Rethinking Therapeutic Strategies for Anorexia Nervosa: Insights From Psychedelic Medicine and Animal Models

Anorexia nervosa has the highest mortality rate of any psychiatric disease, and current medications are largely ineffective partly because the neurobiological drivers are poorly understood. Recent research into psychedelic medicine suggests psilocybin may alleviate symptoms related to serotonin signaling and cognitive inflexibility. Clinical trials for treatment-resistant depression show promise but have methodological biases. The first clinical trial using psilocybin for anorexia nervosa began in 2019, highlighting the need to understand the neurobiological mechanisms. Animal models, such as the activity-based anorexia rodent model, allow detailed study of brain function and behavior without the confounds of expectancy and bias, and are argued to be crucial for informing which patient subpopulations may benefit most from psychedelic medicine.

Study at a glance

Abstract

Anorexia nervosa (AN) has the highest mortality rate of any psychiatric disease, yet available pharmacological treatments are largely ineffective due, in part, to an inadequate understanding of the neurobiological drivers that underpin the condition. The recent resurgence of research into the clinical applications of psychedelic medicine for a range of mental disorders has highlighted the potential for classical psychedelics, including psilocybin, to alleviate symptoms of AN that relate to serotonergic signaling and cognitive inflexibility. Clinical trials using psychedelics in treatment-resistant depression have shown promising outcomes, although these studies are unable to circumvent some methodological biases. The first clinical trial to use psilocybin in patients with AN commenced in 2019, necessitating a better understanding of the neurobiological mechanisms through which psychedelics act. Animal models are beneficial in this respect, allowing for detailed scrutiny of brain function and behavior and the potential to study pharmacology without the confounds of expectancy and bias that are impossible to control for in patient populations. We argue that studies investigating the neurobiological effects of psychedelics in animal models, including the activity-based anorexia (ABA) rodent model, are particularly important to inform clinical applications, including the subpopulations of patients that may benefit most from psychedelic medicine.