Brain scans after LSD treatment for depression show white matter changes

The question

Does LSD change the microscopic structure of the brain’s white matter — the wiring that connects brain regions — in people with major depression, and do those changes track with symptom improvement?

What they did

This was a sub-study of a randomized trial (NCT03866252) in which 61 people with major depressive disorder received either a low dose of LSD (two sessions of 25 micrograms) or a moderate-to-high dose (100 micrograms, then 200 micrograms), given four weeks apart. Brain scans using diffusion tensor imaging, a method that maps the structure of white matter, were available before and after treatment for 35 of these patients, 17 of them in the higher-dose group. Researchers compared changes in a measure called fractional anisotropy, which reflects the organization of white matter fibres, and checked whether those changes lined up with depression scores.

What they found

The higher-dose group showed increases over time in fractional anisotropy in several white matter regions, including the internal and external capsule, the sagittal stratum, and the fornix/stria terminalis, compared with the low-dose group. Within the higher-dose group, the white matter values measured after treatment correlated with improvement in depression symptoms at 2, 6 and 12 weeks, rated both by clinicians and by patients using the Inventory of Depressive Symptomatology. The abstract notes the parent trial reported positive clinical outcomes but does not give those numbers here.

The fine print

Only 35 of the 61 trial participants had usable before-and-after scans, and just 17 were in the higher-dose group, so the analysis is small. The comparison was low-dose versus higher-dose LSD, not LSD versus an inactive placebo, and a low dose may still have effects. Correlations between brain measures and symptom scores do not show that one caused the other, and the abstract gives no correlation strengths or p values. This summary is based on the abstract alone.

What it means

In this small imaging sub-study, a higher dose of LSD was followed by measurable changes in brain white matter that tracked with depression improvement, offering a possible clue about how the drug might work — but it does not establish that the brain changes caused the symptom relief.

Evidence grade: Low. A small brain-imaging sub-analysis of a randomized trial, with 35 of the 61 participants scanned and no inactive placebo group, so the findings are exploratory.

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