Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus
Could psilocybin have potential for tinnitus treatment?
In this review paper the authors look at the potential use of psilocybin in the treatment of tinnitus. The review's central claim is that psilocybin may be a promising future tinnitus treatment because its effects on the serotonin system, glutamate/GABA balance, and neuroplasticity could theoretically reverse some of the maladaptive brain changes thought to underlie tinnitus. However, the evidence is currently preclinical and theoretical rather than clinical, and there is not yet convincing human trial evidence showing that psilocybin reliably improves tinnitus.
Key points
Unveiling the molecular pathways through which 5-HT2A receptors mediate neural plasticity, elucidating their potential pivotal role in tinnitus perception remodelling.
Establishing the first systematic integration of multidimensional associations between psilocybin and tinnitus neural mechanisms, constructing a theoretical framework for serotonergic system regulation.
This study provides novel molecular-level insights into the potential therapeutic application of psilocybin for tinnitus.
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)).
Lu, S., Zhang, Z., Xue, X., Jiang, Y., Zhang, C., Liu, P., He, D., Shen, W., Yang, S., & Wang, F. (2026).Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus. Hearing Research, Article 109701. Advance online publication. Read Paper
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