Cannabinoids treat Tourette Syndrome
Tourette syndrome (also called Tourette's syndrome, Tourette's disorder, Gilles de la Tourette syndrome, GTS or, more commonly, simply Tourette's or TS) is an inheritedneuropsychiatric disorder with onset in childhood, characterized by multiple physical (motor) tics and at least one vocal (phonic) tic. These tics characteristically wax and wane, can be suppressed temporarily, and are preceded by a premonitory urge. Tourette's is defined as part of a spectrum of tic disorders, which includes transient and chronic tics.
Tourette's was once considered a rare and bizarre syndrome, most often associated with the exclamation of obscene words or socially inappropriate and derogatory remarks (coprolalia), but this symptom is present in only a small minority of people with Tourette's. Tourette's is no longer considered a rare condition, but it is not always correctly identified because most cases are mild and the severity of tics decreases for most children as they pass through adolescence. Between 0.4% and 3.8% of children ages 5 to 18 may have Tourette's; the prevalence of transient and chronic tics in school-age children is higher, with the more common tics of eye blinking, coughing, throat clearing, sniffing, and facial movements. Extreme Tourette's in adulthood is a rarity, and Tourette's does not adversely affect intelligence or life expectancy.
Genetic and environmental factors play a role in the etiology of Tourette's, but the exact causes are unknown. In most cases, medication is unnecessary. There is no effective treatment for every case of tics, but certain medications and therapies can help when their use is warranted. Education is an important part of any treatment plan, and explanation and reassurance alone are often sufficient treatment. Comorbid conditions (co-occurring diagnoses other than Tourette's) such as attention-deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD) are present in many patients seen in tertiary specialty clinics. These other conditions often cause more functional impairment to the individual than the tics that are the hallmark of Tourette's, hence it is important to correctly identify comorbid conditions and treat them. The eponym was bestowed by Jean-Martin Charcot (1825–1893) on behalf of his resident, Georges Albert Édouard Brutus Gilles de la Tourette (1859–1904), a French physician and neurologist, who published an account of nine patients with Tourette's in 1885.
Tics are sudden, repetitive, nonrhythmic movements (motor tics) and utterances (phonic tics) that involve discrete muscle groups. Motor tics are movement-based tics, while phonic tics are involuntary sounds produced by moving air through the nose, mouth, or throat. Tourette's is one of several tic disorders, which are classified by the Diagnostic and Statistical Manual of Mental Disorders (DSM) as "disorders usually first diagnosed in infancy, childhood, or adolescence" according to type (motor or phonic tics) and duration (transient or chronic). Transient tic disorder consists of multiple motor tics, phonic tics or both, with a duration between four weeks and twelve months. Chronic tic disorder is either single or multiple, motor or phonic tics (but not both), which are present for more than a year. Tourette's (DSM-IV 307.23) is diagnosed when multiple motor tics, and at least one phonic tic, are present for more than a year. The fifth version of the DSM (DSM-5), due out in May 2013, is likely to reclassify Tourette's as a neurodevelopmental disorder, and to include additional diagnoses to account for tic disorders due to substance abuse or other general medical conditions.
Although Tourette's is the more severe expression of the spectrum of tic disorders, most cases are mild. The severity of symptoms varies widely among people with Tourette's, and mild cases may be undetected. Tics are movements or sounds "that occur intermittently and unpredictably out of a background of normal motor activity", having the appearance of "normal behaviors gone wrong". The tics associated with Tourette's change in number, frequency, severity and anatomical location. Waxing and waning—the ongoing increase and decrease in severity and frequency of tics—occurs differently in each individual. Tics also occur in "bouts of bouts", which vary for each person. Coprolalia (the spontaneous utterance of socially objectionable or taboo words or phrases) is the most publicized symptom of Tourette's, but it is not required for a diagnosis of Tourette's and only about 10% of Tourette's patients exhibit it. Echolalia (repeating the words of others) and palilalia (repeating one's own words) occur in a minority of cases, while the most common initial motor and vocal tics are, respectively, eye blinking and throat clearing.
