this. 20:21 All right, so a bit of, just a bit of a brief history of cannabis in North America, just to give us some background or to contextualize everything that’s happening. 20:32 And it does impact what we do and what we can do with this history. 20:36 So in 1913, the states of California, Maine, Wyoming, and Indiana all banned cannabis, okay, just over a century ago. 20:43 And then 10 years later in Canada, Cannabis was criminalized in 1970 at the federal level in the United States. 20:52 There was prohibition of cannabis. 20:55 And so for most of the past century, you can see cannabis was just illegal in any shape or form until in 1996, California, at the forefront legalizes medical cannabis specifically. 21:08 Okay? And then five years later, medical cannabis is legalized in Canada. 21:14 So, not that long, really, just over 20 years ago. 21:18 And then, in 2012, Colorado and Washington were the two first states to legalize recreational cannabis. 21:27 So, now, no longer just medical, this was recreational cannabis being legalized. 21:32 Same as, you know, you can buy alcohol to have a drink, you could get cannabis. 21:36 And then, increasing number of states have followed suit. 21:39 and in Canada in 2018. 21:43 So recreational cannabis was legalized across Canada. 21:46 And then most recently in 2022, there was a Medical Marijuana and Cannabidiol Research Expansion Act passed at the federal level in the United States. 21:59 Since by the way, this is the New Jersey Center for Tourette Syndrome and I think a lot of the audience is from New Jersey. 22:04 I just wanna say in New Jersey, medical cannabis was legalized in 2010. 22:08 Okay, so just 15 years ago, and then recreational cannabis was legalized in 2020, so five years ago. 22:17 So what I want to, a couple of points here is that one point is this is all very recent. Okay, this is still emerging. We’re still trying to figure these out. 22:27 There’s a lot that we need to figure out still with regards to cannabis and medical cannabis. 22:34 excuse me. 22:35 Another thing is there’s a lot of variation across jurisdictions in terms of what you can do legally. Okay. 22:42 So that’s, that’s, that’s, and what we’ve been able to use medically has changed dramatically over the past 15 years. It’s amazing. 22:50 I have to say, for example, you could use the cannabis herb could be inhaled, but you couldn’t consume it orally. That was illegal in Canada. 22:58 You know, it was lots of striking things like And so as and then the other thing we’re talking about cannabis But then there was all of a sudden all these different cannabis products trying to figure all of these things have been evolving over their recent over recent years and then the other thing I want to say is Recreational cannabis is legalized in much of the United States now and in all of Canada And so you don’t even need medical cannabis is available recreationally. 23:25 You don’t need the doctors or anything like that But is that a good thing to be using it to be accessing just recreational cannabis without any medical guidance? 23:34 So Bring leave that as an open question for now. 23:38 We hope we can come back to it later All right Hype there’s a lot of hype. 23:44 There’s been a slew of private cannabis clinics and Companies that are marketing the products left right and center to everything and these are just some flyers that I receive unsolicited. I’ll show you this one as an example from one of these clinics. 24:00 Commonly treated conditions, anxiety, PTSD, ADHD, depression, insomnia, stress, panic disorder, bipolar disorder, borderline personalities, or my goodness, next thing they’re going to put here is world peace. 24:11 So it’s when something is supposedly such a panacea for so many things, I mean, you’ve got to be suspicious. 24:18 It’s really, it’s, it’s, you know, it makes you think of snake oil, really, Like it’s a good for everything kind of thing. 24:25 So we have to be very careful. 24:27 And indeed, this is a piece written by Ruth Ross, who used to be the chair of the pharmacology department here at the University of Toronto. 24:35 Why we need to press pause on any kind of cannabis promotion. 24:38 Many companies are selling marijuana as if the drug is totally harmless. 24:42 It’s not, okay. 24:43 We have to be very careful and remain clear headed about this, even as promising as it is, okay. 24:51 All right, so cannabis, you know, when we talk about cannabis, the plant, there are many, many compounds in cannabis, and there are two in particular that get a lot of attention. 25:05 And one is THC, 9-delta tetrahydrocannabinol, THC, and that’s one of the main active ingredients. 