Cannabis points to the synaptic pathology of mental disorders: how aberrant synaptic components disrupt the highest psychological functions
.

Cannabis can elicit an acute psychotic reaction, and its long-term use is a risk factor for schizophrenia. The main active psychoactive ingredient ∆9-tetrahydrocannabinol (Δ9-THC) activates cannabinoid 1 (CB1) receptors, which are localized to the terminals of glutamate and GABA neurons in the brain. The endogenous cannabinoids are involved in information processing and plasticity at synapses in the hippocampus, basal ganglia, and cerebral cortex. Exogenously applied CB1 receptor agonists disrupt neuronal dynamics and synaptic plasticity, resulting in cognitive deficits and impairment of the highest psychological functions. Various other pro-psychotic drugs, such as ketamine and methamphetamine, exert their effects in the same microdomain of synaptic spines as Δ9-THC. Additionally, many of the most robust findings in psychiatric genetics include components that localize to dendritic spines and have important roles in information processing and plasticity.
.

La cannabis puede provocar una reacción psicótica aguda y su empleo a largo plazo es un factor de riesgo para esquizofrenia. El principal componente psicoactivo ∆9-tetrahidrocannabinol (Δ9-THC) estimula los receptores cannabinoides CB1, que se localizan en las terminales de las neuronas de glutamato y de GABA cerebrales. Los cannabinoides endógenos participan en el procesamiento de la información y la plasticidad en las sinapsis del hipocampo, los ganglios basales y la corteza cerebral. Los agonistas de CB1 administrados de forma exógena interrumpen la dinámica neuronal y la plasticidad sináptica, lo que se traduce en déficits cognitivos y deterioro de las funciones psicológicas más altas. Varias otras drogas propsicóticas, como la ketamina y la metanfetamina, ejercen sus efectos en el mismo microdominio de espinas sinápticas que el Δ9-THC. Además, muchos de los hallazgos más consistentes en genética psiquiátrica incluyen componentes que se localizan en las espinas dendríticas y tienen funciones importantes en el procesamiento y la plasticidad de la información.

Le cannabis peut provoquer une réaction psychotique aiguë et sa consommation à long terme est un facteur de risque de schizophrénie. Le ∆9-tétrahydrocannabinol (Δ9-THC), principal ingrédient psychoactif, active les récepteurs cannabinoïdes CB1 situés aux extrémités des neurones glutamatergiques et GABAergiques dans le cerveau. Les cannabinoïdes endogènes participent au traitement de l'information et à la plasticité des synapses dans l'hippocampe, les ganglions de la base et le cortex cérébral. Les agonistes CB1 exogènes perturbent la dynamique neuronale et la plasticité synaptique, entraînant des déficits cognitifs et une altération des fonctions psychologiques les plus hautes. D'autres drogues propsychotiques, telles la kétamine et la méthamphétamine, agissent dans le même micro-domaine des épines synaptiques que le Δ9-THC. De plus, de nombreuses recherches en génétique psychiatrique ont mis en évidence des composés qui jouent un rôle important dans le traitement de l'information et la plasticité en se fixant sur les épines dendritiques.

Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial.

Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design. METHODS: We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000361-36). FINDINGS: Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by -94·21 ng/mL (95% interval estimate -161·83 to -35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by -72·02 ng/mL (-135·47 to -19·52) and increased abstinence from cannabis by 0·27 days per week (-0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment. INTERPRETATION: In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use. FUNDING: Medical Research Council.

Synthetic cannabinoid use in psychiatric patients and relationship to hospitalisation: A retrospective electronic case register study.

