Tourette syndrome (TS), named after Gilles de la Tourette in 1885, is a neurodevelopmental and behavioral disorder characterized by motor and phonic tics [1–3]. The American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders defines TS as the presence of chronic motor and phonic tics for at least a year starting before the age of 18 years after excluding possible secondary causes [4]. Most studies estimated the prevalence of TS to be between 0.3 and 0.7% among children and adolescents [5–8]. Nevertheless, experts agree that the condition is usually underdiagnosed with a long duration between the onset of symptoms and diagnosis [9].

The pathophysiology of TS is not entirely understood. However, structural and functional changes in multiple corticostriatal circuits may account for the behavioral manifestations. Involvement of the neurochemical disbalance in the dopaminergic system has also been proposed [10, 11]. TS is a heterogeneous condition in terms of severity of symptoms and comorbidities; fortunately, severe TS is rare. Patients variably become tolerant to tics socially and functionally [9]. Attention deficit hyperactive disorder (ADHD) is the most common comorbidity with TS, co-existing in around 60% of cases and followed by obsessive–compulsive disorder (OCD), and can be disabling more than the tics [10].

Although there is no cure for TS, patients can benefit from controlling tics [12, 13]. Notably, many patients with tics that do not interfere with their lives do not require management. Medications and behavioral management can be provided if tics cause stress, injuries, or interference with daily life [10, 12–14]. Behavioral therapy has demonstrated promising results in reducing the severity of tics and thus can be considered the first-line therapy for TS [10, 12]. On the other hand, patients respond variably to medications. Alpha-2 adrenergic agonists, such as clonidine and guanfacine, are frequently used as a first-line pharmacological approach for suppressing tics associated with TS [15]. Notably, for patients with co-existing attention deficit hyperactivity disorder (ADHD), these medications offer the potential benefit of reducing both tic severity and ADHD symptoms. Treatment options include clonidine alone, a combination of clonidine and methylphenidate (a stimulant medication for ADHD), or guanfacine [3, 10]. Other medications include neuroleptics, topiramate, and anticholinergics [2, 3, 10, 14].

Cannabis sativa has a history of recreational and medicinal use. Its potential therapeutic effects in various conditions have recently gained attention [16]. There are many forms of cannabis-based medicines (CBM), including tetrahydrocannabinol, THX-110 combinations, cannabinoid oils, and synthetic cannabinoids such as palmitoylethanolamide [17]. The human endocannabinoid system (ECS) is a complex signaling system that includes cannabinoid receptors, their endogenous ligands (endocannabinoids), and biosynthetic and hydrolytic enzymes [18]. ECS is crucial in various physiological processes, including cognition, learning, memory, pain perception, gastrointestinal function, and autonomic control [16, 19, 20]. CBM can interact with the ECS by binding to cannabinoid receptors, primarily CB1 and CB2. CB1 receptors are predominantly found in the central nervous system, while CB2 receptors are more abundant in immune cells [16, 19, 21]. This interaction may modulate the ECS's activity and influence various physiological functions. However, the specific mechanisms of CBM are still being investigated [20–30].

Evidence supports the use of medicinal cannabis in conditions such as chronic pain [31, 32], resistant chemotherapy-induced vomiting and nausea [33], and sleep disorders [34, 35]. Their use for controlling tics has recently increased, with many trials and reports showing encouraging results [23–30]. Recent reviews revealed poor-quality evidence and inconclusive results for the efficacy of CBM for neurodevelopmental and movement disorders [20–22].

There is a lack of evidence to recommend to patients for management of TS [14, 36–40]. In this systematic review and meta-analysis, we aimed to provide a comprehensive assessment of the efficacy of CBM in TS by summarizing the totality of evidence to date regarding their efficacy.