Tourette Syndrome

Medical cannabis shows efficacy for MS spasticity (oral cannabis extract), probable efficacy for pain, but probable ineffectiveness for tremor and unclear evidence for epilepsy and other neurological diseases.

AAN guideline (Guideline Development Subcommittee) — systematic review of k=34 studies (of which 8 Class I) on medical cannabis in neurological diseases. For Tourette syndrome: oral cannabinoids of unknown efficacy (insufficient evidence). Risk of serious psychopathological adverse effects ~1%. [RETIRED status]

Several treatments (behavioral intervention, antipsychotics, botulinum toxin, deep brain stimulation) showed high to moderate evidence for tic reduction, but with documented side effects.

American Academy of Neurology guideline based on a systematic review on tic treatment in Tourette syndrome. High confidence for Comprehensive Behavioral Intervention for Tics vs. psychoeducation. Moderate confidence for haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA, 5-ling granule, Ningdong granule and deep brain stimulation of the globus pallidus for tic reduction vs. placebo. Low confidence (possibly effective) for pimozide, ziprasidone, metoclopramide, guanfacine, topiramate and tetrahydrocannabinol. Evidence for various side effects (weight gain, drug-induced movement disorders, increased prolactin levels, sedation, cardiovascular effects).

Cannabinoids show hardly any evidence for improving depression, anxiety disorders, ADHD, Tourette syndrome, PTSD or psychosis; only very weak evidence for small improvement of anxiety symptoms in other conditions, but increased side effects.

Systematic review of cannabinoids (THC/CBD) in mental disorders; for Tourette syndrome: almost no evidence for therapeutic benefit. Negative finding also for depression, anxiety, PTSD, ADHD, psychosis.

Strong evidence for chemotherapy-induced nausea/vomiting and increasing evidence for epilepsy; insufficient evidence for spasticity, neuropathic pain, PTSD and Tourette syndrome.

Systematic review on medical cannabis in children/adolescents; k=22 studies (n=795), 5 RCTs, 5 retrospective studies, 5 case reports, 4 open-label, 2 parent surveys, 1 case series. For Tourette syndrome: insufficient evidence for efficacy. Strongest evidence for chemotherapy-induced nausea, increasing for epilepsy.

Cannabinoid-based medicine showed significant reduction in tic severity (YGTSS) and premonitory urges (PUTS), but no significant effect on obsessive-compulsive symptoms (Y-BOCS).

Systematic review and meta-analysis on cannabis-based medications in Tourette syndrome; k=9 studies (3 in meta-analysis), n=401 adult patients. Significant reduction in YGTSS total score (MD=-23.71, 95% CI [-43.86 to -3.55], p=0.02), PUTS score (MD=-5.36, 95% CI [-8.46 to -2.27], p=0.0007). Search up to February 2024 in PubMed/Cochrane/Scopus/Web of Science.

CBMs significantly reduced tic severity and premonitory urge in Tourette syndrome compared to baseline values.

Systematic review and meta-analysis across k=8 studies (7 in the meta-analysis, n=306 adult Tourette patients) on cannabis-based medicines in Tourette syndrome. Significant reduction in tic severity (YGTSS, MD −13,29; 95% CI −21,67 to −4,91; p=0,002) as well as premonitory urge (PUTS, MD −4,09; 95% CI −7,24 to −0,93; p=0,01). Conclusion: promising evidence for tic reduction; larger placebo-controlled studies needed to confirm efficacy and safety.

Systematic review on pharmacotherapy of tic disorders with recommendations for various medications based on evidence and side effect profiles.

Canadian guideline on evidence-based pharmacological treatment of tic disorders based on a systematic review and multi-institution consensus (14 experts). Strong recommendation for clonidine and guanfacine (children only). Weak recommendation for pimozide, haloperidol, fluphenazine, metoclopramide (children only), risperidone, aripiprazole, olanzapine, quetiapine, ziprasidone, topiramate, baclofen (children only), botulinum toxin injections, tetrabenazine and cannabinoids (adults only). High rates of side effects with antipsychotics justify only weak recommendations despite evidence of efficacy.

Positive signals for several indications, but no confirmed evidence of efficacy due to methodologically weak studies.

