LSD blurs boundaries between the experience of self and other

March 19, 2018

Science Daily/University of Zurich

LSD reduces the borders between the experience of our own self and others, and thereby affects social interactions. Researchers at the University of Zurich have now found that the serotonin 2A receptor in the human brain is critically involved in these intertwined psychological mechanisms. This knowledge could help develop new therapies for psychiatric disorders such as schizophrenia or depression.

Virtually all mental health disorders come with difficulties in interpersonal relations that in the long run negatively affect the progression of the disease. The associated health and social restrictions can only be marginally improved by current forms of therapy. One of the reasons for this is that there has been very little research into the basic neurobiological principles and in particular the neurochemical mechanisms of these kinds of disorders. A further symptom of various psychiatric disorders is distortions of self-experience. People suffering from mental disorders often show either an inflated or weakened sense of self.

Researchers at the University Hospital of Psychiatry Zurich have now investigated the links between changes in the sense of self and changes in social interaction, and the pharmacological mechanisms that play a role in these processes.

LSD impacts self-boundaries

"LSD blurs the boundaries between one's own self and others during a social interactions ," explains Katrin Preller. She led the research team of the Neuropsychology and Brain Imaging group together with Prof. Franz Vollenweider and cooperated with the Max Planck Institute of Psychiatry in Munich on the study. While lying in an MRI scanner, study participants communicated with a virtual avatar by means of eye movements after having been administered a placebo, LSD, or LSD in combination with ketanserin.

Changes in social interaction

"This allowed us to show that brain regions which are important for distinguishing between self and others were less active under the influence of LSD," says Preller. "And this also changed social interactions." The researchers were also able to show that the LSD-induced changes were blocked by ketanserin indicating that the serotonin 2A receptor (5-HT2A receptor) plays a critical role in this mechanism.

Approaches for new drugs

These findings demonstrate that self-experience and social interaction are closely linked. Varying impairments of these intertwined processes could be the result of an impaired transfer of information mediated by the 5-HT2A receptor system. This could be important for the development of new pharmacological therapies. For example, blocking this receptor in patients suffering from an incoherent sense of self such as schizophrenia could improve their symptoms as well as their social abilities. On the other hand, stimulating this receptor could help patients who suffer from an increased self-focus, as is the case with depression, for example.

https://www.sciencedaily.com/releases/2018/03/180319155948.htm

LSD alters perception via serotonin receptors

January 26, 2017

Science Daily/University of Zurich

Researchers from UZH have discovered how the perception of meaning changes in the brain under the influence of LSD. The serotonin 2A receptors are responsible for altered perception. This finding will help develop new courses of pharmacotherapy for psychiatric disorders such as depression, addictions or phobias.

Humans perceive everyday things and experiences differently and attach different meaning to pieces of music, for instance. In the case of psychiatric disorders, this perception is often altered. For patients suffering from addictions, for instance, drug stimuli are more meaningful than for people without an addiction. Or patients with phobias perceive the things or situations that scare them with exaggerated significance compared to healthy people. A heightened negative perception of the self is also characteristic of depressive patients. Just how this so-called personal relevance develops in the brain and which neuropharmacological mechanisms are behind it, however, have remained unclear.

Researchers from the Department of Psychiatry, Psychotherapy and Psychosomatics at Zurich University Hospital for Psychiatry now reveal that LSD influences this process by stimulating the serotonin 2A receptor, one of the 14 serotonin receptors in the brain. Before the study began, the participants were asked to categorize 30 pieces of music as personally important and meaningful or without any personal relevance. In the subsequent experiment, LSD altered the attribution of meaning compared to a placebo: "Pieces of music previously classified as meaningless suddenly became personally meaningful under the influence of LSD," explains Katrin Preller, who conducted the study in conjunction with Professor Franz Vollenweider and the Neuropsychopharmacology and Brain Imaging research team.

LSD works via the serotonin 2A receptors

Such excessive or exaggerated attributions of meaning to experiences and environmental stimuli occur in various psychiatric disorders. Conversely, a coherent self depends on a functioning network of so-called cortical mid-brain structure, as more recent studies reveal. According to this, the network is impaired in various psychiatric disorders. "LSD now seems to affect this very network and influence the experience of meaning," explains Preller.

With the aid of functional magnetic resonance imaging (fMRT), the scientists were also able to demonstrate that study participants attached greater meaning to previously irrelevant stimuli after taking LSD. If, on the other hand, the serotonin 2A receptor was blocked pharmacologically before LSD was taken, all other psychological changes triggered by LSD were also normalized. "This was very surprising," says Preller. "After all, studies on animals revealed that LSD also stimulates other receptors, such as the dopamine D2 system." It was previously assumed that this might be responsible for the euphoria triggered by LSD and that different receptor systems were involved in the development of experiencing meaning. The results of the current study, however, clearly indicate the key role of the serotonin 2A receptor in both the subjective experience under LSD and the changes in brain activity revealed using fMRT.

Possible approaches for courses pharmacotherapy to treat psychiatric problems

This observation sheds light on how LSD affects the brain neuropharmacologically and especially how the pharmacology of meaning perception works. While the serotonin 2A receptor seems to be responsible for generating new meaning, the dopamine system might regulate the relevance of stimuli we generally deem important. These results may therefore one day benefit people suffering from psychiatric disorders characterized by an altered perception of meaning, such as depression, phobias and addictions.

https://www.sciencedaily.com/releases/2017/01/170126123127.htm