A team of neuroscientists has used functional magnetic resonance imaging (MRI) and real-time eye-tracking to determine where and how the psychedelic drug LSD elicits its effects in the brain, providing new insights into the neural mechanisms involved in human self-awareness and social interactions.
This has implications for the development of future drug strategies that could potentially target a particular system of brain receptors and help treat psychiatric disorders.
When the human brain is bombarded with stimuli, there are certain areas, collectively called the cortical midline structures (CMS) because of their location in the brain, that process and distinguish information and store memories that pertain to one’s “self”. These structures also help distinguish “the self” from “the other”, and their function was first proposed in 2004.
Under the influence of the psychedelic drug lysergic acid diethylamide (LSD), awareness of where the self ends and the other begins gets distorted and overly enhanced. These distortions are seen in psychiatric disorders such as schizophrenia (in contrast to diseases such depression, which are characterised by patients being overly self-aware).
Another key aspect of these conditions is the inability to focus on objects, or follow another person’s gaze, or engage in joint attention (JA), all of which allow for normal social interactions. To test the influence of LSD on JA, the researchers employed neural imaging techniques on participants to whom the drug had been administered.
The study recruited 24 physically and mentally healthy volunteers. These were randomly administered three separate treatments at two week intervals. One cohort was given placebo doses; the second received placebo followed by LSD, while the third received the drug ketanserin, a blood pressure treatment known to block the effect of LSD, followed by LSD itself.
Each time the participants were treated, they were subjected to a series of five JA experimental conditions, which involved an interactive gaze-following and an object-focusing game played with an unidentified partner who was represented on their computer screen by a humanoid avatar.
Functional MRI eye-tracking was used to analyse the manner and speed with which the eyes fixed on objects and interacted with the gaze of the avatar. The participants also underwent MRI imaging on the brain to determine whether the areas responsible for social interactions and self-awareness lit up following treatment with LSD.
Preller and colleagues discovered that LSD blurred the boundaries between “the self” and “the other” by acting on CMS regions including the angular gyrus, the precuneus, posterior cingulate cortex and medial prefrontal cortex — all collectively known as the “social brain”.
Importantly, when participants were treated with ketanserin, the effects of the psychedelic were blocked by its interaction with a family of receptors dubbed 5-T2A R, known to have an affinity for LSD.
The researchers suggest these receptors may provide a target for schizophrenia treatment.
Geetanjali Rangnekar is a science communicator and editor, based in Adelaide, Australia.
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