Acute LSD effects on response inhibition neural networks
In a double-blind, placebo-controlled crossover study in 18 healthy volunteers, 100 µg LSD impaired response inhibition and reduced activation in right middle temporal, bilateral frontal, anterior cingulate, left postcentral and cerebellar regions, with altered parahippocampal–prefrontal relationships. These results indicate that 5‑HT2A receptor activation disrupts hippocampal–prefrontal inhibitory control, which may facilitate the emergence of LSD-induced visual imagery and hallucinations.
Authors
- Felix Müller
- Patrick Dolder
- Ulrich Schmidt
Published
Abstract
Background
Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) 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-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR 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-HT2AR 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.
Research Summary of 'Acute LSD effects on response inhibition neural networks'
Introduction
Classic hallucinogens such as lysergic acid diethylamide (LSD) and psilocybin have been used as pharmacological models to probe neurobiological mechanisms underlying psychotic symptoms, particularly visual hallucinations and cognitive disturbances. Activation of 5-hydroxytryptamine2A receptors (5-HT2A R) is thought to mediate the visual hallucinations produced by these substances, and prior work shows that 5-HT2A R antagonists can attenuate both hallucinations and certain cognitive impairments. The introduction frames cognitive control, particularly inhibitory processes, as central to distinguishing internally generated imagery from external perception, and notes clinical observations that patients with visual hallucinations (for example in Parkinson's disease) often show greater prefrontal/executive impairments than those without hallucinations. Schmidt and colleagues set out to test two linked hypotheses in healthy volunteers acutely given LSD: first, that subjective LSD-induced impairments in cognitive control would be positively related to reports of visual imagery; second, that LSD would reduce activation in prefrontal and related regions supporting response inhibition (including middle/superior/inferior frontal gyri, middle temporal gyrus, pre-supplementary motor area, anterior cingulate cortex and putamen) and that such reductions would be associated with LSD-induced visual imagery. The study therefore combines behavioural, subjective and fMRI measures using a Go/No-Go paradigm to probe neural networks of inhibitory control under LSD versus placebo.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Schmidt, A., Müller, F., Lenz, C., Dolder, P. C., Schmid, Y., Zanchi, D., Lang, U. E., Liechti, M. E., & Borgwardt, S. (2018). Acute LSD effects on response inhibition neural networks. Psychological Medicine, 48(9), 1464-1473. https://doi.org/10.1017/s0033291717002914
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