Medicinal Use of Different Cannabis Strains: Results from a Large Prospective Survey in Germany.

BACKGROUND: Up to now, it is unclear whether different medicinal cannabis (MC) strains are differently efficacious across different medical conditions. In this study, the effectiveness of different MC strains was compared depending on the disease to be treated. METHODS: This was an online survey conducted in Germany between June 2020 and August 2020. Patients were allowed to participate only if they received a cannabis-based treatment from pharmacies in the form of cannabis flowers prescribed by a physician. RESULTS: The survey was completed by n=1,028 participants. Most participants (58%) have used MC for more than 1 year, on average, 5.9 different strains. Bedrocan (pure tetrahydrocannabinol to pure cannabidiol [THC:CBD]=22:<1) was the most frequently prescribed strain, followed by Bakerstreet (THC:CBD=19:<1) and Pedanios 22/1 (THC:CBD=22:1). The most frequent conditions MC was prescribed for were different pain disorders, psychiatric and neurological diseases, and gastrointestinal symptoms. Overall, the mean patient-reported effectiveness was 80.1% (range, 0-100%). A regression model revealed no association between the patient-reported effectiveness and the variety. Furthermore, no influence of the disease on the choice of the MC strain was detected. On average, 2.1 side effects were reported (most commonly dry mouth (19.5%), increased appetite (17.1%), and tiredness (13.0%)). However, 29% of participants did not report any side effects. Only 398 participants (38.7%) indicated that costs for MC were covered by their health insurance. CONCLUSIONS: Patients self-reported very good efficacy and tolerability of MC. There was no evidence suggesting that specific MC strains are superior depending on the disease to be treated.

Cannabinoids in the Treatment of Selected Mental Illnesses: Practical Approach and Overview of the Literature.

Although an increasing number of patients suffering from mental illnesses self-medicate with cannabis, current knowledge about the efficacy and safety of cannabis-based medicine in psychiatry is still extremely limited. So far, no cannabis-based finished product has been approved for the treatment of a mental illness. There is increasing evidence that cannabinoids may improve symptoms in autism spectrum disorder (ASD), Tourette syndrome (TS), anxiety disorders, and post-traumatic stress disorder (PTSD). According to surveys, patients often use cannabinoids to improve mood, sleep, and symptoms of attention deficit/hyperactivity disorder (ADHD). There is evidence suggesting that tetrahydrocannabinol (THC) and THC-containing cannabis extracts, such as nabiximols, can be used as substitutes in patients with cannabis use disorder.Preliminary evidence also suggests an involvement of the endocannabinoid system (ECS) in the pathophysiology of TS, ADHD, and PTSD. Since the ECS is the most important neuromodulatory system in the brain, it possibly induces beneficial effects of cannabinoids by alterations in other neurotransmitter systems. Finally, the ECS is an important stress management system. Thus, cannabinoids may improve symptoms in patients with mental illnesses by reducing stress.Practically, cannabis-based treatment in patients with psychiatric disorders does not differ from other indications. The starting dose of THC-containing products should be low (1-2.5 mg THC/day), and the dose should be up-titrated slowly (by 1-2.5 mg every 3-5 days). The average daily dose is 10-20 mg THC. In contrast, cannabidiol (CBD) is mainly used in high doses>400 mg/day.

CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders - Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study.

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21·9%) vs. 3/33 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part III: pharmacological treatment.

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements.

Two Decades of the International Association for Cannabinoid Medicines: 20 Years of Supporting Research and Activities Toward the Medicinal Use of Cannabis and Cannabinoids.

Emerged from the German Association for Cannabis as Medicine (ACM), a handful of enthusiastic medical doctors from Germany, Switzerland, and Austria supported by experts from other countries established the International Association for Cannabinoid Medicines (IACM) in March 2000. During the past 20 years until today, it evolved toward the most important scientific society for clinical research in the field of cannabis-based medicines. The overarching aim of the IACM is to advance the knowledge on cannabis, cannabinoids, the endocannabinoid system, and related topics especially with regard to their therapeutic potential, which would allow more patients to profit from a treatment with cannabis-based medicines and ease legislators to adopt their policies. To reach this goal, the IACM organizes international scientific conferences, biweekly publishes the IACM-Bulletin-currently in six different languages-reaching more than 5000 people worldwide, and is working closely together with patient associations, international partner organizations, and IACM ambassadors. In 2019, a collaborative partnership with the journal Cannabis and Cannabinoid Research was established.

