Low-dose lithium (Buffalo)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Thomas Guttuso Jr, University at Buffalo (SUNY), with Niels Bergsland, Robert Zivadinov and colleagues.

What happened

Lithium is a long-used mood drug. The team's case: it blocks the enzyme GSK-3 beta, calms immune cells and may raise Nurr1, a gene switch dopamine neurons need (landmark 176). Guttuso also hypothesises that lithium in tobacco explains the lower rate of Parkinson's in smokers (landmark 82). That tobacco idea is an author hypothesis, not established.

• Pilot (NCT04273932, 2019–23). Phase 1, open-label, 24 weeks: 16 patients randomised to lithium carbonate (n = 5), 45 mg/day lithium aspartate (n = 6) or 15 mg/day (n = 5), plus 3 untreated controls. Blood Nurr1 mRNA rose 679% at the 45 mg dose, versus 139% in controls. Only six treated patients had MRI. Two of six on 45 mg left for sedation and slowed thinking (IBRO Neurosci Rep 2023).
• Phase 1 (NCT06099886, Oct 2023 to Dec 2024). 15 people took 30 to 45 mg/day for 24 weeks; all completed. Results posted: no clear change in MRI free water (a brain-tissue marker that rises in Parkinson's), blood neurofilament light (a nerve-damage marker) fell 3.6% on average, and motor score worsened by 4 points on average (no control group).
• Randomised Phase 1/2 (NCT06339034). Planned 20 patients, lithium 20 mg/day versus placebo, 24 weeks; started July 2024, primary completion estimated August 2026. Status active, not recruiting (record updated 16 June 2026); that date and the estimated September 2026 completion have both passed and no results are posted (re-checked 22 Oct 2026; the record is unchanged since 16 June 2026).
• Extension (NCT06592014). Planned 35, enrolling by invitation (record updated 25 August 2026); primary completion estimated October 2026, completion November 2026.

Why it moved us toward a cure

It tests whether lithium reaches its targets at a dose people can tolerate. All the trials measure markers, not progression.

Outcome

Pending, overdue. The randomised trial is past its estimated completion (September 2026) with no results yet and no registry update; the extension finishes around November 2026, which is our expected date. No 2026 publication found.

Sources

• Guttuso et al., IBRO Neurosci Rep 2023, DOI 10.1016/j.ibneur.2023.05.001
• ClinicalTrials.gov NCT04273932 · NCT06099886 · NCT06339034 · NCT06592014 (API, 22 Oct 2026)
• Not yet verified: any publication of the Phase 1 results; whether the MDS-UPDRS rise in Phase 1 is a spread or a mean change in the registry; the earlier lithium pilots the brief mentioned beyond this pilot (none found).