Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity
This double-blind, placebo-controlled fMRI study (n=20) examined the effects of a single microdose of LSD (13 μg) on functional brain connectivity in healthy adults. Results show altered connectivity in limbic circuits, specifically between the amygdala and frontal regions, which correlated with subtle increases in positive mood despite negligible subjective effects.
Authors
- Harriet de Wit
- Katrin Preller
- Richard Lee
Published
Abstract
Background
The practice of “microdosing,” or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment.
Methods
The present study was designed to examine the effects of a single low dose of LSD (13 μg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received a placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During the expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labelling scans. Cerebral blood flow, as well as amygdala and thalamic connectivity, were analyzed.
Results
LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and cerebellum and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength.
Conclusions
These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug’s purported antidepressant effect.
Research Summary of 'Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity'
Introduction
Depressive disorders are highly prevalent and current antidepressant treatments, particularly selective serotonin reuptake inhibitors (SSRIs), have limitations including delayed onset, side effects, and variable efficacy. Anecdotal reports and surveys have popularised the practice of “microdosing” LSD — repeated administration of very low doses (typically ~10–15 µg) purported to improve mood and cognition — but controlled empirical data on its behavioural or neural effects are limited. Higher doses of psychedelics alter thalamo-cortical and limbic circuits and have been linked to changes in amygdala reactivity; however, the receptor-level and network effects of very low LSD doses remain poorly understood. This study, led by Bershad and colleagues, set out to examine the acute neural effects of a single low (13 µg) dose of LSD versus placebo in healthy young adults using resting-state fMRI and arterial spin labelling (ASL) to measure cerebral blood flow (CBF). The investigators focused on seed-based connectivity of the right amygdala and bilateral thalamus and explored relationships between connectivity changes and mood assessed immediately after scanning. The 13 µg dose was selected from prior dose-ranging work as producing minimal subjective effects and matches doses reported by microdosing communities, making it relevant to real-world practice and to hypotheses about potential antidepressant mechanisms.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Bershad, A. K., Preller, K. H., Lee, R., Keedy, S., Wren-Jarvis, J., Bremmer, M. P., & de Wit, H. (2020). Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 5(4), 461-467. https://doi.org/10.1016/j.bpsc.2019.12.007
References (16)
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Polito, V., Stevenson, R. J. · PLOS ONE (2019)
Yanakieva, S., Polychroni, N., Family, N. et al. · Psychopharmacology (2018)
De Gregorio, D., Posa, L., Ochoa-Sanchez, R. et al. · Pharmacological Research (2016)
Geyer, M. A., Vollenweider, F. X. · Trends in Pharmacological Sciences (2008)
Lenz, C., Dolder, P. C., Lang, U. E. et al. · Acta Psychiatrica Scandinavica (2017)
Preller, K. H., Burt, J. B., Adkinson, B. et al. · eLife (2018)
Preller, K. H., Razi, A., Zeidman, P. et al. · PNAS (2019)
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Show all 16 referencesShow fewer
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Grimm, O., Kraehenmann, R., Preller, K. H. et al. · European Neuropsychopharmacology (2018)
Carhart-Harris, R. L., Roseman, L., Bolstridge, M. et al. · Scientific Reports (2017)
Kraehenmann, R., Schmidt, A., Friston, K. et al. · NeuroImage (2015)
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