Endocannabinoid System as a New Therapeutic Avenue for the Treatment of Huntington’s Disease

Huntington’s disease (HD) is a progressive, neurodegenerative disorder manifested by chorea as well as a variety of psychiatric abnormalities. Up to this date, only symptomatic treatment exists. Therefore, there is an urgent need for further therapies. Several neuroanatomical circuits are involved in the pathophysiology of HD, mainly the dopaminergic system. Animal studies and limited studies in humans have shown that abnormalities in the endocannabinoid system could also play an important role in the pathophysiology of HD. These findings have important clinical implications since cannabis-based medicines could potentially be used in the treatment of HD. The aim of this chapter is to summarize the current state of the research regarding the involvement of the endocannabinoid system in HD

Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome

Introduction: Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects. Previous studies have suggested that cannabis-based medicine (CBM) might be an alternative treatment in these patients.Material and methods: Two reviewers (KS, NS) searched the electronic database of PubMed on 1 July, 2021 for relevant studies using the search terms: (‘Tourette syndrome’ [MeSH Terms] OR ‘Gilles de la Tourette syndrome’ [MeSH Terms] OR ‘tic disorders’ [MeSH Terms] OR ‘tics’ [MeSH Terms] OR ‘tic disorders’[Title/Abstract]) AND (‘cannabis-based medicine’ [Title/Abstract] OR ‘cannabis’ [Title/Abstract] OR ‘dronabinol’ [Title/Abstract] OR ‘nabiximols’ [Title/Abstract] OR ‘tetrahydrocannabinol’ [Title/Abstract] OR ‘THC’ [Title/Abstract] OR ‘cannabidiol’ [Title/Abstract], limit: ‘humans’. These studies were further reviewed for additional relevant citations. The titles and abstracts of the studies obtained through this search were examined by two reviewers (KS, NS) in order to determine article inclusion. Discrepancies were addressed by the reviewers through discussion and eventually conversation with the senior reviewer (KMV).Results: Although the amount of evidence supporting the use of CBM in GTS is growing, the majority of studies are still limited to case reports, case series, and open uncontrolled studies. To date, only two small randomised controlled trials (RCTs) using tetrahydrocannabinol (THC, dronabinol) have been published demonstrating the safety and efficacy of this intervention in the treatment of tics in patients with GTS. On the other hand, another RCT with Lu AG06466 (formerly known as ABX-1431), a modulator of endocannabinoid neurotransmission, has failed to prove effective in the therapy of GTS. Accordingly, under the guidelines of both the ESSTS and the AAN, treatment with CBM is categorised as an experimental intervention that should be applied to patients who are otherwise treatment-resistant.Conclusions: Increasing evidence suggests that CBM is efficacious in the treatment of tics and psychiatric comorbidities in patients with GTS. The results of ongoing larger RCTs, such as CANNA-TICS (ClinicalTrials.gov Identifier: NCT03087201), will further clarify the role of CBM in the treatment of patients with GTS

Soluble Urokinase Plasminogen Activator Receptor Levels Correlation with Other Inflammatory Factors in Prognosis of Disability and Death in Patients with Ischemic Stroke

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker elevated in cardiovascular diseases. The aim of this 3-year follow-up prospective study was to evaluate suPAR levels in patients with a first ischemic stroke in correlation with CRP, PCT, NT-proCNP and endothelin 1-21 and to investigate the impact of suPAR on the outcome. Fifty-one patients (mean age 73.7+ = 11.9 years, 26 female and 25 male) were included. Samples were collected on the first (suPAR 1), third (suPAR 3) and seventh days after stroke onset (suPAR 7). Plasma samples were analyzed using ELISA. A phone interview was conducted to collect follow-up information after 24 and 36 months (modified Rankin Scale, mRS). A positive correlation between suPAR levels and other inflammatory biomarkers (except endothelin 3) was observed. A positive correlation between suPAR 3 and mRS score at 24 months was observed (p = 0.042). The logistic regression model revealed no significant effect of suPAR on death occurrence in the first 24 months: suPAR 1 (p = 0.8794), suPAR 3 (p = 0.2757), and suPAR 7 (p = 0.3652). The suPAR level is a potential inflammatory marker in ischemic stroke, and there is a correlation with other markers. There is no major impact on mortality. However, the suPAR level is associated with a degree of disability or dependence in daily activities 2 years after a stroke