Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus.
Shuhan Lu, Zhixin Zhang, Xinmiao Xue, Yuke Jiang, Chi Zhang, Peng Liu, Dongdong He, Weidong Shen, Shiming Yang, Fangyuan Wang
Hearing research August 1, 2026 Peer reviewed DOI: 10.1016/j.heares.2026.109701 via PubMed
Summary
Subjective tinnitus, characterized by the perception of noise without external sound, is rising in prevalence. Current treatments have limited efficacy and side effects, highlighting the need for new therapies. Psilocybin, a psychedelic tryptamine, shows promise due to its ability to activate 5-HT2A receptors, leading to increased glutamate and brain-derived neurotrophic factor (BDNF). This enhances neural plasticity, which may offer novel therapeutic pathways for treating tinnitus.
Study at a glance
| Design | review |
|---|---|
| Key finding | Psilocybin activates 5-HT2A receptors, enhancing glutamate release and BDNF levels, which may restore neural plasticity relevant to tinnitus treatment. |
Abstract
Subjective tinnitus is a common auditory disorder characterised by the subjective perception of noise in the absence of external sound sources. Its prevalence has been rising annually due to noise exposure, medication misuse, and population ageing. Current tinnitus treatments employ antidepressants, anticonvulsants, and vasodilators, yet most demonstrate limited efficacy with significant side effects. There is an urgent clinical need for novel therapeutic agents targeting new mechanisms and pathways. In recent years, the natural psychedelic tryptamine psilocybin has garnered attention for its rapid and sustained therapeutic effects following single-dose administration in clinical trials for depression and end-of-life anxiety. Its mechanism involves selectively activating 5-HT2A receptors, triggering substantial glutamate release and subsequently upregulating brain-derived neurotrophic factor (BDNF). This markedly increases dendritic spine density and synaptic protein expression in the hippocampus and prefrontal cortex, thereby restoring neural plasticity. This review systematically integrates the aforementioned neuroplasticity mechanisms with cross-mechanisms of neuroplastic alterations associated with tinnitus, emphasising its synergistic regulatory effects on excitatory neurotransmitters and their receptors (glutamate, dopamine) as well as inhibitory neurotransmitters and their receptors (gamma-aminobutyric acid (GABA)).