Greater subjective effects of a low dose of LSD in participants with depressed mood
This double-blind, randomised, 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.
Authors
- Harriet de Wit
- Richard Lee
Published
Abstract
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.
Research Summary of 'Greater subjective effects of a low dose of LSD in participants with depressed mood'
Introduction
Depression remains a common, disabling condition for which many patients do not respond to standard treatments. Recent clinical and preclinical work has focused on high, single-dose psychedelic treatments (for example psilocybin or LSD combined with psychotherapy), but these approaches are resource intensive and carry risks. Anecdotal reports and surveys have suggested that very low ‘‘microdoses’’ of psychedelics can improve mood, mental health and creativity without overt perceptual disruption, yet controlled studies in healthy volunteers have mostly failed to confirm robust benefits. One important gap is that prior placebo-controlled microdose trials have largely tested healthy adults; it remains possible that low doses produce detectable effects only in individuals who have baseline negative mood or depressive symptoms. Molla and colleagues set out to test whether a single low dose of LSD (26 µg) produces stronger acute and short-term mood effects in volunteers with elevated depressive symptoms compared with non-depressed volunteers. The study used a randomized, double-blind, placebo-controlled, crossover design to compare subjective, physiological, behavioural and 48-hour follow-up mood measures in two groups defined by Beck Depression Inventory-II (BDI) scores at screening (high BDI ≥17, low BDI <17). The investigators aimed to capture both in-session effects and sub-acute changes 48 hours after dosing.
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Study Details
- Study Typeindividual
- Journal
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- APA Citation
Molla, H., Lee, R., Tare, I., & de Wit, H. (2024). Greater subjective effects of a low dose of LSD in participants with depressed mood. Neuropsychopharmacology, 49(5), 774-781. https://doi.org/10.1038/s41386-023-01772-4
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