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Background: Lithium has neuroprotective effects in animal models of stroke, but benefits in humans remain uncertain. This article aims to systematically review the available evidence of the neuroprotective and regenerative effects of lithium in animal models of stroke, as well as in observational and trial stroke studies in humans. Methods: This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Medline, Embase, and PsycINFO for preclinical and clinical studies published between January 2000 and September 2021. A random-effects meta-analysis was conducted from observational studies. Results: From 1625 retrieved studies, 42 were included in the systematic review. Of those, we identified 36 rodent models of stroke using preinsult or postinsult treatment with lithium, and 6 studies were conducted in human samples, of which 4 could be meta-analyzed. The review of animal models was stratified according to the type of stroke and outcomes. Human data were subdivided into observational and intervention studies. Treatment of rodents with lithium was associated with smaller stroke volumes, decreased apoptosis, and improved poststroke function. In humans, exposure to lithium was associated with a lower risk of stroke among adults with bipolar disorder in 2 of 4 studies. Two small trials showed equivocal clinical benefits of lithium poststroke. Conclusions: Animal models of stroke show consistent biological and functional evidence of benefits associated with lithium treatment, whereas human evidence remains sparse and inconclusive. The potential role of lithium in poststroke recovery is yet to be adequately tested in humans.

Introduction: Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and causing increased burden and morbidity. Clinical presentations are pleomorphic and clinical management often requires combinations of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse psychotropic drug events emphasize the need for novel therapeutic options. Objectives: To review the evidence supporting use of medical cannabinoids for treatment of neuropsychiatric symptoms (NPS) of dementia. Methods: We conducted a systematic review of the medical literature to examine scientific publications reporting use of medical cannabinoids for treatment of NPS. Medical Subject Headings (MeSH) were used to search for relevant publications and only papers reporting original clinical information were included. A secondary search was performed within selected publications to capture relevant citations that were not retrieved by the systematic review. The papers selected were categorized according to the level of evidence generated by the studies in relation to this clinical application, i.e. (1) controlled clinical trials;(2) open-label or observational studies; and (3) case reports. Results: Fifteen publications with original clinical data were retrieved: five controlled clinical trials, three open-label/observational studies, and seven case reports. Most studies indicated that use of medical cannabinoids engendered favorable outcomes for treatment of NPS related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior, sleep disorder, and sexual disinhibition. Conclusion: Medical cannabinoids constitute a promising pharmacological approach to treatment of NPS with preliminary evidence of benefit in at least moderate to severe dementia. Controlled trials with longitudinal designs and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration, and concentrations of active compounds (e.g., cannabidiol [CBD]/ Δ 9 -tetrahydrocannabinol [THC] ratio) in commercial preparations of medical cannabinoids.

Background: There is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer’s disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons. Methods: Cortical neurons were treated with lithium chloride at therapeutic and subtherapeutic concentrations (2 mM, 0.2 mM and 0.02 mM) for seven days. Amyloid toxicity was induced 24 h before the end of lithium treatment. Results: Lithium resulted in 120% (2 mM), 180% (0.2 mM) and 140% (0.02 mM) increments in telomere length as compared to untreated controls. Incubation with Aβ1-42 was associated with significant reductions in MTT uptake (33%) and telomere length (83%) as compared to controls. Conclusions: Lithium prevented loss of culture viability and telomere shortening in neuronal cultures challenged with Aβ fibrils.

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