Low-dose LSD and brain responses to reward in people with mild depressed mood

The question

Do very low doses of LSD change how the brain responds to winning or losing money, and does this differ between people with mild depressed mood and people without it?

What they did

Twenty adults with subclinical mild-to-moderate depressed mood and 19 controls with minimal symptoms took part. Each person attended two sessions, receiving either LSD (26 micrograms of LSD tartrate) or a placebo. During each session researchers recorded event-related potentials, which are small electrical brain responses measured from the scalp, while participants did a task involving monetary rewards. Self-reported mood was measured during the sessions and again 48 hours later.

What they found

Compared with placebo, LSD increased the size of one brain response (the late positive potential) to loss feedback rather than win feedback, but only in participants with higher baseline depressed mood. In that group, this brain change was linked to more positive mood during the session and to lower depressed mood 48 hours after the LSD session compared with the placebo session. Across the whole sample, LSD reduced two brain responses (feedback-P3 and the late positive potential) to reward feedback compared with neutral feedback.

The fine print

The study included only 39 people in total, split into two small groups, and participants had subclinical depressed mood rather than a diagnosed depressive disorder. The main outcomes were brain electrical signals, which are indirect markers and not the same as clinical improvement. Mood was followed for only 48 hours, and people can often tell whether they have taken a psychedelic, which can affect self-reported mood. This summary is based on the abstract alone.

What it means

A single low dose of LSD shifted brain responses to reward feedback in people with mild depressed mood, and those shifts tracked with short-term mood changes. This is early, small-scale work on possible mechanisms, not evidence that low-dose LSD treats depression.

Evidence grade: Moderate. Randomized, placebo-controlled study with each person receiving both conditions, but the sample was small, the main outcomes were brain-wave measures rather than clinical improvement, and follow-up was only 48 hours.

This summary is based on the study’s published abstract.