Clinically relevant safety issues associated with St. John's wort product labels

<p>Abstract</p> <p>Background</p> <p>St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA.</p> <p>Methods</p> <p>Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.</p> <p>Results</p> <p>Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of <it>a priori </it>safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness.</p> <p>Conclusion</p> <p>The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.</p

Leptin Does Not Directly Affect CNS Serotonin Neurons to Influence Appetite

Serotonin (5-HT) and leptin play important roles in the modulation of energy balance. Here we investigated mechanisms by which leptin might interact with CNS 5-HT pathways to influence appetite. Although some leptin receptor (LepRb) neurons lie close to 5-HT neurons in the dorsal raphe (DR), 5-HT neurons do not express LepRb. Indeed, while leptin hyperpolarizes some non-5-HT DR neurons, leptin does not alter the activity of DR 5-HT neurons. Furthermore, 5-HT depletion does not impair the anorectic effects of leptin. The serotonin transporter-cre allele (Sert(cre)) is expressed in 5-HT (and developmentally in some non-5-HT) neurons. While Sert(cre) promotes LepRb excision in a few LepRb neurons in the hypothalamus, it is not active in DR LepRb neurons, and neuron-specific Sert(cre)-mediated LepRb inactivation in mice does not alter body weight or adiposity. Thus, leptin does not directly influence 5-HT neurons and does not meaningfully modulate important appetite-related determinants via 5-HT neuron function

Erythropoietin: a multimodal neuroprotective agent

The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent

Serotonin controlling feeding and satiety

Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and ‘true’ satiation and satiety. Currently, 5-HT1B, 5-HT2C and 5-HT6 receptors have been identified to mediate serotonergic satiety in different ways. The recently approved anti-obesity drug lorcaserin is a 5-HT2C receptor agonist. In brain, both hypothalamic (arcuate nucleus, paraventricular nucleus) and extrahypothalamic sites (parabrachial nucleus, nucleus of the solitary tract) have been identified to mediate the serotonergic control of satiety. Serotonin interacts within the hypothalamus with endogenous orexigenic (Neuropeptide Y/Agouti related protein) and anorectic (α-melanocyte stimulating hormone) peptides. In the nucleus of the solitary tract serotonin integrates peripheral satiety signals. Here, the 5-HT3, but possibly also the 5-HT2C receptor play a role. It has been found that 5-HT acts in concert with such peripheral signals as cholecystokinin and leptin. Despite the recent advances of our knowledge, many of the complex interactions between 5-HT and other satiety factors are not fully understood yet. Further progress in research will also advance the development of new serotonergic anti-obesity drugs

Regulation of herbal medicinal products in the EU: An up-to-date scientific review

A new European legislation on herbal medicinal products (HMPs) was developed, in order to harmonise the use of HMPs in the 28 member states of the European Union, according to Directive 2004/24/EC which amended the basic legislation laid down in Directive 2001/83/EC. The objective of this legislation was to ensure the future existence of such products and to consider particular characteristics during the assessment of their quality, efficacy and safety, having defined two categories for herbal medicines: (a) well-established use HMPs, which can be granted a marketing authorisation; and (b) traditional herbal medicinal products which can be granted a registration based on their long-standing safe and efficient use. The Committee on Herbal Medicinal Products was established at the European Medicines Agency in 2004, in order mainly to provide community monographs and list entries on herbal substances and preparations. 120 monographs have been published since then, which offer a scientific and regulatory standard for their safety and efficacy, during their use as medicinal products. The HMPs can be placed in the market after quality, efficacy, and safety have been assessed according to the provisions of the legislation (Directive 2004/24/EC and Directive 2001/83/EC), with adequate labeling information to patients and health care professionals, distinguishing them from other product categories containing herbs like: foods, food supplements, medical devices and cosmetics. © 2014 Springer Science+Business Media

Neurological aspects of medical use of cannabidiol

Background: Cannabidiol (CBD) is among the major secondary metabolites of Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is a resorcinol-based compound with a broad spectrum of potential therapeutic properties, including neuroprotective effects in numerous pathological conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory activities and the modulation of a large number of brain biological targets (receptors, channels) involved in the development and maintenance of neurodegenerative diseases. Objective: The aim of the present review was to describe the state of art about the pre-clinical research, the potential use and, when existing, the clinical evidence related to CBD in the neurological field. Method: Collection of all the pre-clinical and clinical findings carried out investigating the effects of CBD alone, not in combination with other substances, in the neurological arena with the exclusion of studies on neuropsychiatric disorders. Results: Laboratory and clinical studies on the potential role of CBD in Parkinsonâs disease (PD), Alzheimerâs disease (AD), multiple sclerosis (MS), Huntingtonâs disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia, were examined. Conclusion: Pre-clinical evidence largely shows that CBD can produce beneficial effects in AD, PD and MS patients, but its employment for these disorders needs further confirmation from well designed clinical studies. CBD pre-clinical demonstration of antiepileptic activity is supported by recent clinical studies in human epileptic subjects resistant to standard antiepileptic drugs showing its potential use in children and young adults affected by refractory epilepsy. Evidence for use of CBD in PD is still not supported by sufficient data whereas only a few studies including a small number of patients are available

Beyond the wall: Death education at middle school as suicide prevention

This study investigates the psychological effects of participation in Death Education (DeEd) by middle school children in two towns in northeast Italy in which suicides occur to a greater extent than in the rest of the region. The aims of the project \u201cBeyond the Wall\u201d were inherent to the prevention of suicide, address existential issues and enhance the meaning of life through positive intentions for the future and reflection on mortality. It involved eight classes (150 students in four classes in the experimental group; 81 in four classes in the control group) engaging with films, workgroup activities, photovoice and psychodrama. The constructs of resilience, emotional competency and psychological well-being were monitored with the Resilience Scale for Adolescents, the Hopelessness Scale for Children, the Alexithymia Questionnaire for Children and the Stirling Children\u2019s Well-being Scale. The DeEd intervention was found to be significantly related to some of the variables investigated, improving the students\u2019 ability to recognise emotions and communicate them verbally while maintaining stable initial characteristics, such as psychological well-being and positive expectations for the future