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 DOI: 10.1016/j.heares.2026.109701 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Psilocybin Serotonin |
| Keywords | Dopamine Gaba Glutamate Tinnitus |
| Key findings | Psilocybin's activation of 5-HT2A receptors and subsequent neuroplasticity mechanisms may synergistically regulate excitatory and inhibitory neurotransmitter systems relevant to 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)).
Comparable studies
Other narrative reviews on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The pharmacology of psilocybin | 2002 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| Psychedelics, Meditation, and Self-Consciousness | 2018 | Review | |
| The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act | 2018 | Review |
Citations in the library
Cites 43
- 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American Journal of Drug and Alcohol Abuse 2019
- Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior International Journal of Molecular Sciences June 16, 2022
- Classic Psychedelic Drugs: Update on Biological Mechanisms Pharmacopsychiatry January 25, 2022
- Psilocybin induces acute and persisting alterations in immune status in healthy volunteers: An experimental, placebo-controlled study Brain, Behavior, and Immunity September 7, 2023
- Psilocybin-induced stimulus control in the rat. Pharmacology, Biochemistry, and Behavior October 1, 2007
and 38 more in the library