Nitrous oxide (N2O – also known as Hilarious Gas) has recently emerged has a potential fast-acting antidepressant, based on a number of randomized controlled trials (RCT) in young adults with treatment resistant depression (TRD). The antidepressant mechanisms of N2O are not fully understood but may include an antagonist action on NDMA receptors, similar to ketamine. N2O shows additional cerebral effects that may be particularly appropriate for TRD in older adults, including a significant cerebral vasodilatation that facilitates blood brain barrier opening and potentially limits resistance related to poor cerebrovascular functioning. Moreover, N2O may prove to be particularly well-tolerated in this potentially fragile population, notably because it is not metabolized by the kidney or liver which organs may be impaired with aging.

In this talk, we will be reviewing the available data on the efficacy, safety and pathophysiology of N2O, with a specific focus on older adults. We will also present results from our group showing a significant reduction in cerebral connectivity in the anterior cingulate cortex (ACC - as measured with pre and post treatment resting state MRI) and large increase in brain tissue pulsations (as measured with Ultrasound) with a successful treatment with N2O compounds. Finally, perspectives on current studies in older adults from our group (one RCT in non-demented older adults with TRD and one RCT in neurocognitive disorders) will be discussed.

Figure 1

Changes in ACC connectivity after exposure to N2O compounds

Changes Brain Tissue Pulsations as assessed with brain ultrasound during N2O exposure