Reward-related neural activity after low doses of LSD in participants with depressed mood.
James Glazer, Hanna Molla, Royce Lee, Robin Nusslock, Harriet de Wit
Journal of psychopharmacology (Oxford, England) January 13, 2026 DOI: 10.1177/02698811251405686 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 39 |
| Population | Adults with subclinical mild-to-moderate depression (N=20) and controls with minimal symptoms (N=19) |
| Intervention | LSD |
| Dose | 26 μg tartrate |
| Duration | Two sessions; 48-hour follow-up |
| Topics | Depression LSD |
| Keywords | EEG Erp Mood Reward |
| Key findings | LSD increased LPP amplitude to loss feedback only in participants with higher baseline depressed mood, and this effect was associated with acute positive mood and lower depressed mood 48 hours later. |
Abstract
Lysergic acid diethylamide (LSD) has been considered as a potential treatment for depression for over 75 years, but its therapeutic potential has only recently been considered in mainstream psychiatry. Repeated ingestion of low doses of LSD ("microdoses") is thought to reduce depression, but the neurobiology underlying this effect is unknown. We previously reported that low doses of LSD increased event-related potentials (ERPs) during receipt of monetary rewards in healthy adults. LSD also produced more positive subjective effects in participants with mild-to-moderate baseline symptoms of depressed mood, compared to controls. In this report, we examined the effects of LSD on reward ERPs in participants with mild-to-moderate depressed mood and in non-depressed controls. Participants with subclinical mild-to-moderate depression (N = 20) or controls with minimal symptoms (N = 19) received LSD (26 μg tartrate) or placebo on two sessions. Primary measures were ERPs during a reward task, and secondary measures included self-reported mood during and 48 hours after the sessions. LSD (vs placebo) increased late positive potential (LPP) amplitude to loss (vs win) reward feedback only in participants with higher baseline depressed mood, suggesting enhanced affective processing given the role of LPP in emotional valuation of reward. This effect of LSD on LPP was associated with its acute positive mood effects, and with lower depressed mood 48-hour after the LSD (vs placebo) session. In the full sample, LSD (vs placebo) decreased feedback-P3 and LPP amplitude to reward (vs neutral) feedback. Although findings must be interpreted with caution, results support the idea that low doses of LSD have potential anti-depressant effects.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Low-dose LSD increased late positive potential amplitude to loss feedback in participants with higher baseline depressed mood, and this effect was associated with lower depressed mood 48 hours later.
Synthesized
Comparable studies
Other randomized controlled trials on LSD for depression, most cited first.