25:16 That’s the ingredient that gives you the high when people are using the smoking weed at party kind of thing, or not just smoking, or it’s consumed orally, that’s what gives you the high. 25:27 And what it does is it acts on two receptors in the brain, what we call the cannabinoid receptors, and one is CBR1, CBR2, cannabinoid 1 receptor and cannabinoid 2 receptor, okay? 25:42 And these receptors, they’re called cannabinoid receptors because, not because THC binds on them, but because we have endogenous cannabinoids, we call them endocannabinoids in the brain that actually act on these receptors on the system, okay? 25:57 And these receptors are rich throughout the brain, in particular, like the CB1 receptor is rich in the base of ganglia, which are involved in movement and all sorts of things, including, we believe, in tics and turets. 26:13 And what THC does on these receptors, it’s a partial agonist. 26:17 Agonist means it stimulates these receptors, and, but it’s partial. 26:21 It means it doesn’t stimulate them fully, it stimulates them partially. 26:25 Okay, that’s what THC does. 26:26 Another main one is CBD cannabidiol, okay, and it acts on the same two receptors, except it does something different. 26:35 It’s a negative allosteric modulator. 26:38 That’s, that’s, that’s a mouthful. 26:39 Don’t worry, Katie, I won’t ask you to pronounce it. 26:41 But what it does is it it’s a modulator allosteric means it changes the shape of the receptor Negative meaning that it makes it less likely that agonists are going to bind to it and and activate it Okay, so it decreases the effect of THC or endogenous endogenous cannabinoids the endo-cannabinoids So these are the two that get a lot of attention in nature in the cannabis plant Typically, it’s either got high THC and low CBD or the other way around, okay? 27:14 It’s not usual that they both are high, but, you know, these days with technology and whatnot, you can have all sorts of combinations, but this is relevant that I’m mentioning this. 27:26 But while we focus on these two receptors, there are hundreds of other compounds, all understudied in terms of what exactly they’re doing, so a lot to be figured out still. 27:36 And then there are the terpenes. 27:38 The terpenes are compounds that give it its distinct odor and taste. 27:45 And it’s felt that these have an impact in terms of the effect of the other compounds, in particular the THC and CVD. 27:53 People use the term entourage effect. 27:55 So the environment of these compounds will influence how they, what kind of effect they can have. 28:01 Okay? So that’s cannabis. 28:03 I’m going to go through now the actual products, okay? 28:07 What are the cannabinoid products that are available? 28:10 And again, there’s going to be variability by jurisdiction for sure, okay? 28:14 I’m going to talk about the pharmaceuticals, meaning they’re cannabinoids that you can prescribe, like any medication that you prescribe, okay? 28:22 And then I’m going to talk about cannabis itself and how it can be, and it can be inhaled or consumed orally, okay? 28:29 So, with regards to the pharmaceuticals, there’s nabilone. 28:34 Nabilone is a synthetic drug that acts similar to THC, basically. 28:40 It stimulates, it’s a partial agonist of the CB1R and CB2R receptors. 28:46 Okay? So, that’s nabilone. 28:48 And then dronabinol, it’s also synthetic, but it’s basically THC. 28:52 It’s a THC in a pill, basically. 28:56 I’ve prescribed this a fair bit in the past. 28:58 No longer because for whatever reason, it’s no longer available in the market in Canada. 29:02 I’m not sure why, but it is available in other markets. 29:05 Okay. So these are both orally taken prescriptions. 29:08 And then you have Nabiximals. 29:11 Okay. Nabiximals is a spray that is almost equal parts THC and CBD. 29:17 Okay. 29:17 And it’s a spray you spray it on the inside of your mouth and inside of your cheek or under your tongue. 29:22 So that’s another one. 29:24 And then lastly, Cannabidiol. 29:26 Cannabidiol is consumed orally. 29:28 It’s basically CBD that I mentioned, and that is used primarily in epilepsy, in some rare forms of epilepsy, CBD. 29:38 When it comes to cannabis itself, it can be inhaled, either smoking, the good old fashioned way, or it can be vaporized or vaped, and there’s a difference between the two, okay? 29:49 Smoking is not something we recommend, although some of my patients have discovered it as smoking, wanna continue doing that. 29:56 Vaping is one where people hear a lot about vaping is one where the cartridge with a liquid in it And then the product is is in that liquid and that’s that’s heated up That’s how you vape it But then there’s the chemicals from the liquid and whatnot if the person prefers to inhale the favor It would be vaporizing. 30:13 I think it would be the least harmful where it’s the it’s the herb itself that is Warmed up in a vaporizer or a vaporizer releasing the compounds. 