Clinical TrialSingle-armTreatment-Resistant Depression (TRD)PsilocybinPsilocybinCompleted

Imperial College London Open-Label Psilocybin Pilot for Treatment-Resistant Depression (Carhart-Harris / Lyons 2016–2018)

This unregistered trial (n=30) was an open-label, uncontrolled pilot study of psilocybin for treatment-resistant depression in patients and healthy controls, which found that psilocybin reduced pessimism bias and improved depressive symptoms.

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Target Enrollment
20 participants
Study Type
Phase II interventional
Design
Non-randomized

Detailed Description

This synthetic trial has been added to our database because a psychedelic paper (about a clinical trial) references this trial, but no (live) registration can be found. The study investigated the effects of psilocybin on pessimism biases in patients with treatment-resistant depression (TRD) compared to matched healthy controls.

Participants received two oral doses of psilocybin, 10 mg and 25 mg, administered one week apart alongside psychological support. The primary outcomes measured changes in future-event forecasting accuracy and depressive symptom severity using the QIDS-SR scale.

Results indicated that psilocybin treatment significantly decreased pessimism bias and improved depressive symptoms in the TRD group. Furthermore, patients demonstrated more accurate predictions of future life events following treatment, a change not observed in the healthy control group.

Study Arms & Interventions

TRD patients

experimental

Patients with treatment-resistant depression receiving two oral dosing sessions of psilocybin (10 mg and 25 mg) one week apart, with psychological support.

Interventions

  • Psilocybin10 mg
    via Oral• single dose• 1 doses total

    Initial safety dose

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Subsequent treatment dose administered 1 week after the first dose

Control subjects

no intervention

Matched, untreated non-depressed healthy control subjects.

Study Details

Locations

United Kingdom

Related Publications

PaywallindividualLong-term follow-up

Patients’ accounts of increased “Connectedness” and “Acceptance” after psilocybin for treatment-resistant depression

Six months after an open‑label trial, patients with treatment‑resistant depression reported that psilocybin shifted them from disconnection (from self, others and the world) and emotional avoidance towards increased connectedness and acceptance. This suggests psilocybin may relieve depression via mechanisms opposite to those of conventional antidepressant medications and some short‑term talking therapies.

Published
Journal
Journal of Humanistic Psychology
Authors
Watts, R., Day, C. M., Krzanowski, J., Nutt, D. J., Carhart-Harris, R. L.
Open AccessindividualSecondary analysis

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Psilocybin with psychological support produced rapid symptom reductions in treatment‑resistant depression and, on fMRI, elicited post‑treatment decreases in temporal cortex cerebral blood flow including the amygdala (the latter correlating with symptom improvement) alongside increased resting‑state functional connectivity within the default‑mode network. Increased vmPFC–bilateral inferior lateral parietal connectivity and decreased parahippocampal–prefrontal connectivity predicted 5‑week response, prompting the authors to propose a post‑acute “reset” therapeutic mechanism distinct from acute psychedelic effects.

Published
Journal
Scientific Reports
Authors
Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, N., Wall, M. B., Tanner, M., Kaelen, M., Mcgonigle, J., Murphy, K., Leech, R., Curran, V., Nutt, D. J.
Open AccessindividualSecondary analysis

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

This secondary analysis of the Imperial open-label psilocybin depression pilot found that 17 treatment-resistant depression patients were slower than 16 healthy controls on a dynamic emotional face recognition task at baseline, but this difference was remediated 1 week after the 25 mg psilocybin session. Reaction-time improvement correlated with reduced anhedonia, while clinical symptom rows are treated as mechanism context rather than duplicate efficacy results.

Published
Journal
Psychopharmacology
Authors
Stroud, J., Freeman, T. P., Leech, R., Hindocha, C., Lawn, W., Nutt, D. J., Curran, H. V., Carhart-Harris, R. L.
Open AccessindividualSecondary analysis

Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

This open-label study (n=20) found that the quality of the psychedelic experience (10-25mg psilocybin, measured with the ASC -; specifically oceanic boundlessness) predicted therapeutic effect (lower depression scores).

Published
Journal
Frontiers in Pharmacology
Authors
Roseman, L., Nutt, D. J., Carhart-Harris, R. L.
Open AccessindividualSecondary analysis

Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression

This machine-learning study (n=17) was able to predict the therapeutic effectiveness of psilocybin for treatment-resistant depression using an algorithm applied to natural speech data from the baseline interviews. The results were 85% accurate and 75% precise.

Published
Journal
Journal of Affective Disorders
Authors
Carrillo, F., Sigman, M., Fernández Slezak, D., Ashton, M., Fitzgerald, L., Stroud, J., Nutt, D. J., Carhart-Harris, R. L.
Open AccessindividualSecondary analysis

More realistic forecasting of future life events after psilocybin for treatment-resistant depression

This open-label study (n=30) found that psilocybin corrected pessimism biases in depressed patients and that this change in pessimism was significantly correlated with improvement in depressive symptoms.

Published
Journal
Frontiers in Psychology
Authors
Lyons, T., Carhart-Harris, R. L.
Open AccessindividualSecondary analysis

Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression

In 19 patients with treatment-resistant depression, a single open‑label 25 mg dose of psilocybin reduced ventromedial prefrontal cortex–right amygdala functional connectivity during fearful and neutral (but not happy) face processing and increased amygdala connectivity with occipito‑parietal cortices. The decrease in vmPFC–amygdala coupling correlated with one‑week rumination scores, consistent with the hypothesis that psilocybin restores emotional responsiveness as a key therapeutic mechanism.

Published
Journal
Journal of Psychopharmacology
Authors
Mertens, L. J., Wall, M. B., Roseman, L., Demetriou, L., Nutt, D. J., Carhart-Harris, R. L.