LSD-induced entropic brain activity predicts subsequent personality change

Authors: AV Lebedev, M Kaelen, M Lövdén, J Nilsson, A Feilding, DJ Nutt, RL Carhart-Harris.


About the study

Here we find a relationship between LSD-induced ‘entropy’ or ‘chaos’ in the brain and changed personality traits 2 weeks later. The study uses sophisticated analysis techniques to measure ‘sample entropy’ in the fMRI signal – an indicator of more chaotic, less predictable brain dynamics. Ratings of the personality trait ‘openness’ (linked to imagination, aesthetic appreciation, non-conformity, and creativity) were higher 2 weeks after the LSD experience, and those subjects showing the greatest brain entropy on LSD showed the greatest increase in openness 2 weeks later.

This finding suggests that psychedelics’ ‘entropic’ effect on brain activity may be responsible for positive psychological effects, opening the mind up to change that can be profound and lasting in nature. The study therefore not only demonstrates that LSD alters brain dynamics, but also how it can be useful in treating disorders. This is the first time LSD’s therapeutic potential has been directly linked to a biological marker in the brain, helping to build the rationale for developing psychedelic therapies.

Other interesting findings include that the relationship between brain ‘entropy’ and personality change was made even stronger by music: the correlation was the strongest during the music and post-music scans. This suggests that music can help establish the kind of (entropic) brain dynamics required for personality change.

We also found an additional effect of self-reported ‘ego-dissolution’ (the loss of a sense of self and feeling of ‘oneness’ with the world). Those subjects who reported the greatest amount of ‘ego-dissolution’ by music (on a post-scan questionnaire) AND showed the greatest increase in entropy (in certain brain networks) were also those who demonstrated the most marked increase in openness. This suggests that both music and the ‘ego-dissolution’ experience may be desirable in a therapeutic context.



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.

Keywords: LSD-25; neuroplasticity; entropy; personality; transpersonal experience

"It is well known that highly profound psychological experiences, whatever their cause, can lead individuals to question prior assumptions and change their behavior and outlook, sometimes in a fundamental and lasting way. In a similar way, psychedelics may serve as a kind of “existential shock” therapy, confronting individuals with the illusory nature of their self or ego and its attachments."

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