Treatment of patients with tic disorders and Tourette syndrome with cannabis-based medication
By Kirsten Müller-Vahl
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.
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
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Table of Contents
Overview of Tourette Syndrome
Tourette syndrome or Tourette’s is a neuropsychiatric disorder that develops in early childhood.
It falls under the class of ‘tic’ disorders wherein tic denotes an unexpected, nonrhythmic motor movement or vocalization that involves certain muscle groups.
Tics in Tourette’s are characterized by rapid eye blinking, facial contortions, repetitive throat clearing, and at least one vocal tic which might involve an outburst of taboo speech.
Benefits of CBD in Tourette syndrome
The major benefits of using CBD to treat Tourette syndrome are linked with its ability to mediate neurotransmission and act on specific parts of the brain concerned with motor function. CBD reduces both the frequency and intensity of motor and verbal tics. It also helps in treating behavioural disorders such as hyperactivity and aggression. CBD also alleviates obsessive-compulsive tendencies and treats generalized anxiety disorders by activating serotonin receptors in the nervous system.
This action exerts an anxiolytic effect which, in turn, prevents the worsening of tic disorders. CBD usage also increasing the efficacies of conventional TS medical therapies.
1. CBD Reduces the Frequency of Tics
Tourette’s is marked by frequent and severe tics.
A tic denotes an involuntary and unexpected movement or speech which usually lasts for a brief spell and is non-rhythmic. The tics generally imitate regular, everyday behaviour often in the midst of daily activities.
They are commonly associated with a ‘premonitory urge’ or build up sensation to execute such actions and a sense of relief prevails after performing them.
Tics can be categorized as motor or vocal (phonetic). As the names suggest, motor tics are associated with movement whereas vocal tics involve particular sounds.
They can also be simple or complex depending upon the number and type of muscle groups used to perform the actions. Depending upon the onset and duration, they can be clonic (rapid), tonic (gradual), and dystonic (slow).
Simple motor tics include persistent blinking, shrugging, and neck stretching. However, complications arise when these tics include jaw clenching or copropraxia which entails performing socially obscene gestures.
Similarly, vocal tics might range from echolalia (repeating someone else’s speech) to coprolalia which involves spontaneous utterance of taboo or vulgar words.
Reducing the frequency of tics is one of the main areas of interest in TS research. Cannabis-derived compounds have shown considerable potential in this sphere.
A 1998 clinical study by the Medical School Hannover showed that CBD usage reduced the frequency of tics in TS patients by a staggering 82%. Several patients also reported the complete remission of both motor and vocal tics.
As per the results of the study, it was inferred that CBD mediates this effect via cannabinoid receptors present in the nervous system.
The conglomerate of cannabinoid receptors present in the basal ganglia and hippocampus of the brain is intrinsically involved in behavioural and motor control. CBD acts upon these receptors to lower the frequency and severity of tics.
CBD helps in lowering the frequency and intensity of TS-associated tics via the cannabinoid receptors present in the brain.
2. CBD Reduces Aggression and Hyperactivity Disorders
Tourette syndrome is associated with a host of behavioural symptoms including hyperactivity as well as aggression or outbursts of rage.
Around 25% of children suffering from TS are affected by such disorders but behavioural symptoms are sometimes observed in adults as well.
Such sudden bursts of aggression are usually unpredictable and often seem greatly disproportionate when compared with the provocative stimulus.
While the reasons might seem inadequate but the outcome is dangerous as patients often run the risk of severe self-harm and even injury to others.
Barring aggression, TS is often associated with other behavioural problems as 90% of the cases exist in conjunction with hyperactivity disorders like ADHD.
Attention-Deficit/Hyperactivity Disorder is characterized by a host of problems such as difficulties in concentrating and impulsive tendencies marked by periods of hyperactivity.
