The finding that mCPP agonizes 5-HT2C receptors to cause anxiety supports the hypothesis that 5-HT2C abnormalities may be implicated in a subset of human anxiety disorders.Based on findings that 5-HT2C receptor activation and its overexpression in certain areas of the brain can cause anxiety, some researchers theorize that strategic modulation of 5-HT2C receptors could facilitate an anxiolytic effect. Other research by Tran, Schulkin, Ligon, and Greenwood-Van Meerveld (2015) indicates that epigenetic expression within the amygdala, particularly involving histone modification, can affect anxiety levels. On the other hand, medications that inhibit norepinephrine’s stimulation of adrenergic receptors are sometimes useful for the treatment of anxiety disorders. That said, there is some evidence from a 1986 case report to suggest that lithium may prove useful for the management of refractory panic disorder.In this case report by Cournoyer, it was reported that a 40-year-old patient had been treated with clomipramine (225 mg/day) for depression experienced unremitting panic disorder. Moreover, another possibility is that lithium only helps with mood stabilization and has zero significant effect on anxiety level.It might’ve also been interesting to recruit patients with bipolar disorder receiving standalone olanzapine and/or lamotrigine for sufficient duration to stabilize mood. Moreover, it may be worth evaluating the safety and efficacy of low-dose lithium as an adjunct to non-contraindicated serotonergic anxiolytics in humans with refractory anxiety disorders.Muraki, Inoue, Hashimoto, et al. For this reason, it may be worth investigating the anxiolytic potential of lithium plus an SSRI among humans with severe anxiety.An intriguing case report was documented by Cournoyer (1986) in which lithium carbonate was successfully utilized to treat a refractory case of panic disorder. Furthermore, regular supplementation of lithium to ensure that the provisional 1000 mcg/day requirement is being met could also potentiate the therapeutic efficacy of a pharmaceutical anxiolytic. Neuroimaging research in humans diagnosed with bipolar disorder revealed that administration of lithium significantly increases 5-HT1A binding potential. (2010) further highlights the possibility that dysregulation of norepinephrine could induce anxiety disorders. Since leptin signaling has been shown to affect anxiety-like behaviors in mice, it’s possible that lithium-induced alterations in LepR gene expression alleviate anxiety.Although it’s likely that various epigenetic modifications induced by lithium remain undiscovered, the cumulative epigenetic effect of lithium might be an important mechanism by which it decreases symptoms of anxiety in a subset of the population. Results indicated that patients with serum lithium concentrations of 0.60 mEq/L or higher, exhibited the highest rates of remission and greatest symptomatic reduction compared to those with lower serum lithium concentrations. One study examined 51 patients with depression who did not respond to treatment with venlafaxine (a commonly-prescribed antidepressant medication). While it may be a stretch, off-label administration of lithium could be regarded as a last-resort adjunct among persons with treatment-resistant anxiety.Overall, lithium should only be considered for the treatment of anxiety when all practical pharmacological approaches have been tested without any benefit. Montezinho, Duarte, Fonseca, et al. Moreover, a subset of trials in which lithium is tested for the treatment of neuropsychiatric disorders (e.g. Any potential modulation of cyclic AMP as a result of increasing intraneuronal lithium could contribute to an anxiolytic effect.Murphy, O’Donovan, Mullins, et al. And if so, how long will this last? increasing extracellular levels, stimulating 5-HT receptors, etc. Other than this lone case report, there are animal model data indicating that lithium reduces anxiety-like behavior in fear-conditioned rats.It may be worth noting that there are anecdotal reports circulating throughout the internet suggesting that lithium is effective for the alleviation of anxiety. For this reason, we could hypothesize that low-dose lithium plus an inhibitor of MAO-A would treat anxiety in humans. digging, grooming, rearing) during social interactions compared to standard wild-type mice. If a significant anti-inflammatory effect occurs among humans as a result of lithium administration, perhaps this mechanism contributes to an anxiolytic effect.When oxidative stress accumulates, it is known to modify gene expression, protein conformation, and signaling of cells. Is that normal? Research by Dwivedi and Zhang (2015) discovered that, in animals, lithium activates transcription of a specific exon to induce expression of BDNF, Bcl2, and Bcl-XL genes – each of which are implicated in neuroprotection.In addition to increasing expression of genes involved in neuroprotection, lithium decreases expression of pro-apoptotic genes such as Bax, Bad, and capases 3. Some theorize that modulation of inositol concentrations through depletion and/or supplementation may prove useful for the treatment of certain neuropsychiatric conditions, including anxiety. That said, studies by Desai, Borkar, Nakhate, et al. Researchers concluded that subchronic 0.2% lithium carbonate yields adjunct anxiolytic effects when administered with MAO-A inhibitors in animal models of fear.When considering that subchronic 0.2% lithium carbonate significantly increased extracellular concentrations of serotonin, and that extracellular serotonin levels correlated with anxiolytic effects, it’s possible that standalone lithium carbonate may prove useful as a treatment for anxiety.