30:23 Okay, that’s for inhaled cannabis And then for oral cannabis, it’s the oil, is I think what we’re using most commonly these days. 30:32 So it’s the compounds are activated and made into an oil, or it can be capsules or edibles, the famous cookies people talk about. 30:44 There are other forms as well, like drinks and such. 30:47 It’s not something that I go through. 30:50 It’s mostly in the recreational realm. 30:52 All right, I’ve been saying quite a bit actually, I’m going to pause just for a sec. 30:57 Everyone with me? 30:59 Any concerns? 31:00 Is that too fast or are we good? 31:02 Thumbs up if we’re good. 31:04 Thumbs down if I should slow down or do something different. 31:09 Jorgen, a whole bunch of thumbs up. 31:10 So you’re doing good. 31:12 Okay, okay. 31:12 Okay, great, wonderful. 31:14 All right, what are the effects? 31:16 So first the benefits. 31:18 So these compounds have been used in particular pharmaceuticals as antiemetics. 31:23 So anti-nausea, especially when, for people undergoing chemotherapy for cancer and they have a lot of nausea for appetite stimulation, same with the chemotherapy for cancer or with AIDS, they can be helpful for pain. 31:37 They can be helpful for spasms and multiple sclerosis. 31:41 And CBD in particular is an, can be helpful for certain rare forms of epilepsy. 31:46 And I emphasize that because there’s all this excitement about CBD, unfortunately it gets so much hype in the wellness industry that I’ve seen, It’s amazing how the landscape has changed, where I’ve seen patients or parents giving their kids like five drops of CBD oil a day because they have Tourette syndrome and there’s some concept that it’s good for you. 32:04 And no, don’t do that. 32:06 This is, none of this is benign unless you have these rare forms of epilepsy where it can be miraculous, actually. 32:13 It is quite striking, but it’s very particularly useful. 32:17 So this is what we know so far in terms of the potential benefits. 32:20 What about the harms? 32:21 The list is much longer. 32:24 And maybe this should not be surprising. 32:25 I would say this is the case for pretty much any treatment, any of our at least medication pharmaceutical interventions. 32:33 And it’s a long list. 32:35 This is not an exhaustive list, but I’m telling you, I’m going to go through it quickly. 32:38 These are not uncommon things. 32:40 And pretty much all of these things I have seen clinically. 32:44 Okay. 32:44 Dizziness can cause dizziness, sedation, fatigue, psychomotor slowing, this feeling of high. 32:49 And I’m listing it under hearts because patients who are taking it to help them, let’s say to help their tics, they don’t want the high. 32:56 They don’t wanna be feeling high. 32:57 So it’s really a side effect. 32:59 A, motivation, depression, irritability, anxiety, a feeling of derealization, depersonalization, things feeling odd, unreal, altered perception, psychosis, dry mouth and red eyes, okay? 33:11 So these are things to be aware of. 33:12 Doesn’t mean they will happen, but these are side effects and they’re not rare, okay? 33:19 All right. What is the evidence? The evidence. As I said, there’s different kinds of evidence. 33:24 And I’m going to go through retrospective studies, open label studies, and then finally the double blind randomized control trials. 33:32 The retrospective studies are basically mainly you take a bunch of people, you look for a bunch of people who are using cannabis in your clinic, and you ask them, okay, how’s it going? Is this helping? 33:43 And then you report what they share with you. So these are the retrospective studies. 33:47 As you might guess, they’re more likely to be positive. That’s why these patients are taking them, right? 33:52 And there’s going to be bias and what they remember and all of that. Okay? 33:55 So these are the retrospective studies. And a lot of the studies are retrospective. 34:00 I’ll nevertheless go there. It’s worth going through them together. 34:04 Open label studies are basically studies where you give the patient, okay, it’s not going to be just retrospective. 34:10 I’m going to, you maybe not all the next 20, but I’ll choose them carefully and I’m gonna give them and I’m gonna follow them and see what happens, okay? 34:21 So in a way, they’re less biased, you’re following the patients longitudinally, but they’re open and they know that they’re getting the cannabis. 34:26 There could be the placebo effect. 34:28 There’s also, there’s no control, right? 34:30 They’re not comparison to any other intervention. 34:33 So maybe the ticks were gonna get better anyway. 34:35 We know ticks fluctuate. 34:37 So these are the open label studies. 