Systematic review of k=24 RCTs on cannabis/cannabinoids in psychiatric, neurodegenerative and movement disorders; positive RCT findings identified for Tourette syndrome; methodological limitations (insufficient description of blinding, small sample sizes) prevent definitive statements on efficacy.

Limited evidence for acute efficacy on individual psychiatric symptoms, no evidence for medium-term to long-term efficacy of cannabinoid products in psychiatric disorders in adulthood.

Systematic review of k=31 RCTs on cannabinoid products in psychiatric disorders (databases up to September 2020). For Tourette disorder: 2 RCTs identified. The review finds limited evidence for acute symptom improvement in a narrow spectrum of psychiatric symptoms; no evidence for medium- to long-term efficacy. Quality of evidence overall low to moderate.

Some studies suggest potential efficacy, but the findings are too inconsistent between the RCTs to reliably guide clinical application.

Systematic review on CBD efficacy in neurodevelopmental disorders; k=9 RCTs included (ADHD, autism, intellectual disability, Tourette syndrome, complex movement disorders). Some trials show potential efficacy, but evidence too inconsistent for clinical recommendations; study characteristics, treatment properties and outcomes varied greatly.

Cannabinoids show mixed results in RCTs on movement disorders: improvements in quality of life, anxiety and tics in some studies, but no consistent improvements in motor symptoms in Parkinson's or dystonia.

Systematic review of RCTs on cannabinoids in movement disorders; k=2 RCTs on Tourette syndrome showed improvement in tics. Abstract does not report numerical effect sizes for the Tourette subgroup; general conclusion: small, inhomogeneous RCTs do not allow reliable statements.

Pure CBD shows a moderate effect (SMD -0,61), delta9-THC shows a moderate significant effect (SMD -0,65), CBD/delta9-THC mixtures show no significant effect; overall limited and low evidence quality.

SR + meta-analysis of k=21 placebo-controlled RCTs on cannabinoids in anxiety disorders and related disorders; k=7 RCTs on Tourette syndrome included. For pure/enriched CBD preparations: non-significant overall effect size (SMD=-0,40; 95% CI -0,84/0,03); subgroup analysis of pure CBD compounds only: moderate, significant effect size (SMD=-0,61; 95% CI -1,15/-0,07). For Δ9-THC-dominant preparations: moderate, significant effect size (SMD=-0,65; 95% CI -1,06/-0,24). Abstract ends abruptly ("In meta-"); pooled participant number not reported.

It is unclear whether cannabinoids reduce tics in Tourette syndrome; they are probably associated with common side effects.

Epistemonikos SR of k=2 RCTs on cannabinoids in Tourette syndrome; GRADE evidence synthesis states: unclear whether cannabinoids reduce tics; common adverse effects likely. No numerical effect sizes reported in the abstract.

Δ9-THC produced only slight, inconsistent improvements in tic frequency and severity compared with placebo; the evidence is insufficient for any recommendation.

Cochrane SR of k=2 RCTs (n=28) on delta-9-THC vs. placebo in Gilles de la Tourette syndrome. Both studies reported positive effects of delta9-THC on tic frequency and severity; improvements were slight and significant only in some of the outcome measures. Conclusion: insufficient evidence for routine recommendation.

Limited and generally poor quality of evidence for the efficacy of cannabinoid-based products in neuropsychiatric and neurodevelopmental disorders in children and adolescents.

Systematic review on cannabinoids in neuropsychiatric and neurodevelopmental disorders in children/adolescents (≤18 years); k=18 included articles on 8 disorder categories, of which n=3 on Tourette syndrome. Only 1 RCT identified; the rest: 1 open-label study, 3 uncontrolled before-after studies, 2 case series, 11 case reports — high risk of bias. Conclusion: limited and generally poor quality of evidence for cannabinoid efficacy.

Overview of 21 ongoing clinical trials on novel therapeutic approaches for Tourette syndrome and tic disorders; effectiveness of individual interventions is not reported.

Systematic review of current clinical trials in Tourette syndrome and tic disorders; k=21 registered studies identified (WHO and NIH registries). Pharmacological candidates include the dopamine D1 antagonist ecopipam, the phosphodiesterase inhibitor gemlapodect, and cannabis-based therapies. Further approaches: CBIT, neurostimulation (TMS, DBS), traditional Chinese medicine, microbiota transplantation. Overall limited research landscape.

