Acute LSD effects on response inhibition neural networks
Psychological Medicine – October 02, 2017
Source: OpenAlex
Summary
LSD significantly impairs response inhibition, as shown by a study involving 18 healthy participants. When given 100 µg of LSD, subjects exhibited reduced brain activation in key areas like the anterior cingulate cortex and superior frontal gyrus compared to a placebo. Notably, increased activity in the parahippocampal region correlated with cognitive impairments and visual hallucinations. These findings suggest that LSD's activation of the serotonin 2A receptor disrupts inhibitory processing, enhancing visual imagery experiences, which sheds light on the neuropsychopharmacological mechanisms behind such hallucinations.
Abstract
Abstract Background Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT 2A R) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT 2A R activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT 2A R activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations. Methods In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire. Results Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery. Conclusion Our findings show that 5-HT 2A R activation by LSD leads to a hippocampal–prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.