34:39 So the gold standard really are the double-blind randomized control trials, okay? 34:43 So there could be a placebo comparator and people are randomly assigned. 34:48 It’s not like you’re choosing through some bias, bias not necessarily in a negative way, but it could influence the results. 34:56 Who gets what? 34:58 It’s randomized and it’s double blind. 35:00 You don’t know who’s getting what. 35:01 Patients don’t know who’s getting what, at least so we think. 35:04 And so these are considered a gold standard. 35:06 We’ll look at the evidence from such trials as well. 35:10 And we’ll see how the results going to be different based on the kind of studies. Let’s start with the retrospective. 35:17 Okay. There’s quite a few here, but don’t worry. We’ll walk through them quickly. 35:21 And it’s not so much the specifics of each study is not what matters. We want an overall picture. 35:26 So the landmark study, the initial original pioneer study was done by Kirsten Mullerweil. 35:32 I mentioned her name. 35:33 I won’t be mentioning all the names, but her in particular, she’s she’s a neurologist in Hanover in Germany. And she’s really been a pioneer in this area. 35:41 And see her name over and over. 35:44 This was published in 1998, so quite a while ago now, and she asked a series of patients if they’ve ever tried cannabis, and from all the patients she asked, 17 said they had, and of these 17, 14 said that they found that it decreases ticks and related symptoms. 35:59 So 14 out of the 17 that tried it, okay, not bad. 36:04 We did a study much later that we published a few ago now, again retrospective, where we asked the 18 patients we identified to agree to participate and 17 of the 18 patients participated were rated as either very much improved or much improved clinically and we looked at other things as well and we found generally other symptoms tended to be better as well. 36:26 This one is a bit of a better design because they asked a whole bunch of patients who had tried cannabis, who had been prescribed cannabis and not just the ones who are still on And 38 out of 48 patients reported any kind of benefit. 36:41 Okay, still a fair, good amount. 36:44 I want to say that 10 stopped it. 36:46 So that’s important to know. 36:47 And for different reasons, including side effects. 36:51 And there’s mentioned that one developed psychosis, acute psychosis and four developed hallucinations. 36:56 So this is, you know, not insignificant. 36:58 Next, this study larger than all the others, 98 patients is again from Kirsten Muller Weill’s group Germany. And they asked them about different types of cannabis they tried and preferences and such. 37:11 And interestingly, there was a strong preference for THC-rich medical cannabis in comparison to stuff that was not rich with THC or in comparison to the pharmaceuticals. 37:22 And then lastly, the study out of 25 patients, they found 75% reduction in ticks. 37:27 And they also found that there tends to be and increase those over time. 37:31 Like they followed the patients for several years and basically there was suggestion that maybe over time they were requiring more, okay? 37:39 All right, so this is the overall of the retrospective and it looks pretty positive. 37:44 One thing I wanna highlight here is of all of this is mostly in adults. 37:48 There are only seven cases reported in the pediatric age. 37:53 Okay, so all of this work being done in the adults. 37:55 What about the open-label trials? 37:57 And I’m mindful of the time. 37:58 I’m going to speed up a tiny bit here. 38:00 The open-labeled trials are two. 38:02 And basically, one, you see they’re not large trials, 16 adults, 18 adults, open-labeled THC, 10 milligrams. 38:11 And they added this chemical, palmitoyl ethanolamide, the idea that this has a kind of entourage effect that can enhance the THC effect. 38:21 Anyhow, they found a 20% improvement based on the YGTSS total tick score. 38:26 YGTSS is the Yale Global Tick Severity Scale. 38:29 It’s like the gold standard for measuring tick severity. 38:32 And the total tick score from the scale was 20% improvement. 38:35 And in this other trial, it was oral. 38:40 Well, actually, it was not just oral. 38:42 They used it in different ways. 38:43 They averaged those with about 0.6 grams a day, 38% improvement YGTSS. 38:47 Right away, you can see from these two studies, the effects are not as big. 38:52 There’s effects, but they’re not as big as what we see in the retrospective. 38:55 What about the randomized clinical trials? 38:57 Well, here’s what we see. 39:00 So first of all, Kirsten Muller-Vall did the first study back in 2002. 39:06 This was a single dose crossover trial of oral THC versus placebo. 39:11 And there was an effect, a significant effect, in favor of the THC versus the placebo. 