Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.

Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.

Optic disc cupping: prevalence findings from the WESDR.

Increased cupping of the optic disc is considered to be an indication of pressure-related damage of the optic nerve. This paper explores the relationship of intraocular pressure and cupping in persons with diabetes mellitus, a group of people whose optic nerves may be more susceptible to the effects of intraocular pressure. Stereoscopic fundus photographs of the seven standard fields were obtained in all persons participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy at the time of the initial prevalence survey. Measurements of disc and cup diameters in the vertical and horizontal meridia were made by two trained graders. Cup-to-disc ratios were computed for both diameters of each eye and the mean of the two gradings was used. A history of glaucoma was significantly associated with larger cup-to-disc ratios at the prevalence examination. Cup-to-disc ratios were not larger in those with high IOP, nor in those who had panretinal photocoagulation.

Optic disc cupping: four year follow-up from the WESDR.

Change in optic disc cupping was evaluated in a 4-year follow-up of a well defined cohort of people with diabetes mellitus. Cup-to-disc ratios were computed for both vertical and horizontal diameters of each eye at the baseline and 4-year follow-up examinations. Graders were masked as to the identity of participants and to the dates of the photographs. Increases of at least 0.1 between baseline and follow-up were used as clinically significant change in the ratios. None of the following factors at baseline were consistent predictors of such a change: intraocular pressure, age, duration of diabetes, hypertension or severity of diabetic retinopathy. People who developed proliferative retinopathy by the follow-up examination were not more likely to have such an increase in ratio at the follow-up. We conclude that clinically significant increases in cup-to-disc ratio cannot be consistently predicted in people with diabetes from the risk factors evaluated with the grading system used in this study.