Two cases of "cannabis acute psychosis" following the administration of oral cannabis

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur

Antioxidant potential of bitter cumin (Centratherum anthelminticum (L.) Kuntze) seeds in in vitro models

<p>Abstract</p> <p>Background</p> <p>Bitter cumin (<it>Centratherum anthelminticum </it>(L.) Kuntze), is a medicinally important plant. Earlier, we have reported phenolic compounds, antioxidant, and anti-hyperglycemic, antimicrobial activity of bitter cumin. In this study we have further characterized the antioxidative activity of bitter cumin extracts in various in vitro models.</p> <p>Methods</p> <p>Bitter cumin seeds were extracted with a combination of acetone, methanol and water. The antioxidant activity of bitter cumin extracts were characterized in various <it>in vitro </it>model systems such as DPPH radical, ABTS radical scavenging, reducing power, oxidation of liposomes and oxidative damage to DNA.</p> <p>Results</p> <p>The phenolic extracts of bitter cumin at microgram concentration showed significant scavenging of DPPH and ABTS radicals, reduced phosphomolybdenum (Mo(VI) to Mo(V)), ferricyanide Fe(III) to Fe(II), inhibited liposomes oxidation and hydroxyl radical induced damage to prokaryotic genomic DNA. The results showed a direct correlation between phenolic acid content and antioxidant activity.</p> <p>Conclusion</p> <p>Bitter cumin is a good source of natural antioxidants.</p

A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions

Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece

Although several dietary compounds are hypothesized to have anticarcinogenic properties, the role ofpecific micronutrients in the development of breast cancer remains unclear. To address this issue, we assessed intake of retinol, β-carotene, vitamin C and vitamin E in relation to breast cancer risk in a case–control study in Greece. Eight hundrednd twenty women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collectedhrough a 115-item semiquantitative food frequency questionnaire. Data were modelled by logistic regression, with adjustment forotal energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients. Amongost-menopausal women, there was no association between any of the micronutrients evaluated and risk of breast cancer. Amongremenopausal women, β-carotene, vitamin C and vitamin E were each inversely associated with breast cancer risk, but afterutual adjustment among the three nutrients only β-carotene remained significant; the odds ratio (OR) for a one-quintilencrease in β-carotene intake was 0.84 (95% confidence interval 0.73–0.97). The inverse association observed with β-carotene intake, however, is slightly weaker than the association previously observed with vegetable intake in these data,aising the possibility that the observed β-carotene effect is accounted for by another component of vegetables. ©1999 Cancer Research Campaig

Database analysis of children and adolescents with Bipolar Disorder consuming a micronutrient formula

<p>Abstract</p> <p>Background</p> <p>Eleven previous reports have shown potential benefit of a 36-ingredient micronutrient formula (known as EMPowerplus) for the treatment of psychiatric symptoms. The current study asked whether children (7-18 years) with pediatric bipolar disorder (PBD) benefited from this same micronutrient formula; the impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on their response was also evaluated.</p> <p>Methods</p> <p>Data were available from an existing database for 120 children whose parents reported a diagnosis of PBD; 79% were taking psychiatric medications that are used to treat mood disorders; 24% were also reported as ADHD. Using Last Observation Carried Forward (LOCF), data were analyzed from 3 to 6 months of micronutrient use.</p> <p>Results</p> <p>At LOCF, mean symptom severity of bipolar symptoms was 46% lower than baseline (effect size (ES) = 0.78) (<it>p </it>< 0.001). In terms of responder status, 46% experienced >50% improvement at LOCF, with 38% still taking psychiatric medication (52% drop from baseline) but at much lower levels (74% reduction in number of medications being used from baseline). The results were similar for those with both ADHD and PBD: a 43% decline in PBD symptoms (ES = 0.72) and 40% in ADHD symptoms (ES = 0.62). An alternative sample of children with just ADHD symptoms (n = 41) showed a 47% reduction in symptoms from baseline to LOCF (ES = 1.04). The duration of reductions in symptom severity suggests that benefits were not attributable to placebo/expectancy effects. Similar findings were found for younger and older children and for both sexes.</p> <p>Conclusions</p> <p>The data are limited by the open label nature of the study, the lack of a control group, and the inherent self-selection bias. While these data cannot establish efficacy, the results are consistent with a growing body of research suggesting that micronutrients appear to have therapeutic benefit for children with PBD with or without ADHD in the absence of significant side effects and may allow for a reduction in psychiatric medications while improving symptoms. The consistent reporting of positive changes across multiple sites and countries are substantial enough to warrant a call for randomized clinical trials using micronutrients.</p

