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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., Postprint (author's final draft)

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En las últimas décadas diversos estudios han documentado profundos cambios en las prácticas médicas. Los mismos señalan que estaríamos asistiendo a un cambio epistémico donde la medicina se convierte en biomedicina (Keating & Cambrosio, 2003). En el marco de estas transformaciones biomédicas, la presente tesis analiza las prácticas que acompañan a la elaboración del juicio psiquiátrico diagnóstico (JPD), atendiendo a la trama de materialidades y significaciones en que es producido. Abordamos nuestro objeto de estudio desde el ámbito de los Estudios de Ciencia y Tecnología, particularmente desde la perspectiva teórica denominada Teoría del Actor-Red (TAR). Hacemos uso del concepto de "objeto frontera" desarrollado por Susan Star y James Griesemer (1989), para explicar como actúan los psicofármacos en la elaboración del JPD. La noción de objeto frontera discute con el concepto de traducción desarrollado por la TAR, pero ambas figuras constituyen metáforas para describir las vicisitudes de la relacionalidad. Nosotras empleamos ambas nociones a lo largo del trabajo para describir el rol que los psicofármacos desempeñan en las prácticas psiquiátricas y en la realización de un JPD. En primer lugar presentamos una reseña del concepto de diagnóstico y/o juicios diagnósticos basándonos en los estudios de Foucault sobre la psiquiatría de finales del s. XVIII y del s. XIX, y en algunos de los trabajos más importantes del movimiento de la antipsiquiatría. En un segundo momento, utilizando la noción de trayectoria, describimos dos modos en que los psicofármacos proponen o sugieren la forma que tomará el JPD. En la primera trayectoria, damos cuenta del trabajo de traducción psicofarmacológica producido en el cuerpo del paciente. En la segunda, trazamos el recorrido en sentido inverso, es decir, explicamos como en el ejercicio de producción de un JPD, la clínica como experticia, es desplazada hacia los espacios de producción científica o colectivos bioclínicos. En un tercer trabaj, In the last decades many studies have shown profound changes in medical practices. This points out that we are attending to an epistemological shift turning medicine into biomedicine. In this context, our research analyzes the concomitant practices of diagnostic psychiatric judgement (DPJ) elaboration, focusing on the materiality and the significances of diagnosis-making. We address our study object from Actor-Network Theory (ANT), a theoretical perspective derived from the field of Social Studies of Science and Technology. Drawing on the boundary object notion established by Star & Griesemer (1989), we explain how psychotropic drugs act in DPJ production. The notion of boundary objects discusses the translation concept developed by ANT, however both are metaphors which describe the vicissitudes of relationality. We apply both notions in order to describe the role of psychotropic drugs in psychiatric practices and in DPJ. In the first paper, we present a review of the diagnosis concept grounded in Foucault's studies about psychiatry and of some of the most important works from the antipsychiatry movement. In a second paper, the trajectory notion is used to describe two ways as to how psychotropic drugs propose the configuration of DPJ. In the one trajectory, we depict the psychopharmacological translation work produced in the patient's body. In the other, tracing a reverse path, we explain how the clinical expertise is transferred to scientific spaces or bioclinical collectives in DPJ enactment. In a third paper, the tools applied in prior analysis - mediation, in particular translation and delegation - are embodied in the boundary objects category, to get a greater analytical scope for the case study. We put forward that psychotropic drugs as boundary objects support the process of diagnosis-making on a minimun knowledge base, allowing the continuous negotiation of significances. Its interpretive flexibility articulates the distributed and heterogeneous perspective