Intranasal (es)ketamine has shown efficacy in therapy of treatment-resistant depression (TRD). However, its effects on suicidality have not been fully elucidated. We conducted a retrospective longitudinal cohort study of 80 patients affected by TRD, treated with intranasal (es)ketamine. Suicidality was assessed using item 10 of the clinician-rated Montgomery-Åsberg Depression Rating Scale...
Research SquareJuly 9, 2026Samuel Westenhöfer, Yamina Ehrt, Barbora Provaznikova et al.
preprint
Abstract Background : Treatment-resistant depression (TRD) is associated with substantial clinical and socioeconomic burden. Intranasal esketamine has shown efficacy for TRD in clinical trials and real-world studies. However, evidence on optimal maintenance scheduling is limited. We therefore investigated whether two maintenance schedules differing in their inter-dose intervals were associated...
Ketamine combined with psychotherapy has shown promise in treating posttraumatic stress disorder (PTSD), but predictors of clinical benefit remain unclear. In this systematic review and individual participant data meta-analysis (IPDMA), we examined patient- and treatment-level predictors of PTSD symptom change after combined treatment. Eligible studies combined ketamine with psychotherapy in...
Abstract Psilocybin has demonstrated promising antidepressant effects in depression and treatment-resistant depression (TRD) in controlled clinical trials. However, its effectiveness and safety in real-world therapeutic settings remain largely unknown. Although psilocybin is not yet approved as an antidepressant treatment, Switzerland’s unique legal framework allows its limited medical use for...
Ketamine and its enantiomer esketamine are NMDA receptor antagonists that have shown consistent antidepressant effects in major depression disorder (MDD). These effects suggest an active role of glutamate in the pathophysiology of depression. It has been hypothesized that acute increase of glutamate neurotransmission in the prefrontal cortex following treatment with (es)ketamine leads to...
Regular recreational use of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been consistently linked to verbal memory dysfunctions, whose neurobiological origins remain unclear. Although neurochemical, structural, and functional alterations resulting from repeated MDMA intake have been identified in user populations, only limited knowledge exists regarding potential interrelationships...
Meditation, psychedelics, and brain connectivity: A randomized controlled resting-state fMRI study of N,N-dimethyltryptamine and harmine in a meditation retreat.
Both meditation and psychedelics are widely studied for their therapeutic potential in mental health. Recent research suggests potential synergies between mindfulness practice and psychedelics, though empirical studies have primarily focused on psilocybin. This study investigates the distinct and combined effects of mindfulness practice and an ayahuasca-inspired formulation containing...
Nitrous oxide (N2O) has been known since the end of the eighteenth century. Today, N2O plays a huge role as a greenhouse gas and an ozone-depleting stratospheric molecule. The main sources of anthropogenic N2O emissions are agriculture, fuel combustion, wastewater treatment, and various industrial processes. By contrast, the contribution of medical N2O to the greenhouse effect appears to be...
Suicidal thoughts and behaviours are linked to a wide range of mental health conditions. New interest in the psychiatric benefits of nitrous oxide (N2O) has only recently emerged. The broad pharmacological effects of N2O are thought to be due in large part to N-methyl-d-aspartate antagonism and opioid effects. The purpose of this study protocol is to test whether inhalational N2O exerts rapid...
Treatment-resistant depression (TRD) is associated with reduced quality of life and elevated mortality, posing a major challenge to psychiatric care. After non-response to conventional treatments, next-level interventions such as (es)ketamine are recommended, though remission rates remain variable. Identifying reliable markers of treatment response is therefore critical. Recent evidence...
Ayahuasca, a traditional psychoactive Amazonian brew, usually contains N,N-dimethyltryptamine (DMT) and β-carboline (harmine, harmaline, tetrahydroharmine) monoamine oxidase inhibitors. However, the pharmacological interactions between these compounds remain incompletely understood. In this study, we developed an ayahuasca-inspired formulation containing DMT and harmine, aiming to...
Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea,...
Behavioral SciencesAugust 16, 2024Judith Rohde, Elena Hickmann, Marco Buchmann et al.7 citations
This pilot case series investigated the feasibility and efficacy of an eight-week therapy program, combining nasally administered ketamine (0.5 mg/kg) with trauma-focused psychotherapy, for individuals with chronic, treatment-resistant post-traumatic stress disorder (PTSD). Three patients with chronic, treatment-resistant PTSD underwent the eight-week therapy program. Clinical assessments...
Serotonergic psychedelics hold promise as a treatment modality for various psychiatric disorders and are currently applied in psychedelic-assisted psychotherapy. We investigated the learning effects of the serotonin receptor agonist psilocybin in a probabilistic cue-reward task with emotional cues in the form of neutral or fearful faces, presented either consciously or subconsciously. This...
We investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. Patients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from...
Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition....
In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin...
While there's been clinical success and growing research interest in hypnosis, neurobiological underpinnings induced by hypnosis remain unclear. In this fMRI study (which is part of a larger hypnosis project) with 50 hypnosis-experienced participants, we analyzed neural and physiological responses during two hypnosis states, comparing them to non-hypnotic control conditions and to each other....
The common club drug MDMA (also known as ecstasy) enhances mood, sensory perception, energy, sociability, and euphoria. While MDMA has been shown to produce neurotoxicity in animal models, research on its potential neurotoxic effects in humans is inconclusive and has focused primarily on the serotonin system. We investigated 34 regular, largely pure MDMA users for signs of premature...
The chronic intake of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We...
BACKGROUND: Pharmacological and nonpharmacological methods of inducing altered states of consciousness (ASCs) are becoming increasingly relevant in the treatment of psychiatric disorders. While comparisons between them are often drawn, to date no study has directly compared their neural correlates. METHODS: To address this knowledge gap, we directly compared 2 pharmacological methods...
Background: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely used recreational substance inducing acute release of serotonin. Previous studies in chronic MDMA users demonstrated selective adaptations in the serotonin system, which were assumed to be associated with cognitive deficits. However, serotonin functions are strongly entangled with glutamate as well as γ-aminobutyric acid (GABA)...