In contrast to the abnormal movements of other movement disorders (for example, choreas, dystonias, myoclonus, and dyskinesias), the tics of Tourette's are temporarily suppressible, nonrhythmic, and often preceded by an unwanted premonitory urge. Immediately preceding tic onset, most individuals with Tourette's are aware of an urge, similar to the need to sneeze or scratch an itch. Individuals describe the need to tic as a buildup of tension, pressure, or energy which they consciously choose to release, as if they "had to do it" to relieve the sensation or until it feels "just right". Examples of the premonitory urge are the feeling of having something in one's throat, or a localized discomfort in the shoulders, leading to the need to clear one's throat or shrug the shoulders. The actual tic may be felt as relieving this tension or sensation, similar to scratching an itch. Another example is blinking to relieve an uncomfortable sensation in the eye. These urges and sensations, preceding the expression of the movement or vocalization as a tic, are referred to as "premonitory sensory phenomena" or premonitory urges. Because of the urges that precede them, tics are described as semi-voluntary or "unvoluntary,” rather than specifically involuntary; they may be experienced as a voluntary, suppressible response to the unwanted premonitory urge. Published descriptions of the tics of Tourette's identify sensory phenomena as the core symptom of the syndrome, even though they are not included in the diagnostic criteria.
While individuals with tics are sometimes able to suppress their tics for limited periods of time, doing so often results in tension or mental exhaustion. People with Tourette's may seek a secluded spot to release their symptoms, or there may be a marked increase in tics after a period of suppression at school or at work. Some people with Tourette's may not be aware of the premonitory urge. Children may be less aware of the premonitory urge associated with tics than are adults, but their awareness tends to increase with maturity. They may have tics for several years before becoming aware of premonitory urges. Children may suppress tics while in the doctor's office, so they may need to be observed while they are not aware they are being watched. The ability to suppress tics varies among individuals, and may be more developed in adults than children. Although there is no such thing as a "typical" case of Tourette syndrome, the condition follows a fairly reliable course in terms of the age of onset and the history of the severity of symptoms. Tics may appear up to the age of eighteen, but the most typical age of onset is from five to seven. A 1998 study published by Leckman et al. of the Yale Child Study Center showed that the ages of highest tic severity are eight to twelve (average ten), with tics steadily declining for most patients as they pass through adolescence.
The most common, first-presenting tics are eye blinking, facial movements, sniffing and throat clearing. Initial tics present most frequently in midline body regions where there are many muscles, usually the head, neck and facial region. This can be contrasted with the stereotyped movements of other disorders (such as stims and stereotypies of the autism spectrum disorders), which typically have an earlier age of onset, are more symmetrical, rhythmical and bilateral, and involve the extremities (e.g., flapping the hands). Tics that appear early in the course of the condition are frequently confused with other conditions, such as allergies, asthma, and vision problems: pediatricians, allergists and ophthalmologists are typically the first to see a child with tics.
The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved. Genetic epidemiology studies have shown that the overwhelming majority of cases of Tourette's are inherited, although the exact mode of inheritance is not yet known and no gene has been identified. In other cases, tics are associated with disorders other than Tourette's, a phenomenon known as tourettism.
A person with Tourette's has about a 50% chance of passing the gene(s) to one of his or her children, but Tourette's is a condition of variable expression and incomplete penetrance. Thus, not everyone who inherits the genetic vulnerability will show symptoms; even close family members may show different severities of symptoms, or no symptoms at all. Gene(s) may express as Tourette's, as a milder tic disorder (transient or chronic tics), or as obsessive–compulsive symptoms without tics. Only a minority of the children who inherit the gene(s) have symptoms severe enough to require medical attention. Gender appears to have a role in the expression of the genetic vulnerability: males are more likely than females to express tics.
