Clinical Research Directory

Inclusion Criteria: * Fluent in the English language * Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for current single or recurrent episodes of MDD of at least moderate severity but without psychotic features, as defined on the MINI 7.0. * 17-item HAM-D score ≥ 14. * Have failed to respond to 2 or more antidepressants prescribed at the minimum effective dose for at least 6 weeks OR at least 1 antidepressant prescribed at the minimum effective dose for at least 6 weeks AND a course of evidence-based psychotherapy given for at least 6 sessions. * For those aged ≥ 60 years, the first episode of depression must have started prior to their 60th birthday. Exclusion Criteria: Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or bipolar 2) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of psychotic disorder (defined as meeting DSM-5 criteria for any psychotic disorder) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of drug or alcohol dependence syndrome (defined as meeting DSM-5 criteria for any dependence syndrome) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of any personality disorder (defined as meeting DSM-5 criteria for any personality disorder) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist. Diagnosis of any dementia (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist. Personal history of a ≥ 1 suicide attempt in the past year requiring hospitalization, defined using the CSSRS (Q6 (past year) = "y") and confirmation at clinical interview with a psychiatrist. Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin. Depression secondary to other medical conditions Medical diagnosis incompatible with psilocybin treatment Inability to provide a screening blood sample, urine sample or electrocardiogram. Biochemical abnormalities (defined as falling outside the normal reference range) as evaluated by a full blood count, full biochemistry profile and thyroid function tests. Biochemical abnormalities must also be determined as clinically significant by a medical doctor to fulfil the criterion for exclusion. Electrocardiographic abnormalities, defined as any abnormality that is not normal sinus rhythm and determined as clinically significant by a medical doctor. Women of child bearing potential not using adequate contraception. Pregnant or breast-feeding women. Those unable to give informed consent. Non-registration with a GP or failure to consent to sharing of the GP summary care record and any psychiatric assessments held. Those enrolled in another drug trial Hypersensitivity to the IMP or to any of the excipients or placebo