Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review.
Zhen Xuen Brandon Low, Shin Jie Yong, Hayam A Alrasheed, Maha F Al-Subaie, Nawal A Al Kaabi, Mubarak Alfaresi, Hawra Albayat, Jawaher Alotaibi, Ali Al Bshabshe, Ameen S S Alwashmi, Amal A Sabour, Maha A Alshiekheid, Zainab H Almansour, Huda Alharthi, Hani A Al Ali, Adel A Almoumen, Nabil A Alqasimi, Hajir AlSaihati, Alfonso J Rodriguez-Morales, Ali A Rabaan
Progress in neuro-psychopharmacology & biological psychiatry March 20, 2025 DOI: 10.1016/j.pnpbp.2025.111279 (opens in new tab) via PubMed
Summary
AI-generated from the abstractLong COVID, or post-COVID-19 syndrome (PCS), involves persistent symptoms such as fatigue, sleep problems, olfactory dysfunction, and cognitive issues, with no approved treatments. Recent research links PCS severity to low circulating serotonin levels, suggesting serotonin-modulating therapies may help. This review proposes that serotonergic psychedelics, which act mainly on the 5-HT2A serotonin receptor, could alleviate PCS symptoms through effects on inflammation, neuroplasticity, gastrointestinal function, and endothelial dysfunction. The review also discusses potential benefits for specific symptoms like olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges. Emerging evidence indicates these psychedelics may help, but further high-quality research is needed to confirm their safety and efficacy.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Neuroplasticity Serotonin |
| Keywords | Inflammation Long covid Post-covid-19 syndrome Psychedelics |
| Key finding | Serotonergic psychedelics may alleviate symptoms of Long COVID through mechanisms involving inflammation, neuroplasticity, gastrointestinal function, and endothelial dysfunction, but more research is needed. |
Abstract
In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS. Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS. Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges. Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.