Efficacy and Safety of COMP360 Psilocybin Therapy in Anorexia Nervosa: a Proof-of-concept Study

Inclusion Criteria:

1. Any sex and aged 18 years or above at screening.

2. Meeting criteria for AN either restrictive or binge-purging type, according to theDSM-5, based on medical records, clinical assessment, BMI, and documented completionof MINI 7.0.2 and EDE at screening.

3. Have successfully discontinued all prohibited medications for a period of at leasttwo weeks prior to baseline. For fluoxetine (Prozac), immediate cessation atscreening period visit 1a followed by at least four weeks of washout will berequired prior to baseline.

4. Has a history of disordered eating with duration of at least 3 years prior toscreening, that is consistent with AN.

5. BMI ≥15 kg/m2 and ≤20 kg/m2. For participants with a BMI <16 kg/m2 and >18.5 kg/m2at screening, approval from the Medical Monitor will be required. Any participantwith a BMI >18.5 kg/m2 must meet all of the criteria for AN except that, despitesignificant weight loss, the individual's weight is within or above the normalrange.

6. Being otherwise medically stable at screening determined by clinical interview,clinical laboratory values, vital signs, ECG, and medical history.

7. Have at least one documented prior attempt at treatment in the past 3 years.

Exclusion Criteria:

1. Prior or ongoing bipolar disorder, any psychotic disorder, including schizophrenia,schizophreniform disorder, schizoaffective disorder, brief psychotic disorder (unless substance induced or due to a medical condition), antisocial personalitydisorder, or any serious psychiatric comorbidity as assessed by medical history anda structured clinical interview (MINI 7.0.2).

2. Prior or ongoing paranoid, schizoid, schizotypal, histrionic, narcissisticpersonality disorder based on medical history and clinical judgment.

3. Borderline personality disorder as demonstrated by medical history, the MINI Plus -BPD and clinical judgment.

4. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4or 5 on the C-SSRS within the past year, at screening or at baseline, or; (2)suicidal behaviours within the past year or; (3) clinical assessment of significantsuicidal risk during participant interview.

5. Current (within last year) alcohol or substance use disorder as informed by theDSM-5 assessed via the MINI 7.0.2, and urine toxicology at screening.

6. Other personal circumstances and behaviour judged to be incompatible withestablishment of rapport or safe exposure to psilocybin.

7. Exposure to psilocybin, or any other psychedelics, such as ayahuasca, mescaline,LSD, or peyote within the past year.