Dr. Genevieve Newton describes the state of the research on cannabis in the treatment of tic disorders and what her young son's experience with cannabis has been like. Tic disorders are defined by the presence of motor and/or vocal tics. Motor tics are simple or more complex abrupt involuntary movements that can occur all over the body, but most often are located in the face and head. Vocal tics are characterized by meaningless "simple" sounds or noises, but also can be more "complex" including obscene words. Tourette syndrome (TS) is
Tic Disorder Management with Cannabis: A Family’s Tale Meets the Science
Shortly after the COVID pandemic hit in Winter 2020, life took a worrisome turn when my youngest son developed a severe motor tic disorder. My healthy son was 10 at the time. He suddenly became plagued with involuntary movements during all his waking hours. The lockdown and home schooling were almost a blessing. It meant that he wasn’t faced with the loss of his usual activities, like playing hockey and spending time with friends. Given the severity of his symptoms, these activities would have been impossible for him to do. Of course, it also raised the possibility that his condition had been triggered by the stress of the pandemic, which hit young people especially hard.
My son received an extensive medical diagnostic work up. He had a comprehensive blood analysis that included tests for strep antibodies (to rule out Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) and autoimmune encephalitis. All blood work was normal. He had a normal EEG. He had two MRI’s which showed a large cerebellar subarachnoid cyst and a cervical spine syrinx. But these were deemed as incidental findings that were unrelated to the tics. After an almost a week long stay in a pediatric hospital, we were given a diagnosis of a severe provisional tic disorder. It was deemed to be neuropsychological in origin.
The treatments we were offered were twofold. First we were recommended psychotherapy with a therapist specializing in family health. But my son was unable to sit still to participate in Zoom appointments, so he couldn’t participate in this process. His dad and I worked with the therapist to learn strategies to help with the emotional aspects of this difficult experience, including Emotion Focused Family Therapy. This helped us all to cope better, but it did nothing to reduce the tic severity. I also worked with another therapist who specializes in Cognitive Behavioral Therapy for Tics. She helped me to better understand the disorder and provided support through this difficult period. But because my son was not able to work with her in person, the benefit was limited.
Secondly we were offered drug therapies. These are typically reserved for children experiencing severe tics due to their significant side effect profiles. We began using Clonidine, a first line treatment for moderate to severe tics. 1 It was almost entirely ineffective. Next, we tried Risperidone as a second line treatment. 2 At first the Risperidone was combined with Clonidine. Then Clonidine was discontinued leaving Risperidone as a monotherapy. The severity of the tics did reduce a bit with the Risperidone. But the side effects were awful.
Within ten weeks of starting the medication, my son gained 23 pounds. For a very thin child who weighed 72 pounds at the outset of this ordeal, this was significant. It was also traumatic for him. After doing an extensive review of the scientific literature, I asked his doctor to change our drug regimen from Risperidone to Aripiprazole because there is evidence that it is better tolerated and has comparable efficacy. 3 Unfortunately, it also causes weight gain. Within nine months of starting pharmacotherapy, our son had gained 40lbs. And the medications were also only minimally effective at reducing tic severity.
As our journey continued, so did my search for alternatives. I quickly discovered that cannabis has been used in the treatment of tic disorders for many years. After finding a physician who specializes in the use of cannabis for pediatric neurological disorders, we were given a prescription for a cannabinoid medicine. We started using cannabis concurrently with Aripiprazole about five months after the onset of symptoms. After doing this for two months, we began using cannabis-based medicine exclusively.
I will describe the state of the research on cannabis in the treatment of tic disorders, as well as what we have personally experienced using a variety of different cannabis products.
Tic Disorders, Cannabis, and the Pandemic
Tics are involuntary, repetitive twitches, movements and sounds. There are both motor and vocal tics. There are three tic disorders listed in the DSM-V, including Tourette’s Syndrome, Persistent/Chronic Vocal or Motor Tic Disorder, and Provisional Tic Disorder. Tourette’s syndrome (TS) includes both motor and vocal tics. Those with provisional and persistent type disorders have one or the other. The only difference between persistent and provisional disorders is the length of the condition. In persistent disorders, tics have been present for more than a year. In provisional disorders, tics have been present for less than a year. 4 While my son was initially diagnosed with a provisional disorder, it is now considered a persistent disorder due to its duration.