INTRODUCTION AND OBJECTIVES: Cannabis use has been associated with psychosis and with poor outcome in patients with mental illness. Synthetic cannabinoids (SCs) have been suggested to pose an even greater risk to mental health, but the effect on clinical outcome has not been directly measured. In this study, we aimed to investigate the demographics and hospitalisation of psychiatric patients who were SC users. METHODS: We searched the Biomedical Research Centre Clinical Record Interactive Search register for SC users and age- and sex-matched SC non-users who had been psychiatric patients under the South London and Maudsley NHS Trust. We recorded diagnosis, homelessness, cannabis use and the total number of days admitted as an inpatient to secondary and tertiary mental-health services. RESULTS: We identified 635 SC users and 635 age- and sex-matched SC non-users. SC users were significantly more likely to be homeless (χ2=138.0; p<0.0001) and to use cannabis (χ2=257.3; p<0.0001) than SC non-users. SC users had significantly more inpatient days after their first recorded use of SCs than controls (M (SD)=85.5 (199.7) vs. 25.4 (92.32); p<0.0001). Post hoc tests revealed that SC non-users who used cannabis had fewer inpatient days than SC users (p<0.0001), and that non-users of both SC and cannabis had fewer inpatient days than SC non-using cannabis users (p=0.02). CONCLUSIONS: SC use may lead to an increase in the number of days spent in hospital in patients with psychiatric illness. This highlights the need for clinicians to ask specifically about SC use.

Trace metal biomonitoring in the east Gippsland Lakes estuary using the barnacle Amphibalanus variegatus and mussel Mytilus edulis.

The Gippsland Lakes estuary, a Ramsar listed wetland, in Victoria, Australia, is an area of potential concern for metal pollution due to influxes of human population and associated anthropogenic activities. A biomonitoring exercise was undertaken where the concentrations of 9 metals (Cr, Fe, Cu, Zn, As, Se, Ag, Cd and Hg) were analysed in the soft tissue of two common sessile invertebrates: the mussel Mytilus edulis and the barnacle Amphibalanus variegatus from 6 locations on two different occasions throughout the Gippsland Lakes estuary. A salinity gradient exists in the Lakes, from seawater at Lakes Entrance in the east, decreasing down to < 10 PSU in the west at Lake Wellington during times of rainfall, which is a major factor governing the growth and distribution of both species. Dissolved metal levels in general were low; however, Cu at most sites exceeded the 90% trigger values, while all Zn concentrations exceeded the lowest 80% trigger values of the ANZECC marine water quality guidelines for environmental health. Elevated levels of Cu and Zn were found particularly in barnacles at some sites with environmental contamination due to leaching from anti fouling paints and sacrificial zinc anodes. Elevated levels of Ag and Cd were found in mussels at the Hollands Landing site, which is immediately adjacent to a boat ramp, and Cd and Ag at this site are suspected to originate from inland anthropogenic sources. Concentrations of As in M. edulis across all 6 sites in both sampling periods had mean wet weight As concentrations exceeding the maximum level stated in the FSANZ guidelines. A. variegatus contained elevated levels of Hg especially at the North Arm site with a maximum of 13.6 µg Hg/g dry wt., while A. variegatus also showed temporal changes in Hg concentrations across sites. The maximum Hg concentration found in Mytilus edulis was 1.49 µg Hg/g dry wt. at the Hollands Landing site. Previous contaminant studies of biota in the Lakes have targeted sampling of singular predatory or migratory species, such as Black Bream (Acanthopagrus butcheri) and the Burrunan dolphin (Tursiops australis). This is the first biomonitoring study conducted on sessile organisms to assess metal contamination in the system.

Influence of Human Activities on Broad-Scale Estuarine-Marine Habitats Using Omics-Based Approaches Applied to Marine Sediments.

