AV Lebedev, M Kaelen, M Lövdén, J Nilsson, A Feilding, DJ Nutt, RL Carhart‐Harris
5 min
This study investigates the neurobiological mechanisms underlying the long-term personality changes often reported after psychedelic experiences. Specifically, the researchers tested whether LSD-induced shifts in brain entropy—a measure of the unpredictability or complexity of neural activity—could predict lasting changes in the personality trait of openness, as measured two weeks after the drug session.
Nineteen healthy adults participated in a placebo-controlled, balanced-order study. Participants underwent resting-state functional MRI (fMRI) scans while under the influence of either LSD or a placebo. During the scanning sessions, participants were instructed to rest with their eyes closed, with one scan specifically involving music listening. The researchers used information theory to calculate sample entropy from the fMRI data, evaluating how LSD affected the complexity of brain activity across various functional networks. They then correlated these acute neural changes with changes in personality scores (using the NEO-PI-R) assessed two weeks later.
LSD was found to significantly increase global brain entropy, affecting both primary sensory networks and higher-order cognitive systems. These increases in entropy were not merely transient; they served as a significant predictor of subsequent increases in trait openness. The predictive power of these entropy shifts was most pronounced during music-listening sessions and in individuals who reported higher levels of ego-dissolution during the acute experience. These results support the entropic brain hypothesis, which posits that psychedelics induce a state of primary consciousness characterized by increased neural disorder, which may facilitate lasting psychological transformation.
This research provides a potential biological mechanism for the therapeutic potential of psychedelics. By linking acute, drug-induced neurophysiological changes to enduring personality shifts, the study offers a framework for understanding how "existential shock" or peak experiences can lead to meaningful, long-term psychological growth. It also highlights the importance of environmental factors, such as music, in shaping the neurobiological and psychological outcomes of psychedelic-assisted therapy.
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.
Alex: That's a tidy story. Which is usually when a careful reader starts looking for where it might break.
Sam: Right. The most immediate constraint is sample size. The correlation between entropy and Openness is statistically significant, but the confidence intervals are wide, and this needs replication in a larger cohort before you'd want to weight it heavily.
Alex: And the confounding structure seems genuinely difficult here.
Sam: It is. Set and setting — the participant's expectations, the therapeutic context, the music, the relationship with the guide — all of these vary across sessions and are hard to orthogonalize from the pharmacological effect. The entropy measure captures neural dynamics, but those dynamics are themselves shaped by the psychological context. So you can't cleanly attribute the Openness change to the drug alone, or to the entropy alone, or to the subjective experience alone. They're entangled.
Alex: Did they address motion artifacts? That's a standing concern with fMRI under psychedelics — participants aren't exactly lying still.
Sam: Standard motion correction pipelines were applied, but it's a legitimate concern. Psychedelic states can involve subtle but systematic movement patterns that correlate with the subjective intensity of the experience — which is exactly the variable you're trying to measure. It's not a fatal flaw, but it's where a careful referee would push back and ask for additional sensitivity analyses.
Alex: So the broader picture is: a plausible neural mechanism linking acute drug effects to trait-level change, but a causal chain with several links that each need independent validation.
Sam: That's a fair read. What the paper does well is frame a testable mechanistic hypothesis — entropy as the mediating variable between pharmacology and personality — and provide initial evidence that the correlation exists. What it doesn't yet establish is the full causal structure. The logical next step would be designs that manipulate the entropic state more directly, or that use real-time neural feedback to test whether modulating entropy during the session actually shifts the Openness outcome.
Alex: A mechanistic foothold, then, rather than a settled answer. Thanks for walking through it, Sam, and thanks to everyone listening to ResearchPod.