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

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 activitybased anorexia (ABA) rodent model, are particularly important to inform clinical applications, including the subpopulations of patients that may benefit most from psychedelic medicine.

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

“…For example, preclinical efficacy has been shown in inflammatory conditions such as high-fat diet-induced obesity and diabetes (Flanagan et al, 2019b), gut inflammatory challenges (Nau et al, 2013(Nau et al, , 2015, and asthma (Flanagan et al, 2019a). Possible utility in other psychiatric conditions, such as eating disorders, has been hypothesized and should be further explored (Foldi et al, 2020).…”

Examining the Potential Synergistic Effects Between Mindfulness Training and Psychedelic-Assisted Therapy

“…Psychedelics have recently been investigated as an alternative treatment for treating various psychiatric conditions with promising results. Most of these studies however suffer from low methodological validity and are mostly open-label, yet they have yielded preliminary evidence for the capacity of psychedelic substances for treating addiction, depression, anxiety, and eating disorders (29)(30)(31)(32)(33)(34)(35). In recent years, several randomised controlled trials (RCTs) have robustly demonstrated ayahuasca, ketamine and psilocybin's potent anti-depressive effects (36)(37)(38).…”

Psilocybin as a Novel Pharmacotherapy for Treatment-Refractory Anorexia Nervosa

“…The insula, a brain region that plays a critical role in switching between the salience network, executive control network (ECN) and default mode network (DMN) (Figure 2), known as the 'connector hubs' [159]. The ECN is important for the integration of sensory and memory information, regulation of cognition and behaviour as well as cognitive flexibility [153].…”