Such manifestations are quite similar to the tics seen in Tourette’s. A 2014 study conducted by the Yale School of Medicine has revealed that both TS and ADHD might have similar genetic components and occur in conjunction due to perinatal risk factors.
The research showed that children exposed to risk factors such as low birth weights and maternal smoking exhibited a greater tendency of developing both Tourette’s and ADHD.
Curbing the expression of unwarranted aggression and excessive hyperactivity will provide symptomatic relief in case of a neuropsychiatric disorder like TS.
Several studies have been conducted that promote the use of cannabis products like CBD in relieving the behavioural symptoms of TS.
A 2017 randomized placebo-controlled clinical study by the King’s College London showed that CBD usage helped in reducing the symptoms of ADHD and associated aggressive behaviour as seen in TS patients.
As CBD reduces the hyperactive and aggressive behaviour, it helps in relieving the complications associated with Tourette’s.
3. CBD Alleviates Obsessive-Compulsive Disorders
Tourette syndrome is often accompanied by another set of complicated behavioural problems known as obsessive-compulsive behaviour or, simply, OCD.
This disorder is often characterized by repetitive behaviour wherein individuals feel the need to constantly go over certain routines or obsess over certain thoughts.
OCD is often linked with the onset of tics as seen in TS. In fact, several patients suffering from Tourette’s develop OCD at some point in time.
While initially the obsessive rituals and thoughts are often an extension of the tics but gradually they tend to negatively affect the quality of life. The obsessive behaviour usually includes repeated handwashing, counting, and many more.
The need for such compulsive behaviour or thoughts is to overcome any anxiety or prevent the occurrence of some stressful event.
Patients may not often realize that performing these routines might not have any fruitful outcome. These behaviours are time-consuming and often adversely affect the person’s life.
Complicated motor tics in TS patients are aggravated by the development of OCD.
Hence, such compulsive behaviour must be overcome in order to reduce the symptoms of Tourette’s. Lowering OCD is, therefore, an active area of interest in the field of medical research.
A 2012 review by the Universidade Federal de Minas Gerais evaluated the role of CBD in the treatment of psychiatric disorders, particularly anxiety disorders like OCD.
It was established that cannabidiol alleviates such disorders by stimulating 5-HT1A(hydroxytryptamine)-mediated neurotransmission. As a result, TS patients can enjoy symptomatic relief.
As CBD helps in promoting neurotransmission, it helps in alleviating problems relating to OCD as seen in some TS patients.
4. CBD Relieves TS-induced Anxiety
Anxiety can exacerbate the symptoms of Tourette’s. A noteworthy percentage of school-going children suffering from Tourette’s often have to deal with associated stress and anxiety disorders.
Most children experience from social anxiety as they get worried about the perceptions regarding their tics.
Therefore, in order to their diagnosis of TS, they might also be suffering from a spectrum of anxiety disorders.
Barring social anxiety, children might also feel separation anxiety which is further aggravated by the diagnosis of obsessive-compulsive disorders. Generalized anxiety disorders are marked by feelings of nervousness, fear, and constant worrying.
Getting diagnosed with anxiety might initiate a vicious cycle for TS patients. Tic disorders actually create stressful situations that increase feelings of anxiety and nervousness and these sensations, in turn, increase the frequency and intensity of the tics.
Extreme anxiety attacks might result in palpitations, increased heart rates, generalized motor tics, and violent outbursts of aggressive behaviour.
A 2010 study by the University at Buffalo identified anxiety and panic attacks as the most serious comorbid disorders associated with Tourette syndrome.
Generalized anxiety can lead to the development of severe disabilities and alcohol/drug dependency in TS patients.
To counter this problem, significant research has been conducted to find anxiolytic drugs.
A 2015 study by the New York University School of Medicine has investigated the role of cannabidiol in the treatment of anxiety and panic disorders. The anxiolytic effect of CBD was attributed to its ability to activate the 5-HT1A (hydroxytryptamine) serotonin receptor.
