LSD not efficacious in reducing ADHD symptoms compared with placebo: JAMA

Microdosing of psychedelics has become of growing interest for its possible therapeutic application in psychiatric conditions, such as ADHD. LSD, especially, has been proposed to increase cognitive flexibility and executive function. But its efficacy for the treatment of ADHD symptoms is not established. To find an answer to this, a phase 2A, multicenter, double-blind, placebo-controlled trial was done at the University Hospital in Basel, Switzerland, and Maastricht University in the Netherlands.

The trial recruited 53 adult patients aged 18-65 years with a previous diagnosis of ADHD and moderate to severe symptoms (Adult Investigator Symptom Rating Scale [AISRS] score ≥26 and Clinical Global Impression Severity score ≥4). Participants were randomized to receive low-dose LSD (20 μg) or placebo twice weekly for six weeks (12 doses total). The main outcome was the difference in AISRS scores from baseline to week 6.

Key Finding

• The LSD group had a mean AISRS improvement of -7.1 points (95% CI, -10.1 to -4.0).

• The placebo group had a mean AISRS improvement of -8.9 points (95% CI, -12.0 to -5.8).

• There was no significant difference between the LSD and placebo groups in symptom reduction.

• LSD was physically safe and psychologically well tolerated.

This clinical trial concluded that repeated low-dose administration of LSD is safe but fails to decrease ADHD symptoms over placebo. These results identify the necessity of further research on alternative treatments for ADHD while further emphasizing the relevance of evidence-based practice in psychedelic medicine.

Reference:

Mueller L, Santos de Jesus J, Schmid Y, et al. Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults: A Randomized Clinical Trial. JAMA Psychiatry. Published online March 19, 2025. doi:10.1001/jamapsychiatry.2025.0044