39:16 But this was single doses. 39:18 She then followed suit and did an actual ongoing treatment study. 39:23 it was a six weeks randomized control trial, THC versus placebo. 39:27 Again, it was favorable for the THC, but the effects were inconsistent, not at all time points, not so clear cut. 39:35 And notice when both of these were published over 20 years ago, and then there was a big gap, there was very little done in the meantime. 39:42 She then published another study, more recently published this in 2021, and this one used something different. 39:49 It’s not cannabis, it’s It’s the compound that inhibits the enzyme that breaks down the endogenous cannabinoids, the endocannabinoids. 40:02 Okay? 40:02 So the idea that if you’re breaking them down less, then you have more endogenous cannabinoids and you have more transmission in the cannabinoid system. 40:13 However, this study was significant in favor of placebo. 40:17 So the placebo arm did better than the drug arm, OK? 40:21 I was hesitant, to be honest, whether to show this one or not, because it’s really not actual cannabis. 40:27 But nevertheless, there you have it. 40:28 This is one of the RCTs that was done. 40:30 And then there were three other RCTs. 40:32 And those I’m going to show in a little bit more detail, OK? 40:35 One from Kirsten Mullerweil. 40:36 Again, I told you, so her name keeps coming up. 40:38 One from us and one from a group in Australia. 40:41 And I think we can learn from each one of these. 40:44 The one from Kirsten Mullerweil in Germany, 97 patients were randomized to either get nabiximols or placebo. 40:51 Nabiximols, if you remember, is the spray where you have almost equal amounts THC and CBD. 40:57 And they were randomized in a two-to-one fashion, meaning more patients were randomly assigned to get nabiximols than placebo, twice as many. 41:06 And they used between one and 12 puffs a day, okay, maximum 32 milligrams of THC it came to, which is not an insignificant amount. 41:17 And they could adjust those based on how to get benefit and to avoid side effects, okay. 41:23 There was during four weeks was when the dose was adjusted, once it was adjusted, they stayed on a stable dose for nine weeks for a total of 13 weeks, okay. 41:31 And this is what she found. 41:33 The red arm is the placebo, the red line is placebo, and the blue is the nabiximol’s arm, okay? 41:43 And you can see that there’s a reduction, and both of them, there’s a reduction, okay? 41:47 Here they go back up because here they stopped the treatment, they had a follow-up after, okay? 41:51 You can see there’s a reduction in both cases, and you can see that the reduction in the nabiximol’s arm is larger. 41:57 However, it did not statistically separate from each other. 42:01 So statistically, it was not significant, it was negative. 42:05 But the other thing is, regardless of the statistical significance, if you look at the amount of change, the degree of change, it’s not huge really. 42:13 Like if you look at the YGTSS total tick score, like the difference between placebo and the naboximals is like two points on the scale. 42:21 So not a huge effect. 42:24 95% reported at least one adverse effect, okay? 42:28 Now, almost all were mild, so there was only one or two serious adverse effects, but they don’t go into detail to describing what exactly those were, but anyhow, they described them as pretty much all mild, but still the majority experienced something that was adverse. 42:45 Next poll question, which component of cannabis do you believe will decrease ticks the most? 42:50 THC, CBD, either THC or CBD, neither THC nor CBD. 43:13 Okay, we’re going to let it go for a couple more seconds. 43:29 Okay, so it looks like THC1 with 63%, CBD had 21%, and then either THC or CBD had 17%. 43:45 Okay. Okay. Not a clear cut consensus like before, but the majority is thinking THC. 43:50 Interesting. Interesting. All right. 43:53 So I think we have clues from the studies that I just went over, including their perspective, but this is the study we did was precisely to answer this question. Okay. It was a single dose trial crossover of vaporized cannabis. Okay. 44:09 Crossover, meaning each participant got a quarter of a gram of either THC or a combo of THC-CBD or CBD or placebo, okay, in a double-blind fashion. 44:23 And what did we find? 44:26 Well, these are, I want to show you these results. 44:31 So, the modified rush video tick rating scale. 44:35 So, this is where you take a video of the patient and then you rate someone who was completely not involved directly, rates the ticks they see. 44:43 What did we see? 44:44 The turquoise color is the THC arm and you can see a signal here that the ticks go down with this one, okay, with the cannabis. 