During the COVID pandemic, there has been an increase in tic-like behavior among young people, especially girls. This condition has been termed Functional Neurological Disorder and is thought to be related to psychological distress. The tic patterns are different from the three previously mentioned disorders listed in the DSM-V. The tics in Functional Neurologic Disorder are also unique in that they aren’t preceded by an urge. 5 Although my son’s condition presented during the COVID pandemic, it did not fit the pattern of this disorder.
What the Literature Says
There are many scientific publications related to the use of cannabinoids in the treatment of tic disorders. A PubMed search using the terms “Tourette’s and Cannabis” yields 80 results, many of which are relevant. A search for “Tic Disorder and Cannabis” yields fewer results. This shows that the bulk of the literature has focused on the TS diagnosis. I will touch on some of the most notable publications related to observational research, clinical trials, and treatment recommendations.
Several observational studies have investigated the association between the use of cannabis and the symptoms of tic disorders. In 2019, researchers in Europe conducted a survey of patients with a history of using cannabis-based medicine to treat TS. They found that many preferred cannabis to pharmaceutical drugs. The majority reported a subjective improvement of tics and associated co-morbidities. The most striking finding was an improvement in quality of life in 93% of subjects. Patients also reported that they preferred cannabis to either nabiximols (a preparation with a specified quantity of specific cannabinoids and other phytoconstituents) or dronabinol (isolated THC). 6 Also in 2019, an Israeli group reported that 38 of 42 TS patients taking medical cannabis reported reduced tic severity, better sleep, and improved mood with treatment. 7 Similarly, a study published in 2017 found that 18 of 19 TS patients using medical cannabis reported that they were “much improved” with the use of cannabis. However, many reported side effects including feeling impaired and experiencing decreased concentration. 8 Unfortunately these studies don’t provide reliable information on the effective doses or the chemical profiles of the cannabis being used.
Several clinical trials have studied cannabis-based medicine in the treatment of tic disorders using controlled conditions. Some of the first studies were published in the early 2000’s by a research group from Germany. Initially, researchers investigated whether treatment with THC impaired cognitive performance in adults with TS. 9 After finding that cannabis didn’t impair cognitive function, a single dose, randomized placebo-controlled trial was conducted in 2002. It examined doses of THC at 5mg, 7.5mg, or 10mg. It was found that tic severity was reduced when the 7.5 and 10mg groups were pooled and analyzed as a single group, as was associated obsessive-compulsive disorder. The changes were correlated to plasma levels of THC, 11-OH-THC, and THC-COOH. 10 The next year, a six-week randomized controlled trial found a slight reduction in tics with THC at levels up to 10mg per day. 11
A more recent 2019 systematic review and meta-analysis published in Lancet Psychiatry concluded that the quality of clinical research evidence on cannabis for TS was low. The resulting findings are considered neutral. 12 An earlier review by the Cochrane Collaboration cited similar methodological concerns. 13 Currently, the CANNA-TICS study is underway which is a high quality, large randomized multicenter controlled trial. It is investigating the effect of nabiximols on tics. 14 Results are expected to be published soon after the time of this writing.
More recently, a new cannabinoid pharmaceutical has been developed called THX-110 that incorporates THC with other compounds. This product is manufactured by Therapix Biosciences Ltd and is “based on Dronabinol” and PEA (an endocannabinoid-like molecule) to “induce the entourage effect”. THX-110 consists of up to 10mg THC with 800MG PEA. 15 In autumn of 2021, results from a phase-2 pilot study of THX-110 found an improvement in tic symptoms in 16 adults with TS over a 12-week treatment period. 16
Because of the extensiveness of research using cannabis-based medicine for the treatment of tic disorders, comprehensive evidence reviews and treatment guidelines are available. A 2019 systematic review of treatments for people with TS and chronic tic disorders concluded that people with tics receiving THC are “possibly more likely than those receiving placebo to have reduced tic severity”. This study also reviewed risk of harm, such as weight gain and sedation. It did not find risk associated with THC treatment, unlike for pharmaceutical drugs like clonidine, risperidone, and aripiprazole. 17
What about treatment guidelines? A 2021 review on the use of cannabis-based medicine in the treatment of TS reported that the European Society for the Study of Tourette Syndrome (ESSTS) and the American Academy of Neurology (AAN) recommend behavioral therapy and pharmacotherapy with antipsychotics as first line treatments for tics. Cannabis-based medicine is classified as “an experimental intervention that should be applied to patients who are otherwise treatment-resistant”. 18 Given the experience of my family, this is a troubling recommendation. There is a high prevalence of side effects associated with the recommended pharmacotherapies. This is not the case with cannabis-based medicine.
