Preliminary Evidence on Cannabis Effectiveness and Tolerability for Adults With Tourette Syndrome

We identified 22 patients who had been using cannabis for TS in our Tourette Syndrome Neurodevelopmental Clinic at the Toronto Western Hospital (Toronto, Ontario, Canada). Our inclusion criteria were diagnosis of TS according to DSM-5 criteria and using cannabis regularly for 6 months or longer. Exclusion criteria were significant cognitive delay, current polysubstance abuse, or current alcohol abuse. Of the 22 patients we identified, one was excluded because the patient had been using cannabis for less than 6 months. Twenty-one patients met our inclusion criteria and were invited to take part in the study. Of these, 19 were willing to participate (a response rate of 90%) and were recruited into the study after signing informed consent forms. The study was approved by the institutional research ethics board.

Clinical charts for all participants were reviewed for demographic, medical and medication history, psychiatric history, and symptomatology of tics and comorbidities. All 19 participants were invited to the clinic for semistructured interviews, which were carried out by two clinic psychiatrists who have extensive experience with TS (EA-J and PS). The following standardized questionnaires (current and prior to cannabis use) were administered: the Yale Global Tic Severity Scale (YGTSS)¹⁴; PUTS [Premonitory Urges for Tics Scale]¹⁵; Y-BOCS [Yale-Brown Obsessive Compulsive Scale]¹⁶; the Adult ADHD Self-Report Scale, version 1.1¹⁷ (ASRS); the Structured Clinical Interview for DSM-IV Axis I Disorders, with psychotic screen, Patient Edition¹⁸ (SCID-I/P); and the short version of the Marijuana Effect Expectancy Questionnaire (MEEQ),¹⁹ a structured list of specific effects previously reported with the use of cannabis or THC. Assessment for adverse effects associated with cannabis was based on open-ended questions, as well as the SCID-I/P psychosis interview and the MEEQ. Finally, clinicians completed the Clinical Global Impressions Improvement (CGI-I) and Clinical Global Impressions Severity (CGI-S) scales.

YGTSS questionnaires were completed by the study psychiatrists retrospectively to assess tic severity prior to treatment with cannabis and for current symptom severity during cannabis treatment. The retrospective YGTSS questionnaires were based on clinical information in the patient’s chart supplemented by patient recollection. The primary efficacy endpoints were the mean change from baseline in YGTSS-total tic score (YGTSS-TTS) and the percentage of patients rated as “much improved” or “very much improved” on the CGI-I. Tolerability endpoints included spontaneous and structured adverse effects reporting via the MEEQ and the SCID-I/P psychosis interview. In addition, the percentage of patients experiencing side effects leading to discontinuation of treatment was noted.

Data analysis was conducted with SPSS 22 (IBM SPSS Statistics for Windows, Version 22.0. Armonk, N.Y., IBM Corp.). Continuous variables were compared with paired sample two-tailed t tests, and categorical variables were compared using chi-square tests. A threshold value of p<0.05 was used for statistical significance.

We conducted a retrospective study of cannabis effectiveness and tolerability in adult patients with TS by interviewing eligible patients in our clinic. Of the 21 patients who were contacted, 19 participated in the study, for a response rate of 90%. These patients had moderate to severe symptoms overall, based on the baseline severity scores of their tic and comorbid symptoms, their baseline CGI-S ratings, and their complex medication histories (Table 1). Based on our two primary outcome measures, the patients appear to have had striking improvements in symptoms, with an average 60% reduction in YGTSS-TTS scores (from 30.5±7.2 to 12.2±8.6, p<0.001) (Table 3, Figure 1) and 18 of the 19 participants (94.7%) being rated as “very much improved” or “much improved” on the CGI-I (Table 3). In addition, there were substantial improvements in comorbid symptomatology (Tables 2 and 3).

