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.
Highlights
THE RESURGENCE OF PSYCHEDELIC MEDICINE AND THERAPEUTIC POTENTIAL FOR ANPsychedelics were first investigated as therapeutic agents for mental disorders in the 1950s (Neill, 1987) and more than 1000 clinical papers were published on classical psychedelics between 1950 and the mid-1960s (Grinspoon and Bakalar, 1981)
Recent clinical trials have put the spotlight on the therapeutic potential of psychedelics, psilocybin, for a range of psychiatric disorders
New treatment strategies for AN are urgently needed, considering that up to 50% of patients with AN never recover
Summary
Psychedelics were first investigated as therapeutic agents for mental disorders in the 1950s (Neill, 1987) and more than 1000 clinical papers were published on classical psychedelics between 1950 and the mid-1960s (Grinspoon and Bakalar, 1981). Much of our argument is likely to be applicable to the therapeutic potential of other serotonergic or “classical” psychedelic compounds, including lysergic acid diethylamide (LSD) and ayahuasca, we focus here on psilocybin for three reasons: (1) the two FDA designations as a “breakthrough therapy” for treatment-resistant depression; (2) its prevailing use in numerous clinical trials for mental disorders; and (3) the proximity to approval as the first widely used psychedelic in medicine and therapy. We argue that fundamental research in animal models is necessary to reach a comprehensive understanding of the therapeutic effects of psychedelics in psychiatric disease The well-established potential for psychedelics to increase cognitive flexibility (Bouso et al, 2012, 2013; Carhart-Harris et al, 2016b) is consistent with the intriguing possibility that they may play a therapeutic role in addressing perseverative thinking and behavior in AN
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