Separate or inseparable? Serotonin and dopamine system interactions may underlie the therapeutic potential of psilocybin for anorexia nervosa

Psilocybin, a serotonergic psychedelic, has emerged as a promising treatment for a range of mental health conditions, including anorexia nervosa. Recent insights from animal models and human imaging studies suggest psilocybin enhances cognitive flexibility and modifies reward processing – two core processes disrupted in anorexia nervosa. Both cognitive flexibility and reward processing are highly dependent on interactions between serotonin (5-HT) and dopamine (DA) systems in key brain regions such as the prefrontal cortex and nucleus accumbens. Psilocybin’s influence on neuroplasticity, particularly in promoting structural and functional changes in neural circuits, underpins its therapeutic potential. While its effects are predominantly attributed to activity of the 5-HT2A receptor subtype, recent evidence suggests a broader network of brain receptor interactions, particularly those with dopaminergic pathways, plays a crucial role. Investigations using rodent models reveal that psilocybin induces both rapid and enduring neuroplastic changes, improving cognitive flexibility through these complex neurochemical mechanisms. Advances in real-time in vivo neurochemical recording now allow simultaneous monitoring of 5-HT and DA signalling, which will provide essential insights into their distinct and coordinated actions during cognitive performance. This integrative framework highlights the need for further research into psilocybin’s dual modulation of 5-HT and DA systems to optimize its therapeutic applications for anorexia nervosa, a life-threatening condition that is characterized by impairments in cognitive flexibility and reward processing.