Greater subjective effects of a low dose of LSD in participants with depressed mood

This double-blind, randomized, placebo-controlled, crossover trial (n=39) finds a low dose of LSD (26μg) to produce greater positive mood, stimulant-like, and psychedelic effects in people with mild depression (BDI-II≥17) compared to non-depressed controls. Self-rated depression scores decreased more 48 hours after LSD for the mildly depressed group. Both groups showed expected physiological and subjective drug effects. This suggests low-dose LSD may have therapeutic potential for depression.

Abstract of Greater subjective effects of a low dose of LSD in participants with depressed mood

“Recent studies and anecdotal reports suggest that psychedelics can improve mood states, even at low doses. However, few placebo-controlled studies have examined the acute effects of low doses of LSD in individuals with psychiatric symptoms. In the current study, we examined the acute and sub-acute effect of a low dose of LSD (26 µg) on subjective effects and mood in volunteers with mild depressed mood. The study used a randomized, double-blind, crossover design to compare the effects of LSD in two groups of adults: participants who scored high (≥17; n = 20) or low (<17; n = 19) on the Beck Depression-II inventory (BDI) at screening. Participants received a single low dose of LSD (26 µg) and placebo during two 5-h laboratory sessions, separated by at least one week. Subjective, physiological, and mood measures were assessed at regular intervals throughout the sessions, and behavioral measures of creativity and emotion recognition were obtained at expected peak effect. BDI depression scores and mood ratings were assessed 48-h after each session. Relative to placebo, LSD (26 µg) produced expected, mild physiological and subjective effects on several measures in both groups. However, the high BDI group reported significantly greater drug effects on several indices of acute effects, including ratings of vigor, elation, and affectively positive scales of a measure of psychedelic effects (5D-ASC). The high BDI group also reported a greater decline in BDI depression scores 48-h after LSD, compared to placebo. These findings suggest that an acute low dose of LSD (26 µg) elicits more pronounced positive mood and stimulant-like effects, as well as stronger altered states of consciousness in individuals with depressive symptoms, compared to non-depressed individuals.”

Authors: Hanna Molla, Royce Lee, Ilaria Tare & Harriet de Wit

Summary of Greater subjective effects of a low dose of LSD in participants with depressed mood

Depression is a debilitating and highly prevalent mental health condition, and many patients fail to respond to standard medications. One promising new candidate treatment is the administration of single high doses of psychedelic compounds combined with supportive psychotherapy.

Microdosing LSD, a popular but medically unsanctioned practice, has been shown to improve depression and mental health and enhance cognitive functions without producing disruptive perceptual effects. However, most studies have failed to support the claims of beneficial psychiatric effects.

Participants who scored high on the Beck Depression Inventory-II were compared to participants with low scores in their mood, cardiovascular and behavioural responses to a single low dose of LSD or placebo.

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Greater subjective effects of a low dose of LSD in participants with depressed mood

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Cite this paper (APA)

Molla, H., Lee, R., Tare, I., & de Wit, H. (2023). Greater subjective effects of a low dose of LSD in participants with depressed mood. Neuropsychopharmacology, 1-8.

Study details

Compounds studied

Topics studied
Microdosing Healthy Subjects Depression

Study characteristics
Original Placebo-Controlled Double-Blind Within-Subject Randomized

49 Humans


Institutes associated with this publication

University of Chicago
Research with psychedelics is taking place at the Human Behavioral Pharmacology Lab at the University of Chicago.

Compound Details

The psychedelics given at which dose and how many times

LSD 26 μg | 1x