Journal of affective disorders
April 15, 2026
Gia Han Le, Sabrina Wong, Danica E Johnson et al.
4 citations
Ketamine and esketamine rapidly reduce depression in people with treatment-resistant depression and bipolar depression, but the synaptic mechanisms behind dosing and durability are unclear. This review of 61 clinical and 17 preclinical studies found that a single 0.5 mg/kg intravenous infusion produces antidepressant effects peaking at 24 hours and fading over 2-3 days. Early neurophysiological changes appear within 3-8 hours, consolidate by 24 hours, and are rarely detected beyond 3 days. Twice-weekly and thrice-weekly dosing produce comparable four-week outcomes, and weekly maintenance reduces relapse risk. Ketamine may open a plasticity window lasting about 2-3 days, and aligning dosing intervals with this window could optimize durability while minimizing drug exposure.
Psychiatry Research
February 19, 2026
Trisha Menon, Andy Lu, Akhilan Arulmozhi et al.
Ketamine, esketamine, repetitive transcranial magnetic stimulation (rTMS), and electroconvulsive therapy (ECT) are associated with reductions in suicidal ideation in people with major depressive disorder. The strongest evidence from randomized controlled trials supports rapid, short-term effects, particularly for ketamine and esketamine. Further research is needed to characterize the durability of these antisuicidal effects and to determine whether reductions in suicidal ideation translate into reduced severity of suicidal behavior.
Pharmacopsychiatry
February 5, 2026
Tianyi Xu, Sabrina Wong, Gia Han Le et al.
Lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine activate the 5-hydroxytryptamine 2B receptor, a pathway known to cause drug-induced valvular heart disease. This systematic review of 17 studies found no research on psilocybin, dimethyltryptamine, or mescaline. Both lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine show high or moderate affinity for this receptor and promote signaling linked to fibrotic changes in heart valve tissue. In vivo studies confirm serotonin-induced valvulopathy, and chronic 3,4-methylenedioxymethamphetamine use has been associated with valve abnormalities in humans. No clinical cases of lysergic acid diethylamide-induced valvulopathy have been reported, but preclinical data suggest potential for fibrotic signaling under sustained exposure. Preliminary evidence supports the need for cardiac safety monitoring in psychedelic research.