Non-genetic, environmental, post-infectious, or psychosocial factors—while not causing Tourette's—can influence its severity. Autoimmune processes may affect tic onset and exacerbation in some cases. In 1998, a team at the USNational Institute of Mental Health proposed a hypothesis based on observation of 50 children that both obsessive–compulsive disorder (OCD) and tic disorders may arise in a subset of children as a result of a poststreptococcalautoimmune process. Children who meet five diagnostic criteria are classified, according to the hypothesis, as having Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). This contentious hypothesis is the focus of clinical and laboratory research, but remains unproven.
Some forms of OCD may be genetically linked to Tourette's. A subset of OCD is thought to be etiologically related to Tourette's and may be a different expression of the same factors that are important for the expression of tics. The genetic relationship of ADHD to Tourette syndrome, however, has not been fully established.
According to the revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), Tourette’s may be diagnosed when a person exhibits both multiple motor and one or more vocal tics (although these do not need to be concurrent) over the period of a year, with no more than three consecutive tic-free months. There are no specific medical or screening tests that can be used in diagnosing Tourette's.
The diagnosis is made based on observation of the individual's symptoms and family history. The treatment of Tourette's focuses on identifying and helping the individual manage the most troubling or impairing symptoms. Most cases of Tourette's are mild, and do not require pharmacological treatment; instead, psychobehavioral therapy, education, and reassurance may be sufficient. Treatments, where warranted, can be divided into those that target tics and comorbid conditions, which, when present, are often a larger source of impairment than the tics themselves. Not all people with tics have comorbid conditions, but when those conditions are present, they often take treatment priority.
There is no cure for Tourette's and no medication that works universally for all individuals without significant adverse effects. Knowledge, education and understanding are uppermost in management plans for tic disorders. The management of the symptoms of Tourette's may include: pharmacological, behavioral and psychological therapies. While pharmacological intervention is reserved for more severe symptoms, other treatments (such as supportive psychotherapy or cognitive behavioral therapy) may help to avoid or ameliorate depression and social isolation, and to improve family support. Educating a patient, family, and surrounding community (such as friends, school, and church) is a key treatment strategy, and may be all that is required in mild cases. Medication is available to help when symptoms interfere with functioning. Medications are quite strong and many individuals have adverse reactions to them or simply cannot tolerate them.
Tourette syndrome is a spectrum disorder—its severity ranges over a spectrum from mild to severe. The majority of cases are mild and require no treatment. In these cases, the impact of symptoms on the individual may be mild, to the extent that casual observers might not know of their condition. The overall prognosis is positive, but a minority of children with Tourette syndrome have severe symptoms that persist into adulthood.
Regardless of symptom severity, individuals with Tourette's have a normal life span. Several studies have demonstrated that the condition in most children improves with maturity. Tics may be at their highest severity at the time that they are diagnosed, and often improve with understanding of the condition by individuals and their families and friends. The statistical age of highest tic severity is typically between eight and twelve, with most individuals experiencing steadily declining tic severity as they pass through adolescence.
It is not uncommon for the parents of affected children to be unaware that they, too, may have had tics as children. Because Tourette's tends to subside with maturity, and because milder cases of Tourette's are now more likely to be recognized, the first realization that a parent had tics as a child may not come until their offspring is diagnosed. It is not uncommon for several members of a family to be diagnosed together, as parents bringing children to a physician for an evaluation of tics become aware that they, too, had tics as a child. Children with Tourette's may suffer socially if their tics are viewed as "bizarre". A person who was misunderstood, punished, or teased at home or at school will fare worse than children who enjoyed an understanding and supportive environment.
Tourette syndrome is found among all social, racial and ethnic groups and has been reported in all parts of the world. Up to 1% of the overall population experiences tic disorders, including chronic tics and transient tics of childhood. Tourette syndrome was once thought to be rare: in 1972, the US National Institutes of Health (NIH) believed there were fewer than 100 cases in the United States, and a 1973 registry reported only 485 cases worldwide. However, multiple studies published since 2000 have consistently demonstrated that the prevalence is much higher than previously thought.