Rapid urban expansion and increased human activities have led to the progressive deterioration of many marine ecosystems. The diverse microbial communities that inhabit these ecosystems are believed to influence large-scale geochemical processes and, as such, analyzing their composition and functional metabolism can be a means to assessing an ecosystem's resilience to physical and chemical perturbations, or at the very least provide baseline information and insight into future research needs. Here we show the utilization of organic and inorganic contaminant screening coupled with metabolomics and bacterial 16S rRNA gene sequencing to assess the microbial community structure of marine sediments and their functional metabolic output. The sediments collected from Moreton Bay (Queensland, Australia) contained low levels of organic and inorganic contaminants, typically below guideline levels. The sequencing dataset suggest that sulfur and nitrite reduction, dehalogenation, ammonia oxidation, and xylan degradation were the major metabolic functions. The community metabolites suggest a level of functional homogeneity down the 40-cm core depth sampled, with sediment habitat identified as a significant driver for metabolic differences. The communities present in river and sandy channel samples were found to be the most active, with the river habitats likely to be dominated by photoheterotrophs that utilized carbohydrates, fatty acids and alcohols as well as reduce nitrates to release atmospheric nitrogen and oxidize sulfur. Bioturbated mud habitats showed overlapping faunal activity between riverine and sandy ecosystems. Nitrogen-fixing bacteria and lignin-degrading bacteria were most abundant in the sandy channel and bioturbated mud, respectively. The use of omics-based approaches provide greater insight into the functional metabolism of these impacted habitats, extending beyond discrete monitoring to encompassing whole community profiling that represents true phenotypical outputs. Ongoing omics-based monitoring that focuses on more targeted pathway analyses is recommended in order to quantify the flux changes within these systems and establish variations from these baseline measurements.

Antimicrobial Activity of Agastache Honey and Characterization of Its Bioactive Compounds in Comparison With Important Commercial Honeys.

There is an urgent need for new effective antimicrobial agents since acquired resistance of bacteria to currently available agents is increasing. The antimicrobial activity of Mono-floral Agastache honey produced from Australian grown Agastache rugosa was compared with the activity of commercially available honeys derived from Leptospermum species and with Jarrah honey for activity against clinical and non-clinical strains of Staphylococcus aureus (methicillin-susceptible and methicillin-resistant strains), Pseudomonas aeruginosa, and Escherichia coli. The minimum inhibitory concentration (MIC) for Agastache honey was in the range of 6-25% (w/v) for all species examined. The MICs for Leptospermum honeys were generally similar to those of Agastache honey, but MICs were higher for Super manuka and Jarrah honeys and lower for Tea tree honey. Staphylococci were more susceptible to all honeys than Pseudomonas aeruginosa and Escherichia coli. Pretreatment of honey with catalase increased the bacterial growth at MIC of Tea tree honey (35%), Super Manuka (15%), Jarrah honeys (12%), and Agastache honey (10%), indicating variable contributions of hydrogen peroxide to antimicrobial activity. Manuka and Jelly bush honeys retained their antimicrobial activity in the presence of catalase, indicating the presence of other antimicrobial compounds in the honey. An LC-MS/MS method was developed and used to identify possible antimicrobial phenolic compounds in Agastache honey and flowers, and five commercial honeys. The chemical markers characteristic of Agastache honey and honeys of Leptospermum origin were phenyllactic acid and methyl syringate. Overall, the bioactive compounds with antimicrobial and antioxidant activity in Agastache honey suggested a possible use for topical application and in wound care.

Influence of bioaugmentation and biostimulation on PAH degradation in aged contaminated soils: Response and dynamics of the bacterial community.

Polycyclic aromatic hydrocarbons (PAHs) represent a group of hazardous compounds that are ubiquitous and persistent. The main aim of this study was to investigate the degradation of PAHs in chronically contaminated, aged and weathered soils obtained from a former gas plant of Australia. Biostimulation and bioaugmentation using individual isolates (Rhodococcus sp. (NH2), Achromobacter sp. (NH13), Oerskovia paurometabola (NH11), Pantoea sp. (NH15), Sejongia sp. (NH20), Microbacterium maritypicum (NH30) and Arthrobacter equi (NH21)) and a consortium of these isolates were tested during mesocosm studies. A significant reduction (99%) in PAH concentration was observed in all the treatments. In terms of the abundance of PAH-degrading genes and microbial community structure during PAH degradation, qPCR results revealed that Gram-positive bacteria were dominant over other bacterial communities in all the treatments. 16S sequencing results revealed that the inoculated organisms did not establish themselves during the treatment. However, substantial bacterial community changes during the treatments were observed, suggesting that the natural community exhibited sufficient resilience and diversity to enable an active, but changing degrading community at all stages of the degradation process. Consequently, biostimulation is proposed as the best strategy to remediate PAHs in aged, weathered and chronically contaminated soils.

