LSD-induced entropic brain activity predicts subsequent personality change
In a placebo‐controlled resting‑state fMRI study, intravenous LSD robustly increased sample entropy across sensory and higher‑order brain networks. These LSD‑induced entropy increases—most predictive during music listening and when ego‑dissolution was reported—forecasted enduring increases in the personality trait openness at a two‑week follow‑up.
Authors
- Robin Carhart-Harris
- David Nutt
- Amanda Feilding
Published
Abstract
Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced‐order, placebo‐controlled study, we investigated biological predictors of post‐lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO‐PI‐R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5‐min eyes‐closed resting‐state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time‐series. Mixed‐effects models were used to evaluate drug‐induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2‐week follow‐up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music‐listening scans and when “ego‐dissolution” was reported during the acute experience. These results shed new light on how LSD‐induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203–3213, 2016. © 2016 Wiley Periodicals, Inc.
Research Summary of 'LSD-induced entropic brain activity predicts subsequent personality change'
Introduction
Lebedev and colleagues situate their work within renewed scientific interest in classic psychedelics after decades of prohibition, noting preliminary therapeutic signals from small-scale studies. Earlier research has shown that single high-dose psychedelic sessions can produce persistent increases in the personality domain openness, especially when accompanied by so-called mystical or peak experiences that involve ego-dissolution and a sense of unity. Neuroimaging and electrophysiological studies have suggested that psychedelics disrupt typical brain organisation, producing desegregation of network activity and a shift toward more random, higher-entropy dynamics; the "entropic brain" hypothesis frames altered states along a continuum from highly organised (secondary) consciousness to more disordered (primary) consciousness, the latter being associated with experiences such as ego-dissolution. This study tested whether acute LSD-induced increases in brain entropy predict subsequent lasting changes in personality. Specifically, the investigators hypothesised that LSD would raise sample entropy of fMRI time-series, that entropy increases in higher-order networks (for example, frontoparietal, salience, default-mode) would positively predict increases in trait openness measured 2 weeks later, and that these relationships would be enhanced by in-scan music listening and by reported ego-dissolution during the acute drug state. The Introduction also summarises screening and safety steps and notes that most participants had prior psychedelic experience but had abstained for at least two weeks before the first study day.
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Study Details
- Study Typeindividual
- Journal
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- APA Citation
Lebedev, A., Kaelen, M., Lövdén, M., Nilsson, J., Feilding, A., Nutt, D., & Carhart‐Harris, R. (2016). LSD-induced entropic brain activity predicts subsequent personality change. Human Brain Mapping, 37(9), 3203-3213. https://doi.org/10.1002/hbm.23234
References (26)
Papers cited by this study that are also in Blossom
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)
Carhart-Harris, R. L., Leech, R., Erritzoe, D. et al. · Schizophrenia Bulletin (2012)
Carhart-Harris, R. L., Leech, R., Shanahan, M. et al. · Frontiers in Human Neuroscience (2014)
Carhart-Harris, R. L., Kaelen, M., Bolstridge, M. et al. · Psychological Medicine (2016)
Frecska, E., Móré, C. E., Vargha, A. et al. · Journal of Psychoactive Drugs (2012)
Kirchner, K. · Journal of Psychopharmacology (2014)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Griffiths, R. R. · Journal of Psychopharmacology (2008)
Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)
Show all 26 referencesShow fewer
Hendricks, P. S., Thorne, C. B., Clark, B. et al. · Journal of Psychopharmacology (2015)
Johnson, M. W., Richards, W. A., Griffiths, R. R. · Journal of Psychopharmacology (2008)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
Kaelen, M., Barrett, F. S., Roseman, L. et al. · Psychopharmacology (2015)
Kometer, M., Pokorny, T., Seifritz, E. et al. · Psychopharmacology (2015)
Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)
Lebedev, A. V., L€ Ovd En, M., Rosenthal, G. et al. · Human Brain Mapping (2015)
Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)
Majic, T., Schmidt, T. T., Gallinat, J. · Journal of Clinical Psychopharmacology (2015)
Muthukumaraswamy, S. D., Carhart-Harris, R. L., Moran, R. J. et al. · Journal of Neuroscience (2013)
Osório, F. L., Sanches, R. F., Macedo, L. et al. · brazilian Journal of Psychiatry (2015)
Passie, T., Halpern, J. H., Stichtenoth, D. O. et al. · CNS Neuroscience and Therapeutics (2008)
Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)
Tagliazucchi, E., Roseman, L., Kaelen, M. et al. · Current Biology (2016)
Thomas, G., Lucas, P., Rielle Capler, N. et al. · Current Drug Abuse Reviews (2013)
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
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Singleton, S. P., Luppi, A. I., Carhart-Harris, R. L. et al. · Nature Communications (2022)
