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Strategic Neurodelivery of Psychedelic Compounds: Bridging Molecular Pharmacology with Therapeutic Innovation in CNS Disorders.

Shikha Baghel Chauhan, Naziya Akhtar, Chirag Jain, Indu Singh

CNS & Neurological Disorders - Drug Targets March 11, 2026 DOI: 10.2174/0118715273434237251212095005 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Peer reviewed
Key points The abstract argues that psychedelics act primarily via 5-HT2A receptor agonism to activate BDNF-TrkB-mTOR signaling, enhancing neuroplasticity and synaptogenesis, with recent evidence of direct TrkB binding and sustained cortical remodeling underlying rapid, durable antidepressant effects. It contends that advanced drug delivery systems, microfluidics, AI-based dosing, and non-invasive routes can improve brain targeting, safety, and personalized dosing in psychedelic-assisted therapy.

Abstract

Psychedelic compounds such as psilocybin, Lysergic Acid Diethylamide (LSD), N,Ndimethyltryptamine (DMT), and 3,4-methylenedioxymethamphetamine (MDMA) are emerging as novel therapeutics for neuropsychiatric disorders, including depression, Post-Traumatic Stress Disorder (PTSD), and addiction. Acting primarily through serotonin 5-HT2A receptor agonism, they activate intracellular cascades involving Brain-Derived Neurotrophic Factor (BDNF), Tropomyosin receptor kinase B (TrkB), and the mammalian target of rapamycin (mTOR) pathway, leading to enhanced neuroplasticity and synaptogenesis. Recent evidence demonstrates direct TrkB binding and sustained cortical remodeling, underlying their rapid and durable antidepressant effects. Advanced Drug Delivery Systems (DDS)-including liposomes, Solid Lipid Nanoparticles (SLNs), and Poly(lactic-co-glycolic acid) (PLGA) carriers-are being engineered to achieve controlled, braintargeted, and stimuli-responsive release while minimizing systemic toxicity. Integration with microfluidic fabrication, Artificial Intelligence (AI)-based dosing, and non-invasive routes such as intranasal and transdermal delivery improves precision and patient adherence. By merging neuropharmacology with materials science, these innovations are redefining psychedelic-assisted therapy through enhanced safety, personalized dosing, and translational potential for central nervous system disorders.

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