First-generation versus second-generation long-acting injectable antipsychotic drugs and time to relapse.

BACKGROUND: The development of long-acting injectable formulations (LAIs) of second-generation antipsychotic drugs (SGAs) has been suggested as having advantage over first-generation antipsychotic (FGA) LAIs. In this study, we investigated the hypothesis that there was a longer time to relapse in patients with schizophrenia started on SGA LAI versus FGA LAI. METHODS: Patients with a diagnosis of schizophrenia or schizoaffective disorder who were started on an SGA LAI while on an inpatient ward were identified through searching of the anonymised historical medical records at the South London and Maudsley NHS Foundation Trust. Patients starting FGA LAIs matched for diagnosis, age and date of hospital admission were identified. Time to readmission, discontinuation of LAI or death were identified. Kaplan-Meier plots were generated for each group, and the difference between groups analysed using log-rank methods. RESULTS: There were 157 patients identified in each group. There was no difference in time to readmission, medication discontinuation or death in patients on SGA LAI versus FGA LAI. CONCLUSIONS: We found no evidence of advantage in terms of maintaining response in SGA LAI versus FGA LAI. Prescriber choice should be guided by other factors such as side-effect profile, patient acceptability and price.

Spicing it up - synthetic cannabinoid receptor agonists and psychosis - a systematic review.

Synthetic cannabinoid receptor agonists (SCRAs) are suggested to have increased potential to induce psychosis compared to natural cannabis (NC). In this review we synthesise current knowledge about the association of SCRA use with psychotic symptoms. Following a literature search we identified 2 toxicology reports, 4 case-control studies, 3 cross-sectional studies and 15 case reports. In each of the case reports, we identified the presence or absence of symptoms based on the items of the Postitive and Negative Syndrome Scele (PANSS). The toxicology reports highlighted the main presenting features as being toxic psychosis and delirium (40%), agitation (10%) and hallucinations (4-7%). The median age was 25 years, and around 80% cases were male. Cross-sectional studies reported that SCRA use was present in approximately 10-13% patients presenting to acute psychiatric services, and was often the cause of their presentation, and that psychotic symptoms were present in 15% patients attending emergency departments following SCRA use. Case-control studies reported that SCRA use was significantly associated with psychotic symptoms and that SCRA users had higher levels of positive psychotic symptoms than NC users. The case reports supported the association of SCRA use with a wide range of positive and negative psychotic symptoms as well as with self-harm, agitation and aggressive behaviour. SCRA use is relatively prevalent in patients with psychosis and may lead to psychotic symptoms in individuals with no past psychiatric history. Further work is required to understand the long term risks of SCRA use and optimal management strategies.

Spatial Distribution of Novel and Legacy Brominated Flame Retardants in Soils Surrounding Two Australian Electronic Waste Recycling Facilities.

Informal recycling of electronic waste (e-waste) has been shown to cause significant brominated flame retardant (BFR) contamination of surrounding soils in a number of Asian and West African countries. However, to the authors' knowledge, there have been no published studies demonstrating polybrominated diphenyl ether (PBDE) and novel brominated flame retardant (NBFR) soil contamination from regulated "formal" e-waste processing facilities in developed countries. This study reports on PBDEs (-28, -47, -99, -100, -153, -154, -183, and -209) and NBFRs (PBT, PBEB, HBB, EH-TBB, BTBPE and DBDPE) in 36 soil samples surrounding two Australian e-waste recycling plants and a further eight reference soils. Overall ∑PBDE concentrations ranged 0.10-98 000 ng/g dw (median; 92 ng/g dw) and ∑NBFRs ranged ND-37 000 ng/g dw (median 2.0 ng/g dw). Concentrations in soils were found to be significantly negatively associated with distance from one of the e-waste facilities for ∑penta-BDEs, BDE-183, BDE-209, and ∑NBFR compound groups. ANOVA tests further illustrated the potential for e-waste recycling to significantly elevate concentrations of some BFRs in soils over distances up to 900 m compared to references sites. This study provides the first evidence of soil contamination with PBDEs and NBFRs originating from formal e-waste recycling facilities in Australia, which may have implications for e-waste recycling practices throughout the world.