Disruption of Retinoic Acid Receptor Alpha Reveals the Growth Promoter Face of Retinoic Acid

Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity.We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling.In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA

Acute reduction of serum 8-iso-PGF2-alpha and advanced oxidation protein products in vivo by a polyphenol-rich beverage; a pilot clinical study with phytochemical and in vitro antioxidant characterization

<p>Abstract</p> <p>Background</p> <p>Measuring the effects of the acute intake of natural products on human biomarker concentrations, such as those related to oxidation and inflammation, can be an advantageous strategy for early clinical research on an ingredient or product.</p> <p>Methods</p> <p>31 total healthy subjects were randomized in a double-blinded, placebo-controlled, acute pilot study with post-hoc subgroup analysis on 20 of the subjects. The study examined the effects of a single dose of a polyphenol-rich beverage (PRB), commercially marketed as "SoZo^®", on serum anti-inflammatory and antioxidant markers. In addition, phytochemical analyses of PRB, and <it>in vitro </it>antioxidant capacity were also performed.</p> <p>Results</p> <p>At 1 hour post-intake, serum values for 8-iso-PGF2-alpha and advanced oxidation protein products decreased significantly by 40% and 39%, respectively. Additionally, there was a trend toward decreased C-reactive protein, and increased nitric oxide levels. Both placebo and PRB treatment resulted in statistically significant increases in hydroxyl radical antioxidant capacity (HORAC) compared to baseline; PRB showed a higher percent change (55-75% versus 23-74% in placebo group), but the two groups did not differ significantly from each other.</p> <p>Conclusions</p> <p>PRB produced statistically significant changes in several blood biomarkers related to antioxidant/anti-inflammatory effects. Future studies are justified to verify results and test for cumulative effects of repeated intakes of PRB. The study demonstrates the potential utility of acute biomarker measurements for evaluating antioxidant/anti-inflammatory effects of natural products.</p

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

Human-Mediated Emergence as a Weed and Invasive Radiation in the Wild of the CD Genome Allotetraploid Rice Species (Oryza, Poaceae) in the Neotropics

BACKGROUND: The genus Oryza is being used as a model in plant genomic studies although there are several issues still to be resolved regarding the spatio-temporal evolution of this ancient genus. Particularly contentious is whether undated transoceanic natural dispersal or recent human interference has been the principal agent determining its present distribution and differentiation. In this context, we studied the origin and distribution history of the allotetraploid CD rice genome. It is endemic to the Neotropics but the genus is thought to have originated in the Paleotropics, and there is relatively little genetic divergence between some orthologous sequences of the C genome component and their Old World counterparts. METHODOLOGY/PRINCIPAL FINDINGS: Because of its allotetraploidy, there are several potential pitfalls in trying to date the formation of the CD genome using molecular data and this could lead to erroneous estimates. Therefore, we rather chose to rely on historical evidence to determine whether or not the CD genome was present in the Neotropics before the arrival of Columbus. We searched early collections of herbarium specimens and studied the reports of explorers of the tropical Americas for references to rice. In spite of numerous collectors traveling inland and collecting Oryza, plants determined as CD genome species were not observed away from cultivated rice fields until 1869. Various arguments suggest that they only consisted of weedy forms until that time. CONCLUSIONS/SIGNIFICANCE: The spatio-temporal distribution of herbarium collections fits a simple biogeographical scenario for the emergence in cultivated rice fields followed by radiation in the wild of the CD genome in the Neotropics during the last four centuries. This probably occurred from species introduced to the Americas by humans and we found no evidence that the CD genome pre-existed in the Old World. We therefore propose a new evolutionary hypothesis for such a recent origin of the CD genome. Moreover, we exemplify how an historical approach can provide potentially important information and help to disentangle the timing of evolutionary events in the history of the Oryza genomes