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Background The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. Methods Changes in multimodal electroencephalography, single-photon emission computed tomography, and subjective effects following the acute administration of salvinorin-A are reported. The study included 2 sub-studies that employed a double-blind, crossover, randomized, placebo-controlled design. Results The electroencephalography measures showed a marked increase in delta and gamma waves and a decrease in alpha waves while subjects were under the effect of salvinorin-A. Regarding single-photon emission computed tomography measures, significant decreases in regional cerebral blood flow were detected in multiple regions of the frontal, temporal, parietal, and occipital cortices. Significant regional cerebral blood flow increases were observed in some regions of the medial temporal lobe, including the amygdala, the hippocampal gyrus, and the cerebellum. The pattern of subjective effects induced by salvinorin-A was similar to those observed in relation to other psychotomimetic drugs but with an evidently dissociative nature. No dysphoric effects were reported. Conclusion The salvinorin-A–mediated KOR agonism induced dramatic psychotomimetic effects along with a generalized decrease in cerebral blood flow and electric activity within the cerebral cortex.

Although psychotropic drugs are used to treat mental health disorders, little evidence analyses the effects the 2008 economic downturn had on psychotropic drug consumption in the case of Spain. We analyse these effects, considering both gender and employment situation. Participants We used the microdata from the face-to-face cross-sectional population-based Spanish National Health Survey for two periods: 2006–2007 (n=28 954) and 2011–2012 (n=20 509). Our samples included adults (>15 years old). Methods The response variables are consumption (or not) of antidepressants or sedatives and the explanatory variables are the year of the survey, gender and employment status. Covariates are mental health problems, mental health index General Health Questionnaire (GHQ-12) and self-reported health outcome variables such as self-rated health, chronic diseases, smoking behaviour, sleeping hours, body mass index, physical activity in the workplace, medical visits during the past year, age, region of residence (autonomous communities), educational level, marital status and social class of the reference person. Finally, we include interactions between time period, gender and employment status. We specify random effects logistic regressions and use Bayesian methods for the inference. Results The economic crisis did not significantly change the probability of taking antidepressant drugs (OR=0.56, 95% CI 0.18 to 2.56) nor sedatives (OR=1.21, 95% CI 0.26 to 5.49). In general, the probability of consuming antidepressants among men and women decreases, but there are differences depending on employment status. The probability of consuming sedatives also depends on the employment status. Conclusions While the year of the financial crisis is not associated with the consumption of antidepressants nor sedatives, it has widened the gap in consumption differences between men and women. Although antidepressant use dropped, the difference in consumption levels between men and women grew significantly among the retired, and in the case of sedatives, risk of women taking sedatives increased in all groups except students. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial

Mephedrone (4-methylmethcathinone) is a novel psychoactive substance popular among drug users because it displays similar effects to MDMA (3,4-methylenedioxymethamphetamine, ecstasy). Mephedrone consumption has been associated with undesirable effects and fatal intoxications. At present, there is no research available on its pharmacological effects in humans under controlled and experimental administration. This study aims to evaluate the clinical pharmacology of mephedrone and its relative abuse liability compared with MDMA. Twelve male volunteers participated in a randomized, double-blind, crossover, and placebo-controlled trial. The single oral dose conditions were: mephedrone 200 mg, MDMA 100 mg, and placebo. Outcome variables included physiological, subjective, and psychomotor effects, and pharmacokinetic parameters. The protocol was registered in ClinicalTrials.gov (NCT02232789). Mephedrone produced a significant increase in systolic and diastolic blood pressure, heart rate, and pupillary diameter. It elicited stimulant-like effects, euphoria, and well-being, and induced mild changes in perceptions with similar ratings to those observed after MDMA administration although effects peaked earlier and were shorter in duration. Maximal plasma concentration values for mephedrone and MDMA peaked at 1.25 h and 2.00 h, respectively. The elimination half-life for mephedrone was 2.15 h and 7.89 h for MDMA. In a similar manner to MDMA, mephedrone exhibits high abuse liability. Its earlier onset and shorter duration of effects, probably related to its short elimination half-life, could explain a more compulsive pattern of use as described by the users. Funding is supported in part by grants from Instituto de Salud Carlos III (ISCIII, FIS-FEDER, PI11/01961), ISCIIIRed de Trastornos Adictivos (RTA RD12/0028/0009), and The European Commission (Drug Prevention and Information Programme 2014–16, Contract no. JUST/2013/ DPIP/AG/4823, EU-MADNESS project and Drugs Policy Initiatives, Justice Programme 2014-2020, Contract no.HOME/2014/JDRU/AG/DRUG/7082, PREDICT Project). EP has a Rio Hortega fellowship (ISC-III, CM13/00016) and CP-M has a Juan Rodes fellowship (ISC-III, JR15/00005).

Purpose Evidence of whether the recent economic crisis has or has not had an effect on psychotropic drug consumption is very scarce. Our objective was to determine if there had in fact been an increase in psychotropic drug use as a result of the financial crisis. Methods In our study a retrospective cohort (between January 1, 2005, and December 31, 2012) was made up of individuals from the general population in a region in the northeast of Catalonia, Spain. We specified a generalized linear mixed model along with combined ‘selection on observables’ as (propensity scoring) matching and ‘selection on unobservables’ as (random coefficient) the panel data model methods, and performed inferences using a Bayesian framework. Results In the period following the economic crisis (post 2009), there was an increase in the consumption of psychotropic drugs which was significantly higher among those who had already been consuming psychotropic drugs prior to 2009 and those most likely to be unemployed. The increase was of greater significance when consumption was measured by the number of drugs being taken, rather than by the defined daily dose (DDD), with the greatest increase occurring in 2011; the very year in which Spain was most affected by the crisis. Conclusions Once the financial crisis had ended, there was an increase in the severity, rather than the intensity, of mental health disorders in individuals who had already had disorders before the crisis. This increase occurred in those most likely to be unemployed, and the severity was accentuated in the toughest year of the economic crisis

BACKGROUND: The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. METHODS: Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. RESULTS: The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, P