The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of...
The novel antidepressant ketamine has been shown to achieve what most classic antidepressants, such as Selective Serotonin Reuptake Inhibitors, have not been able to. A rapid onset of symptomatic improvement across multiple domains; mood, anhedonia, and suicidal ideation. The exact neuropsychopharmacological mechanisms of this unique phenomenon are still unknown, although many theories are...
Obsessive-compulsive disorder (OCD) is a common and disabling condition. A large proportion of patients fail to respond to first-line treatment with serotonin reuptake inhibitors either selective serotonin reuptake inhibitors (SSRIs) or clomipramine. Preliminary evidence suggests psilocybin, a serotonin receptor agonist, might be efficacious. We conducted a pharmacological challenge study to...
Alpha-methyltryptamine (AMT), 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT) are three synthetic tryptamines with hallucinogenic properties that are widely abused worldwide. The hallucinogenic effects of tryptamines are primarily related to activation of the 5-HT receptor, and among the many subtypes of 5-HT receptors, the 5-HT2A receptor is...
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder marked by motor symptoms due to dopaminergic degeneration and non-motor symptoms such as depression, anxiety, and cognitive impairment, which significantly affect patients' quality of life. Traditional dopaminergic therapies address motor symptoms but offer limited efficacy for neuropsychiatric manifestations. Psilocybin, a...
Biological PsychiatryJune 25, 2025Kevin G Mulvihill, Gemma J Cockcroft, Angela C Roberts2 citations
Individual variability in pharmacological treatment efficacy remains a persistent obstacle to ameliorating clinical anxiety. This may originate, in part, from the different neural aetiologies underlying pathological anxiety. To provide novel insights into patient heterogeneity in anxiolytic responsiveness we compare the efficacy of distinct anxiolytic drugs, a Selective Serotonin Re-uptake...
Abstract Serotonergic psychedelics alter self-boundaries and can induce out-of-body experiences (OBEs)—the sense of being located outside one’s physical body. While OBEs also occur in clinical conditions and can be experimentally induced, their neural basis under psychedelics remains underexplored. In an open-label, baseline-controlled MRI study of 62 healthy adults administered psilocybin, we...
Drugs AgingJune 24, 2025Lou Vinarcsik, Charles Smoller, George Grossberg1 citation
The use of drugs with psychedelic and dissociative effects for the treatment of psychiatric illnesses has become increasingly popular in recent years. However, few trials have been conducted to determine the efficacy of these agents in the specific setting of treatment-resistant major depressive disorder (MDD) in older adults. In this paper, we review notable aspects of treatment-resistant MDD...
Ketamine and esketamine are two closely related compounds with fast-acting antidepressant properties that have reshaped the treatment landscape for individuals with treatment-resistant depression (TRD). Originally developed as anesthetic agents, both have since demonstrated rapid and robust antidepressant effects in patients who have not responded to conventional treatments such as selective...
Patients with Major Depressive Disorder (MDD) have more dysfunctional attitudes than healthy individuals and these pessimistic biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in depression. Secondary analysis of a two-arm randomized controlled trial assessing the effect of psilocybin therapy versus escitalopram on 'maladaptive' cognitive biases...