Psychedelic drugs to treat eating disorders

Sarah Bunn; Stephen Naulls

Overview

POST has published briefings on the use of psychedelics to treat depressive disorders, anxiety disorders and PTSD. This is part of our wider work on the use of psychedelics to treat mental health conditions. POST will publish a major briefing on this later in 2024.

This briefing focusses specifically on eating disorders and covers:

the different types of eating disorders
existing treatments for eating disorders
research into the use of psychedelics to treat eating disorders.

Eating disorders can become long-term illnesses. A review reported that that two thirds of adults with anorexia nervosa, and one third with bulimia nervosa had not recovered after 9 years. The average duration of binge eating disorder is reported at 14 years. People with eating disorders are at increased risk of dying, particularly those with anorexia nervosa, when compared with people with other psychiatric illnesses.

There are no approved drug treatments approved in the UK to treat eating disorders. Where used, drugs are prescribed to treat co-existing mental health conditions such as anxiety and depression, which can be a barrier to recovery. There is specific interest as to whether psychedelic drugs can be as, or more, effective in this context.

Eating disorders

In international medical diagnostic guidance (the ICD-11), feeding or eating disorders involve:

“abnormal eating or feeding behaviours that are not better accounted for by another medical condition and are not developmentally appropriate or culturally sanctioned. Feeding disorders involve behavioural disturbances that are not related to body weight or shape concerns, such as eating of non-edible substances or voluntary regurgitation of foods. Eating disorders involve abnormal eating behaviour and preoccupation with food accompanied in most instances by prominent body weight or shape concerns.”

There are seven disorders in the ICD-11, but the most common and the focus for psychedelic research are:

Anorexia nervosa presents with significantly low body weight for age/height, rapid weight loss or failure to gain weight, not due to medical conditions or food availability. It involves persistent restrictive eating (restrictive subtype) or purging (binge-purge subtype), extreme fear of weight gain, excessive preoccupation with body weight/shape, and overvaluing low weight.
Bulimia nervosa involves frequent binge eating episodes where individuals feel a loss of control over eating, followed by inappropriate compensatory behaviours to prevent weight gain, occurring at least once a week for a month. It also involves excessive preoccupation with body weight/shape, causing marked distress or impairment, as distinct from anorexia nervosa.
Binge Eating Disorder is characterised by frequent episodes of binge eating, occurring at least once a week for three months, where individuals feel a loss of control over eating. Unlike bulimia, these episodes are not followed by compensatory behaviours. Symptoms cause marked distress or impairment and are not due to other medical or mental conditions.

Existing treatments for eating disorders

Psychotherapy

Cognitive Behavioural Therapy (CBT) is the first-line treatment for most eating disorders. It helps individuals identify and challenge distorted thoughts and beliefs about food, weight and body image. It teaches coping skills to manage triggers and develop healthier eating behaviours.
Family-Based Treatment is particularly effective for adolescents with eating disorders, actively involving parents/carers in their child’s treatment. It aims to empower parents to support their child’s nutritional rehabilitation and weight restoration.
Interpersonal Psychotherapy focuses on addressing interpersonal difficulties and relationship conflicts contributing to the development or maintenance of eating disorders. It helps individuals improve communication skills, resolve conflicts and build social support.
Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) is a talking therapy that focuses on understanding an eating disorder and its effects, to help individuals focus on their needs and preferences to change behaviours.

Pharmacological treatments

There are no drugs approved to treat eating disorders in the UK, but co-existing mental health conditions can be treated with drugs. This is important because conditions such as depression are likely to impede recovery.

Selective Serotonin Reuptake Inhibitors (SSRIs) increase serotonin (a chemical transmitter) levels in the brain, contributing to mood stabilisation. Drugs such as fluoxetine may be prescribed to help manage symptoms of depression, anxiety, or obsessive-compulsive disorder commonly associated with eating disorders.
Atypical Antipsychotics act on chemical transmitters in the brain, particularly the dopamine system. Drugs such as olanzapine or quetiapine may be prescribed to help reduce binge eating and improve mood stability in individuals with severe eating disorders. The side effect of increased weight gain results from drug effects to increase appetite, but weight gain is a concern to patients.
Stimulants that act on the brain are also of interest. In the US, lisdexamfetamine dimesylate is approved by the Food and Drug Administration to treat Binge Eating Disorders in adults.

Patient with eating disorders can also encounter a range of physical health issues due to their low weight, and abnormalities resulting from imbalances in levels of salts and minerals. These sometimes require inpatient treatment and dietary interventions, such as instigating regular eating. These are not included in this briefing. Information about supporting the physical health of patients with eating disorders is detailed here.

Psychedelics in the treatment of eating disorders

The research evidence examining psychedelic-assisted psychotherapy for eating disorders is less comprehensive than for other conditions. Most evidence comes from case reports (a study of one patient) or case series (a study of a small number of patients) or is cross-sectional (participants are observed at a single time point of time with no intervention).

This limits the strength of the conclusions that can be drawn as to the effectiveness of psychedelic drugs. However, a small number of clinical trials are underway.

