Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by the presence of multiple motor and at least one vocal tic with a minimal duration of one year (1). On average, tics start at the age of five to seven years with peak severity occurring between the age of 10 to 12 years (2, 3). According to the American Academy of Neurology (AAN) (4) and the European Society for the Study of Tourette Syndrome (ESSTS) (5) the first-line therapy for tics include behavioral therapy and/or pharmacotherapy with antipsychotics or alpha-agonists. In otherwise treatment-refractory cases, only limited alternative treatment options are available including cannabis-based medicine (CBM) (5).

While there is an increasing evidence that CBM reduces tics in adults with TS (6–15), evidence in children and adolescents is very limited (16–19). Only recently, the first large randomized controlled trial (N = 97) investigating efficacy and safety of the cannabis extract nabiximols in adult patients with TS provided evidence for its effectiveness in this population, although the primary endpoint was narrowly missed (15). Interestingly, additional exploratory subgroup analyses revealed a larger improvement of tics in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder (ADHD) suggesting that these subgroups may benefit better from CBM treatment. There were no relevant safety issues.

In contrast, in children and adolescents with TS, so far only five case reports are available including a total of six patients as well as preliminary data from a small phase I/II double-blind, cross-over pilot study including ten patients, all describing acute effects of CBM and one study using real world data from teenagers and adults. The first case study was published as early as 1988 and reported two adolescents aged 15 and 17, who self-medicated with inhaled cannabis and experienced an improvement of tics of about 50% and comorbid symptoms including obsessive-compulsive disorder (OCD), self-injurious behavior (SIB), and attention problems (20). Twenty-two years later, in 2010, the first case of a treatment-resistant 15-year-old adolescent with TS and co-existing ADHD was published, whose symptoms significantly improved after treatment with pure tetrahydrocannabinol (THC, maximum dose = 15 mg THC/day) (16). Over a period of nine weeks, an improvement of tics and quality of life was clinically observed and measured before and after therapy with THC using standardized interviews, questionnaires and a video protocol (16).

More recently, our group reported three minors who benefitted significantly from treatment with different CBMs without any severe adverse effects (17–19). Jakubovski et al. (19) described a 16-year old adolescent with TS who struggled with a variety of speech problems such as palilalia, vocal blocking as well as change of melody and rhythm of speech. Since conventional therapy was not effective, treatment with oral THC (maximum dose = 33.6 mg THC/daily, later switched to vaporized THC-dominant medicinal cannabis flowers with a daily dose of 1.8 g) was started. At follow-up of up to eight months a marked reduction of motor and vocal tics including an improvement of speech fluency was reported by the patient. He further described an improvement of psychiatric symptoms such as impulsive behaviors, rage attacks, anxiety, and OCD and, in addition, reported no side effects due to the medication.

In 2025, results have been published from a double-blind, controlled pilot study in ten adolescents (mean age 14.8 years, range, 12–18 years, 50% male) performed in Australia (21). The primary aim was to investigate, whether the study protocol is feasible and acceptable using a CBM containing THC 10 mg/mL (depending on weight: max THC 10 mg/day, if < 50 kg or max THC 20 mg/day, > 50 kg) and cannabidiol (CBD) 15 mg/mL over 10 weeks. Overall, CBM was well tolerated, 7/10 participants completed the study, 2/10 discontinued due to adverse events (one on CBM, one placebo). The most common adverse event was dizziness (67%).

In a real-setting study from Israel published in 2024, a mixed sample of patients was evaluated regarding beneficial effects of CBM (oily solution or cannabis flowers) (22). They also report a significant improvement in quality of life, employment status, reduction in the number of other medications as well as improvements in OCD and anxiety. However, follow-up lasted only 6 months. Since only 7 out of 70 patients were minors and these results were not reported separately, clinical effects specifically in this subgroup remain unclear.

Alongside the limited amount of data regarding the use of CBM in children, there are also some reports in other neuropsychiatric disorders in pediatric populations, mainly in autism spectrum disorder (ASD) where CBD can improve behavioral problems, anxiety, and sleep (23–26). According to a recently published systematic review of the very limited number of RCTs in minors, a modest positive effect of CBM in ASD has been found (26).

Here, we report tic severity and commonly associated comorbidities such as ADHD, OCD, and depression as well as overall performance at long-term follow-up of two cases published recently by our group (17, 18). Both cases are still the only available reports describing acute effects of CBM in children with TS.

While this limited number of case studies suggests that CBM may be useful for the acute management of tics – and possibly also psychiatric comorbidities - in minors with TS, we do not have any information about efficacy and, in particular, safety of this treatment as continuous medication. This is of great relevance since there are general concerns regarding repercussions of CBM treatment in children (27). The main considerations are related to the risk of psychiatric side effects and a negative impact on academic performance as well as cognitive functioning (28–31). In this study, we therefore also conducted assessments of cognitive domains such as processing and working speed. Furthermore, we analyzed school reports to assess academic functioning. All tests were either self-administered or administered by clinician and researchers with experience in tics. For both cases, patients and parents provided written informed consent for publication of the cases (please refer to the Statement of Ethics section). For treatments as part of an individual therapeutic trial, no ethical approval is required in Germany.

We present, for the first time, long-term follow-up outcomes of CBM treatment at five and six years, respectively, in two children with TS. In these two patients, long-term treatment with different THC-containing cannabinoids resulted not only in a constant improvement of tics, psychiatric comorbidities, and quality of life, but also did not cause severe adverse effects and in particular no psychological symptoms such as anxiety, psychosis, and substance abuse including CUD. Most importantly, neurocognitive test results during the course of therapy showed no evidence that the patients cognitive abilities had become below average. There was also no indication of behavioral abnormalities, social problems, neglection of social interests, or loss of interests, motivation, and drive. This is remarkable, since in both patients CBM treatment was initiated before puberty and doses of THC were relatively high.