There is very limited research on CBD in the treatment of tic disorders. A 2016 case study assessed whether Sativex (10.8mg THC and 10mg CBD) reduced severe motor and vocal tics. Treatment was over a four week period. The treatment resulted in a “marked improvement” in both the frequency and severity of both types of tics. 19 Similarly, a 2019 case report found that a daily dose of 10mg THC with 20mg CBD resulted in a “rapid and highly significant” reduction in tics. 20
While most of the published literature has examined adult patients with tics, a 2019 case report in the journal Medical Cannabis and Cannabinoids looked at the effectiveness of cannabis-based medicine in a pediatric subject. 21 A 12-year-old boy with TS experienced an initial reduction in tics when consuming vaporized THC equivalent to 4.4 mg. When the boy’s condition worsened, oral THC drops were added to the regimen at a daily dose of 12.5mg THC. No adverse events were reported. However, the author noted that treatment with cannabis in pediatric populations should be regarded as a “last-line treatment when well-established treatments have failed to improve tics”. As already mentioned, I would challenge that statement given the high incidence of significant side effects associated with the first-line pharmacotherapies. This general approach is consistent with the reluctance to use cannabis-based medicine as a first line medical therapy.
A study measuring levels of endocannabinoids in the cerebrospinal fluid of adult TS patients found that anandamide (AEA), 2-arachidonoylglycerol (2-AG), and palmitoylethanolamide (PEA) were significantly increased relative to controls. The authors hypothesize that this demonstrates alterations in endocannabinoid system function in patients with TS. This may be either a primary cause or a secondary change resulting from alterations in other systems. 23 A 2004 study investigated whether common polymorphisms in the CB1 gene were associated with TS. The researchers did not find an association in the population studied. 23 However, a 2020 study found a significant association between a CB1 gene variant and TS. 24 These results certainly implicate the ECS in TS, but this remains poorly understood.
CBD has been the primary cannabinoid that has been used for my son’s treatment over the last 15 months. We’ve mostly used oil-based preparations. These have taken several forms, including liquid products, gelcaps, water-soluble preparations, and inhalation. Here’s a breakdown the different modes of administration in regards to our experience:
Oils: Taking an oil preparation can be challenging for a child. At first, we used a broad-spectrum oil extracted from cannabis (not hemp). It had a very strong taste due to the terpene profile. To make it more palatable, I put it in some lemon syrup. Subsequently we moved onto a hemp-derived CBD isolate oil. It had a less diverse chemical profile but was mostly tasteless and odorless. I put the oil into his morning smoothie. Another challenge is the slow onset and poor bioavailability. When taken on an empty stomach, studies have shown that the bioavailability of oil soluble CBD is only about 6%. 25 If taken with a high fat meal, bioavailability goes up fourfold. 26 Peak levels of lipid-soluble CBD also take at least 90 minutes to achieve. 27 Tic severity varies widely during the day, waxing and waning in response to stress and fatigue. Therefore, when there is a flare, it is difficult to use CBD oil treatment because of the slow onset. However, it can be used on a regular dosing schedule. We use CBD oil in the morning as described. After school, he takes a CBD oil gel cap which makes consumption easier if we’re on the go with after school activities.
In our experience, oral CBD oil has only a modest effect on tic severity. The effects are complicated by issues including the “as needed” medicinal effects related to tic severity fluctuation. There is also the difficulty of timing peak concentrations due to limited absorption. However, we have noted an anxiolytic and calming effect.
My son noted that the CBD oil helps him to feel calm and focused in the morning. Our cannabis physician prescribed CBD oil starting at 20mg twice daily, with incremental increases to determine the optimal dose. We found that our optimal dose was 40mg twice daily.
Water-Soluble: Water-soluble CBD has been shown to be absorbed much faster than lipid soluble preparations. In fact, its bioavailability was shown to be 4.5 times greater in a recent pharmacokinetic study. It is also easily dissolved in water and has no taste or odor. In addition, it has a very fast onset and appears in the blood in as little as 15 minutes. 27 This makes it a viable option for treating “tic flares” when they arise.
