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With the help of the psychedelic drug LSD, researchers now have an understanding of how our brains attribute meaning to things in our lives, like music or particular experiences. The findings are published in a Current Biology study.

Katrin Preller and colleagues asked participants to take a placebo, LSD, or LSD plus ketanserin, a drug that counteracts LSD’s effects by blocking a specific receptor. The participants then ranked the meaningfulness a series of songs they had previously identified as particularly meaningful, neutral, or without meaning. For the participants on LSD, previously meaningless songs became meaningful. This effect was reduced when they were given the drug ketanserin.

Katrin Preller gives valuable insights into which receptors and brain regions are involved in perceiving things as meaningful.

What motivated this study?

Attribution of meaning and personal relevance is important for our everyday lives. In psychiatric disorders, the attribution of meaning is often altered, and the mechanisms causing this were unknown. LSD has also been shown to alter the attribution of meaning and personal relevance to the environment and our sense of self. However, the exact mechanism and brain structures had not been investigated yet. Therefore, LSD offered a unique opportunity to investigate these phenomena.

How does meaning affect our lives?

In our everyday life, we constantly evaluate our environment and attribute personal relevance to sensory perceptions, thereby rendering things like friends, personal items, or our favorite kind of music meaningful for our self. This attribution of personal relevance is typically impaired in a number of psychiatric disorders. In addiction, for example, personal relevance is excessively attributed to drug contexts, but decreased for nondrug stimuli. Exaggerated attribution of personal meaning to objects is also found in phobia, like arachnophobia. An unusual over-attribution of meaning to minor cues with little relevance can contribute to the development of psychotic experiences and paranoid behavior.

What was found in this study?

This study highlights for the first time that the 2A subtype of serotonin receptors is key in LSD-induced psychotropic effects and in changes of the perceived personal relevance of sensory stimuli. We demonstrate that the psychedelic effects of LSD can be fully blocked with the selective serotonin 2A receptor ketanserin.

By combining functional brain imaging and behavioral assessments using music pieces, we were able to explain personal relevance processing in the brain. We found that personal meaning attribution and LSD’s effect on it comes from the 5-HT2A receptor and cortical midline structures that are also involved in our sense of self. Taken together, the data sheds new light on self-experience and personal meaning attribution. This finding is important in further understanding the impaired meaning that comes with various psychiatric diseases.

Why was music music?

Music is a very powerful stimulus to induce personal relevance and meaning processing. We combined functional brain imaging and detailed behavioral assessments with LSD and ketanserin which blocks the serotonin 2A receptor.

Could this lead to new treatments for psychiatric disorders?

Yes, the study revealed the 5-HT2A receptor as a potential target for the treatment of psychiatric illnesses that alter personal relevance attribution

What’s Next? Can LSD can unlock more of the mind?

We‘re looking at the role of the 5-HT2A receptor in different cognitive processes that are important in clinical populations. We are especially interested in finding out whether our results can be generalized to other senses, such as visual or tactile stimuli, and how our findings may be relevant for the understanding of clinical disorders involving dysfunctional meaning making. Next, we are going to design research protocols which step into altered visual meaning attribution.

So far there are only very few studies investigating the effects of LSD with modern state-of-the-art study designs and neuroimaging methods. Therefore, there certainly are more aspects of LSD that have not been studied yet that will tell us more about how the brain and mind works.


Current Biology, Preller et al.: “The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation” http://www.cell.com/current-biology/fulltext/S0960-9822(16)31510-X

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