Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity

In this double-blind, placebo-controlled study, a microdose of LSD (13 µg) was found to increase and decrease connectivity in various areas of the brain. One of these effects correlated positively with mood increases, but overall mood changes were variable.

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 expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labeling 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 the 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.”

Authors: Anya K. Bershada, Katrin H. Preller, Royce Lee, Sarah Keedy, Jamie Wren-Jarvis, Michael P.Bremmer & Harriet de Wit

Notes

This paper was included a the systematic review on microdosing psychedelics by Ona & Bouso (2020).

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