No evidence that LSD microdosing affects recall or the balance between distracter resistance and updating

Introduction

Interest in LSD and other classic psychedelics has re‑emerged, yet their cognitive effects—especially at very low ‘‘microdose’’ levels that do not produce overt changes in consciousness—remain incompletely characterised. Working memory, the short‑term retention and manipulation of information needed for goal‑directed behaviour, is a key cognitive domain that must balance stability (resisting distraction) and flexibility (updating representations). Previous work implicates both dopaminergic and serotonergic (notably 5‑HT2A) signalling in these processes, and computational models predict that pharmacological modulation can produce opposing effects on distracter resistance versus updating. Despite widespread anecdotal reports that microdosing LSD improves cognition, few placebo‑controlled laboratory studies have examined these hypotheses and tasks such as the n‑back conflate stability and flexibility, limiting inference about dissociable effects. Fallon and colleagues set out to test whether very low doses of LSD (5 µg, 10 µg and 20 µg) alter working memory performance in older adults and whether any effects are differentially expressed for ignoring distractors versus updating working memory. They used a randomised, double‑blind, placebo‑controlled design and a modified delay‑match‑to‑sample task that explicitly separates trials requiring maintenance, ignoring novel stimuli, or updating with novel stimuli, enabling direct assessment of stability versus flexibility in working memory.