Abstract
The practice of “microdosing”, or the use of repeated, very low doses of 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 micrograms) vs placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, aged 18-35, participated in two fMRI scanning sessions in which they received 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 BOLD and ASL 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. NCT03790358
Bershad, Anya K