Case Reports or Case Series

Psilocybin

A 1959 case report described a patient with AN treated with two doses of psilocybin, exhibiting possible therapeutic effects like improved mood and weight gain. The patient gained insight into the cause of condition; she relapsed a year after treatment.

Ketamine

One patient with bulimia nervosa achieved remission after three courses of ketamine-assisted psychotherapy over three months, leading to reduced purging and binge-eating and complete cessation of behavioural symptoms, sustained for over one year.
Other studies tested intravenous ketamine infusions for anorexia nervosa, leading to weight restoration and sustained cessation of symptoms for six months. The researchers noted that this resulted from the infusions and a diet high in fat and low in carbohydrate.
One patient with anorexia nervosa and major depressive disorder reported reductions in suicidality after ketamine treatment.There was a significant improvement, but this was short-lived, possibly linked to a specific stressor event.
A case series of four individuals with eating disorders and treatment-resistant depression showed improvement in depression and eating disorder symptoms in three out of the four patients.
Another case series studied five individuals with eating disorders who all had a co-existing major depressive disorder. Participants also had either a generalised anxiety disorder or PTSD. Some participants showed improvements to these co-existing disorders following group-based ketamine-assisted psychotherapy. These effects were measured over 24 hours only.

Cross-sectional studies

A survey following 28 participants with a lifetime eating disorder diagnosis reported significant improvements in depression and psychological well-being after taking classic psychedelics (this drug class is discussed in the POST article on their use to treat depression).
Another survey, involving participants without eating disorders, found that more frequent psychedelic use correlated with reduced disordered eating symptoms. The researchers reported that this effect was mediated through enhanced spirituality and emotional regulation.
Two exploratory studies, one with 16 participants, the other with 13, interviewed individuals with eating disorders participating in ayahuasca (containing the psychedelic drug DMT) ceremonies, reporting subjective improvements of eating disorder thoughts and symptoms, particularly in negative body perception.
The perspectives of those with eating disorders on engaging with psychedelic research have been studied. One study found 60% viewed it as worthwhile, despite some concerns, such as receiving treatment in a safe, controlled setting.

Clinical trials

Individual reports and survey data such as the above are prone to bias, which is why they are often used as the rationale for developing large, more robust clinical trials. For example, recruiting people to a survey based on them previously having used a psychedelic substance means they may be more likely to consider them favourably, possibly increasing the chances they will report improvement after their use.

Studies using robust research methods are needed. Early data has been published from some of these more robust clinical trials:

A trial suggested that ketamine infusions might treat compulsive eating behaviour in anorexia nervosa. Of 15 patients treated, nine showed a positive impact on compulsive behaviours and depressive symptoms, for up to three weeks.
A trial of MDMA-assisted therapy for PTSD included 89 participants with PTSD, of whom 13 had clinical eating disorder symptoms and 28 were observed to be at risk of an eating disorder. There was a significant improvement in eating disorder symptoms for those participants who received MDMA-assisted psychotherapy compared with a placebo.
A study of 10 female participants with anorexia nervosa showed significant decreases in symptoms at three-month follow-up, after one dose of psilocybin with psychological support. It found that any adverse effects were short-lived. This is important as the low weight in patients with severe anorexia nervosa can precipitate other physical problems (for instance, patients with severe anorexia nervosa are at increased risk of abnormal heart rhythms).

Ongoing and future research

There are four trials assessing psilocybin as a treatment:

A study at Imperial College London has enrolled 21 individuals with anorexia nervosa to receive three doses of psilocybin with psychological support over six weeks. The results are expected in late 2024.
A study at Johns Hopkins University is assessing changes in depression and anxiety among 22 patients with chronic anorexia nervosa. It will report in 2024.
A safety and feasibility study by Tryp Therapeutics is assessing the use of psilocybin as a possible treatment for binge eating disorder.
An international study by COMPASS Pathways, with 60 participants, is comparing the safety and efficacy of 1mg and 25mg psilocybin with psychological support, to treat anorexia nervosa. One of the study sites is King’s College London.

Two planned studies in Australia will also examine psilocybin-assisted therapy to treat anorexia nervosa.

A study by Lykos Therapeutics will begin in 2024. Recruiting 36 participants, it will examine MDMA-assisted psychotherapy to treat anorexia nervosa and binge eating disorder.

A study comparing oral ketamine to a placebo in 60 participants with both anorexia nervosa and major depressive disorder will begin in 2025 at King’s College London in collaboration with Neurocentrx Pharma Ltd.

Acknowledgements

POST is grateful to Dr Stephen Naulls, Clinical Research Fellow at POST, for researching this briefing.

POST would like to thank Hannah Douglass, PhD Student, Centre for Psychedelic Research, Division of Psychiatry at Imperial College London, and Dr Johanna Keeler, Postdoctoral Research Associate, Centre for Research in Eating and Weight Disorders, Institute of Psychiatry, Psychology & Neuroscience at King’s College London, who acted as external peer reviewers in preparation of this article.