What is Tourette’s Syndrome?
Tourette’s Syndrome is a neurodevelopmental condition that is characterised by the presence of involuntary movements and sounds called ‘tics’. The types of tics can vary from person to person but they are difficult to suppress and are often associated with feelings of discrimination, lower rates of employment, and a reduced quality of life. Tourette’s Syndrome is generally diagnosed in childhood and adolescence. While the condition was long believed to be rare, more recent studies indicate that prevalence could be as high as 1%.
Treatment of Tourette’s Syndrome focuses mainly on symptom management and can involve the use of drugs (α2-adrenergic agonists or dopamine antagonists) and behavioural therapy. However, these therapies are not always effective with some patients continuing to experience tics. Therefore, the development of effective alternative therapies is needed.
Medical Cannabis and Tourette’s Syndrome
Some compounds derived from the cannabis plant – namely the cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD) – have been suggested as an area to explore within Tourette’s Syndrome research. These cannabinoids are known to modulate the endocannabinoid system (ECS) – a receptor system that plays a role in a number of cognitive and physiological processes.
Of particular interest in this setting is the cannabinoid CB1 receptor (CB1R) which is densely concentrated in the basal ganglia, believed to be the pathobiological nexus of Tourette’s Syndrome. Stimulation of the CB1R has been found to provide retrograde inhibition of excitatory synaptic activity. Furthermore, uncontrolled observational studies have highlighted an association between cannabis use and change in tic severity. These include a number of placebo-controlled studies that assessed the effects of various THC formulations and a single case study of nabiximols.
However, no placebo-controlled clinical trials have been conducted to explore the potential of CBD and THC, in combination, for Tourette’s Syndrome. Therefore, in a recent study, published in June 2023, researchers initiated a 16-week randomised, double-blind, placebo-controlled crossover trial to examine the effects of a commercially available oral solution containing THC and CBD in a 1:1 ratio on tic severity in patients with Tourette’s Syndrome.
Methods of the Study
The study was conducted at the Wesley Medical Research Institute (WMR) in Brisbane, Australia. It comprised two 6-week treatment periods (4 weeks of dose escalation followed by 2 weeks of stable dosing) separated by a 4-week washout period.
Participants between the ages of 18 and 70 were recruited from across Australia through the Tourette Syndrome Association of Australia. Each participant had a confirmed diagnosis of Tourette’s Syndrome made by a neurologist or psychiatrist, with at least a moderate-to-severe burden of tics with a total tic score of ≥20 of 50 on the Yale Global Tic Severity Scale (YGTSS).
The use of antidepressant and benzodiazepine medications was continued during the study if prescribed for depression and/or anxiety but participants taking other tic-suppressing medication (e.g., tetrabenazine, antipsychotic agents, clonidine), as well as those using cannabis-based products outside of the trial, were excluded.
The active cannabis preparation (an oral formulation containing 5 mg/ml of THC and 5 mg/ml of CBD) or placebo was administered in doses starting at 1 ml per day and increased by 1 ml every day up to a maximum of 4 ml daily. The primary outcome was the total tic score as measured on the YGTSS, a clinician-led rating of number, frequency, intensity, complexity, and interference from motor and vocal tics. Secondary outcomes included YGTSS global score, a video-based assessment of tic severity, depressive symptoms, anxiety symptoms, and obsessive-compulsive symptoms.
Results of the Study
A total of 22 (including 8 female) participants were randomly assigned to either medical cannabis and placebo. As a cohort, participants had a severe burden of tics, moderate levels of obsessive-compulsive disorder and anxiety, and mild levels of depression. Only six participants had not previously used cannabis. While all participants completed the first period of treatment, three withdrew (two receiving placebo, one receiving active drug) before the second period of treatment.
The oral 1:1 THC:CBD formulation titrated upward over a 6-week period to a maximum daily dose of 20mg THC and 20mg CBD was associated with a significant change in tic severity as measured by the total tic scores on the YGTSS.
Tic reduction was also observed in both interviewer-led and video-based assessments of tic severity conducted by independent raters, who were also blinded to treatment allocation and other outcome ratings. Active treatment with CBD and THC was also associated with a significant reduction in obsessive-compulsive symptoms and anxiety, but not depressive symptoms.
No serious adverse events were reported throughout the study; however, mild to moderate events were reported in both the placebo period and the active treatment period. In the placebo period, the most common adverse effect was headache (n = 7). In the active treatment period, it was cognitive difficulties, including slowed mentation, memory lapses, and poor concentration (n=8) and one participant reported auditory hallucinations on 1 day.
The results of this study add to a growing body of evidence in suggesting that combined CBD and THC affect tics associated with Tourette’s Syndrome.
The researchers also note that the adverse events (including sedation and increased appetite) observed in this study are similar in nature to those commonly reported with antipsychotic agents. They conclude that “larger and longer trials taking the adverse-effect profile of these agents into consideration are warranted.” Furthermore, a study such as this requires follow up with larger sample sizes as well to distinguish the exact effect of medical cannabis.