Psilocybin Therapy Guide
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Anorexia nervosa is the most fatal psychiatric disorder — with no FDA-approved pharmacological treatments and recovery rates below 50%. A growing body of evidence now suggests psilocybin may address the cognitive rigidity that standard therapies cannot reach. Here's what the Phase 1 data, active Phase 2 trials, and preclinical research show.
Anorexia nervosa (AN) has the highest mortality rate of any psychiatric disorder. Mortality is approximately 11–18 times higher than the general population, around 5% of patients die within 4 years of diagnosis, and the suicide rate is reported to be up to 56 times the global average (Imperial College London, 2021). Despite this severity, there are no FDA-approved pharmacological treatments that reverse AN's core symptoms, fewer than half of patients achieve recovery, and relapse approaches 50% (Kaye & Bulik, JAMA Psychiatry, 2021).
Binge eating disorder (BED) is the most prevalent eating disorder, affecting an estimated 2–3% of the US population, yet effective pharmacological options remain minimal. Fluoxetine is the only FDA-approved medication for bulimia nervosa; nothing is approved for AN or BED.
This profound treatment gap has driven researchers to investigate psilocybin — a compound that, in depression and OCD, has shown the ability to break rigid thought patterns through a mechanism that may be directly relevant to eating disorder neurobiology.
| Study | Design | Key Finding | Evidence |
|---|---|---|---|
| Peck et al., 2023 Nature Medicine / UCSD + Compass | Phase 1, open-label, n=10 adult females with AN or partial remission AN; single 25 mg psilocybin dose | Safe, tolerable, no serious adverse events; significant reductions in ED psychopathology in some participants; 80% rated session top-5 most meaningful experience; 70% reported shift in personal identity | Early |
| Dallery et al., 2026 Journal of Eating Disorders | Open-label pilot, binge eating disorder, single 25 mg dose + preparatory psychotherapy | Reductions in binge eating frequency sustained through week 14 in all participants; improvements in depression, anxiety, and psychological inflexibility; fMRI signals of prefrontal connectivity change | Early |
| Conn et al., 2024 Molecular Psychiatry / Monash University | Preclinical; activity-based anorexia (ABA) rat model; psilocybin post-acute administration | Psilocybin improved body weight maintenance and cognitive flexibility in female rats; effects mediated via 5-HT1A and 5-HT2A receptor mechanisms; provides neurobiological rationale for human trials | Early |
| Bevione et al., 2025 Eating & Weight Disorders — systematic review | Systematic review; PubMed, EMBASE, Cochrane; all psilocybin ED studies through July 2024 | 2 studies met inclusion criteria; 6 trials registered; initial evidence shows psilocybin safe and tolerable in AN; promising results warrant enlarged trials | Early |
Understanding psilocybin's potential requires understanding what eating disorders — particularly AN — actually are at a neurobiological level. AN is not simply about food. It is a disorder of cognitive rigidity: the brain's inability to shift attention, challenge rigid beliefs about body image, and adapt behaviours in response to new information. This is the same cognitive inflexibility that characterises OCD, and the overlap is not coincidental — AN and OCD share neural substrates in the orbitofrontal cortex and striatal circuits.
Eating disorders are associated with serotonin dysregulation, particularly involving 5-HT2A receptors — the primary target of psilocybin. Individuals with AN show reduced 5-HT2A receptor activity in the prefrontal cortex and altered serotonin binding in the anterior cingulate cortex and insula — regions governing emotional regulation, interoception (awareness of bodily sensations), and the sense of self. Psilocybin's agonism at 5-HT2A receptors in these regions may help restore impaired signalling (MDPI Brain Sciences review, 2025).
Psilocybin is not proposed to work by changing attitudes about food directly during the session. The therapeutic hypothesis is that the neuroplasticity window and the shift in perspective it provides — often described as a loosening of rigid self-identity — makes integration therapy after the session more effective. As one Phase 1 participant described: "a shift in personal identity and overall quality of life." The drug opens a door; therapy walks through it.
The landmark study published in Nature Medicine (July 2023) was the first prospective clinical trial of psilocybin therapy in anorexia nervosa. Ten adult female participants meeting DSM-5 criteria for AN or partial remission AN (mean BMI 19.7 kg/m²) received a single 25 mg synthetic psilocybin dose (COMP360, Compass Pathways) with structured psychological support.
Primary outcomes (safety): No serious adverse events. No clinically significant changes in ECG, vital signs, laboratory values, or suicidality. Two participants experienced asymptomatic hypoglycaemia that resolved within 24 hours.
Secondary outcomes: Results were variable across participants, as expected in a feasibility study. Of those completing the Eating Disorder Examination (EDE), four showed clinically significant reductions in eating disorder psychopathology at one-month follow-up. BMI changes were not statistically significant on average. Qualitatively, 90% reported feeling more positive about life endeavours; 80% rated the session as one of the top five most meaningful experiences of their lives; 70% reported a shift in personal identity and quality of life. Notably, 90% felt one session was not enough, suggesting dose or protocol optimisation is needed.