Research and Studies
Scientific Evidence of Efficacy in Humans A number of studies since 1999 have shown that TS patients have an improvement in tics and in other associated behaviors (such as obsessive-compulsive behaviors) with use of THC, the main natural medicinal compound in cannabis, and no cognitive impairment was noted. In 2003, the previous findings were confirmed with another well-designed study that was published in the Journal of Clinical Psychiatry. In this study, TS patients received either THC or placebo for six weeks and scored the level of daily tics. Patients who were receiving THC had significant reduction of the tics and suffered no detrimental effects on learning, recall, or verbal memory. Researchers concluded that for adult TS patients, “Therapy with delta-9-THC should be tried…” For those patients who have not found relief from symptoms with conventional therapy, who have adverse side effects from current treatment, or who prefer a natural treatment, medical cannabis is a viable and reasonable alternative.
As for mode of action, there is a growing scientific literature concerning the body’s ability to make substances called endocannabinoids, which resemble the active compounds in marijuana. Our bodies contain various enzymes that make these endogenous cannabinoids, and two specific types of receptors for these substances are distributed throughout our body, including the brain. It appears that the cannabinoids can modulate major neurotransmitter systems in the brain – including those involving GABA and glutamine. These pathways provide one hypothesis for why marijuana sometimes has the effect of reducing tics. The American Medical Association stated in an online report "Medical Marijuana (A-01)" (accessed on Jan. 10, 2007): "Only limited data exist on the effects of marijuana in patients with Tourette’s syndrome who respond inadequately to standard treatment, consisting of 4 case histories that report beneficial effects of smoked marijuana and 1 who reported substantial benefit from oral 9-THC (10 mg)." The Institute of Medicine published in its Mar. 1999 report titled “Marijuana and Medicine: Assessing the Science Base”: "The movement disorders most often discussed as candidates for marijuana-based therapies are dystonias, Huntington's disease, Parkinson's disease and Tourette's syndrome.
As a general consideration, it is important to note that stress and anxiety tend to worsen the symptoms of movement disorders. Thus, marijuana's calming effect could be a primary reason why some patients claim that it brings them relief." Kirsten R. Müller-Vahl, MD, Director of the Tourette Syndrome Clinic at the Medical School of Hannover, stated in her Oct. 2003 article "Cannabinoids Reduce Symptoms of Tourette's Syndrome," published in Expert Opinion on Pharmacology: "Currently, the treatment of Tourette's syndrome (TS) is unsatisfactory. Therefore, there is expanding interest in new therapeutical strategies. Anecdotal reports suggested that the use of cannabis might improve not only tics, but also behavioural problems in patients with TS.
A single-dose, cross-over study in 12 patients, as well as a 6-week, randomised trial in 24 patients, demonstrated that delta-9-tetrahydrocannabinol (THC), the most psychoactive ingredient of cannabis, reduces tics in TS patients. No serious adverse effects occurred and no impairment on neuropsychological performance was observed. If well-established drugs either fail to improve tics or cause significant adverse effects, in adult patients, therapy with delta-9-THC should be tried. At present, it remains unclear whether herbal cannabis, different natural or synthetic cannabinoid CB1-receptor agonists or agents that interfere with the inactivation of endocannabinoids, may have the best adverse effect profile in TS." Kirsten R. Müller-Vahl, MD, Director of the Tourette Syndrome Clinic at the Medical School of Hannover, stated in her Oct. 2003 article "Cannabinoids Reduce Symptoms of Tourette's Syndrome," published in Expert Opinion on Pharmacology: "Currently, the treatment of Tourette's syndrome (TS) is unsatisfactory. Therefore, there is expanding interest in new therapeutical strategies. Anecdotal reports suggested that the use of cannabis might improve not only tics, but also behavioural problems in patients with TS.
A single-dose, cross-over study in 12 patients, as well as a 6-week, randomised trial in 24 patients, demonstrated that delta-9-tetrahydrocannabinol (THC), the most psychoactive ingredient of cannabis, reduces tics in TS patients. No serious adverse effects occurred and no impairment on neuropsychological performance was observed. If well-established drugs either fail to improve tics or cause significant adverse effects, in adult patients, therapy with delta-9-THC should be tried. At present, it remains unclear whether herbal cannabis, different natural or synthetic cannabinoid CB1-receptor agonists or agents that interfere with the inactivation of endocannabinoids, may have the best adverse effect profile in TS." Reuven Sandyk, MD, Assistant to the Editor-in-Chief at the International Journal of Neuroscience, and Gavin Awerbuch, MD, a Neurologist and Pain Management/ Sleep Disorder Specialist, stated in their Dec., 1988 letter to the Journal of Clinical Psychopharmacology titled "Marijuana and Tourette's Syndrome": "We recently encountered three patients with TS [Tourette's syndrome] who experienced incomplete responses to conventional anti-TS drugs but noted a significant amelioration of symptoms when smoking marijuana
It is reasonable to assume that the effects of marijuana in TS may be largely related to its anxiety-reducing properties, although a more specific antidyskinetic effect cannot be excluded." A review of the scientific literature reveals several clinical trials investigating the use of cannabinoids for the treatment of TS. Writing in the March 1999 issue of the American Journal of Psychiatry, investigators at Germany's Medical School of Hanover, Department of Clinical Psychiatry and Psychotherapy, reported successful treatment of Tourette's syndrome with a single dose of 10 mg of delta-9-THC in a 25-year-old male patient in an uncontrolled open clinical trial. Investigators reported that the subject's total tic severity score fell from 41 to 7 within two hours following cannabinoid therapy, and that improvement was observed for a total of seven hours. "For the first time, patients' subjective experiences when smoking marijuana were confirmed by using a valid and reliable rating scale," authors concluded. Investigators again confirmed these preliminary results in a randomized, double-blind, placebo-controlled, crossover, single dose trial of THC in 12 adult TS patients. Researchers reported a "significant improvement of tics and obsessive-compulsive behavior (OCB) after treatment with delta-9-THC compared to placebo." Investigators reported no cognitive impairment in subjects following THC administration and concluded, "THC is effective and safe in treating tics and OCB in TS."
Investigators confirmed these results in a second randomized, double-blind, placebo-controlled trial involving 24 patients administered daily doses of up to 10 mg of THC over a six-week period. Researchers reported that subjects experienced a significant reduction in tics following long-term cannabinoid treatment, and suffered no detrimental effects on learning, recall or verbal memory. A trend toward significant improvement of verbal memory span during and after therapy was also observed. Summarizing their findings in the October 2003 issue of the journal Expert Opinions in Pharmacotherapy, investigators concluded that in adult TS patients, "Therapy with delta-9-THC should be tried if well established drugs either fail to improve tics or cause significant adverse effects.
REFERENCES
[1] Muller-Vahl et al. 1999. Treatment of Tourette's syndrome with delta-9-tetrahydrocannabinol. American Journal of Psychiatry 156: 495. [2] Muller-Vahl et al. 2002. Treatment of Tourette's syndrome with Delta-9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry 35: 57-61. [3] Muller-Vahl et al. 2001. Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance. Pharmacopsychiatry 34: 19-24. [4] Muller-Vahl et al. 2002. op. cit. [5] Muller-Vahl et al. 2003. Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. Journal of Clinical Psychiatry 64: 459-65. [6] Muller-Vahl et al. 2003. Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance. Neuropsychopharmacology 28: 384-8. [7] Kirsten Muller-Vahl. 2003. Cannabinoids reduce symptoms of Tourette's syndrome. Expert Opinions in Pharmacotherapy 4: 1717-25.
