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Exploring How Our Brains Produce Meaning, With The Help Of A Little LSD

The concept of ‘self’ is one that has perplexed researchers since the dawn of neuroscience. Each person possesses an intricate, innumerable set of interests and experiences that make up the recipe that makes them, them. Whether it be a certain song, type of food, a fond pastime, et cetera, it seems that we have a way of giving meaning or finding meaningfulness in certain things more than others, but what occurs in the brain when we attribute meaning to something? With the help of the psychedelic substance known as LSD, a team of researchers at Zürich University Hospital for Psychiatry believe they have uncovered the region of the brain in which meaning is produced. Their findings have since been published in Current Biology.

Previous studies involving LSD have shown that the substance can have an effect on an individual’s attribution of meaning and personal relevance to their surroundings. It is also common to hear of LSD changing the way in which a person perceives themselves, as the separation between the self and one’s surroundings begins to blur. What scientists have been unable to determine, however, is the specific region of the brain that is altered by the LSD in order to induce this heightened attribution of meaning.

For the ZU study, the team of researchers designed a systematic investigation in which participants were asked to blindly undergo one of three treatments: a placebo pretreatment followed by a placebo dose, a placebo pretreatment followed by a dose of LSD, or a ketanserin pretreatment followed by a dose of LSD. Ketanserin is substance that has been found to inhibit the effectiveness of LSD by preventing it from interacting with serotonin receptors in the brain known as 5-HT2ARs.

After receiving their pretreatment and subsequent dose of LSD or placebo, the participants were then presented with a series of songs that they were asked to rank in order of personal meaningfulness. Some of the songs on the list were ones that the participants had already considered to be meaningful, while the others they had considered to be neutral or without much meaning.

Those who were under the effect of the uninhibited LSD managed to find special meaning in musical pieces that they had previously deemed meaningless. However, those who had received either the placebo treatment or the ketaserin pretreatment demonstrated no change in their attribution of meaningfulness, despite the fact that ketaserin does not prevent LSD from interacting with the brain’s dopamine receptors. fMRI scans of these three varying states of the brain with only the uninhibited LSD treatment resulting in induced meaning attribution allowed the researchers to distinguish that the 5-HT2A receptors must be the culprit.

"By combining functional brain imaging and detailed behavioral assessments using a specific experimental paradigm to investigate personal relevance or meaning of music pieces, we were able to elucidate the neurobiological correlates of personal relevance processing in the brain," says Katrin Preller of the Zürich University Hospital for Psychiatry. "We found that personal meaning attribution and its modulation by LSD is mediated by the 5-HT2A receptors and cortical midline structures that are also crucially involved in enabling the experience of a sense of self."

She continues, "Excessive stimulation of 5-HT2A receptors seems to underlay the experience of loosening of self/ego boundaries, disrupted self-referential processing and thus the related impairment of making meaning and attributing personal relevance to percepts and experiences seen in various psychiatric disorders. Therefore, it is important to consider this receptor subtype as potential target for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution."

Further studies for understanding the brain’s tendency to attribute meaning to experiences will involve visual or tactile stimuli. With a conclusive collection of data regarding this behavior of the brain, the researchers hope to explore the relevance of their findings in possible treatments for those who suffer from dysfunctional attributions of meaning because of an underlying psychiatric disorder.


Preller, K. H., M. Herdener, T. Pokorny, A. Planzer, R. Kraehenmann, P. Stampfli, M. E. Liechti, E. Seifritz, and F. X. Vollenweider. "The Fabric of Meaning and Subjective Effects in LSD Induced States Depend on Serotonin 2A Receptor Activation." Cell. Current Biology, n.d. Web.

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