I live in Canada. It is illegal to ship or transport cannabinoids internationally. There are water-soluble products available in my country. But their cost is extremely high. Also there has been limited research into the safety of nanoparticles. 28 Given my son’s young age, I prefer to err on the side of caution and avoid nano products. There are water-soluble CBD products that are in micromolar size. I have found that these provide a good alternative to lipid-soluble CBD. They have the added benefit of a quick onset and easy incorporation into any food or beverage.
The micromolar CBD products have provided an anxiolytic and calming effect with a modest change on tic severity. Because of the higher bioavailability of water-soluble CBD, a lower dose can be taken. We find that 15mg of water-soluble CBD provides comparable benefits to 40mg of CBD oil as a liquid or in gelcaps. For tic flares, 30mg of water-soluble CBD provides a rapid calming effect.
Inhaled: The fluctuating nature of tic disorders makes therapies with a fast onset a primary goal. This will not be the case with any orally ingested product, although water-soluble products will have a much faster onset than lipid-soluble preparations. Inhaled cannabinoids provide the fastest onset and greatest bioavailability, with an onset and peak within minutes following ingestion. 26 To treat my son’s acute tic flares, we occasionally use a CBD “puffer” that uses the same technology and delivery method as an asthma inhaler. These are metered inhalers which provide a measured dose of CBD, usually less than 5 mg per puff. We use a CBD-only inhaler and find that it provides some relief from the tics and anxiolytic effects at a dose of approximately 10mg.
CBDA (cannabidiolic acid) is the precursor to CBD and the form found in the raw plant. CBDA undergoes degradation to CBD in the presence of heat, light, and oxidants, which begins spontaneously after the plant is harvested. 26 CBDA is more easily absorbed than CBD. CBDA decreases inflammation by inhibiting the activity of the enzyme cyclooxygenase-2 (COX-2) (which mediates the synthesis of pro-inflammatory prostaglandins) and is structurally similar to salicylic acid. 29,30
I became interested in trying CBDA after observing that my son’s tics were greatly diminished when taking Aleve to treat an ear infection. Like CBDA, Aleve is a COX2 inhibitor. Although I have been unable to find any published research looking at either Aleve or CBDA in the treatment of tics, NSAIDS have been found to decrease flares in the related conditions PANS and PANDAS. 31 Unfortunately, CBDA is not widely available outside of the United States. I did have access to it when we spent a few months living in Florida. We found CBDA to be quite effective at reducing tic severity.
In our experience, CBDA does a better job at reducing tic severity but does not have as much of a calming and anxiolytic effect as CBD. But they can be used together to complement each other. We use 10-15mg of CBDA per treatment dose.
As already described, research on using cannabinoids for tic disorders has primarily been focused on using whole plant cannabis and THC. I admit I had an initial reluctance to use THC with my son out of concern over its psychoactive effects. However, we found that he was able to take the initially prescribed dose of 2.5mg THC balanced with 5mg of CBD without any noticeable impairment. But this wasn’t a high enough dose to have much effect on the tics. We found that a dose of 5mg of THC was required for maximum effect. This is a level that induces some noticeable impairment. My son reports his eyes feel heavy and he becomes slightly lethargic. For this reason, we reserve the higher dose of THC only when we are in what I call a “tic crisis”. Also, THC can be balanced with CBD at a 2:1 ratio to reduce some of THC’s psychoactive effects.
We use THC taken in gelcaps, which presents the issue of delayed onset of action and low bioavailability. We have only ever used THC in the evenings for two reasons. First, we want to avoid any potential psychoactive effects in school. Second, my son’s tics are usually much worse in the evening. A more rapid onset of action could be achieved by using an inhalation delivery method. Inhalers are now available with different ratios of CBD and THC, but we have been unable to get one in Canada.
Pediatric Considerations and Product Safety Considerations
Using cannabis-based medication with a child can present challenges. It may be difficult to find a medical practitioner who has experience with pediatric populations. The coordination of care between the cannabis physician and regular pediatrician or GP can be tricky if they are not knowledgeable about these treatments. When we told our GP about our intention to medicate with cannabinoids, she seemed shocked. But she did not attempt to discourage us from doing so. Others may not be so lucky.
There is also a social stigma associated with pediatric cannabis use, which stems from the nearly 100-year prohibition of the plant. We have never had to ask our son’s school to administer cannabinoid medication because our dosing regimen does not require this. But if it does, one should be prepared with the appropriate medical documentation. Sharing this information with other parents can also be tricky. I always preface our son’s use of cannabis-based medication with a clarification that he has a medical cannabis prescription from a physician. I also share some of the research that has been done on cannabis and tic disorders. People with little knowledge about cannabis-based medicine may assume that products such as CBD and CBDA are psychoactive and think you are giving your child something to make them “high”. We should educate and inform others using the best available information.
