The Endocannabinoid System: A Putative Role in Neurodegenerative Diseases

BACKGROUND: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations. OBJECTIVES: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases. MATERIALS AND METHODS: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed. RESULTS: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases. CONCLUSIONS: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology

L’ossessione del mangiare sano: la misurazione dell’ortoressia nervosa attraverso la scala ortho-15

Alla luce dell’interesse clinico mostrato verso il costrutto di "ortoressia", dell’attualità del tema e delle sue potenziali ricadute applicative sui comportamenti e sulla salute psicologica dell’individuo, l'obiettivo del presente lavoro sarà quello di investigare con maggiore dettaglio le proprietà psicometriche della ORTHO-15 nel contesto italiano al fine di renderlo uno strumento attendibile e valido

Substance-related psychopathology and aggressiveness in a nightlife holiday resort: Results from a pilot study in a psychiatric inpatient unit in Ibiza

Objectives: We aimed to describe a sample of subjects admitted to a psychiatric unit after the intake of psychoactive substances for recreational purposes. Methods: Between June and September 2015, 49 subjects were included. Sociodemographic characteristics and psychopathological aspects were investigated, and urine samples for further analysis were collected. Three subgroups (cannabinoids, stimulants, and depressors users) were identified, according to the structured interview regarding substance use and urinalysis. Results: Level of aggressiveness was found to be significantly higher (p <.05) in the cannabinoids subgroup. Self-reported symptom severity was comparable among groups, but trends could be identified: SCL-90 results showed a prevalence of anxiety symptoms among depressors users, hostility or aggression in the tetrahydrocannabinol subgroup, and psychoticism in the stimulants subgroup. Conclusions: The use of psychoactive substances was be characterised by poly-use of both traditional and novel substances. The presence of aggressiveness emerged as a main feature associated with the use of cannabis and other cannabinoids. Binge drinking and sleep deprivation also represented a relevant component in almost all the evaluated subjects

Party hard: Drug-related fatalities in Ibiza from 2010 to 2016

IntroductionIllicit drug use is well known as an important contributor to the global burden of diseases, but the physical and psychopathological risks of recreational drugs misuse are often underestimated and drug-related fatalities in specific settings are under-investigated.Objectives and methodsIn the framework of the EU-funded project “EU-Madness”, we collected and analysed all the reports of drug-related fatalities in Ibiza from January 2010 to September 2016, with the aim of characterising the sample, and identifying the involved substances and the nature of deaths associated with their consumption.ResultsOverall, 58 drug-related fatalities were registered from 2010 to September 2016 (87.9% males, 12.1% females, mean age 33.16; females were significantly younger than males). Most of the deceased were Britons (36.2%), followed by Spanish (22.4%), Italians (6.9%) and Germans (5.2%). In half the cases, the substance identified in post-mortem analyses was a stimulant; in 24.1% of the sample it was a depressor a prescription drug or more than two substances in 22.4%. Most of the fatalities were due to cardiovascular accidents (62%); 22.4% were deaths by drowning, 12% by fall from heights and 3.4% were due to mechanical asphyxia.ConclusionsAccording to the results from our sample, stimulants (mainly MDMA and cocaine) are the substances of abuse involved in most drug-caused fatalities. The number of fatalities per year has been steadily increasing, but the growing diffusion of novel psychoactive substances (NPS) does not seem to be a direct cause (although better methods of their analysis in post-mortem samples should be designed).Disclosure of interestThe authors have not supplied their declaration of competing interest.</jats:sec

A Phosphosite Mutant Approach on LRRK2 Links Phosphorylation and Dephosphorylation to Protective and Deleterious Markers, Respectively

The Leucine Rich Repeat Kinase 2 (LRRK2) gene is a major genetic determinant of Parkinson’s disease (PD), encoding a homonymous multi-domain protein with two catalytic activities, GTPase and Kinase, involved in intracellular signaling and trafficking. LRRK2 is phosphorylated at multiple sites, including a cluster of autophosphorylation sites in the GTPase domain and a cluster of heterologous phosphorylation sites at residues 860 to 976. Phosphorylation at these latter sites is found to be modified in brains of PD patients, as well as for some disease mutant forms of LRRK2. The main aim of this study is to investigate the functional consequences of LRRK2 phosphorylation or dephosphorylation at LRRK2’s heterologous phosphorylation sites. To this end, we generated LRRK2 phosphorylation site mutants and studied how these affected LRRK2 catalytic activity, neurite outgrowth and lysosomal physiology in cellular models. We show that phosphorylation of RAB8a and RAB10 substrates are reduced with phosphomimicking forms of LRRK2, while RAB29 induced activation of LRRK2 kinase activity is enhanced for phosphodead forms of LRRK2. Considering the hypothesis that PD pathology is associated to increased LRRK2 kinase activity, our results suggest that for its heterologous phosphorylation sites LRRK2 phosphorylation correlates to healthy phenotypes and LRRK2 dephosphorylation correlates to phenotypes associated to the PD pathological processes