title: Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.
abstract: BACKGROUND
  Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.
  
  
  METHODS
  In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.
  
  
  RESULTS
  Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.
  
  
  CONCLUSIONS
  This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.
  
  
  BACKGROUND
  Medical Research Council.
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. Electronic address: r.carhart-harris@imperial.ac.uk.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Carhart-Harris
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bolstridge
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK; The Institute of Psychiatry, Psychology and Neuroscience, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Rucker
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Camilla M J
authors.initials: CM
authors.lastname: Day
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Mendel
authors.initials: M
authors.lastname: Kaelen
authors.affiliation: Department of Psychiatry, University College London, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Bloomfield
authors.affiliation: Barts Health Pharmaceuticals, Barts Health NHS Trust, The Royal London Hospital, London, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Rickard
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
authors.affiliation: The Beckley Foundation, Beckley Park, Oxford, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Feilding
authors.affiliation: Department of Pharmacy and Pathology, South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Taylor
authors.affiliation: Clinical Psychology and Clinical Effectiveness, University College London, London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Pilling
authors.affiliation: Clinical Psychopharmacology Unit, University College London, London, UK.
authors.forename: Valerie H
authors.initials: VH
authors.lastname: Curran
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000328:Adult; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000523:psychology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011562:Psilocybin / Q000009:adverse effects / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D012944:Social Support; D016896:Treatment Outcome
chemical_list: D017366:Serotonin Receptor Agonists; D011562:Psilocybin