What makes your world colorful? Many people would think of experiences, music, people, or even objects that significantly impacted their lives. So why might an experience be meaningful to us, but not to others? According to Katrin Preller, a psychopharmacologist at the University Hospital for Psychiatry Zürich in Switzerland,1 certain neurochemicals and receptors in the brain are responsible for creating that sense of meaningfulness. But Preller’s research has a unique twist: some of her study participants have been given LSD (lysergic acid diethylamde), a highly potent synthetic hallucinogen2 that is known to stimulate dopamine receptors.

Earlier studies indicated that LSD alters the way people attribute meaning to their environment, but researchers were not exactly sure what parts of the brain and which neurochemicals were responsible. Thus, for this study, Preller and her colleagues began by confirming the effects of LSD on the participants’ state of consciousness, mood, and anxiety.1 They then compiled a series of songs that were either neutral, or had previously been identified as meaningful by the participants. The researchers subsequently administered either a placebo, LSD, or LSD with ketanserin (another drug) to the participants and asked them to rank the meaningfulness of the songs.

For the individuals under the influence of LSD, previously neutral songs took on meaning, but Preller and her colleagues found that the psychedelic effects of LSD disappeared for participants who also took ketanserin, a drug that hinders the ability of LSD to act on serotonin receptors (known as 5-HT2ARs)1.

A molecule of LSD bound to a larger serotonin receptor. The orange bar keeps LSD bound to the receptor.3

Using brain imaging studies, Preller confirmed “that personal meaning attribution and its modulation by LSD is mediated by the 5-HT2A receptors” and she identified the “cortical midline structures that are also crucially involved in enabling the experience of a sense of self”.1 According to Preller, excessive stimulation of the 5-HT2A receptors can lead to the “experience of loosening of self/ego boundaries” and the eventual “impairment of making meaning and attributing personal relevance to percepts and experiences seen in various psychiatric disorders.” As a result, Preller believes that 5-HT2A receptors should be targeted in treatment of psychiatric disorders in which affected individuals experience dysfunctional attributions of meaning.1

Preller also hopes to eventually test whether the results of this study are similar in response to visual and tactile stimuli. Ultimately, her research helps to reveal and explore the scientific mechanisms that color our world with meaning—all with the help of a little LSD.

References

  1. Katrin H. Preller, Marcus Herdener, Thomas Pokorny, Amanda Planzer, Rainer Kraehenmann, Philipp Stämpfli, Matthias E. Liechti, Erich Seifritz, Franz X. Vollenweider. The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation. Current Biology 2017, 27, 451-457.

  2. LSD. http://www.cesar.umd.edu/cesar/drugs/lsd.asp (accessed 2/20/17), part of Center of Substance Abuse Research.

  3. This is LSD attached to a brain cell serotonin receptor. https://www.med.unc.edu/pharm/news/faculty-news/this-is-lsd-attached-to-a-brain-cell-serotonin-receptor (accessed 2/21/17), part of UNC School of Medicine.

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