Developing Topics.

Background: We present Phase 1 trial data using the Neuropsychiatric Inventory ("NPI") domains, NPI-delusions and NPI-hallucinations as symptoms of psychosis in participants with Alzheimer's ("AD") receiving IGC-AD1, a combination of low concentration delta 9-tetrahydrocannabinol ("THC") and melatonin. Cannabis use is considered an established risk factor for psychosis in young people. Psychosis is prevalent in AD patients, with around 50% experiencing it, generating safety concerns regarding the use of THC in these patients.

Developing Topics.

Background: This study investigates the impact of IGC-AD1, a combination comprising of low concentration of delta-9 tetrahydrocannabinol ("THC") and melatonin on blood serum potassium levels in patients with Alzheimer's disease ("AD"). Loss of intracellular compartmentalization of potassium is a characteristic of AD pathology, with supporting studies indicating significantly lower potassium levels in intracellular compartments of AD brains and an associated increase in serum potassium levels in AD subjects. Here, we present preliminary safety lab data from a Phase I trial of AD patients administered with IGC-AD1.

Developing Topics.

Background: Sleep disturbances are prevalent in Alzheimer's disease (AD), impacting cognition and quality of life. Trials have also shown increased subjective sleepiness with melatonin doses compared to placebo. High melatonin doses may increase drowsiness, headache, and dizziness, as indicated by a systematic review.

Developing Topics.

Background: Alzheimer's Disease ("AD") presents a significant global health burden, often requiring medication management of comorbidities, some of which are metabolized by the polymorphic enzyme CYP2C9. We investigated the impact of CYP2C9 polymorphism on the reduction of Neuropsychiatric Inventory (NPI-12) scores following administration of IGC-AD1, comprising THC and melatonin, in AD patients.

Method: Thirteen Puerto Rican AD patients (mean age: 80.

Developing Topics.

Background: Alzheimer's disease (AD) affects millions of Americans, with potential future increases without breakthroughs in treatment. IGC-AD1, a novel formulation comprising of delta-9 tetrahydrocannabinol ("THC") and melatonin, is being studied in AD-associated agitation. THC is predominantly metabolized by cytochrome P450 and specifically by CYP2C9.

Developing Topics.

Background: Cannabis-based therapies have gained interest in treating different ailments in the elderly population, including severe or chronic pain, sleep disturbances, and more recently Alzheimer's Disease. This raises the importance of understanding the influence of age on the pharmacokinetics ("PK") of delta-9 tetrahydrocannabinol ("THC"). IGC-AD1 comprises THC at a low concentration and melatonin.

Developing Topics.

Background: IGC-AD1 comprises of Tetrahydrocannabinol ("THC") and melatonin. The two active pharmaceuticals are known for their neuroprotective properties. In this analysis we studied multiple dosing of IGC-AD1 in Alzheimer's ("AD") populations vulnerable to hepatic complications.

Consumer attitudes towards animal welfare and their willingness to pay.

The interest of European consumers towards animal welfare can be influenced by several variables, both related to the consumers themselves and to the different countries of the EU. In order to assess animal welfare at farm level, it is essential to develop animal-based measures in accordance with the animals' actual welfare state in terms of their behaviour, health and physiology. The search for valid and reliable indicators is a key objective of several research programs especially for assessing welfare at farm level and the tools may include surveys addressed to farmers.

Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo.

Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems.

Role of lipid rafts/caveolae in the anticancer effect of endocannabinoids.

The endocannabinoid system comprises the cannabinoid receptors type 1 (CB1) and type 2 (CB2), their endogenous ligands (endocannabinoids) and the whole apparatus appointed of their synthesis and degradation. Recent studies investigated the possibility that drugs targeting the endocannabinoid system might be used to retard or block cancer growth. CB1, CB2 and metabolic enzymes of endocannabinoids, function in the context of lipid rafts, specialized membrane microdomains enriched in cholesterol, sphingolipids and glycosphingolipids which may be important in modulating signal transduction.

Rimonabant inhibits human colon cancer cell growth and reduces the formation of precancerous lesions in the mouse colon.

The selective CB1 receptor antagonist rimonabant (SR141716) was shown to perform a number of biological effects in several pathological conditions. Emerging findings demonstrate that rimonabant exerts antitumor action in thyroid tumors and breast cancer cells. In our study, human colorectal cancer cells (DLD-1, CaCo-2 and SW620) were treated with rimonabant and analyzed for markers of cell proliferation, cell viability and cell cycle progression.

Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents.

Cannabinoids (the active components of Cannabis sativa) and their derivatives have received renewed interest in recent years due to their diverse pharmacological activities. In particular, cannabinoids offer potential applications as anti-tumour drugs, based on the ability of some members of this class of compounds to limit cell proliferation and to induce tumour-selective cell death. Although synthetic cannabinoids may have pro-tumour effects in vivo due to their immunosuppressive properties, predominantly inhibitory effects on tumour growth and migration, angiogenesis, metastasis, and also inflammation have been described.

Rimonabant: just an antiobesity drug? Current evidence on its pleiotropic effects.

The advent of the highly selective cannabinoid receptor (CB1) antagonist, rimonabant (SR141716; Acomplia) can revolutionize the ability of the clinicians to manage obesity. Large-scale clinical trials have demonstrated that rimonabant therapy can reduce obesity. Although, the precise mechanisms of action of rimonabant have to be further dissected, it is emerging, from both preclinical and clinical research, that not only is rimonabant an antiobesity drug, but also its pleiotropic functions affect a broad range of diseases, from obesity-related comorbidities to drug dependence and cancer.

Anandamide inhibits adhesion and migration of breast cancer cells.

The endocannabinoid system regulates cell proliferation in human breast cancer cells. We reasoned that stimulation of cannabinoid CB1 receptors could induce a non-invasive phenotype in breast metastatic cells. In a model of metastatic spreading in vivo, the metabolically stable anandamide analogue, 2-methyl-2'-F-anandamide (Met-F-AEA), significantly reduced the number and dimension of metastatic nodes, this effect being antagonized by the selective CB1 antagonist SR141716A.

Plasma membrane and lysosomal localization of CB1 cannabinoid receptor are dependent on lipid rafts and regulated by anandamide in human breast cancer cells.

In this report we show, by confocal analysis of indirect immunofluorescence, that the type-1 cannabinoid receptor (CB1R), which belongs to the family of G-protein-coupled receptors, is expressed on the plasma membrane in human breast cancer MDA-MB-231 cells. However, a substantial proportion of the receptor is present in lysosomes. We found that CB1R is associated with cholesterol- and sphyngolipid-enriched membrane domains (rafts).

Arvanil inhibits T lymphocyte activation and ameliorates autoimmune encephalomyelitis.

This study examined the immunomodulatory effect of arvanil, a synthetic capsaicin-anandamide hybrid. Arvanil inhibits lymphocyte proliferation and IFN-gamma production. The phenotype of activated CD4+T cells treated with arvanil shows a down-regulation of T cell activation markers such as CD25, HLA-DR and CD134/OX40.

Aldosterone synthase gene (CYP11B2) C-344T polymorphism, plasma aldosterone, renin activity and blood pressure in a multi-ethnic population.

Background: The aldosterone synthase gene (CYP1B2) locus is a candidate region involved in the development of hypertension.

Objective: To study the relationship between the C-344T CYP1B2 polymorphism, plasma aldosterone, renin activity and blood pressure in a multi-ethnic population.

Design: Population-based, cross-sectional study of 1313 middle-aged men and women (456 white, 441 of African origin and 416 South Asian).