It appears that medical cannabis has been generally well tolerated by this group of patients, all of whom had been using cannabis for at least 2 years. The MEEQ did not suggest ongoing adverse effects overall, and the SCID-I/P was negative for psychotic disorders. Nevertheless, on open-ended questioning, most patients did report one or more adverse effect, including feeling “high,” cognitive effects, and anxiety. One patient had to temporarily discontinue treatment due to difficulties with irritability.

Overall, these study participants experienced substantial improvements in their symptoms. This is particularly striking given that almost all participants had failed at least one anti-tic medication trial. Our findings are consistent with those of Müller-Vahl and colleagues, who found that most patients in their case series had reported at least a moderate improvement in tic symptoms.⁷ It is noteworthy that the improvements reported in that study, as well as those described in ours, are much larger than what was seen in the trials with oral THC.^8,9 This may be due to the uncontrolled nature of the observational studies. Nevertheless, it is interesting that our patients appear to have had much greater improvement in their symptoms using inhaled cannabis compared with pure oral THC, THC/CBD oromucosal spray, or the oral cannabinoid nabilone. Thus, one might wonder whether inhaled medical cannabis is more effective for tics, possibly as a result of the impact of one or more of the various different compounds that it contains in addition to THC and CBD, and perhaps enhanced by a route that avoids first-pass hepatic metabolism. It is also worth considering the issue of dosing. There is little information on comparing oral and inhaled doses of cannabinoids, and the limited information available is specific to THC. If one accepts various assumptions, a conversion factor of 2.5 can be used to estimate an oral THC equivalent of a certain quantity of inhaled cannabis.^20,21 If we further assume that the average percentage of THC in the cannabis used by our participants to be 10%, their median total daily amount of 1 g of cannabis would entail 100 mg of THC. Multiplying 100 mg by the conversion factor of 2.5 would yield 250 mg equivalent of oral THC. This would be much higher than the up to 10 mg used in the previous trials with oral THC.

Nevertheless, it is important to highlight the limitations of our retrospective observational study. There is likely a selection bias, as patients who would have tried cannabis and found it to be ineffective or intolerable would be unlikely to remain on it for long or may not be receptive to it as a treatment option. Such patients would not have been eligible for our study. On the other hand, according to the case series of consecutively interviewed patients by Müller-Vahl and colleagues, 82% of patients who had tried cannabis had experienced improvement in symptoms.⁷ Another limitation to our study is the potential for recall bias given the retrospective nature of the baseline assessments. These assessments included reviewing the patient charts for supporting clinical notes, including objective clinical examinations at various clinical visits. Still, this cannot completely eliminate the effect of recall bias in the assessments for the present study. An additional limitation of an observational study is the lack of a control. Therefore, it is possible that some of the improvement, perhaps in our younger adult patients, is related to the natural history of tics, which typically improves by early adulthood for most patients. However, this is unlikely to account for the improvements seen in older patients, most of whom had tried multiple other treatments with limited benefit. Still, there could be a regression to the mean effect, especially given the known waxing and waning nature of tics. In addition, there could be an enhanced placebo effect at play with inhaled cannabis, especially given the sociocultural issues surrounding the use of medical cannabis, the administrative process to obtain it, and the ritualized procedure to utilize it. It is noteworthy, however, that eight of our patients had discovered the use of cannabis for tics only serendipitously when they personally experienced notable reduction in their tics after using cannabis recreationally. Nevertheless, to adequately address this issue and other limitations raised here, one would need to conduct a randomized trial that is properly controlled and blinded for inhaled cannabis.

In conclusion, cannabis seems to be a promising treatment option for tics and associated symptoms. However, despite the substantial improvements reported here, some patients continued to take other medications in addition to cannabis. Moreover, while cannabis appears to be generally well tolerated, side effects were common. Importantly, the strength of our conclusions is limited by the retrospective nature of our study. Therefore, to better characterize the benefits and risks of medical cannabis in TS, including the roles of various cannabinoid compounds, there is a need for well-designed prospective, well-controlled studies.

The authors thank all the patients who participated in this study.