The Safety and Efficacy of Psilocybin as an Adjunctive Therapy in Participants with Treatment-Resistant Depression

A recent open label study of the effects of psilocybin in participants with treatment-resistant depression (TRD) showed rapid significant decrease of depressive symptoms after treatment with psilocybin coupled with psychological support. Over 40% of participants sustained response at 3 months. In this study, the aim is to explore effectiveness of 25 mg of psilocybin as an adjunctive therapy in participants with TRD.

Inclusion Criteria:

1. Signed ICF.
2. 18 years of age or older
3. At least moderate MDD
4. Hamilton Depression Rating Scale (17 item) score ≥18
5. Currently receiving treatment with a selective serotonin reuptake inhibitor
6. Failure to respond to an adequate dose and duration of 2, 3, or 4 pharmacological treatments
7. McLean Screening Instrument for Borderline Personality Disorder <7 at Screening (V1).
8. Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.

Exclusion Criteria:

Psychiatric Exclusion Criteria:

1. Current or past history of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, or borderline personality disorder, as assessed by medical history, McLean Screening Instrument for Borderline Personality Disorder and a structured clinical interview (version 7.0.2 MINI).

2. Prior electroconvulsive therapy and/or ketamine for current episode.

3. Ongoing use of an antidepressant medication, including augmentation or combination therapies, other than a single SSRI

4. Current psychological therapies that will not remain stable within 21 days of the psilocybin session. Psychological therapies cannot be initiated within 21 days of baseline.

5. Current (within the last year) alcohol or substance use disorder as informed by DSM 5 (diagnosed by MINI 7.0.2) at Screening (V1).

6. Significant suicide risk as defined C-SSRS within the past year

7. Depression secondary to other severe medical conditions according to clinicians' judgement.

8. Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin, including exposure to psilocybin within the past year and use of psychedelics, such as ayahuasca, during the current depressive episode.

   General Medical Exclusion Criteria:

9. Women who are pregnant, nursing or planning a pregnancy.

10. Cardiovascular conditions

11. Uncontrolled or insulin dependent diabetes.

12. Seizure disorder.

13. Positive urine drug screen for illicit drugs or drugs of abuse

14. Current enrolment in any investigational drug or device study or participation in such within 30 days prior to Screening (V1).

15. Current enrolment in another clinical study of an investigational medical or participation in such within 30 days of Screening (V1).

16. Abnormal and clinically significant results on the physical examination, vital signs, ECG or laboratory tests at Screening (V1).

17. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study.

Up to 3 weeks

Safety analysis set - All participants who receive study drug.