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

The FDA “black box” warning on antidepressant suicide risk in young adults: More harm than benefits?

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications

Clinical presentation of strokes confined to the insula: a systematic review of literature

BACKGROUND AND PURPOSE: The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive the appropriate treatment (e.g. thrombolysis). METHODS: We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords "insular stroke" and "insular infarction", to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. RESULTS: We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. CONCLUSIONS: The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations

Focal Cerebral Infarction in Newborn: Description of Three Cases:

We observed 3 full-term newborns with focal ischemic injury of the middle cerebral artery (MCA), in which diagnosis of MCA stroke was suspected by US and confirmed by CT scan and MRI. A four-year follow-up was carried out to study the effect of neonatal stroke on neurodevelopmental outcome. All children had a history of pre-perinatal risk factors: neonatal cerebral infarction in term infants, in fact, has many possible causes, including bacterial meningitis, inherited or acquired coagulopathies, trauma and hypoxia-ischemia. The prognosis of neonatal MCA infarction depends on early diagnosis, on the CNS plasticity mechanism and, finally, on medical therapy and neuropsychological rehabilitation

Low-Dose Topiramate in Alcohol Dependence: A Single-Blind, Placebo-Controlled Study

Introduction:Topiramate (TOP) and anticonvulsants in general are considered safe and effective drugs for the treatment of alcohol dependence, even though TOP-induced adverse events are quite common, especially for high initial doses or if titration to 300 mg/d is too rapid. The aim of the present study was to assess the efficacy and tolerability profile of low-dose TOP for relapse prevention. METHODS: After detoxification, 52 patients were randomized into 2 groups as follows: 26 patients received 100 mg of TOP (oral, twice daily), titrated over 2 weeks, and 26 patients received placebo (PLA). Both groups underwent rehabilitation twice a week. RESULTS: After 6 weeks of treatment, compared with the PLA group, patients receiving TOP showed the following: (1) fewer drinking days (P < 0.05); (2) less daily alcohol consumption (P < 0.05); (3) more days of treatment (P < 0.05); (4) reduced levels of craving (Obsessive-Compulsive Drinking Scale) and withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol-Revised); and (5) improvement of anxiety, depression, and obsessive-compulsive symptom severity (Symptom Check List 90 Revised). CONCLUSIONS: Despite the small sample size and the short follow-up period, the present PLA-controlled study demonstrated the potential usefulness of TOP, even when administered at a dosage of 100 mg/d, for the treatment of detoxified alcohol-dependent subjects, confirming results from previous studies testing higher doses of TOP

A comprehensive overview on Kratom

Kratom (Mitragyna speciosa Korth) is a tropical tree, indigenous to South East Asia. Historically, the plant is locally used as a stimulant, a remedy in traditional medicine and in social context. Imported to Western countries, Kratom is classified as a novel psychoactive substance (NPS). A systematic review of the literature on Mitragyna speciosa and its main constituents was carried by our international multidisciplinary group. Results were qualitatively analysed in three main areas of interest: in-vitro and preclinical data on pharmacology and behavioral effects, laboratoristic techniques for identification/characterization, epidemiological/toxicological reports on humans. At present, there is no systematic data on the prevalence of Kratom use in all the native countries, but it seems to be considerable. In South-East Asia, Kratom, even if banned, might be still considered a better option than other illicit drugs, an alternative opioid treatment, a “natural” remedy with no real social stigma attached to its consumption. In parallel, this ethno-drug seems to be popular in Western countries, largely unregulated, easily available on the Internet. Kratom pharmacology appears to be complex, with many alkaloids involved. The subjective effects in humans are very peculiar and seem to be dose-dependent, ranging from psycho-stimulant to sedative-narcotic. Available data on Kratom suggest caution: this psychoactive plant could exhibit a serious harmful potential. Kratom use seems to be associated with drug dependency, development of withdrawal symptoms, craving, serious adverse effects and life-threatening effects in a multidrug-intoxicating scenario. On the other hand, its anxyiolitic, antidepressant and analgesic properties deserve to be further studied

Inflammatory markers and suicidal attempts in depressed patients: A review

Major depressive disorder is a chronic and invalidating psychiatric illness and is associated with a greater risk of suicidal behaviors. In recent decades many data have supported a biological link between depressive states and inflammation. Pro-inflammatory cytokines have been found to rise, first of all TNF-α and IL-6. Suicidal behaviors have been consistently associated with increased levels of IL-6 and decreased levels of IL-2. The aim of this review is to investigate the relationship between inflammatory markers in depressed patients with or without suicidal attempts compared to healthy controls

May second generation long-acting injectable antipsychotics be prescribed as a first-line treatment of first episode in patients with schizophrenia? An overview.

Schizophrenia is a chronic and disabling disorder, characterized by positive, negative, cognitive and affective symptoms. The first episode of schizophrenia (FES) usually occurs after a variable period of prodromic symptoms and the importance of early detection and treatment of FES has been raised in psychiatric literature from long time. In fact, it has been suggested that the first years of the schizophrenic disorder may be a critical period for long-term prognosis, as the relationship between the poor medication adherence and poorer outcome is well demonstrated. Longacting injectable formulations of second-generation antipsychotics (SGAs-LAIs) provide constant medication delivery and the potential for improved adherence. Currently, four SGAs-LAIs are available for the treatment of schizophrenia, risperidone long-acting injectable, olanzapine pamoate, paliperidone palmitate and aripiprazole. Several studies have also demonstrated efficacy and safety of such drugs in patients with schizophrenia. In the present paper the literature on SGAs-LAIs atypical antipsychotics in the treatment of FES will be reviewed and practical advice will be given concerning the use of this drug in the everyday clinical practice

The melatonergic system in mood and anxiety disorders and the role of agomelatine: implications for clinical practice

Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in “real world” clinical practice will be also discussed