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.
Authors
- Robin Carhart-Harris
- Thomas Lyons
Published
Abstract
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 (10 and 25 mg) 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), g = 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.
Conclusion
These findings suggest that psilocybin with psychological support might correct pessimism biases in TRD, enabling a more positive and accurate outlook.
Research Summary of 'More realistic forecasting of future life events after psilocybin for treatment-resistant depression'
Introduction
Major depressive disorder (MDD) is a major contributor to global disease burden and roughly 30% of patients meet criteria for treatment-resistant depression (TRD). Cognitive accounts of depression emphasise biased negative beliefs about the self, the world and the future, whereas the depressive realism hypothesis argues that depressed individuals may actually perceive reality more accurately. Recent empirical work tends to support the cognitive-bias account, showing that depressed patients exhibit pessimistic biases when forecasting future events. Meanwhile, classical psychedelics such as psilocybin have been reported to produce enduring increases in optimism, psychological wellbeing and trait openness after single doses in healthy volunteers, and early clinical research has shown rapid antidepressant effects in patients with cancer-related and treatment-resistant depression. Neurobiological targets implicated in both depression and the psychedelic state include the serotonin 2A receptor (5-HT2A R) and the default mode network (DMN). The present study aimed to test whether patients with TRD display an unjustified pessimism bias when predicting personal future life events, and whether a composite intervention involving psilocybin plus psychological support could remediate that bias. Using a behavioural forecasting task—the Prediction Of Future Life Events (POFLE)—the investigators compared TRD patients before and after two oral psilocybin dosing sessions (10 mg then 25 mg one week apart) and contrasted any change with that seen in matched, untreated healthy control subjects assessed over the same interval. The primary hypothesis was that TRD patients would show a baseline pessimism bias that would be reduced following psilocybin therapy.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
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- APA Citation
Lyons, T., & Carhart-Harris, R. L. (2018). More realistic forecasting of future life events after psilocybin for treatment-resistant depression. Frontiers in Psychology, 9. https://doi.org/10.3389/fpsyg.2018.01721
References (28)
Papers cited by this study that are also in Blossom
Carhart-Harris, R. L., Bolstridge, &. M., Day, C. M. J. et al. · Psychopharmacology (2017)
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Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
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Show all 28 referencesShow fewer
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Psychopharmacology (2011)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Hendricks, P. S., Thorne, C. B., Clark, B. et al. · Journal of Psychopharmacology (2015)
Kraehenmann, R., Preller, K. H., Scheidegger, M. et al. · Biological Psychiatry (2015)
Krebs, T. S., Johansen, P. ˚. Ø. · PLOS ONE (2013)
Liechti, M. E. · Neuropsychopharmacology (2017)
Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)
Nichols, D. E. · Current Topics in Behavioral Neurosciences (2017)
Osório, F. L., Sanches, R. F., Macedo, L. et al. · brazilian Journal of Psychiatry (2015)
Palhano-Fontes, F., Andrade, K. C., Tófoli, L.F. et al. · PLOS ONE (2015)
Ross, S., Bossis, A. P., Guss, J. et al. · Journal of Psychopharmacology (2016)
Schmid, Y., Enzler, F., Gasser, P. et al. · Biological Psychiatry (2015)
Speth, J., Speth, C., Kaelen, M. et al. · Journal of Psychopharmacology (2016)
Studerus, E., Kometer, M., Hasler, F. et al. · Journal of Psychopharmacology (2010)
Watts, R., Day, C. M., Krzanowski, J. et al. · Journal of Humanistic Psychology (2017)
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