Ayotunde Anidugbe

Background: Depression and diabetic neuropathy (DN) commonly complicate diabetes and impair glycemic control and quality of life. Ketamine and its S-enantiomer, esketamine, provide rapid antidepressant and analgesic effects, yet diabetes-related pathophysiology and co-therapies may modify exposure, response, and safety. Methods: We conducted a scoping review following PRISMA-ScR. MEDLINE/PubMed, CINAHL, and APA PsycInfo were searched (January 2020–31 May 2025). Eligible human and animal studies evaluated ketamine, esketamine, or norketamine in the context of diabetes (type 1 [T1DM], type 2 [T2DM], gestational [GDM]), or DN, and reported psychiatric, analgesic, metabolic, or mechanistic outcomes. Two reviewers independently screened and charted data; no formal risk-of-bias assessment was performed. Results: Eleven studies met inclusion criteria: four human case reports/series (three T1DM, one T2DM), one randomized trial in GDM, two narrative reviews of topical ketamine for DN, and four preclinical rodent studies using streptozotocin- or diet-induced diabetes models. Short-term improvements were reported for treatment-resistant depression and neuropathic pain, including opioid-sparing postoperative analgesia in GDM. Glycemic effects varied across settings, with both hyperglycemia and hypoglycemia reported. Mechanistic and clinical drug–drug and drug-disease interactions (particularly involving metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and CYP3A4/CYP2B6 modulators) remain insufficiently studied. We outline a forward-looking population pharmacokinetic (popPK) and pharmacokinetic-pharmacodynamic (PK-PD) research agenda, including priority covariates (eGFR, hepatic function, inflammatory status, HbA1c, genotype, co-medications) and sparse-sampling windows for future model-informed precision dosing. Conclusions: Current evidence supports cautious, selective use of ketamine for refractory depression and DN within multidisciplinary diabetes care. Purpose-built popPK/PK-PD studies in both human and preclinical diabetic models cohorts are needed to quantify variability, define drug–disease–drug interactions and glycemic risk, and inform individualized dosing strategies.

Per- and polyfluoroalkyl substances (PFASs), commonly known as “forever chemicals”, are synthetic compounds with highly stable carbon–fluorine bonds, making them resistant to environmental degradation. These chemicals accumulate in ecosystems and water supplies, posing significant risks to human health, including cancer, immune system dysfunction, and neurological disorders. However, the mental health impacts of PFAS exposure remain underexplored, particularly in marginalized communities. This review examines the emerging evidence linking PFAS exposure to mental health issues such as anxiety, depression, and cognitive decline, with a focus on communities of color who face heightened vulnerability due to environmental and social health disparities. The review highlights the persistence of PFASs in the environment, common exposure pathways, and the disproportionate effects on populations living near contaminated sites. Despite some regulatory progress, U.S. regulations on PFASs are limited, especially compared to international standards. The review calls for stronger policy frameworks and emphasizes the need for environmental justice, health equity, and public awareness. By connecting environmental health, social justice, and mental well-being, the review aims to guide future research and policy reforms to mitigate the mental health consequences of PFAS exposure in vulnerable populations.