When purchasing any cannabis product, it’s always important to do your due diligence. This is especially important when administering cannabinoids to children. Only buy products that have undergone third party testing for pesticides, residual solvents, molds, heavy metals, and mycotoxins and avoid unnecessary flavorings. Of course, you should buy products that have been recommended and prescribed by your physician. In Canada, the cannabis market is legalized and regulated which means that all products have undergone safety testing and approval. I always buy products through one of the dispensaries recommended by our cannabis physician. Although I have found on more than one occasion that the prescribed product has been unavailable through the dispensary. When this happens, I’ve had to purchase a comparable product through a government store.
Many people experience tic disorders decreasing in severity over time, especially into adolescence. 32 For us, the four-month period following sudden onset was very severe. Gradually the intensity of the tics lessened. When we started using cannabis-based medicine, we discontinued the use of pharmaceutical drugs. At that point, we found the condition to be quite manageable. My son does experience flare ups, though.
As described by the American Academy of Child & Adolescent Psychiatry, tics can be exacerbated by “anxiety, tiredness, and certain medications”. 33 We have certainly found this to be the case. Any stressful situation can bring on a tic flare. Late nights or early mornings are almost invariably followed by a “bad day” until sufficient rest is achieved. My son has also experienced an exacerbation following a concussion, probably due to the associated neuroinflammation. His most severe increase in symptoms was following the second dose of the COVID-19 vaccine. We managed it with cannabis-based medicine along with over-the-counter anti-inflammatories.
With tic disorders, there are good days and bad days. Sometimes tics flare up when you least expect it. Thankfully, cannabis-based medicine is available in different forms for acute and ongoing treatment. For flare ups, delivery methods such as inhalation or water-soluble preparations provide a faster onset of action. Oils and gel caps can be taken on a regular schedule. CBD and CBDA are non-psychoactive cannabinoids that can help to reduce anxiety and tic severity. THC can be used when tics are more severe. We use a variety of different cannabinoids as our primary therapy and follow different regimens depending on the situation. This has been very effective and most of the time does not cause any side effects.
My family is grateful for the support of physicians who courageously support pediatric populations with cannabis-based medicine.
Dr. Genevieve Newton spent 19 years as a researcher and educator in the field of nutritional sciences. A series of personal health crises led her to discover the benefits of medicinal cannabis, and she soon found herself engrossed in studying the endocannabinoid system and therapeutic applications of cannabis/cannabinoids in mental health, pain, sleep, and neurological disorders. She is the Scientific Director at Fringe, a medical education company that is focused on whole person health.
More By Dr. Newton
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Treatment of patients with tic disorders and Tourette syndrome with cannabis-based medication
Dr. Kirsten R. Müller-Vahl is a Professor of Psychiatry at the Department of Psychiatry, Socialpsychiatry and Psychotherapy at the Hannover Medical School (MHH), Germany. She is a specialist in both neurology and adult psychiatry. From 1997 to 2003 she was a grant holder of the German government (Dorothea-Erxleben-Stipendium) for scientific research related to Tourette syndrome (TS). During the last 20 years she has investigated more than 1500 patients with TS (children and adults) and is the head of the Tourette-Syndrome outpatient department (since 1995). From, 2012-2016 she was the vice president of the European Society of the study of Tourette syndrome (ESSTS). She was a German representative of the COST Action BM0905 (“European Network for the Study of Gilles de la Tourette Syndrome”). She is a full partner and a working group leader in the EU funded programmes “European Multicentre Tics in Children Studies” (EMTICS) and “TS-EUROTRAIN-Interdisciplinary training network for Tourette Syndrome”. She is a member of the Medical Advisory Board of the Tourette Association of America (TAA) and an author of the guidelines for the treatment of TS of both ESSTS and the American Academy of Neurology. Since 1998, she is a member and 2. Chairwoman of the Association for Cannabinoid Medicines (ACM). She was a founding member of the International Association for Cannabinoid Medicines (IACM) and from 2007-2009 1. Chairwoman and since 2015 vice president of the IACM.
