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

Authors: Robin L Carhart-Harris, Mark Bolstridge, James Rucker, Camilla M J Day, David Erritzoe, Mendel Kaelen, Michael Bloomfield, James A Rickard, Ben Forbes, Amanda Feilding, David Taylor, Steve Pilling, Valerie H Curran, David J Nutt.

Published in: Lancet Psychiatry.

 

About the Study

This landmark study provides the first clinical evidence that psilocybin might help in the treatment of depression.

We gave oral psilocybin to 12 patients with treatment-resistant depression (meaning they had tried at least 2 other treatment methods and none had worked). The average length of depression was over 18 years, and severity ranged from moderate to severe. Participants received 2 doses (10 and 25mg) 7 days apart, accompanied by psychological support before, during, and after each session.

Following both session, all participants showed improvement in depressive symptoms. On standard measures of depression severity, 67% scored at levels considered ‘in remission’ (depression-free) 1 week after the treatment, and 42% were still in remission 3 months post-treatment.

Also important is that treatment was well-tolerated by all of the patients, with only a small number of minor adverse events (side effects), such as anxiety, confusion, nausea, and headache, none of which were unexpected.

Although this was a very small study with no control group, placebo, or ‘blinding’ (meaning participants were fully aware what they were getting), it shows that psilocybin is safe to give to depressed patients, and that further research into this area is warranted.

This fits well with other recent studies showing therapeutic potential for psilocybin in treating end-of-life anxiety, cigarette smoking, and alcoholism.

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What’s next?

All participants also underwent brain scans; we have recruited 8 more participants, and are now in the process of analysing the brain imaging data, which will show how psilocybin produces its remarkable effects.

 

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.

Psilocybin with psychological support for treatment resistant depression

“It is very exciting that our latest psilocybin study paves the way for a new treatment for depression. For the first time in many years, people who were at the end of the road with currently available treatments, reported decreased anxiety, increased optimism and an ability to enjoy things. This is an unparalleled success and could revolutionize the treatment of depression”.
Amanda Feilding

Link to the article (PDF)

Download the one-page study summary (PDF)