Stress triggers inflammation in the brain, a pattern also seen in the blood of people with depression. This stress-induced inflammation may contribute to treatment-resistant depression. The rapid-acting antidepressant ketamine works partly by reducing inflammation through effects on the HPA axis, the kynurenine pathway, or by suppressing cytokines. Understanding the link between ketamine, inflammation, and stress could reveal how ketamine works and lead to new rapid-acting antidepressants that target inflammation.
Psychiatric disorders are the leading cause of disability globally, and interest in psychedelic substances as potential treatments has recently revived. This review examines the therapeutic potential and safety concerns of psilocybin, DMT, LSD, and MDMA, including their possible interactions with psychotherapy. It covers active and recently completed clinical trials drawn from published literature, conference abstracts, clinical trial registries, and press releases. The review suggests that these compounds may offer new avenues for treating psychiatric disorders, though safety considerations remain important.
Ketamine's rapid antidepressant effects spurred the development of a new class of medications called rapid-acting antidepressant drugs (RAADs), some already approved for clinical use. These drugs work primarily by boosting brain-derived neurotrophic factor (BDNF) or activating GABAA receptors, mechanisms that produce fast and lasting relief from depressive symptoms. This review covers the latest developments in this area of pharmacology and drug discovery.
Indole-based compounds are versatile molecules used in drugs for cancer, viral infections, neurological disorders, and other diseases. This review systematically examines FDA-approved, withdrawn, and investigational indole-containing drugs from the past decade, focusing on clinical outcomes, regulatory decisions, and therapeutic repositioning. It describes a shift from cytotoxic to targeted anticancer agents, the rise of indole-based antivirals during the COVID-19 pandemic, and growing interest in neuroactive indoles, including psychedelic compounds. The review also notes the underrepresentation of indole-based antibiotics and outlines progress in epigenetic and metabolic modulators, providing a framework for future drug development.