What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial

Looking at the use of LSD microdosing for major depressive disorder

This open-label study (n=17) of LSD microdosing for major depressive disorder found that participants reported enhanced self-determination, increased connectedness, and improved emotional well-being, though some experienced negative effects or no improvement, and the lack of placebo control limits causal conclusions.

“Background:

Depressive disorders affect approximately 280 million globally, with many finding treatments ineffective or limited by side effects. Growing evidence suggests that psychedelic therapies may help alleviate depressive symptoms. Among these, lysergic acid diethylamide (LSD) microdosing shows promise for major depressive disorder (MDD). However, research on LSD microdosing in clinical populations remains limited.

Objectives:

This study aimed to understand the experiences of individuals participating in an open-label trial of LSD microdosing for MDD.

Design:

Open-label pilot trial in target population (MDD; phase IIa).

Methods:

Seventeen participants with MDD completed an 8-week LSD microdosing regimen, dosing twice weekly. Following the intervention, participants underwent semi-structured interviews regarding their experiences. Data were analysed using thematic analysis.

Results:

Themes were grouped into five categories: enhanced self-determination, increased connectedness, improved cognitive processing, better emotional well-being, and negative effects.

Conclusion:

Reported effects appeared to reinforce one another; that is, self-determination led to feeling more connected, which enhanced cognitive processing and ultimately improved emotional well-being and reduced depressive symptoms. However, this effect was not universal; some individuals reported negative effects or no significant improvement from microdosing LSD. This variability may be due to individual differences in response, insufficient dosage, or the treatment’s lack of effectiveness for some individuals. The presence of side effects highlights the need for a careful titration protocol, while the lack of symptom improvement in some cases reinforces that microdosing is not a guaranteed solution, and expectations should remain realistic. The absence of a placebo control represents a key limitation as it precludes attribution of observed changes specifically to LSD.

Notes

The findings captured how participants experienced and made sense of microdosing, rather than proving clinical efficacy.

Reported improvements appeared to cluster in a reinforcing cycle: increased agency → stronger connectedness → clearer cognition → enhanced emotional well-being.

Because the trial was open-label (no placebo control), improvements could partly reflect expectations, placebo effects, or general engagement with a novel intervention.

The study highlights the value of qualitative measures in understanding subjective change in psychedelic research and points to key domains for future placebo-controlled work.

Participants with major depression who microdosed LSD reported:

• Greater motivation and engagement,

• Enhanced connectedness,

• Improved emotional and cognitive functioning, but also some side effects and response variability. These lived experiences suggest possible psychological shifts associated with microdosing in a clinical context yet causal effects remain unproven without controlled trials. Expectations and placebo effects can’t be ruled out: because the trial lacked a placebo control, causation can’t be attributed directly to LSD

• Not all participants improved: some reported negative effects or no changes.

Joy Donegan, C., Daldegan-Bueno, D., Sumner, R. L., Forsyth, A., Evans, W., Hoeh, N. R., ... & Reynolds, L. (2025). What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial. Therapeutic Advances in Psychopharmacology, 15, 20451253251396253. Read Paper

For more psychedelic news and research, visit the psychedelic health professional network homepage.