‘Synthetic cannabis’: A dangerous misnomer

The term 'synthetic cannabis' has been widely used in public discourse to refer to a group of cannabinoid receptor agonists. In this paper we detail the characteristics of these drugs, and present the case that the term is a misnomer. We describe the pharmacodynamics of these drugs, their epidemiology, mechanisms of action, physiological effects and how these differ substantially from delta-9-tetrahydrocannabinol (THC). We argue that not only is the term a misnomer, but it is one with negative clinical and public health implications. Rather, the substances referred to as 'synthetic cannabis' in public discourse should instead be referred to consistently as synthetic cannabinoid receptor agonists (SCRAs), a drug class distinct from plant-derived cannabinoids. SCRAs have greater potency and efficacy, and psychostimulant-like properties. While such terminology may be used in the scientific community, it is not widely used amongst the media, general public, people who use these drugs or may potentially do so. A new terminology has the potential to reduce the confusion and harms that result from the misnomer ‘synthetic cannabis’. The constant evolution of this distinct drug class necessitates a range of distinct policy responses relating to terminology, harm reduction, epidemiology, treatment, and legal status

How Furiously Can Colourless Green Ideas Sleep? Sentence Acceptability in Context

We study the influence of context on sentence acceptability. First we compare the acceptability ratings of sentences judged in isolation, with a relevant context, and with an irrelevant context. Our results show that context induces a cognitive load for humans, which compresses the distribution of ratings. Moreover, in relevant contexts we observe a discourse coherence effect which uniformly raises acceptability. Next, we test unidirectional and bidirectional language models in their ability to predict acceptability ratings. The bidirectional models show very promising results, with the best model achieving a new state-of-the-art for unsupervised acceptability prediction. The two sets of experiments provide insights into the cognitive aspects of sentence processing and central issues in the computational modelling of text and discourse

Photocatalytic reactions of a nickel(II) annulene complex incorporated in polymeric structures

The photochemical reactions of the Ni(II) annulene complex, [NiII([5,7,12,14]-tetra methyl dibenzo[2,3- b:2,3-b,i][1,4,8,11]tetraaza[14]annulenate)], grafted into a poly(isobutylene-alt-maleate) backbone were investigated in aqueous media. The grafted Ni(II) complex becomes soluble in aqueous and organic solvents where the strands form aggregates with medium-dependent shapes. Irradiation of the polymer at 532 or 351 nm produce charge-separated macrocyclic pendants, CS, with a lifetime s 30 ns. CS reacts with electron donors and acceptors before it decays with a lifetime s 1 ms. In parallel to the decay of CS, an excited state-excited state annihilation process gives rise to luminescence whose spectrum spans wavelengths shorter than the wavelength of the irradiation, lex > 500 nm. Theoretical calculations were carried out with the aim of understanding the morphology and structures of strand aggregates, to confirm the nature of reaction products and to account for the spectroscopic and photochemical properties of the Ni(II) pendants. The endothermic reduction of CO2 to CO by S(IV) species was used as a test of the Ni(II) complex´s ability to photocatalyze the reaction. In the photoprocess, the Ni(II) complex fulfills the double role of antenna and catalyst.Fil: Estiu, G.. University Of Notre Dame-indiana; Estados UnidosFil: Ferraudi, G.. University Of Notre Dame-indiana; Estados UnidosFil: Lappin, A. G.. University Of Notre Dame-indiana; Estados UnidosFil: Ruiz, Gustavo Teodosio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Vericat, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Costamagna, J.. Universidad de Santiago de Chile; ChileFil: Villagrán, M.. Universidad de Santiago de Chile; Chil

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic

Microdosing and other phase 0 clinical trials: facilitating translation in Drug Development

Increasing costs of drug development and ethical concernsabout the risks of exposing humans and animals to novelchemical entities favor limited exposure clinical trials suchas microdosing and other phase 0 trials. An increasing bodyof research supports the validity of extrapolation from thelimited drug exposure of phase 0 approaches to the full,therapeutic exposure. An increasing number of applicationsand design options demonstrate the versatility and exibilitythese approaches offer to drug developers

Prevalence and Characteristics Associated with Chronic Noncancer Pain in Suicide Decedents: A National Study

Objective: The aims were to estimate the prevalence of CNCP in suicide decedents, and compare sociodemographic and clinical characteristics of people who die by suicide (i) with and without a history of CNCP and (ii) among decedents with CNCP who are younger (<65 years) and older (65 + years). Method: We examined all closed cases of intentional deaths in Australia in 2014, utilizing the National Coronial Information System. Results: We identified 2,590 closed cases of intentional deaths in Australia in 2014 in decedents over 18 years of age. CNCP was identified in 14.6% of cases. Decedents with CNCP were more likely to be older, have more mental health and physical health problems, and fewer relationship problems, and were more likely to die by poisoning from drugs, compared with decedents without CNCP. Comparisons of older and younger decedents with CNCP found that compared to younger (<65 years) decedents with CNCP, older decedents (65 + years) were less likely to have mental health problems. Conclusions: This is the first national study to examine the characteristics of suicide deaths with a focus on people with CNCP. Primary care physicians should be aware of the increased risk for suicide in people living with CNCP, and it may be useful for clinicians to screen for CNCP among those presenting with suicidal behaviors