Cannabidiol: A Promising Drug for Neurodegenerative Disorders?

Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration. Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective. In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.     

Hypertonic saline: first-line therapy for cerebral edema?

This article highlights the experimental and clinical data, controversies and postulated mechanisms surrounding osmotherapy with hypertonic saline (HS) solutions in the neurocritical care arena and builds on previous reviews on the subject. Special attention is focused on HS therapy on commonly encountered clinical paradigms of acute brain injury including traumatic brain injury (TBI), post-operative "retraction edema", intracranial hemorrhage (ICH), tumor-associated cerebral edema, and ischemia associated with ischemic stroke.     

Review: On TRAIL for malignant glioma therapy?

J. M. A. Kuijlen, E. Bremer, J. J. A. Mooij, W. F. A. den Dunnen and W. Helfrich (2010) Neuropathology and Applied Neurobiology 36, 168–182
On TRAIL for malignant glioma therapy? Glioblastoma (GBM) is a devastating cancer with a median survival of around 15 months. Significant advances in treatment have not been achieved yet, even with a host of new therapeutics under investigation. Therefore, the quest for a cure for GBM remains as intense as ever. Of particular interest for GBM therapy is the selective induction of apoptosis using the pro‐apoptotic tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL). TRAIL signals apoptosis via its two agonistic receptors TRAIL‐R1 and TRAIL‐R2. TRAIL is normally present as homotrimeric transmembrane protein, but can also be processed into a soluble trimeric form (sTRAIL). Recombinant sTRAIL has strong tumouricidal activity towards GBM cells, with no or minimal toxicity towards normal human cells. Unfortunately, GBM is a very heterogeneous tumour, with multiple genetically aberrant clones within one tumour. Consequently, any single agent therapy is likely to be not effective enough. However, the anti‐GBM activity of TRAIL can be synergistically enhanced by a variety of conventional and novel targeted therapies, making TRAIL an ideal candidate for combinatorial strategies. Here we will, after briefly detailing the biology of TRAIL/TRAIL receptor signalling, focus on the promises and pitfalls of recombinant TRAIL as a therapeutic agent alone and in combinatorial therapeutic approaches for GBM.     

Vagus nerve stimulation. A potential therapy for resistant depression?

VNS builds on a long history of investigating the relationship of autonomic signals to limbic and cortical function and is one of the newest methods to physically alter brain function. VNS is a clinically useful anticonvulsant therapy in treatment resistant patients with epilepsy, and pilot data suggest that it has potential as an antidepressant therapy. The known anatomic projections of the vagus nerve suggest that VNS also might have other neuropsychiatric applications. Additional research is needed to clarify the mechanisms of action of VNS and the potential clinical utility of this intriguing new somatic portal into the CNS.     

Whither cognitive-behavioral therapy for schizophrenia?

Clinical studies of cognitive therapy and rehabilitation for persons with schizophrenia have generated promising findings of improvements in patients' cognitive and clinical status. However, the results do not appear to be specific to a particular form of intervention, and long-term evaluations of cognitive therapy, as an element in a comprehensive system of care, need to be conducted for clinical validation. Rehabilitation efforts should be congruent with laboratory findings of specific cognitive deficits, including those that are "vulnerability indicators" and endure beyond symptomatic episodes. With the demonstration that chronic schizophrenic patients can learn a variety of cognitive and behavioral skills through Integrated Psychological Therapy and other psychosocial treatments, the future appears bright for a profusion of new modalities aimed at cognitive-behavioral rehabilitation, especially those that emerge from what is known about information-processing deficits in schizophrenia.     

Mast cells: new targets for multiple sclerosis therapy?

Growing evidence suggests that mast cells (MCs) play a crucial role in the inflammatory process and the subsequent demyelination observed in patients suffering from multiple sclerosis (MS). Although no consensus exists on the role of mast cells in multiple sclerosis, recent results from animal models clearly indicate that these cells act at multiple levels to influence both the induction and the severity of disease. In addition to changing our views on the pathophysiology of multiple sclerosis, the concept that mast cells are critical for the outcome of the disease could have an important impact on the development of new therapeutic approaches.     

Oxidative injury in epilepsy: potential for antioxidant therapy?