Psilocybin and MDMA reduce costly punishment in the Ultimatum Game.

Disruptions in social decision-making are becoming evident in many psychiatric conditions. These are studied using paradigms investigating the psychological mechanisms underlying interpersonal interactions, such as the Ultimatum Game (UG). Rejection behaviour in the UG represents altruistic punishment - the costly punishment of norm violators - but the mechanisms underlying it require clarification. To investigate the psychopharmacology of UG behaviour, we carried out two studies with healthy participants, employing serotonergic agonists: psilocybin (open-label, within-participant design, N = 19) and 3,4-methylenedioxymethamphetamine (MDMA; placebo-controlled, double-blind, crossover design, N = 20). We found that both MDMA and psilocybin reduced rejection of unfair offers (odds ratio: 0.57 and 0.42, respectively). The reduction in rejection rate following MDMA was associated with increased prosociality (R2 = 0.26, p = 0.025). In the MDMA study, we investigated third-party decision-making and proposer behaviour. MDMA did not reduce rejection in the third-party condition, but produced an increase in the amount offered to others (Cohen's d = 0.82). We argue that these compounds altered participants' conceptualisation of 'social reward', placing more emphasis on the direct relationship with interacting partners. With these compounds showing efficacy in drug-assisted psychotherapy, these studies are an important step in the further characterisation of their psychological effects.

The antipsychotic landscape: dopamine and beyond.

Until recently, the actions of antipsychotic and pro-psychotic drugs have largely been evaluated in the framework of neuronal doctrine - namely, that neurons communicate by releasing transmitters, and that psychiatric disorders are caused by neurotransmitter imbalances. Moreover, the majority of studies have focused on single transmitter systems - neglecting the fact that in the nervous system, different transmitter systems work in concert and impact on not only their immediate receptors but also downstream pathways that shape structural plasticity. In this review, we discuss the history of understanding the antipsychotic and pro-psychotic actions of drugs, recent developments and future perspectives.

Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects.

BACKGROUND: Aberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-D-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system. OBJECTIVE: To test the attenuation of the ketamine-induced BOLD signal by pretreatment with either a metabotropic glutamate receptor (mGluR) 2/3 or a mGluR2 agonist in healthy volunteers METHODS: We used a ketamine challenge pharmacological magnetic resonance imaging (phMRI) paradigm to assess the modulatory effects of single acute doses of LY2140023 (pomaglumetad methionil), the methionine prodrug of the mGluR2/3 agonist LY404039 (10, 40, and 160 mg; N = 16 subjects) and of LY2979165, and the alanine prodrug of the selective orthosteric mGluR2 agonist 2812223 (20 and 60 mg; N = 16 subjects). RESULTS: A reduction in the ketamine-evoked BOLD phMRI signal relative to placebo was observed at the highest doses tested of both LY2140023 and LY2979165. A relationship was observed between reduction of the BOLD signal and increasing plasma levels of 2812223 in the LY2979165 cohort. CONCLUSIONS: These results identify pharmacologically active doses of the group II mGluR agonist prodrugs LY2140023 and LY2979165 in humans. They also extend the classes of compounds that have been experimentally shown to reverse the ketamine-evoked phMRI signal in humans, further supporting the use of this method as a neuroimaging biomarker for assessing functional effects.

Concentrations of legacy and novel brominated flame retardants in indoor dust in Melbourne, Australia: An assessment of human exposure.

