Ketamine is the prototypal rapid-acting antidepressant (RAAD) for TRD with approved indication for esketamine-nasal spray (ESK-NS). Distinctly, arketamine (R-KET) demonstrates enhanced antidepressant effects and neuroplasticity changes compared to esketamine, with fewer dissociative side effects and abuse potential. This study focuses on R-ketamine's therapeutic implications, safety, and...
Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in...
Psychedelics (hallucinogenic 5-HT2A agonists such as psilocybin) are gaining recognition for their potential to treat a range of conditions, including anxiety-related psychopathology. Despite early promising results, the mechanisms by which psychedelic therapy alleviates anxiety are not well understood. Here, we review neural and cognitive mechanisms underlying anxiety-related psychopathology...
There is controversy about a causal role of serotonin (5-HT) in depression, some arguing that there is no proof for impaired brain 5-HT function in depressed patients. Major depressive disorder comes with multiple endophenotypes; not surprisingly classical antidepressants (tricyclics, MAO inhibitors, SSRIs, SNRIs) are not universally effective. Most antidepressants target the 5-HT system,...
Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming from its dysregulated acquisition and extinction. The primary treatment for these disorders, exposure therapy (ET), relies heavily on fear extinction (FE) principles. Adolescence, a vulnerable period for developing psychiatric...
Reunion Neuroscience , a start-up focused on mental health, has raised a $103 million series A round, co-led by MPM BioImpact and the Novo Nordisk Foundation's investment arm Novo Holdings. The company's lead asset, RE104, is a novel psychedelic that is being developed to treat adjustment disorder in cancer patients as well as postpartum depression. RE104 is a prodrug of 4-OH-DiPT, which acts...
Depression is a devastating mood disorder that causes significant disability worldwide. Current knowledge of its pathophysiology remains modest and clear biological markers are lacking. Emerging evidence from human and animal models reveals persistent alterations in endoplasmic reticulum (ER) homeostasis, suggesting that ER stress-related signaling pathways may be targets for prevention and...
Recent research with classic psychedelics suggests significant therapeutic potential, particularly for neuropsychiatric disorders. A mediating influence behind symptom resolution is thought to be the personal insight - at times, bordering on the mystical - one acquires during the acute phase of a psychedelic session. Indeed, current clinical trials have found strong correlations between the...
Recent interest in the potential therapeutic effects of psychedelics has led to investigations into their influence on molecular signaling pathways within the brain. Integrated review and analysis of different studies in this field. A systematic search was conducted across international databases including Embase, Scopus, Web of Science, and PubMed from inception to 9 July 2023. Eligibility...
The relationship between consciousness and individual agency is examined from a bottom-up evolutionary perspective, an approach somewhat different from other ways of dealing with the issue, but one relevant to the question of animal consciousness. Two ways are identified that would decouple the two, allowing consciousness of a limited kind to exist without agency: (1) reflex pathways that...