Trends in Pharmacological Sciences
August 1, 2008
M Geyer, F Vollenweider
435 citations
The history of serotonin research is closely tied to hallucinogenic drugs that activate serotonin-2A receptors. Early discoveries of LSD, psilocybin, and serotonin led to the idea that psychotic states in disorders like schizophrenia may involve abnormalities in serotonin systems. Sixty years of study have confirmed a significant relationship between serotonin and both drug-induced and disorder-based psychotic states. Modern biochemical, pharmacological, behavioral, neuroimaging, genetic, and molecular biological sciences are converging to understand how serotonin systems interact with other monoaminergic and glutamatergic systems to modulate consciousness and contribute to psychotic disorders like schizophrenia. This review summarizes experimental assessments of the serotonergic hallucinogen model psychosis in relation to the serotonin hypothesis of schizophrenia.
Trends in Pharmacological Sciences
September 24, 2021
Lily R. Aleksandrova, Anthony G. Phillips
255 citations
Ketamine and classical psychedelics (psilocybin, LSD, and DMT) work as fast-acting antidepressants by promoting neuroplasticity. Evidence from preclinical and clinical studies shows these compounds trigger synaptic, structural, and functional changes, especially in pyramidal neurons of the prefrontal cortex. They increase glutamate release, activate AMPA receptors, and stimulate BDNF and mTOR signaling, leading to the expression of synaptic proteins and synaptogenesis. This adaptive rewiring of pathological neurocircuitry may explain their robust and sustained therapeutic effects.
Trends in Pharmacological Sciences
September 22, 2017
Evan J. Kyzar, Charles D. Nichols, Raul R. Gainetdinov et al.
155 citations
Psychedelic drugs like LSD, mescaline, and psilocybin produce strong effects on the brain and behavior. After decades of research difficulties, they are being tested again as possible treatments for hard-to-treat medical conditions. Preclinical research, human brain imaging, and early clinical trials suggest these compounds may help with addiction, depression, anxiety, and other disorders. However, many questions about how they work, their safety, and their effectiveness remain. This review summarizes recent preclinical and clinical data, discusses their pharmacological mechanisms, and outlines key areas for future research to maximize the potential benefits of psychedelic medicine for patients.
Trends in Pharmacological Sciences
September 16, 2025
Sonia Sonda, Diana Pendin, Stefano Comai et al.
11 citations
Psilocybin, a serotonergic psychedelic, shows rapid and lasting therapeutic effects for depression and other hard-to-treat neuropsychiatric conditions, likely due to its ability to enhance neuronal plasticity. While these effects are often attributed to activation of the serotonin 2A (5-HT2A) receptor, emerging evidence indicates a more complex pharmacological profile involving multiple serotonin receptor subtypes and non-serotonergic targets like TrkB. This review integrates current findings on the molecular interactome of psilocin, the active metabolite of psilocybin, focusing on receptor selectivity, biased agonism, and intracellular receptor localization. These insights provide a refined framework for understanding psilocybin's enduring effects and guiding the development of next-generation neuroplastogens with improved specificity and safety.