¿Media la dopamina los efectos psicóticos del Cannabis? Revisión e integración de los hallazgos a través de disciplinas / Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines

Los estudios epidemiológicos efectuados en la población general han demostrado sistemáticamente que el consumo de Cannabis aumenta de modo dependiente de la dosis el riesgo de desarrollar trastornos psicóticos. Aunque los indicios epidemiológicos entre el consumo de Cannabis y las psicosis han obtenido una atención considerable, apenas se conoce el mecanismo biológico mediante el que esta droga aumenta el riesgo de psicosis. La investigación en estudios efectuados en animales sugiere que el delta- 9-tetrahidrocanabinol (THC, el componente psicoactivo principal del Cannabis) aumenta los niveles de dopamina en diversas regiones del cerebro, incluido el núcleo estriado y el área prefrontal. Dado que se ha formulado la hipótesis de que la dopamina representa una vía final común decisiva entre la biología del cerebro y la experiencia real de psicosis, inicialmente prestar atención a este neurotransmisor podría ser productivo en el examen de los efectos psicotomiméticos del Cannabis. Por consiguiente, en la presente revisión se examinan las pruebas concernientes a las interacciones entre el THC, los endocanabinoides y la dopamina en la región tanto cortical como subcortical implicadas en las psicosis, y se consideran los posibles mecanismos por los que una disregulación de la dopamina inducida por el consumo de Cannabis podría dar lugar a delirios y alucinaciones. Se concluye que podrían emprenderse productivamente estudios adicionales sobre los mecanismos subyacentes que relacionan el consumo de Cannabis y las psicosis desde una perspectiva de una sensibilización progresiva del desarrollo, como consecuencia de interacciones genes-ambiente (AU)

General population epidemiological studies have consistently found that cannabis use increases the risk of developing psychotic disorders in a dose-dependent manner. While the epidemiological signal between cannabis and psychosis has gained considerable attention, the biological mechanism whereby cannabis increases risk for psychosis remains poorly understood. Animal research suggests that delta-9- tetrahydrocannabinol (THC, the main psychoactive component of cannabis) increases dopamine levels in several regions of the brain, including striatal and prefrontal areas. Since dopamine is hypothesized to represent a crucial common final pathway between brain biology and actual experience of psychosis, a focus on dopamine may initially be productive in the examination of the psychotomimetic effects of cannabis. Therefore, this review examines the evidence concerning the interactions between THC, endocannabinoids and dopamine in the cortical as well as subcortical regions implicated in psychosis, and considers possible mechanisms whereby cannabis-induced dopamine dysregulation may give rise to delusions and hallucinations. It is concluded that further study of the mechanisms underlying the link between cannabis and psychosis may be conducted productively from the perspective of progressive developmental sensitization, resulting from gene-environment interactions (AU)

Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the Æsop First-Onset Psychosis Study

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78age- and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naý¨ve), 26 werereceiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls (+22percent , p=0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15 percent larger in antipsychotic-free patients (p¼0.028), 17 percent larger in patients receiving atypicals (p¼0.01), and 30 percent larger in patients receiving typicals (p=0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together (11 percent, p¼0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24 percent larger in patients with schizophrenia/schizophreniform disorder (n¼40, p=0.001), 19 percent larger in depressed patients (n¼13, p¼0.022), 16 percent larger in bipolar patients (n¼16, p¼0.037), and 12 percent larger in those with other psychoses (n¼9, p¼0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presenceof antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effecton pituitary volume, likely to be related to activation of prolactin-secreting cells...