Research and Studies continued
Medical marijuana has potential to be a treatment for a slew of neurological disorders. Tourette's syndrome happens to be a neurological disorder, one that adversely affects the lives of hundreds of thousands of people in the United States alone. Mild Tourette's syndrome affects many more than that. Estimates put the rate of mild to barely noticeable Tourette's at roughly one in every hundred people. The neurological symptoms of this condition vary greatly. However, they are all involuntary movements and sounds that may be calmed by medical marijuana. The symptoms of Tourette's typically appear between the ages of three and nine and are at least three times more common in males. All of the symptoms are known as tics or vocalizations, though they differ even among the individual types. Tics can range from simple involuntary blinking or shrugging to twisting. In complex tics, several movements can occur at the same time. For example, an individual with Tourette's syndrome might blink while jumping. Vocalizations range from grunting to swearing. These symptoms can interfere with a person's life. Tics can even cause self-harm.
The mechanisms for treatment of Tourette's with medical marijuana are not as well understood as that for other conditions. That is likely because there is very little research in this area and Tourette's syndrome is a complex neurological disorder that has some psychiatric components, such as obsessions and compulsions. Nonetheless, the research that does exist shows some improvement of tics in users of medical marijuana. Furthermore, the testimonies of individuals with Tourette's syndrome who use medical marijuana are generally positive.
Medical Marijuana and Tourette's Syndrome
TREATMENT OF TOURETTE'S SYNDROME WITH MEDICAL MARIJUANA VERSUS SUPPRESSION There is some stigma surrounding the tics involved with Tourette's syndrome. There is also stigma surrounding marijuana use, even for medical purposes. Some Tourette's sufferers have noticeable, though not substantial, success suppressing their tics. This can lead to extreme discomfort and eventual forceful return of the tic. While it might look like Tourette's sufferers are performing these acts on purpose, that is not the case.
Medical marijuana is not counterproductive in the way that attempting suppression is. It may not eliminate the tics and only mildly relieve them, but there is no evidence to suggest that marijuana can exacerbate them. A study done at the Birmingham and Solihull Mental Health Trust concluded that there were only small improvements in tics with use of medical marijuana. Nonetheless, their findings did not include any adverse effects as it pertained to the tics and obsessive-compulsive behaviors.
MEDICAL MARIJUANA AND TOURETTE'S SYNDROME RESEARCH Even the earliest research involving Tourette's syndrome and medical marijuana suggest that the cannabis component that is helping the tics is THC. The first observed treatment of Tourette's syndrome with medical marijuana was conducted on a 25-year-old man with severe Tourette's. He had been displaying symptoms from an early age and was initially diagnosed with ADHD. He was later diagnosed with Tourette's. He found independently that smoking marijuana was helping his condition. Doctors gave him a 10-milligram dose of THC three days after having him stop smoking and observed the results. Within 30 minutes, his symptoms began decreasing. There was roughly 70% fewer symptoms and the medication lasted roughly 7 hours.
A later randomized, double blind, controlled study showed that there was a notable difference between the patients who were given placebo and those who were given THC. The study began with 24 individuals and eventually dropped down to 17. However, that was not due to side effects in six of the dropouts. This is a significant increase in test subjects over the first study conducted on the one young man. The similar results even in a double blind, controlled study is strong evidence that THC can have a positive effect on Tourette's syndrome tics. Further research along this vein could lend some insight into the syndrome itself.
It is essential that more research be conducted into the mechanisms of treatment of Tourette's syndrome with medical marijuana so that more specific medication and doses can be catered to the condition. The current medications are proving insufficient. Medical marijuana could become the treatment of choice, especially if one of the non-psychoactive components of the drug is found to help as well, as that would allow for a look at treatment of children with no cognitive side effects.
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