Biological ill effects of oxidative injury from excess free radical production are implicated in many human conditions. Epilepsy is a chronic, dynamic neurological disorder associated with ongoing neuronal damage, particularly when uncontrolled. Oxidative injury may play a role in the initiation and progression of epilepsy, and therapies aimed at reducing oxidative stress may ameliorate tissue damage and favorably alter the clinical course. There is abundant in vivo evidence of oxidative injury in animal models of epilepsy and for efficacy of antioxidant therapy in reducing this injury in animal models of epileptogenesis. However, there is sparse direct clinical data on the use of antioxidants in human epilepsy. This review examines the evidence for the role of oxidative injury in epilepsy, the rationale for use of antioxidant therapy in epilepsy and appraises the current clinical performance of the studies of antioxidant therapies.     

Statin therapy for Alzheimer's disease: will it work?

Disease-modifying therapies are being developed for Alzheimer's disease (AD). These are expected to slow the clinical progression of the disease or delay its onset. Cerebral accumulation of amyloid beta (A beta) peptides is an early and perhaps necessary event for establishing AD pathology. Consequently therapies aimed at attenuating brain amyloidosis are expected to be disease modifying. Based on the epidemiological evidence pointing to a link between cholesterol metabolism and AD and the numerous laboratory studies implicating cholesterol in the process of A beta production and accumulation, it is now believed that cholesterol-lowering therapies will be of value as disease modifying agents. Several epidemiological studies revealed that statin use for the treatment of coronary arterial disease is associated with a decreased prevalence or a decreased risk of developing AD. These observations require both preclinical and clinical validation. The former involves testing statins in one or more animal models of AD in order to establish which disease features are affected by statin treatment, the relative efficacy with which different statins modify these features and the mechanism(s) by which statins affect AD phenotypes. The latter requires prospective, randomized, placebo controlled trials to evaluate the effect of statin treatment on cognitive and AD biomarker outcomes. We have initiated a study aimed at determining the effects of atorvastatin (Lipitor), a statin with the largest US market share, on brain A beta deposition in the PSAPP transgenic mouse model of Alzheimer's amyloidosis. Our results indicate that Lipitor treatment markedly attenuates A beta deposition in this animal model.     

Cognitive–behavioral therapy for irritable bowel syndrome: A meta-analysis

Objective

To establish whether cognitive behavioral therapy (CBT) improves the bowel symptoms, quality of life (QOL) and psychological states of irritable bowel syndrome (IBS) patients.

Methods

Randomized controlled trials (RCTs) of CBT for adult patients with IBS were searched by using PubMed, Scopus and Web of Science. The standardized mean difference (SMD) with 95% confidence intervals (CIs) of the evidence-based outcome measures of the IBS bowel symptoms, QOL and psychological states at post-treatment and follow-up was calculated. Prespecified subgroup analysis was performed.

Results

Eighteen RCTs satisfied our inclusion criteria. In the subgroup analyses, CBT was more effective in reducing IBS bowel symptoms, QOL and psychological states than waiting list controls at the end of the intervention and short-term follow-up. When compared with controls of basic support and medical treatment, the effect sizes were found to favor CBT for the improvement of IBS bowel symptoms at post-treatment and short-term follow-up, but CBT was not superior to controls in improving QOL and psychological states. When comparing CBT with other psychological controls, the effect sizes were almost non-significant.

Conclusions

For IBS patients, CBT was superior to waiting list, basic support or medical treatment at the end of treatment but not superior to other psychological treatments. The meta-analysis might be limited by the heterogeneities and small sample sizes of the included studies.     

Technology insight: therapy for Duchenne muscular dystrophy-an opportunity for personalized medicine?

Since the identification of dystrophin as the protein product of the Duchenne and Becker muscular dystrophy locus, many different mutations, encompassing the entire spectrum of gene mutations ranging from point mutations to large deletions, have been found. These discoveries have led to the investigation of a variety of methods aimed at the treatment of muscular dystrophy, including strategies for gene replacement, gene correction, and modification of the gene product. The preferred approach in each case depends on the nature of the gene defect. In this Review, we focus on methods that have been developed for gene correction and for the modification of gene products. This mutation-focused approach offers the opportunity for 'personalized' gene therapy for muscular dystrophy and might also be a logical strategy for the treatment of other genetic disorders.     

Video technology--a medium for milieu therapy?

Video technology has been in use in the psychiatric field for more than 20 years for diagnostic, scientific, co-therapeutic or educational purposes. However, little is known of its potential applications and impact as an instrument in psychotherapy or environmental therapy. For this reason a new cinematographic project applying widespread video technology in environmental therapy, too, has been launched. All patients at our psychiatric hospital are involved in film selection, can cooperate at different organizational levels, and have regular opportunities to see films. The technical, the organizational and, in particular, the legal preconditions are set out, followed by a report on experience gained in use of video films within the setting of a psychiatric hospital. Reference is also made to economic aspects, therapeutic effects and contraindications.