The Therapeutic Efficacy of Psilocybin in a Preclinical Model of Depressive- and Anxiety-Like Symptomology

Depressive and anxiety disorders are debilitating psychiatric illnesses that affect a substantial portion of the world population. Current pharmaceutical interventions, such as selective serotonin reuptake inhibitors, are generally regarded as front-line treatments but are not universally effective at reducing symptomology. Psilocybin, the active component in Psilocybe cubensis mushrooms, is a potent hallucinogenic substance that has shown promise as a pharmacological intervention for depression and anxiety in clinical trials. However, the mechanisms by which psilocybin exerts a therapeutic impact have not been thoroughly investigated. Preclinical (i.e., animal) research provides the opportunity to systematically assess the utility of drugs that may have medicinal applications under tightly controlled methodological conditions. The aim of this thesis is to determine whether a single administration of psilocybin reduces pathological behavioural tendencies in a preclinical model of depressive- and anxiety-like symptomology.

Shortly after birth, rats were exposed to early maternal separation, which is an established preclinical analogue for early chronic perinatal stress. Baseline behaviour was assessed with the Affective Disorders Test (ADT), which is a novel preclinical assay developed to test for depressive- and anxiety-like behaviour in animals over time. After 5 days of consecutive baseline testing, animals were administered one of two active doses of psilocybin (8 or 16mg/kg) or saline. Behaviour was then assessed again with the ADT for 3 consecutive days directly after administration (i.e., acute effects), and then again for 6 consecutive days 12 days post-treatment (i.e., chronic effects). Although the results obtained were mixed and largely inconclusive, this research constitutes an important contribution to the limited number of preclinical investigations of psilocybin in the context of depression and anxiety. This thesis also suggests numerous alternative directions and critical methodological factors for future researchers to consider.