Journal of affective disorders
August 1, 2026
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
Journal of Psychopharmacology
July 16, 2026
Robert F. Dougherty, Nadav Liam Modlin, Niall M. Mcgowan et al.
In a 12-week clinical trial of 25 mg COMP360 psilocybin for 22 participants with post-traumatic stress disorder, audio recordings showed that during drug-administration sessions speech by either party was rare: silence filled 78% of the time on average, compared to 25% to 30% in non-administration sessions. Thematic analysis of post-dosing interviews revealed that support was minimally enacted but experientially salient, autonomy was promoted through the introspective state and non-directive support, and primary modes of support during altered states included reassurance and validation. The minimal verbal interaction distinguishes this monitoring and support from conventional psychotherapies and MDMA-assisted therapy.
EBioMedicine
December 1, 2025
Kiranpreet Gill, Angharad N De Cates, Chantelle Wiseman et al.
Nitrous oxide, a gas that blocks the N-methyl-d-aspartate receptor, shows rapid but short-lived antidepressant effects in early-phase trials. Pooled results from three trials using a single 50% dose found significant reductions in depressive symptoms at 2 hours and 24 hours after inhalation, but not at one week. Side effects were mild and temporary, with the 25% dose being better tolerated. Most trials were small, early-phase studies focused on short-term outcomes in adults with major depressive disorder or treatment-resistant depression. Whether nitrous oxide will become a useful clinical treatment depends on whether its effects can be sustained through optimized or repeated dosing.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2025
Ella Williams, Ursule Taujanskaite, Sunjeev K Kamboj et al.
Nitrous oxide (N2O), a gas used for sedation and pain relief, shows rapid-acting antidepressant effects in treatment-resistant depression. Subanaesthetic doses (50%) can disrupt the reconsolidation of maladaptive memories in healthy people and across disorders. Negative memory biases contribute to depression, and disrupting affective memory reconsolidation may be how N2O works. This narrative review introduces evidence for N2O's antidepressant profile, evaluates its clinical use versus other treatments, and proposes a memory-based mechanism of action.