Because of overall beneficial effects, parents and patients decided for continued treatment with CBM over many years. Based on self-assessments, in both children premonitory urges initially decreased after start of CBM treatment but increased at long-term follow-up. However, this can presumably be attributed to patients’ age, since children with TS often are unaware of premonitory urges and awareness increases with age (42).

There is evidence that cannabis use depending on dose, frequency, and age of onset can have negative effects on episodic and working memory, processing speed, executive functioning and may disrupt developmental processes leading to a poorer cognitive outcome (31, 43–45). In our study, overall, there was no evident impact of CBM on cognitive functioning However, working memory assessed with the WISC was slightly below average (34% for both cases). Since we did not apply the aforementioned psychological tests before the start of therapy, we cannot conclude whether CBM treatment actually affected patients’ working memory. However, neither patients nor parents noticed any changes in general memory performance and school performance. With respect to detrimental effects of cannabis on memory, it should be noted that all these reports were based on data in children using cannabis recreationally, but not on CBM in different patient groups supervised by physicians. There are several important differences between use of CBM compared to recreational use of cannabis from other sources. Firstly, recreational cannabis often comes from illegal sources and it is not clear what it contains and how it was produced. Accordingly, content of THC and CBD are unknown. It is also known that recreational cannabis usually has a quite high content of THC, while CBM, even if containing a higher percentage of THC, is usually more balanced with CBD and other substances to prevent side effects (so called “entourage effect”) (46, 47). On the contrary, CBM is produced in a controlled environment and its major ingredients, similarly to other medical products, are exactly determined and known. Secondly, recreational cannabis is usually smoked, which makes it more difficult to control. On the contrary, CBM is either vaporized or administered orally as oils, capsules, and mouth sprays. These differences in the form of administration are crucial for pharmacokinetics and pharmacodynamics and, as a result, efficacy and the profile of side effects. Thirdly, recreational cannabis is taken without any medical supervision which often leads to overuse, misuse, and even addiction (48–50), while, administration of CBM is per definition initiated and supervised by a treating physician, which is known to increase compliance and prevent overuse (51). Also, the treating physician can adjust the dose according to clinical efficacy and the profile of side effects (52). Furthermore, psychological factors, such as doctor-patient relationship may play a role in patients’ compliance. Fourthly, treating physicians screen for a history of psychiatric disorders - including family history - before starting treatment with CBM, since history of psychosis increases the risk of psychiatric side effects (53, 54). Finally, it has been suggested that TS may be caused by a deficiency or dysfunction in the endocannabinoid system (9), which might result in an altered side effect profile in this specific group of patients.

In both cases, at no time there was an uncontrolled or unwanted increase of CBM, inability to reduce the dose if wanted, any other symptoms suggesting the incidence of CUD, additional use of cannabis from other sources, or use of other drugs. This aspect is of particular interest in Case 1, since he suffers from comorbid ADHD, in which substance use disorder including CUD is a well-known and common comorbid condition (55). Based on the data presented there is no evidence that long-term THC exposure had a negative impact on brain development and cognitive function, since one boy’s school performance remained unchanged over years and the other one’s even improved. It should also be taken into account that other factors may have influenced patients’ academic performance such as the COVID-19 pandemic, which occurred during the period of assessment, as well as pubertal development.

Although findings are encouraging, a number of limitations should be acknowledged. Firstly, although according to YGTSS-TTS tic severity significantly improved after CBM treatment, it cannot be excluded that tic improvement is, at least in part, due to the typical waxing and waning course of tics. In addition, since on average tic maximum occurs at the age of 10-12, it is possible that tic improvement may be caused by a spontaneous tic improvement with increasing age. Furthermore, placebo effect cannot be excluded. Secondly, it is not possible to decide, whether improvement in patients’ quality of life and global impairment is primarily related to the improvement of tics or alternatively due to an improvement of comorbidities such as depression and ADHD. However, there is evidence that in patients with TS, cannabinoids improve not only tics but also psychiatric comorbidities (10, 15, 56, 57). Because of the sustained long-term effects, in our opinion, it can be excluded that self-reported beneficial effects are caused by THC-induced psychological effects such as euphoria. Thirdly, we measured cognitive performance using WISC only at last follow-up, but not at baseline before initiation of CBM treatment. Accordingly, no conclusion can be drawn on possible changes in patients’ cognitive strengths and weaknesses after treatment of CBM was initiated. Furthermore, we only measured working memory and processing speed, but did not perform a more extensive cognitive testing. Results of the only two domains assessed cannot be extrapolated to the total IQ results, as this was not assessed. Fourthly, in one case, CBM treatment was initiated, modified, and supervised by the patient’s parents who both are medical doctors. This may have an impact on the treatment outcome and the general attitude toward treatment.

In summary, we present two cases of minors with TS who started CBM treatment before puberty at the age of eight and 12 years, respectively, and continued treatment for five to six years resulting in sustained clinically relevant symptom improvement without severe adverse effects or negative impact on cognitive and academic performance. Although generalizability from our case reports of two single patients is limited, we suggest to take treatment with THC-containing drugs into consideration in severely affected and otherwise treatment refractory children and adolescents before thinking of surgical treatment using deep brain stimulation.

From the patient perspective, long-term treatment with CBM resulted in a clinically relevant improvement of tics and psychiatric comorbidities without causing severe adverse effects such as neurocognitive or behavioral problems and thus made it possible to attend school normally, make friends and pursue hobbies without any problems.