44:53 The red is the placebo and then the other two are the other colors. 44:56 And this was not statistically significant. 44:58 It did not separate, okay, here. 45:01 But we also looked at the pre-monitory urge for tick scale and the subjective units of the stress scale. 45:06 And you can see here a clear effect of the THC arm. 45:11 Here as well, clear effect of THC arm, very significant in both cases. 45:16 And nothing from, not the case for the other, for the others. 45:21 The other thing that’s interesting, and this is sorry, it’s a bit of a crowded slide, but don’t worry, I’ll just point out the main things. 45:27 As we look, got the blood levels of the cannabinoids and their metabolites. 45:32 And what we found is that for the THC, there was a clear correlation with regards to what you saw, including on the video tick rating scale, where the higher the level of in particular hydroxy THC, which is the main active metabolite of THC, okay, when it gets broken down, that’s the main activity comes from higher, and so the higher that was, the lower the ticks were, lower the PUD scores were, and the lower the subjective units of the stress scores, okay. 45:59 Whereas in the CBD, there was no correlation whatsoever. 46:03 It doesn’t matter what your blood level of CBD was, it did not impact your ticks in any way, shape or form. 46:09 Okay. 46:10 So the point being here, if there’s any positive effect against the ticks, it seems to be coming from the THC really and really nothing from the CBD based on the blood levels and the earlier slide that I showed you. 46:23 The other thing though is there’s no free lunch. 46:25 The adverse effects were coming mainly from the THC as well. 46:30 And this is a total adverse effect. 46:32 Again, the turquoise is the THC. 46:34 And you can see it was much higher than the other two arms. 46:36 And here’s the placebo. 46:37 It’s the one that had the least adverse effects. 46:39 And most of them coming from cognitive effects. 46:43 Okay? So not benign. 46:45 And then lastly, I’m going to quickly go over the Australian study. 46:49 So the Australian study, they had 22 patients. 46:52 Each got a combo of equal amounts of THC and CBD versus placebo as a comparator, okay? 47:01 They dosed it over four weeks and then they, and this was a crossover trial, meaning that they took one, either placebo or cannabis for six weeks. 47:13 Then there was a four-week washout, then they took the other for six weeks. 47:17 What was the result? 47:18 This is a bit of a crowded slide, but don’t worry. 47:21 It’s, I’ll walk you through it, and it’s really neat, actually, how they presented. 47:25 The dots are the symptoms of the patients. 47:27 Each one is an individual participant. 47:30 Okay? In green, it’s the cannabis. 47:32 In yellow, it’s the placebo. 47:33 Okay? And these are the scores based on the YGTSS total tick score. 47:38 And you can see they’re pretty much overlapping, the individual. 47:41 And these are the averages for the placebo and for the cannabis. 47:45 And what they show is at two weeks, at four weeks, and at six weeks, Over time, what happens is they start to separate. 47:52 And the placebo is not going down as much, but the cannabis arm is going down, okay? 47:58 And you can see by the end, the clear separation between the cannabis and the placebo. 48:04 They also did it for the global score of the YGTSS where they add the impairment scale as well, clear cut separation. 48:12 And they also did the video tick rating scale, clear separation. 48:16 So this was a fairly positive study showing and an effect of the cannabis compared to the placebo. 48:23 In terms of, they also did blood levels and did correlations and their results, I’m not going to go through these graphs because of time, but suffice it to say that the results are very similar to what we found. 48:33 There were correlations with the THC, but not with the CBD. 48:38 Okay. 48:40 And then similarly, you have way more adverse effects in the THC arm compared to, sorry, in the cannabis arm compared to the placebo arm include in particular cognitive difficulties, 40% had cognitive difficulties in the cannabis arm versus 9.5% placebo. 48:58 Okay. 49:00 All right, in practice, so we’re coming close to the end now, but I want to talk about in practice what can be done here before we go to the Q &A. 49:09 So, I mentioned the American Academy of Neurology Guidelines, okay. 49:14 So, what do they say? 49:15 They say that for adults, you can, you may offer THC if they are treatment resistant, meaning that they’ve tried all the treatments, the main treatments and they’re, it’s not working. 49:29 They continue having significant symptoms. 49:31 You can, you may offer cannabis, or if they’re already using cannabis themselves efficiently, it’s good to offer them, you can offer it to the medical. 