Polybrominated diphenyl ethers (PBDEs) and novel brominated flame retardants (NBFR) have been used in a range of polymers to inhibit the spread of fires but also have a propensity to migrate out of consumer materials and contaminate indoor dust. In this study, a total of 57 dust samples were collected from 12 homes, eight offices and eight vehicles in Melbourne, Australia and analysed for eight PBDEs (-28, -47, -99, -100, -153, -154, -183 and -209) and seven NBFRs (PBT, PBEB, HBB, EH-TBB, BEH-TEBP, BTBPE and DBDPE) to determine human exposure risks from dust ingestion. Samples were analysed using selective pressurized liquid extraction (S-PLE) and gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). Legacy and replacement flame retardants were detected in all samples with overall ∑PBDE concentrations ranging from 120 to 1700,000 ng/g (median 2100 ng/g) and ∑NBFRs ranging from 1.1 to 10,000 ng/g (median 1800 ng/g). BDE-209 and DBDPE were the dominant compounds in dust samples, followed by congeners associated with commercial Penta-BDE formulations (-47, -99, -100, -153 and -154) and then EH-TBB of the FireMaster 550 and BZ-54 products. ∑Penta-BDE concentrations were elevated in office samples compared with homes and vehicles, while EH-TBB and BDE-209 measured higher concentrations in vehicles compared with their respective levels in homes and offices. Risk assessment estimates revealed the majority of exposure to occur in the home for both adults and toddlers in the City of Melbourne. Generally, body weight adjusted exposure to PBDEs and NBFRs was predicted to be 1 to 2 orders of magnitude higher for toddlers than adults. Estimated rates of BDE-47, -99, -153 and -209 ingestion were each 2 orders of magnitude or more below the USEPA's prescribed oral reference dose values (RfDs) for typical exposure scenarios. However, exposure rates for BDE-47 and -99 reached as high as 52 and 95% of RfDs, respectively, for adults and 4.4 and 7.4%, respectively, for toddlers in high exposure scenarios. This study provides the first wide-ranging survey of NBFRs in indoor dust from homes, offices and vehicles in Australia and offers further evidence of human exposure to legacy and novel brominated flame retardants via dust ingestion.

Detection of Foodborne Pathogens Using Proteomics and Metabolomics-Based Approaches.

Considering the short shelf-life of certain food products such as red meat, there is a need for rapid and cost-effective methods for pathogen detection. Routine pathogen testing in food laboratories mostly relies on conventional microbiological methods which involve the use of multiple selective culture media and long incubation periods, often taking up to 7 days for confirmed identifications. The current study investigated the application of omics-based approaches, proteomics using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) and metabolomics using gas chromatography-mass spectrometry (GC-MS), for detection of three red meat pathogens - Listeria monocytogenes, Salmonella enterica and Escherichia coli O157:H7. Species-level identification was achieved within 18 h for S. enterica and E. coli O157:H7 and 30 h for L. monocytogenes using MALDI-ToF MS analysis. For the metabolomics approach, metabolites were extracted directly from selective enrichment broth samples containing spiked meat samples (obviating the need for culturing on solid media) and data obtained using GC-MS were analyzed using chemometric methods. Putative biomarkers relating to L. monocytogenes, S. enterica and E. coli O157:H7 were observed within 24, 18, and 12 h, respectively, of inoculating meat samples. Many of the identified metabolites were sugars, fatty acids, amino acids, nucleosides and organic acids. Secondary metabolites such as cadaverine, hydroxymelatonin and 3,4-dihydroxymadelic acid were also observed. The results obtained in this study will assist in the future development of rapid diagnostic tests for these important foodborne pathogens.

The effects of cannabidiol on persecutory ideation and anxiety in a high trait paranoid group.

