Clinical Trial

.2016 Jul;3(7):619-27.

doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Robin L Carhart-Harris¹, Mark Bolstridge², James Rucker³, Camilla M J Day², David Erritzoe², Mendel Kaelen², Michael Bloomfield⁴, James A Rickard⁵, Ben Forbes⁶, Amanda Feilding⁷, David Taylor⁸, Steve Pilling⁹, Valerie H Curran¹⁰, David J Nutt²

Affiliations

¹ Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. Electronic address: r.carhart-harris@imperial.ac.uk.
² Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
³ Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK; The Institute of Psychiatry, Psychology and Neuroscience, London, UK.
⁴ Department of Psychiatry, University College London, London, UK.
⁵ Barts Health Pharmaceuticals, Barts Health NHS Trust, The Royal London Hospital, London, UK.
⁶ Institute of Pharmaceutical Science, King's College London, London, UK.
⁷ The Beckley Foundation, Beckley Park, Oxford, UK.
⁸ Department of Pharmacy and Pathology, South London and Maudsley NHS Foundation Trust, London, UK.
⁹ Clinical Psychology and Clinical Effectiveness, University College London, London, UK.
¹⁰ Clinical Psychopharmacology Unit, University College London, London, UK.

PMID:27210031
DOI: 10.1016/S2215-0366(16)30065-7

Free article

Clinical Trial

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Robin L Carhart-Harris et al. Lancet Psychiatry.2016 Jul.

Free article

.2016 Jul;3(7):619-27.

doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.

Authors

Affiliations

¹ Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. Electronic address: r.carhart-harris@imperial.ac.uk.
² Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
³ Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK; The Institute of Psychiatry, Psychology and Neuroscience, London, UK.
⁴ Department of Psychiatry, University College London, London, UK.
⁵ Barts Health Pharmaceuticals, Barts Health NHS Trust, The Royal London Hospital, London, UK.
⁶ Institute of Pharmaceutical Science, King's College London, London, UK.
⁷ The Beckley Foundation, Beckley Park, Oxford, UK.
⁸ Department of Pharmacy and Pathology, South London and Maudsley NHS Foundation Trust, London, UK.
⁹ Clinical Psychology and Clinical Effectiveness, University College London, London, UK.
¹⁰ Clinical Psychopharmacology Unit, University College London, London, UK.

PMID:27210031
DOI: 10.1016/S2215-0366(16)30065-7

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.

Findings: 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.

Interpretation: 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.

Funding: Medical Research Council.

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Comment in

Altered states: psilocybin for treatment-resistant depression.
Cowen P.Cowen P.Lancet Psychiatry. 2016 Jul;3(7):592-3. doi: 10.1016/S2215-0366(16)30087-6. Epub 2016 May 17.Lancet Psychiatry. 2016.PMID:27210032No abstract available.
Psilocybin: panacea or placebo?
Hendrie C, Pickles A.Hendrie C, et al.Lancet Psychiatry. 2016 Sep;3(9):805-6. doi: 10.1016/S2215-0366(16)30103-1.Lancet Psychiatry. 2016.PMID:27568263No abstract available.
Question-based Drug Development for psilocybin.
Dijkstra FM, Jacobs GE, Cohen AF.Dijkstra FM, et al.Lancet Psychiatry. 2016 Sep;3(9):806-7. doi: 10.1016/S2215-0366(16)30214-0.Lancet Psychiatry. 2016.PMID:27568265No abstract available.

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Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

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Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

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