Anxiety rates are climbing worldwide (Wang et al., 2025). As demand grows for safer, integrative solutions, research is shining a light on an overlooked trace mineral: low-dose lithium.

Naturally present in water, leafy greens, legumes, and root vegetables, lithium—notably in the form of lithium orotate—can modulate the nervous system, reduce stress-related inflammation, and enhance brain resilience, having strong implications for anxiety.

Research Highlights: Low-Dose Lithium for Anxiety

• Clinical evidence.  In a six-week open-label trial, patients with bipolar depression taking low-dose lithium experienced significant reductions in anxiety, with over half reaching full remission of symptoms (Jones et al., 2022).
• Genetic insights. Individuals with stress-sensitivity genes, such as the CACNA1C allele, appear to benefit even more from lithium’s anxiety-reducing effects (Dickerson & Reed, 2024).
• Population studies. Communities with higher natural lithium levels in drinking water consistently report lower rates of suicide, depression, and anxiety (Szklarska & Rzymski, 2019).
• Real-world use. Surveys of over-the-counter lithium orotate show consistent improvements in mood and anxiety at low daily doses (around 10 mg elemental lithium) (Strawbridge et al., 2025).
• Alcohol & anxiety. In individuals with alcohol dependence—where anxiety often fuels relapse—low-dose lithium orotate supported long-term sobriety and improved both mood and anxiety (Sartori, 1986).
• Neuroprotection.  A landmark Nature study reported that people with mild cognitive impairment and Alzheimer’s disease had markedly lower lithium levels in the brain. Lithium helps block tau phosphorylation, amyloid-β42 accumulation, and oxidative stress, reinforcing neural integrity and protecting against anxiety vulnerability (Aron et al., 2025). 

Mechanisms of Action: How Lithium Supports Anxiety

Lithium’s ability to reduce anxiety stems from its impact on multiple brain and body functions.

Brain Health & Resilience
Lithium upregulates, or boosts neurotrophic factors— including brain-derived neurotrophic factor (BDNF) and BCL-2—pomoting synaptic plasticity, neuronal survival, and stronger connectivity in anxiety-related circuits (De Vasconcellos et al., 2006); Vo et al., 2015; Aron et al., 2025). By protecting neurons and reinforcing brain pathways, lithium builds long-term resilience against stress and anxiety

Neurotransmitter Balance

Lithium enhances serotonin and GABA—key calming neurotransmitters—while balancing excitatory glutamate and dopamine (Rijal et al., 2021). This re-centers the brain toward an inhibitory tone, easing hyperarousal and mood instability.

It also works with vitamin B12 and folate to recycle tetrahydrobiopterin (BH4), essential for making serotonin, dopamine, and melatonin. Without adequate BH4, neurotransmitter production slows, fueling anxiety, mood shifts, and sleep issues. Lithium further modulates monoamine oxidase (MAO) and supports methylation pathways, ensuring neurotransmitter signaling remains smooth and efficient (Haj-Mirzaian & Haj-Mirzaian, 2016; Szklarska & Rzymski, 2019).

Stress & Neuroimmune Regulation

Chronic stress overstimulates the HPA axis and immune system, creating a cycle of inflammation, neuronal excitability, and anxiety. Lithium disrupts this feedback loop by calming HPA activity, lowering inflammatory cytokines, and reducing oxidative stress (Rijal et al., 2021); (Haj-Mirzaian et al., 2016); (Won & Kim, 2020).

Circadian Rhythm & Signaling Balance

Lithium inhibits glycogen synthase kinase-3β (GSK-3β), a master enzyme influencing more than 40 proteins involved in mood and signaling. Through this action, lithium helps regulate circadian clock genes, which are integral for sleep quality, emotional balance, and stress resilience (Hamstra et al., 2023). Circadian rhythm and adequate sleep are pivotal for anxiety.

Low-dose lithium offers a multifaceted, integrative approach to anxiety, helping restore balance across brain and body while supporting emotional and nervous system resilience.