BACKGROUND: Previous studies have suggested that cannabidiol has anxiolytic and antipsychotic properties, raising hopes that cannabidiol will translate to the psychiatric clinic. Cannabidiol may be particularly useful for anxiety and paranoia in those at-risk of major mental illness. METHODS: Immersion in a controlled 3D virtual-reality scenario was used to assay persecutory ideation and anxiety in a sample of non-clinical volunteers ( n=32) pre-selected for high paranoid traits. Participants were randomised to receive oral cannabidiol (600 mg) or placebo 130 min prior to entering virtual-reality. Well-validated rating scales were used to assay persecutory thinking and anxiety. Salivary cortisol concentration, heart rate and blood pressure were measured over the course of the experimental session. RESULTS: Immersion in the virtual-reality session elicited anxiety as indexed by the Beck's anxiety inventory ( p<0.005), and increased cortisol concentration ( p=0.05), heart rate ( p<0.05) and systolic blood pressure ( p<0.05). However, cannabidiol had no impact upon any of these effects, except for a strong trend to increase anxiety ( p=0.09). Cannabidiol had no effect on persecutory ideation as assayed by the Community Assessment of Psychic Experiences questionnaire or the State Social Paranoia Scale. CONCLUSIONS: In contrast to previous studies, there was no evidence of any benefits of cannabidiol on anxiety or persecutory ideation in healthy volunteers with high trait paranoia. However, a larger sample will be required for a definitive study.

Chemometric Analysis of Lavender Essential Oils Using Targeted and Untargeted GC-MS Acquired Data for the Rapid Identification and Characterization of Oil Quality.

Standard raw material test methods such as the ISO Standard 11024 are focused on the identification of lavender oil and not the actual class/quality of the oil. However, the quality of the oil has a significant effect on its price at market. As such, there is a need for raw material tests to identify not only the type of oil but its quality. This paper describes two approaches to rapidly identifying and classifying lavender oil. First, the ISO Standard 11024 test method was evaluated in order to determine its suitability to assess lavender oil quality but due to its targeted and simplistic approach, it has the potential to miss classify oil quality. Second, utilizing the data generated by the ISO Standard 11024 test methodology, an untargeted chemometric predicative model was developed in order to rapidly assess and characterize lavender oils (Lavandulaangustifolia L.) for geographical/environmental adulteration that impact quality. Of the 170 compounds identified as per the ISO Standard 11024 test method utilizing GC-MS analyses, 15 unique compounds that greatly differentiate between the two classes of lavender were identified. Using these 15 compounds, a predicative multivariate chemometric model was developed that enabled lavender oil samples to be reliably differentiated based on quality. A misclassification analysis was performed and it was found that the predictions were sound (100% matching rate). Such an approach will enable producers, distributers, suppliers and manufactures to rapidly screen lavender essential oil. The authors concede that the validation and implementation of such an approach is more difficult than a conventional chromatographic assay. However, the rapid, reliable and less problematic screening is vastly superior and easily justifies any early implementation validation difficulties and costs.

A New Method for the Fast Analysis of Trihalomethanes in Tap and Recycled Waters Using Headspace Gas Chromatography with Micro-Electron Capture Detection.

Chemical disinfection of water supplies brings significant public health benefits by reducing microbial contamination. The process can however, result in the formation of toxic compounds through interactions between disinfectants and organic material in the source water. These new compounds are termed disinfection by-products (DBPs). The most common are the trihalomethanes (THMs) such as trichloromethane (chloroform), dichlorobromomethane, chlorodibromomethane and tribromomethane (bromoform); these are commonly reported as a single value for total trihalomethanes (TTHMs). Analysis of DBPs is commonly performed via time- and solvent-intensive sample preparation techniques such as liquid-liquid and solid phase extraction. In this study, a method using headspace gas chromatography with micro-electron capture detection was developed and applied for the analysis of THMs in drinking and recycled waters from across Melbourne (Victoria, Australia). The method allowed almost complete removal of the sample preparation step whilst maintaining trace level detection limits (>1 ppb). All drinking water samples had TTHM concentrations below the Australian regulatory limit of 250 µg/L but some were above the U.S. EPA limit of 60 µg/L. The highest TTHM concentration was 67.2 µg/L and lowest 22.9 µg/L. For recycled water, samples taken directly from treatment plants held significantly higher concentrations (153.2 µg/L TTHM) compared to samples from final use locations (4.9-9.3 µg/L).