People under the influence of LSD experience an alteration of their sense of self, but also a blurring of the fine line between the self and others. Researchers at the University of Zurich have found a neurochemical mechanism by which LSD causes this effect, which can affect social interactions. The findings could play a major role in the development of new therapies that target psychiatric disorders like depression or schizophrenia.

Social interaction is impaired in several psychiatric disorders. At the same time, people suffering from mental disorders also have a distorted sense of self, which can either be inflated or weakened. For instance, paranoid personality disorder is characterized by a pervasive distrust of others, including even friends, family, and partners. Such people typically use projection, attributing one’s unacceptable thoughts and feelings to other people. But while studies have shown that mental disorders can affect a person’s ability to interact with others — and, conversely, difficulties in social interactions can favor the occurrence of mental disorders — the neurochemical mechanisms that underpin such disorders are poorly understood. Identifying these mechanisms is critical in order to target them with drugs.

Katrin Preller, a postdoctoral researcher at the University Hospital of Psychiatry Zurich, along with colleagues, investigated the link between changes in the sense of self and changes in social interactions. Study participants were given either LSD; ketanserin, a drug that blocks the effects of LSD; or a placebo prior to engaging in a gaze-following game with a virtual human-like character. While completing the task, each participant had their brain activity recorded with functional magnetic resonance imaging. An eye-tracking system objectively told the researchers where the participant’s attention was focused and for how long.

During the social task, the researchers found that LSD reduced activity in the posterior cingulate cortex and the temporal cortex, which are areas of the brain involved in establishing one’s sense of self.  It was no longer clear if the participant or the virtual character took the lead in directing attention.

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“Our study suggests that the effect of LSD to alter self-experience (ie ego-dissolution) also impacts self-experience during social interaction in a way that the borders between self and other are more blurry than usual. Furthermore, this has an impact on basic social abilities,” Preller told ZME Science in an e-mail.

LSD reduced activity in the posterior cingulate cortex and the temporal cortex, brain areas important for establishing one's sense of self. Credit: JNeurosci.

LSD reduced activity in the posterior cingulate cortex and the temporal cortex, brain areas important for establishing one’s sense of self. Credit: JNeurosci.

After taking ketanserin, a drug designed for hypertension that also targets the serotonin 2A receptor (5-HT2A receptor), the participants under the influence of LSD completely came down from the high, showing it blocked LSD’s effects. This was a breakthrough moment in the study, “which meant that LSD-induced effects were dependent on one specific receptor – the serotonin 2A receptor,” Preller said.

“This study suggests that the serotonin 2A receptor is crucial for the modulation of the intertwined processes of self-experience and social cognition. Therefore, it should be considered for the development of new medication for the treatment of symptoms in psychiatric patients suffering from alterations in self-experience and deficits in social abilities,” Preller added. 

For instance, blocking this receptor in patients suffering from an incoherent sense of self, like is the case with schizophrenia, could improve their symptoms as well as their social abilities. Patients who suffer from depression and are too self-focused, on the other hand, could benefit from stimulating this receptor.

Next, the researchers plan to “further investigate the neuropharmacology of psychedelics in order to inform clinical application as well as the development of novel and more effective pharmacotherapies,” Preller told me.

The findings appeared in the Journal of Neuroscience.