49:42 They also say you must provide medical supervision. 49:45 You should, you must use the lowest dose possible while still having the effect. 49:50 You must periodically reevaluate the need, the need to continue. 49:54 You must advise them against, about driving and the risks to drive when using cannabis, okay? 50:01 Coming back to the cannabinoid products I mentioned before, okay? 50:06 Often, when I, I will explain all of these to patients, I say in general, People tend to have more effect on cannabis itself compared to the pharmaceuticals, but it’s not uncommon that patients don’t want to go to cannabis right away and want to try the pharmaceuticals. 50:22 And I think those can be tried for ticks. 50:25 Any of these can be tried, not CBD. 50:27 I would not recommend cannabidiol. 50:29 I think it does nothing for ticks. 50:31 The Nebiximol’s, the spray I mentioned, this was a negative study from Kirsten Muller-Vile, and it’s quite expensive. 50:38 And from what I’ve heard from patients, it tastes quite awful. 50:40 So, we’re left with nabilone or dronabinol. 50:43 Dronabinol, if it’s available in your jurisdiction, otherwise, it’s nabilone, which is what I’ve used here in Canada more recently. 50:52 The inhaled, I don’t recommend. 50:54 Why not spare your lungs? 50:56 But I will acknowledge there’s an advantage because you feel what patients like is you get the effect immediately and you can titrate very easily to not get adverse effects or to get the beneficial effect. 51:08 but also the effect doesn’t last as long, okay? 51:11 So I do not recommend that, but I will acknowledge there are some patients that prefer it, nevertheless. 51:17 When it comes to oral, I tend to go with the oils, they’re very easy to titrate, it’s like any prescription, and I start low and go slow. 51:26 I would start with something like, depending on if the patient has exposure, prior exposure to cannabis, what’s their, you know, they might have some tolerance or not, but I generally prefer to start low, It could be as low as one milligram of THC equivalent taken at night, and then you can take it, and then you gradually increase it by, you know, it could be as little as one milligram a week, at least a week to see the effect, and in divided doses, twice a day, sometimes three times a day. 51:52 Okay? 51:53 And so this is, it’s basically like a prescription, but you’re giving guidance to the patient in terms of how much, how much to use and how fast. 52:05 Some notes of caution, we don’t want to forget about the harms, okay. 52:11 This is not just, we want to think these are not, like any prescription really, it comes, there can be risks. 52:18 When I think about the functional impact, how much are the ticks affecting their function? 52:23 How much is the treatment affecting their function? 52:26 There are risks in particular psychosis and mania, and these are age-related, so particularly concerned with younger patients. 52:34 This is more for the physicians to be aware that there can be interactions with other drugs. 52:38 Cannabis is broken down by these enzymes in the liver. 52:41 So any drugs that inhibits these enzymes will interfere with the effect of cannabis. 52:48 I generally recommend against smoking it because of the risk to the lungs. 52:52 The driving is a complex issue. 52:54 And we need to give caution about that. 52:56 And I’m happy to get into more questions about what people want. 52:58 People want the legalities will vary a lot by jurisdiction. 53:03 And for example, and then traveling can be an issue. 53:06 So for example, it’s legal in Canada, but you can’t travel with it. 53:09 So if they, people are using it, it’s working for them, but they wanna go away on vacation, you cannot, you cannot even know doctor’s prescription or anything. 53:16 It’s simply illegal to cross borders with it. 53:19 And then last, oh yeah. 53:22 So just in conclusion, we think not just about the impact is coming from the THC. 53:29 I think everything is pointing that. 53:30 That’s where the benefit for ticks is coming from, but that’s also where most of the harms are coming from. 53:35 The CBD, there’s no point. 53:37 There’s no clear anti-tick effect. 53:38 All the evidence is consistent with that. 53:41 We need to really proceed very cautiously. 53:43 The evidence is still emerging. 53:44 We need to have a collaborative relationship between the clinicians and the patients. 53:49 And at this point, it’s almost entirely in adults. 53:52 I will say I have a very few pediatric patients on it when things have been really stuck, But at this point, this should be a really last resort in this population. 54:01 And I think that’s it. 54:03 And I’m happy for us to go into Q &A. 54:08 Thank you so, so much. I know it’s seven. 