Treatment of Gilles de la Tourette Syndrome with Cannabis-Based Medicine: Results from a Retrospective Analysis and Online Survey.

Introduction: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder that is characterized by motor and vocal tics and psychiatric comorbidities, including attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive behavior/disorder (OCB/OCD). From anecdotal reports and preliminary controlled studies, it is suggested that cannabis-based medicine (CBM) may improve tics and comorbidities in adults with GTS. This study was designed to further investigate efficacy and safety of CBM in GTS and specifically compare effects of different CBM. Materials and Methods: First, we performed a retrospective data analysis including all those adult patients seen at our clinic, who had used CBM for the treatment of GTS at some time. All these patients were asked to complete an online survey (second study part) to receive more detailed data about treatment with CBM. Results: From medical records, we identified 98 patients who had used CBM (most often street cannabis followed by nabiximols, dronabinol, medicinal cannabis) for the treatment of GTS: Of the 38 patients who were able to judge, 66% preferred treatment with medicinal cannabis, 18% dronabinol, 11% nabiximols, and 5% street cannabis. Altogether, CBM resulted in a subjective improvement of tics (of about 60% in 85% of treated cases), comorbidities (55% of treated cases, most often OCB/OCD, ADHD, and sleeping disorders), and quality of life (93%). The effects of CBM appear to persist in the long term. Adverse events occurred in half of the patients, but they were rated as tolerable. Dosages of all CBM varied markedly. Patients assessed cannabis (with a preference for tetrahydrocannabinol [THC]-rich strains) as more effective and better tolerated compared with nabiximols and dronabinol. These data were confirmed by results obtained from the online survey (n=40). Conclusion: From our results, it is further supported that CBM might be effective and safe in the treatment of tics and comorbidities at least in a subgroup of adult patients with GTS. In our sample, patients favored THC-rich cannabis over dronabinol and nabiximols, which might be related to the entourage effect of cannabis. However, several limitations of the study have to be taken into considerations such as the open uncontrolled design and the retrospective data analysis.

Obsessive-compulsive disorder is a heterogeneous disorder: evidence from diffusion tensor imaging and magnetization transfer imaging.

BACKGROUND: Current models of obsessive compulsive disorder (OCD) propose abnormalities of cortico-striatal circuits that involve the orbitofrontal cortex, anterior cingulate cortex, thalamus and the striatum. Nevertheless, during the last years, results of morphometric studies were contradictory. Since fully automated whole-brain voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are used to assess structural changes in OCD patients, increased consistent evidence has been reported that brain abnormalities are not limited exclusively to the "affective" orbitofronto-striatal circuit. Moreover, several studies conducted using a symptom dimensional approach demonstrated that different symptoms are mediated by distinct neural systems. METHOD: We investigated structural brain abnormalities in 14 carefully selected adult (≥18 years), male and unmedicated patients with OCD - separately for obsession and compulsion scores (Y-BOCS) - compared to 20 healthy controls as reflected according to white matter changes by fractional anisotropy and apparent diffusion coefficient. Moreover, this is the first study in OCD patients, using magnetization transfer imaging (MTI). This method is said to be more sensitive to subtle structural brain changes than conventional volumetric imaging. RESULTS: In our study, we show a positive correlation between MTR and Y-BOCS obsession scores with an increased integrity of tissue structure in the parietal cortex, including myelination and axonal density reflected by the magnetization transfer ratio (MTR) which was used for the first time in our study. Furthermore, Y-BOCS scores for compulsions correlated negatively with ADC-maps in the left nucleus lentiformis and the cingulum. CONCLUSION: The results support the hypothesis that OCD is a heterogeneous disorder with distinct neural correlates across symptom dimensions and call for a substantial revision of such a model that takes into account the heterogeneity of the disorder.

Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms.

BACKGROUND: Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS "only" (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. RESULTS: Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. CONCLUSIONS: Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.

The medicinal use of cannabis and cannabinoids--an international cross-sectional survey on administration forms.

Cannabinoids, including tetrahydrocannabinol and cannabidiol, are the most important active constituents of the cannabis plant. Over recent years, cannabinoid-based medicines (CBMs) have become increasingly available to patients in many countries, both as pharmaceutical products and as herbal cannabis (marijuana). While there seems to be a demand for multiple cannabinoid-based therapeutic products, specifically for symptomatic amelioration in chronic diseases, therapeutic effects of different CBMs have only been directly compared in a few clinical studies. The survey presented here was performed by the International Association for Cannabinoid Medicines (IACM), and is meant to contribute to the understanding of cannabinoid-based medicine by asking patients who used cannabis or cannabinoids detailed questions about their experiences with different methods of intake. The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoid-based medicine performed so far. In general, herbal non-pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids. However, the number of patients who reported experience with pharmaceutical products was low, limiting conclusions on preferences. Nevertheless, the reported data may be useful for further development of safe and effective medications based on cannabis and single cannabinoids.

Treatment of Tourette syndrome with cannabinoids.

Cannabinoids have been used for hundred of years for medical purposes. To day, the cannabinoid delta-9-tetrahydrocannabinol (THC) and the cannabis extract nabiximols are approved for the treatment of nausea, anorexia and spasticity, respectively. In Tourette syndrome (TS) several anecdotal reports provided evidence that marijuana might be effective not only in the suppression of tics, but also in the treatment of associated behavioural problems. At the present time there are only two controlled trials available investigating the effect of THC in the treatment of TS. Using both self and examiner rating scales, in both studies a significant tic reduction could be observed after treatment with THC compared to placebo, without causing significant adverse effects. Available data about the effect of THC on obsessive-compulsive symptoms are inconsistent. According to a recent Cochrane review on the efficacy of cannabinoids in TS, definite conclusions cannot be drawn, because longer trials including a larger number of patients are missing. Notwithstanding this appraisal, by many experts THC is recommended for the treatment of TS in adult patients, when first line treatments failed to improve the tics. In treatment resistant adult patients, therefore, treatment with THC should be taken into consideration.

Tourette's syndrome.

Tourette's syndrome (TS) is a chronic disorder characterized by motor and vocal tics and a variety of associated behaviour disorders. Because current therapy is often unsatisfactory, there is expanding interest in new therapeutic strategies that are more effective, cause less side effects and ameliorate not only tics but also behavioural problems. From anecdotal reports and preliminary controlled studies it is suggested that - at least in a subgroup of patients - cannabinoids are effective in the treatment of TS. While most patients report beneficial effects when smoking marijuana (Cannabis sativa L.), available clinical trials have been performed using oral Δ9-tetrahydrocannabinol (THC). In otherwise treatment-resistant TS patients, therefore, therapy with THC should not be left unattempted. To date, it is unknown whether other drugs that interact with the endocannabinoid receptor system might be more effective in the treatment of TS than smoked marijuana or pure THC. Since it has been suggested that abnormalities within the endocannabinoid receptor system might underlie TS pathophysiology, it would be of interest to investigate the effect of substances that for example bind more selectively to the central cannabinoid receptor or inhibit the uptake or the degradation of different endocannabinoids.

Cannabis and schizophrenia: towards a cannabinoid hypothesis of schizophrenia.

Highlighting the association between schizophrenia and Cannabis sativa and the endogenous cannabinoid receptor system, respectively, two opposite aspects are of major relevance. On the one hand, cannabis is the most widely used illegal drug. There is substantial evidence that cannabis has to be classified as an independent risk factor for psychosis that may lead to a worse outcome of the disease. This risk seems to be increased in genetically predisposed people and may depend on the amount of cannabis used. On the other hand, during the last few years, an endogenous cannabinoid receptor system (including two known cannabinoid [CB(1) and CB(2)] receptors and five endogenous ligands) has been discovered. There are several lines of evidence suggesting that, at least in a subgroup of patients, alterations in the endocannabinoid system may contribute to the pathogenesis of schizophrenia (e.g., increased density of CB(1) receptor binding and increased levels of cerebrospinal fluid endocannabinoid anandamide). Accordingly, beside the 'dopamine hypothesis' of schizophrenia, a 'cannabinoid hypothesis' has been suggested. Interestingly, there is a complex interaction between the dopaminergic and the endocannabinoid receptor system. Thus, agents that interact with the cannabinoid receptor system, such as the nonpsychoactive cannabidiol, might be beneficial in the treatment of psychosis.

