Vitor Tumas

Cannabidiol for the treatment of psychosis in Parkinson’s disease:

The management of psychosis in Parkinson’s disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson’s Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.

Role of Nitric Oxide on Motor Behavior

AbstractThe present review paper describes results indicating the influence of nitric oxide (NO) on motor control. Our last studies showed that systemic injections of low doses of inhibitors of NO synthase (NOS), the enzyme responsible for NO formation, induce anxiolytic effects in the elevated plus maze whereas higher doses decrease maze exploration. Also, NOS inhibitors decrease locomotion and rearing in an open field arena.These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), NG-nitro-L-arginine methylester (L-NAME), NG-monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration.Acute administration of L-NOARG has an additive cataleptic effect with haloperidol, a dopamine D2 antagonist. The catalepsy is also potentiated by WAY 100135 (5-HT1a receptor antagonist), ketanserin (5HT2a and alfa1 adrenergic receptor antagonist), and ritanserin (5-HT2a and 5HT2c receptor antagonist). Atropine sulfate and biperiden, antimuscarinic drugs, block L-NOARG-induced catalepsy in mice.L-NOARG subchronic administration in mice induces rapid tolerance (3 days) to its cataleptic effects. It also produces cross-tolerance to haloperidol-induced catalepsy. After subchronic L-NOARG treatment there is an increase in the density NADPH-d positive neurons in the dorsal part of nucleus caudate-putamen, nucleus accumbens, and tegmental pedunculupontinus nucleus. In contrast, this treatment decreases NADPH-d neuronal number in the substantia nigra compacta.Considering these results we suggest that (i) NO may modulate motor behavior, probably by interfering with dopaminergic, serotonergic, and cholinergic neurotransmission in the striatum; (ii) Subchronic NO synthesis inhibition induces plastic changes in NO-producing neurons in brain areas related to motor control and causes cross-tolerance to the cataleptic effect of haloperidol, raising the possibility that such treatments could decrease motor side effects associated with antipsychotic medications.Finally, recent studies using experimental Parkinson’s disease models suggest an interaction between NO system and neurodegenerative processes in the nigrostriatal pathway. It provides evidence of a protective role of NO. Together, our results indicate that NO may be a key participant on physiological and pathophysiological processes in the nigrostriatal system.

Salivary α-synuclein and DJ-1: potential biomarkers for Parkinson's disease

Sir, Parkinsons disease is a neurodegenerative disorder belonging to a group of heterogeneous diseases characterized by a progressive and relatively selective loss of anatomically or physiologically related neuronal systems (Lang and Lozano, 1998; Silvers and Som, 1998). The identification of Parkinsons disease specific biomarkers, particularly at early stages, is critical for Parkinsons disease diagnosis, monitoring disease progression and patient management as well as the development of therapeutic interventions. Thus far, the proteins α-synuclein (α-Syn) and DJ-1 have been tested rigorously in Parkinsons disease. In our recent study published in Brain (Hong et al. , 2010), where a large cohort of patients with Parkinsons disease and controls were included, we provided evidence that α-Syn, along with DJ-1, decreases in Parkinsons disease CSF, providing high sensitivity and specificity for Parkinsons disease diagnosis. However, even though CSF is close to the main site of pathology in Parkinsons disease and other neurodegenerative disorders in the CNS, it cannot be readily obtained in most clinical settings (Shi et al. , 2010). To address this issue, several groups have examined serum/plasma concentrations of α-Syn and DJ-1 as potential biomarkers of Parkinsons disease. Unfortunately, a major drawback in assessing serum/plasma α-Syn and DJ-1 levels is the fact that >95% of total blood α-Syn and DJ-1 are derived from red blood cells. After controlling for several major variables, we concluded in a recent investigation that, unlike CSF, these two markers in plasma are unable to differentiate patients with Parkinsons disease from controls (Shi et al. , 2010). Of note, blood contamination of human CSF is also a major problem when assessing levels of α-Syn and DJ-1 in CSF (Hong et al. , 2010; Shi et al. , 2010). In an effort to look for other potential sources of clinically accessible samples for Parkinsons disease diagnosis …

Quantifying brain iron deposition in patients with Parkinson's disease using quantitative susceptibility mapping, R2 and R2*

PURPOSE To evaluate the sensitivity and specificity of quantitative magnetic resonance (MR) iron mapping including R2, R2* and magnetic susceptibility to differentiate patients with Parkinsons disease (PD) from healthy controls. MATERIALS AND METHODS Thirty (30) healthy controls (HC) (64±7years old) and 20 patients with idiopathic PD (66±8years old) were studied using a 3T MR imaging scanner. R2 maps were generated from GRASE sequence while R2*, and quantitative susceptibility mapping (QSM) were obtained from a conventional multi-echo gradient-echo sequence. R2, R2* and relative susceptibility (Δχ) values of structures in the basal ganglia were measured for each patient and control. An analysis of sensitivity and specificity and unpaired t-test was applied to the two groups. RESULTS A significant difference (p<0.05) was found for R2 and ∆χ values in the substantia nigra as a whole and in the pars compacta for PD patients. The R2* values were different significantly (p<0.05) only on the substantia nigra pars compacta. QSM presented the highest sensitivity and specificity to differentiate the two populations. CONCLUSION The QSM map was the most sensitive quantitative technique for detecting a significant increase of iron for PD. The highest significant difference between controls and patients was found in the substantia nigra pars compacta using QSM.

Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: A case series

Cannabidiol (CBD) is the main non‐psychotropic component of the Cannabis sativa plant. REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during REM sleep associated with nightmares and active behaviour during dreaming. We have described the effects of CBD in RBD symptoms in patients with Parkinsons disease.

Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial

Introduction: Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. Methods: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H1-MRS). Results: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H1-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05). Conclusions: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.

Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania:

Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by d-amphetamine (d-AMPH). In the first model (reversal treatment), rats received saline or d-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or d-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the d-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the d-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against d-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.

Validity of a Brazilian version of the Zung self-rating depression scale for screening of depression in patients with Parkinson's disease☆

INTRODUCTION Parkinsons disease (PD) is a neurodegenerative disorder with prominent motor manifestations and many other non-motor symptoms that significantly decrease quality-of-life and are frequently under-recognized, for example depression. OBJECTIVE To study the validity of a Brazilian version of the Zung Self-rating Depression Scale (SDS) for the diagnosis of depression in patients with PD. METHODS We evaluated 78 consecutive non demented patients over the age of 40 with diagnosis of PD at a Movement Disorders Outpatient Clinic, who could read and understand questionnaires. They completed the SDS and the Geriatric Depression Scale with 15 items (GDS-15). The diagnosis of depression was made after a structured clinical interview based on DSM-IV criteria for the diagnosis of major depression (SCID-CV). RESULTS The prevalence of major depression was 23.1%. Cronbachs alpha was 0.73 and the area under the ROC curve was 0.93 for the SDS. The score index of 55 had a sensitivity of 88.9% and a specificity of 83.3% for the diagnosis of depression. The total scores of the SDS and GDS-15 were highly correlated (0.652, p < 0.0001) and correlated weakly with the scores of a motor scale. DISCUSSION The SDS is a valid tool for screening depression in patients with PD since the specific SDS index of 55 is adopted. Two shortened versions could be used with good results.

Increased dopamine transporter density in Parkinson's disease patients with social anxiety disorder☆

Social Anxiety Disorder (SAD) is more common among PD patients than in the general population. This association may be explained by psychosocial mechanisms but it is also possible that neurobiological mechanism underlying PD can predispose to SAD. The aim of this study was to investigate a possible dopaminergic mechanism involved in PD patients with SAD, by correlating striatal dopamine transporter binding potential (DAT-BP) with intensity of social anxiety symptoms in PD patients using SPECT with TRODAT-1 as the radiopharmaceutical. Eleven PD patients with generalized SAD and 21 PD patients without SAD were included in this study; groups were matched for age, gender, disease duration and disease severity. SAD diagnosis was determined according to DSM IV criteria assessed with SCID-I and social anxiety symptom severity with the Brief Social Phobia Scale (BSPS). Demographic and clinical data were also collected. DAT-BP was significantly correlated to scores on BSPS for right putamen (r=0.37, p=0.04), left putamen (r=0.43, p=0.02) and left caudate (r=0.39, p=0.03). No significant correlation was found for the right caudate (r=0.23, p=0.21). This finding may reinforce the hypothesis that dopaminergic dysfunction might be implicated in the pathogenesis of social anxiety in PD.

Frontal assessment battery in a Brazilian sample of healthy controls: normative data

OBJECTIVE To show data on the performance of healthy subjects in the Frontal Assessment Battery (FAB), correlating with gender, age, education, and scores in the Mini-Mental State Examination (MMSE). METHODS Two hundred and seventy-five healthy individuals with mean age of 66.4 ± 10.6 years-old were evaluated. Mean total FAB scores were established according to the educational level. RESULTS Mean total FAB scores according to the educational level were 10.9 ± 2.3, for one to three years; 12.8 ± 2.7, for four to seven years; 13.8 ± 2.2, for eight to 11 years; and 15.3 ± 2.3, for 12 or more years. Total FAB scores correlated significantly with education (r=0.47; p<0.0001) and MMSE scores (r=0.39; p<0.0001). No correlation emerged between FAB scores, age, and gender. CONCLUSION In this group of healthy subjects, the Brazilian version of the FAB proved to be influenced by the education level, but not by age and gender.