Tripping on High-Dose LSD Shows Promise for Depression Relief

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High-Dose LSD Shows Stronger Antidepressant Effects in New Clinical Trial

A fresh wave of research reveals that higher doses of LSD may significantly ease depression symptoms, opening new doors for psychedelic therapy.

In Basel, Switzerland — the birthplace of LSD, where chemist Albert Hofmann first synthesized and self-administered the psychedelic in 1943 — a team of researchers has found that higher doses of LSD, paired with supportive therapy, may significantly reduce symptoms of major depression.

The results come from a randomized, double-blind, phase 2 trial conducted at the University of Basel’s Department of Psychiatry. Published in Med on June 6, 2025, the study compared the effects of high-dose versus low-dose LSD-assisted therapy in people diagnosed with moderate-to-severe major depressive disorder (MDD).

Participants were divided into two groups: One received 100 micrograms of LSD in the first session and 200 micrograms in the second, while the other group received two sessions of 25 micrograms. All participants underwent a structured course of supportive psychotherapy over 19 weeks. The researchers assessed changes in depressive symptoms at several time points: two weeks after the second dosing session, and again at weeks 5, 9, 13, and 19.

The main takeaway? Higher doses of LSD led to greater and more sustained reductions in depression scores. “High-dose-LSD-assisted therapy reduced depressive symptoms more than low-dose therapy,” wrote the study’s authors. “Improvements in depression scores persisted up to 12 weeks after treatment.”

The findings offer the most comprehensive modern evidence yet for LSD’s potential as an antidepressant — one that acts rapidly and endures well beyond a single trip. At the study’s primary endpoint, clinician-rated depression scores (IDS-C) dropped by nearly 13 points in the high-dose group compared to just 3.6 points in the low-dose group. The difference, statistically significant, had a moderate-to-large effect size. Self-rated scores followed the same trend.

However, the researchers noted that some of these findings lost statistical strength after controlling for baseline differences. Still, the overall picture remained consistent. “All secondary endpoints at all time points were in the same direction,” the authors wrote, suggesting a treatment effect that held steady across measures.

The trial enrolled 61 participants with an average of 17 years living with depression. Nearly all had tried psychotherapy and antidepressants before. The sample included individuals with comorbid anxiety disorders and prior hospitalizations, making it a notably representative clinical population.

Therapy sessions took place in cozy, living room-like spaces. Participants were encouraged to recline on couches, listen to music, and turn inward. Integration sessions followed each dosing day to help process the experience. Importantly, participants and therapists were blind to dosage, although both groups were fairly accurate in guessing assignments — a challenge common in psychedelic research. “Blinding was not effective in a considerable number of cases,” the researchers acknowledged.

Acute effects were notably more intense in the high-dose group, as expected. On a standard measure of altered states of consciousness (5D-ASC), participants reported nearly double the subjective effects compared to the low-dose group. Interestingly, even the 25 microgram dose — often labeled a “microdose” — produced noticeable alterations in consciousness, calling into question assumptions about its subtlety.

Safety was closely monitored. While both groups experienced adverse events, they were generally mild and similar in frequency. A few participants in the high-dose group dropped out after experiencing dysphoria or anxiety. One person who had withdrawn from the study months earlier later died by suicide — a tragic incident, though the authors emphasized it occurred well outside the study window and was judged unrelated to the treatment. Still, the risk underscores the need for caution and comprehensive screening.

“LSD could be used safely within the framework of this study,” the researchers concluded. They also highlighted one of LSD’s defining features: Its long duration of action. While this can be a therapeutic asset, it also demands more clinical time and resources compared to shorter-acting psychedelics like psilocybin.

Limitations of the trial include a modest sample size and issues with blinding. And yet, despite these caveats, the signal is strong: LSD-assisted therapy, particularly at higher doses, holds real potential for treating depression.

“The findings of this exploratory trial support further investigations of LSD as a treatment option for major depression in a larger phase 3 trial,” wrote the authors. Given the scale of unmet need in mental health care — and the limitations of existing antidepressants — it’s a path worth exploring.

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