The study was sponsored by Compass Pathways, the company developing COMP360 for a Phase 3 AN trial anticipated in 2026.
A single-site Phase 2 trial at UCSF is currently enrolling young adults with refractory AN. The protocol includes three preparatory sessions, two psilocybin dosing sessions (20 mg followed by up to 25 mg, with integration sessions between), and three final integration sessions. Family member involvement is incorporated — one family member attends portions of the preparatory and integration sessions. The primary hypothesis is that psilocybin will increase cognitive flexibility and that this increase will predict long-term changes in cognitive rigidity, habitual eating, and exercise behaviours.
An ongoing pilot study at Imperial College London is assessing the feasibility, brain mechanisms, and preliminary outcomes of psilocybin-assisted therapy for AN. The trial incorporated extensive patient and public involvement (PPI), with 11 individuals with lived experience of AN informing the protocol design. This is one of several AN trials sponsored or co-funded through Compass Pathways' COMP360 program.
Published in the Journal of Eating Disorders (January 2026), this open-label pilot of psilocybin-assisted therapy for BED found reductions in self-reported binge eating frequency across all participants, sustained through week 14. Improvements were also observed in depression, anxiety, and psychological inflexibility. fMRI analyses found preliminary signals of increased functional activation in the middle frontal gyrus and angular gyrus in response to food cues — suggesting changes in the neural evaluation of food. The study's small open-label design precludes causal inference but provides directions for future adequately powered trials.
A 2025 systematic review (Bevione et al.) identified six registered ClinicalTrials.gov studies of psilocybin in eating disorders. Beyond those above: one Baltimore-based trial (completed, results not yet published) used up to 4 sessions of 20–30 mg psilocybin in AN; one additional AN trial in London had estimated completion of June 2029; and one BED study in Gainesville, Florida (NCT05035927) completed enrollment. Results from completed but unpublished trials are anticipated in 2026.
Psilocybin in eating disorder populations — particularly AN — requires additional safety precautions beyond standard psilocybin protocols, due to the physiological vulnerabilities associated with malnutrition. A 2024 narrative safety review (Downey et al., Journal of Eating Disorders) identified the key considerations:
Anorexia nervosa is associated with electrolyte abnormalities — particularly hypokalemia — which can prolong the QTc interval and create cardiovascular risk. Psilocybin causes transient increases in heart rate and blood pressure during sessions. All published AN trials screen for and correct electrolyte levels before dosing. The Nature Medicine Phase 1 trial found no clinically significant ECG changes, but cardiac screening is considered essential prior to any psilocybin session in AN populations.
Medical stability — including adequate nutritional status — is a prerequisite in all AN trials. Severely underweight patients may face increased cardiovascular and metabolic risk from psilocybin's acute physiological effects. Weight stabilisation prior to psilocybin sessions is standard in all current protocols.
Eating disorders carry elevated suicide risk. All trials require thorough psychiatric screening and structured psychological support throughout the protocol. The psychedelic experience in AN may surface difficult material around body image and identity — making experienced psychological support critical.
Psilocybin is contraindicated in individuals with a personal or family history of psychosis or schizophrenia. Eating disorders carry some comorbidity with psychotic features in a minority of presentations — screening for this is an essential clinical gatekeeping step before any psilocybin protocol.
Based on published trial eligibility criteria, psilocybin for eating disorders has been studied in adults who broadly meet the following profile:
Several active AN trials — including the UCSF trial — incorporate family members into the protocol, requiring at least one family member to attend portions of preparatory and integration sessions. This reflects the recognition that eating disorder recovery often requires systemic support beyond the individual patient.
Psilocybin has no FDA approval for any eating disorder indication and has not received Breakthrough Therapy designation for this use. Legal access pathways are limited but real.
The primary legal access route. Search clinicaltrials.gov for "psilocybin eating disorder" or "psilocybin anorexia" to find currently recruiting trials. The UCSF trial (NCT06399263) and Imperial College London trial are the most advanced active AN studies. Participation is typically free; participants may receive compensation for time and travel.
Oregon and Colorado's regulated psilocybin programs allow supervised adult use without a specific diagnosis requirement. Adults with eating disorder-related distress may legally access supervised sessions through licensed facilitators in these states. This is not a clinical treatment protocol, but the supervised setting and integration support built into Oregon/Colorado programs are consistent with the therapeutic approach being studied in trials. See Retreats and Legal Status for access pathways.
Planning a session? Psilocybin Therapy Guide covers the full three-phase protocol (preparation, dosing, integration), Trip Preparation covers the week-by-week lead-up, and the Integration Workbook covers post-session work. Eating-disorder-specific considerations (cardiac monitoring, caloric/nutritional state) are covered in the Safety section above.