54:10 No, that’s OK. 54:11 I know it’s seventy seven fifty five right now. 54:14 So we’re going to hop into Q &A. 54:16 We might go a little bit over eight o ‘clock if that’s OK with everybody. 54:19 Just give me a thumbs up. 54:24 OK, awesome. Thank you, guys. 54:27 So thank you so much, Dr. 54:30 Now we’re going to hop into Q &A. 54:32 First, I’ll ask the submitted questions, and then we’ll switch over to the verbal Q &A, which is when we will stop recording. 54:39 So our first question is, you indicated that ticks drop with age, but not always. 54:44 My 26-year-old son’s ticks have increased as he has aged. 54:48 When that happens, what does that imply? 54:53 You know, I’m, I’m, I’m worried to give, to give an answer that is kind of like definitive because we don’t know. 55:01 There’s a lot of variability from person to person, life circumstances and such. 55:06 But overall, it implies that likely, likely, they will not improve on their own, okay? 55:12 Most of the improvement, if it happens, will happen during, over the course of adolescence. 55:17 So, if you’re an adult by this point, you’re in your mid-twenties and the ticks are where they are, they’re likely roughly gonna be where they are, but what I will say though is often when I see adults and I’m getting their history, often they’re tying the ticks to what’s happening in their lives. 55:32 So for example, if they’re in a very common situation, they’ll say, oh, I was in this very stressful work environment, and then when I say just change jobs, a much better workplace, things were better. 55:42 I’m not saying your son should change jobs or anything like that, but just to say that the ticks can nevertheless be responsive to circumstances, not always. 55:50 But and then even if they are not and the ticks are still significant, how significant are they? 55:55 Are they really impairing his life? If they’re not then he just has ticks. 55:59 That’s fine It’s having ticks has no implications and not of themselves. 56:02 It’s they can but if they are impacting him There are treatments available and I hope you can find a treatment that can be helpful So much and another question that we have before we hop into to the verbal Q &A is, is there a specific type of cannabis that helps but does not give a high? 56:23 I recall a CNN special where young women had seizures who benefited from low THC without a high. 56:29 Oh, I mean, first of all, I’m surprised that THC for the seizures, really the two seizure conditions, which are Lennox-Gastaut syndrome and Dravet syndrome, it’s CBD, it’s high dose CBD, and that shouldn’t give you a high, It can have its own side effects, but that shouldn’t. 56:46 But nevertheless, I don’t know everything and there could be such a situation. 56:49 You mentioned low dose THC. 56:51 Well, the key there is in what you said, the low dose. 56:53 The high is very much dose related. 56:55 So if it’s low dose, you’re much less likely to get a high. 56:59 The other thing is the high comes from the peak. 57:02 You’re less likely to get a high if you’re consuming it orally versus if you’re inhaling. 57:08 If you’re inhaling, it goes to the lungs and then straight to the brain, there’s gonna be a peak, so more likely a high. 57:12 But if you’re taking it orally, it goes, you have to wait, it’ll go through your stomach, to your intestines, and it’s absorbed, slowly goes to the liver, some breakdown, and it rises more slowly and much less likely to cause a high that way. 57:25 But it’s not a full proof. 57:26 People might still experience some kind of cognitive effects, but it’s really very much those related. 57:31 So the lower the dose, the less likely the high. 57:34 Thank you. 57:35 So before we switch to verbal questions, for those watching the recorded version, thank you so much for attending. 57:41 Please complete the exit survey an archive recording of this webinar will be posted to our website njcts.org under the program’s tab. 57:49 The blog is now open and accessible under the archive webinar. 57:53 All questions submitted during the recorded viewing will be posted there. 57:56 Our presenter will be answering all questions posted until Tuesday, February 4th. Any personal information will not be included. 58:02 Our next presentation will be Game-Based CBT for Child Abuse and Trauma presented by Dr. Justin Miserel. 58:10 It’s scheduled for Wednesday, February 26th at 7 p.m., with the recording the following day, Thursday, February 27th at 2 p.m. 58:18 We offer professional development certifications for school professionals and school nurses that attend the live or recording of the webinar. 58:27 To register for either time, please visit njcts.org slash webinars. And with that, I’m going to stop the recording.