The influence of different food and drink on tics in Tourette syndrome.

AIM: Tourette syndrome (TS) is characterized by waxing and waning motor and vocal tics. Because standard medication often remains unsatisfactory, many patients seek alternative medicine. The aim of this study was to increase experience about the influence of food and drinks in TS. METHODS: A standardized questionnaire was sent to 887 people recruited from our Tourette outpatient clinic and the German TS self-aid group. Respondents should assess whether 32 different foods influenced their tics. RESULTS: Two hundred twenty-four questionnaires could be used for analyses. A significant positive correlation (tic deterioration) was found for caffeine- and theine-containing drinks such as coke (p<0.001), coffee (p<0.001) and black tea (p<0.001) as well as for preserving agents (p<0.001), refined sugar (p<0.001) and sweeteners (p<0.001). A significant negative correlation (tic improvement) was not found. CONCLUSIONS: Results from this first survey investigating the influence of special foods and drinks on tics demonstrated that 34% and 47% of responders, respectively, assessed that coffee and coke deteriorate tics. It, therefore, can be speculated that caffeine may further stimulate an already overactive dopaminergic system in TS and thus increases tics. However, from these preliminary data, no further general recommendations regarding special diets and food restrictions can be made.

Avances en el tratamiento del síndrome de Tourette / Advances in the treatment of Tourette's syndrome

Tics are the hallmarks of a Tourette syndrome (TS). Dopamine receptor antagonists are the approved treatment, although neuroleptic treatment is often unsatisfactory due to side effects. Therefore, there is expanding interest in new therapeutic strategies. From anecdotal reports it has been suggested that Cannabis sativa L. might reduce tics. Two controlled studies in a small number of TS patients demonstrated that delta-9- tetrahydrocannabinol (THC), the most psychoactive ingredient of cannabis, is effective in the treatment of tics without causing serious adverse effects. In addition, no impairment in neuropsychological performance was observed. Therefore, THC should be added to the list of those drugs that are suitable to reduce tics. We recommend THC treatment in TS patients who did not respond to well-established drugs or develop significant side effects. So far, it is unclear, whether herbal cannabis, other natural or synthetic cannabinoid receptor agonists, or agents that interfere with the inactivation of endocannabinoids may have the best adverse effect profile in the treatment of tics. Available data suggest that the endogenous central cannabinoid CB1 receptor system might regulate motor activity in the basal ganglia. It, therefore, can be speculated that the CB1 receptor system might be involved in the pathophysiology of TS

Los tics son el sello distintivo del síndrome de Gilles de la Tourette (ST). Los antagonistas dopaminérgicos constituyen el tratamiento de elección aunque los neurolépticos frecuentemente presentan efectos colaterales poco satisfactorios. Por tanto, existe un creciente interés en obtener nuevos enfoques terapéuticos. Algunos informes anecdóticos sugirieron que Cannabis sativa podría disminuir los tics. Dos estudios controlados en un número pequeño de pacientes demostraron que el delta-9- tetrahidrocannabinol (THC) ­el ingrediente más psicoactivo de la marihuana­ fue efectivo para controlar los tics sin inducir efectos adversos serios. Además, no se observaron alteraciones del desempeño neuropsicológico. Por lo tanto, el THC debiera incorporarse al listado de fármacos útiles para el tratamiento de los tics. Nosotros recomendamos la utilización de esta molécula en los pacientes con ST que no respondieron al tratamiento con las drogas de referencia o presentaron efectos adversos significativos. Hasta el momento, no queda claro si la planta de cannabis, los agonistas naturales o sintéticos de los receptores cannabinoides o los agentes que interfieren con la inactivación de los endocannabinoides poseen el mejor perfil de efectos adversos en el tratamiento de los tics. Los datos disponibles sugieren que el sistema del receptor cannabinoide central endógeno CB1 podría regular la actividad motora de los ganglios de la base. Por lo tanto, se puede especular que este sistema de receptores podría estar relacionado con la fisiopatología del ST

Cannabinoids reduce symptoms of Tourette's syndrome.

Currently, the treatment of Tourette's syndrome (TS) is unsatisfactory. Therefore, there is expanding interest in new therapeutical strategies. Anecdotal reports suggested that the use of cannabis might improve not only tics, but also behavioural problems in patients with TS. A single-dose, cross-over study in 12 patients, as well as a 6-week, randomised trial in 24 patients, demonstrated that Delta9-tetrahydrocannabinol (THC), the most psychoactive ingredient of cannabis, reduces tics in TS patients. No serious adverse effects occurred and no impairment on neuropsychological performance was observed. If well-established drugs either fail to improve tics or cause significant adverse effects, in adult patients, therapy with Delta9-THC should be tried. At present, it remains unclear whether herbal cannabis, different natural or synthetic cannabinoid CB1-receptor agonists or agents that interfere with the inactivation of endocannabinoids, may have the best adverse effect profile in TS.

Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial.

BACKGROUND: Preliminary studies suggested that delta-9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa L., might be effective in the treatment of Tourette syndrome (TS). This study was performed to investigate for the first time under controlled conditions, over a longer-term treatment period, whether THC is effective and safe in reducing tics in TS. METHOD: In this randomized, double-blind, placebo-controlled study, 24 patients with TS, according to DSM-III-R criteria, were treated over a 6-week period with up to 10 mg/day of THC. Tics were rated at 6 visits (visit 1, baseline; visits 2-4, during treatment period; visits 5-6, after withdrawal of medication) using the Tourette Syndrome Clinical Global Impressions scale (TS-CGI), the Shapiro Tourette-Syndrome Severity Scale (STSSS), the Yale Global Tic Severity Scale (YGTSS), the self-rated Tourette Syndrome Symptom List (TSSL), and a videotape-based rating scale. RESULTS: Seven patients dropped out of the study or had to be excluded, but only 1 due to side effects. Using the TS-CGI, STSSS, YGTSS, and video rating scale, we found a significant difference (p <.05) or a trend toward a significant difference (p <.10) between THC and placebo groups at visits 2, 3, and/or 4. Using the TSSL at 10 treatment days (between days 16 and 41) there was a significant difference (p <.05) between both groups. ANOVA as well demonstrated a significant difference (p =.037). No serious adverse effects occurred. CONCLUSION: Our results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesized that the central cannabinoid receptor system might play a role in TS pathology.

Treatment of Tourette syndrome with delta-9-tetrahydrocannabinol (delta 9-THC): no influence on neuropsychological performance.

Previous studies provide evidence that marijuana (Cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, respectively, are effective in the treatment of tics and behavioral problems in Tourette syndrome (TS). It, therefore, has been speculated that the central cannabinoid receptor system might be involved in TS pathology. However, in healthy marijuana users there is an ongoing debate as to whether the use of cannabis causes acute and/or long-term cognitive deficits. In this randomized double-blind placebo-controlled study, we investigated the effect of a treatment with up to 10 mg Delta(9)-THC over a 6-week period on neuropsychological performance in 24 patients suffering from TS. During medication and immediately as well as 5-6 weeks after withdrawal of Delta(9)-THC treatment, no detrimental effect was seen on learning curve, interference, recall and recognition of word lists, immediate visual memory span, and divided attention. Measuring immediate verbal memory span, we even found a trend towards a significant improvement during and after treatment. Results from this study corroborate previous data suggesting that in patients suffering from TS, treatment with Delta(9)-THC causes neither acute nor long-term cognitive deficits. Larger and longer-duration controlled studies are recommended to provide more information on the adverse effect profile of THC in patients suffering from TS.