Oral S-ketamine (S-KETPO) is being explored as an alternative to intravenous maintenance treatment (S-KETIV) in treatment-resistant depression (TRD). However, the first-pass effect with S-KETPO significantly alters S-ketamine's bioavailability and the systemic exposure of its active metabolites, raising potential safety and efficacy concerns. This study characterized the pharmacodynamic and...
This study aimed to investigate a set of pharmacodynamic biomarkers reflecting acute, delayed and sustained central nervous system effects of S-ketamine, used as a tool compound for rapid-acting antidepressant activity, with the goal of informing biomarker strategies for delayed antidepressant effects. In this randomized, double-blind, double-dummy, placebo-controlled, 4-way crossover study in...
Abstract Ketamine is an NMDA receptor antagonist with rapid-antidepressant properties when administered at a sub-anesthetic dose. Preclinical models indicate that a direct injection of ketamine into lateral habenula (Hb), a small midbrain structure with an evolutionarily preserved role in aversive learning across mammals, can rapidly relieve depression-like behavior. However, there is limited...
Depression remains a global public health challenge, prompting interest in translational targets which allow for more effective and rapidly acting interventions. Nitrous oxide (N2O), an N-methyl-d-aspartate receptor antagonist, has demonstrated potential as a rapid-acting antidepressant. This study synthesised existing data on the efficacy and safety of N2O in depressive disorders. We...
Abstract Recent clinical trial data suggests that ratings on depression scales are lowered after psilocybin therapy compared to placebo, though it is unclear what neuropsychological mechanisms underpin these effects. This study compared psilocybin, with an established antidepressant, escitalopram, to investigate whether there are shared or distinct effects on emotional information processing....
Ketamine's potential as a rapid-acting antidepressant was first identified in 2000, despite its long-standing use as an anesthetic agent. Clinically, ketamine alleviates depressive symptoms, including the difficult to treat symptom of anhedonia, within hours, with the effects of a single dose lasting for days. Since then, research has focused on uncovering the mechanisms underlying its rapid...
There is an ongoing need to identify novel pharmacological agents for the effective treatment of depression. One emerging candidate, which has demonstrated rapid-acting antidepressant effects in treatment-resistant groups, is nitrous oxide (N2O)-a gas commonly used for sedation and pain management in clinical settings and with a range of pharmacological effects, including antagonism of NMDA...
Depression is a leading cause of disability worldwide and its prevalence is on the rise. One of the most debilitating aspects of depression is the dominance and persistence of depressive rumination, a state of mind that is linked to onset and recurrence of depression. Mindfulness meditation trains adaptive attention regulation and present-moment embodied awareness, skills that may be...
Ketamine, classical psychedelics and sleep deprivation are associated with rapid effects on depression. Interestingly, these interventions also have common psychotomimetic actions, mirroring aspects of psychosis such as an altered sense of self, perceptual distortions and distorted thinking. This raises the question whether these interventions might be acute antidepressants through the same...
Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug...