Project ID NS-MH2024_58


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Mental Health & Psychological Sciences, Department of PsychologyWebsite

Co Supervisor 1B Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Institute of Pharmaceutical ScienceWebsite

Additional Supervisor Prof. James Rubin and Dr Matt Butler

Examining the role of placebo effects in the neurocognitive response to psychedelics

Accumulating evidence suggests that psychedelic drugs show therapeutic promise for a range of mental health conditions and have the potential to inform our understanding of the neural bases of psychopathology and perception. Despite recent progress, multiple lines of evidence point to the potential roles of non-pharmacological factors, including placebo and nocebo effects, in the effects of psychedelics. However, it remains unknown whether placebos can reproduce the neurophysiological and cognitive effects of psychedelics. Moreover, there has not yet been a comprehensive attempt to disambiguate placebo and pharmacological effects in the neurocognitive response to psychedelics.

This project will first examine whether a deceptive placebo intervention (medical air presented as nitrous oxide) can reproduce classic psychedelic effects including acute neurophysiological (increased EEG signal complexity), phenomenological, cognitive, and affective changes. Next, we will contrast the impact of the placebo intervention versus nitrous oxide on these metrics and adverse event reporting to quantify the relative magnitude of placebo/nocebo contributions to any psychedelic effects. These experiments will also investigate predictors of responsiveness on the above metrics to determine whether the same trait measures predict responses to both placebos and psychedelics. The results are expected to advance understanding of the role of placebo and nocebo effects in psychedelics with implications for their clinical, scientific and recreational use.

Training: The project will be supervised by a team of leading researchers with expertise in psychopharmacology and psychedelics, EEG, and placebo/nocebo. The PhD candidate will complete training in the administration of nitrous oxide and the placebo, the administration and analysis of EEG, cognitive and psychometric assessments, and participant recruitment.

Year 1: Training, public involvement and piloting, and completion of first EEG experiment.
Year 2: EEG analysis and completion of second EEG experiment, conference presentation, journal publications.
Year 3: EEG analysis, thesis write-up, conference presentation, journal publications.

Representative Publications

Parsons, R., Bergmann, S., Wiech, K., & Terhune, D. B. (2021). Direct verbal suggestibility as a predictor of placebo hypoalgesia responsiveness. Psychosomatic Medicine, 83, 1041-1049.

Polychroni, N., Herrojo Ruiz, M., & Terhune, D. B. (2022). Introspection confidence predicts EEG decoding of self-generated thoughts and meta-awareness. Human Brain Mapping, 43, 2311-2327. perception: A randomised, double-blind, placebo-controlled trial. Psychopharmacology, 236, 1159-1170.

Heller, M. K., Chapman, S. C., & Horne, R. (2022). Beliefs About Medicines Predict Side-Effects of Placebo Modafinil. Annals of Behavioral Medicine, 56(10), 989-1001.

Horne, R., Chapman, S., Glendinning, E., Date, H. L., Guitart, J., & Cooper, V. (2019). Mind matters: treatment concerns predict the emergence of antiretroviral therapy side effects in people with HIV. AIDS and Behavior, 23, 489-498.

Watkinson, A., Chapman, S. C., & Horne, R. (2017). Beliefs about pharmaceutical medicines and natural remedies explain individual variation in placebo analgesia. The Journal of Pain, 18(8), 908-22.