Nabiximols showed numerically higher responder rates than placebo (21,9% vs. 9,1%), but did not formally achieve superiority in the primary endpoint; secondary analyses indicated substantial improvements in tics, depression and quality of life.

Multicentre phase IIIb RCT of nabiximols vs. placebo in adults with Tourette/chronic tic disorders (n=97, 2:1 randomisation). Primary endpoint (≥25% tic reduction after 13 weeks) formally not met, but responder rate nabiximols 21,9% vs. placebo 9,1%. Secondary analyses showed substantial trends for improvement in tics, depression and quality of life; exploratory subgroup analyses suggest benefit for men, more severe tics and comorbid ADHD. No relevant safety concerns.

THC/CBD reduced tic scores significantly more than placebo (8,9 vs. 2,5 point reduction on the YGTSS), with a significant interaction between treatment and visit number (P=0.008).

Double-blind crossover RCT (n=22, 8 female) of THC+CBD (5mg/mL each, oral) vs. placebo in severe Tourette syndrome. Two 6-week phases with 4-week washout. Reduction in YGTSS total score (0-50) week 6 vs. baseline: -8.9 (±7.6) active vs. -2.5 (±8.5) placebo; significant treatment×visit interaction (coefficient=-2.28, 95% CI [-3.96 to -0.60], p=0.008). Correlation between plasma 11-carboxy-THC and primary outcome. Most common adverse event active: cognitive difficulties (n=8); placebo: headache (n=7).

THC showed significant or trend-significant improvements in tics on several rating scales (TS-CGI, STSSS, YGTSS, video rating) compared with placebo with good safety.

RCT (n=24, double-blind, placebo-controlled, 6 weeks): THC up to 10 mg/day significantly reduced tics in Tourette syndrome versus placebo (TS-CGI, YGTSS, STSSS, video rating: p<0,05; ANOVA p=0,037). No serious adverse events. First controlled long-term study with THC in TS.

Delta-9-THC had no negative influence on neuropsychological performance in Tourette patients.

n=24 Tourette patients, delta-9-THC up to 10 mg over 6 weeks vs. placebo; no negative influence on learning curve, interference, recall, visual memory, or divided attention; trend toward significant improvement in immediate verbal memory under THC (p-value in trend); THC shows neither acute nor long-term cognitive deficits in TS patients.

Tic symptoms improved significantly under THX-110 treatment with an average improvement of over 20% (7-point decrease on the YGTSS scale).

12-week uncontrolled pilot study of THX-110 (Δ9-THC max. 10 mg/day + palmitoylethanolamide 800 mg) in adults with Tourette (n=16). Yale Global Tic Severity Scale (YGTSS) improved significantly within 1 week; average tic reduction >20% (7-point decrease YGTSS). 12/16 participants chose the 24-week extension. Side effects common, manageable through dose adjustment.

Significant improvement of tics and compulsive behavior under delta(9)-THC compared to placebo, with significant correlation between tic improvement and 11-OH-THC plasma concentration.

Randomized, double-blind, placebo-controlled crossover study with single dose of delta-9-THC (5,0–10,0 mg) in n=12 adult Tourette patients. Significant improvement in tics (TSSL, p=0,015) and compulsive behavior (p=0,041) compared to placebo. Investigator rating: significant improvement of complex motor tics (p=0,015). No serious adverse events; 5 patients reported mild, transient side effects. Pilot character (n<20, single dose); long-term data pending.

Three participants showed marked improvement on the CGI-Improvement scale under medicinal cannabis versus one participant under placebo; no significant difference, feasibility study with small sample size.

Double-blind crossover pilot study (n=10 adolescents, 12-18 years) on medical cannabis (THC 10mg/mL + CBD 15mg/mL) vs. placebo in Tourette syndrome. Two 10-week phases with 4-week washout. 7/10 completed protocol; 100% adherence at visits/blood tests, 97.6% for questionnaires. CGI-Improvement: 3 participants 'much improved' under cannabis vs. 1 under placebo after 10 weeks. Most common side effect: dizziness (67%). No serious adverse events.

No significant effect on the primary outcome (MRVTRS), but THC 10% significantly better than placebo on secondary outcomes (PUTS, SUDS, CGI-I); more side effects under all cannabis products.