Tic disorders are defined by the presence of motor and/or vocal tics. Motor tics are simple or more complex abrupt involuntary movements that can occur all over the body, but most often are located in the face and head. Vocal tics are characterized by meaningless “simple” sounds or noises, but also can be more “complex” including obscene words. Tourette syndrome (TS) is complex neurological-psychiatric disorder defined by the presence of both multiple motor and at least one vocal tic.
Tic disorders and Tourette syndrome
TS is a neurodevelopmental disorder and therefore age at onset is in childhood – most typically at age 6 to 8 years. The vast majority of patients with TS, however, suffer not only from motor and vocal tics, but also from one or more behavioral problems such as attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive behavior (OCB), anxiety, depression, rage attacks, self-injurious behavior, sleeping disorder, but also leaning problems and autism spectrum disorder. Therefore, in many patients quality of life is substantially impaired.
Treatment of patients with tic disorders and Tourette syndrome
Due to the complex symptomatology and changes in clinical presentation over time, treatment of patients with TS is often challenging. Until today, tics cannot be cured. Established treatment strategies for tics include either behavioral therapy or pharmacotherapy with anti-psychotic drugs. While behavioral therapy does not cause adverse events, on average a tic improvement of only 30% can be achieved. Compared to behavioral therapy, pharmacotherapy with antipsychotics is more effective and often results in a tic reduction of about 50%. However not all patients benefit from antipsychotic medication and in many patients it is associated with relevant side effects such as sedation, weight gain, and sexual dysfunction. Patients, who suffer in addition from clinically relevant psychiatric disorders, need a combined treatment, since until today there is no therapeutic approach known that improves not only tics, but also psychiatric comorbidities. Therefore, many patients with TS are unsatisfied with available treatment strategies and seek for alternative medicine.
Against this background, new treatment strategies are urgently needed for this group of patients. Ideally, these new treatments (i) are associated with lesser side effects compared to available substances, (ii) result in a better improvement – or even a complete remission – of tics, (iii) are also effective in otherwise treatment resistant and severely affected patients, and (iv) improve not only tics, but the whole spectrum of the disease including different psychiatric symptoms such as ADHD, OCB, and depression.
Cannabis-based medication for patients with tic disorders and Tourette syndrome
In 1988, for the first time it has been suggested that cannabis might be such an alternative treatment option for patients suffering from TS. In this report, three male patients at ages 15, 17 and 39 years were described, who experienced a reduction in motor tics and premonitory urge sensations, an improvement in self-injurious behavior tendencies, attention, and hypersexual behavior as well as a generalized feeling of relaxation when smoking cannabis. No side effects occurred and treatment effect was stable over time and did not decrease. Since this initial report, a small number of case studies has been published describing beneficial effects of cannabis as well as other cannabis-based medications in patients with TS. There are no reports available about severe side effects or cannabis addiction. In most of these case studies, the authors report about beneficial effects on both tics and psychiatric symptoms. In many of the patients pharmacotherapy with other substances (such as antipsychotics for the treatment of tics, methylphenidate for the treatment of ADHD, or antidepressants for the treatment of depression, anxiety, and OCB) could be stopped.
Retrospective studies of cannabis
In 1998, in Germany a survey has been performed among patients with TS exploring the frequency and effect of (illegal) cannabis use. Of 64 patients, who were interviewed, 17 (27%) reported the use of cannabis and of these 14 (82%) reported that they felt cannabis improved their tics and premonitory urges as well as behavioral symptoms such as OCB and ADHD.
In line with this data, only recently researchers from Canada reported results from a retrospective evaluation on the effectiveness and tolerability of cannabis in 19 adults with TS. On average, they found a tic reduction of 60%, and 95% of patients were rated as at least “much improved.” In several patients, in addition, an improvement of psychiatric problems was reported. Cannabis was generally well tolerated and only mild side effects occurred such as decreased concentration, motivation and short-term memory, anxiety, increased appetite, sedation, and dry mouth and eyes.
In a retrospective study, we analyzed data from 98 patients with TS (mean age = 28.2 (+13.7) years) treated with different cannabis-based medications in our specialized Tourette outpatient clinic at Hannover Medical School, Hannover, Germany (unpublished data). Most of our patients used illegal cannabis (from different sources) (71%) for the treatment of TS. Only 37% of patients were treated with tetrahydrocannabinol (THC, dronabinol, the most psychoactive ingredient in cannabis), 32% received treatment with nabiximols (Sativex®, a cannabis extract standardized for THC and cannabidiol (CBD) at a 1:1 ratio), and 22% had access to (standardized) medicinal cannabis (from a pharmacy). The high percentage of illegal cannabis use – compared to the low percentage of treatments with medicinal cannabis – is related to the fact that in Germany only in March 2017 national laws changed and only since that time cannabis can be prescribed by medical doctors. Before March 2017, treatment with medical cannabis was restricted to a small group of patients, who have had received a specific permission by the German federal opium agency. However, when asking patients about the preferred kind of cannabis-based medication (if available), interestingly, 2/3 of patients answered that they would prefer inhaled medicinal cannabis (from a pharmacy) over other cannabis-based medications. In line with this preferred choice, medicinal cannabis was reported as more effective in reducing tics than other cannabis-based medications (in descending order): in 100% (N=21) of patients using medicinal cannabis, in 90% (=67) using illegal cannabis, in 77% (N=35) using THC (dronabinol), and in 76% (N=33) using nabiximols (Sativex®) (multiple answers possible). Accordingly, patients also assessed cannabis (both from illegal sources and medicinal cannabis from a pharmacy) more effective than nabiximols (Sativex®) and THC (dronabinol) in reducing psychiatric symptoms including OCB, ADHD, depression, anxiety disorders, self-injurious behavior, rage attacks, and sleeping problems. Altogether, patients assessed cannabis superior compared to both nabiximols (Sativex®) and THC (dronabinol).
Placebo-controlled trials using THC
Currently, only two preliminary controlled trials have been conducted to investigate the efficacy and safety of orally administered THC (dronabinol) in patients with TS. In a pilot study, a single dose of THC was compared to placebo in a crossover study of 12 adults. In a follow-up study, efficacy and tolerability of THC was compared to placebo in a 6 week trial of 24 adults. In both studies, treatment with THC resulted in a significant improvement of tics. No severe side effects occurred, but transient mild adverse events such as dizziness and tiredness.
Side effects profile of cannabis-based medication
Interestingly, there is some evidence that tolerability and side effects profile of cannabis and cannabis-based medication may be different in patients with TS compared to healthy people. In parallel to the above mentioned controlled trials, neuropsychological performance and cognitive function have been investigated before, during and after treatment with THC (dronabinol). In these studies, no detrimental effects of THC were seen on any of assessments used. Measuring immediate verbal memory span, there was even a trend towards an improvement during treatment with THC (dronabinol). Completely in line with these findings, in a single case study, treatment of a 42 year old patient with TS with THC resulted not only in a 75% tic reduction, but also in an improvement of his driving ability as measured by standardized driving tests.
Summary and perspective
Based on these results from clinical reports and preliminary controlled studies, it has been suggested that cannabis-based medication may be a new and promising treatment strategy for patients with TS. However, it has also been speculated that TS might be caused by a dysfunction in the endocannabinoid system in the brain. This hypothesis fits perfectly with the clinical observation that treatment with cannabis-based medication results in an improvement of both tics and behavioral problems without causing clinically relevant impairment on concentration and psychomotor functions. Since it is well-known that the endocannabinoid system modulates several other neurotransmitter systems in the brain (including the dopaminergic, GABAergic, serotonergic and glutaminergic systems), a dysfunction in the central endocannabinoid system will result in imbalances in several other transmitter system and, thus, may explain the complex clinical symptomatology in TS.
Motivated by these promising data, several clinical studies have been initiated to further investigate the efficacy and tolerability of different cannabis-based medications in the treatment of patients with TS including nabiximols (Sativex®), THC (dronabinol) , and medicinal cannabis. In addition, pilot studies have already been initiated or are in preparation investigating the effects of cannabinoid modulators as well as the so called “entourage effect” in this group of patients. The entourage effect can be achieved by substances that enhance the action of endogenous cannabinoids such as anandamide. These studies are funded by either pharmaceutical companies or the German Research Society (DFG). Thus, our knowledge about the effects of cannabis-based medicine in patients with TS will definitely increase within the next few years. This is important and will be very helpful for patients with TS, because until today – at least in Germany and many other European countries – many doctors hesitate to prescribe medicinal cannabis, health insurances often refuse to cover the costs for this kind of treatment, and patients are often stigmatized as recreational cannabis users and cannabis-addicted, instead of being generally accepted as patients simply using that medication that is most effective for the treatment of their symptoms.