LAUSR

brain activity – a state resembling the kappa opioid receptor electroencephalographic profile. These mechanisms are ostensibly induced to mitigate drug-induced neurotoxicity. Problematically, though, chronic dynorphin/kappa opioid receptor activation is thought to undergird a plethora of negative affective states, including depression. Therefore, in addition to clinical dysregulation of continuous attention processes, chronic exposure to trace N2Omay also lead to a compensatory pro-depressant phenotype characterized, at least in part, by corticolimbic serotonergic deficits. While the use of psychostimulants to buttress a depleted dopaminergic tone in ADHD has been generally accepted by the medical establishment and the treatment-seeking public, the repeated use of “medical” N2O to treat refractory depression is different in that the stimulation of dopamine is not its only effect. The irreversible inactivation of cobalamin is a consequence that can affect one-carbon metabolism more broadly. The ethics of inoculating patients with cobalamin or other essential nutrients as a pre-treatment for a chronic treatment regimen that can be expected to cause metabolic harm should be concerning to all involved. Although the acute, antidepressant effects of N2O may plausibly exist (as described herein), it is alarming that “medical” exposure to N2O—a compound that also exists as an environmental air pollutant and is a suspected etiological trigger for MDD and other psychiatric morbidities—is seriously being considered as a rapid antidepressant therapy.