A distorted “sense of self” underlies certain psychiatric disorders, like schizophrenia and depression. In these illnesses, losing one’s sense of self — or experiencing a sharp increase in self-focus — can be overwhelming, as doing so overrides a person’s consciousness and self-representation. A recent effort to create better treatments for these people has revealed the ability of lysergic acid diethylamide — better known as LSD — to alter activity in the brain involved in differentiating between oneself and others can help.

As scientists explain in a study released Monday in the Journal of Neuroscience, taking LSD reduces activity in the brain areas involved with self-processing and social cognition. The resulting cognitive changes make it difficult for acid-dropping study participants to distinguish between themselves and virtual characters on a screen.

These effects, explain the authors from the University Hospital for Psychiatry Zurich, the Max Planck Society, and the Ludwig-Maximilians University of Munich, could be used to help people with psychiatric disorders that alter a person’s sense of self.

LSD
Participants received either LSD, ketanserin, or a placebo. 

In the study, 24 participants received either LSD, a placebo, or LSD together with ketanserin, a drug designed to inhibit alterations to the serotonin 2A receptor, which is thought to mediate the effects of LSD in the brain.

During each of the three trials, the scientists observed the participants as they attempted to interact with an anthropomorphic virtual character on a screen, alternating between coordinating their movements with those of the character or telling the character where to move. As they did so, their eye motion and brain activity were tracked.

The data showed people on LSD had reduced activity in the posterior cingulate cortex and the temporal cortex — the parts of the brain important for establishing a sense of self. The lines between their sense of reality also became blurred. When asked to follow the gaze of the virtual character, they had trouble coordinating their attention, and it became unclear whether they or the character were taking turns or performing actions as one.

LSD
A tab of LSD.

Meanwhile, participants who took LSD along with ketanserin were able to retain their sense of self. This was exactly what the scientists were hoping to find. Because LSD-induced effects were blocked by ketanserin, they deduced that loss of self must be linked to the stimulation of the serotonin 2A receptors. When a person trips on acid, their body confuses LSD for serotonin and thus allows LSD to bind to serotonin receptors — which is what results in altered states of consciousness and a state of “oneness” with the external world.

Here, ketanserin acted like a goalie, blocking LSD before it could mess with the serotonin 2A receptors. That was good news for the scientists because previous studies have found that this receptor system is impaired in samples of people with personality disorders, depression, and schizophrenia. If this receptor system can be targeted, then there’s hope for more effective treatments for these disorders.