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Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinCompleted

Assessing the subjective intensity of oral psilocybin in patients with treatment-resistant depression: a pilot study (PSILODEP-PILOT)

This open-label trial (n=12), also known as PSILODEP-PILOT is the first to test psilocybin in patients in the UK. The study found psilocybin (10-25mg, x2) to be well-tolerated.

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

Detailed Description

Open-label, interventional Phase II pilot in treatment-resistant major depression testing two single oral doses of psilocybin (10 mg and 25 mg) given one week apart in the same participants.

Primary outcome: QIDS measured at baseline, one day and one week post-dose; secondary outcomes include BDI, HAM-D and MADRS. Safety and tolerability were reported and multiple peer-reviewed results publications are linked to the registry record.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Study Arms & Interventions

Psilocybin

experimental

Open-label treatment with two oral psilocybin doses separated by one week (within-subject).

Interventions

  • Psilocybin10 - 25 mg
    via Oral• two sessions• 2 doses total

    Two oral doses: 10 mg and 25 mg, separated by one week.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • 1. Major depression of a moderate to severe degree (17+ on the 21-item HAM-D)
  • 2. No improvement despite two courses of antidepressant treatment for adequate duration (≥6 weeks) within current episode
  • 3. No magnetic resonance imaging (MRI) contraindications

Exclusion Criteria

  • 1. Current or previously diagnosed psychotic disorder
  • 2. Immediate family member with a diagnosed psychotic disorder
  • 3. Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure etc)
  • 4. History of suicide attempts
  • 5. History of mania
  • 6. Blood or needle phobia
  • 7. Positive pregnancy test at screening or during the study
  • 8. Current drug or alcohol dependence
  • 9. Allergy to gelatine or lactose
  • 10. Lack of appropriate use of contraception
  • 11. Breastfeeding

Primary Results(6 publications)

Participants

N = 19M. et al. 2018 →
N = 20L. et al. 2018 →
N = 19Mean age: 43.1 across armsM. et al. 2022 →

Δ in QIDS-SR from Baseline

Change from Baseline

PsilocybinΔ-11.8 [-14.35, -9.15]Day 7·L. et al. 2016 →
Psilocybin—Day 7·M. et al. 2018 →

Δ in BDI-II from Baseline

Change from Baseline

Psilocybin—Day 7·L. et al. 2018 →

Response Rates

Complete remission: BDI score ≤9

8/12(66.7%)·L. et al. 2016 →
5/12(41.7%)·L. et al. 2016 →

Response: ≥50% reduction in BDI score relative to baseline

7/12(58.3%)·L. et al. 2016 →

Remission (BDI 9)

?/?·L. et al. 2018 →

Response (>50% reduction)

?/?·L. et al. 2018 →

≥50% reduction from baseline in QIDS-SR16 (responder status)

13/16(81.3%)·D. et al. 2024 →
12/16(75.0%)·D. et al. 2024 →
11/16(68.8%)·D. et al. 2024 →
12/16(75.0%)·D. et al. 2024 →
9/16(56.3%)·D. et al. 2024 →
7/16(43.8%)·D. et al. 2024 →
7/16(43.8%)·D. et al. 2024 →

Adverse Events (from all publications)

Arm / GroupnAny TEAESevereSeriousDiscont.
Psilocybinexperimental1212(100.0%)0(0.0%)0(0.0%)0(0.0%)
Psilocybinexperimental7————
Psilocybinexperimental19————
Psilocybinexperimental20————
Psilocybinexperimental19————
Psilocybinexperimental16————

* Open-label single-arm study; adverse events were monitored during the two dosing sessions and up to 3 months of follow-up. Reported adverse reactions were transient anxiety during drug onset (all patients), transient confusion or thought disorder (9), mild transient nausea (4), transient headache (4), and paranoia in 1 patient. No serious, unexpected, or prolonged psychotic adverse events occurred; no patients discontinued due to adverse events were reported.

* The paper excerpt provided reports outcomes on nature relatedness, political perspective, and depressive symptoms, but does not include an adverse event table or any TEAE/SAE/discontinuation summary for the psilocybin arm. Safety counts could not be extracted from the supplied text.

* This paper is a qualitative interview study nested within a larger psilocybin depression trial and does not report treatment-emergent adverse event summary counts. It mentions one participant disliked the music in the first session and switched playlist for the second session, but no TEAE counts, severity, seriousness, discontinuations, or special-interest adverse events are provided.

* The provided text does not include a safety/adverse event table or explicit TEAE counts. It only reports that the study was described as safe in the conclusion. 19 completed post-treatment fMRI scans, but the treatment cohort was 20 participants.

* The extracted text does not report a safety/adverse event table or any summary counts for treatment-emergent adverse events. It describes 19 participants receiving psilocybin (10 mg then 25 mg) but provides no TEAE, severe TEAE, SAE, discontinuation, or special-interest AE counts.

* Open-label psilocybin monotherapy dataset for treatment-resistant depression; the provided text reports efficacy/neuroimaging analyses and does not include a treatment-emergent adverse event summary table or counts.

Study Details

Locations

Imperial Clinical Research Facility — London, United Kingdom

Related Publications

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

Published
Authors
Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M., Nutt, D. J., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., Taylor, D., Pilling, S., Curran, H. V.

Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression

Published
Authors
Lyons, T., Carhart-Harris, R. L.

The hidden therapist: evidence for a central role of music in psychedelic therapy

Published
Authors
Kaelen, M., Giribaldi, B., Raine, J., Evans, J., Timmermann, C., Roseman, L., Feilding, A., Nutt, D. J., Carhart-Harris, R. L., Rodrigues, N. B.

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression

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

Body mass index (BMI) does not predict responses to psilocybin

Published
Authors
Giribaldi, B., Lyons, T., Rosas, F. E., Kartner, L., Buchborn, T., Douglass, H., Roseman, L., Timmermann, C., Erritzoe, D., Nutt, D. J., Carhart-Harris, R. L., Spring, P.

Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression

Published
Authors
Wall, M., Nutt, D. J., Kaelen, M., Carhart-Harris, R. L., Roseman, L.

Brain dynamics predictive of response to psilocybin for treatment-resistant depression

Published
Authors
Vohryzek, J., Cabral, J., Lord, L. D., Fernandes, H. M., Roseman, L., Nutt, D. J., Carhart-Harris, R. L., Deco, G., Kringelbach, M. L.

Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity

Published
Authors
Copa, D., Erritzoe, D., Giribaldi, B., Nutt, D. J., Carhart-Harris, R. L., Tagliazucchi, E.

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