More Realistic Forecasting of Future Life Events After Psilocybin for Treatment-Resistant Depression
Open accessAbstract
Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes. Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD). Methods: Patients with TRD (n=15) and matched, untreated non-depressed controls (n=15) performed the Prediction Of Future Life Events (POFLE) task. The POFLE task requires participants to predict the likelihood of certain life events occurring within a 30-day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias. Psilocybin was administered in two oral dosing sessions (10mg and 25mg) one week apart. Main outcome measures were collected at baseline and one week after the second dosing session. Results: Patients showed a significant pessimism bias at baseline (t(14)=-3.260, p=0.006; 95% CI [-0.16,-0.03], g=1.1) which was related to the severity of their depressive symptoms (rs=-0.55, p=0.017). One week after psilocybin treatment, this bias was significantly decreased (t(14)=-2.714, p=0.017; 95% CI [-0.21,-0.02], g=0.7) and depressive symptoms were greatly improved (t(14)=7.900, p<0.001; 95% CI [16.17,28.23], d=1.9); moreover, the magnitude of change in both variables was significantly correlated (r=-0.57, p=0.014). Importantly, post treatment, patients became significantly more accurate at predicting the occurrence of future life events (t(14)=1.857, p=0.042; 95% CI [-0.01,0.12], g=0.6) whereas no such change was observed in the control subjects. Conclusions: These findings suggest that psilocybin with psychological support might correct pessimism biases in treatment-resistant depression, enabling a more positive and accurate outlook.
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Evens, R., Schmidt, M. E., Majić, T., & Schmidt, T. T. (2023) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253231172254 · Cited by 56 · see citing works
“48 Four studies reported on the two subscales ‘attitudes toward life and self’ of the Persisting Effects Questionnaire.”
BackgroundClinical specificity profile for novel rapid acting antidepressant drugs
Scala, M., Fanelli, G., De Ronchi, D., Serretti, A., & Fabbri, C. (2023) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000488 · Cited by 41 · see citing works
Psilocybin, an Effective Treatment for Major Depressive Disorder in Adults - A Systematic Review
Watford, T., & Masood, N. (2024) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.23.1120 · Cited by 23 · see citing works
Scala, M., Fabbri, C., Fusar-Poli, P., Di Lorenzo, G., Ferrara, M., Amerio, A., Fusar-Poli, L., Pichiecchio, A., Asteggiano, C., Menchetti, M., et al. (2024) · CNS Spectrums · doi:10.1017/s1092852924002268 · Cited by 9 · see citing works
Fang, Q., Chan, V. K. Y., Chan, S. S. M., Jiao, Y., Wang, J., & Li, X. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.115960 · Cited by 9 · see citing works
- Authors
- Lyons, T., & Carhart-Harris, R. L.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Lyons, Taylor
- Venue
- Frontiers in Psychology
- Publisher
- Frontiers Media SA
- Published
- 2018-10-12
- Volume
- 9
- Pages
- 1721-1721
- ISSN
- 1664-1078 (ISSN-L)
- PMC
- PMC6194345
- OpenAlex
- W2889504249
- Cited by
- 77
- References
- 93
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 15 · 2023: 24 · 2022: 9 · 2021: 4 · 2020: 8 · 2019: 6
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Psychology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Medical Research Council (MR/J00460X/1)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Social Psychology › Psychological Well-being and Life Satisfaction
- Keywords
- psilocybin, treatment-resistant depression, pessimism bias, optimism, forecast accuracy, classical psychedelics, depressive symptoms, psychological support
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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