Eight weeks of low-dose LSD in 19 people with depression: an open-label safety trial

The question

Is an eight-week course of very low (‘microdose’) doses of LSD safe, tolerable and practical to deliver for people with major depression?

What they did

Nineteen adults with major depressive disorder (15 of them male) took part in a phase 2A open-label trial, meaning everyone knew they were getting LSD and there was no placebo comparison. Most participants (15) were already taking an antidepressant. They took 16 doses of LSD over eight weeks, starting at 8 micrograms and then 6-20 micrograms twice weekly at home, with the first dose given in the clinic. Researchers tracked side effects, blood tests, heart tracings (ECG), heart ultrasound (echocardiography), and depression scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

What they found

No serious or severe adverse events were reported, and the safety tests showed no clinically meaningful changes. This was the first study to check for heart valve damage after repeated psychedelic dosing in people, and none was found. One participant withdrew because of anxiety while dosing; all scheduled clinic visits were attended. Depression scores on the MADRS fell by 59.5 percent by the end of the eight weeks, and the authors report the reduction was sustained up to six months, with improvements also noted in anxiety, rumination, stress and quality of life.

The fine print

There was no placebo group and no blinding, so the large drop in depression scores could partly reflect expectation, extra clinical contact or natural improvement over time. The sample was very small (19 people) and mostly male, and most participants were also taking antidepressants, making it hard to separate the effect of LSD. The trial was designed to test feasibility and tolerability, not to prove the treatment works. This summary is based on the abstract only.

What it means

Repeated low doses of LSD appeared tolerable and practical to deliver in this small group, including on heart-safety checks, but the study design cannot show whether the improvement in depression came from the drug itself. Randomized, placebo-controlled trials are needed next.

Evidence grade: Very low. A small open-label trial with 19 participants, no placebo group and no blinding, so improvements cannot be separated from expectation or natural recovery.

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