As CBD promotes the serotonin receptor, it has an anti-anxiety effect and helps in reducing TS-induced anxiety attacks.
5. CBD Increases the Efficacies of Conventional TS Drugs
There is no known cure for Tourette syndrome. The treatment is mostly directed against the onset of tics and aims to lower the frequency and severity of such events.
Medication is also administered to treat the comorbid disorders associated with Tourette’s such as ADHD, OCD, and generalized anxiety disorders. Behavioural therapies are aimed at reducing aggression.
The conventional drug therapies for TS include medications that block the neurotransmitter, dopamine, which has been implicated in tic disorders.
Haloperidol and pimozide control tics but the side effects include weight gain and some involuntary movement. Botulinum injections might also help in treating the affected muscle groups.
Methylphenidate can help increase concentration and treat TS-associated ADHD. However, in some cases, such medications might actually increase the frequency of the tics.
Central adrenergic inhibitors might help in improving behavioural control by preventing rage attacks. However, the side-effects include drowsiness. Antidepressants can also control symptoms of anxiety.
However, research has shown that CBD has great potential in alleviating all the major symptoms and comorbid disorders associated with TS without causing any mind-altering side-effects.
An early study published in the Life Sciences journal established that cannabinoids like CBD increase the effectiveness of conventional TS drugs when administered as adjuncts to them.
As CBD helps in increasing the efficiencies of conventional TS drugs, it helps in reducing symptoms like tic disorders as well as comorbid disorders.
It is advisable to consult a medical practitioner before consuming medications containing THC. The dosage depends on the mode of delivery as the CBD products can be orally ingested or inhaled by a vaporizer.
There is no prescribed dosage for using CBD oil to completely treat Tourette syndrome as it has no cure.
Nevertheless, symptomatic relief can still be provided. Small doses of 40-50mg should be consumed, initially, and the optimum dose should be decided as per the individual’s tolerance capacity.
Vaporizers containing CBD oil can be used to provide an immediate relief from motor tics as well as anxiety attacks and 10 mg should be inhaled.
The plant-derived cannabinoid, CBD, has very few known side-effects. Regular oral doses of up to 500mg can be had for as long as 5-6 months.
A 2011 review stated that even high doses of 1500mg can be tolerated daily for a period of almost 3 months without producing any unwarranted complications.
CBD products usually contain variable amounts of the psychotropic agent, tetrahydrocannabinol (THC), which is responsible for some of the side-effects.
While the quantity of THC permitted in medicinal products is quite scarce but sensitive individuals might still experience the hallucinatory effect.
CBD inhibits the activity of cytochrome p450, a class of liver enzymes involved in the metabolism of drugs and therefore, CBD usage lessens the efficacies of certain medications.
Medicines containing an excess of THC might cause confusion, dizziness, disorientation, nausea, vomiting, fatigue, impaired balance, hallucinations, and paranoia.
They might also cause tachycardia, a condition wherein the heart rate gets abnormally raised for a short duration.
Cannabis products which have a moderate amount of THC should not be accompanied by alcohol.
Pregnant and lactating women should consult a gynaecologist before consuming CBD-containing medicines. Caution should also be maintained while administering THC-containing products to children and adolescents as it might affect their CNS differently.
To summarize, it can be said that CBD confers several benefits in relieving the symptoms of Tourette’s.
Most importantly, it helps in lowering the frequency of motor and vocal tics by acting upon specific areas of the brain.
It also helps in treating behavioural complications such as ADHD and aggressive outbursts.
By activating the 5-HT1A serotonin receptor, it helps in exerting an anxiolytic effect which combats the development of OCD and anxiety disorders.
Using CBD as an adjunct therapy to conventional approaches helps in enhancing the effectiveness of the more common TS drugs.
CBD can help in Tourette Syndrome in several ways. It reduces both the frequency and intensity of motor and verbal tics, helps in treating behavioural disorders such as hyperactivity and aggression.