Molecular Signalling Mechanisms of Psychoactive Drugs: Implications for Addiction and Psychiatric Illness

Psychoactive substances profoundly influence brain function by altering neurotransmission, intracellular signaling cascades, and gene regulatory programs. Many of these compounds act on conserved molecular targets such as G protein-coupled receptors, ligand-gated ion channels, monoamine transporters, and neuromodulatory signaling complexes. Through these interactions, psychoactive drugs reshape synaptic transmission, neuronal excitability, and circuit-level plasticity, producing both therapeutic effects and maladaptive changes associated with substance use disorders and psychiatric illness.

Advances in molecular neuroscience have revealed that repeated exposure to psychoactive drugs can induce long-lasting alterations in intracellular signaling pathways, chromatin regulation, and synaptic architecture. These molecular adaptations contribute to behavioral sensitization, dependence, tolerance, and relapse, while also providing insights into the pathophysiology of psychiatric disorders, including depression, anxiety, schizophrenia, and post-traumatic stress disorder. Understanding how psychoactive compounds engage specific signaling networks across neuronal and glial populations therefore remains a central challenge for both addiction biology and neuropsychopharmacology.

This Research Topic aims to bring together studies that dissect the molecular and cellular signaling mechanisms through which psychoactive compounds influence neuronal function in both physiological and pathological contexts. We aim to clarify how drug-induced signaling events reshape synaptic and circuit dynamics, and how these mechanisms contribute to addiction, psychiatric disease, and emerging therapeutic strategies.

We welcome submissions employing biochemical, genetic, electrophysiological, imaging, pharmacological, and computational approaches, including work in genetically engineered model organisms, rodent models of drug exposure or addiction, human-derived cellular systems, and advanced in vitro preparations. Studies that link drug-induced molecular signaling changes to defined cellular, synaptic, circuit-level, or behavioral outcomes are particularly encouraged.

Topics of interest include, but are not limited to:

• Molecular targets and signaling pathways engaged by psychiatric and recreational drugs
• Drug-induced modulation of neurotransmitter systems
• Intracellular signaling cascades and second messenger systems underlying drug action
• Activity-dependent transcriptional and epigenetic changes induced by chronic drug exposure
• Molecular and cellular mechanisms contributing to addiction, tolerance, and relapse
• Synaptic and structural plasticity driven by psychoactive drug exposure
• Receptor pharmacology and signaling bias in neuropsychopharmacology
• Effects of recreational drugs on molecular signalling and synaptic function in the context of psychiatric disorders, including studies in human-derived cellular systems and animal models of depression, anxiety, schizophrenia, and related conditions
• Emerging pharmacological strategies targeting signaling pathways for the treatment of substance use disorders and psychiatric illness

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: psychoactive, receptor, signalling pathway, drug, addiction, neuropsychiatric

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.