Pilot RCT (n=9 completers of 12 randomised) on vaporised cannabis in adults with Tourette syndrome, crossover design with THC 10%, THC/CBD 9%/9%, CBD 13% vs. placebo (single dose 0.25g). No significant effect on primary endpoint (Modified Rush Video-Based Tic Rating Scale, MRVTRS). THC 10% significantly superior vs. placebo on secondary outcomes: Premonitory Urge for Tics Scale (PUTS), Subjective Units of Distress Scale (SUDS), Clinical Global Impression-Improvement (CGI-I); significant correlation between THC plasma levels and MRVTRS/PUTS/SUDS. More side effects (particularly cognitive/psychomotor effects) under THC 10%.

Medical cannabis significantly reduces tic severity and premonitory urge sensations in GTS patients.

n=18 adult GTS patients, open-label study over 12 weeks of medical cannabis (THC/CBD titration, mostly smoking 80%). YGTSS-Total (0-100) decreased by an average of 38% (p=0.002); Premonitory Urge for Tic Scale (PUTS) by 20% (p=0.043). Common side effects: dry mouth (66,7%), fatigue (53,3%), dizziness (46,7%); 40% cognitive side effects.

Improvement in quality of life, employment status and reduction of medications; no significant improvements in motor and vocal tics.

Real-world registry with n=70 Tourette patients under medical cannabis (mean daily dose THC 123 mg, CBD 50,5 mg) over 6 months; significant improvement in quality of life (p<0,005) and employment status (p=0,027), 67% of OCD patients and 89% of anxiety patients reported improvement. No significant reduction of motor tics (p=0,375) or vocal tics (p>0,999). Most common side effects: dizziness (n=4), increased appetite (n=3).

CBM led to subjective tic reduction and improved quality of life in the majority of GTS patients, with a preference for THC-rich medicinal cannabis.

n=98 GTS patients (retrospective) + online survey n=40; subjective tic improvement ~60% in 85% of those treated; improvement of comorbidities (OCB/OCD, ADHD, sleep disorders) in 55%; quality of life improvement in 93%. Adverse events in 50% classified as tolerable. Patients prefer THC-rich cannabis (entourage effect).

82% of cannabis users with Tourette syndrome reported reduction or remission of tics and associated symptoms.

n=64 Tourette patients surveyed; 17 (27%) reported cannabis use; 14 of 17 (82%) experienced reduction or complete remission of motor and vocal tics as well as improvement of premonitory urges and compulsive symptoms. No control group; hypothesis: cannabinoid system played a key role in TS pathology.

Cannabis reduced tic scores by 60% and led to marked clinical improvement in nearly all participants.

n=19 adults with Tourette syndrome; retrospective assessment of cannabis; tic scores reduced by 60%; 18 of 19 participants rated as at least "markedly improved". Cannabis generally well tolerated; most participants reported side effects.

Cannabis-based medications led to significant improvement of vocal blocking tics and comorbid conditions in both patients.

Two young patients with treatment-refractory Tourette syndrome and severe vocal blocking tics; Case 1 (19 years): cannabis 0,1 g/day; Case 2 (16 years): dronabinol up to 33,6 mg/day. Both showed significant improvement of vocal blocking tics and comorbidities with good tolerability.

Subjective and objective measurements showed marked improvement in frequency and severity of motor and vocal tics following treatment with Sativex.

Single case report: treatment-resistant Tourette syndrome, therapy with Sativex® (10.8 mg THC + 10 mg CBD daily, 2× oro-mucosal sprays). Assessment pre-treatment and at week 1/2/4. Subjective (Yale Global Tic Severity Scale) and objective measurement (Original Rush Videotape Rating Scale, blinded raters) showed marked improvement in frequency and severity of motor/vocal tics. Good inter-rater reliability.

The patient showed a rapid and highly significant improvement on the Yale Global Tic Severity Scale after administration of 10 mg delta-9-THC combined with 20 mg CBD.

Case report of a patient with treatment-refractory Tourette syndrome; monotherapy with THC 10 mg/day ineffective, combination of THC 10 mg + CBD 20 mg/day led to rapid and highly significant improvement on the Yale Global Tic Severity Scale.