Ornelas, I. M., Cini, F. A., Wießner, I. et al. · Experimental Neurology (2022)
Herrmann, Z., Earleywine, M., De Leo, J. et al. · Journal of Psychoactive Drugs (2022)
Dourron, H. M., Strauss, C., Hendricks, P. S. · Pharmacological Reviews (2022)
Stoliker, D., Egan, G. F., Friston, K. J. et al. · Pharmacological Reviews (2022)
Kaypak, A. C., Raz, A. · Transcultural Psychiatry (2022)
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Hipólito, I., Mago, J., Rosas, F. E. et al. · Psyarxiv (2022)
Arnaud, K. O. S., Sharpe. D. · Journal of Adult Development (2022)
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Whitney, S., Yaden, D. B., Lipson, J. et al. · Frontiers in Psychology (2022)
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Orłowski, P., Ruban, A., Szczypiński, J. et al. · Journal of Psychopharmacology (2022)
Aharon-Almagor, A., Barrett, F. S. · Research Square (2022)
Vollenweider, F. X., Smallridge, J. W. · Pharmacopsychiatry (2022)
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Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)
Doss, M. K., Madden, M. B., Gaddis, A. et al. · Brain (2021)
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Perry, C. M., Malina, M. · Psychopharmacology (2021)
McGovern, H., Leptourgos, P., Hutchinson, B. et al. · Psyarxiv (2021)
Dos Santos, R. G., Rocha, J. M., Rossi, G. N. et al. · Frontiers in Psychiatry (2021)
Lebedev, A. V., Acar, K., Garzón, B. et al. · Scientific Reports (2021)
Kočárová, C., Horacek, J., Carhart-Harris, R. L. · Frontiers in Psychiatry (2021)
Healy, C. J., Lee, K. A. · Chronic Stress (2021)
Savino, A., Nichols, C. D. · Biorxiv (2021)
Studerus, E., Vizeli, P., Harder, S. et al. · Journal of Psychopharmacology (2021)
Payne, J. E., Chambers, R., Liknaitzky, P. · ACS Pharmacology and Translational Science (2021)
Pallavicini, C., Cavanna, F., Zamberlan, F. et al. · Journal of Psychopharmacology (2021)
Luppi, A. I., Carhart-Harris, R. L., Roseman, L. et al. · NeuroImage (2021)
Sanz, C., Pallavicini, C., Carrillo, F. et al. · Consciousness and Cognition (2021)
Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)
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Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)
Varley, T. F., Carhart-Harris, R., Roseman, L. et al. · NeuroImage (2020)
Vollenweider, F. X., Preller, K. H. · Nature Reviews Neuroscience (2020)
Girn, M., Mills, C., Roseman, L. et al. · NeuroImage (2020)
Girn, M., Roseman, L., Bernhardt, B. et al. · Biorxiv (2020)
Pasquini, L., Palhano-Fontes, F., Araújo, D. B. · Journal of Psychopharmacology (2020)
Barnett, L., Muthukumaraswamy, S., Carhart-Harris, R. L. · NeuroImage (2020)
Aday, J. S., Mitzkovitz, C. M., Bloesch, E. K. et al. · Neuroscience and Biobehavioral Reviews (2020)
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Kettner, H., Gandy, S., Haijen, E. C. H. M. et al. · International Journal of Environmental Research and Public Health (2019)
Timmermann, C., Roseman, L., Schartner, M. et al. · Scientific Reports (2019)
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Roseman, L., Haijen, E. C. H. M., Idialu-Ikato, K. et al. · Journal of Psychopharmacology (2019)
Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)
Erritzoe, D., Smith, J. M., Fisher, P. M. et al. · Journal of Psychopharmacology (2019)
Carhart-Harris, R. L. · Current Opinion in Psychiatry (2019)
Richards, W. A., Garcia-Romeu, A. · International Review of Psychiatry (2018)
Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)
Hendricks, P. S. · International Review of Psychiatry (2018)
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Hartogsohn, I. · Frontiers in Human Neuroscience (2018)
Swanson, L. R. · Frontiers in Pharmacology (2018)
Moroz, M., Carhart-Harris, R. L. · IEEE Explore (2018)
Nichols, D. E. · ACS Chemical Neuroscience (2018)
Bouso, J. C., Dos Santos, R. G., Hallak, J. E. · Neuroscience and Biobehavioral Reviews (2018)
Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)
Carhart-Harris, R. L., Roseman, L., Bolstridge, M. et al. · Scientific Reports (2017)
Griffiths, R. R., Johnson, M. W., Richards, W. A. et al. · Journal of Psychopharmacology (2017)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Personality and Individual Differences (2017)
Carhart-Harris, R. L., Nutt, D. J. · Journal of Psychopharmacology (2017)
Viol, A., Palhano-Fontes, F., Onias, H. et al. · Scientific Reports (2017)
Slevc, L. R., Barrett, F. S., Robbins, H. et al. · Frontiers in Psychology (2017)
Liechti, M. E., Dolder, P. C., Grünblatt, E. et al. · Frontiers in Pharmacology (2017)
Sampedro, F., de la Fuente Revenga, M., Valle, M. et al. · International Journal of Neuropsychopharmacology (2017)
Millière, R. · Frontiers in Human Neuroscience (2017)
Liechti, M. E. · Neuropsychopharmacology (2017)
Nour, M. R., Evans, J., Carhart-Harris, R. L. · Journal of Psychoactive Drugs (2017)
Schartner, M., Carhart-Harris, R. L., Barrett, A. B. et al. · Scientific Reports (2017)
Kaelen, M. · Imperial College London (2017)
Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)
Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)
Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)
Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)
McKenna, D., Riba, J. · Current Topics in Behavioral Neurosciences (2016)
Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)
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