LSD microdosing for depression: mood, drug levels and tolerance in a small open-label trial

The question

Does taking very small (“micro”) doses of LSD over eight weeks change day-to-day mood and depression symptoms in people with major depressive disorder, and how does the drug behave in the body?

What they did

Nineteen people with major depressive disorder (15 of them men, 79%) took 16 sublingual LSD doses over eight weeks in an open-label trial, meaning everyone knew they were getting the drug and there was no placebo comparison. The first dose was 8 micrograms taken on site, with blood samples collected at eight time points to measure drug levels; later doses were taken twice weekly at home and could be adjusted between 6 and 20 micrograms. Participants filled in daily questionnaires rating depression severity (a self-reported version of the Hamilton Depression Rating Scale) and mood, plus ratings of drug effects on each dosing day. Statistical models compared dosing days with the one and two days afterwards.

What they found

Participants reported a mean symptom reduction of 60% over the trial. Daily ratings showed higher scores for mood-related states such as feeling more creative and happier on dosing days compared with the days after (p values ranging from 0.009 to 0.039), but daily depression scores did not differ between dosing and non-dosing days (p = 0.291). There was no sign of tolerance (needing more for the same effect) or sensitisation over the eight weeks (p > 0.081). For the 8 microgram dose, blood levels peaked at an average of 212 pg/mL about 1.17 hours after dosing, with average total exposure (AUC) of 836 pg.h/mL.

The fine print

This was an open-label trial with no placebo group, so the 60% symptom reduction cannot be attributed to LSD itself; expectation and the repeated attention of a trial can produce large improvements in depression. Only 19 people took part, most of them men, and doses were self-adjusted at home for most of the schedule. The mood effects measured were short-term, day-of-dosing changes. This summary is based on the abstract alone.

What it means

Microdosed LSD was linked to small same-day lifts in mood but not to day-to-day changes in depression scores, and the authors themselves say controlled trials are needed before any conclusions about benefit can be drawn.

Evidence grade: Very low. Small open-label trial with only 19 participants, no placebo group and no blinding, so improvements cannot be separated from expectation effects.

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